We aimed to characterize the parent experience of caring for an infant with neonatal encephalopathy. In this mixed-methods study, we performed semistructured interviews with parents whose infants were enrolled in an existing longitudinal cohort study of therapeutic hypothermia between 2011 and 2014. Thematic saturation was achieved after 20 interviews. Parent experience of caring for a child with neonatal encephalopathy was characterized by 3 principal themes. Theme 1: Many families described cumulative loss and grief throughout the perinatal crisis, critical neonatal course, and subsequent missed developmental milestones. Theme 2: Families experienced entangled infant and broader family interests. Theme 3: Parents evolved into and found meaning in their role as an advocate. These data offer insight into the lived experience of parenting an infant with neonatal encephalopathy. Primary data from parents can serve as a useful framework to guide the development and interpretation of parent-centered outcomes.
Lhermitte-Duclos disease is a rare hamartomatous tumor of the cerebellum resulting from a mutation in the phosphatase and tensin homolog (PTEN) gene: it has been reported in fewer than 10 infants. Rapamycin treatment has not yet been described in Lhermitte-Duclos disease. The infant underwent shunt placement shortly after birth for aqueductal stenosis. Her clinical progression included failure to thrive, seizures, episodes of decerebrate posturing, loss of respiratory drive, and pituitary insufficiency from mass effect. The characteristic "tiger stripe" sign on imaging prompted diagnosis. Rapamycin therapy was initiated at 18 months. Within 5 months, our patient has become responsive to her surroundings and had return of spontaneous breathing. Repeat magnetic resonance imaging (MRI) reveals lack of brainstem compression or distortion of pituitary stalk. Rapamycin should be considered in cases of Lhermitte-Duclos disease where surgical removal may not be an option, as in our case where the cerebellum was entirely involved.
The objective of this study was to identify a relationship between cerebrospinal fluid (CSF) volume removal and change in CSF pressure in children with suspected idiopathic intracranial hypertension (IIH).
We performed a cross-sectional study of children 22 years and younger who underwent a lumbar puncture (LP) and had a documented opening pressure, closing pressure, and volume removed. Relationship between volume removal and pressure change was determined using a fractional polynomial regression procedure.
In the 297 patients who met the inclusion criteria, CSF pressure decreased by 1 cm H2O for every 0.91 mL of CSF removed if the maximum change in pressure was less than 15 cm H2O (R 2 = 0.38).
A linear relationship exists between the volume of CSF removed and the amount of pressure relieved when the desired pressure change is less than 15 cm H2O.
To describe pontine axonal anomalies across diverse brain malformations. Institutional review board–approved review of magnetic resonance imaging (MRI) and genetic testing of 31 children with brain malformations and abnormal pons by diffusion tensor imaging. Anomalous dorsal pontocerebellar tracts were seen in mid-hindbrain anomalies and in diffuse malformations of cortical development including lissencephaly, gyral disorganization with dysplastic basal ganglia, presumed congenital fibrosis of extraocular muscles type 3, and in callosal agenesis without malformations of cortical development. Heterotopic and hypoplastic corticospinal tracts were seen in callosal agenesis and in focal malformations of cortical development. There were no patterns by chromosomal microarray analysis in the non-lissencephalic brains. In lissencephaly, there was no relationship between severity, deletion size, or appearance of the pontocerebellar tract. Pontine axonal anomalies may relate to defects in precerebellar neuronal migration, chemotactic signaling of the pontine neurons, and/or corticospinal tract pathfinding and collateral branching not detectable with routine genetic testing.
We evaluated whether perfusion brain abnormalities by single-photon emission computed tomography (SPECT) imaging improves diagnostic and prognostic assessment in Sydenham chorea. Twenty-three children with acute autoimmune chorea underwent technetium-99m hexamethylpropyleneamine oxime brain SPECT imaging. In 16 children, SPECT was repeated during the follow-up. A pattern of basal ganglia hyperperfusion was observed in 20 (87%) patients. In 4 of 10 patients with generalized chorea, perfusion was comparable in right and left striatum and right and left thalamus. In 13 patients with hemi-chorea and in 3 with generalized chorea, unilateral hyperperfusion was detected. Three patients with generalized chorea had normal perfusion. Tracer uptake of basal ganglia of the patients at the acute phase was higher than at the follow-up (P < .001). SPECT seems a useful noninvasive tool in pediatric patients with Sydenham chorea to support the clinicians during the acute phase of disease and to monitor the course of autoimmune chorea.
The authors conducted a cross-sectional survey of Massachusetts school nurses examining return-to-learn practices for children recovering from concussion in prekindergarten through high school. Regardless of school setting, all students received academic accommodations to support learning during recovery. School nurses perceived less benefit to prolonged cognitive rest (>4 days) for high school students relative to students in elementary school, but provided academic accommodations to them for comparatively longer periods of time (10-14 days vs 6-10 days). In all settings, respondents indicated a need for improved communication among treating physicians, parents, and school personnel, as well as improved education and standardized management tools for younger children and those who sustain non-sport-related injuries. Despite serving children at different developmental stages, school return-to-learn practices are essentially the same in primary and secondary schools, highlighting the need for standardized, developmentally appropriate return-to-learn plans and additional education for the providers and school personnel who implement them.
The authors aimed to compare the opening pressures of children with demyelinating disease to children with primary intracranial hypertension. Medical records were reviewed for a primary diagnosis of demyelinating disease, or primary intracranial hypertension. Diagnosis of demyelinating disease was made according to either the 2007 or 2012 International Pediatric Multiple Sclerosis Study Group criteria. Primary intracranial hypertension diagnosis was confirmed by presence of elevated opening pressure, normal cerebrospinal fluid composition and neuroimaging. The authors compared 14 children with demyelinating disease to children with primary intracranial hypertension in 1:1 and 1:2 fashions. There was a statistically significant higher BMI in the primary intracranial hypertension group compared to the demyelinating group (P = .0203). The mean cerebrospinal fluid white blood cell count was higher in the demyelinating disease group compared to primary intracranial hypertension (P = .0002). Among both comparisons, the cerebrospinal fluid opening pressure, glucose, protein and red blood cell counts in children with demyelinating disease were comparable to age- and sex-matched controls with primary intracranial hypertension.
Internal carotid artery pseudoaneurysm is an uncommon complication of retropharyngeal and parapharyngeal abscess in children. Treatment of the pseudoaneurysm has evolved in recent years from surgical ligation to endovascular techniques. Neurologic sequelae most commonly consist of Horner’s syndrome with cerebral ischemia being uncommon. The clinical course of a 2-year-old boy with retropharyngeal abscess complicated by internal carotid artery pseudoaneurysm, is described and the literature is reviewed. A conventional angiogram confirmed the presence of a large pseudoaneurysm with no anterograde flow distal to the pseudoaneurysm and substantial collateral flow across the circle of Willis, with filling of the left anterior and middle cerebral arteries via the anterior and posterior communicating arteries. Endovascular occlusion resulted in nonfilling of the left internal carotid artery, pseudoaneurysm, and left internal jugular vein at the base of the skull. Following the procedure, the patient developed transient mild right hemiparesis associated with frontal lobe ischemia.
Attention Deficit Hyperactivity Disorder (ADHD) is associated with altered cerebellar volume and cerebellum is associated with cognitive performance. However there are mixed results regarding the cerebellar volume in young patients with ADHD. To clarify the size and direction of this effect, we conducted the analysis on the large public database of brain images. The aim of this study was to confirm that cerebellar volume in ADHD is smaller than in control subjects in currently the largest publicly available cohort of ADHD subjects.We applied cross-sectional case control study design by comparing 286 ADHD patients (61 female) with age and gender matched control subjects. Volumetric measurements of cerebellum were obtained using automated segmentation with FreeSurfer 5.1. Statistical analysis was performed in R-CRAN statistical environment. Patients with ADHD had significantly smaller total cerebellar volumes (134.5±17.11cm3 vs.138.90±15.32 cm3). The effect was present in both females and males (males 136.9±14.37 cm3 vs. 141.20±14.75 cm3; females 125.7±12.34 cm3 vs. 131.20±15.03 cm3). Age was positively and significantly associated with the cerebellar volumes. These results indicate either delayed or disrupted cerebellar development possibly contributing to ADHD pathophysiology.
Motor stereotypy behaviors are patterned, coordinated, repetitive behaviors that are particularly evident in those with an autistic spectrum disorder and intellectual disabilities. The extent to which motor stereotypy behavior severity is associated with motor skills and maladaptive behavior, measures of adaptive functioning, along with fundamental movement skills and degree of autistic spectrum disorder symptomology is assessed in this preliminary report. Twelve participants, aged 7 to 16 years, with a reported motor stereotypy behavior and either mild or severe intellectual disability comprising developmental or global delay took part in the study. Spearman rho correlational analysis showed that severity of motor stereotypy behavior was significantly positively correlated with autistic spectrum disorder symptomology (P = .008) and maladaptive behavior (P = .008) but not fundamental movement skills (P > .05). An increase in fundamental movement skills score was associated with a decrease in autistic spectrum disorder symptomology (P = .01) and an increase in motor skills (P = .002). This study provides evidence showing a significant relationship between motor stereotypy behavior severity with degree of autistic spectrum disorder symptomology and maladaptive behavior.
Anti–N-methyl-
Limb girdle muscular dystrophy 2I is a slowly progressive muscular dystrophy due to mutations in the Fukutin-related protein (FKRP) gene. Clinicians are frequently asked if physical activity is harmful for pediatric patients with limb girdle muscular dystrophy 2I. The primary objective of this study was to determine if there is a relationship between self-reported childhood activity level and motor function and respiratory function in older children and adults with limb girdle muscular dystrophy 2I. We compared retrospective self-reported middle school activity level and sport participation with age at onset of weakness, 10-meter walk test, and forced vital capacity later in life in 41 participants with FKRP mutations. We found no relationship between activity level in childhood and disease course later in life, suggesting that self-directed physical activity in children with limb girdle muscular dystrophy 2I does not negatively affect disease progression and outcome.
The objective of this study was to determine the efficacy and safety of levetiracetam in treatment of neonatal seizures due to hypoxic ischemic encephalopathy. Seizures often persist in neonates with hypoxic ischemic encephalopathy despite phenobarbital. A retrospective single-center study was conducted in neonates ≥36 weeks gestation with hypoxic ischemic encephalopathy. A total of 127 neonates were identified born 2008-2015. Clinical seizures occurred in 83 infants. Fifty-one neonates (61%) had cessation of seizures with only phenobarbital. Thirty-two neonates received levetiracetam after phenobarbital, and the seizures stopped in 27 of these neonates. The mean total loading dose of levetiracetam was 63 mg/kg. Mean maintenance dose of levetiracetam was 65 mg/kg/d. We found no negative side effects in neonates following levetiracetam use. Our study finds that levetiracetam is an efficacious medication in treatment of seizures in the setting of neonatal hypoxic ischemic encephalopathy. Future prospective studies should explore its use as a first-line medication.
This study aimed to detect DRD4 receptor gene polymorphisms in attention-deficit hyperactivity disorder (ADHD) children and to correlate their phenotype-genotype. Fifty children with ADHD were diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and were subjected to Conners Parent Rating Scale. All cases and controls were subjected to history taking, physical examination, IQ assessment, and dopamine receptor D4 (DRD4) exon 3 genotyping. The 7-repeat allele was present only in controls, whereas 2-repeat allele was present in the ADHD children (heterozygous 2-repeat allele in 16% and homozygous in 26% of cases). Eight percent of cases had homozygous 4-repeat allele vs 28% of controls, whereas 10% of cases had heterozygous 4-repeat allele vs 6% of controls, with its predominance in controls. The 2-repeat and 4-repeat alleles have been associated with more inattention, hyperactivity, and impulsivity phenotypes. In conclusion, children with ADHD had a significant presence of the 2-repeat allele and absence of the 7-repeat allele.
Safe maximal surgical resection is the initial treatment of choice for pediatric brainstem low-grade gliomas. Optimal therapy for incompletely resected tumors or that progress after surgery is uncertain. We reviewed the clinical characteristics, therapy, and outcomes of all children with nontectal brainstem low-grade gliomas treated at the University of Michigan between 1993 and 2013. Median age at diagnosis was 6 years; histology was confirmed in 23 of 25 tumors, 64% were pilocytic astrocytoma. Nineteen patients underwent initial tumor resection; 14/19 received no upfront adjuvant therapy. Eight patients in the study had progressive disease; 5 initially resected tumors received chemotherapy at tumor relapse, all with partial or complete radiographic responses. Ten-year progression-free survival is 71% and overall survival, 100%. This single-institution retrospective study demonstrates excellent survival rates for children with brainstem low-grade gliomas. The efficacy of the well-tolerated chemotherapy in this series supports its role in the treatment of unresectable or progressive brainstem low-grade gliomas.
Vibratory feedback can be a useful tool for rehabilitation. We examined its use in children with dystonia to understand how it affects muscle activity in a population that does not respond well to standard rehabilitation. We predicted scaled vibration (ie, vibration that was directly or inversely proportional to muscle activity) would increase use of the vibrated muscle because of task-relevant sensory information, whereas nonscaled vibration would not change muscle use. The study was conducted on 11 subjects with dystonia and 14 controls. Each subject underwent 4 different types of vibration on the more dystonic biceps muscle (or nondominant arm in controls) in a 1-dimensional, bimanual myocontrol task. Our results showed that only scaled vibratory feedback could bias muscle use without changing overall performance in children with dystonia. We believe there may be a role in rehabilitation for scaled vibratory feedback to retrain abnormal muscle patterns.
The SCN1A gene has been implicated in the etiology of various forms of epilepsy. New research has linked this gene to specific types of epilepsy, all of which present in infancy or early childhood. This study examines the time course and pathology of pediatric patients who have a mutation in the SCN1A gene in order to open a discussion regarding the key trends of this form of epilepsy as well as important clinical considerations in management for patients who present with symptoms relating to the SCN1A mutations. We retrospectively examined 20 patients who presented to the clinic with focal seizures, as well as were positive for an SCN1A genetic mutation. Despite the small sample size, we were able to find important trends in the time course of the disorder as well as important areas of clinical practice that must be taken into consideration for these patients.
Wiedemann-Steiner syndrome is a rare genetic disorder characterized by short stature, hairy elbows, facial dysmorphism, and developmental delay. It can also be accompanied by musculoskeletal anomalies such as muscular hypotonia and small hands and feet. Mutations in the KMT2A gene have only recently been identified as the cause of Wiedemann-Steiner syndrome; therefore, only 16 patients from 15 families have been described, and new phenotypic features continue to be added. In this report, we describe 2 newly identified patients with Wiedemann-Steiner syndrome who presented with variable severity. One girl exhibited developmental dysplasia of the hip and fibromatosis colli accompanied by other clinical features, including facial dysmorphism, hypertrichosis, patent ductus arteriosus, growth retardation, and borderline intellectual disability. The other patient, a boy, showed severe developmental retardation with automatic self-mutilation, facial dysmorphism, and hypertrichosis at a later age. Exome sequencing analysis of these patients and their parents revealed a de novo nonsense mutation, p.Gln1978*, of KMT2A in the former, and a missense mutation, p.Gly1168Asp, in the latter, which molecularly confirmed the diagnosis of Wiedemann-Steiner syndrome.
TUBB2A is a gene that has recently been reported in association with structural brain abnormalities. Only 3 cases have been reported to date with disparate brain morphologic abnormalities, although all patients have presented with developmental delay and infantile-onset epilepsy. We report a fourth patient with a de novo variant in TUBB2A that is predicted to be pathogenic, presenting with developmental delay, spastic diplegia, exaggerated startle, and anterior temporal pachygyria in the absence of epilepsy. This report serves to further delineate the phenotype of the TUBB2A-related disorders. Focal anterior temporal pachygyria may facilitate recognition of additional cases of this tubulinopathy.
The natural history of spinal muscular atrophy type I (SMA-I) has changed as improved medical support has become available. With investigational drugs for spinal muscular atrophy now in clinical trials, efficient trial design focuses on enrolling recently diagnosed infants, providing best available supportive care, and minimizing subject variation. The quandary has arisen whether it is ethically appropriate to specify a predefined level of nutritional and/or ventilation support for spinal muscular atrophy type I subjects while participating in these studies. We conducted a survey at 2 spinal muscular atrophy investigator meetings involving physician investigators, clinical evaluators, and study coordinators from North America, Europe, and Asia-Pacific. Each group endorsed the concept that having a predefined degree of nutritional and ventilation support was warranted in this context. We discuss how autonomy, beneficence/non-maleficence, noncoercion, social benefit, and equipoise can be maintained when a predefined level of supportive care is proposed, for participation in a clinical trial.
The Hypertonia Assessment Tool is a 7-item instrument that discriminates spasticity, dystonia, and rigidity on 3 levels: item scores, subtype, and hypertonia diagnosis for each extremity. We quantified the inter- and intrarater reliability using Kappa statistics, Gwet’s first-order agreement coefficient (both with 95% confidence interval), and percentage agreement for all levels. For validity, we compared the Hypertonia Assessment Tool subtype with the clinical diagnosis provided by the physicians. Two physiotherapists tested 45 children with neuromotor disorders. The interrater reliability (n = 45) of the Hypertonia Assessment Tool subtype was moderate to substantial whereas the intrarater reliability (n = 42) was almost perfect. The Hypertonia Assessment Tool showed good agreement in detecting spasticity. On the contrary, there was a higher presence of dystonia of 24% to 25% tested with the Hypertonia Assessment Tool compared to the clinical diagnosis. Even some individual items showed lower agreement between raters; the Hypertonia Assessment Tool subtypes and diagnosis were reliable. Validity of the Hypertonia Assessment Tool to test spasticity is confirmed, whereas, for dystonia and rigidity, further studies are needed.
Mucopolysaccharidosis type III, or Sanfilippo syndrome, is an autosomal recessive disorder characterized by impairment in the degradation of Heparan sulfate. Here the authors describe the natural history of 5 related individuals; all associated through a large pedigree which reports a total of 11 affected members, originally from the Boyacá region in Colombia, diagnosed with MPS IIIC who all harbor a novel mutation in HGSNAT. The authors report an unusually high incidence of the disease in this population. The clinical features are similar to previously described patients, although some differences in the degree of severity and end-stage of the disease are seen in this specific group. The authors consider that the high degree of endogamy in this specific population could underlie modifying factors for the severity of presentation in these patients. Future studies might provide more information on the functional effect of this novel mutation, which could define this group as a genetic isolate.
Alexander disease is a leukodystrophy caused by dominant missense mutations in the gene encoding the glial fibrillary acidic protein. Individuals with this disorder often present with a typical neuroradiologic pattern including white matter abnormalities with brainstem involvement, selective contrast enhancement, and structural changes to the basal ganglia/thalamus. In rare cases, focal lesions have been seen and cause concern for primary malignancies. Here the authors present an infant initially diagnosed with a chiasmatic astrocytoma that was later identified as having glial fibrillary acidic protein mutation-confirmed Alexander disease. Pathologic and radiologic considerations that were helpful in arriving at the correct diagnosis are discussed.
Magnetic resonance imaging (MRI) signs of elevated intracranial pressure and idiopathic intracranial hypertension have been well characterized in adults but not in children. The MRIs of 50 children with idiopathic intracranial hypertension and 46 adults with idiopathic intracranial hypertension were reviewed for optic nerve head protrusion, optic nerve head enhancement, posterior scleral flattening, increased perioptic cerebrospinal fluid, optic nerve tortuosity, empty or partially empty sella, tonsillar herniation, enlargement of Meckel’s cave meningoceles, and transverse venous sinus stenosis(TSS). Compared to adolescents (11-17 years, n = 40) and adults (>17 years, n = 46), prepubescent children (<11 years, n = 10) had lower frequencies of scleral flattening (50% vs 89% and 85%, P = .02), increased perioptic cerebrospinal fluid (60% vs 84% and 89%, P = .08), optic nerve tortuosity (20% vs 46% and 59%, P = .07), empty or partially empty sella (56% vs 78% and 93%, P = .007), and TSS (67% vs 93% and 96%, P = .04). Children with idiopathic intracranial hypertension have similar MRI findings as adults, but they are less frequent in prepubescent children.
We characterized a cohort of patients with posterior reversible encephalopathy syndrome with spinal cord involvement. We encountered 2 children and identified an additional 19 patients from the internet databases. Of the 21 patients analyzed, 8 were children. The mean peak systolic blood pressure in adults was significantly higher than in children (221.8 ± 14.3 vs 191.4 ± 31.3 mm Hg; P < .01). Regardless of age, the most common clinical symptom was headache (90%) and the least common clinical symptom was seizures (28%). Atypical neuroimaging was more common in children (63%) than in adults (8%). Abnormal cerebrospinal fluid results were frequently found in children (83%). All children recovered uneventfully, but 3 adults had sequelae. A broader clinicoradiologic spectrum makes the diagnosis of children more complex than in adults. Awareness of the atypical features with a meticulous management of hypertension is imperative to avoid unnecessary invasive workups and to achieve an uneventful recovery.
Efficient eye movements provide a physical foundation for proficient reading skills. We investigated the effect of in-school saccadic training on reading performance. In this cross-over design, study participants (n = 327, 165 males; mean age [SD]: 7 y 6 mo [1y 1 mo]) were randomized into treatment and control groups, who then underwent eighteen 20-minute training sessions over 5 weeks using King-Devick Reading Acceleration Program Software. Pre- and posttreatment reading assessments included fluency, comprehension, and rapid number naming performance. The treatment group had significantly greater improvement than the control group in fluency (6.2% vs 3.6%, P = .0277) and comprehension (7.5% vs 1.5%, P = .0002). The high-needs student group significantly improved in fluency (P < .001) and comprehension (P < .001). We hypothesize these improvements to be attributed to the repetitive practice of reading-related eye movements, shifting visuospatial attention, and visual processing. Consideration should be given to teaching the physical act of reading within the early education curriculum.
Intrathecal baclofen therapy is widely accepted as a treatment option for patients with severe spasticity. The current treatment of spasticity in patients with Sjögren-Larsson syndrome is largely symptomatic, given that no effective causal therapy treatments are available. We report the outcome of 2 patients with Sjögren-Larsson syndrome who had pump implantation for intrathecal baclofen. We observed a positive response, with a decrease of spasticity, reflecting in the Modified Ashworth Scale, and parents and caregivers observed a functional improvement in both patients. One patient experienced skin irritation 15 months after surgery, necessitating pump repositioning. No infection occurred. Our report shows that intrathecal baclofen therapy can have a positive therapeutic effect on spasticity in patients with Sjögren-Larsson syndrome, and therefore may be a promising addition to current treatments.
Given the increased survival rates in patients with pediatric central nervous system tumors, late effects such as treatment- and/or illness-related neurologic sequelae as well as neuropsychological deficits and social difficulties have moved into focus in follow-up care. In order to provide personalized treatment recommendations for pediatric brain tumor survivors, it is crucial not only to assess cognitive impairments but also to measure a patient’s functional deficiencies, for example, restricted participation in everyday social activities. Thus, this article introduces the International Classification of Functioning–Children and Youth version (ICF-CY) as a conceptual framework for quantifying functional limitations and informing long-term care in pediatric neuro-oncology. A standardized self-report and proxy-report questionnaire for measuring participation is briefly discussed and specific recommendations based on so-called core sets for clinical practice in pediatric neuro-oncology are provided.
Impairments in executive function, such as working memory, are almost universal in children with chromosome 22q11.2 deletion syndrome. Delineating the neural underpinnings of these functions would enhance understanding of these impairments. In this study, children and adolescents with 22q11 deletion syndrome were compared with healthy control participants in a functional magnetic resonance imaging (MRI) study of working memory. When the 2-back condition was contrasted with the 1-back and 0-back conditions, the participants with 22q11 deletion syndrome showed lower activation in several brain areas involved in working memory—notably dorsolateral prefrontal cortex, anterior cingulate, and precuneus. This hypoactivation may be due to reduced gray matter volumes or white matter connectivity in the frontal and parietal regions, differences that have previously been documented in children with 22q11 deletion syndrome. Understanding differences in brain function will provide a foundation for future interventions to address the wide range of neurodevelopmental deficits observed in 22q11 deletion syndrome.
The majority of children with febrile seizures have viral infections and viruses were detected in 22% to 63% of children in published studies. Using molecular methods, viruses were also detected in asymptomatic persons. A prospective study was conducted to detect respiratory and enteric viruses in 192 children with febrile seizures and compare the detection rates to those found in 156 healthy age-matched controls. A respiratory or enteric virus was detected in 72.9% of children with febrile seizures and in 51.4% of healthy controls. The viruses most strongly associated with febrile seizures were influenza, respiratory syncytial virus, parainfluenza, human coronavirus, and rotavirus. Compared to healthy controls, the age-adjusted odds ratios for nasopharynx virus positivity in febrile seizure patients were 79.4, 2.8, 7.2, and 4.9 for influenza virus, parainfluenza virus, respiratory syncytial virus, and human coronavirus, respectively, and 22.0 for rotavirus in stool. The detected virus did not influence clinical features of febrile seizure.
Gilles de la Tourette syndrome is a chronic neuropsychiatric disorder that can have a detrimental impact on the health-related quality of life of children with the condition. To date no patient-reported health-related quality of life measures have been developed for children and adolescents in the English language. This study validated the first disease-specific scale for the quantitative assessment of health-related quality of life in 118 children and adolescents with Gilles de la Tourette syndrome (C&A-GTS-QOL) following language adaptation from Italian to English in the United Kingdom. Standard statistical methods were used to test the psychometric properties of the rating scale. Principal component factor analyses led to the identification of six health-related quality of life domains (cognitive, copro-phenomena, psychological, physical, obsessive-compulsive, and activities of daily living), explaining 66.7% of the overall variance. The C&A-GTS-QOL demonstrated satisfactory scaling assumptions and acceptability; validity was supported by interscale correlations (range 0.2-0.7), confirmatory factor analysis, and correlation patterns with other rating scales and clinical variables.
Bell’s palsy is the most common cause of acute peripheral facial nerve paralysis, but the optimal dose of corticosteroids in pediatric patients is still unclear. This retrospective study aimed to evaluate the efficacy of low-dose corticosteroid therapy compared with high-dose corticosteroid therapy in children with Bell’s palsy. Patients were divided into 2 groups based on the dose of oral prednisolone regimen initiated. The severity of idiopathic facial nerve paralysis was graded according to the House-Brackmann Grading Scale. The patients were re-assessed in terms of recovery rate at the first, third, and sixth months of treatment. There was no significant difference in complete recovery between the 2 groups after 1, 3, and 6 months of treatment. In our study, we concluded that even at a dose of 1 mg/kg/d, oral prednisolone was highly effective in the treatment of Bell’s palsy in children.
To gain a better understanding of the clinical and genetic features associated with agenesis of corpus callosum, we enrolled and characterized 162 patients with complete or partial agenesis of corpus callosum. Clinical and genetic protocols allowed us to categorize patients as syndromic subjects, affected by complex extra-brain malformations, and nonsyndromic subjects without any additional anomalies. We observed slight differences in sex ratio (56% males) and agenesis type (52% complete). Syndromic agenesis of corpus callosum subjects were prevalent (69%). We detected associated cerebral malformations in 48% of patients. Neuromotor impairment, cognitive and language disorders, and epilepsy were frequently present, regardless of the agenesis of corpus callosum subtype. Long-term follow-up allowed us to define additional indicators: syndromic agenesis of corpus callosum plus patients showed the most severe clinical features while isolated complete agenesis of corpus callosum patients had the mildest symptoms, although we observed intellectual disability (64%) and epilepsy (15%) in both categories. We achieved a definitive (clinical and/or genetic) diagnosis in 42% of subjects.
Central neurocytomas are well-differentiated tumors of neuronal origin. These are relatively uncommon in the pediatric population. Anaplastic features reflected by brisk mitotic activity, microvascular proliferation, necrosis, and MIB-1 labeling index >2% or 3% have been proposed to indicate aggressive behavior. Because of its rarity, there is paucity of data regarding the histologic spectrum and outcome of central neurocytomas in children. With this short series, we describe our observations of the clinicopathologic characteristics and outcome of this tumor in children over a 5-year period.
Although neuropsychological studies have demonstrated specific cognitive impairments in children with childhood absence epilepsy (CAE), the potential role of the frontal lobe in these cognitive deficits remains unclear. We therefore evaluated cognitive functions related to and unrelated to the functionality of the frontal lobe in childhood absence epilepsy patients and control subjects. Thirty-seven childhood absence epilepsy patients and 37 age- and gender-matched healthy control subjects were recruited and assessed using a computerized neuropsychological test battery. Childhood absence epilepsy patients, especially a drug-naïve subgroup, showed cognitive deficits in reasoning, visual attention, and executive function, which are typical cognitive functions of the frontal lobe. In contrast, treated childhood absence epilepsy patients only exhibited cognitive deficits in visual attention. There were no significant between-group differences for other cognitive tests. Our findings suggest that frontal lobe–related cognitive deficits represent the characteristic neuropsychological profile associated with childhood absence epilepsy.
We conducted the present study to examine cognitive function and serum heat shock protein 70 levels among children with temporal lobe epilepsy. The Stanford-Binet Intelligence Test was carried out to examine cognitive function in 30 children with temporal lobe epilepsy and 30 controls. Serum heat shock protein 70 levels were determined with an enzyme-linked immunosorbent assay. The epilepsy group had significantly lower cognitive function testing scores and significantly higher serum heat shock protein 70 levels than the control group; there were significant negative correlations between serum heat shock protein 70 levels and short-term memory and composite scores. Children with uncontrolled seizures had significantly lower verbal reasoning scores and significantly higher serum heat shock protein 70 levels than children with controlled seizures. Children with temporal lobe epilepsy have cognitive dysfunction and elevated levels of serum heat shock protein 70, which may be considered a stress biomarker.
Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder (incidence 1:33 000-40 000) characterized by formation of central nervous system tumors, due to mutation in the NF2 gene on chromosome 22q12. Vestibular schwannomas are the hallmark lesion, affecting 95% of individuals and typically occur bilaterally. Schwannomas commonly occur on other nerves intracranially and in the spinal compartment, along with meningiomas, ependymomas, and gliomas. Although histologically benign, tumors are associated with significant morbidity due to multiple problems including hearing and vision loss, gait abnormalities, paralysis, pain, and seizures. Risk of early mortality from brainstem compression and other complications is significant. Severity of disease is higher when NF2 presents during childhood. Children have a more variable presentation, which can be associated with significant delays in recognition of the condition. Careful examination of the skin and eyes can identify important clinical signs of NF2 during childhood, allowing timely initiation of disease-specific surveillance and treatment. Monitoring for complications comprises clinical evaluation, along with functional testing including audiology and serial neuroimaging, which together inform decisions regarding treatment. Evidence for disease-specific medical treatment options is increasing, nevertheless most patients will benefit from multimodal treatment including surgery during their lifetime. Patient enrolment in international natural history and treatment trials offers the best opportunity to accelerate our understanding of the complications and optimal treatment of NF2, with a view to improving outcomes for all affected individuals.
Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development–Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age.
To assess the long-term outcome of childhood tuberculous meningitis treated with modern 4-drug antitubercular regimens and to determine predictors of survival and morbidity.
In this single-center prospective cohort, outcome of children with tuberculous meningitis treated with standard regimens was assessed at 6 months and 12 months after discharge using the Pediatric Cerebral Performance Category Scale.
Of 130 children, 38 died in hospital and 34 were either severely disabled or comatose/vegetative at discharge. At 6 and 12 months, 87% of the survivors were either normal (n = 62) or mildly disabled (n = 17, on the Pediatric Cerebral Performance Category scale). On multivariate analysis, the factors associated with poor outcome at 12 months were stage III at admission (adjusted odds ratio 4.4, 95% confidence interval, 1.7-11.2, P = .002) and presence of infarcts on neuroimaging (adjusted odds ratio 2.6, 95% confidence interval, 1.1-6.6, P = .037).
Despite the high in-hospital mortality, in resource-constraint settings, the survivors showed remarkable improvement, with two-thirds returning to a normal functional status at 6 months’ follow-up.
Data of 829 infants with obstetric brachial plexus palsy were reviewed to identify any cases that could not be fitted into the any of the well-known types of palsy. These unusual cases were studied in detail with regard to clinical presentation and electrophysiological findings as well as management and spontaneous motor recovery. Erb’s, extended Erb’s, and total palsies were seen in 42.8%, 28.8%, and 28.0% of cases, respectively. Three cases (0.4%) did not fit into any of the classic types. One case had bilateral palsy, and the remaining 2 cases had unilateral palsy. All affected limbs presented with "abducted arms," "flexed forearms," and electrophysiological evidence of denervation of shoulder adductors and triceps. All cases had excellent spontaneous recovery within 6-12 months. It was concluded that these cases represent mild "intermediate" types of palsy in which the C7 root was the predominant site of injury. Good spontaneous recovery is expected.
Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients’ seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.
Freely available software, derived from the past 2 decades of neuroimaging research, is significantly more flexible for research purposes than presently available clinical tools. Here, we describe and demonstrate the utility of rapidly deployable analysis software to facilitate trainee-driven translational neuroimaging research. A recipe and video tutorial were created to guide the creation of a NeuroDebian-based virtual computer that conforms to current neuroimaging research standards and can exist within a HIPAA-compliant system. This allows for retrieval of clinical imaging data, conversion to standard file formats, and rapid visualization and quantification of individual patients’ cortical and subcortical anatomy. As an example, we apply this pipeline to a pediatric patient’s data to illustrate the advantages of research-derived neuroimaging tools in asking quantitative questions "at the bedside." Our goal is to provide a path of entry for trainees to become familiar with common neuroimaging tools and foster an increased interest in translational research.
SUCLA2 defects have been associated with mitochondrial DNA (mtDNA) depletion and the triad of hypotonia, dystonia/Leigh-like syndrome, and deafness. A 9-year-old Brazilian boy of consanguineous parents presented with psychomotor delay, deafness, myopathy, ataxia, and chorea. Despite the prominent movement disorder, brain magnetic resonance imaging (MRI) was normal while 1H-magnetic resonance spectroscopy (MRS) showed lactate peaks in the cerebral cortex and lateral ventricles. Decreased biochemical activities of mitochondrial respiratory chain enzymes containing mtDNA-encoded subunits and mtDNA depletion were observed in muscle and fibroblasts. A novel homozygous mutation in SUCLA2, the first one in the ligase coenzyme A (CoA) domain of the protein, was identified. Escalating doses of CoQ10 up to 2000 mg daily were associated with improvement of muscle weakness and stabilization of the disease course. The findings indicate the importance of screening for mitochondrial dysfunction in patients with complex movement disorders without brain MRI lesions and further investigation for potential secondary CoQ10 deficiency in patients with SUCLA2 mutations.
Medulloblastoma accounts for nearly 10% of all childhood brain tumors. These tumors occur exclusively in the posterior fossa and have the potential for leptomeningeal spread. Treatment includes a combination of surgery, radiation therapy (in patients >3 years old). Patients >3 years old are stratified based on the volume of postoperative residual tumor and the presence or absence of metastases into "standard risk" and "high risk" categories with long-term survival rates of approximately 85% and 70%, respectively. Outcomes are inferior in infants and children younger than 3 years with exception of those patients with the medulloblastoma with extensive nodularity histologic subtype. Treatment for medulloblastoma is associated with significant morbidity, especially in the youngest patients. Recent molecular subclassification of medulloblastoma has potential prognostic and therapeutic implications. Future incorporation of molecular subgroups into treatment protocols will hopefully improve both survival outcomes and posttreatment quality of life.
Our objective was to describe the types of providers who refer children with autism spectrum disorder (ASD) for brain magnetic resonance imaging (MRI), the referral reason, and MRI results. The most common referral reasons were autism spectrum disorder with seizures (33.7%), autism spectrum disorder alone (26.3%), and autism spectrum disorder with abnormal neurologic examination or preexisting finding (24%). Neurology (62.5%), general pediatric (22.3%), and developmental/behavioral practitioners (8.9%) referred the most patients. The prevalence of definite pathology was highest in children referred for autism spectrum disorder with abnormal neurologic examination/preexisting finding (26.2%, 95% CI: 16.8%-36%), headaches (25.7%, 95% CI: 11.2%-40.2%), or seizures (22%, 95% CI: 14.6%-29.5%), and was lowest in children referred for autism spectrum disorder alone (6.5%, 95% CI: 1.5%-11.6%). We concluded that there is a low prevalence of definite pathology in children with autism spectrum disorder undergoing brain MRI. In children with abnormal neurologic examination or preexisting finding, seizures, or headaches, one may consider performing brain MRI given the higher prevalence of pathology.
The aim of this prospective pilot study was to evaluate the predictive value of discrimination and habituation, which was measured by mismatch negativity in 17 healthy very preterm (mean gestational age 27.4 weeks; range 25.0-31.3) and 16 term (mean gestational age 40.3 weeks; range 37.9-41.7) born infants at term equivalent age. Developmental outcome was measured by Bayley Scales of Infant Development–I in 13 preterm and 13 term-born children at a mean age of 21.7 months (±2.18) and 18.5 months (±1.9), respectively. No differences in amplitude and latency of the mismatch negativity were found between both groups at term equivalent age. Within the preterm group habituation capacity was positively correlated with the Mental Developmental Index (r = .654, P = .008) and Performance Developmental Index (r = .482, P = .048) at 21 months. Early learning capability, as measured by habituation, may be associated with a better prognosis for early mental development in healthy preterm infants.
The aim is to evaluate normal-appearing brain regions in isolated unilateral polymicrogyria patients and compare them with controls by using diffusion-weighted imaging and apparent diffusion coefficient. The diffusion-weighted images (b = 0-1000 s/mm2) of 10 pediatric patients (7 boys, 3 girls; mean age = 5.8 ± 4.3 years) with isolated unilateral polymicrogyria and age-sex matched 10 control patients were assessed retrospectively. There was a significant increase in apparent diffusion coefficient values of white matter underlying polymicrogyria, uninvolved white matter, deep gray matter (thalami, lentiform nuclei, caudate nuclei) and corpus callosum in polymicrogyria patients compared to control group (P < .01). The whole brain might be affected in isolated unilateral polymicrogyria patients. The abnormal deep gray matter in polymicrogyria patients would indicate a new point of view for pediatric neurologists about the probability of additional future neurological disorders.
In 2 unrelated patients with axial hypotonia, developmental delay and a hyperkinetic movement disorder, a missense mutation was found in codon 209 of the GNAO1 gene. From the still scarce literature on GNAO1 mutations, a clear genotype-phenotype correlation emerged. From the 26 patients reported thus far, 12 patients had epileptic encephalopathy, and 14 had a developmental delay and a hyperkinetic movement disorder. All but 1 of the latter patients had missense mutations in GNAO1 codon 209 or 246, which thus appear to be mutation hotspots. At least 2 sibling pairs showed that the recurrence risk after 1 affected child with a GNAO1 mutation might be relatively high (5-15%), due to apparent gonadal mosaicism in the parents.
The purpose of this study was to assess school nurses’ perceptions of barriers to optimal management of seizures in schools. Eighty-three school nurses completed an electronic survey. Most agreed they felt confident they could identify a seizure (97.6%), give rectal diazepam (83.8%), and handle cluster seizures (67.1%), but fewer were confident they could give intranasal midazolam (63.3%), had specific information about a student’s seizures (56.6%), or could swipe a vagus nerve stimulator magnet (47.4%). Nurses were more likely to be available at the time of a seizure in rural (17/20) (85%) versus suburban (21/34) (62%) or urban (8/25) (32%) schools (P = .001). School nurses are comfortable managing seizures in the school setting. However, a specific seizure plan for each child and education on intranasal midazolam and vagus nerve stimulator magnet use are needed. A barrier in urban schools is decreased availability of a nurse to identify seizures and administer treatment.
The authors enrolled 95 patients in a primary care office who presented with a concussion. Of these patients, 63% were sport concussions. The authors matched 90 of these patients to children in the authors’ practice presenting for sports physicals or regular check-ups in the following demographics: age, participating in a particular sport, having attention-deficit disorder/attention-deficit hyperactivity disorder, gender, and grade. The authors found the odds of recurrent concussions, in a primary care pediatric office, to be a ratio of 2.909 (95% confidence interval 1.228-7.287). Recovery time for repeat concussion versus an initial concussion was analyzed. Patients with a recurrent concussion after a year recovered an average of 12.0 days after injury versus 13.4 days for those with no previous concussion (NS). Patients with a recurrent concussion within a year recovered a mean of 6.27 (SD 1.29) days sooner than patients with no previous concussion (P < .0001). This unexpected finding is preliminary, and the authors encourage further research.
The authors aimed to collect all brain magnetic resonance imaging (MRI) performed in critically ill children in the authors’ medical pediatric intensive care unit over a 2-year period (2012-2013) to (1) describe the findings and (2) assess its contribution on practical patient care.
This is a single-center and retrospective study. All children without traumatic brain injury who underwent a brain MRI during pediatric intensive care unit stays were included. To assess the exam’s contribution, the patient’s medical condition at the time of the MRI exam was blindly and separately exposed to a pediatric neurologist and a pediatric intensivist.
During the study period, 87 patients (7.5%) underwent a brain MRI. Median age was 4 months and 13 children (14.9%) died in pediatric intensive care unit. The most common final diagnosis was postanoxic encephalopathy. Brain MRI was abnormal in 68 patients (78.2%). No serious adverse event occurred during the transport. The neurologist and the intensivist considered brain MRI as indicated during pediatric intensive care unit stay in 65 (74.7%) and 68 patients (78.2%). They deemed that brain MRI had a diagnostic contribution in 76 (87.4%) and 60 (69.0%) patients, respectively. A therapeutic change consecutive to MRI findings occurred in 19 patients (21.8%) and MRI results were associated with a decision to withdraw life-sustaining treatment in 21 patients (24.1%).
Brain MRI is one component of neuromonitoring, and this study suggests a substantial diagnostic contribution, although its therapeutic impact appears limited to specific diagnoses.
The clinical expression of bilirubin-induced neurological dysfunction varies according to severity and location of the disease. Definitions have been proposed to describe different bilirubin-induced neurological dysfunction subtypes. Our objective was to describe the severity and clinico-radiological-neurophysiological correlation in 30 consecutive children with bilirubin-induced neurological dysfunction seen over a period of 5 years. Thirty children exposed to acute neonatal bilirubin encephalopathy were included in the study. The mean peak total serum bilirubin level was 625 μmol/L (range 480-900 μmol/L). Acoustic brainstem responses were abnormal in 73% (n = 22). Pallidal hyperintensity was observed on magnetic resonance imaging in 20 children. Peak total serum bilirubin levels correlated with motor severity (P = .03). Children with severe motor impairment were likely to manifest severe auditory neuropathy (P < .01). We found that in a resource-constrained setting, classical kernicterus was the most common bilirubin-induced neurological dysfunction subtype, and the majority of children had abnormal acoustic brainstem responses and magnetic resonance imaging.
There is a new emphasis on the team approach to pediatric concussion management, particularly in the classroom. However, it is expected that educators are unfamiliar with the "Returning to Learning" recommendations. The authors’ primary objective was to assess and improve high school educators’ knowledge regarding concussions and management interventions using an online education tool. A total of 247 high school educators completed a 12 question pretest to assess core knowledge of concussions and classroom management followed by a 20-minute online literature-based education module. Participants then completed an identical posttest. The improvement in core knowledge was statistically significant (P < .001). Initial areas of weakness were the description and identification of concussions. Questions regarding concussion classroom management also showed a statistically significant increase in scores (P < .001). This study identifies the deficits in the knowledge of educators regarding concussions and classroom management as well as the significant improvement after an online educational module.
Juvenile myasthenia gravis presents before 18 years of age with different characteristics according to racial background and pubertal development. The authors aimed to determine the clinical characteristics of children and adolescents of Korean ethnicity with myasthenia gravis, and evaluate the presentation and clinical outcomes according to the sex and onset age of the patients. The authors recruited 88 Korean juvenile myasthenia gravis patients between September 2005 and August 2015. Worse clinical severity from presentation, more aggressive treatment strategies, and worse final treatment outcomes were noted in girls with postpubertal onset than in the other patients. The symptoms were milder (pure ocular presentation in 96.6% [85/88]) and the disease course was more benign (94.3% [83/88]) in this study than in the literature. The homogenous racial background might have contributed to these results. These findings highlight the influence of pubertal development and the need for timely and appropriate active treatment, including thymectomy, to improve prognosis.
Immediate cognitive and physical rest in the concussed patient is almost universally recommended in the concussion literature. The authors conducted a prospective observational in a primary care pediatric office to examine the effect of delayed cognitive and physical rest had on recovery time in pediatric concussion. The authors found that patients who started cognitive and physical rest immediately after injury were more likely to recover within 30 days compared to patients who delayed cognitive and physical rest for 1-7 days after their injury (67% vs 35%, P = .016). Within the group of patients who recovered within 30 days those with immediate cognitive and physical rest recovered 4.6 days sooner than those with delayed cognitive and physical rest (10.29 ± 5.83 vs 14.42 ± 6.15 days, P = .005). These data support the recommendation that cognitive and physical rest should be implemented immediately after injury in concussed patients.
We aimed to decrease practice variation in treatment of neonatal status epilepticus by implementing a standardized protocol. Our primary goal was to achieve 80% adherence to the algorithm within 12 months. Secondary outcome measures included serum phenobarbital concentrations, number of patients progressing from seizures to status epilepticus, and length of hospital stay. Data collection occurred for 6 months prior and 12 months following protocol implementation. Adherence of 80% within 12 months was partially achieved in patients diagnosed in our hospital; in pretreated patients, adherence was not achieved. Maximum phenobarbital concentrations were decreased (56.8 vs 41.0 µg/mL), fewer patients progressed from seizures to status epilepticus (46% vs 36%), and hospital length of stay decreased by 9.7 days in survivors. In conclusion, standardized, protocol-driven treatment of neonatal status epilepticus improves consistency and short-term outcome.
Neurofibromatosis type 1 is a common neurogenetic disorder characterized by significant clinical variability. As such, numerous studies have focused on identifying clinical, radiographic, or molecular biomarkers that predict the occurrence or progression of specific clinical features in individuals with neurofibromatosis type 1. One of these clinical biomarkers, macrocephaly, has been proposed as a prognostic factor for optic pathway glioma development. In the current study, the authors demonstrate that macrocephaly is not associated with the development of these brain tumors or the need to institute treatment for clinical progression. These findings suggest that macrocephaly is not a robust biomarker of optic pathway glioma formation or progression in children with neurofibromatosis type 1.
Whole exome sequencing enables scanning a large number of genes for relatively low costs. The authors investigate its use for previously undiagnosed pediatric neurological patients. This retrospective cohort study performed whole exome sequencing on 57 patients of "Magen" neurogenetic clinics, with unknown diagnoses despite previous workup. The authors report on clinical features, causative genes, and treatment modifications and provide an analysis of whole exome sequencing utility per primary clinical feature. A causative gene was identified in 49.1% of patients, of which 17 had an autosomal dominant mutation, 9 autosomal recessive, and 2 X-linked. The highest rate of positive diagnosis was found for patients with developmental delay, ataxia, or suspected neuromuscular disease. Whole exome sequencing warranted a definitive change of treatment for 5 patients. Genetic databases were updated accordingly. In conclusion, whole exome sequencing is useful in obtaining a high detection rate for previously undiagnosed disorders. Use of this technique could affect diagnosis, treatment, and prognostics for both patients and relatives.
Pediatric tumefactive lesions remains challenging to clinicians in terms of diagnosis and treatment. The authors describe 11 children with biopsy-proven central nervous system tumefactive demyelination. The mean age of onset was 11 years. Clinical and radiological data coupled with biopsy aided in the diagnosis of tumefactive demyelination. Of the 6 cases in which oligoclonal band data were available, only 3 showed oligoclonal band in the cerebrospinal fluid. Due to poor recovery despite treatment with high-dose glucocorticosteroids, intravenous immunoglobulin, and/or plasmapheresis, 6 cases went on to receive cyclophosphamide with marked improvement. Long-term data were available on 9 cases. Eight of 9 cases were started on preventative multiple sclerosis therapy after initial presentation; 1 is pending discussion with family. Five of the 8 cases had clinical relapse during treatment. Seven cases met 2010 McDonald criteria for multiple sclerosis at follow-up, (1 developed secondary progressive multiple sclerosis), and 2 cases remained as clinically isolated syndrome on treatment.
The purpose of this study is to investigate the clinical, pathological, and prognostic characteristics of pediatric skull base meningiomas. A retrospective analysis of 44 pediatric skull base patients younger than 18 years who underwent surgery at Beijing Tiantan Hospital was performed. The study group included 20 males and 24 females. Multiple lesions were seen in 8 patients. WHO grade I was found in 28 patients and higher grade was seen in 16 patients. Recurrence or progression occurred in 10 patients after the initial operation. The overall survival rate in the follow-up period for the entire cohort was 89.7%. The authors found no sex predominance in pediatric skull base meningiomas. In addition, this lesion was more often seen in their second decades. In contrast to skull base meningiomas in adult patients, pediatric skull base meningiomas had a higher incidence of nonbenign histopathological variants and a higher rate of recurrence.
The epileptic encephalopathies are devastating conditions characterized by frequent seizures, severely abnormal electroencephalograms (EEGs), and cognitive slowing or regression. The cognitive impairment in the epileptic encephalopathies may be more concerning to the patient and parents than the epilepsy itself. There is increasing recognition that the cognitive comorbidity can be both chronic, primarily due to the underlying etiology of the epilepsy, and dynamic or evolving because of recurrent seizures, interictal spikes, and antiepileptic drugs. Much of scholars’ understanding of the neurophysiological underpinnings of cognitive dysfunction in the epileptic encephalopathies comes from rodent studies. Frequent seizures and interictal EEG discharges in rats lead to considerable spatial and social-cognitive deficits. Paralleling these cognitive deficits are dyscoordination of dynamic neural activity within and between the neural networks that subserve normal cognitive processes.
Anticipating potential therapies for Glut 1 deficiency syndrome (Glut1DS) emphasizes the need for effective clinical outcome measures. The 6-minute walk test is a well-established outcome measure that evaluates walking ability in neurological diseases. Twenty-one children with Glut 1 deficiency syndrome and 21 controls performed the 6-minute walk test. Fatigue was determined by comparing distance walked in the first and sixth minutes. Gait was analyzed by stride length, velocity, cadence, base of support, and percentage time in double support. Independent sample t-tests examined differences between group. Repeated-measures analysis of variance evaluated gait parameters over time. Glut 1 deficiency syndrome patients walked less (P < .05), had slower velocities (P < .0001), had shorter stride lengths (P < .0001), spent more time in double support (P < .001), and had increasing variability in base of support (P = .009). Glut 1 deficiency syndrome patients have impaired motor performance, walk more slowly, and have poor balance. The 6-minute walk test with gait analysis may serve as a useful outcome measure in clinical trials in Glut 1 deficiency syndrome.
There are indications that preexisting mitochondrial disorders or beta-oxidation defects predispose for propofol infusion syndrome. This review aimed at investigating if propofol infusion syndrome occurs exclusively in patients with mitochondrial disorder and if propofol can unmask a mitochondrial disorder. Propofol infusion syndrome has been reported in genetically confirmed mitochondrial disorder patients. In addition, muscle biopsy of patients with propofol infusion syndrome revealed complex IV or complex II deficiency. In animal studies propofol disrupted the electron flow along the respiratory chain and decreased complex I, complex II, and complex III of the respiratory chain. In addition, propofol disrupted the permeability transition pore and reduced the mitochondrial membrane potential. In conclusion, propofol is mitochondrion-toxic and mitochondrial disorder patients should not receive propofol in high dosages over a prolonged period of time. Short-term application of propofol should be safe even in mitochondrial disorder patients. Not only does propofol infusion syndrome occur in mitochondrial disorder patients, but mitochondrial disorder patients are likely at higher risk to develop propofol infusion syndrome. Patients who develop propofol infusion syndrome should be screened for mitochondrial disorder. Propofol infusion syndrome is preventable if risk factors are thoroughly assessed, and if long-term propofol is avoided in patients at risk for propofol infusion syndrome.
The objective was to identify unique features of the photoparoxysmal response seen in patients with neuronal ceroid lipofuscinosis type 2 as compared to patients with a photoparoxysmal response associated with other epilepsy syndromes.
Electroencephalograms from patients with neuronal ceroid lipofuscinosis type 2 seen at the authors’ institution in the past 10 years as well as electroencephalograms (EEGs) reported to have a photoparoxysmal response during a single year were reviewed.
A photoparoxysmal response was seen in 60% of the patients with neuronal ceroid lipofuscinosis type 2. This was most commonly seen with low frequency intermittent photic stimulation (76%) which often occurred in a time-locked fashion (63%) and was seen on the patient’s initial EEG (78%). A unique pattern the authors called "sentinel" discharge was identified in 30% of EEGs in patients with neuronal ceroid lipofuscinosis.
Photoparoxysmal responses in patients with neuronal ceroid lipofuscinosis type 2 have features which are distinguishing from photoparoxysmal responses seen in other epilepsies.
Many studies on Duchenne muscular dystrophy children support the hypothesis of a specific neuropsychological phenotype affecting mostly phonological skills. This prospective study aimed to shed light on the role of phonological abilities. Fourteen Duchenne muscular dystrophy children and 7 healthy children underwent mismatch negativity. Moreover, verbal intelligence, visuospatial attention, immediate verbal memory, working memory, grammar, vocabulary, visuomotor skills, reading, text comprehension, writing, and arithmetic were tested in Duchenne muscular dystrophy children. No significant difference between control and Duchenne muscular dystrophy children was found neither for mismatch negativity amplitude (P = .191 and .116, respectively) nor for latency (P = .135). Eight (57.14%) patients showed an impairment of immediate verbal memory and of visuomotor skills, 7 (63.64%) patients had a deficit in writing and arithmetic skills, even with a mean normal intelligence quotient. Taken together, the results put in evidence a heterogeneous neuropsychological profile not explainable on the basis of a phonological deficit.
Metachromatic leukodystrophy is accompanied by severe motor and cognitive dysfunction. This is the first survey of metachromatic leukodystrophy caregiver perspectives to identify relevant clinical/quality-of-life outcomes for patients/caregivers. Interviews and 1 focus group were conducted with 30 caregivers representing 23 patients. Caregivers were asked about their experiences, including diagnostic process, signs/symptoms, symptoms affecting caregivers’ and patients’ lives, and treatment priorities. Caregivers reported loss of physical autonomy, weight loss, limited social relationships, frequent crying, and challenging sibling relationships. Most troublesome symptoms were immobility (9/30) and respiratory difficulties (6/30). Health care visits were frequent: 8/22 patients had experienced ≥11 hospitalizations since diagnosis, and 14/22 caregivers reported that these lasted ≥4 days. Caregivers also experienced work problems, feelings of fear/sadness, and loss of social relationships. Caregivers/physicians consider a therapy that could improve decline in mobility, pain, cognitive ability, communication, or food intake as conferring the greatest benefit. In conclusion, a so-far-unreported physical/economic burden in these families is presented.
Hypoxic ischemic encephalopathy is the most frequent cause of neonatal encephalopathy and yields a great degree of morbidity and mortality. From an ethical and clinical standpoint, neurological prognosis is fundamental in the care of neonates with hypoxic ischemic encephalopathy. This qualitative study explores physician perspectives about neurological prognosis in neonatal hypoxic ischemic encephalopathy. This study aimed, through semistructured interviews with neonatologists and pediatric neurologists, to understand the practice of prognostication. Qualitative thematic content analysis was used for data analysis. The authors report 2 main findings: (1) neurological prognosis remains fundamental to quality-of-life predictions and considerations of best interest, and (2) magnetic resonance imaging is presented to parents with a greater degree of certainty than actually exists. Further research is needed to explore both the parental perspective and, prospectively, the impact of different clinical approaches and styles to prognostication for neonatal hypoxic ischemic encephalopathy.
Neurodevelopmental treatment is an advanced therapeutic approach for the neural rehabilitation of children with cerebral palsy. Cerebral palsy represents a spectrum of neurological disorders primarily affecting gross motor function. The authors investigated the effects of neurodevelopmental treatment on serum levels of transforming growth factor-β1 (TGF-β1), a neuroprotective cytokine, and improvements to motor skills. Serum TGF-β1 levels and total score of the Gross Motor Function Measure–88 (GMFM-88) were significantly higher in children with cerebral palsy who underwent neurodevelopmental treatment compared to untreated patients (P < .01). Furthermore, the improved GMFM-88 total scores after neurodevelopmental treatment were significantly higher in children under the age of 3 with cerebral palsy than in older patients (P < .01). The authors demonstrate that the integration of TGF-β1 levels and GMFM-88 total score could be used to assess the efficacy of neurodevelopmental treatment. Moreover, the findings provide further scientific support for the early intervention and neurological rehabilitation of young children with cerebral palsy.
The aim of this 1HMRS study was to identify hemispheric asymmetries in metabolismus in healthy children. The study group consisted of children of both sexes aged 6 to 15. Concentrations of 6 metabolites occurring in the brain were determined for 6 locations: hippocampus, frontal lobe, and basal ganglia in the left and right hemispheres. There were no hemispheric differences in the metabolites’ concentrations in the brain in children when the variable of sex was disregarded. Only in the group of boys and in the group of girls did the findings show few discrepancies. In none of these groups, relative concentrations to creatine concentration were found to be significantly different between hemispheres. In clinical practice, concentrations of specific metabolites are most frequently determined relative to the concentration of creatine. Consequently, the analysis of standard 1HMRS examinations in children does not need to take into account interhemispheric differences.
In a sample of children with traumatic brain injury, this magnetic resonance imaging (MRI)–based investigation examined whether presence of a focal lesion uniquely influenced cortical thickness in any brain region. Specifically, the study explored the relation of cortical thickness to injury severity as measured by Glasgow Coma Scale score and length of stay, along with presence of encephalomalacia, focal white matter lesions or presence of hemosiderin deposition as a marker of shear injury. For comparison, a group of children without head injury but with orthopedic injury of similar age and sex were also examined. Both traumatic brain injury and orthopedic injury children had normally reduced cortical thickness with age, assumed to reflect neuronal pruning. However, the reductions observed within the traumatic brain injury sample were similar to those in the orthopedic injury group, suggesting that in this sample traumatic brain injury, per se, did not uniquely alter cortical thickness in any brain region at the group level. Injury severity in terms of Glasgow Coma Scale or longer length of stay was associated with greater reductions in frontal and occipitoparietal cortical thickness. However, presence of focal lesions were not related to unique changes in cortical thickness despite having a prominent distribution of lesions within frontotemporal regions among children with traumatic brain injury. Because focal lesions were highly heterogeneous, their association with cortical thickness and development appeared to be idiosyncratic, and not associated with group level effects.
Understanding patterns of medical comorbidity in attention-deficit/hyperactivity disorder (ADHD) may lead to better treatment of affected individuals as well as aid in etiologic study of disease. This article provides the first systematic evaluation on the medical comorbidity of ADHD in a nationally representative sample (National Comorbidity Replication Survey–Adolescent Supplement; N = 6483) using formal diagnostic criteria. Survey-weighted odds ratios adjusted for demographics, additional medical, and mental disorders were calculated for associations between ADHD and medical conditions. Models adjusted for demographics revealed significantly increased odds of allergy, asthma, enuresis, headache/migraine, and serious stomach or bowel problems. After adjusting for comorbidity, across the medical conditions, enuresis and serious stomach problems were the strongest correlates of ADHD. These findings confirm the pervasive medical comorbidity of ADHD reported in previous clinical and community-based studies. The intriguing salience of enuresis and serious stomach or bowel conditions may also provide an important clue to multisystem involvement in ADHD.
In 2011, the American Academy of Neurology (AAN) released guidelines for return seizure visits detailing 8 points that should be addressed during such visits. These guidelines are designed to improve routine follow-up care for epilepsy patients. The authors performed a quality improvement project aimed at increasing compliance with these guidelines after educating providers about them. The authors performed a chart review before and after an intervention which included: education regarding the guidelines, providing materials to remind providers of the guidelines, and templates to facilitate compliance. The authors reviewed charts at 2 and 6 months after the intervention. Significant improvement in documentation of 4 of the 8 measures was observed after this educational intervention. This suggests that simple educational interventions may help providers change practice and can improve compliance with new guidelines while requiring minimal time and resources to implement.
The authors aimed to evaluate preoperative amplitude-integrated electroencephalography (aEEG) patterns for predicting neurodevelopmental outcome among infants undergoing major surgery in the neonatal period. They retrospectively reviewed the preoperative aEEG data of 58 neonates who had undergone major neonatal surgery between 2006 and 2008. The authors classified aEEGs using a weighted background score. Neurodevelopmental outcome was assessed at 3 years of age using the Bayley Scales of Toddler and Infant Development III. Over a third of infants (36%) showed an abnormal aEEG background. Seizure activity was identified in 11 (19%) infants. The majority (68%) of infants had developmental delay, with no significant differences between cardiac and other surgery groups. Logistic regression found no statistically significant but some clinically important associations between aEEG background and neurodevelopmental outcome. Comorbidity was associated with worse outcomes. While the predictive utility of aEEG in this population remains unclear, the findings suggest that further research is warranted.
The purpose was to examine whether children diagnosed with motor problems in the preschool period still exhibit motor problems at school age and the impact of these difficulties on participation.
The study group comprised 60 children 7-12 years old who were referred to occupational therapy 4-6 years prior to study initiation due to motor difficulties. The control group comprised 28 age-matched children with typical development. Parents completed the Participation, Developmental Coordination Disorder and Performance Skill Questionnaire 4-6 years after treatment.
Significant differences were found between children with and without motor difficulties in motor function, but not in any of the participation domains except for parental satisfaction. Children in the control group had significantly higher scores than children with motor difficulties in motor and process skills.
Motor difficulties persist into school years. Children with motor difficulties manifest performance skill problems, however they succeed in narrowing the gap and participate similar to their peers.
Pediatric convulsive status epilepticus with fever is common in the emergency setting but leads to severe neurological sequelae in some patients. To explore the epidemiology of convulsive status epilepticus with fever, a retrospective cohort covering all convulsive status epilepticus cases with fever seen in the emergency department of a tertiary care children’s hospital were consecutively collected. Of the 381 consecutive cases gathered, 81.6% were due to prolonged febrile seizure, 6.6% to encephalopathy/encephalitis, 0.8% to meningitis, and 7.6% to epilepsy. In addition, seizures were significantly longer in encephalopathy/encephalitis cases than in prolonged febrile seizure cases (log rank test, P < .001). These results provide for the first time the pretest probability of final diagnoses in children with convulsive status epilepticus with fever in the emergency setting, and will help optimize the management of pediatric patients presenting to the emergency department with convulsive status epilepticus with fever.
Color vision deficiency has been associated with educational difficulties among male children, as well as attention-deficit hyperactivity disorder (ADHD). We examined the association of color vision deficiency with functional conditions, including ADHD, irritable bowel syndrome, enuresis and somatoform disorders, in a large population of male adolescents. We included all Israeli male adolescents that underwent medical and cognitive examinations during conscription between the years 2007 and 2013. The prevalence of ADHD, irritable bowel syndrome, enuresis, and somatoform disorders among color vision deficiency patients was compared to a control group. The study included 305 964 males aging 17 ± 0.6, of which 7584 (2.5%) had color vision deficiency. Using a multivariable analysis, the probability for irritable bowel syndrome, enuresis, and somatoform disorders among color vision deficiency patients was increased by 1.41, 1.94, and 3.87, respectively (P < .05). No significant association was found between ADHD and color vision deficiency. Color vision abnormalities are associated with functional disorders in male adolescents, including irritable bowel syndrome, enuresis, and somatoform disorders.
Childhood encephalitis is a potentially devastating condition with significant morbidity and mortality. Researchers currently lack biomarkers for differentiating infectious encephalitis from those with autoimmune causes which may delay adequate treatment. The authors studied the possibility of using cerebrospinal fluid cytokine and chemokine levels for this purpose. Children admitted to hospital care fulfilling criteria for encephalitis were prospectively included. Children who underwent lumbar puncture but were not classified as central nervous system infections served as controls. Cytokine and chemokine levels in the cerebrospinal fluid obtained upon initial presentation were analyzed using Luminex technology. In children with infectious encephalitis (n = 13), the cerebrospinal fluid displayed markedly elevated mean levels of IL6, IL7, and IL13 as compared to N-methyl-D-aspartate receptor (NMDAR) encephalitis (n = 4) and controls (n = 13). The expression of IL6 appeared to precede that of IL13. Analysis of selected cerebrospinal fluid cytokines may thus allow differential diagnosis of infectious and NMDAR encephalitis already at the initial lumbar puncture and enable immediate therapy.
The objective was to investigate contribution of the dopamine receptor 5 (DRD5) gene variants in the symptoms of attention-deficit/hyperactivity disorder (ADHD) probands since brain regions identified to be affected in these group of patients have higher expression of the DRD5 receptor. Out of 22 exonic variants, 19 were monomorphic in the Indo-Caucasoid individuals. rs6283 "C" and rs113828117 "A" exhibited significant higher occurrence in families with ADHD probands. Several haplotypes showed biased occurrence in the probands. Early and late onset groups exhibited significantly different genotypic frequencies. A new G>A substitution was observed in the control samples only. The late onset group exhibited higher scores for hyperactivity as compared to the early onset group. The authors infer that the age of onset of ADHD may at least partially be affected by DRD5 variants warranting further investigation on the role of DRD5 in the disease etiology.
Glucose transporter type 1 deficiency syndrome is a genetically determined, treatable, neurologic disorder that is caused by an insufficient transport of glucose into the brain. It is caused by a mutation in the SCL2A1 gene, which is so far the only known to be associated with this condition. Glucose transporter type 1 deficiency syndrome consists of a wide clinical spectrum that usually presents with cognitive impairment, epilepsy, paroxysmal exercise-induced dyskinesia, acquired microcephaly, hemolytic anemia, gait disturbance, and dyspraxia in different combinations. However, there are other clinical manifestations that we consider equally peculiar but that have so far been poorly described in literature. In this review, supported by a video contribution, we will accurately describe this type of clinical manifestation such as oculogyric crises, weakness, paroxysmal kinesigenic and nonkinesigenic dyskinesia in order to provide an additional instrument for a correct, rapid diagnosis.
This study was conducted to assess the safety and efficacy of recombinant human erythropoietin in young children with cerebral palsy aged between 6 months and 3 years. All participants received subcutaneous recombinant human erythropoietin and 8 weeks of rehabilitation therapy. Adverse events, changes of vital signs, and hematologic tests were monitored up to 8 weeks postinjection. Functional measures of development at 4 and 8 weeks postinjection were compared with baseline values, and improvements were compared with those of an age-matched historical control group. Nine participants completed the trial from June 2012 to February 2015. No adverse events were related to recombinant human erythropoietin. Erythropoiesis was noted, although within normal range. Functional improvements were observed in all participants (P < .05) and increases in motor function were higher in recombinant human erythropoietin group than the control group. Accordingly, recombinant human erythropoietin administration was safe without any significant adverse events and improved the functional outcomes in young children with cerebral palsy.
Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder worldwide, but its etiology is still not fully understood. Previous studies have reported that perinatal hypoxic-ischemic conditions may be a potential cause of ADHD.
An online search of potential English studies published before September 2015 was conducted using the PsycINFO, EMBASE, Web of Science, and PubMed databases. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects models.
Ten studies were included, with 45 821 cases and 9 207 363 controls. The metaresults found that the following were associated with ADHD: preeclampsia (OR 1.31; 95% CI 1.26-1.37), an Apgar score <7 at 5 minutes (OR 1.31; 95% CI 1.12-1.54), breech/transverse presentations (OR 1.14; 95% CI 1.06-1.23), and a prolapsed/nuchal cord (OR 1.10; 95% CI 1.06-1.15).
Our results support that perinatal hypoxia-ischemia may contribute to ADHD. However, more clinical studies are warranted.
Drooling is a common problem in children with progressive dystonia. The authors noted a 58% incidence of drooling in 22/38 children with MEGDEL, a rare neurodegenerative cause of dystonia and report on the clinical course of four patients. Drooling of varying severity and subsequent respiratory problems were treated at the authors’ multidisciplinary saliva-control outpatient clinic. One patient improved on antireflux medication, the second after medication with drooling as side effect was changed. Two other patients underwent salivary gland surgery, one of whom significantly improved; the other died shortly after surgery. The heterogeneity of the cases presented shows the need for stepwise and personalized treatment. The authors recommend the following: (1) optimize the treatment of the underlying neurological condition and replace medication that stimulates saliva secretion; (2) treat constipation, scoliosis, and gastroesophageal reflux if there is still a risk of chronic aspiration of saliva; (3) perform more intense/invasive treatment (botulinum toxin, salivary gland surgery).
The aim of the study was to investigate clinical features of headache associated with minor versus moderate to severe traumatic brain injury and of posttraumatic versus primary headache in children and adolescents. Study group included 74 patients after mild (n = 60) or moderate to severe (n = 14) traumatic brain injury identified by retrospective review of the computerized files of a tertiary pediatric headache clinic. Forty patients (54%) had migraine-like headache, 23 (31.1%) tension-like headache, and 11 (14.9%) nonspecified headache. Fourteen patients (53.8%) had allodynia. In comparison with 174 control patients, the study group had a significantly lower proportion of patients with migraine-like headache and a higher proportion of male patients and patients with allodynia. There was no statistically significant correlation of any of the clinical parameters with the type or severity of the posttraumatic headache or rate of allodynia. The high rate of allodynia in the study group may indicate a central sensitization in posttraumatic headache.
The present study examined the natural history of fracture and vitamin D levels in Duchenne muscular dystrophy patients, who are vulnerable to osteoporosis and fractures. Retrospective analysis of a cohort of 48 Duchenne muscular dystrophy patients revealed that 43% of patients experienced ≥1 fracture. Fracture probabilities at ages 6, 9, 12, and 15 years were 4%, 9%, 31%, and 60% respectively, accelerating around the time of ambulation loss (mean age 11.8 ± 2.7 years). Chronic corticosteroid therapy was utilized in 69% of patients and was associated with all vertebral fractures. A history of vitamin D deficiency occurred in 84%, and 35% were currently deficient. Despite chronic vitamin D supplementation, 38% remained deficient. These results demonstrate that osteoporosis and fracture remain major concerns in Duchenne muscular dystrophy. Bone health should be optimized well before loss of ambulation, however current levels of vitamin D supplementation may be inadequate given high levels of deficiency.
Anti-N-methyl-
Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins.
Because of the lack of studies comparing the efficacy and safety of levetiracetam and valproate before the induction of general anesthesia in the treatment of convulsive refractory status epilepticus in children, we aimed to compare the effectiveness of these antiepileptic drugs in patients with convulsive status epilepticus admitted to the Pediatric Intensive Care Unit between 2011 and 2014. Forty-six (59%) of the 78 patients received levetiracetam, and 32 (41%) received valproate for the treatment of refractory status epilepticus. The response rate was not significantly different between the 2 groups. Although no adverse event was noted in patients who received levetiracetam, 4 (12.5%) patients in the valproate group experienced liver dysfunction (P = .025). According to our results, levetiracetam and valproate may be used in the treatment of refractory status epilepticus before the induction of general anesthesia. Levetiracetam appears as effective as valproate, and also safer.
The study assessed the 5-year follow-up outcome and possible prognostic factors of migraine subtypes with onset in childhood or adolescence. A total of 343 patients meeting the International Classification of Headache Disorders (ICHD)-II criteria for migraine without aura (MO), migraine with aura (MA), or both MO+MA (ie, 1.1, 1.2) were contacted by phone and underwent structured follow-up headache interviews. Of the original sample patients, 22.7% were headache-free at follow-up, 14.1% had a transformed headache diagnosis (tension-type headache: 8.2%, chronic daily headache: 5.8%), and 63.3% still had migraine fulfilling the criteria for ICHD-II 1.1. or 1.2, but those who were still migraineurs at follow-up were older at baseline (respectively 12.93, 9.99, and 11.02 years for MO, MA and MO+MA, P = .0005). The probability of having the same migraine subtype diagnosis at baseline and at 5-year follow-up was 55.2%, 95.1%, and 31.1% for ICHD-II 1.1, 1.2, and both 1.1 and 1.2, respectively.
Diffuse intrinsic pontine glioma is the most common brainstem tumor in pediatric patients. This tumor remains one of the most deadly pediatric brain tumors. The diagnosis primarily relies on clinical symptoms and imaging findings. Conventional MRI provides a noninvasive accurate method of diagnosis of these tumors. Advanced MRI techniques are becoming more widely used and studied as additional noninvasive methods to assist clinicians in initial diagnosis and staging, monitoring disease, as well as in surgical and radiation planning. This article will provide an overview of DIPG and describe the typical imaging findings with a focus on advanced imaging techniques.
This study aimed to determine the impact of multiple doses of whole-body vibration on heel strike, spatial and temporal gait parameters, and ankle range of motion of children with idiopathic toe walking. Whole-body vibration was applied for 5 sets of 1 minute vibration/1 minute rest. Gait measures were collected pre intervention, 1, 5, 10, and 20 minutes postintervention with the GaitRite® electronic walkway. Ankle range of motion was measured preintervention, immediately postintervention, and 20 minutes postintervention. The mean (SD) age of the 15 children (n = 10 males) was 5.93 (1.83) years. An immediate increase in heel contact (P = .041) and ankle range of motion (P = .001 and P = .016) was observed. These changes were unsustained 20 minutes postvibration (P > .05). The gait improvement from whole-body vibration could potentially be due to a rapid increase in ankle range of motion or a neuromodulation response.
Friedreich ataxia is a progressive degenerative disease with neurologic and cardiac involvement. This study characterizes comorbid medical conditions in a large cohort of patients with Friedreich ataxia. Patient diagnoses were collected in a large natural history study of 641 subjects. Prevalence of diagnoses in the cohort with Friedreich ataxia was compared with prevalence in the population without Friedreich ataxia. Ten patients (1.6%) had inflammatory bowel disease, 3.5 times more common in this cohort of individuals with Friedreich ataxia than in the general population. Four subjects were growth hormone deficient, reflecting a prevalence in Friedreich ataxia that is 28 times greater than the general population. The present study identifies specific diagnoses not traditionally associated with Friedreich ataxia that are found at higher frequency in this disease. These associations could represent coincidence, shared genetic background, or potentially interactive disease mechanisms with Friedreich ataxia.
We categorized the causes of acute ataxia in the pediatric population—referred to the Division of Neurology—at a large, urban pediatric medical center. Of the 120 cases identified over the past 11 years, post-infectious cerebellar ataxia was the most commonly diagnosed (59%), followed by drug intoxication, opsoclonus-myoclonus ataxia syndrome, episodic ataxia, acute cerebellitis, cerebellar stroke, ADEM, meningitis, cerebral vein thrombosis, Leigh’s disease, Miller-Fisher syndrome, and concussion. Among the patients with post-infectious cerebellar ataxia, 85% were 1–6 years old and all had a history of antecedent viral illness. CSF pleocytosis was present in 40% of patients; all had normal brain MRIs. The majority (91%) recovered within 30 days. We conclude that post-infectious cerebellar ataxia remains the most common cause of acute ataxia in childhood and that it carries a good prognosis. We also differentiate acute post-infectious cerebellar ataxia from other causes with similar presentations.
This study sought to evaluate the radiological and clinical spectrum of posterior reversible encephalopathy syndrome (PRES) in pediatric population. A retrospective evaluation of the pediatric patients with posterior reversible encephalopathy syndrome seen over the last 5 years in the authors’ hospital was done. The magnetic resonance imaging (MRI) findings were analyzed, and a review of literature was performed. Out of 32 pediatric patients of posterior reversible encephalopathy syndrome, 10 (31.25%) were males and 22 (68.75%) were females, with a mean age of 10.6 years. Renal disease (62.5%) was the most common primary disease, followed by chemotherapy for hemato-oncologic malignancies (15.6%). Hypertension was present in 81.2% of cases. Atypical MRI findings were seen in 62.5% cases. Frontal involvement was common and seen in 56% of the cases. Overall, MRI findings considered atypical in adults were found to be common in the series of pediatric posterior reversible encephalopathy syndrome. The understanding of the clinical settings and familiarity with radiological findings in pediatric posterior reversible encephalopathy syndrome patients is important to adequately treat these patients and to avoid misdiagnosis.
ADCY5 mutations have been reported as a cause of early onset hyperkinetic movements associated with delayed motor milestones, hypotonia, and exacerbation during sleep. The movement disorder may be continuous or episodic, and can vary considerably in severity within families and in individuals. The authors report a case series of 3 patients with ADCY5 mutations treated with deep brain stimulation after unsuccessful medication trials. All had extensive imaging, metabolic, and genetic testing prior to confirmation of their ADCY5 mutation. Two of the patients had the c.1252C>T; p.R418W mutation, while the youngest and most severely affected had a de novo c.2080_2088del; p.K694_M696 mutation. All had variable and incomplete, but positive responses to deep brain stimulation. The authors conclude that deep brain stimulation may provide benefit in ADCY5-related movement disorders. Long-term efficacy remains to be confirmed by longitudinal observation. ADCY5 should be considered in the differential diagnosis of early onset hyperkinetic movement disorders, and may respond to deep brain stimulation.
It is well known that iodine plays an important role in the process of early growth and development of most organs, especially the brain. However, iodine concentration in the colostrum and its association with the neurobehavioral development of infants remains unclear. Colostrums from 150 women were collected, and their iodine concentrations were measured. The median colostrum iodine level was 187.8 μg/L. The Bayley Scales of Infant and Toddler Development–III test was performed when the infants were about 18 months. The mean cognitive, language, and motor composite scores were 105.3 ± 9.8, 105.2 ± 11.1, and 104.6 ± 6.7, respectively. And the mean scores of the 5 subtests were 11.1 ± 2.0, 9.3 ± 2.0, 12.4 ± 2.3, 11.1 ± 1.2, and 10.4 ± 1.2, respectively. No statistically significant difference was observed in the cognition, language, or motor development of infants across different levels of colostrum iodine. After adjusting for a range of confounding factors, colostrum iodine concentration was a predictor of motor development, specifically gross motor development.
Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of disorders characterized by lower extremity spasticity and weakness. Recently, the first de novo mutations in KIF1A were identified in patients with an early-onset severe form of complicated hereditary spastic paraplegia. We report two additional patients with novel de novo mutations in KIF1A, hereby expanding the genetic spectrum of KIF1A-related hereditary spastic paraplegia. Both children presented with spastic paraplegia and additional findings of optic nerve atrophy, structural brain abnormalities, peripheral neuropathy, cognitive/language impairment, and never achieved ambulation. In particular, we highlight the progressive nature of cerebellar involvement as captured on sequential magnetic resonance images (MRIs), thus linking the neurodegenerative and spastic paraplegia phenotypes. Exome sequencing in patient 1 and patient 2 identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q) and c.595G>A (p.G199 R), respectively. Therefore, our report contributes to expanding the genotypic and phenotypic spectrum of hereditary spastic paraplegia caused by mutations in KIF1A.
Friedreich ataxia is an inherited disorder characterized by degeneration of the peripheral and central nervous system and hypertrophic cardiomyopathy. Homozygous mutations in the frataxine (FXN) gene reduce expression of frataxin and cause accumulation of iron in the mitochondria. Deferiprone, an oral iron chelator, has been shown effective in cell and animal models of Friedreich ataxia. The results of a 6-month randomized, double blind placebo-controlled study suggested that deferiprone 20 mg/kg/day may reduce disease progression. The authors present their experience of 5 Friedreich ataxia patients treated with deferiprone (20 mg/kg/day), in addition to idebenone treatment, followed over a period of 10-24 months, under off-label authorization. The patients were monitored for laboratory parameters, cardiac assessment, neurological evaluations, and quality of life. The authors conclude that combined therapy of a low dose of deferiprone with idebenone is relatively safe, might improve neurological function, and seems to improve heart hypertrophy, warranting further studies.
Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis.
Midazolam, lorazepam, and diazepam were recommended as emergent initial therapy for status epilepticus. However, there are no current studies to confirm the best agent for pediatric status epilepticus. We compared the efficacy of midazolam, lorazepam, and diazepam in treating pediatric status epilepticus using a network meta-analysis method. In total, 16 randomized controlled trials containing 1821 patients were included. Nonintravenous midazolam, intravenous lorazepam, and intravenous diazepam were more successful in achieving seizure cessation when compared with nonintravenous diazepam (odds ratio = 2.23, 95% credibility interval: 1.62, 3.10; odds ratio = 2.71, 95% credibility interval: 1.25, 5.89; odds ratio = 2.65, 95% credibility interval: 1.12, 6.29; respectively). Among lorazepam, midazolam, and diazepam, midazolam had the highest probability (surface under the cumulative ranking area [SUCRA] = 0.792) of achieving seizure cessation, and lorazepam had the largest probability (surface under the cumulative ranking area = 0.4346) of being the best treatment in reduction of respiratory depression. In conclusion, nonintravenous midazolam and intravenous lorazepam were superior to intravenous or nonintravenous diazepam, and intravenous lorazepam was at least as effective as nonintravenous midazolam in treating pediatric status epilepticus.
Sailing might produce a positive effect on a patient’s general health and become an integrated part of rehabilitation. Our hypothesis was that a specific technological rehabilitation program might be used to prepare a group of disabled subjects for sailing. Seventeen patients (age range: 9-20) with impairments in motor coordination and balance and 15 healthy subjects participated in the study. The study was divided into the virtual-technological sailing phase, theory-practice phase, and sports phase. Proprioceptive platforms were used to evaluate balance, and the Child Health Questionnaire–PF50 was used to evaluate quality of life. Trunk displacement and the center of pressure velocity improved significantly after the virtual-technological sailing program. As regards quality of life, the physical and psychosocial score significantly improved at the end of the program. A technological rehabilitation training improved balance in disabled subjects and may be used to prepare them for a real sailing course. Sailing improves the quality of life of disabled subjects and could be used in the rehabilitation.
Opsoclonus-myoclonus syndrome is a rare but serious neurological condition resulting in loss of control of eye movements, often accompanied by difficulties in posture and movement control with reports of sensory sensitivities potentially impacting on behavior. This pilot study characterizes the presence of atypical sensory behaviors in opsoclonus-myoclonus syndrome through questionnaire survey of a cohort of families. The Short Sensory Profile, Vineland Adaptive Behavior Scale, and Developmental Behaviour Checklist were distributed to 30 families; 16 were returned anonymously. Atypical sensory behaviors were identified in a large proportion (62.5%). Children reported as being more anxious showed greater sensitivity to auditory stimuli, U(14) 11, P = .026. This is consistent with recent recognition of more extensive disease neurocognitive effects in Opsoclonus-myoclonus syndrome. Further research is needed to increase understanding of the complex pathology of this disease and to provide indicators for sensory and behavioral as well as pharmacological interventions.
Prevalence of autism spectrum disorders has increased over recent years, however, little is known about the identification and management of autism spectrum disorder in Africa. This report summarizes a workshop on autism spectrum disorder in Africa under the auspices of the International Child Neurology Association and the African Child Neurology Association through guided presentations and working group reports, focusing on identification, diagnosis, management, and community support. A total of 47 delegates participated from 14 African countries. Although there was a huge variability in services across the countries represented, numbers of specialists assessing and managing autism spectrum disorder was small relative to populations served. Strategies were proposed to improve identification, diagnosis, management and support delivery for individuals with autism spectrum disorder across Africa in these culturally diverse, low-resource settings. Emphasis on raising public awareness through community engagement and improving access to information and training in autism spectrum disorder. Special considerations for the cultural, linguistic, and socioeconomic factors within Africa are discussed.
The emotional and behavioral problems associated with pediatric multiple sclerosis remain unclear. Participants with pediatric multiple sclerosis or clinically isolated syndrome (n = 140; ages 5-18 years) completed self- and parent ratings using the Behavioral Assessment System for Children, Second Edition, neurologic exam, the Fatigue Severity Scale, and neuropsychological assessment. Mean self- and parent-ratings on the Behavioral Assessment System for Children, Second Edition, were in the typical range across all scales. However, 33.1% indicated a clinically significant problem on a least 1 scale. Although the type of clinical problems varied across participants, attention problems, somatization, and anxiety were found to be most common. Disease features including duration, age of onset, neurologic disability, and fatigue did not distinguish those with and without clinical problems. However, cognitive functioning significantly predicted the presence of a clinical problem (P = .02). Pediatric multiple sclerosis is associated with a range of nonspecific emotional and behavioral clinical problems, occurring more frequently in those patients with cognitive involvement.
The outcome for patients attempting dietary therapy for epilepsy a second time is unknown. Twenty-six subjects treated with the ketogenic diet as children who then began either the ketogenic diet or a Modified Atkins Diet (MAD) at least 6 months later were evaluated. The mean age at the first diet trial was 5.6 years and at the second diet trial was 11.5 years. Most restarted dietary therapy because of persistent seizures (65%) or recurrence after seizure freedom (19%). Overall, 77% had a ≥50% seizure reduction with the first diet, and 50% with the second diet, P = .04. Individual subject responses were largely similar, with 14 (54%) having identical seizure reduction both times, 9 worse (35%) with the second attempt, and 3 (16%) improved. The second diet trial was more likely to lead to >50% seizure reduction if the first trial was started at a later age (7.4 vs 3.9 years, P = .04).
Acute cerebellitis is a rare inflammatory condition. It may have a benign, self-limiting course or present as a fulminant disease resulting in severe cerebellar damage or even sudden death. We present the clinical, laboratory, and radiologic data in 9 children diagnosed with acute cerebellitis, who were identified by database search in our pediatric medical center from January 2000 to November 2014. The main presenting symptom was headache, and the main presenting sign was ataxia. Bilateral diffuse hemispheric involvement was the most common imaging finding at presentation. Mycoplasma pneumoniae was the most common infectious pathogen found. Treatment included steroids in all cases, antibiotics in 4, and intravenous immunoglobulins in 6. Six patients had a full recovery, and 3 had residual neurologic complications. Magnetic resonance imaging (MRI) is the modality of choice for diagnosis. The course of acute cerebellitis varies from a commonly benign and self-limiting disease to an occasionally fulminant disease, resulting in severe cerebellar damage or sudden death.
Children with myelomeningocele have a high prevalence of obesity and excess fat accumulation in their lower extremities. However, it is not known if this is subcutaneous or intramuscular fat, the latter of which has been associated with insulin resistance and metabolic disorders. This study quantified lower leg bone, muscle, and adipose tissue volume in children with myelomeningocele, classifying adipose as subcutaneous or muscle-associated. Eighty-eight children with myelomeningocele and 113 children without myelomeningocele underwent lower leg computed tomographic scans. Subcutaneous and muscle-associated adipose were classified based on location relative to the crural fascia. No differences were seen in subcutaneous adipose. Higher level disease severity was associated with increased muscle-associated adipose volume and decreased muscle volume. Bone volume tended to decrease with higher levels of involvement. Increases in lower leg adiposity in children with myelomeningocele are primarily attributable to accumulation of muscle-associated adipose, which may signify increased risk for metabolic disorders.
A national multicenter study identified 17 South African children with vertically acquired HIV-1 infection and HIV-associated vasculopathy. Five of the children (all indigenous African ancestry) had progressive vascular disease, consistent with moyamoya syndrome. Median presentation age 5.8 years (range 2.2-11). The children with moyamoya syndrome presented with abnormal CD4 counts and raised viral loads. Clinical features included motor deficits, neuroregression, and intellectual disability. Neuroimaging supported progressive vascular disease with preceding clinically silent disease course. Neurologic recovery occurred in 1 patient with improved CD4 counts. Four of the 5 children presented during the era when access to antiretroviral therapy was limited, suggesting that with improved management of HIV-1, progressive vasculopathy is less prevalent. However the insidious disease course illustrated indicates that the syndrome can progress "silently," and manifest with misleading phenotypes such as cognitive delay or regression. Sub-Saharan Africa has limited access to neuroimaging and affected children may be underdiagnosed.
The authors aimed to find evidence for a central component of the impairment of movement of the affected arm in children with obstetric brachial plexus palsy. The authors performed a cross-sectional study in 19 children (median age 5 years) with obstetric brachial plexus palsy who were able to voluntarily abduct their affected arm beyond 90 degrees. They were asked to perform 4 tasks designed to provoke automatic arm movements to maintain balance. The authors assumed automatic motor programming to be impaired when 2 of 3 investigators agreed using video recordings that the affected arm did not abduct beyond 90 degrees while the unaffected arm did. Children abducted the affected arm less often than the healthy one (generalized binary logistic model of all 4 tasks, P = .001). The deficit during automatic arm abduction was not observed during voluntary movements and therefore cannot be explained by a peripheral deficit, suggesting a central component.
Benign paroxysmal torticollis of infancy is an unusual movement disorder, often accompanied by a family history of migraine. Some benign paroxysmal torticollis cases are associated with CACNA1A mutations. The authors sought to determine the frequency of CACNA1A mutations in benign paroxysmal torticollis by testing 8 children and their parents and by searching the literature for benign paroxysmal torticollis cases with accompanying CACNA1A mutations or other disorders linked to the same gene. In our 8 benign paroxysmal torticollis cases, the authors found 3 different polymorphisms, but no pathogenic mutations. By contrast, in the literature, the authors found 4 benign paroxysmal torticollis cases with CACNA1A mutations, 3 with accompanying family histories of 1 or more of familial hemiplegic migraine, episodic ataxia, and paroxysmal tonic upgaze. Thus, CACNA1A mutations are more likely to be found in children with benign paroxysmal torticollis if accompanied by family histories of familial hemiplegic migraine, episodic ataxia, or paroxysmal tonic upgaze.
The purpose of this study was to evaluate the feasibility of a 35-week exercise program and its efficacy on neurocognitive and psychological variables in children with benign epilepsy with centrotemporal spikes. Ten children with benign epilepsy with centrotemporal spikes (aged 8 to 12 years) completed a 35-week exercise program consisting of supervised sport activities for 5 weeks and home-based exercise program for 30 weeks. The children and their parents participated in neurocognitive and psychological evaluations including measures of attention, executive function, behaviors, and quality of life at baseline and postexercise follow-up at the 35th week. At postintervention evaluation, significant improvements were seen relative to baseline in neurocognitive domains such as psychomotor speed, sustained attention, divided attention, and inhibition-disinhibition ability, and in psychological domains including internalizing behavior problems, general health, and general quality of life. Long-term exercise intervention may have benefits for some aspects of neurocognitive and psychological function in children with benign epilepsy.
Concussion is a known risk in youth soccer, but little is known about subconcussive head impacts. The authors provided a prospective cohort study measuring frequency and magnitude of subconcussive head impacts using accelerometry in a middle school–age soccer tournament, and association between head impacts and changes in (1) symptoms, (2) cognitive testing, and (3) advanced neuroimaging. A total of 17 youth completed the study (41% female, mean 12.6 years). There were 73 head impacts >15g measured (45% headers) and only 2 had a maximum peak linear acceleration >50g. No youth reported symptoms consistent with concussion. After correction for multiple comparisons and a sensitivity analysis excluding clear outliers, no significant associations were found between head impact exposure and neuropsychological testing or advanced neuroimaging. The authors conclude that head impacts were relatively uncommon and low in acceleration in youth playing a weekend soccer tournament. This study adds to the limited data regarding head impacts in youth soccer.
This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment.
This study aimed to investigate the functional and developmental outcomes in school age children diagnosed with global developmental delay before 2 years old and to verify the association between their final diagnosis and environmental and biological factors. Forty-five Brazilian children (26 boys), mean age 95.84 (7.72) months, who attended regular school and were diagnosed with global developmental delay before they were 2 years old had their functions evaluated. Children with global developmental delay were diagnosed with several conditions at school age. Students with greater chances of receiving a diagnosis were those whose mothers were younger at the time their children were born (OR = 1.47, CI = 1.04-2.09, P = .03), who had impaired motor performance, specially balance (OR = 1.33, CI = 1.01-1.75, P = .04), and who needed help during cognitive and behavioral tasks at school (OR = 1.08, CI = 1.00-1.17, P = .048). Interdisciplinary evaluation contributed to defining the specific diagnosis and to identifying the necessity of specialized support.
The purpose of this study was to characterize children with Down syndrome and attention-deficit hyperactivity disorder (ADHD) with disruptive behaviors using the Aberrant Behavior Checklist (ABC), and to measure the treatment effects of guanfacine on maladaptive behaviors. Subjects were enrolled from a group of outpatients who visited our clinic between 2002 and 2007. Subjects (N = 23) were children with Down syndrome ages 4 to 12 years (mean 7.4 ± 4.1), who met criteria for ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Aberrant Behavior Checklist Irritability and Hyperactivity subscales each showed a significant decrease (P < .0001) at follow-up. The mean decline on Hyperactivity was 25% (–7.8 points), and for Irritability, 25% (–3.5 points). The mean composite score also declined by 24% (–12 points). Effect size differences on Irritability were moderate, whereas differences on Hyperactivity and composite score appeared large. Clinically important target behaviors were reduced. Medication was generally well tolerated and the incidence of treatment emergent side effects remained low.
As part of the special issue on Pediatric Neuro-Oncology, this article will focus on 4 of the rarer tumors in this spectrum, including atypical teratoid rhabdoid tumors, embryonal tumors with multilayered rosettes, choroid plexus tumors, and pleomorphic xanthoastrocytoma. Incidence and current understanding of the molecular pathogenesis of these tumors are discussed, and avenues of therapy both current and prospective are explored.
Neurologists are often consulted for diagnosis and management of neurologic complications in patients undergoing therapy for cancer. Pediatric patients with cancer, often undergoing the same types of therapy as adults with cancer, may experience different adverse events. The set of neurologic complications in children differs from that in adults and the neurologist must take into account the continuing growth and development of the patient as well as significant differences in primary diagnosis across the population. Correctly recognizing complications and initiating prompt treatment may reduce pain and prevent further progression and permanent deficits. Herein, we review the most recent literature on the neurological complications of cancer therapy organized by frequency in the pediatric population.
The various childhood suprasellar tumors, while pathologically distinct, present similar clinical and surgical challenges as a result of their common anatomic location. These lesions are in close proximity to or may invade the optic nerve and chiasm, pituitary gland and infundibulum, hypothalamus, and third ventricle, leading to presenting features including visual field loss, impairment in visual acuity, endocrine dysfunction, and hydrocephalus. Though many suprasellar lesions are relatively benign in pathology, treatment may be complicated by high surgical morbidity resulting from damage to the hypothalamic-pituitary axis. Here we review the most frequent pediatric lesions occurring in the suprasellar region: craniopharyngioma, chiasmatic glioma, germ cell tumor, Rathke cleft and arachnoid cysts, pituitary adenoma, and histiocytosis. This review outlines both common presenting features and differentiating aspects of these lesions. It also includes classic radiographic presentations and treatment considerations for each lesion.
Over the past 150 years since Virchow’s initial characterization of ependymoma, incredible efforts have been made in the classification of these tumors and in the care of pediatric patients with this disease. While the advent of modern neurosurgery and the optimization of radiation have provided significant gains, a more complex but incomplete picture of pediatric ependymomas has begun to form through a combination of international collaborations and detailed genetic and histologic characterizations. This review includes and synthesizes the clinical understanding of pediatric ependymoma and their developing molecular insight into what is truly a family of malignancies in which distinct members require different surgical approaches, radiation plans, and targeted therapies.
The etiology of most childhood cancer remains largely unknown, but is likely attributable to random or induced genetic aberrations in somatic tissue. However, a subset of children develops cancer in the setting of an underlying inheritable condition involving a germline genetic mutation or chromosomal aberration. The term "neurocutaneous syndrome" encompasses a group of multisystem, hereditary disorders that are associated with skin manifestations as well as central and/or peripheral nervous system lesions of variable severity. This review outlines the central nervous system tumors associated with underlying neurocutaneous disorders, including neurofibromatosis type 1, neurofibromatosis type 2, schwannomatosis, tuberous sclerosis complex, Von Hippel Lindau, and nevoid basal cell carcinoma syndrome. Recognizing the presence of an underlying syndrome is critically important to both optimizing clinical care and treatment as well as genetic counseling and monitoring of these affected patients and their families.
Diffuse intrinsic pontine glioma is a lethal brain cancer that arises in the pons of children. The median survival for children with diffuse intrinsic pontine glioma is less than 1 year from diagnosis, and no improvement in survival has been realized in more than 30 years. Currently, the standard of care for diffuse intrinsic pontine glioma is focal radiation therapy, which provides only temporary relief. Recent genomic analysis of tumors from biopsies and autopsies, have resulted in the discovery of K27M H3.3/H3.1 mutations in 80% and ACVR1 mutations in 25% of diffuse intrinsic pontine gliomas, providing renewed hope for future success in identifying effective therapies. In addition, as stereotactic tumor biopsies at diagnosis at specialized centers have been demonstrated to be safe, biopsies have now been incorporated into several prospective clinical trials. This article summarizes the epidemiology, clinical presentation, diagnosis, prognosis, molecular genetics, current treatment, and future therapeutic directions for diffuse intrinsic pontine glioma.
Pediatric brain tumors are the leading cause of cancer-related death during childhood. Since the first pediatric brain tumor clinical trials, the field has seen improved outcomes in some, but not all tumor types. In the past few decades, a number of promising new therapeutic agents have emerged, yet only a few of these agents have been incorporated into clinical trials for pediatric brain tumors. In this review, the authors discuss the process of and challenges in pediatric clinical trial design; this will allow for highly efficient and effective clinical trials with appropriate endpoints to ensure rapid and safe investigation of novel therapeutics for children with brain tumors.
The aim of the study was to estimate quality of life and determine the adjusted association of migraine with the quality of life in a sample of students. This population-based study was performed among 857 high school students in Boukan City (with a Kurdish language–speaking population, about 600 km west of the city of Tehran, Iran). The World Health Organization Quality of Life questionnaire was used along with International Headache Society criteria. Multiple linear regression models were applied. The mean scores of quality of life domains of physical health, psychological, environmental, and social relationships were 69.1 (standard deviation = 16.5), 61.5 (standard deviation = 18. 1), 66.3 (standard deviation = 20. 8), and 65.2 (standard deviation = 17. 8) out of 100, respectively. Migraine after adjusting for the other factors was associated significantly with the scores in the physical (P = .002), social (P = .002), and environmental (P = .033) domains. Migraine is associated with reducing the physical, environmental, and social aspects of the students’ quality of life.
Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder, with onset in the first or second year of life. Mutations in the PLA2G6 gene encoding iPLA2-VI, a calcium-independent phospholipase, have been identified in these children. In classic infantile neuroaxonal dystrophy–affected children, psychomotor regression is the most frequent presentation, usually with ataxia and optic atrophy, followed by the development of tetraparesis. We report a child carrying a homozygous mutation in the PLA2G6 gene with neonatal onset of disease and somewhat different clinical phenotype such as severe congenital hypotonia, marked weakness, and bulbar signs suggesting that infantile neuroaxonal dystrophy can start at birth with atypical phenotype.
The ability to assess the quality of life of children with cerebral palsy to inform and evaluate individual care plans, service planning, interventions, and policies is crucial. In this article, the recent evidence on quality of life in children with cerebral palsy is reviewed, with attention to the determinants of quality of life and role of this construct as a practical outcome indicator in clinical trials. Quality of life measurement advances for children with cerebral palsy are discussed with a focus on condition-specific quality of life measures, particularly, the Cerebral Palsy Quality of Life–Child, which is the first condition-specific quality of life measure for children with cerebral palsy. The article presents an overview for clinicians and researchers intending to use quality of life measures on children with cerebral palsy and provides recommendations for future research that will better inform practice in the field.
The spectrum of neurodevelopmental disabilities was studied in a cohort of patients in Hungary. A search for etiologies and assessment of the degree of intellectual disability were carried out. The study included 241 (131 boys) patients. Disability occurred without any prenatal, perinatal, and/or neonatal adverse events in 167 patients. They were classified into the following subgroups: genetic syndromes with recognized etiology, global developmental delay/intellectual disability in association with dysmorphic features but unknown etiology, global developmental delay/intellectual disability without dysmorphic features and recognized etiology, brain malformations, inborn errors of metabolism, leukoencephalopathies, epileptic syndromes, developmental language impairment, and neuromuscular disorders. Adverse events occurred in 74 children classified into subgroups such as cerebral palsy after delivery preterm or at term, and disabilities without cerebral palsy. The etiology was identified in 66.4%, and genetic diagnosis was found in 19.5%. Classification of neurodevelopmental disorders contribute to etiological diagnosis, proper rehabilitation, and genetic counseling.
Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007 to 2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments led to >50% further seizure reduction in 18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs 15%, P = .08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit).
Prader-Willi syndrome is a common and complex disorder affecting multiple systems. Its main manifestations are infantile hypotonia with a poor sucking reflex, a characteristic facial appearance, mild mental retardation, hypogonadism and early-onset obesity. Prader-Willi syndrome is due to the absence of paternally expressed imprinted genes at 15q11.2-13, and 3 main mechanisms are known to be involved in its pathogenesis: paternal microdeletions, maternal uniparental disomy events, and imprinting defects. DNA methylation analysis can detect almost all individuals with Prader-Willi syndrome but is unable to distinguish between the molecular classes of the disease. Thus, additional methods are necessary to identify the molecular classes. Here, we employed chromosomal microarray analysis–single nucleotide polymorphism for diagnosis and detected a long-contiguous stretch of homozygosity on chromosome 15, which is highly predictive of maternal uniparental disomy on chromosome 15. Other methods, including fluorescence in situ hybridization, chromosomal microarray analysis–comparative genomic hybridization, genotyping and family linkage analysis, were performed for further validation. In conclusion, our study highlights the use of long-contiguous stretch of homozygosity detection for the diagnosis of Prader-Willi syndrome.
Various micronutrients are essential for optimal functioning of the peripheral nervous system. Serum vitamin E, vitamin B12, and folic acid were estimated in childhood acute lymphoblastic leukemia survivors aged between 5 and 18 years in first continuous remission within 3 years of completion of vincristine-based chemotherapy with and without electrophysiologically defined neuropathy. A total of 80 children were studied. Neuropathy was seen in 27 (33.75%) children electrophysiologically. None of the children had vitamin E deficiency. However, the alpha tocopherol/(cholesterol + triglyceride) ratio was significantly lower in children with neuropathy (P = .05). The prevalence of folate (P = .48) and vitamin B12 (P = .21) deficiency in children with and without neuropathy was not significantly different. Thus, the prevalence of deficiencies of these micronutrients was not significantly different in childhood acute lymphoblastic leukemia survivors with or without electrophysiologically defined neuropathy.
Joubert syndrome is a neurologic disorder with a pathognomonic "molar tooth sign" on brain imaging. The purpose of this study was to identify potential mutations in a Chinese patient with Joubert syndrome by targeted massively parallel sequencing. Taking advantage of high-throughput DNA sequencing technologies, 18 Joubert-causing genes of a Chinese patient with classic Joubert syndrome were sequenced at a time, and 2 novel variants in the CEP290 gene (c.7323_7327delAGAAG and c.6012-2A>G) were identified in this patient. Sanger validation showed that 2 variants were inherited from each parents, respectively. Both variants are located in the C-terminal region of the CEP290 protein and are predicted to be deleterious. The results support that the combination of targeted genes enrichment and next-generation sequencing is valuable molecular diagnostic tool and suitable for clinical application.
The International Classification of Functioning, Disability and Health (ICF) utilizes domains of body functions and structures, activities and participation, as well as environmental and personal factors to fully encapsulate the concepts of health and disability. The International Classification of Functioning, Disability and Health provides a rich and holistic understanding of functioning that is particularly valuable in the setting of childhood disability and rehabilitation. With applicability that enhances a nuanced understanding of each child within their family, school, and community, the International Classification of Functioning, Disability and Health also ensures facile and meaningful communication between professionals. Use of the International Classification of Functioning, Disability and Health promotes improved treatment plans for individual children and for larger programmatic decisions. This article demonstrates how the International Classification of Functioning, Disability and Health has reinvented the language and understanding of childhood disability and rehabilitation.
Acute focal neurologic deficits are a rare but known presentation of ornithine transcarbamylase deficiency, particularly in females. We describe here a 6-year-old girl with newly diagnosed ornithine transcarbamylase deficiency who presents with an episode of acute cortical blindness lasting for 72 hours in the absence of hyperammonemia. Her symptoms were associated with a subcortical low-intensity lesion with overlying cortical hyperintensity on fluid-attenuated inversion recovery magnetic resonance imaging (MRI) of the occipital lobes. Acute reversible vision loss with these MRI findings is an unusual finding in patients with ornithine transcarbamylase deficiency. Our findings suggest a role for oxidative stress and aberrant glutamine metabolism in the acute clinical features of ornithine transcarbamylase deficiency even in the absence of hyperammonemia.
We describe the case of a 41/2-year-old girl with prolonged febrile status followed by abnormal behavior and loss of speech. Interesting findings on diffusion-restricted imaging were noted. The clinicoradiologic possibilities are discussed.
Primary varicella infection may be associated with neurologic complications, such as cerebritis and meningoencephalitis. Several cases of varicella infection with elevated intracranial pressure have been reported. We describe a 13-year-old immunocompetent girl who presented with a clinical picture of headaches and elevated intracranial pressure as the only manifestation of primary varicella zoster infection. The working diagnosis at first was pseudotumor cerebri based on complaints of headache of 2 weeks’ duration, in addition to vomiting and papilledema, without fever or skin eruption. On lumbar puncture, opening pressure was 420 mmH2O, but mild pleocytosis and mildly elevated protein level ruled out the diagnosis of pseudotumor cerebri. Our patient had no history of previous varicella infection, and she did not receive the varicella zoster vaccine. Serology tests, done on admission and repeated 2 months later, suggested primary varicella infection. The literature on varicella infection associated with pseudotumor cerebri or elevated intracranial pressure is reviewed.
The frequency of cranial autonomic symptoms in children affected by primary headaches is uncertain. The aim of our study was to estimate the frequency of symptoms in pediatric headaches and correlate it with main migraine characteristics. A questionnaire investigating the presence of cranial autonomic symptoms was administered to all children with primary headache for 2 years. A total of 230 children with primary headache (105 males, 125 females) were included. Two hundred two children were affected by migraine and 28 (12.2%) by other primary headaches. Cranial autonomic symptoms were significantly complained by migraineurs (55% vs 17.8%) (P < .001) and by children with higher frequency of migraine attacks (odds ratio = 2.6, confidence interval = 1.4-4.7, P = .001). Our findings show that cranial autonomic symptoms are rather common during pediatric migraine attacks. The association between cranial autonomic symptoms and higher frequency of attacks might suggest the role of the trigeminal-autonomic reflex in migraine pathophysiology.
This study aimed to establish reference values for the length and area of the fetal cisterna magna using the multiplanar mode of 3-dimensional ultrasonography. A cross-sectional study including 224 normal pregnant women between 17 weeks 0 days and 29 weeks 6 days of gestation was carried out. The area and length of the fetal cisterna magna were measured in the axial plane at the level of the cerebellar transverse diameter. Reliability was determined by intraclass correlation coefficient. The mean length and area of the fetal cisterna magna ranged from 0.50 ± 0.10 to 0.79 ± 0.18 cm and 0.95 ± 0.18 to 3.09 ± 0.62 cm2, respectively. Intraobserver reliability for the length and area (intraclass coefficients: 0.86 and 0.91, respectively) and interobserver reliability (intraclass coefficients: 0.64 and 0.82, respectively) were good. Three-dimensional ultrasonography using the multiplanar mode is a reliable method for the determination of reference values for the length and area of the fetal cisterna magna.
Nonketotic hyperglycinemia (OMIM no. 605899) is an autosomal recessively inherited glycine encephalopathy, caused by a deficiency in the mitochondrial glycine cleavage system. Here we report 2 neonates who were admitted to the hospital with complaints of respiratory failure and myoclonic seizures with an elevated cerebrospinal fluid/plasma glycine ratio and diagnosed as nonketotic hyperglycinemia. We report these cases as 2 novel homozygous mutations; a missense mutation c.593A>T (p.D198 V) in the glycine decarboxylase gene and a splicing mutation c.339G>A (Q113Q) in the aminomethyltransferase gene were detected. We would like to emphasize the genetic difference of our region in inherited metabolic diseases once again.
We performed a retrospective review of 65 children with developmental delay. The male-to-female ratio was 2.25 : 1, and the mean age was 5.8 years; performance IQ was 94.8, verbal IQ was 83, and full-scale IQ was 87.4. Twenty-three (35%) children had normal language development, 13 (20%) had below average language development, and 29 (45%) had developmental language disorder. Performance IQ was significantly better than verbal IQ in all children (P < .001), and there was no difference within the 3 language groups. The performance IQ (P = .007) of children with developmental language disorder and specific language impairment was significantly lower than that of children with normal language development. Performance IQ was found to be correlated with language score (r = .309, P = .012). The children with language impairment were associated with lower IQ scores. The discrepancy between performance IQ and verbal IQ persisted in children with developmental delay, not only in children with language disorder.
In this case study, a 9-year-old ambulatory girl with dystrophinopathy due to a mosaic translocation mutation participated in dynamic training. Because the role of exercise is unclear in both boys and girls with dystrophinopathy, a recently developed assisted bicycle training regimen was evaluated for its feasibility and effectiveness in this girl. The girl trained at home, first 15 minutes with her legs and then 15 minutes with her arms, 5 times a week, for 24 weeks. This case study showed that the training was feasible and safe. In addition, we found that no physical deterioration occurred during the training period: the Motor Function Measure and the Assisted 6-Minute Cycling Test results remained stable. Slight improvements in quantitative muscle ultrasound intensity were found, indicating less fatty infiltration in the muscles. These results suggest that physical training could be beneficial in females with dystrophinopathy who express low levels of dystrophin.
To investigate clinical correlates of Tourette syndrome and to identify the impact of comorbidities, we retrospectively recruited 92 young people affected by Tourette syndrome compared with 102 healthy controls. Neuropsychological assessment included: Youth Quality of Life–Research, Multidimensional Anxiety Scale for Children, Children’s Depression Inventory, and Conner’s and Child Behavior Checklist; moreover, Tourette syndrome patients completed the Yale Global Tic Severity Rating Scale and the Yale-Brown Obsessive Compulsive Scale. Four clinical subgroups were identified: pure Tourette syndrome (49.8%), Tourette syndrome plus attention-deficit hyperactivity disorder (ADHD) (22.2%), Tourette syndrome plus obsessive-compulsive disorder (21.5%), and Tourette syndrome plus ADHD plus obsessive-compulsive disorder (6.5%). Our findings suggested that emotional lability appeared in all Tourette syndrome subgroups, independently from comorbidities, representing a clinical feature of Tourette syndrome itself. Moreover, our data suggested that all 4 clinical subgroups had higher statistically significant behavioral problems compared with the healthy controls (P = .000), whereas affective and anxiety symptoms were overrepresented in Tourette syndrome plus comorbidities subgroups. Finally, Tourette syndrome patients had a lower quality of life compared with the healthy controls. These differences were statistically significant between the pure Tourette syndrome subgroups and Tourette syndrome plus comorbidities subgroups, as well as Tourette syndrome plus comorbidities subgroups and healthy controls.
Intracranial tuberculoma in infants are a rare occurrence. We report a 7-month-old male infant presenting to our tertiary care referral center with complaints of global developmental delay and right hemiparesis for 3 months. Radiologic imaging was suggestive of large left frontoinsular space–occupying lesion with initial differential of primitive neuroectodermal tumor or desmoplastic infantile ganglioglioma. Considering the clinicoradiologic findings and no history suggestive of immunodeficiency or contact with tuberculosis, surgical decompression was done. Final histopathology revealed multiple epithelioid granulomas suggestive of tubercular etiology or intracranial Langerhans cell histiocytosis. He was started on antitubercular therapy after ruling out Langerhans cell histiocytosis using CD1a and Langerin immunohistochemistry staining. Interpretation of tuberculous etiology in infants can be challenging for clinicians, radiologists, and pathologists. A high index of suspicion is necessary to diagnose such lesions, predominantly in endemic regions.
There is little consistency in the literature concerning factors that influence motor coordination in children. A hypothesis-free "exposome" approach was used with 7359 children using longitudinal information covering 3 generations in regard to throwing a ball accurately at age 7 years. The analyses showed an independent robust negative association with mother’s unhappiness in her midchildhood (6-11 years). No such association was present for study fathers. The offspring of parents who described themselves as having poor eyesight had poorer ability. This hypothesis-free approach has identified a strong negative association with an unhappy childhood. Future studies of this cohort will be used to determine whether the mechanism is manifest through differing parenting skills, or a biological mechanism reflecting epigenetic effects.
Access solutions may facilitate communication in children with limited functional speech and motor control. This study reviews current trends in access solution development for children with cerebral palsy, with particular emphasis on the access technology that harnesses a control signal from the user (eg, movement or physiological change) and the output device (eg, augmentative and alternative communication system) whose behavior is modulated by the user’s control signal. Access technologies have advanced from simple mechanical switches to machine vision (eg, eye-gaze trackers), inertial sensing, and emerging physiological interfaces that require minimal physical effort. Similarly, output devices have evolved from bulky, dedicated hardware with limited configurability, to platform-agnostic, highly personalized mobile applications. Emerging case studies encourage the consideration of access technology for all nonverbal children with cerebral palsy with at least nascent contingency awareness. However, establishing robust evidence of the effectiveness of the aforementioned advances will require more expansive studies.
Accurate and well-targeted measurement of a child’s abilities and participation in daily activities pre- and post-intervention is essential to understanding the effects of therapies provided by pediatric practitioners. There is growing interest in identification of outcome core sets for specified client groups. This article elaborates on the concepts to consider when selecting and interpreting measures from an outcomes toolbox for children with cerebral palsy. Principles discussed include use of self-report measures to open a dialogue with the child/parent; a holistic assessment approach to identify a child’s challenges, strengths, and contextual factors that can influence functioning; links between measurement and heightened engagement of the child/family in the rehabilitation process and goals; and the need to plan the evaluation and dialogue aspects of the assessment process. If clinicians across the international rehabilitation community draw from the same toolbox, the end result could be a cohesive approach and common language to outcome measurement.
Low levels of physical activity are a global health concern for all children. Children with cerebral palsy have even lower physical activity levels than their typically developing peers. Low levels of physical activity, and thus an increased risk for related chronic diseases, are associated with deficits in health-related physical fitness. Recent research has provided therapists with the resources to effectively perform physical fitness testing and physical activity training in clinical settings with children who have cerebral palsy, although most testing and training data to date pertains to those who walk. Nevertheless, on the basis of the present evidence, all children with cerebral palsy should engage, to the extent they are able, in aerobic, anaerobic, and muscle-strengthening activities. Future research is required to determine the best ways to evaluate health-related physical fitness in nonambulatory children with cerebral palsy and foster long-term changes in physical activity behavior in all children with this condition.
Cerebral palsy describes a group of disorders of movement and posture that result from disturbances in the developing brain. Although the brain lesion is nonprogressive, the secondary physical symptoms change with time and growth. If left untreated, symptoms may result in the development of physical impairment and impede independent performance of daily tasks. Intramuscular injection of botulinum neurotoxin A is a relatively safe and effective adjunct to upper limb therapy. Botulinum neurotoxin A primarily aims to reduce muscle overactivity, thereby reducing the development of increased muscle stiffness that can lead to permanent changes. With a specific focus on the physiological action of botulinum neurotoxin A, this article describes the secondary symptoms of cerebral palsy and their different contributions. To highlight research directions and future implications for clinical practice, this article also documents the recent scientific evidence for upper limb botulinum neurotoxin A and proposes a preventive clinical model that aims to mitigate the effects of increasing upper limb impairment.
Children with unilateral cerebral palsy experience difficulties with unimanual and bimanual upper limb function, impacting independence in daily life. Targeted upper limb therapies such as constraint-induced movement therapy, bimanual training, and combined approaches have emerged in the last decade. This article reviews the scientific rationale underpinning these treatments and current evidence to improve upper limb outcomes and goal attainment. Intensive models of therapy achieved modest to strong effects to improve upper limb function compared to usual care. Dose-matched comparisons of bimanual and unimanual training demonstrated similar gains in upper limb outcomes. The optimum timing, dose and impact of repeat episodes of intensive upper limb therapies require further investigation. Characteristics of children who achieve clinically meaningful outcomes remain unclear. Key components of intervention include collaborative goal setting with families and intensive repetitive, incrementally challenging, task practice. Choice of treatment approach should be governed by child/family goals and preferences, individual, and contextual factors.
Approximately, 90% of patients with Angelman syndrome present with epileptic seizures. Obtaining an electroencephalogram (EEG) with sleep improves the chances of detecting ictal, interictal, and benign abnormal rhythms in Angelman syndrome. However, electroencephalograms, even when obtained during sleep, can be challenging in this population because of tactile sensitivities as well as anxiety related to a novel environment. We tested the hypothesis that 1 hour of sleep on an electroencephalogram would provide as much information as an entire night of electroencephalogram recording, yet more than a routine electroencephalogram conducted during the day. Overnight polysomnograms were collected in 14 children with Angelman syndrome seen at Vanderbilt University. All patients who obtained sleep within the first hour of the overnight electroencephalogram had interictal discharges recorded. Our results show that when sleep is obtained, a 1-hour electroencephalogram yields just as much information as recording an entire night.
We present a case of a 1-year-old female child who was referred to the Early Intervention Clinic for evaluation of developmental delay and progressively enlarging head size. Developmental assessment revealed significant motor delay with borderline cognitive impairment. MRI of the brain revealed generalized ventriculomegaly secondary to narrowing of the spinal canal at the cervicomedullary junction. Targeted array-based comparative genomic hybridization showed deletion of approximately 602 kbp from band p12.2 region of the short arm of chromosome 16, which encompasses 16p12.1 microdeletion syndrome. The 16p12.1 microdeletion syndrome has been recently recognized as an important contributor of developmental delay and other neuropsychiatric phenotypes in the child. To date, no case of cervicomedullary spinal canal stenosis with hydrocephalus has been reported with 16p12.1 microdeletion syndrome.
Peripheral facial nerve paralysis in children might be an alarming sign of serious disease such as malignancy, systemic disease, congenital anomalies, trauma, infection, middle ear surgery, and hypertension. The cases of 40 consecutive children and adolescents who were diagnosed with peripheral facial nerve paralysis at Baskent University Adana Hospital Pediatrics and Pediatric Neurology Unit between January 2010 and January 2013 were retrospectively evaluated. We determined that the most common cause was Bell palsy, followed by infection, tumor lesion, and suspected chemotherapy toxicity. We noted that younger patients had generally poorer outcome than older patients regardless of disease etiology. Peripheral facial nerve paralysis has been reported in many countries in America and Europe; however, knowledge about its clinical features, microbiology, neuroimaging, and treatment in Turkey is incomplete. The present study demonstrated that Bell palsy and infection were the most common etiologies of peripheral facial nerve paralysis.
Roger A. Brumback, MD (1953-2013), a renaissance man, shared with the world his knowledge and opinions on many subjects. Thus, it should come as no surprise that ethics did not escape Dr Brumback’s consideration. Reading Dr Brumback’s vitae, I came across several publications that afford insights into topics that tugged at his moral fabric. Dr Brumback was a steadfast defender of the scientific method. Reading his commentaries, one gets the sense that Dr Brumback felt personally attacked when quackery challenged science. In addition, and as long-time Editor-in-Chief of the Journal of Child Neurology, Dr Brumback considered it a personal affront every time a paper he published, or for that matter published by any scientific journal, had to be retracted or corrected. In the following paragraphs, I review a selection of Dr Brumback’s ethics writings.
A 7-year-old boy presented with episodic blindness for the last 2 months with occipital paroxysms and fixation-off sensitivity on electroencephalography (EEG). The clinico-EEG features were suggestive of idiopathic childhood occipital epilepsy of Gastaut. The interesting phenomenon of fixation-off sensitivity is discussed.
Classification systems in health care are usually based on current understanding of the condition. They are often derived empirically and adopted applying sound principles of measurement science to assess whether they are reliable (consistent) and valid (true) for the purposes to which they are applied. In the past 15 years, the authors have developed and validated classification systems for specific aspects of everyday function in people with cerebral palsy—gross motor function, manual abilities, and communicative function. This article describes the approaches used to conceptualize each aspect of function, develop the tools, and assess their reliability and validity. We report on the utility of each system with respect to clinical applicability, use of these tools for research, and the uptake and impact that they have had around the world. We hope that readers will find these accounts interesting, relevant, and applicable to their daily work with children and youth with disabilities.
This article focuses on conceptual and practical considerations in family-centered care for children with cerebral palsy and their families. In the last 5 years, there have been important advances in our understanding of the components of family-centered care, and initial attempts to understand the client change processes at play. Recent research elaborates on family-centered care by delving into aspects of family-provider partnership, and applying family-centered principles to organizational service delivery to bring about organizational cultures of family-centered care. Recent research has also begun to consider mediators of client change, and new practice models have been proposed that embrace family-centered principles and illustrate the "art" of practice. Future research directions are discussed, including explorations of causal relationships between family-centered care principles, elements of caregiving practice, client change processes, and child and family outcomes. The meaning of the recent literature for pediatric neurology practice is considered.
In the context of the development of the International Classification of Functioning, Disability and Health Core Sets for children and youth with cerebral palsy, an evidence-based methodology was implemented to select the most relevant categories out of the entire classification. The aim of this study was to describe the contribution of the clinical perspective to select categories of functioning in children and youth with cerebral palsy. We conducted a chart review of clinical assessments of children and youth with cerebral palsy aged 0 to 18 years in a tertiary level center. In total, 129 International Classification of Functioning categories were covered in clinical encounters: representing 19% body structures, 33% body functions, 37% activity and participation, and 11% environmental factors. Our findings can guide clinical assessments and goal-setting of this population. This important perspective will inform the development of the International Classification of Functioning, Disability and Health Core Sets for children and youth with cerebral palsy.
Neonatal seizures have been associated with the later development of postneonatal epilepsy, mainly beginning within the first year of life. Mechanisms of epileptogenesis in the immature brain still need to be fully elucidated but a two-hit hypothesis, showing that an early insult heightens later susceptibility to seizure-induced brain damage, has been demonstrated in animal models. We describe 2 cases of preterm babies sustaining recurrent neonatal seizures in the context of a severe perinatal brain damage who presented with symptomatic epilepsy only after the occurrence of an episode of febrile status epilepticus. In the context of preexisting perinatal brain damage, febrile status epilepticus acted as a second hit for developing epilepsy, confirming animal evidence.
Children and youth with cerebral palsy receive ongoing physical and occupational therapy services to improve their functional performance and participation in activities at home, school, and in the community. Over the past 2 decades, rehabilitation interventions have become more functional and goal oriented. In this article, we discuss factors that have influenced emerging intervention approaches. These factors include greater involvement of families in decision making, changing conceptual frameworks and theories underlying skill development and improved outcome measures. New research findings indicate that rehabilitation interventions embracing family-centered services and focusing on functional improvement can be more effective in promoting participation. This knowledge can serve as the platform for further examination of the most effective rehabilitation interventions for children and youth with cerebral palsy.
Virtual reality is the use of interactive simulations to present users with opportunities to perform in virtual environments that appear, sound, and less frequently, feel similar to real-world objects and events. Interactive computer play refers to the use of a game where a child interacts and plays with virtual objects in a computer-generated environment. Because of their distinctive attributes that provide ecologically realistic and motivating opportunities for active learning, these technologies have been used in pediatric rehabilitation over the past 15 years. The ability of virtual reality to create opportunities for active repetitive motor/sensory practice adds to their potential for neuroplasticity and learning in individuals with neurologic disorders. The objectives of this article is to provide an overview of how virtual reality and gaming are used clinically, to present the results of several example studies that demonstrate their use in research, and to briefly remark on future developments.
There is very little data correlating lumbar puncture pressures to formal intracranial pressure monitoring despite the widespread use of both procedures. The hypothesis was that lumbar puncture is a single-point measurement and hence it may not be a reliable evaluation of intracranial pressure. The study was therefore carried out to compare lumbar puncture opening pressures with the Camino® bolt intracranial pressure monitor in children. Twelve children with a mean age of 8.5 years who had both lumbar puncture and intracranial pressure monitoring were analyzed. The mean lumbar puncture opening pressure was 22.4 mm Hg versus a mean Camino bolt intracranial pressure of 7.8 mm Hg (P < .0001). Lumbar puncture therefore significantly overestimates the intracranial pressure in children. There were no complications from the intracranial pressure monitoring, and the procedure changed the treatment of all 12 children avoiding invasive operative procedures in most of the patients.
Pyridoxine-dependent epilepsy is an autosomal recessively inherited disorder of lysine catabolism caused by mutations in the ALDH7A1 gene. We report 2 patients with normal neurocognitive outcome (full-scale IQ of 108 and 74) and their more than 10 years’ treatment outcome on pyridoxine monotherapy. Both patients had specific borderline impairments in visual processing speed. More long-term treatment outcome reports will increase our knowledge about the natural history of the disease.
There are currently no objective criteria to evaluate pediatric hypotonia. The purpose of this pilot study was to identify diagnostic criteria for assessing hypotonia in children with neurofibromatosis type 1. Fifty-five subjects between the ages of 1 and 7 years with a diagnosis of neurofibromatosis type 1 were evaluated. A physical therapist recorded a subjective tone assessment and objective tone metrics, including ankle dorsiflexion, knee extension, hip abduction, triceps fat percentage, grip strength, and head lag during a pull-to-sit test. Multivariate logistic regression analysis showed the presence of head lag paired with increased hip range of motion was a significant predictor of hypotonia. The presence of head lag on a pull-to-sit test paired with increased hip range of motion is an accurate predictor of hypotonia in children with neurofibromatosis type 1. These objective measures should be prospectively evaluated in other pediatric populations for their ability to predict hypotonia.
A 9-year-old boy presented with intolerance to noise that was a trigger for violent temper tantrums that occasionally resembled complex partial seizures. The condition was also a cause for withdrawal from all activities and settings that could potentially be associated with noise. Both electroencephalography and magnetoencephalography clearly demonstrated a left temporal (T5) epileptic focus, although the child never had convulsive seizures. Genetic studies failed to reveal a GRIN2A mutation. We suggest that the hyperacusis in the reported child is another variation of the Landau-Kleffner spectrum.
Magnetic resonance imaging (MRI) could improve prognostication in neonatal brain injury; however, factors beyond technical or scientific refinement may impact its use and interpretation. We surveyed Canadian neonatologists and pediatric neurologists using general and vignette-based questions about the use of MRI for prognostication in neonates with hypoxic-ischemic injury. There was inter- and intra-vignette variability in prognosis and in ratings about the usefulness of MRI. Severity of predicted outcome correlated with certainty about the outcome. A majority of physicians endorsed using MRI results in discussing prognosis with families, and most suggested that MRI results contribute to end-of-life decisions. Participating neonatologists, when compared to participating pediatric neurologists, had significantly less confidence in the interpretation of MRI by colleagues in neurology and radiology. Further investigation is needed to understand the complexity of MRI and of its application. Potential gaps relative to our understanding of the ethical importance of these findings should be addressed.
Mitochondrial DNA depletion syndromes are an important cause of mitochondrial cytopathies in both children and adults. We describe a newborn with multiple congenital malformations including a right aberrant subclavian artery and a trachea-oesophageal fistula in whom mitochondrial depletion syndrome was unmasked by perioperative muscle relaxation. After vecuronium infusion, the infant developed an irreversible postoperative paralysis, leading to death 32 days after surgery. The present case highlights (a) the clinical heterogeneity of mitochondrial depletion syndrome; (b) the importance of rigorous antemortem and postmortem investigations when the cause of a severe myopathy is uncertain; (c) the possible coexistence of mitochondrial depletion syndrome and congenital malformations as a result of a likely abnormal antenatal embryofetal development and (d) the importance of a careful anaesthetic management of children with mitochondrial depletion syndrome, which could be prone to complications related to the possible depressive effects on mitochondrial electron transport chain mediated by some anaesthetic agents.
Our objective is to characterize the long-term course of Glut1 deficiency syndrome. Longitudinal outcome measures, including Columbia Neurological Scores, neuropsychological tests, and adaptive behavior reports, were collected for 13 participants with Glut1 deficiency syndrome who had been followed for an average of 14.2 (range = 8.9-23.6) years. A parent questionnaire assessed manifestations throughout development. The 6-Minute Walk Test captured gait disturbances and triggered paroxysmal exertional dyskinesia. All longitudinal outcomes remained stable over time. Epilepsy dominated infancy and improved during childhood. Dystonia emerged during childhood or adolescence. Earlier introduction of the ketogenic diet correlated with better long-term outcomes on some measures. Percent-predicted 6-Minute Walk Test distance correlated significantly with Columbia Neurological Scores. We conclude that Glut1 deficiency syndrome is a chronic condition, dominated by epilepsy in infancy and by movement disorders thereafter. Dietary treatment in the first postnatal months may effect improved outcomes, emphasizing the importance of early diagnosis and treatment.
Tuberous sclerosis complex is an autosomal dominant disorder characterized by hamartomas in multiple organ systems. Mutations in the 2 large genes TSC1 and TSC2 have been demonstrated to be associated with tuberous sclerosis complex by various mutation screening methods. Targeted next-generation sequencing for genetic analysis is performed in the current study and is proved to be less cost, labor, and time consuming compared with Sanger sequencing. Two de novo and 1 recurrent TSC2 mutation in patients with tuberous sclerosis complex were revealed. Clinical details of patients were described and the underlying mechanism of the 2 novel TSC2 mutations, c.245G>A(p.W82X) and c.5405_5408dupACTT(p.P1803Lfs*25), were discussed. These results added to variability of TSC mutation spectrum and suggest that targeted next-generation sequencing could be the primary choice over Sanger sequencing in future tuberous sclerosis complex genetic counseling.
In autism spectrum disorders, many parents resort to alternative treatments and these are generally perceived as risk free. Among these, the most commonly used is the gluten-free, casein-free diet. The objective of this work was to conduct a systematic review of studies published from 1970 to date related to the gluten-free, casein-free diet in autism spectrum disorder patients. Few studies can be regarded as providing sound scientific evidence since they were blinded randomized controlled trials, and even these were based on small sample sizes, reducing their validity. We observed that the evidence on this topic is currently limited and weak. We recommend that it should be only used after the diagnosis of an intolerance or allergy to foods containing the allergens excluded in gluten-free, casein-free diets. Future research should be based on this type of design, but with larger sample sizes.
Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated virus, showing inflammation, neurodegeneration, and demyelination. Although many factors are emphasized in the pathogenesis of subacute sclerosing panencephalitis, the exact mechanism of neurodegeneration remains unknown. Micro-RNAs are small, noncoding RNAs that regulate gene expression at the posttranscriptional levels. Micro-RNAs are essential for normal immune system development; besides they are also implicated in the pathogenesis of many chronic inflammatory disorders. The aim of this study is to investigate the expression patterns of micro-RNAs 146a, 181a, and 155 in peripheral blood mononuclear cells of patients with subacute sclerosing panencephalitis. We enrolled 39 patients with subacute sclerosing panencephalitis and 41 healthy controls. Quantitative analysis of micro-RNAs 146a, 181a, and 155 were performed using specific stem-loop primers followed by real-time polymerase chain reaction. All of 3 micro-RNAs were upregulated in subacute sclerosing panencephalitis patients. In addition, the level of micro-RNA 155 expression was higher in stage 3 patients. But, micro-RNA 146a and 181a expression levels showed no association or correlation with clinically relevant data. Alteration of peripheral blood mononuclear cell micro-RNAs in subacute sclerosing panencephalitis may shed new light on the pathogenesis of disease and may contribute to the aberrant systemic rise in mRNA levels in subacute sclerosing panencephalitis.
Cerebral candidiasis is a devastating disease which contributes to a high mortality. Most of the cerebral candidiasis are never microbiologically or radiologically confirmed. In this case, a 4-year-old boy who developed cerebral candidiasis was successfully rescued and presented. The diagnosis of cerebral candidiasis was established based on both microbiologic and radiologic examinations. The pathogen was revealed to be Candida albicans by cerebrospinal fluid and central venous catheter cultures, and the cerebral involvement was recorded by series head magnetic resonance imaging (MRI) with an appearance of special encephalitis demonstrated. The imaging studies played a critical role throughout the diagnosis and treatment. Familiarity with the imaging findings in the appropriate clinical setting may result in a heightened level of awareness of this infection and, consequently, in earlier diagnosis and treatment.
Normal levels of the methyl CpG–binding protein 2 (MeCP2) are critical to neurologic functioning, and slight alterations result in intellectual disability and autistic features. It was hypothesized that children with MECP2 duplication (overexpression of MeCP2) and Rett syndrome (underexpression of MeCP2) would exhibit distinct electroencephalographic (EEG) indices of auditory stimulus discrimination. In this study, gamma-band oscillatory responses to familiar and novel voices were examined and related to social functioning in 17 children (3-11 years old) with MECP2 duplication (n = 12) and Rett syndrome (n = 5). Relative to the stranger’s voice, gamma activity in response to the mother’s voice was increased in MECP2 duplication but decreased in Rett syndrome. In MECP2 duplication, greater mother versus stranger differences in gamma activity were associated with higher social functioning. For the first time, brain responses in a passive voice discrimination paradigm show that overexpression and underexpression of MeCP2 have differential effects on cortical information processing.
In recent years, it has been suggested that defects in energy metabolism may accompany Prader Willi syndrome. Mutations in the mitochondrial cytochrome b gene have been commonly associated isolated mitochondrial myopathy and exercise intolerance, rarely with multisystem disorders. The authors describe a novel mutation (mt. 15209T>C) in mitochondrial cytochrome b gene in a 2-year-old girl with Prader-Willi syndrome with a clinical history of lactic acidosis attacks, renal sodium loss, hepatopathy, progressive cerebral atrophy, and sudden death. The authors suggest that atypical clinical findings in patients with Prader-Willi syndrome should direct the physician to search for a mitochondrial disease.
A preterm neonate presenting with respiratory distress after birth was found to have a clival encephalocele, which is a variant of a basal encephalocele, and hypoplasia of the cerebellum. Genetic studies revealed a small deletion of the long arm of chromosome 5: 5q15 deletion. We report a rare variant of a basal encephalocele with a cerebellar malformation and 5q15 deletion.
The optimal therapeutic time-window and protective mechanism of hyperbaric oxygen in hypoxic-ischemic brain damage remain unclear. This study aimed to determine the neuroprotective effects of hyperbaric oxygen. Following hypoxic-ischemic brain damage modeling in neonatal rats, hyperbaric oxygen was administered at 6, 24, 48, and 72 hours and 1 week after hypoxia, respectively, once daily for 1 week. Fourteen days after hypoxic-ischemic brain damage, cell density and apoptosis rate, number of Fas-L+, caspase-8+, and caspase-3+ neuronal cells, levels of nitric oxide, malondialdehyde, and superoxide dismutase in hippocampus were examined. Morris water maze test was conducted 28 days after insult. Significant improvements were found in cell density, rate of apoptosis, oxidative stress markers, FasL, and caspases in rats treated with hyperbaric oxygen within 72 hours compared to hypoxic-ischemic injury. Similarly, time-dependent behavioral amelioration was observed in pups treated with hyperbaric oxygen. Our findings suggest that hyperbaric oxygen protects against hypoxic-ischemic brain damage by inhibiting oxidative stress and FasL-induced apoptosis, and optimal therapeutic time window is within 72 hours after hypoxic-ischemic brain damage.
The authors aimed to study the effects of postnatal exposure to phthalate on anxiety-like behavior in mice and anxiety proneness in children. Male Imprinting Control Region (ICR) mice aged 4 weeks were administered 20 to 540 mg/kg of di-(2-ethylhexyl) phthalate (DEHP) or vehicle and assessed in the Open Field Test. A group of 277 children aged 8-11 years (150 males) was recruited from South Korea. A cross-sectional examination of urinary DEHP and dibutylphthalate metabolite concentrations was conducted, and the children were scored on the Trait Anxiety Inventory for Children (TAIC). DEHP metabolite concentrations in the urine were significantly and negatively correlated with TAIC scores in the female population but not in the male population. There were no significant group differences in the percentage of distance moved or time spent in the central area in male mice treated with DEHP or vehicle. Our results suggest a sex-dependent effect of DEHP on anxiety proneness in childhood.
Mechanism of seizure refractoriness to antiepileptic drugs in children with Lennox-Gastaut syndrome is not known. Efflux of antiepileptic drugs due to increased expression/function of P-glycoprotein, a multidrug efflux transporter protein on the cell surface is a proposed mechanism. The authors studied the expression/function of P-glycoprotein on peripheral blood mononuclear cells of 29 children with Lennox-Gastaut syndrome, 23 children with other epilepsies, and 19 healthy children. The authors found a higher P-glycoprotein expression/function in Lennox-Gastaut syndrome, a higher percent positive cells as compared to children with other epilepsy (P < 0.001) and to healthy controls (P = 0.012), higher P-glycoprotein expression as compared to healthy controls (P = 0.003), a higher total P-glycoprotein expression (relative florescence intensity x percent positive cells) as compared to children with other epilepsies (P < 0.001) and healthy controls (P < 0.001), and a higher P-glycoprotein function as compared to children with other epilepsies (P = 0.001) and healthy controls (P = 0.002). These findings may explain seizure refractoriness to anti-epileptic drugs in Lennox-Gastaut syndome.
Accelerometry provides information on habitual physical capability that may be of value in the assessment of function in Duchenne muscular dystrophy. This preliminary investigation describes the relationship between community ambulation measured by the StepWatch activity monitor and the current standard of functional assessment, the 6-minute walk test, in ambulatory boys with Duchenne muscular dystrophy (n = 16) and healthy controls (n = 13). All participants completed a 6-minute walk test and wore the StepWatch™ monitor for 5 consecutive days. Both the 6-minute walk test and StepWatch accelerometry identified a decreased capacity for ambulation in boys with Duchenne compared to healthy controls. There were strong, significant correlations between 6-minute walk distance and all StepWatch parameters in affected boys only (r = 0.701-0.804). These data proffer intriguing observations that warrant further exploration. Specifically, accelerometry outcomes may compliment the 6-minute walk test in assessment of therapeutic interventions for Duchenne muscular dystrophy.
The aim of this study was to determine the alterations in thyroid function during carbamazepine or valproate monotherapy in a prospective study. Forty patients treated with valproate, 33 patients treated with carbamazepine, and 36 control patients, all aged between 2 and 18 years, were enrolled in our study. Serum levels of thyroid hormones were measured before the beginning of the antiepileptic therapy and at 6 and 12 months of treatment. Carbamazepine-treated patients showed mean serum thyroid hormone levels significantly lower than baseline evaluation and the control group. Thyroid-stimulating hormone levels at 6 and 12 months were not significantly different in carbamazepine treated patients. Serum hormone levels did not change during valproate treatment. Thyroid-stimulating hormone levels were significantly higher at the 12th month of valproate treatment. Our data suggest that although carbamazepine causes significant alterations in thyroid hormone levels, these changes do not lead to clinical symptoms at the follow-up period of 12 months.
Autism spectrum disorders are neurodevelopmental disorders that are thought to be caused by a gene-by-environment interaction and in which various immune alterations are reported. We investigate CD4+ T-cell cytokine profiles and subpopulations in 19-year-old monozygotic twins with autism and different comorbidities. CD4+ T cells from the twin with epilepsy produce more interferon-gamma, less interleukin-17, and have an increased interferon-/interleukin-4 ratio. CD4+ T cells from the twin with multiple sclerosis exhibit a cytokine profile similar to an age and gender-matched control and a higher percentage of T regulatory (Treg) cells. The twins’ mother’s T cells produce very high levels of both interleukin-17 and interferon-. Cytokine and CD4+ T-cell abnormalities in the twins could contribute to or be a result of the manifestation of their divergent comorbidities. A proinflammatory, autoimmune-polarized cytokine profile is observed in this unique family with autism.
Assumed to be underreported and underrecognized, lymphocytic choriomeningitis presents as a febrile illness transmitted by the common house mouse, Mus musculus. Although asymptomatic or mild febrile illnesses are commonplace, meningitis and meningoencephalitis may develop after symptoms have seemed to improve. Neurologic sequelae are not typical but have been reported and can persist for months. We report a documented case of lymphocytic choriomeningitis in which a previously healthy 17-year-old girl experienced debilitating recurrent headaches and arthralgias for more than a year after discharge. Neuropsychological testing and visual changes were also documented. Further research is needed to estimate the prevalence of this infection, although it has been estimated that 5% of American adults have antibodies to lymphocytic choriomeningitis virus. Education and awareness of the medical community as well as the general public will be critical in prevention as well as advancing future treatment modalities of lymphocytic choriomeningitis virus.
Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes. We present early-onset cases in the Polish population that amounted to 21% of our total population with facioscapulohumeral muscular dystrophy. More than 27% of them presented with severe phenotypes (wheelchair dependency). The residual D4Z4 repeat sizes ranged from 1 to 4 units. In addition, even within early-onset facioscapulohumeral muscular dystrophy type 1 phenotypes, some cases had uncommon features (head drop, early disabling contractures, progressive ptosis, and respiratory insufficiency and cardiomyopathy).
Objectives of this review were to examine definitions and background of palliative care, as well as address whether there is an increased need for palliative care education among neurologists. The review also explores what literature exists regarding palliative care within general neurology and child neurology. A literature review was conducted examining use of palliative care within child neurology. More than 100 articles and textbooks were retrieved and reviewed. Expert guidelines stress the importance of expertise in palliative care among neurologists. Subspecialties written about in child neurology include that of peripheral nervous system disorders, neurodegenerative diseases, and metabolic disorders. Adult and child neurology patients have a great need for improved palliative care services, as they frequently develop cumulative physical and cognitive disabilities over time and cope with decreasing quality of life before reaching the terminal stage of their illness.
In recent years, there has been an increasing incidence of inflammatory bowel disease in children and adolescents. Neurologic involvement has been mainly reported in adults, and information in pediatrics is based primarily on individual case reports. In this study, we explored the prevalence and spectrum of neurologic manifestations of 50 children with inflammatory bowel disease in comparison to healthy controls. Based on clinical reports and neurologic evaluation, 34 patients (68%) exhibited neurologic manifestations compared with 10 children (23.8%) in the control group (P < .001). The main symptoms associated with inflammatory bowel disease in comparison to the control subjects were headache: 46% vs 3% (P < 0.001), dizziness: 26% vs none (P < .001), hypotonia: 10% vs none (P = .06), attention-deficit hyperactivity disorder (ADHD): 28% vs 7.1% (P < .001), tics and sensory complaints: 16% vs 2.4% (P = .036). Seizures and neuropsychiatric disorders were less characteristic. A larger-scale prospective study is required to further clarify this association.
Guillain-Barré syndrome is an acute inflammatory autoimmune polyradiculoneuritis. Progressive motor weakness and areflexia are essential for its diagnosis. Hyperreflexia has rarely been reported in the early healing period of Guillain-Barré syndrome following Campylobacter jejuni infection in patients with acute motor axonal neuropathy with antiganglioside antibody positivity. In this study, we report a 12-year-old girl presenting with complaints of inability to walk, numbness in hands and feet, and hyperactive deep tendon reflexes since the onset of the clinical picture, diagnosed with acute motor-sensory axonal neuropathy type of Guillain-Barré syndrome.
This report describes gelastic seizures in patients with optic nerve hypoplasia and hypothalamic dysfunction without hypothalamic hamartoma. All participants (n = 4) from the optic nerve hypoplasia registry study at Children’s Hospital Los Angeles presenting with gelastic seizures were included. The clinical and pathology characteristics include hypothalamic dysgenesis and dysfunction, but no hamartomas. Optic nerve hypoplasia is the only reported condition with gelastic seizures without hypothalamic hamartomas, suggesting that hypothalamic disorganization alone can cause gelastic seizures.
A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athetoid movements of extremities. Fundus showed bilateral chorioretinitis. Electroencephalography showed periodic complexes. Measles antibody titers were elevated in both serum and cerebrospinal fluid, consistent with subacute sclerosing panencephalitis. Neuroimaging showed discontiguous involvement of splenium of the corpus callosum and ventral pons with sparing of cortical white matter. Our case highlights the atypical clinical and radiologic presentations of subacute sclerosing panencephalitis. Pediatricians need to be aware that necrotizing chorioretinitis in a child and/or atypical brain stem changes could be the heralding feature of this condition in endemic countries.
Lysosomal storage disorders are a group of rare, genetically inherited metabolic disorders. Because the literature on epidemiologic data is scanty from India, we attempted to determine their relative frequency and regional distribution. Our retrospective study included 1558 patients with clinical suspicion of various lysosomal storage disorders referred to Sandor Lifesciences Pvt Ltd during 2007 to 2012. About 30% of the cases were tested positive, with sphingolipidoses as the most common subgroup, followed by mucopolysaccharidoses, and Gaucher disease as the most frequently occurring individual lysosomal storage disorder. Our data indicates that lysosomal storage disorders are more common in males than females and infants comprise the most common age group followed by juvenile. The burden of these disorders is predicted to be high in India because of the large population, coupled with the practice of consanguineous marriages. This study emphasizes the importance of epidemiologic studies in order to implement appropriate preventive measures.
Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation of IKBKG. This disorder has a classic dermatologic presentation, but neurologic involvement, with seizures and cortical infarction, can arise shortly after birth. There are no specific therapies available for the manifestations of incontinentia pigmenti. Here, we describe the clinical, electrographic, and neuroradiologic effect of systemic glucocorticoid therapy in a neonate with incontinentia pigmenti manifesting an epileptic encephalopathy. Treatment with dexamethasone led to a dramatic reduction in seizure activity and improvement in bullous lesions. A novel mutation in IKBKG is also reported.
This study examines trends in corticosteroid use for males with Duchenne muscular dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular dystrophy family history. Firstborn males (n = 521) selected from a population-based surveillance system of Duchenne muscular dystrophy were analyzed using Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid initiation decreased from 8.2 to 7.1 years. Hispanics and non-Hispanic Black males used steroids less frequently and delayed initiation compared to white males. Compared to males without a Duchenne muscular dystrophy family history, males with known family history were half as likely to use steroids. Duration of steroid use increased over time and age at initiation decreased. Racial/ethnic disparities exist for steroid use and should be addressed to improve outcome and quality of life for boys with Duchenne muscular dystrophy.
Tuberous sclerosis complex is a genetic disorder characterized by benign tumor growth including lesions in the ventricular system of the brain known as subependymal giant cell astrocytomas. This analysis focuses on the clinical presentation, management, and associated burden of subependymal giant cell astrocytomas in patients with tuberous sclerosis complex in the United States. An institutional review board–approved web-based survey of tuberous sclerosis complex patients and caregivers collected information, and descriptive analyses were conducted on age-based subgroups. A total of 116 tuberous sclerosis complex–subependymal giant cell astrocytoma patients or caregivers responded (17% of the total tuberous sclerosis complex sample). Mean and median patient ages were 25.5 and 23.5 years. Besides subependymal giant cell astrocytomas, patients also experienced skin lesions (72%), seizures (65%), and cognitive concerns (60%). Forty-five percent reported having brain surgery (22% for subependymal giant cell astrocytoma). In the past year, 42% of patients were admitted at least once to the hospital whereas 39% went to the emergency department. Results demonstrate that tuberous sclerosis complex–subependymal giant cell astrocytoma is associated with significant clinical burden, resource utilization, and decreased well-being.
We report a young boy who presented with progressive weakness of lower extremities associated with areflexia and abnormal electrophysiological findings initially suggestive of chronic inflammatory demyelinating polyneuropathy. Initial lumbosacral spinal magnetic resonance imaging (MRI) showed thickened descending spinal nerve roots only. Immunomodulating therapy was given but with limited clinical response. Repeated spine magnetic resonance imaging showed cauda equina and also new spinal cord extramedullary contrast enhancement. The initial extensive investigations including open biopsy did not point to any specific diagnosis. Only through pursuing a repeated biopsy, the diagnosis of the spinal peripheral primitive neuroectodermal tumor was confirmed. This case highlights the diagnostic challenges of the spinal peripheral primitive neuroectodermal tumor that could have an initial chronic inflammatory demyelinating polyneuropathy-like presentation. The literature review confirms that this is a rare condition and cauda equina origin has only been reported in adults and teenagers, and this is the first reported case in a young child.
Animal experiments indicate that repeated exposure to ketamine adversely affects the developing brain. Whether it has the same effect on infants remains unclear. We recruited infants who were scheduled for 1 to 3 outpatient laser surgery treatments of benign facial growths with ketamine anesthesia. Patients were assigned to the Ket1, Ket2, or Ket3 group, according to the number of treatments. The Bayley Scales of Infant Development–Second Edition (BSID-II) was used to assess neurodevelopmental outcomes before the first and after the last therapy. Levels of S-100β were also measured. Bayley Scales of Infant Development–Second Edition scores after the last procedure were lower than those before the first surgery in the Ket3 group (P < .05). S-100β levels after the last procedure were significantly higher than those before the first surgery in all groups (P < .05). Our results suggest that 3 or more exposures to anesthetic ketamine have the potential to adversely affect neurodevelopment in infants.
Neurofibromatosis type 1 disease is an autosomal dominant disorder associated with numerous ophthalmic and systemic manifestations. Organic causes of visual loss include optic pathway gliomas, orbital plexiform neurofibroma, and glaucoma. In this study, the authors analyzed the prevalence of ametropia as a cause for visual loss in children with neurofibromatosis type 1 disease younger than age 12 years compared to matched controls. Only children with normal neuroimaging were evaluated. Myopia, hyperopia, astigmatism, and anisometropia were all more common in children with neurofibromatosis type 1 disease; however, statistically significant differences were observed in mild myopia and astigmatism alone. A higher need for optical correction was found in children with neurofibromatosis type 1 disease (33.3% vs 17.1% of controls, P = .049). In conclusion, children with neurofibromatosis type 1 disease have a higher prevalence of ametropia, especially mild myopia and astigmatism, often requiring optical correction. Routine refraction screening is recommended for limiting preventable visual loss.
To determine a reference range of fetal transverse cerebellar diameter in Brazilian population. This was a retrospective cross-sectional study with 3772 normal singleton pregnancies between 18 and 24 weeks of pregnancy. The transverse cerebellar diameter was measured on the axial plane of the fetal head at the level of the lateral ventricles, including the thalamus, cavum septum pellucidum, and third ventricle. To assess the correlation between transverse cerebellar diameter and gestational age, polynomial equations were calculated, with adjustments by the determination coefficient (R2). The mean of fetal transverse cerebellar diameter ranged from 18.49 ± 1.24 mm at 18 weeks to 25.86 ± 1.66 mm at 24 weeks of pregnancy. We observed a good correlation between transverse cerebellar diameter and gestational age, which was best represented by a linear equation: transverse cerebellar diameter: –6.21 + 1.307*gestational age (R2 = 0.707). We determined a reference range of fetal transverse cerebellar diameter for the second trimester of pregnancy in Brazilian population.
There is scanty data regarding the efficacy and tolerability of the modified Atkins diet in children with Lennox-Gastaut syndrome. This study was a retrospective review of children with Lennox-Gastaut syndrome treated with the modified Atkins diet from May 2009 and March 2011. The diet was initiated in those children who persisted to have daily seizures despite the use of at least 3 appropriate antiepileptic drugs. Twenty-five children were started on a modified Atkins diet, restricting carbohydrate intake to 10 g/d. After 3 months, 2 patients were seizure-free, and 10/25 children had >50% reduction in seizure frequency. At 6 months, of 11 patients on the diet, 3 were seizure free and 8 had >50% reduction in seizure frequency. At 1 year, all 9 children on diet had >50% reduction in seizure frequency. The side effects of the diet were mild. The modified Atkins diet was found to be effective and well tolerated in children with Lennox-Gastaut syndrome.
Intrathecal chemotherapy including methotrexate is well documented for neurotoxicity of diverse clinical manifestation. Acute or chronic leukoencephalopathy is the most common type of methotrexate-induced neurotoxicity, and subacute myelopathy is rare. Although its pathogenesis is not fully understood, it is postulated that direct damage of methotrexate to the central nervous system plays a major part and elevated levels of homocysteine and its excitatory amino acid neurotransmitter metabolites (homocysteic acid and cysteine sulfinic acid) could mediate, in part, MTX-associated neurotoxicity. On the while, subacute combined degeneration is a progressive degeneration of the dorsal and lateral columns of the spinal cord, mostly due to vitamin B12 deficiency. The authors report a case of a 15-year-old boy with Burkitt leukemia who developed progressive myelopathy after intrathecal triple therapy (methotrexate, cytarabine, and hydrocortisone) whose clinical and radiologic features were compatible with subacute combined degeneration. The pathogenic mechanism could be explained by biochemical alteration by methotrexate and a possible treatment strategy was discussed.
Succinyl–coenzyme A synthase is a mitochondrial matrix enzyme that catalyzes the reversible synthesis of succinate and adenosine triphosphate (ATP) from succinyl–coenzyme A and adenosine diphosphate (ADP) in the tricarboxylic acid cycle. This enzyme is made up of α and β subunits encoded by SUCLG1 and SUCLA2, respectively. We present a child with severe muscular hypotonia, dystonia, failure to thrive, sensorineural deafness, and dysmorphism. Metabolic investigations disclosed hyperlactacidemia, moderate urinary excretion of methylmalonic acid, and elevated levels of C4-dicarboxylic carnitine in blood. We identified a novel homozygous p.M329V in SUCLA2. In cultured cells, the p.M329V resulted in a reduced amount of the SUCLA2 protein, impaired production of mitochondrial ATP, and enhanced production of reactive oxygen species, which was partially reduced by using 5-aminoimidazole-4-carboxamide ribonucleotide in the culture medium. Expanding the array of SUCLA2 mutations, we suggested that reactive oxygen species scavengers are likely to impact on disease prognosis.
We compared the social communication deficits of children with moderate to severe acquired brain injury or autism spectrum disorder, while accounting for the role of attention-deficit hyperactivity disorder (ADHD) symptoms. Parents of 20 children aged 6 to 10 years (10 acquired brain injury; 10 autism spectrum disorder) completed the Social Communication Questionnaire, and Conners 3 Parent Short. A multivariate analysis of covariance revealed significant differences between groups in Social Communication Questionnaire restricted repetitive behavior scores, but not reciprocal social interaction or social communication. Multiple linear regressions indicated diagnosis did not predict reciprocal social interaction or social communication scores and that Conners 3 Parent Short Form hyperactivity scores were the strongest predictor of Social Communication Questionnaire reciprocal social interaction scores after accounting for age and Intelligence Quotient. The lack of difference in social communication deficits between groups may help in understanding the pathophysiology underlying the behavioral consequences of acquired brain injury. The link between hyperactivity and reciprocal interaction suggests that targeting hyperactivity may improve social outcomes in children following acquired brain injury.
The founding and early development of the Southern Pediatric Neurology Society was in many ways parallel to that of the Child Neurology Society. The organization started out as the Southern Child Neurology Society but the name was changed at the time of incorporation so as to avoid confusion of identity and purpose with the larger Child Neurology Society. Although there are archives of early days and the later development of the Southern Pediatric Neurology Society, the details have never been set down in a narrative explaining the events that led to the development of the organization. In this paper, we try to produce a written record of the history of the founding and early development of the Southern Pediatric Neurology Society.
Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P < .0001), whereas the shape of the skull was significantly rounder compared to controls. Temporal muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship.
The authors hypothesized that among extremely preterm infants, elevated concentrations of inflammation-related proteins in neonatal blood are associated with cerebral palsy at 24 months. In 939 infants born before 28 weeks gestation, the authors measured blood concentrations of 25 proteins on postnatal days 1, 7, and 14 and evaluated associations between elevated protein concentrations and cerebral palsy diagnosis. Protein elevations within 3 days of birth were not associated with cerebral palsy. Elevations of tumor necrosis factor-α, tumor necrosis factor-α-receptor-1, interleukin-8, and intercellular adhesion molecule-1 on at least 2 days were associated with diparesis. Recurrent-persistent elevations of interleukin-6, E-selectin, or insulin-like growth factor binding protein-1 were associated with hemiparesis. Diparesis and hemiparesis were more likely among infants who had at least 4 of 9 protein elevations that previously have been associated with cognitive impairment and microcephaly. Repeated elevations of inflammation-related proteins during the first 2 postnatal weeks are associated with increased risk of cerebral palsy.
There is no information about the role of transforming growth factor–beta 1 (TGF-β1) in the pathogenesis of pediatric migraine. This study included 100 consecutive children and adolescents in whom migraine was diagnosed and 88 healthy children and adolescents. The isolated genomic DNA was used as a template for TGFβ-1 (–800G/A, –509C/T, 869T/C [codon 10] and 915G/C [codon 25]) genotyping. The allelic frequency of 509C/T was significantly different between control and migraine without aura patients (P = .04). Codon 10 C/T genotypic and C10 C allelic frequency of TGF-β1 polymorphisms were significantly higher in migraine and migraine without aura patients versus healthy controls (P = .00; P = .00). To our knowledge, this is the first report dealing with the relationship between TGF-β1 genotype and migraine in the pediatric age group. Further studies related to this subject are needed, along with a search for new therapeutic agents with anti-inflammatory properties.
Cerebral sinovenous thrombosis is unusual during childhood and requires early and accurate management because of its detrimental consequences. We report on the case of a 2-year-old boy with mild psychomotor delay, who presented with nonfebrile acute ataxia. A brain computed tomographic (CT) scan showed complete thrombosis of the superior sagittal sinus, confirmed by magnetic resonance angiography and associated with a right frontal hemorrhagic infarction. Systematic screening for thrombophilia revealed homocystinuria linked to cystathionine β-synthase deficiency with underlying compound heterozygosity. The evolution was favorable after anticoagulant therapy, specific diet, and vitamin supplementation. This case is of interest because of the unusual clinical presentation as a pediatric cerebral sinovenous thrombosis. Furthermore, homocystinuria is rarely revealed by cerebral sinovenous thrombosis at the onset of the disease and should systematically be ruled out in pediatric stroke.
Toe walking has been associated with language disorders and autism. To better understand the association between persistent toe walking and sensory and motor variables in children with autism, the degree of toe walking was compared with an estimate of the severity of sensory integration dysfunction symptoms and the presence of residual components of the tonic labyrinthine in supine reflex pattern in 61 children younger than 37 months of age with newly diagnosed autism. There was no association between the presence of toe walking and sensory symptoms (P = .5298) or language age (P = .6142), but there was an association between toe walking and the presence of components of the tonic labyrinthine reflex (P = .04222). These preliminary results support the contribution of subtle motor deficits to the evolution of some behaviors associated with autism.
The aim of this study was to see whether the scores of the Bayley Infant Neurodevelopmental Screener of 45 high-risk preterm infants (gestational age 26-37 wk) between the ages of 3 and 24 months predicted neurodevelopmental status at 7 to 10 years of age. Neurodevelopmental status of 45/122 preterm infants, grouped according to their gestational ages of 26 to 29, 30 to 32, and 33 to 37 weeks, were previously evaluated by Bayley Infant Neurodevelopmental Screener. The scores were categorized as low or high-moderate. Verbal and performance scores of Wechsler Intelligence Scale for Children–Revised (WISC-R) of those patients were assessed between 7 and 10 years. The patients with high-moderate-risk scores of Bayley Infant Neurodevelopmental Screener at all times, regardless of their gestational age, had lower performance, verbal, and total scores of WISC-R than those of who had low Bayley Infant Neurodevelopmental Screener risk scores. High-moderate risk score of Bayley Infant Neurodevelopmental Screener at 7 to 10, and 16 to 20 months, of all patients especially showed good prediction for identifying lower verbal and performance scales. For 7 to 10 months, verbal scale: positive predictive value = 92.3%, negative predictive value = 44.4%, sensitivity = 70.58%, and specificity = 80%; performance scale: positive predictive value = 100%, negative predictive value = 30%, sensitivity = 68.18%, and specificity = 100%. For 16 to 20 months, verbal scale: positive predictive value = 90%, negative predictive value = 37.5%, sensitivity = 64.3%, and specificity = 80%; performance scale: positive predictive value = 90%, negative predictive value = 12.5%, sensitivity = 56.3%, and specificity = 50%. Bayley Infant Neurodevelopmental Screener shows good prediction of later verbal and performance scores of Wechsler Intelligence Scale–Revised for Children as early as 7 to 10 months, which gives us the opportunity to start early intervention.
Proximal spinal muscular atrophy is an autosomal recessive disorder characterized by symmetrical muscle weakness due to degeneration of alpha motor neurons in the spinal cord. Homozygous deletions in the SMN1 have been reported in more than 90% of spinal muscular atrophy cases. Compound heterozygous patients account for approximately 4% of spinal muscular atrophy cases. In this study, we performed a quantitative test in 20 of 87 spinal muscular atrophy patients who did not have homozygous deletion of SMN1. Mutation screening of SMN1 gene was performed in 4 patients who have only 1 copy of SMN1 to identify intragenic mutations. In addition to a previously described missense mutation in exon 4 (p.A188S/ c.562G>T), we identified 2 novel mutations including a single nucleotide insertion in exon 7 (c.861_862insT/p.R288X) and a deletion of nucleotide G in exon 3 (c.286delG/p.D96Tfs*53). Our results suggested that about 4% of spinal muscular atrophy patients have subtle mutations and might be considered in laboratory examination.
Extrapontine myelinolysis is characterized by symmetric demyelination following rapid shifts in serum osmolality in the supratentorial compartment. Extrapontine myelinolysis in children is rare compared to adults. The most common underlying pathophysiology is rapid correction of hyponatremia. Only 2 cases were published after diabetic ketoacidosis without electrolyte imbalance in the English literature. This study presents an unusual and possibly the youngest case of extrapontine myelinolysis that occurred in the setting of diabetic ketoacidosis and complicated cerebral edema without electrolyte imbalance, along with a review of the literature.
Extensive optic nerve demyelinating lesions on magnetic resonance imaging (MRI) in adults could indicate a diagnosis other than multiple sclerosis with worse prognosis such as neuromyelitis optica. We report the frequency of longitudinally extensive lesions in children with first events of optic neuritis. Subjects had brain or orbit MRI within 3 months of onset and were evaluated at the University of California, San Francisco, Pediatric Multiple Sclerosis Center. Lesion length, determined by T2 hyperintensity or contrast enhancement, was blindly graded as absent, focal or longitudinally extensive (at least 2 contiguous segments of optic nerve). Of 25 subjects, 9 (36%) had longitudinally extensive optic neuritis. Extensive lesions were not associated with non–multiple sclerosis versus multiple sclerosis diagnosis (P = 1.00). No association between age and lesion extent was observed (P = .26). Prospective studies are needed to determine if longitudinally extensive optic neuritis can predict visual outcome.
We report the unique neuropathologic study of an adult brain of a patient with fetal alcohol syndrome who developed the well-recognized complication of schizophrenia in adolescence. The major finding was asymmetric formation of the lateral temporal lobes, with marked enlargement of the right superior temporal gyrus, suggesting that alcohol is preferentially toxic to temporal lobe patterning during gestation. Critical maturational changes unique to adolescence can unmask psychotic symptomatology mediated by temporal lobe pathology that has been clinically dormant since birth. Elucidating the neuropathologic basis of the secondary psychiatric disorders in fetal alcohol syndrome can help provide insight into their putative developmental origins.
Congenital dermal sinus tract is a rare entity which lined by epithelial cells and can end anywhere between subcutaneous planes to thecal sac. These tracts may be accompanied with other pathologies such as lipomyelomeningocele, myelomeningocele, split cord malformation, tethered cord, filum abnormality and inclusion tumors and treatment includes resection of tract with intradural exploration. The authors review their experience with 16 cases. Clinical, radiological appearance and treatment of these lesions discussed with literature review.
The relationship between superior longitudinal fasciculus microstructural integrity and neuropsychological functions were examined in 49 healthy children (range: 5-17 years) using diffusion tensor imaging. Seven major cognitive domains (intelligence, fine-motor, attention, language, visual-spatial, memory, executive function) were assessed. Data analyses used correlational methods. After adjusting for age and gender, fractional anisotropy and axial diffusivity values in the superior longitudinal fasciculus were positively correlated with executive functions of set shifting, whereas left superior longitudinal fasciculus fractional anisotropy values correlated with attention and language. Apparent diffusion coefficient values in the left superior longitudinal fasciculus negatively correlated with inhibitory control. In the left arcuate fasciculus, fractional anisotropy correlated with IQ and attention, whereas radial diffusivity values negatively correlated with IQ, fine-motor skills, and expressive language. Findings from this study provide an examination of the relationship between superior longitudinal fasciculus integrity and children’s neuropsychological abilities that can be useful in monitoring pediatric neurologic diseases.
Absence seizures associated with myoclonic phenomena have been associated with 4 seizure types. Recently, a new seizure type of neck myoclonia with absences was described. We present a case of 9-year-old girl who presented with abnormal head shaking and vacant stare for the past 5 months with an ictal electroencephalograph (EEG) record showing 3-Hz spike-and-wave discharges. The seizures were easily controlled with valproate and clobazam. Neck myoclonia with absences might be a new idiopathic generalized epilepsy syndrome in development.
The study was designed to compare the Full Outline of UnResponsiveness score with Glasgow Coma Scale as a predictor of mortality and poor functional outcome at hospital discharge in children with nontraumatic impairment of consciousness. Seventy children aged 5 to 18 years admitted with impaired consciousness were enrolled. The scores were applied by the Pediatric Neurology fellow within 2 hours of admission. The primary outcome studied was in-hospital mortality. Receiver operating characteristic curves were used to compare the 2 scores. The area under the curves for Glasgow Coma Scale and Full Outline of UnResponsiveness scores were 0.916 and 0.940, respectively. However, the difference between the areas under curve for the 2 scores was not statistically significant (0.023; 95% confidence interval: –0.0115 to 0.058). Our data indicate that both the scores are good predictors for in-hospital mortality and functional outcome. However, no significant difference was observed between the ability of the 2 scores to predict the outcomes.
ADEM is a central nervous disease that leads to myelin damage as a result of autoimmune response that develops after infections or vaccination. Herpes Simplex Virus (HSV) infection rarely leads to ADEM.
25-month-old male due to urinary retention, paradoxical respiration and muscle weakness after herpetic gingivostomatitis diagnosed as transverse myelitis. In follow-up with cranial and spinal magnetic resonance imaging multiple lesions were demonstrated. Electroneuromyography findings were compatible with acute sensorimotor neuropathy, serum anti-GM2 antibodies and Herpes Simplex Virus (HSV) Type 1/2 IgM / IgG detected negative and positivite, respectively. With these findings he was diagnosed acute disseminated encephalomyelitis (ADEM) following HSV infection. Although acyclovir, intravenous immunoglobulin, methylprednisolone and plasmapheresis therapies, he is still in intensive physical therapy program with heavy sequel.
In our case, ADEM demonstrated transverse myelitis clinic after HSV infection which is rarely seen in literature. As well as clinic and spinal imaging findings, cranial imaging findings helped establishment of ADEM diagnosis.
To our best knowledge, HSV is a rare etiological and probably the poor prognostic factor of ADEM.
We report the case of a boy with cutis marmorata telangiectatica congenita, strokelike episodes, and a pinpoint stenosis of the left internal carotid artery. To our knowledge, this is the first report of a stenosis of an intracranial artery in a patient with cutis marmorata telangiectatica congenita.
The effect of prenatal lead exposure on child development has been a topic of public health concern for decades. To estimate prenatal lead exposure effects on early childhood development, maternal blood (n = 364) and umbilical cord blood (n = 224) samples were collected during pregnancy and at delivery. Mental development was assessed using the Harold Ireton Early Child Development Inventory from 174 children. Maternal whole blood lead levels in the first trimester were significantly higher in children with developmental scores <20% than in those with normal scores (mean ± standard deviation: 6.3 ± 1.9 vs 4.0 ± 2.4 µg/dL, respectively, P = .01). Maternal blood lead levels in the first trimester were also inversely associated with the development scores (r = –0.155, P = .041). Logistic regression analysis showed a significant relationship between increasing maternal blood lead levels in the first trimester with low development scores (odds ratio = 1.74, 95% confidence interval = 1.18-2.57, P = .005). The findings of the present study showed a relatively low level of prenatal lead exposure (mean < 6.5 µg/dL) associated with lower developmental scores in early childhood.
Neurofibromatosis type 1 is associated with executive dysfunctions and comorbidity with attention-deficit hyperactivity disorder (ADHD) in 30% to 50% of children. This study was designed to clarify the neurocognitive phenotype observed in neurofibromatosis type 1 by testing the hypothesis that children with neurofibromatosis type 1 have specific planning deficits independently from intellectual level and ADHD comorbidity. Eighteen children with neurofibromatosis type 1 were pair-matched to 18 children with ADHD and 18 healthy controls. All groups were assessed on the presence of ADHD symptoms (Conners Scales) and planning deficits (Tower of London). Compared with control group, groups with neurofibromatosis type 1 and ADHD demonstrated significant impairment of planning and problem solving. The lack of correlation between Tower of London results and Conners subscale scores in neurofibromatosis type 1 group confirmed that the planning and problem-solving deficit is not directly related to inattention level. These findings suggested that the executive impairment probably represents a peculiar trait of neurofibromatosis type 1 neurocognitive phenotype.
Arteriovenous malformations are the most common cause of spontaneous intracerebral hemorrhages in older children. Intracerebral hematoma can cause serious lasting neurologic, cognitive, and language deficits, or even possible death. We present the case of a 16-year-old boy who had language impairments after suffering a large hemorrhagic stroke in the left temporoparietal region. All language components, verbal and nonverbal communication, reading, and writing, were found to be affected. These impairments were expected as they are characteristic of the location of the hematoma. After a year of speech language rehabilitation, there was an almost complete recovery of language skills. Quick diagnosis and adequate therapeutic interventions are important to diminish the influence of intracerebral hemorrhage on cognitive and language functions in children.
The electrographic hallmark of childhood absence seizures is 3 Hz generalized spike and wave discharges; however, there is likely a focal thalamic or cortical onset that cannot be detected using scalp electroencephalography (EEG). The purpose of this study was to study the earliest preictal changes in children with absence epilepsy. In this report, magnetoencephalography recordings of 44 absence seizures recorded from 12 children with drug-naïve childhood absence seizures were used to perform time frequency analysis and source localization prior to the onset of the seizures. Evidence of preictal magnetoencephalography frequency changes were detected a mean of 694 ms before the initial spike on the EEG. A consistent pattern of focal sources was present in the frontal cortex and thalamus during this preictal period, but source localization occurred synchronously so that independent activity between the 2 structures could not be distinguished.
Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients.
A retrospective analysis was conducted in a French pediatric hospital in Lyon. Subjects were 16 patients diagnosed with acute viral encephalitis with identified causative agents who were admitted to the pediatric intensive care unit from 2008 to 2011. The median length of stay was 6 days. The outcome was favorable for 77% of the patients. Analysis of biological and clinical findings based on causative agents did not reveal clinical patterns or neurological findings specific to the causal viruses. Nevertheless, uncommon clinical pictures and severe neurological complications were highlighted, in particular for children with influenza-related encephalitis and herpes simplex encephalitis. This case series exemplifies the difficulties, even pitfalls, in establishing a diagnosis of encephalitis, especially in neonates. It points out significant differences in the clinical presentation of encephalitis in children compared with clinical pictures described in previously published large-scale studies on encephalitis mainly conducted in adults.
This study aimed to determine the potential predisposing factors for the development of febrile seizures among children with upper respiratory tract infection in the eastern Chinese region. Participants were individuals aged 6 months and 6 years (n = 189) who were diagnosed with febrile seizure, complicated with upper respiratory tract infection, and 174 age-matched children who had upper respiratory tract infection without seizures as controls. The viral antigens including influenza A and B, parainfluenza, adenovirus, and respiratory syncytial virus were detected from nasopharyngeal aspirates. The incidence of influenza A infection was much higher in patients with febrile seizure than controls, especially those children aged >36 months. Patients with influenza A infection had higher body temperatures at seizure occurrence, shorter seizure duration, and shorter fever duration before seizure onset. Influenza A infections are frequently associated with febrile seizure in children with upper respiratory tract infection. During an influenza epidemic, effective vaccination of children, especially those with a past history of febrile seizure, may minimize the development of febrile seizure.
A child with the major form of hyperekplexia is presented who stopped ambulating because of frequent unexpected falls associated with acoustic and visual stimuli. A combination of clobazam and clonazepam was well tolerated and was rapidly and dramatically effective in eliminating the falls and restoring ambulation.
Late-onset glutaric aciduria type II has been described recently as a rare but treatable cause of proximal myopathy in teenagers and adults. It is an autosomal recessive disease affecting fatty acid, amino acid, and choline metabolism. This is usually a result of 2 defective flavoproteins: either electron transfer flavoprotein (ETF) or electron transfer flavoprotein–ubiquinone oxidoreductase (ETF:QO). We present a 14-year-old boy with a background of autistic spectrum disorder who presented with severe muscle weakness and significant rhabdomyolysis. Before the onset of muscle weakness, he was very active but was completely bedridden at presentation. Diagnosis was established quickly by urine organic acid and plasma acylcarnitine analysis. He has shown significant improvement after starting oral riboflavin supplementation and is now fully mobile. This case highlights that late-onset glutaric aciduria type II is an important differential diagnosis to consider in teenagers presenting with proximal myopathy and rhabdomyolysis and it may not be associated with hypoglycemia.
We describe a patient with hemiconvulsion-hemiplegia-epilepsy syndrome. The pathophysiology of hemiconvulsion-hemiplegia-epilepsy syndrome remains uncertain and there are probably multiple potential contributing factors. Our patient had a chromosomal 16p13.11 microdeletion that confers susceptibility to various types of epilepsy. This is the first report detailing an association of hemiconvulsion-hemiplegia-epilepsy syndrome with a 16p13.11 deletion and identifies another potential causal factor for hemiconvulsion-hemiplegia-epilepsy syndrome.
We report 2 pediatric patients who presented initially with seizures followed by subacute language regression characterized by a verbal auditory agnosia. These previously normal children had no evidence of expressive aphasia during their symptomatic periods. Further, in both cases, auditory agnosia was associated with sleep-activated electroencephalographic (EEG) epileptiform activity, consistent with Landau-Kleffner syndrome. However, both cases are unique since the episodic auditory agnosia and sleep-activated EEG epileptiform activity rapidly responded to combination therapy with pulse benzodiazepine and corticosteroids. Further, in each case, recurrences were characterized by similar symptoms, EEG findings, and beneficial responses to the pulse benzodiazepine and corticosteroid therapy. These observations suggest that pulse combination high-dose corticosteroid and benzodiazepine therapy may be especially effective in Landau-Kleffner syndrome.
Horner syndrome may be seen in infants with extended Erb obstetric brachial plexus palsy. However, its prognostic value in these infants has not been previously investigated. A total of 220 infants with extended Erb palsy were included and divided into 2 groups: group I (n = 209) were infants with extended Erb palsy without Horner syndrome, and group II (n = 11) were infants with extended Erb palsy and concurrent Horner syndrome. The rate of good spontaneous recovery of elbow flexion was 59% in group I and 27% in group II, and the difference was significant (P = .038). The rate of good spontaneous recovery of wrist extension was 61% in group I and 0% in group II, and the difference as highly significant (P < .0001). Concurrent Horner syndrome in infants with extended Erb palsy may be considered as a poor prognostic sign for recovery of the sixth and seventh cervical roots.
Vitamin B12 deficiency in children can rarely cause neurologic manifestations. In this series, 14 pediatric cases (median age 11 months) have been described in whom association of vitamin B12 deficiency with developmental delay or regression was observed. Severe to profound delay was present in 8 (57%) patients. All the patients were exclusively or predominantly breast-fed and 10 of 12 mothers had low serum vitamin B12 levels. Three to 6 months after treatment, a mean gain of development quotient of 38.8 points was seen in 7 follow-ups. In settings with a high prevalence of vitamin B12 deficiency, this association should be actively searched for.
The authors undertook long-term neurologic outcomes of 27 patients aged 0 to 15 years with enterovirus 71–related acute flaccid paralysis from June 1998 to July 2012. Motor function outcome was graded from class I (complete recovery) to class V (permanent paralytic limbs). Twelve of 20 patients (60%) who received intravenous immunoglobulin for treatment of acute flaccid paralysis had motor function outcomes in classes III to V. The median duration of follow-up was 6 months, during which time 7 of 13 patients (54%) with central nervous system infection, 3 of 6 patients (50%) with autonomic nervous system dysregulation, and 3 of 8 patients (37%) with heart failure showed motor function outcomes in classes III to V. These findings suggested that the usage of intravenous immunoglobulin and the severity of disease staging at disease onset might not be able to predict long-term motor function outcomes.
Congenital cytomegalovirus infection is the most common infectious cause of congenital brain injury. Type and severity of congenital cytomegalovirus infection–related brain abnormalities depend on the developmental stage of the central nervous system at the time of fetal infection. The aim of this study was to follow the course of leukoencephalopathy in a patient with congenital cytomegalovirus infection. We describe brain magnetic resonance imaging (MRI) findings of a boy with symptomatic congenital cytomegalovirus infection performed at the age of 3 weeks, 13 months, and 4 and 7 years. Neonatal brain MRI showed most of characteristic findings in congenital cytomegalovirus infection with most prominent white matter abnormalities and cortical dysplasia. MRI follow-up images showed that cortical dysgenesis remained unchanged and static, whereas white matter abnormalities evolved over the years. We propose that leukoencephalopathy in congenital cytomegalovirus infection is not only nonprogressive or static but even evolutive and suggests both underlying disruption and delay of myelination.
SOX6, a member of the SOX gene family, plays a key role in the development of several mammalian tissues and organs, including the central nervous system. Specifically, this gene modulates the differentiation and proliferation of interneurons in the medial ganglionic eminence, as well as oligodendrocytes in the spinal cord. We describe the case of a 4-year-old girl with global developmental delay and a spinal cord syrinx who presented with recurrent episodes of parkinsonian symptoms subsequent to febrile illnesses. The symptoms included gait instability, tremor, and dysarthria, with a progressive relapsing-remitting course over the span of 2 years. The patient was later found to have a large deletion-type mutation in the SOX6 gene. This case is the first report in humans implying a role for SOX6 in basal ganglia function, as well as spinal cord development.
Stroke is an extremely rare complication of congenital heart block in children. We report a 2-year-old girl with congenital complete heart block who presented with acute-onset right middle cerebral artery territory stroke. The congenital heart block was secondary to maternal lupus.
Neurocysticercosis is a common parasitic infection of the central nervous system. Intraparenchymal giant cysticercosis has been described in literature, but this is a rare report of a thalamic giant cysticercosis in a young child where the diagnosis could be made on follow-up. A 11/2-year-old male child presented with seizures, hemiparesis, and features of raised intracranial pressure. Initial neuroimaging findings of thalamic swelling with minimal edema and contrast enhancement with choline peak on magnetic resonance spectroscopy were attributed to thalamic glioma. Subsequent imaging revealed a ring enhancing lesion with an eccentric nodule suggestive of neurocysticercosis. It later resolved with residual gliosis. The presence of a pathognomic scolex and the resolution of size and symptoms without definitive treatment helped in making the diagnosis. This report reinforces the importance of considering cysticercosis in diagnosis of acute presentations of large cerebral masses in infants, particularly in prevalent regions, and emphasizes the follow-up of these patients.
Duane retraction syndrome consists of abduction deficit and palpebral fissure narrowing, upshoots, or downshoots on adduction. Infants with abduction deficit should be considered to have Duane retraction syndrome until disproven, because congenital abducens nerve palsy is extremely rare. The abducens nerve on the affected side is absent in type 1 Duane retraction syndrome and in some type 3 patients. The authors present a 7-month-old girl who showed limitation of abduction simulating Duane retraction syndrome. High-resolution magnetic resonance imaging (MRI) revealed atrophic lateral rectus and present abducens nerve. This report is important because this case showed that congenital abducens nerve palsy exists, although it is extremely rare, and high-resolution MRI could be pivotal for the differentiation of Duane retraction syndrome and congenital abducens nerve palsy in infancy.
The aim of this study was to describe psychological, behavioral, and adjustment problems in children and adolescents with acquired brain lesions of different origins. Three groups of patients with acquired brain lesions (15 patients with infectious origin, 37 with vascular origin, and 15 with other origin), ranging in age from 4 to 18 years, received a psychological evaluation, including the Child Behavior Checklist for ages 4 to 18 and the Vineland Adaptive Behavior Scale. About half of the total sample (47.8%) showed psychological problems. Difficulties varied according to the cause of the brain lesions. The most problematic patients were children with brain lesions of infectious origin, whereas children with brain lesions of vascular origin scored lower on most of the Child Behavior Checklist scales. The authors conclude that psychological and behavioral difficulties are very common among school-aged children with acquired brain lesions, and their relevance and impact must necessarily be considered.
Myoclonus dystonia syndrome is often misdiagnosed in young children and appropriate treatment is delayed, which has a negative impact on motor development, participation, and emotional well-being. In severely affected patients, deep brain stimulation of the globus pallidus internus has been used successfully to treat both dystonia and myoclonus. Here, the authors present a case of early successful treatment of myoclonus dystonia syndrome by pallidal deep brain stimulation in a patient at the age of 17 years leading to 83% reduction in dystonia score and 89% reduction in myoclonus. The patient gained significant improvement in motor function as well as increased participation and reduced stigma.
Deoxyguanosine kinase (DGUOK) gene mutations have been identified in the hepatocerebral form of mitochondrial DNA depletion syndromes. We report here clinical and laboratory features of 3 infants with novel DGUOK gene mutations, c.130G>A (Glu44Lys), c.493G>A (Glu165Lys), and c.707+3_6delTAAG.
Acute encephalitis in children is a life-threatening neurological emergency. However, little is reported about the outcome of this devastating illness in the United States. The authors retrospectively reviewed the charts of patients admitted to a regional pediatric intensive care unit with the diagnosis of acute encephalitis between 2006 and 2011. In 41 cases that met the inclusion criteria, the most common presenting symptoms were fever (65.9%), altered mental status (61%), and seizures (58.5%). Eight patients (19.5%) who presented with refractory status epilepticus had a longer median length of stay in the pediatric intensive care unit (46 vs 4 days; P < .0001) and a significant worsening of Pediatric Cerebral Performance Category score on discharge by 2 or more points (odds ratio 20.38; 95% confidence interval, 2.89-143.52). All children survived to hospital discharge. In conclusion, children with acute encephalitis who present with refractory status epilepticus have a worse neurological outcome and a longer stay in the pediatric intensive care unit.
Many neurodegenerative diseases can be misdiagnosed as cerebral palsy. The correct diagnosis is reached when the condition recurs in families or when there are specific clinical signs. The clinical and imaging features of 3 children, from 2 unrelated families, presenting with global developmental delay and dystonia are described, in whom the presence of cyanosis and methemoglobinemia confirmed the diagnosis of recessive hereditary methemoglobinemia type 2. Magnetic resonance imaging showed significant cerebellar atrophy in 2 of the 3 babies. In dark-skinned children, this condition is underdiagnosed, as mild cyanosis is difficult to detect. Screening for methemoglobinemia in children with dystonia, microcephaly, and progressive cerebellar atrophy can be helpful in identifying more cases. As there is no curative treatment for this autosomal recessive condition, the exact diagnosis offers the best chance for prenatal screening, by detecting deficient NADH - cytochrome b5 reductase enzyme activity or by identifying the specific mutation in cultured amniotic fluid cells.
In this study, the authors examined the clinical manifestations, skeletal muscle pathological characteristics, and neuroimaging results of 2 cases of Leigh syndrome in a Chinese family. The 2 patients presented with general weakness, and 1 of them presented with an impairment of vision. Skeletal muscle biopsies showed a deficiency in cytochrome c oxidase levels. Brain magnetic resonance imaging showed increased T1 and T2 signal intensities in the centrum ovale and dentate nucleus. Diffusion-weighted imaging showed a high-intensity signal. Magnetic resonance spectroscopy showed elevated levels of lactic acid in lesions. The examination of 1 patient at disease onset and during disease remission showed that the lesions detected by magnetic resonance imaging and diffusion-weighted imaging, and the peak for lactic acid detected by magnetic resonance spectroscopy, decreased during remission. These data suggest that changes in the imaging results of patients with Leigh syndrome correlate with disease course and pathogenetic condition.
This study evaluated the prevalence of pre- and perinatal risk factors in a cohort of children with autism spectrum disorders compared with the New Jersey population. Our cohort included 268 individuals with an autism spectrum disorder. Birth histories were obtained by a self-administered questionnaire. The autism spectrum disorders cohort rates of 7 perinatal risk factors were significantly higher than New Jersey state rates: mother’s age 35 years or older, low birth weight, multiple gestation, prematurity, vaginal bleeding, prolonged labor, and hypoxia. Analysis of clustering of risk factors in the cohort showed no significant differences across maternal and paternal age groups. Older mothers in the cohort had a higher risk of infant hypoxia. Multiple risk factors during pregnancy appear to be associated with a higher risk of autism spectrum disorders in offspring, supporting the hypothesis that environmental influences in conjunction with genetics contribute to the causes of autism spectrum disorders.
Clinical trials in children with attention-deficit hyperactivity disorder (ADHD) show variability in behavioral responses to the selective norepinephrine reuptake inhibitor atomoxetine. The objective of this study was to determine whether transcranial magnetic stimulation–evoked short interval cortical inhibition might be a biomarker predicting, or correlating with, clinical atomoxetine response. At baseline and after 4 weeks of atomoxetine treatment in 7- to 12-year-old children with ADHD, transcranial magnetic stimulation short interval cortical inhibition was measured, blinded to clinical improvement. Primary analysis was by multivariate analysis of covariance. Baseline short interval cortical inhibition did not predict clinical responses. However, paradoxically, after 4 weeks of atomoxetine, mean short interval cortical inhibition was reduced 31.9% in responders and increased 6.1% in nonresponders (analysis of covariance t 41 = 2.88; P = .0063). Percentage reductions in short interval cortical inhibition correlated with reductions in the ADHD Rating Scale (r = 0.50; P = .0005). In children ages 7 to 12 years with ADHD treated with atomoxetine, improvements in clinical symptoms are correlated with reductions in motor cortex short interval cortical inhibition.
We hypothesize that the imbalance between oxidant and antioxidant systems might be involved in the pathophysiology of breath-holding spells. The aim of this study is to evaluate the oxidant-antioxidant status in children with breath-holding spells compared to healthy children. In a case control study, 67 children with breath-holding spells were compared with 60 healthy children. Malondialdehyde values of the patients were significantly higher than those in control. Levels of selenium, glutathione peroxidase, and superoxide dismutase of the patient group are significantly lower than those in control. The present study gives helpful data about oxidant-antioxidant systems alterations in breath-holding spells in such a large patient group. These data give support to the hypothesis of the imbalance between oxidant and antioxidant systems, and selenium deficiency might be involved in the pathophysiology of breath-holding spells, suggesting the role of this system dysregulation in breath-holding spells.
To contribute to characterize electroencephalographic (EEG) activity in pediatric anti-N-methyl-
Williams syndrome is a relatively rare genetic disorder caused by the hemizygous microdeletion of a region in chromosome 7q11.23. Individuals with Williams syndrome typically present with a highly social, overfriendly, and empathic personality. Comorbid medical and neuropsychiatric disorders are common. Reports of effective pharmacological treatment of associated neuropsychiatric disorders are limited. The authors describe the successful treatment of interfering anger, aggression, and hair-pulling with N-acetylcysteine in a 19-year-old woman with Williams syndrome. The neuropsychiatric symptoms emerged 1 week following an upper gastrointestinal endoscopy, for which fentanyl, midazolam, and propofol were used as anesthetics. The patient’s treatment course and hypothesized mechanisms underlying the clinical presentation and symptom resolution are described.
The purpose of this study was to test for differences in brain shape among children with cleft palate only (n = 22), children with cleft lip and palate (n = 35), and controls (n = 39) using Euclidean distance matrix analysis. Sixteen percent of interlandmark distances differed between children with cleft palate only and controls, 10% differed between children with cleft lip and palate and controls, and 10% differed between children with cleft palate only and children with cleft lip and palate. Major differences in brain shape associated with cleft lip and/or palate included posterior expansion of the occipital lobe, reorientation of the cerebellum, heightened callosal midbody, and posterior displacement of the caudate nucleus and thalamus. Differences in brain shape unique to cleft palate only and to cleft lip and palate were also identified. These results expand upon previous volumetric studies on brain morphology in individuals with cleft lip and/or palate and provide additional evidence that the primary defect in cleft lip and/or palate results in both facial and brain dysmorphology.
The outcomes of children with cryptogenic seizures most probably arising from the frontal lobe are difficult to predict. We retrospectively collected data on 865 pediatric patients with epilepsy. In 78 patients with cryptogenic frontal lobe epilepsy, the age at first seizure was inversely correlated with the outcome, including the degree of intellectual disability/developmental delay (P = .002) and seizure frequency (P = .02) after adequate treatment. Intellectual disability was more prevalent in children with a first seizure at 0 to 3 years old (P = .002), and seizures were more frequent in those with a first seizure at 0 to 6 years old than at 7 to 16 years old (P = .026). For pediatric cryptogenic frontal lobe epilepsy, the age at first seizure is important and inversely correlated with outcome, including seizure frequency and intellectual disability.
Expression levels of monoamine oxidase A (MAOA), the enzyme that related to monoamine neurotransmitters metabolism such as serotonin, are related to schizophrenia and autism spectrum disorder. Forkhead box protein P2 (FOXP2), a transcription factor, is associated with abnormal language development and is expressed in several areas of the central nervous system in response to serotonin. For this reason, we undertook interaction analysis between MAOA and FOXP2 in autism spectrum disorder, including testing the verbal communication score of the childhood autism rating scale. In interaction analysis, the FOXP2-TCGC (rs12531289-rs1350135-rs10230087-rs2061183) diplotype and MAOA-TCG (rs6323-rs1801291-rs3027407) haplotype were significantly associated with autism spectrum disorder in males. However, when the interaction term was omitted, neither MAOA nor FOXP2 was associated with autism spectrum disorder or verbal communication. These results indicate that language and speech ability is affected by an interaction between FOXP2 and MAOA, but not by either gene separately.
Epileptic encephalopathies represent a clinically and genetically heterogeneous group of disorders, majority of which are of unknown etiology. We used whole-exome sequencing of a parent-offspring trio to identify the cause of early infantile epileptic encephalopathy in a boy with neonatal seizures, movement disorders, and multiple congenital anomalies who died at the age of 17 months because of respiratory illness and identified a de novo heterozygous missense mutation (c.3979A>G; p.Ile1327Val) in SCN8A (voltage-gated sodium-channel type VIII alpha subunit) gene. The variant was confirmed in the proband with Sanger sequencing. Because the clinical phenotype associated with SCN8A mutations has previously been identified only in a few patients with or without epileptic seizures, these data together with our results suggest that mutations in SCN8A can lead to early infantile epileptic encephalopathy with a broad phenotypic spectrum. Additional investigations will be worthwhile to determine the prevalence and contribution of SCN8A mutations to epileptic encephalopathies.
Deficiency of vitamin B12 causes megaloblastic anemia and nervous system demyelination. Structures affected in the nervous system include spinal cord, cranial and peripheral nerves, and brain white matter. A 9-year-old boy presented with knuckle hyperpigmentation and oral ulcers for 3 years, pallor and easy fatigability for 6 months, gait abnormalities for 3 months, and abnormal speech and behavioral abnormalities for 3 days. On examination, he had physical signs of megaloblastic anemia, mood swings with intermittent hallucinations, and features of cerebellar impairment. Blood investigations revealed megaloblastic anemia, and pernicious anemia was ruled out. Brain magnetic resonance imaging (MRI) revealed bilateral cerebellar signal changes. He received treatment for vitamin B12 deficiency and appropriate nutritional counseling. Three months later, he showed significant clinical and radiologic resolution. To our knowledge, isolated cerebellar involvement as the sole neurologic manifestation of vitamin B12 deficiency has not been described previously in children.
The data on the rate of brain imaging abnormalities in autistic spectrum disorders are still inconsistent. A recent study on patients with high-functioning autism found that approximately 90% of children had normal magnetic resonance imaging (MRI) scans whereas an unexpected high rate of MRI abnormalities was reported in 77 nonsyndromic autistic children with or without intellectual disability. The aim of this study was to evaluate the prevalence of neuroradiologic findings in low-functioning autistic children compared to controls matched for age. Minor brain abnormalities were found in 44% of patients and 22% of controls. Our main result is the high rate of mega cisterna magna in autistic patients. High rate of minor neuroradiologic abnormalities in low-functioning autistic patients could contribute to the research about the various endophenotypes and complete the clinical assessment of children with autistic spectrum disorder and intellectual disability.
This study investigates the craniospinal flows of blood and cerebrospinal fluid using phase-contrast magnetic resonance imaging (MRI) on 23 control neonates and infants (5 d-68 mo old). Mean arterial cerebral blood flow increased with age of infant from 180 mL/min after birth to 1330 mL/min around 6 years of age. This corresponds to 51 mL/min/100 g and 95 mL/min/100 g, respectively. Cervical cerebrospinal fluid stroke volume increased from 38 x 10–3 mL to 752 x 10–3 mL per cardiac cycle. After arterial systolic blood inflow, we observed a delay of the venous outflow that was always preceded by cerebrospinal fluid flushing out through the spinal canal. These results highlighted the importance of compliance of the spinal compartment and the interaction of blood and cerebrospinal fluid dynamics. The capacity of the spinal compartment to receive intracranial cerebrospinal fluid in presence of fontanels was demonstrated. We provide reference values to understand the physiology of cerebrospinal fluid and cerebral blood.
Understanding what patients and their parents want is essential to plan appropriate patient-centered care. Questionnaires were distributed to 500 consecutive children and parents seen for their first pediatric neurology consultation. Both patients and their families answered questions about their expectations of the consultation, their level of worry, and the Penn State Worry Questionnaire. The 5 most important issues for the parents were to get information, to work with the doctor to manage the problem, to have questions answered, to find out what was wrong, and to discuss the impact on the child’s life. The children had very similar priorities. The 5 least important concerns for parents were to get a prescription, blood tests, to talk to others with similar problems, to get a radiograph/computed tomography/magnetic resonance imaging (MRI) and to be told nothing is wrong. The pediatric neurologists did well in anticipating these priorities but had more difficulty appreciating parent and patient level of worry.
The purpose of this article is to provide an overview of preimplantation genetic diagnosis and identify the relevant moral questions it raises. In the course of this discussion, the scope of parental rights and the inherent difficulty in defining disease/disability will be considered.
Quantification of orienting responses can be used to differentiate between children with cerebral visual impairment and infantile nystagmus syndrome. To further improve the sensitivity of this method, we compared orienting responses to a Cartoon stimulus, which contains all sorts of visual information, to stimuli that contain only Contrast, Form coherence, Motion coherence, Color and Motion detection. The stimuli were shown on an eye tracker monitor using a preferential looking paradigm. We found that both groups of children showed general slowing in orienting responses compared to controls. The children with cerebral visual impairment had significantly prolonged responses to Cartoon compared to the children with nystagmus, whereas the children with nystagmus had prolonged responses to Motion detection and larger fixation areas. Previously reported differences in orienting responses to Cartoon were replicated. Application of specific visual information did not alter the sensitivity of the method to distinguish between children with visual processing deficits.
We conducted a retrospective cohort study to investigate the association between prepregnancy obesity in women and risk of cerebral palsy and epilepsy in their children using data from the South Carolina Medicaid program. The cohort included 83,901 maternal-child pairs; 100 cases of cerebral palsy were initially identified, followed by 53 cases that had at least 2 cerebral palsy diagnoses. For confirmed epilepsy, diagnosed on at least 5 occasions or by more than 1 provider, 83,472 observations were included with 338 cases. There was no association between maternal body mass index and risk of childhood epilepsy. A significant association between increasing maternal body mass index and any diagnosis of cerebral palsy was found, and morbid obesity was associated with increased risk of any and confirmed cerebral palsy. In conclusion, there appears to be an association of maternal body mass index with cerebral palsy, but there is no evidence to support an association with epilepsy.
Animal studies suggest that hypothermia decreases seizure burden, whereas limited human data are inconclusive. This retrospective cohort study examines the relationship between therapeutic hypothermia and seizure in neonates with hypoxic-ischemic encephalopathy. Our center admitted 224 neonates from July 2004 to December 2011 who met institutional cooling criteria. Seventy-three neonates were born during the pre-cooling era, prior to November 2007, and 151 were born during the cooling era. Among neonates with moderate encephalopathy, the incidence of seizure in cooled infants was less than half the incidence in those not cooled (26% cooling, 61% pre-cooling era; risk ratio = 0.43, 95% confidence interval = 0.30-0.61). Among neonates with severe encephalopathy, there was no difference in the incidence (83% vs 87%; risk ratio = 1.05, 95% confidence interval = 0.78-1.39). These results support animal data and suggest a mechanism by which neonates with moderate encephalopathy can benefit more from cooling than neonates with severe encephalopathy.
Rett syndrome is a neurodevelopmental disorder that manifests itself early in childhood, progresses with the evolution of characteristic clinical signs and symptoms and is confirmed by mutation in the methyl-CpG-binding protein 2 gene. Seizures are present in a majority of Rett patients. Respiratory dysrhythmia in the awake state is present in two-thirds of patients, leading in some cases to severe nonepileptic paroxysmal events. There are no optimal treatment recommendations thus far. The aim of this case study is to present the electro-clinical correlation of severe respiratory dysrhythmia mimicking seizures in 2 Rett patients and effective treatment with topiramate.
Detecting silent cerebral infarcts on magnetic resonance images (MRIs) in children with sickle cell anemia is challenging, yet reproducibility of readings has not been examined in this population. We evaluated consensus rating, inter-, and intra-grader agreement associated with detecting silent cerebral infarct on screening MRI in the Silent Infarct Transfusion Trial. Three neuroradiologists provided consensus decisions for 1073 MRIs. A random sample of 53 scans was reanalyzed in blinded fashion. Agreement between first and second consensus ratings was substantial ( = 0.70, P < .0001), as was overall intergrader agreement ( = 0.76, P < .0001). In the test-retest sample, intragrader agreement ranged from of 0.57 to 0.76. Consensus decisions were more concordant when MRIs contained more than one larger lesions. Routine use of MRI to screen for silent cerebral infarcts in the research setting is reproducible in sickle cell anemia and agreement among neuroradiologists is sufficient.
Ketogenic diet is a structured effective treatment for children with intractable epilepsy. Several reports have indicated poor linear growth in children on the diet but the mechanism of poor growth has not been elucidated. We aimed to explore whether the protein to energy ratio plays a role in linear growth of children on ketogenic diet. Data regarding growth and nutrition were, retrospectively, collected from the clinical histories of 35 children who were treated with ketogenic diet for at least 6 months between 2002 and 2010. Patients were stratified into groups according to periods of satisfactory or poor linear growth. Poor linear growth was associated with protein or caloric intake of <80% recommended daily intake, and with a protein-to-energy ratio consistently ≤1.4 g protein/100 kcal even when protein and caloric intakes were adequate. We recommend a protein-to-energy ratio of 1.5 g protein/100 kcal be prescribed to prevent growth retardation.
Children with Down syndrome show hypotonia and ligamentous laxity that are associated with motor development delay. Neurologic disorders are common in children with Down syndrome; however, in literature the presence of periodic movement disorders has not yet been described. We report 2 different types of periodic movement disorders in 2 infants with Down syndrome. In the first case, we described an 8-month-old girl with involuntary head nodding and absence of any other neurologic or ophthalmologic abnormalities. In the second case, we described a 6-month-old boy with abnormal but painless head rotation and inclination, alternating from side to side. Episodes of head tilting were often associated with a state of general uneasiness. Neurologic examination between attacks was normal. The aim of this paper is to provide practical information on recognition and management of movement disorders in Down syndrome.
Parkinsonism caused by infection is uncommon in children. We report 2 previously healthy children with acute self-limiting parkinsonism following Mycoplasma pneumoniae infection, with normal brain magnetic resonance imaging (MRI). Our case report expands the phenotype of parkinsonism associated with M pneumoniae infection. We recommend that children with acute parkinsonism preceded by a period of febrile illness, even with a normal brain MRI, should be investigated for M pneumoniae infection.
This study explored predictors of response to vagus nerve stimulation in childhood-onset epilepsy. This retrospective chart review included all patients with new vagus nerve stimulator insertion between January 1, 2006, and December 31, 2011. Primary outcome was change in seizure frequency classified on the International League Against Epilepsy scale. Overall, 67.4% (95% confidence limits 53.3%-81.6%) of the patients had outcome of class 4 or better, and 4 patients (9.3%, 95% confidence interval 0.5%-18.1%) achieved complete seizure freedom (mean follow-up 3.5 y). Absence of magnetic resonance imaging (MRI) lesion (odds ratio 6.068, 95% confidence interval 1.214-30.329, P = .028) and duration of epilepsy before implantation (odds ratio 1.291, 95% confidence interval 1.015-1.642, P = .038) were found to be statistically significant predictors of good outcome and provided a sufficient fit to the data (area under the receiver operating characteristic curve .80, Hosmer-Lemeshow goodness of fit P = .92). This study provides preliminary evidence that nonlesional patients are significantly more likely to have better outcome with vagus nerve stimulation.
Wernicke encephalopathy represents a well-known entity characterized by a set of cognitive and neurologic alterations. Wernicke encephalopathy is rare and under-recognized in childhood and may be fatal. Few cases have been documented in pediatric oncology. We report on 2 Wernicke encephalopathy cases that occurred in children having a brain tumor. The diagnosis of Wernicke encephalopathy was suggested by clinical manifestations associated with the typical radiologic findings and a laboratory evidence of thiamine deficiency. No large series have been published to support the evidence that pediatric malignancies represent a demonstrated factor of increased risk to develop a Wernicke encephalopathy. Moreover, the diagnosis may be even more difficult in brain tumors, considering the overlapping symptoms and the risk of encephalopathy related to both the disease and the treatment. Wernicke encephalopathy should be considered in all children with cancer presenting a neurologic deterioration, mainly in brain tumors. An early diagnosis is imperative for a prompt therapy that might prevent or minimize the irreversible brain damage related to this condition.
Narcolepsy with cataplexy is a severely disabling disorder very often arising in childhood. Data on neuropsychological impairment in children are scant. We administered standardized neuropsychological tests to 13 children with narcolepsy with cataplexy. Overall, our patients displayed multiple patterns of cognitive and behavioral dysfunction, and often academic failure (7 cases out of 13). All children had a normal full intelligence quotient (IQ), but 3 patients presented a significantly higher and 2 a significantly lower Verbal IQ compared to Performance IQ, respectively. Mean sleep latency was significantly correlated (P < .05) to alertness functions. Eight patients displayed behavioral problems: emotional symptoms and conduct problems prevailed. Childhood narcolepsy with cataplexy represents a risk factor for subtle and heterogeneous cognitive impairments potentially resulting in academic failure, despite the normal IQ. These children also have a certain psychopathological risk. All this seems to be at least partially detached from the direct effects of daytime sleepiness.
Periventricular leukomalacia is the most common type of brain injury in premature infants. Our aim is to describe the frequency and the features of epilepsy in a single-center population of 137 children with periventricular leukomalacia. Forty-two of the 137 (31%) patients presented epilepsy. Twelve percent of these patients presented West syndrome, whereas 19% showed a pattern of continuous spike-waves during slow sleep syndrome. In the latter group, outcome was frequently unfavorable, with a greater number of seizures and more drug resistance. A significant association was found between epilepsy and neonatal seizures, spastic tetraplegia, and mental retardation. Although less common than in other forms of brain injury, epilepsy is nevertheless a significant complication in children with periventricular leukomalacia. The fairly frequent association with continuous spike-waves during slow sleep syndrome deserves particular attention: electroencephalographic sleep monitoring is important in order to provide early treatment and prevent further neurologic deterioration.
Primary diffuse leptomeningeal gliomatosis is a disease with an aggressive course that can result in death. To date, 82 cases have been reported. Here, the case of a 3-year-old male patient presenting with strabismus, headache, and restlessness is reported. Physical examination revealed paralysis of the left abducens nerve, neck stiffness, and bilateral papilledema. Tuberculous meningitis was tentatively diagnosed, and antituberculosis treatment was initiated when cranial imaging revealed contrast enhancement around the basal cistern. Craniocervical magnetic resonance imaging (MRI) was performed when there was no response to treatment, and it revealed diffuse leptomeningeal contrast enhancement around the basilar cistern, in the supratentorial and infratentorial compartments, and in the spinal region. Primary diffuse leptomeningeal gliomatosis was diagnosed by a meningeal biopsy.
We report an unusual case of Leigh syndrome due to the m.10191T>C mutation in the complex I gene MT-ND3. This mutation has been associated with a spectrum of clinical phenotypes ranging from infant lethality to adult onset. Despite infantile onset and severe symptoms, our patient has survived to early adulthood because of a strict dietary regimen and parental care. This patient is an extreme example of the frequently prolonged course of Leigh syndrome due to this particular mutation.
Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. The syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects. The prevalence of Mowat-Wilson syndrome is currently unknown, but it seems that Mowat-Wilson syndrome is underdiagnosed, particularly in patients without Hirschsprung disease. We report here the first Egyptian case of Mowat-Wilson syndrome who was conceived by intracytoplasmic sperm injection. The patient manifested bilateral sensorineural hearing loss—a new feature not previously reported in cases of Mowat-Wilson syndrome. This report describes the first Egyptian patient of Mowat-Wilson syndrome who was conceived after intracytoplasmic sperm injection, and provides a new evidence for the inclusion of deafness among the congenital defects of the syndrome.
Neuronal migration disorders are a group of disorders that cause structural brain abnormalities and varying degrees of neurocognitive impairment, resulting from abnormal neuronal migration during brain development. There are several mutations that have been associated with these disorders. Here the case of a 4-year-old autistic boy is presented, who was found to have evidence of a neuronal migration disorder on magnetic resonance imaging (MRI) during a workup for seizures. Genetic testing did not reveal any of the gene mutations known to be associated with neuronal migration disorders but did reveal a microduplication at chromosome 15q13.3, a locus that has been previously associated with autism, cognitive impairment, and seizures. Although the concurrent presence of the genetic and structural abnormalities does not necessarily imply causality, the simultaneous independent occurrence of both conditions is certainly unusual. It is possible that there may be an association between this duplication syndrome and aberrant neuronal migration.
A 4-year-old boy was admitted with acute onset of hemiplegia of the right side that was secondary to a traffic accident. Initial computed tomography revealed a traumatic subarachnoid hemorrhage, and follow-up computed tomography showed a more localized hematoma of the left sylvian cistern. After a few days of conservative treatment, magnetic resonance imaging (MRI) revealed a cerebral infarction of the left lenticulostriate territory, even though magnetic resonance angiography showed preserved middle cerebral artery flow. Thus, we realized that the hematoma of the sylvian cistern was the so-called dense middle cerebral artery sign. This case of posttraumatic infarction suggested the importance of meticulous investigations and clinical correlations of imaging studies in pediatric patients with head injuries.
We assessed 10 youth football players (13.4 ± 0.7 y) immediately before and after their season to explore the effects of football participation on selected clinical measures of neurologic function. Postseason postural stability in a closed-eye condition was improved compared to preseason (P = .017). Neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery revealed that reaction time was significantly faster at postseason (P = .015). There were no significant preseason versus postseason differences in verbal memory (P = .507), visual memory (P = .750), or visual motor speed (P = .087). Oculomotor performance assessed by the King-Devick test was moderately to significantly improved (P = .047-.115). A 12-week season of youth football did not impair the postural stability, neurocognitive function, or oculomotor performance measures of the players evaluated. Though encouraging, continued and more comprehensive investigations of this at-risk population are warranted.
Continuous spike and wave in slow-wave sleep (CSWS) is an electroencephalographic (EEG) pattern characterized by generalized spike-wave discharges occurring for at least 85% of non–rapid eye movement (non-REM) sleep, with marked attenuation during rapid eye movement (REM) sleep. It has been described in a large number of structural and nonstructural neurologic conditions and is associated with epilepsy, behavioral disturbances, and severe neuropsychiatric impairment. We describe continuous spike and wave in slow-wave sleep in 2 patients (one with Rett syndrome and the other with Lhermitte-Duclos syndrome). To our knowledge, continuous spike and wave in slow-wave sleep has not been previously described in these conditions.
Because signs of nocturnal seizures can overlap with sleep respiratory events, clinicians can have difficulty distinguishing abnormal events related to sleep disorders from epileptic seizures. We describe the case of a 3-year-old child presenting with ictal electroencephalographic (EEG) activity associated with a particular form of atypical obstructive sleep apnea, characterized by increased respiratory rate, paradoxical breathing, desaturations, and tonic-dystonic posture associated with movement artifacts. Following cardiorespiratory polysomnography, the patient was initially misdiagnosed as having severe obstructive sleep apnea syndrome.
Frontonasal dysplasia is an etiologically heterogeneous development alteration including a set of anomalies affecting the eyes, forehead, and nose as a result of a malformation of the frontonasal elevation. It could occur either in isolation or as part of a syndrome such as frontonasal dysplasia associated with periventricular heterotopia. Our goal is to document the first clinical case of prenatal diagnosis for frontonasal dysplasia associated with periventricular heterotopia by fetal magnetic resonance imaging (MRI) at weeks 19.5 and 29 and postnatal MRI. In conclusion, the presence of frontonasal dysplasia in a prenatal ultrasonography should always be followed by a fetal MRI with routine screening for periventricular nodular heterotopias so as to establish a more adequate prognosis for the family.
Although much of children’s motor skills have a heredity component, at least half of the variance is likely to be influenced by the environment. It is important to ascertain features of the environment that are responsible so that toxins can be avoided, children at risk can be identified, and beneficial interventions initiated. This review outlines the results of published studies and recommends the areas where further research is required. We found much confusion with little comparability concerning the ages or measures used. Few studies had sufficient power and few allowed for confounders. We found that research to date implicates associations with prenatal drinking ≥4 drinks of alcohol per day; diabetes; taking antidepressant drugs; being deficient in iodine or iron; dietary fish; and postnatal depression. The child appearing to be most at risk was born of low birth weight (but not due to preterm delivery) or with neonatal problems.
Churg-Strauss syndrome is a rare form of small-vessel vasculitis. In the current report, we describe the case of a 17-year-old Czech girl predominantly characterized by peripheral neuropathy, the presence of cardiac and pulmonary involvement, hypereosinophilia, asthma, and sinusitis that led to the diagnosis of Churg-Strauss syndrome.
The ability to anticipate deficits would help with implementation of interventions for children affected by stroke. The Pediatric Stroke Outcome Measure (Measure) measures neurological impairment after stroke, but there has been little research examining the relationship between the Measure and functional outcomes. We hypothesized the Measure correlates with cognitive and behavioral outcomes. Thirty-six children with stroke were assessed with the Measure, and tested for cognitive ability, problem behavior, adaptive behavior, and social participation. We examined the correlation between the total Measure and outcomes and determined how subscale scores associated with outcomes. Higher total Measure scores correlated with poorer outcomes in cognitive ability, problem behaviors, adaptive behaviors, and social participation. Specific subscale scores correlated with poorer outcomes in multiple domains. The total Measure can be used to anticipate poor outcomes in multiple domains after stroke and can help the clinician in the treatment of children as they recover.
We used at-home assessments in a clinical trial to relieve the visit burden for participants. A total of 57 patients with type II or III spinal muscular atrophy were enrolled and 10 of them (7 type II and 3 type III) received at-home assessments. The primary end points were Gross Motor Function Measure, Manual Muscle Test, and serum biomarker. The secondary endpoints were Modified Hammersmith Functional Motor Scale and forced vital capacity. The correlation coefficients and analysis of covariance showed good reliability and validity of all outcome measures. Except for Gross Motor Function Measure and Modified Hammersmith Functional Motor Scale, there were no significant differences in measures between in-hospital and at-home groups (intersubject) or among 3 patients who received both at-home and in-hospital visits (intrasubject). We concluded that at-home assessments could provide sufficient reliability in a controlled trial. This modification could help design a successful clinical trial for spinal muscular atrophy.
Subacute sclerosing panencephalitis, a progressive neurodegenerative disorder of the central nervous system, can present atypically with uncharacteristic electroencephalographic (EEG) features at its onset albeit typically with progressive mental deterioration, behavioral changes, and myoclonic jerks. An atypical presentation of subacute sclerosing panencephalitis can lead to a delay in diagnosis, thus hindering early treatment. Herein, we describe a 14-year-old girl who presented with insomnia, amnesia, auditory and visual hallucinations. The patient’s electroencephalography on admission showed an alpha coma pattern. In spite of antipsychiatric treatment (olanzapine 20 mg/d) for 3 months, a progressive deterioration in neurologic function was observed. Subacute sclerosing panencephalitis was suspected and diagnosis was confirmed by increased titers of measles antibodies in the cerebrospinal fluid. The attention of pediatricians should be drawn to psychiatric symptoms as possible initial presentations of subacute sclerosing panencephalitis in order to avoid needless diagnostic and treatment procedures.
There is growing evidence that steroids are not beneficial for treatment of paediatric patients with Bell's palsy. To investigate, we conducted a retrospective longitudinal study examining notes of 100 children, over 12 years coded for facial nerve palsy. Of the 79 diagnosed with Bell's palsy, all recovered, and for 46 patients we had data on interval from onset of symptoms to resolution (median duration in treated group = 5 weeks, range = 39; median duration in untreated group = 6 weeks, range = 11; P = .86). From our results, we conclude that all children with Bell's palsy recovered, with or without steroid treatment, with no statistically significant difference in symptoms duration. Complications of unresolved Bell's palsy can have important long-term functional and psychosocial consequences. Therefore, we need further research on use of steroids in children with complete/severe cases; it would be a shame to omit treatment due to "absence of evidence" rather than "evidence of absence."
Wound healing is a key component of recovery for children with neurologic conditions undergoing neurosurgical procedures. Understanding factors that can impair wound healing aids in planning long-term clinical care. Children with neurofibromatosis type 1 are at risk for vasculopathies in the brain (including moyamoya vasculopathy) and in other organs, including the heart, lung, and skin. Neurofibromatosis 1 is caused by mutations in the gene for neurofibromin, a protein that plays a role in tissue maintenance and repair as well as tumor suppression. The authors report 2 children with neurofibromatosis 1–associated moyamoya vasculopathy who developed significant wound healing complications after pial synangiosis surgery. They discuss possible contributors to these complications, including the role of neurofibromin and the possibility of vasculopathy affecting the skin, and the implications of poor wound healing in pediatric neurology patients.
The progression of Duchenne muscular dystrophy is expected to negatively influence the patients’ health-related quality of life, but knowledge of the relationship with disease severity is limited. We investigated the relationship between health-related quality of life (KIDSCREEN-52 questionnaire) and disease severity (clinical assessments of body functions and activities) in 40 boys with Duchenne muscular dystrophy (19 ambulant, 21 wheelchair dependent) who were in different phases of the disease and underwent life-limiting events such as the loss of the ability to ambulate and the ability to lift the arms. In addition, we compared boys’ health-related quality of life perceptions with that of their parents. The participants’ health-related quality of life was similar to healthy peers’ and not influenced by disease severity, except for the physical domain. Parents scored much lower than the boys on the KIDSCREEN-52 domains Self Perception, Moods and Emotions, and Bullying. The latter finding needs attention in the management of Duchenne muscular dystrophy.
Circulating biomarkers such as somatic chromosome mutations are novel diagnostic tools to detect cancer noninvasively. We describe focal deletions found in a patient with atypical teratoid rhabdoid tumor, a highly aggressive early childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and histopathology to study the tumor anatomy. Next, we used whole genome sequencing (Next Gen Sequencing) and Bioinformatics interrogation to discover the presence of 3 focal deletions in tumor tissue and 2 of these 3 focal deletions in patient’s blood also. About 20% of the blood DNA sequencing reads matched the tumor DNA reads at the SMARCB1 gene locus. Circulating, tumor-specific DNA aberrations are a promising biomarker for atypical teratoid rhabdoid tumor patients. The high percentage of tumor DNA detected in blood indicates that either circulating brain tumor cells lyse in the blood or that contents of brain tumor cells traverse a possibly compromised blood-brain barrier in this patient.
Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P–Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP–Lambert-Eaton myasthenic syndrome). Lambert-Eaton myasthenic syndrome is a very rare disorder in children younger than age 12 years. Herein, we report a 25-year-old man with NP–Lambert-Eaton myasthenic syndrome, which onset was at the age of 10 years. To date, this is the most long-term follow-up of NP–Lambert-Eaton myasthenic syndrome in childhood. In our patient, the only symptomatic treatment with 3,4-diaminopyridine phosphate has been sufficient to guarantee him a good quality of life. Our data remind physicians to keep in mind the diagnosis of Lambert-Eaton myasthenic syndrome in children with a proximal myopathic pattern and they confirm the specificity of compound muscle action potential incremental pattern after brief maximal effort in Lambert-Eaton myasthenic syndrome.
Tuberous sclerosis complex is a genetic disorder caused by mutations in either the TSC1 or TSC2 gene that can result in the growth of hamartomas in multiple organ systems. Subependymal giant cell astrocytomas are slow-growing brain tumors associated primarily with tuberous sclerosis complex. They are usually located in the ventricles, often near the foramen of Monro, where they can cause an obstruction if they grow too large, leading to increased intracranial pressure. Surgery to remove a tumor has been the mainstay of treatment but can be associated with postoperative morbidity and mortality. Not all tumors and/or patients are suitable for surgery. The recent development of mammalian target of rapamycin inhibitors that target the pathway affected by TSC1/TSC2 mutations offers a novel pharmacotherapeutic option for these patients. We review the timing and use of surgery versus pharmacotherapy for the treatment of subependymal giant cell astrocytoma in patients with tuberous sclerosis complex.
The aim of this study is to evaluate the types and clinical characteristics of peripheral facial palsy in children. The hospital charts of children diagnosed with peripheral facial palsy were reviewed retrospectively. A total of 81 children (42 female and 39 male) with a mean age of 9.2 ± 4.3 years were included in the study. Causes of facial palsy were 65 (80.2%) idiopathic (Bell palsy) facial palsy, 9 (11.1%) otitis media/mastoiditis, and tumor, trauma, congenital facial palsy, chickenpox, Melkersson-Rosenthal syndrome, enlarged lymph nodes, and familial Mediterranean fever (each 1; 1.2%). Five (6.1%) patients had recurrent attacks. In patients with Bell palsy, female/male and right/left ratios were 36/29 and 35/30, respectively. Of them, 31 (47.7%) had a history of preceding infection. The overall rate of complete recovery was 98.4%. A wide variety of disorders can present with peripheral facial palsy in children. Therefore, careful investigation and differential diagnosis is essential.
Proactive nutritional management for children with spinal muscular atrophy type I can provide insight into improved spinal muscular atrophy care. This observational study consisted of a nutritional and medical history survey of children with spinal muscular atrophy type I collected in 2009-2011. Forty-four caregiver survey responses were evaluated using descriptive statistics. Average age of spinal muscular atrophy type I subjects was 5 years (5 mo-16 y). The subject cohort was composed of 22 males, 21 females, and 1 unreported. Nutrition support via feeding tube was utilized by 43 of 44 subjects. A majority of respondents reported using elemental or semi-elemental formula for subjects’ essential caloric intake (34 of 44). Formula intolerance issues were reported by many caregivers (27 of 44). Half of caregivers implemented dietary changes on their own or with guidance from other families; 15 caregivers consulted a registered dietitian. Survey responses and comments indicate need for evidence-based nutritional guidelines for spinal muscular atrophy.
Autism spectrum disorders are characterized by difficulties with reciprocal social interactions and restricted patterns of behavior and interest; one of these characteristic behaviors is food selectivity. The objective of this study was to perform a systematic review of the literature published between 1970 and 2013 concerning this eating behavior. The articles identified were analyzed in terms of sample size, study design, and criteria for assessment and intervention, as well as the results, level of evidence and grade of recommendation. The main search was conducted in Medline, Cochrane Library, Scielo, ScienceDirect, and Embase). There is empirical evidence and an overall scientific consensus supporting an association between food selectivity and autism spectrum disorders.
Anti-N-methyl-
Pachymeningitis is a rare disease of diverse etiology mainly affecting the adult population. Only 4 pediatric cases have been reported till now. We report the youngest child with pachymeningitis from India. Our case responded very well to antitubercular therapy with near complete recovery. Antitubercular therapy can be considered in children from endemic countries with hypertrophic pachymeningitis before labeling their condition as idiopathic hypertrophic pachymeningitis.
Idiopathic stabbing headache is a primary headache defined as "transient stabs of pain in the head that occur spontaneously in the absence of underlying organic disease." Although its variant form, stabbing pain with extracephalic distribution, has been reported in rare adult cases, pediatric presentation is extremely rare. We report an 8-year-old boy suffering from severe stabbing pain in the left side of the chest, right side of the abdomen, and right knee lasting 2 to 3 minutes with increasing frequency. He was completely normal between attacks. The attack was not accompanied with headache initially. Investigation showed no abnormality. A diagnosis of extracephalic stabbing pain was made. The patient’s symptoms were ameliorated by administration of valproic acid. This report illustrates that extracephalic stabbing pain can occur in pediatric patients. It is important to be aware of this peculiar condition because the pain is so severe, and it can be treatable with medication.
Development of both Crohn disease and Guillain-Barré syndrome likely involves autoimmunity associated with excessive inflammatory cytokines. We treated a girl who developed Guillain-Barré syndrome during the course of Crohn disease. Although high-dose -globulin therapy administered initially for Guillain-Barré syndrome was ineffective, plasmapheresis ameliorated her acute neuropathic symptoms. Crohn disease was managed with Salazopyrin administration and enteral feeding. Chronic inflammation of the intestinal mucosa caused by Crohn disease can allow presentation of microbial intestinal antigens normally hidden from the immune system. Such presentation could incite an extraintestinal immune response on the basis of molecular mimicry, leading to activation of systemic autoimmunity against the nervous system. Accordingly, concurrence of Guillain-Barré syndrome and Crohn disease in our patient appeared to result from shared autoimmune mechanisms and systemic and local increases in cytokine concentrations. The patient also developed erythema nodosum and gall stones, relatively common complications of Crohn disease. However, Guillain-Barré syndrome is rare.
Behçet disease is a systemic vasculitis of unknown etiology that can affect the neurologic system. Neuro-Behçet disease is not well defined in children and adolescents, and the diagnosis is difficult to make in this population as they often present with insufficient symptoms to meet diagnostic criteria. Psychiatric symptoms as the initial manifestation of neuro-Behçet disease has rarely been reported. We describe a 17-year-old boy who presented with acute psychosis and was subsequently diagnosed with neuro-Behçet disease. A rare combination of both cerebral venous thrombosis and parenchymal central nervous system involvement was identified by neuroimaging. Although treatment guidelines for neuro-Behçet disease are limited, the patient made demonstrative clinical and radiographic improvement with a combination of corticosteroids, anticoagulation, and immunosuppressants, including a tumor necrosis factor-α (TNFα) blocking agent.
Migraine equivalents are a group of periodic and paroxysmal neurologic diseases. Because headache is not a prominent symptom, the diagnosis might be challenging. The objective of the study was to evaluate the frequency and outcome of migraine equivalents. This was a retrospective study. We included benign paroxysmal torticollis of infancy, benign paroxysmal vertigo of infancy, abdominal migraine, cyclic vomiting, aura without migraine, and confusional migraine. We evaluated the frequency of events, treatment, and outcome. Out of 674 children with headache, 38 (5.6%) presented with migraine equivalents. Twenty-one were boys and the mean age was 6.1 years. Fifteen had abdominal migraine, 12 benign paroxysmal vertigo, 5 confusional migraine, 3 aura without migraine, 2 paroxysmal torticollis, and 1 cyclic vomiting. Prophylactic treatment was introduced in 23 patients; 4 lost follow-up and 19 had significant improvement. We conclude that the correct diagnosis of migraine equivalents enables an effective treatment with an excellent outcome.
Acute disseminated encephalomyelitis confined to the brainstem is associated with poor prognosis. We describe a case of a 10-year-old boy with acute disseminated encephalomyelitis in the brainstem that developed after influenza A infection. A 10-year-old boy presented with fever and prolonged disturbance of consciousness and was admitted to our hospital. Magnetic resonance imaging (MRI) of the midbrain, with T2-weighted and fluid-attenuated inversion recovery images, suggested acute disseminated encephalomyelitis accompanied by a brainstem lesion. Lumbar puncture showed pleocytosis and increased protein content, including myelin basic protein, interleukin-6, and immunoglobulin G, all suggestive of acute disseminated encephalomyelitis. Treatments such as methylprednisolone pulse therapy, intravenous immunoglobulin, and therapeutic hypothermia were performed. Although the patient presented with anisocoria with increased intracranial pressure monitoring during hypothermia, prompt therapy with
Ischemic strokes in children and young adults are fortunately rare. Contrasted with adult ischemic strokes, pediatric stroke etiologies vary greatly and are often unknown. Childhood lacunar strokes and trauma-induced strokes represent particularly uncommon subsets and have been reported infrequently in the literature. It is unique to find a combination of the 2—a lacunar stroke induced by trauma. Underreporting of these trauma-induced ischemic strokes could be responsible for perpetuating the lack of recognition. Here we present a lacunar stroke in a young woman associated with a water sport accident and explore relevant literature encircling deep brain ischemia coinciding with trauma.
We report on a child with Mild Encephalopathy with Reversible Splenial Lesion (MERS) associated with influenza infection and present a case series of neurological complications associated with influenza infections in children who presented to a tertiary children's hospital in Australia over a period of one year.
Fragile X syndrome (FXS) is one of the most frequent causes of mental retardation, intellectual disability, and autism. Most cases are the result of an expansion of the CGG trinucleotide repeat in the 5' untranslated region of the FMR1 gene and the subsequent functional loss of the related protein. We describe the case of a 4-year-old boy who clinically presents mild psychomotor delay without any major clinical dysmorphisms. Molecular analysis of the FMR1 gene showed mosaicism in terms of size and methylation, with one normal and 1 fully mutated allele, which is very rare in this syndrome. Physicians should therefore consider a diagnosis of FXS even if the patient’s phenotype is mild. Although rare, diagnosing this condition has important consequences for the patient’s rehabilitation and the family planning of parents and relatives.
Multiple sclerosis in children is characterized by more frequent relapses than in adult patients. Diagnosing and treating youth with multiple sclerosis present a number of challenges including differentiating organic relapses from functional symptoms. However, there is no literature describing coexistence of functionality in pediatric multiple sclerosis. Here, we report 2 cases in which inconsistency between clinical history, physical examination, imaging, and atypical disease progression led to suspicion of functional relapses. The purpose of this study is to raise awareness of functional relapses, as prompt recognition can prevent overtreatment and iatrogenic risks in children and adolescents with multiple sclerosis. Underlying psychiatric issues also need to be addressed.
Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients.
Arterial aneurysms, mostly aortic and intracranial, have been occasionally reported in patients with tuberous sclerosis complex. Brain magnetic resonance imaging reports of 404 patients with definite and 16 patients with either probable or possible tuberous sclerosis complex were revised for intracranial aneurysms. Among these patients, brain images of 220 patients with definite and 16 with probable or possible tuberous sclerosis complex were reviewed. Intracranial aneurysms were reported in 3 of 404 patients with a definite diagnosis (0.74%) (general population: 0.35%), including 2 children. A fourth intracranial aneurysm was found in a patient with probable tuberous sclerosis complex, who did not have tubers or subependymal nodules but had clinical manifestations related to neural crest derivatives, including lymphangioleiomyomatosis and extrarenal angiomyolipomas. The authors hypothesize that neural crest dysfunction can have a major role in intracranial arteriopathy in tuberous sclerosis complex, as smooth muscle cells in the forebrain vessels are of neural crest origin.
Nemaline myopathy is a type of the heterogeneous group of congenital myopathies. Generalized hypotonia, weakness, and delayed motor development are the main clinical features of the typical congenital form. Histopathology shows characteristic nemaline rods in the muscle biopsy. Mutations in at least 7 genes, including nebulin gene (NEB), proved to be responsible for this muscle disease. We present a boy with nemaline myopathy type 2 (NEM2) caused by compound heterozygosity for 2 novel mutations, a deletion and a duplication in the NEB gene. The deletion was inherited from the father and the duplication from the mother. Testing all family members supports genetic counseling.
Tuberous sclerosis complex is a genetic, multisystemic disorder characterized by circumscribed benign lesions (hamartomas) in several organs, including brain. This is the result of defects in the TSC1 and/or TSC2 tumor suppressor genes, encoding the hamartin-tuberin complex that inhibits the mammalian target of rapamycin pathway. Specific inhibitors of this pathway have been shown to reduce the volume of subependymal giant cell astrocytomas associated with tuberous sclerosis. Congenital lymphedema is rarely seen in association with tuberous sclerosis, with only a few reported cases. Although this association can be coincidental, the dysgenetic lymphatic system can represent a hamartia as a consequence of gene mutation. We describe a child with congenital lymphedema in tuberous sclerosis and associated subependymal giant cell astrocytoma who experienced lymphangitis under treatment with mammalian target of rapamycin inhibitors. Because our patient did not show worsening of lymphedema, congenital lymphedema does not seem to be a contraindication for this therapy.
Cerebral sinovenous thrombosis is a rare condition presenting with a wide spectrum of nonspecific symptoms that can make early diagnosis difficult. Cerebral sinovenous thrombosis has been associated with various etiologies. Iron deficiency anemia associated with cerebral sinovenous thrombosis in teenagers is rare. We present a teenage patient with complete thrombosis of the vein of Galen, straight sinus, and left internal cerebral vein associated with iron deficiency anemia due to severe menorrhagia. Mechanisms that can explain the association between iron deficiency anemia and thrombosis are discussed.
Transcranial direct current stimulation is a noninvasive brain stimulation technique that has been studied for the treatment of neuropsychiatric disorders in adults, with minimal side effects. The objective of this study is to report the feasibility, tolerability, and the short-term adverse effects of transcranial direct current stimulation in children from 5 to 12 years of age. It is a naturalistic study of 14 children who underwent 10 sessions of transcranial direct current stimulation as an alternative, off-label, and open-label treatment for various languages disorders. Frequency, intensity, adverse effects, and perception of improvement reported by parents were collected. The main side effects detected were tingling (28.6%) and itching (28.6%), acute mood changes (42.9%), and irritability (35.7%). Transcranial direct current stimulation is a feasible and tolerable technique in children, although studies regarding plastic and cognitive changes in children are needed to confirm its safety. In conclusion, this is a naturalistic report in which we considered transcranial direct current stimulation as feasible in children.
Propofol infusion syndrome is a recognized complication of prolonged propofol use in the pediatric population, but little is reported on other metabolic effects of propofol, especially in children with mitochondrial disorders. We report on a child with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome who received a single dose of propofol for procedural sedation. The patient’s initial presentation was consistent with a mild exacerbation of her underlying disease. She received a single dose of propofol and non–dextrose-containing fluids during a magnetic resonance imaging (MRI) study to rule out stroke and progressed to develop severe acidosis, neurologic deterioration, and cardiorespiratory compromise. This is the first case report of severe metabolic disturbances after a single dose of propofol administered for procedural sedation in a patient with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome and it questions the safety of propofol and absence of dextrose infusions during an acute illness in patients with mitochondrial disorders.
Spinal muscular atrophy with respiratory distress type 1 (SMARD1), a notably common form of non-5q-spinal muscular atrophy, can be confused with infantile spinal muscular atrophy and is characterized by the early onset of diaphragmatic palsy and predominantly distal muscle weakness. The defective gene, immunoglobulin mu-binding protein 2 (IGHMBP2), is located on chromosome 11q13-q21. In this study, we screened the IGHMBP2 gene in 53 unrelated Han Chinese non-5q-spinal muscular atrophy patients and 100 healthy controls. Two novel mutations (c.711+1G>C and c.1817G>A) and 5 nucleotide polymorphisms (c.57T>C, c.1554C>T, c.1914G>A, c.2080C>T, and c.2270G>C) were identified. However, only 1 patient harbored the compound heterozygous mutations (c.711+1G>C, c.1817G>A). Furthermore, the homozygous c.2636C>A (p.T879 K) variation, which has been included as a mutation in the Human Gene Mutation Database, was found both in patients and healthy individuals. In conclusion, the IGHMBP2 gene was not found to be a major causative gene linked to Han Chinese non-5q-spinal muscular atrophy patients.
We conducted the present study to assess melatonin secretion in a sample of children with migraine, to describe their sleep patterns and problems, and to examine the impact of sleep problems on migraine disability. The parents of 18 children with migraine completed the Children's Sleep Habits Questionnaire and Pediatric Migraine Disability Assessment Score in Arabic. The parents of 18 healthy controls also completed the Children's Sleep Habits Questionnaire. Urinary 6-sulphatoxymelatonin levels were determined with the enzyme-linked immunosorbent assay method. There was no significant difference in urinary 6-sulphatoxymelatonin between the migraine and control groups (Z = –0.127, P = .889). There were no significant differences between groups in Children's Sleep Habits Questionnaire subscales or total scores. There were significant correlations between bedtime resistance, parasomnias subscales, and migraine disability. Our findings indicate that nocturnal production of melatonin is not reduced in children with migraine, and sleep disturbances impact the degree of migraine disability.
The currently available scales for quantitative measurement of the severity of childhood dystonia require human observer ratings and provide poor granularity in the scores for individual limbs. We evaluated the use of new-generation high-quality touchscreens (an iPad®) according with the Fitts law, which is a mathematical model that takes into account the relation between movement time and the task accuracy. We compared the abilities of healthy subjects and children with dystonia. The linear relation described by Fitts law held for all the groups. The movement time and the information transmitted were age and severity related. Our results provide evidence for the usability and validity of using Fitts law as a quantitative diagnostic tool in children with dystonia. Furthermore, testing on touchscreen tablets may help to guide the design of user interfaces to maximize the communication rate for children who depend upon assistive communication devices.
Melanotic neuroectodermal tumor of infancy is a rare melanin-containing neoplasm with locally aggressive and rapid expansile growth, usually involving the maxilla, skull, and mandible of early infancy. Radical surgery is critical for a long-term outcome. We present a case of 14-month-old girl with rapid-growing subcutaneous mass arising in the right temporal bone and extending intracranially on computed tomographic scan. Radical surgery was performed. A brownish-black tumor composed of large pigmented epithelioid cells, positive for cytokeratins and HMB-45, and nests of small neuroblast-like cells positive for neuron-specific enolase and synaptophysin, was diagnosed as melanotic neuroectodermal tumor of infancy. The patient remained well without evidence of recurrence for 1 year after surgery. Clinicopathological features, management alternatives and outcome were discussed.
In Sub-Saharan Africa, intrarectal diazepam is the first-line anticonvulsant mostly used in children. We aimed to assess this standard care against sublingual lorazepam, a medication potentially as effective and safe, but easier to administer. A randomized controlled trial was conducted in the pediatric emergency departments of 9 hospitals. A total of 436 children aged 5 months to 10 years with convulsions persisting for more than 5 minutes were assigned to receive intrarectal diazepam (0.5 mg/kg, n = 202) or sublingual lorazepam (0.1 mg/kg, n = 234). Sublingual lorazepam stopped seizures within 10 minutes of administration in 56% of children compared with intrarectal diazepam in 79% (P < .001). The probability of treatment failure is higher in case of sublingual lorazepam use (OR = 2.95, 95% CI = 1.91-4.55). Sublingual lorazepam is less efficacious in stopping pediatric seizures than intrarectal diazepam, and intrarectal diazepam should thus be preferred as a first-line medication in this setting.
Neuronal ceroid lipofuscinosis is the most common childhood neurodegenerative disorder in the world, with an incidence of 1 in 100 000 live births. More than 400 mutations in at least 14 different genes are linked to multiple clinical variants. These progressive genetic disorders primarily manifest in the central nervous system due to an extensive loss of neurons, primarily in the cerebral and cerebellar cortices. Juvenile neuronal ceroid lipofuscinosis is the most common form and is primarily due to mutations in CLN3, which encodes a protein of unknown function. The most common such mutation in CLN3 is a 1.02-kb deletion that results in a frameshift and subsequent premature termination codon. Here we describe a patient with juvenile neuronal ceroid lipofuscinosis who has a novel c.1135_1138delCTGT mutation in CLN3. This deletion induces a frameshift and premature termination codon in CLN3 messenger ribonucleic acid that is likely recognized by nonsense-mediated decay and degraded, subsequently leading to decreased CLN3 protein abundance.
Primary hypertension is associated with decreased performance on neurocognitive testing and a blunted cerebrovascular reactivity to hypercapnia. Parents of 14 children with hypertension and prehypertension completed the Behavior Rating Inventory of Executive Functions. Children underwent 24-hour ambulatory blood pressure monitoring and transcranial Doppler with reactivity measurement using time-averaged maximum mean velocity and end-tidal carbon dioxide during hypercapnia-rebreathing test. Comparing the reactivity slope for the patients to historical controls showed a statistically significant difference (t = –5.19, df = 13, P < .001), with lower slopes. Pearson correlations of the Behavior Rating Inventory of Executive Functions scores with the reactivity slopes showed a statistically significant inverse relationship with Behavioral Regulation Index (r = –.60, P = .02), Metacognition Index (r = –.40, P = .05), and the Global Executive Component (r = –.53, P = .05). Children with hypertension have decreased executive function, and this correlates to low transcranial Doppler-reactivity slopes, suggesting that the brain is a target organ in hypertensive children.
Noonan syndrome is a common autosomal dominant neurodevelopmental disorder caused by gain-of-function germline mutations affecting components of the Ras-MAPK pathway. The authors present the case of a 6-year-old male with Noonan syndrome, Chiari malformation type I, shunted benign external hydrocephalus in infancy, and unique cerebrovascular changes. A de novo heterozygous change in the RAF1 gene was identified. The patient underwent brain magnetic resonance imaging, computed tomography angiography, and magnetic resonance angiography to further clarify the nature of his abnormal brain vasculature. The authors compared his findings to the few cases of Noonan syndrome reported with cerebrovascular pathology.
A malignant neoplasm in the central nervous system with diffuse white matter changes on magnetic resonance imaging (MRI) is rare in children. It could be misdiagnosed as acute disseminated encephalomyelitis. This report presents our experience based on 4 patients (3 male, 1 female; aged 7-13 years) whose MRI showed diffuse lesions in white matter and who were initially diagnosed with acute disseminated encephalomyelitis. All of the patients received corticosteroid therapy. After brain biopsy, the patients were diagnosed with gliomatosis cerebri, primitive neuroectodermal tumor and central nervous system lymphoma. We also provide literature reviews and discuss the differentiation of central nervous system neoplasm from acute disseminated encephalomyelitis.
We analyzed serum alpha-tocopherol, beta-carotene, retinol, and ascorbic acid levels and malondialdehyde and reduced glutathione concentrations on erythrocyte and cerebrospinal fluid in 30 patients with subacute sclerosing panencephalitis to evaluate oxidant and antioxidant status. Serum alpha-tocopherol, beta-carotene, retinol, ascorbic acid levels, and erythrocyte and cerebrospinal fluid reduced glutathione concentrations were decreased; however, erythrocyte and cerebrospinal fluid malondialdehyde levels were increased in the patients. Cerebrospinal fluid malondialdehyde levels were different between clinical stages of the disease (P < .05). Higher cerebrospinal fluid malondialdehyde level was associated with the more severe clinical stage. A positive correlation was found between cerebrospinal fluid malondialdehyde level and clinical stages (r = 0.42; P < .05) and between erythrocyte malondialdehyde level and clinical stages (r = 0.40; P < .05). Our findings showed presence of oxidative damage in subacute sclerosing panencephalitis and that antioxidants were increased as defense mechanisms of the organism against oxidative damage.
We report the unique case of late-onset pancraniosynostosis presenting with rapid visual deterioration, without other symptoms of increased intracranial pressure. A 10-year-old girl had episodes of blurry vision for 1 month. Magnetic resonance imaging (MRI) demonstrated a borderline Chiari I malformation. Ophthalmologic exam confirmed papilledema and decreased visual acuity. Opening pressure on lumbar puncture was 55 mmH2O. The patient was diagnosed with pseudotumor cerebri and prescribed Diamox. Four days later, she re-presented with worsening vision and increased papilledema and was taken for emergent ventriculo-peritoneal shunt placement. A postoperative computed tomographic scan showed the absence of all cranial sutures. Vision had not improved. A cranial vault expansion and optic nerve fenestration was performed. Pancraniosynostosis must be considered in a child with rapid visual deterioration and increased intracranial pressure, or with the presumptive diagnosis of pseudotumor cerebri. Assurance of normal cranial suture anatomy by computed tomographic scan is imperative in patients with an atypical presentation of pseudotumor cerebri.
Previous bio-engineering studies showed that intrapartum peak forces applied by the clinician were lower in routine deliveries than difficult deliveries. A total of 751 cases of obstetric brachial plexus palsy were included and divided into two groups: group I (248 patients) were born following routine deliveries and group II (503 patients) were born following difficult deliveries. Both groups were compared regarding the type of palsy and the rate of good/poor spontaneous motor recovery from the palsy. Group I subjects were more likely to have upper Erb palsy whereas those in group II were more likely to develop total palsy (P < .0001). The percentage of newborns with poor functional recovery was significantly higher (P < .05) in group II with regards to shoulder, wrist, and hand function. It was concluded that higher peak forces applied by the clinician in difficult deliveries affect the type of obstetric brachial plexus palsy.
Neurodevelopmental delays in intensive care neonates are common but difficult to predict. In children, hemisphere differences in cortical processing of speech are predictive of cognitive performance. We hypothesized that hemisphere differences in auditory event-related potentials in intensive care neonates are predictive of neurodevelopment in infancy, even in those born preterm. Event-related potentials to speech sounds were prospectively recorded in 57 infants (gestational age 24-40 weeks) prior to discharge. The Developmental Assessment of Young Children was performed at 6 and 12 months. Hemisphere differences in mean amplitudes increased with postnatal age (P < .01) but not with gestational age. Greater hemisphere differences were associated with improved communication and cognitive scores at 6 and 12 months, but decreased in significance at 12 months after adjusting for socioeconomic and clinical factors. Auditory cortical responses can be used in intensive care neonates to help identify infants at higher risk for delays in infancy.
Leber hereditary optic neuropathy is a well-known mitochondrial disorder that leads to bilateral subacute visual failure. Although visual impairment is often the sole clinical feature, additional and severe neurologic abnormalities also have been documented for this disease. We report on a 13-year-old boy who has presented with severe visual failure since early childhood in a context of prematurity. In the first years of his life, clinical features included delayed psychomotor development and ataxia. The clinical presentation, which was initially attributed to prematurity, worsened thereafter, and the child developed acute neurologic degradation with the typical radiological findings of Leigh syndrome. The mitochondrial DNA point mutation 11778G>A was identified in the ND4 gene. The probable influence of environmental background on clinical expression of Leber optic neuropathy, particularly those of prematurity and oxygen therapy, is discussed in our manuscript.
The neuronal ceroid lipofuscinoses are the most common autosomal recessive neurodegenerative disorders in children, with a worldwide incidence of 1 in 100 000 live births. Multiple clinical variants are caused by more than 400 mutations in at least 14 different genes. These progressive genetic disorders primarily manifest in the central nervous system because of an extensive loss of neurons, specifically in the cerebral and cerebellar cortices. Patients with mutations in CLN1, which encodes palmitoyl-protein thioesterase 1 (PPT1), primarily manifest with infantile neuronal ceroid lipofuscinosis (Haltia-Santavuori disease). Affected children usually present between 1 and 2 years of age and typically die by 8 to 13 years of age. We describe a patient with infantile neuronal ceroid lipofuscinosis with a novel c.776_777insA mutation in CLN1. This insertion induces a frameshift and a premature stop codon late within the CLN1 messenger RNA (mRNA) transcript which is likely recognized by nonsense-mediated translation repression, decreasing PPT1 abundance.
Weakness and fatigue are captured by the 6-minute walk test, but the relationship between these symptoms is uncertain. Comparison across neuromuscular diseases has not been examined. A cohort study of 114 patients with spinal muscular atrophy, Duchenne/Becker muscular dystrophy, myasthenia gravis, and energy failure syndromes were included. Percent-predicted distance on the 6-minute walk test was computed from normative values to determine weakness. Fatigue was determined by the decrement in distance from the first to sixth minute. Weakness was seen across all groups (61.9%) but significant fatigue was seen only in spinal muscular atrophy (21.0%). Other groups showed little fatigue. Correlation between weakness and fatigue was significant only in spinal muscular atrophy (R = –0.71; P < .001). Longitudinally, distance walked declined only in Duchenne/Becker muscular dystrophy. In spinal muscular atrophy, weakness did not change, but fatigue increased significantly. These findings suggest independent mechanisms underlying weakness and fatigue in diverse neuromuscular conditions.
The neuronal ceroid lipofuscinoses represent a group of disorders characterized by neurodegeneration and intracellular accumulation of an auto-fluorescent lipopigment (ceroid lipofuscin). Together, they represent the most prevalent class of childhood neurodegenerative disease. The neuronal ceroid lipofuscinoses encompass several distinct biological entities that vary in age of onset, specific neurologic phenotype, and rate of progression. In this review, we describe 9 major forms and present a classification scheme. Understanding the age of onset, clinical features, and natural history can inform rational diagnostics. Better knowledge of the natural histories of these disorders is necessary to shed light on the underlying pathobiology and to develop new therapeutics.
The neuronal ceroid lipofuscinoses, collectively the most common neurodegenerative disorders of childhood, are primarily caused by an autosomal recessive genetic mutation leading to a lysosomal storage disease. Clinically, these diseases manifest at varying ages of onset, and associated symptoms include cognitive decline, movement disorders, seizures, and retinopathy. The underlying cell biology and biochemistry that cause the clinical phenotypes of neuronal ceroid lipofuscinoses are still being elaborated. The 2012 Neurobiology of Disease in Children Symposium, held in conjunction with the 41st Annual Meeting of the Child Neurology Society, aimed to (1) provide a survey of the currently accepted forms of neuronal ceroid lipofuscinoses and their associated genetic mutations and clinical phenotypes; (2) highlight the specific pathology of Batten disease; (3) discuss the contemporary understanding of the molecular mechanisms that lead to pathology; and (4) introduce strategies that are being translated from bench to bedside as potential therapeutics.
We examined flurothyl gas–induced seizure latencies and phenotype in 2 mouse models of neuronal ceroid lipofuscinoses: the nclf (Cln6 mutant) variant late-infantile model and the mnd (Cln8 mutant) Northern epilepsy model. Mnd mice on postnatal days 35 to 42 had increased latency to loss of posture compared with wild-type controls. Nclf, mnd, and wild-type mice on postnatal days 21 days to 25 displayed similar latency profiles during repeated seizure induction (kindling) and retesting; seizure phenotypes were different, however. Kindled wild-type mice reexposed to flurothyl after a 28-day recovery displayed brainstem generalized seizures exclusively. Neuronal ceroid lipofuscinoses mutants demonstrated a lack of brainstem seizures at retesting after 28 days. Repeated induction of generalized seizures delayed weight gain in both nclf and mnd mice compared with wild-type mice. These and our previous results suggest that abnormal seizure-related neuronal connectivity and/or plasticity are shared characteristics of the neuronal ceroid lipofuscinoses.
The prevalence and the burden of vincristine-induced neuropathy have been poorly documented in childhood acute lymphoblastic leukemia survivors. This cross-sectional study was carried out at a tertiary care center in northern India from October 2011 to June 2012. Eighty consecutive acute lymphoblastic leukemia survivors aged 5 to 18 years, within 3 years of completion of their chemotherapy, were enrolled. After clinical evaluation, detailed nerve conduction studies were performed and the reduced version of the Total Neuropathy Score was calculated. The mean age at the time of evaluation was 11.2 ± 3.2 years. 33.75% had neuropathy electrophysiologically. Symmetric motor axonal polyneuropathy was the most common pattern of involvement seen in 19 (23.8%) children. There was significant improvement with time, as revealed by lower prevalence of neuropathy with increasing interval following vincristine injection. 33.75% of the children had Reduced version of Total Neuropathy Score ≥ 1.
Plasticity of language function after brain damage can depend on maturation of the brain. Children with left-hemisphere perinatal (n = 7) or childhood stroke (n = 5) and 12 controls were investigated using functional magnetic resonance imaging. The verb generation and the sentence comprehension tasks were employed to activate the expressive and receptive language areas, respectively. Weighted laterality indices were calculated and correlated with results assessed by neuropsychological test battery. Compared to controls, children with childhood stroke showed significantly lower mean scores for the expressive (P < .05) and receptive (P = .05) language tests. On functional magnetic resonance imaging they showed left-side cortical activation, as did controls. Perinatal stroke patients showed atypical right-side or bilateral language lateralization during both tasks. Negative correlation for stroke patients was found between scores for expressive language tests and laterality index during the verb generation task. (Re)organization of language function differs in children with perinatal and childhood stroke and correlates with neurocognitive performance.
Pelizaeus-Merzbacher disease is a severe X-linked disorder of central myelination caused by mutations affecting the proteolipid protein gene. We describe 3 new PLP1 splicing mutations, their effect on splicing and associated phenotypes. Mutation c.453_453+6del7insA affects the exon 3B donor splice site and disrupts the PLP1-transcript without affecting the DM20, was found in a patient with severe Pelizaeus-Merzbacher disease and in his female cousin with early-onset spastic paraparesis. Mutation c.191+1G>A causes exon 2 skipping with a frame shift, is expected to result in a functionally null allele, and was found in a patient with mild Pelizaeus-Merzbacher disease and in his aunt with late-onset spastic paraparesis. Mutation c.696+1G>A utilizes a cryptic splice site in exon 5, causes partial exon 5 skipping and in-frame deletion, and was found in an isolated patient with a severe classical Pelizaeus-Merzbacher. PLP1 splice-site mutations express a variety of disease phenotypes mediated by different molecular pathogenic mechanisms.
This study aims to determine if stroke volume as measured on diffusion-weighted imaging is associated with neurologic outcome in children with acute arterial ischemic stroke. A cohort of patients presenting to a tertiary care children's hospital with acute ischemic stroke were studied. The relationship between stroke volume, clinical characteristics, and neurologic outcome utilizing the Glasgow Outcome Scale were analyzed. In children with poor outcome, the median volume of infarction on diffusion-weighted imaging was larger when compared with children who had a good outcome. Children with stroke volume >10% of total brain volume were more likely than patients with stroke volume <5% total brain volume to have a poor outcome. Seizures were associated with a 10.5-fold increase in the risk of a poor outcome. Stroke volume, in conjunction with clinical characteristics, can assist practitioners in identifying a subset of patients with acute ischemic stroke who might benefit from aggressive medical and/or surgical management.
Mucopolysaccharidosis-IIIB or Sanfilippo-B syndrome is caused by deficiency of lysosomal α-N-acetylglucosaminidase that leads to accumulation of heparan-sulphate and degeneration of central nervous system with progressive dementia, hyperactivity, and aggressive behavior. Mucopolysaccharidosis-III remains underdiagnosed as a cause of developmental delay and hyperactivity both in adults and children because in contrast to other mucopolysaccharidoses, they have little somatic disease, coarse facial features, hepatosplenomegaly or skeletal changes, and a high incidence of false-negative results on the urinary screening tests. We describe here a girl with the classic phenotype of mucopolysaccharidosis-IIIB to alert pediatricians to the possibility of this disorder in children with unexplained speech delay and hyperactivity and prevent unnecessary investigations.
The International Pediatric Multiple Sclerosis Study Group requires the presence of encephalopathy to diagnose acute disseminated encephalomyelitis. Clinical characteristics of encephalopathy are inadequately delineated in the pediatric demyelinating literature. The authors’ purpose was to better define encephalopathy in pediatric acute disseminated encephalomyelitis by describing the details of the mental status change. A retrospective chart review was conducted for 25 children diagnosed with acute disseminated encephalomyelitis according to the International Pediatric Multiple Sclerosis Study Group guidelines. Frequency of encephalopathy-defining features was determined. Clinical characteristics, cerebrospinal fluid findings, and electroencephalography (EEG) findings were compared between patients with different stages of encephalopathy. The authors found irritability (36%), sleepiness (52%), confusion (8%), obtundation (20%), and coma (16%) as encephalopathy-defining features in acute disseminated encephalomyelitis. Twenty-eight percent had seizures, and 65% demonstrated generalized slowing on EEG. Approximately half of the patients in this study were diagnosed with encephalopathy based on the presence of irritability and/or sleepiness only. Such features in young children are often subtle and transient and thus difficult to objectively determine.
This study sought to investigate cognitive outcomes following pediatric arterial ischemic stroke and explore predictors. Participants included 36 children with perinatal or childhood arterial ischemic stroke and a comparison group of 15 children with asthma. Outcomes included cognitive ability, executive functions, and neurological function (Pediatric Stroke Outcome Measure). Magnetic resonance imaging measured lesion location and volume. Mean cognitive scores were at the low end of the average range. Children with arterial ischemic stroke performed significantly below normative populations and significantly below the asthma group on inhibitory control (Cohen’s d = .68). Both the Pediatric Stroke Outcome Measure and lesion volume were negatively correlated with cognitive outcome (Spearman r = –.01 to –.42 Pediatric Stroke Outcome Measure; r =–.14 to –.32 Volume). Following arterial ischemic stroke, children performed at the low end of the average range on measures of cognitive functioning. Cognitive outcomes depend on a variety of factors.
Increased motor cortex excitability is a common finding in dystonia, and transcranial direct current stimulation can reduce motor cortex excitability. In an earlier study, we found that cathodal direct-current stimulation decreased motor overflow for some children with dystonia. To investigate this observation further, we performed a sham-controlled, double-blind, crossover study of 14 children with dystonia. We found a significant reduction in overflow following real stimulation, when participants performed the experimental task with the hand contralateral to the cathode. While these results suggest that cathodal stimulation may help some children to reduce involuntary overflow, the size of the effect is small. Further research will need to investigate ways to increase the magnitude of the effect of cathodal transcranial direct current stimulation.
Dysembryoplastic neuroepithelial tumors are rare, surgically curable, neuronal-glial neoplasms affecting young patients with intractable epilepsy. Its recognition is needed to avoid unnecessary adjuvant therapy. The authors reviewed the records of 15 patients with dysembryoplastic neuroepithelial tumors who underwent epilepsy surgery using intraoperative electrocorticography monitoring, including 8 males and 7 females (mean age, 15.8 years). Neuroimaging showed a predominantly intracortical location, the presence of septations, a triangular pattern of distribution, a lack of contrast enhancement, and an absence of peritumoral edema. Eleven cases were classified as complex type, 3 as simple type, and 1 as "nonspecific" type. Associated cortical dysplasia was found in 5 cases and leptomeningeal involvement in 1 case. Its immunophenotype suggested a pluripotential neuroepithelial origin. The mean follow-up was 37.5 months; 2 patients had tumor recurrence. Although they are generally benign neoplasms, recurrences sometimes occur. Complete resection of the tumor with the epileptogenic zone is important for a favorable outcome.
We reviewed neurologic complications after renal transplantation in children over a 20-year period. Neurologic complications were classified as early (within 3 months) and delayed (beyond 3 months). Of 115 children, 10 (8.7%) had complications. Early complications were found in 4.35% of patients: seizures in 4 (posterior reversible leukoencephalopathy syndrome due to immunosuppressant toxicity [2], sepsis/presumed meningitis [1], and indeterminate [1]) and headaches in 1. One patient with seizures received levetiracetam for 6 months and 1 with headaches received amitriptyline prophylaxis. Late complications were noted in 4.35% of patients: seizures in 3 (posterior reversible leukoencephalopathy syndrome due to hypertension [2], hypertensive encephalopathy [1]), headaches in 2, and tremors in 1. Two patients with seizures were treated with anti-epilepsy medications; 1 with migraine received cyproheptadine prophylaxis. Neurologic complications develop in children after renal transplantation. Seizures due to posterior reversible leukoencephalopathy syndrome were the commonest complication. Early detection and appropriate management of these complications is important.
The authors conducted a systematic literature review of preventive pharmacological treatments for episodic childhood migraines searching several databases through May 20, 2012. Episodic migraine prevention was examined in 24 publications of randomized controlled trials that enrolled 1578 children in 16 nonrandomized studies. Single randomized controlled trials provided low-strength evidence that propranolol would result in complete cessation of migraine attacks in 713 per 1000 children treated (95% confidence interval, 452-974); trazodone and nimodipine decreased migraine days, while topiramate, divalproex, and clonidine were no more effective than placebo in preventing migraines. Migraine prevention with multidisciplinary drug management was not sustained at 6 months. Divalproex resulted in treatment discontinuation due to adverse effects, and topiramate increased the risk of paresthesia, upper respiratory tract infection, and weight loss. Long-term preventive benefits and improvement in disability and quality of life are unknown. No studies examined quality of life or provided evidence for individualized treatment decisions.
Hans Berger was a German neuropsychiatrist and head of the neurology department at the University of Jena, who discovered the human electroencephalogram (EEG). Many sources state that Berger was forced into retirement and suicide by the Nazis because he was at odds with the regime. In fact, Berger helped select his Nazi successor Berthold Kihn (complicit in "euthanasia" murders), financially supported the Nazi Schutzstaffel (SS), and was a willing participant on Nazi genetic health higher courts that reviewed appeals for forced sterilizations of neuropsychiatric patients. His motivations could be related to avoiding Nazi harassment, indoctrination by Nazi ideology, or less likely, career opportunism. His actions stand in contrast to colleagues who partially resisted the Nazis, and hopefully will serve as an example to future generations of neurologists regarding the danger of allowing one’s professional standing to be used as a tool to support the policies of tyranny and oppression.
Vigabatrin is an antiepileptic drug that results in higher gamma-aminobutyrate levels in the brain and retina. Vigabatrin-induced visual field defects are usually asymptomatic and only detectable by perimetry. Further, perimetry requires good cooperation, and children aged under 10 years cannot do it. Electroretinogram response amplitude to full-field 30-Hz flicker shine has been offered to be more specific in predicting visual field defects. This study is scheduled to investigate the vigabatrin-associated visual complications in 67 epileptic children taking vigabatrin using full-field electroretinogram. Electroretinographic surveys showed normal range parameters despite 3 months of vigabatrin treatment, and just 3 (4.47%) children had been visually impaired at the end of 6-month treatment. Among these 3 cases, 1 patient had persistent electroretinogram abnormality despite vigabatrin discontinuation. Our study suggests that vigabatrin is secure for short-term pediatric antiepileptic treatment, with few cases of visual impairments and that are often reversible.
Primary myoclonus-dystonia is a childhood-onset autosomal-dominant movement disorder with myoclonic jerks and dystonia. The authors report 9 children (4 boys, 5 girls) with myoclonus-dystonia from 8 families seen over a 4-year period at Cleveland Clinic. The mean age of onset of symptoms was 2.8 years, but the diagnosis was made at a mean of 7.3 years. Myoclonus was the presenting symptom in 8 children. A known pathogenic mutation in the -sarcoglycan gene (SGCE) was identified in 4 of the 9 children, and 2 other children had novel mutations in the same gene. Good response to trihexyphenidyl and clonazepam was seen. Two patients underwent deep brain stimulation surgery of the bilateral globus pallidus pars interna. In 7 children, the diagnosis of myoclonus-dystonia was not considered by the referring child neurologists, which led to extensive investigations and a delay in the final diagnosis. In this report, the authors highlight the need for increased awareness of this entity among child neurologists.
Focal cortical dysplasia is the most common malformation of cortical development, causing intractable epilepsy. This study investigated the relationship between brain perfusion and microvessel density in 7 children with focal cortical dysplasia. The authors analyzed brain perfusion measurements obtained by magnetic resonance imaging of 2 of the children and the microvessel density of brain tissue specimens obtained by epilepsy surgery on all of the children. Brain perfusion was approximately 2 times higher in the area of focal cortical dysplasia compared to the contralateral side. The microvessel density was nearly double in the area of focal cortical dysplasia compared to the surrounding cortex that did not have morphological abnormalities. These findings suggest that hyperperfusion can be related to increased microvessel density in focal cortical dysplasia rather than only to seizures. Further investigations are needed to determine the relationship between brain perfusion, microvessel density, and seizure activity.
Children with Charcot-Marie-Tooth disease frequently suffer ankle sprain and experience chronic ankle instability; however, no pediatric self-reported measures of chronic ankle instability exist. The aim was to modify and validate the most reliable measure of chronic ankle instability in adults: the Cumberland Ankle Instability Tool. The Cumberland Ankle Instability Tool–Youth was tested for reliability, construct validity, and sensitivity to discriminate between 104 children aged 8 to 16 years: 31 children with Charcot-Marie-Tooth disease, 31 unaffected children with a history of ankle sprains, and 42 controls. Children with Charcot-Marie-Tooth disease had lower scores compared to unaffected children with a history of sprains (2 = 15.10; P < .001) and controls (2 = 33.69; P < .001). Scores moderately correlated to visual analog scale scores of ankle steadiness (r s = 0.684; P < .001), and "good" test-retest reliability was identified (ICC2,1 = 0.73). The Cumberland Ankle Instability Tool–Youth demonstrated excellent sensitivity and construct validity, identifying chronic ankle instability as a common problem for children with Charcot-Marie-Tooth disease.
Microscopic polyangiitis associated with antineutrophil cytoplasmic antibodies directed against myeloperoxidase rarely affects the central nervous system, and this is common in the presence of other organ involvement. The authors report the case of a 12-year-old girl who presented with multiple acute parieto-occipital hematomas as the only manifestation of presumed microscopic polyangiitis. Early treatment with immunosuppression resulted in complete recovery and a favorable outcome.
Neurologists increasingly recognize that critically ill patients are at high risk for seizures, particularly nonconvulsive seizures, and that neuromonitoring is a useful tool for diagnosing seizures and assessing brain function in these patients. Amplitude-integrated electroencephalography (EEG) is a simplified bedside neurophysiology tool that has become widely used in neonates over the past decade. Despite widespread interest by both neurologists and neonatologists in continuous brain monitoring, amplitude-integrated EEG has been largely ignored by neurologists, forcing neonatologists to "go it alone" when interpreting data from this bedside tool. Although amplitude-integrated EEG cannot replace conventional EEG for background monitoring and detection of seizures, it remains a useful instrument that complements conventional EEG, is being widely adopted by neonatologists, and should be supported by neonatal neurologists.
Muscular dystrophies are progressive, genetic disorders of muscle degeneration. The current gold standard for diagnosis is muscle biopsy or genetic studies. Muscle biopsy is an invasive procedure and genetic testing facilities are available only in a few centers. Thus, a diagnostic test that is easily available, simpler, and less invasive is desirable. Over the past 2 decades, skin biopsy has been evolving as a suitable option. Two cases of sarcoglycanopathy are described here, which have been correctly diagnosed by skin biopsy. Muscle biopsy has been used as the gold-standard diagnostic method. Skin biopsy can substitute for muscle biopsy as the preliminary diagnostic tool directing appropriate molecular testing. However, these results require validation in studies with an adequate sample size. This holds promise for the future when repeated biopsies will be required for evaluating protein rescue in trials of novel treatment options in these disorders.
We investigated the plasma cytokine profiles of children with febrile seizures or severe acute encephalitis using multiplex cytometry to evaluate the role of cytokines in these diseases. Interleukin-6, -10, -12p70, -17A, -2, -4, -5, -9, -13, -22, and -1β, interferon-, and tumor necrosis factor-α were measured in the plasma from children with febrile seizures (n = 9) or severe acute encephalitis (n = 21). In multivariate analysis, interleukin-6 was significantly increased in the plasma of the febrile seizure patients compared to those with severe acute encephalitis, suggesting that interleukin-6 is activated during the acute stage of a febrile seizure. A lower plasma interleukin-6 concentration was significantly associated with severe acute encephalitis. The cytokine network may be deregulated in severe acute encephalitis via the persistence of an uncontrolled inflammatory state in the brain.
In addition to the typical infantile spasm symptoms, several other symptoms, such as eye movements, have been reported to be associated with infantile spasms, although the relationship between the typical spasms and these other events is not fully understood. Here we present a case with West syndrome. We observed the appearance of periodic eye movements followed by the onset of typical spasms and the appearance/disappearance of periodic eye movements during withdrawal/increases of vigabatrin. We believe that the case strongly supports the notion that periodic eye movements and typical spasms represent a spectrum of symptoms related to the same phenomenon of West syndrome.
Basilar artery occlusion has poor outcome in adults; little is known regarding outcomes in children. Whether intra-arterial treatments improve adult outcomes is controversial. Safety and efficacy of intra-arterial treatments in children are unknown. We report 5 cases of basilar artery occlusion and review published cases. We estimated National Institute of Health Stroke Scale (NIHSS) and modified Rankin Score (mRS) of published cases, compared scores between non–intra-arterial treatments and intra-arterial treatments groups, and examined the correlation between NIHSS and mRS. Of our cases, 4 had good outcomes and 1 died. Of 63 published cases, 45 had no intra-arterial treatments and 18 had intra-arterial treatments. In the non–intra-arterial treatments group 24 had good outcomes. In the intra-arterial treatments group 13 had good outcomes. There was strong correlation between the NIHSS and the mRS. Children with basilar artery occlusion have better outcomes than adults. Certain children with basilar artery occlusion may be treated conservatively. A registry for childhood basilar artery occlusion is urgently needed.
For 4 millennia, seizures in infancy were believed to be of supranatural origin and were dealt with by incantations, exorcising rituals, and protective amulets. Instead of pursuing scientific research into their causes, gods, devils, mothers, wet nurses, midwives, or obstetricians were blamed. Help from protective gods and patron saints was sought, and amulets against the "evil eye" were recommended by physicians, mostly in the form of necklaces. Infants were despised and hidden away from the community. Among the medical conditions associated with seizures, those most prominent were dentition, gastrointestinal irritation, and "bad" mother’s milk. Medical treatment consisted of cutting or rubbing the gums with a hare’s brain during dentition, and applying peony or theriac. Even during the 20th century, when laboratory methods, electroencephalography, brain imaging, and powerful pharmaceutical techniques were available, effective treatment evolved empirically rather than systematically.
Dosing of phenytoin is difficult in children because of its variable pharmacokinetics and protein binding. Possible covariates for this protein binding have mostly been univariately investigated in small, and often adult, adult populations. We conducted a study to identify and quantify these covariates in children. We extracted data on serum phenytoin concentrations, albumin, triglycerides, urea, total bilirubin and creatinine concentrations and data on coadministration of valproic acid or carbamazepine in 186 children. Using nonlinear mixed effects modeling the effects of covariates on the unbound phenytoin fraction were investigated. Serum albumin, serum urea concentrations, and concomitant valproic acid use significantly influenced the unbound phenytoin fraction. For clinical practice, we recommend that unbound phenytoin concentrations are measured routinely. However, if this is impossible, we suggest to use our model to calculate the unbound concentration. In selected children, close treatment monitoring and dose reductions should be considered to prevent toxicity.
This study determined the extent to which parents of adolescents with cerebral palsy seek out complementary and alternative medicine services. A regional sample of 166 adolescents (15.5 ± 2.4 years) with cerebral palsy were recruited. Parents completed a questionnaire identifying the complementary and alternative medicine services received over the past year. Most (73.2%) did not currently utilize any of the listed services; 7.3% used 2 or more services. The most commonly used services were massage (15.4%), hyperbaric oxygen (9.6%), and osteopathy (5.7%). Youth with limited hand function were more likely (P = .01) to undergo hyperbaric oxygen. Massage therapy services were more frequent in youth with greater activity limitations (P < .005). Sociodemographic factors were not predictive of use. Approximately one quarter of families sought out these services for their adolescents with cerebral palsy. Many are expensive privately funded treatments. Physicians should openly discuss these options with families, highlighting the current state of knowledge on their efficacy.
Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate.
Discontinuation of antiepileptic drugs should be a first step in treatment of nonepileptic seizures without comorbid epilepsy. However, clinical practices vary and standardized guidelines are not available. The aim of this study was to survey members of the American Epilepsy and Child Neurology Societies about factors that influence their decision about antiepileptic drug management in patients with nonepileptic seizures. A total of 236 respondents completed this survey, of whom 84% were academic pediatric neurologists and 96.2% were very willing to discontinue antiepileptic drugs in these patients. Clinicians with sufficient knowledge about nonepileptic seizures had fewer concerns about the potential for medical errors, were less influenced by requests made by patients or parents to continue antiepileptic drugs, and were comfortable making this decision if patients receive ongoing psychiatric care. Results of this survey highlight the need to examine if the same factors are involved in a large sample of community clinicians.
A 4-year-old boy presented with progressive neurodegeneration, mild coarsening of facies and spasticity. The classical neuroimaging guided the subsequent investigation of enzyme assay which confirmed the diagnosis of fucosidosis.
Lymphocytic choriomeningitis virus is a rodent-borne arenavirus that can cause congenital infection affecting the developing central nervous system. When the infection occurs during pregnancy, the virus targets the fetal brain and retina, potentially causing ventriculomegaly, hydrocephalus, chorioretinitis, and neurodevelopmental abnormalities. It has been previously suggested that lymphocytic choriomeningitis virus be added to the list of congenital infections currently included in the TORCH acronym (toxoplasmosis, rubella, cytomegalovirus, herpes, and syphilis). We present 2 neonates with antenatally known ventriculomegaly that were diagnosed with congenital lymphocytic choriomeningitis virus infection after birth. In addition to ventriculomegaly, one had nonimmune hydrops fetalis and the other had intracranial hemorrhage. In view of the seroprevalence of lymphocytic choriomeningitis virus (4.7%-10%), our findings suggest that screening for congenital lymphocytic choriomeningitis virus infection should be considered in fetuses and newborns with ventriculomegaly as well as other abnormal neuroimaging findings such as intracranial hemorrhage.
Classical lissencephaly may be associated with cerebellar hypoplasia and when significant cerebellar abnormalities occur, defects in proteins encoded by TUBA1A, RELN, and very-low-density lipoprotein receptor (VLDLR) genes have been reported. We present a neonate with a severe neurologic phenotype associated with hypotonia, oropharyngeal incoordination that required a gastric tube for feeding, intractable epilepsy, and congenital cataracts. Her brain magnetic resonance imaging (MRI) showed classical lissencephaly, ventriculomegaly, absent corpus callosum, globular and vertical hippocampi, and severe cerebellar and brainstem hypoplasia. She died at 6 weeks of age. No specific molecular diagnosis was made. This likely represents a previously undescribed genetic lissencephaly syndrome.
Macro creatine kinase type 1 is a complex formed by the creatine kinase isoenzyme BB and monoclonal IgG and occurs in about 1% of patients studied. First identified as a cause of spurious elevation of the total serum creatine kinase in patients suspected of myocardial infarction, the test has been largely replaced by the measurement of troponin levels. We present a child with delayed milestones and persistently elevated total serum creatine kinase measurements (~1000-4000 IU) normal electromyogram and brisk myotatic reflexes. Creatine kinase isoenzymes and brain imaging showed the presence of macro creatine kinase type 1 and extensive signal abnormality of the cerebral white matter. Macro creatine kinase type 1 has been associated with several conditions though it has not been described in association with leukoencephalopathy or in patients this young. Macro creatine kinase type 1 can be a cause of elevated total creatine kinase in patients without primary muscle disease. The significance of the relationship of the macro creatine kinase to the leukoencephalopathy in this patient is unknown.
Infantile Pompe disease, resulting from deficiency of lysosomal acid α-glucosidase, requires enzyme replacement therapy with recombinant human acid α-glucosidase. Most patients develop antirecombinant human acid α-glucosidase antibodies, leading to reduced response to enzyme therapy in a subgroup of them. Aiming to improve treatment response, several immune tolerance induction strategies have been explored. We describe a patient with life-threatening infusion-associated reactions presenting anti-recombinant human acid α-glucosidase antibodies. He was successfully treated with an immune tolerance induction protocol, consisting of plasma exchange combined with a single dose of rituximab. Immediate reduction of antibody titer was obtained and enzyme therapy was resumed without infusion-associated reactions. Twenty-two months later, immunoglobulin G titer remained below 1:100. In conclusion, we applied a short-course immune tolerance induction strategy in a patient with severe infusion-associated reactions and anti-recombinant human acid α-glucosidase antibodies, leading to early and persisting reduction of antibody titer, in the absence of significant adverse events.
Encephalocraniocutaneous lipomatosis is a rare neurocutaneous syndrome characterized by classical cutaneous and ocular lesions with central nervous system anomalies. We describe an infant with classical encephalocraniocutaneous lipomatosis characterized by probable naevus psiloliparus, frontal subcutaneous lipomas, ocular limbal dermoids and arachnoid cysts, and ventriculomegaly. He also had giant congenital nevus with leptomeningeal melanosis. This case represents a rare association between encephalocraniocutaneous lipomatosis and neurocutaneous melanosis.
This study systematically evaluated the symptoms associated with congenital and childhood myotonic dystrophy, and how these symptoms affect health related quality of life. We conducted interviews with patients affected by congenital or childhood myotonic dystrophy and their affected parent to identify which symptoms have the greatest effect on their lives. Each interview was recorded, coded, and analyzed using a qualitative framework technique. In 34 interviews with 13 parents and 21 patients, we identified 189 symptoms, representing 22 themes in physical, emotional, social, and disease-specific quality of life. Communication difficulties, cognitive impairment, and social role limitations were the most frequently identified themes. These interviews identified multiple themes and symptoms, some previously under-recognized, which play a key role in the disease burden associated with congenital and childhood myotonic dystrophy.
The purpose of this retrospective study was to analyze the effect of peripheral nerve injury on the skeletal maturation process. The bone ages of the affected and unaffected hand-wrists of 42 children with obstetrical brachial palsy were determined according to the Greulich and Pyle atlas. In 23 patients, the bone ages of the both sides were identical (bone-age-symmetrical group), in 19 patients the bone age of the affected side was delayed (bone-age-delayed group). The mean bone age of the affected side was delayed 0.48 ± 0.25 years that of the unaffected side (P = .000), and the delay of bone age was inversely correlated with chronological age (R 2 = .45, P < .02) in the bone-age-delayed group. Skeletal retardation can be recognized after appearance of ossification centers by plain radiography, dating from the third month of life, in early infancy. Thus, bone age determination method might be helpful for predicting potential future limb shortness.
Few cases of mosaicism involving a normal cell line and an unbalanced autosomal translocation have been reported so far. No cases of partial trisomy 13 and partial monosomy 8 mosaicism have been published. The authors report a new patient with partial trisomy 13 and partial monosomy 8 mosaicism due to an unbalanced translocation (13/8). A postzygotic mitotic exchange of nonhomologous chromatids followed by the loss of one of the translocated chromatids has been hypothesized as the potential underlying mechanism. Although a clear correlation of the clinical features of the patient with his chromosomal abnormality can be challenging, dysmorphic features, hyperactive behavior, moderate developmental delay, and tonic-clonic seizures can be interpreted as secondary to the particular genotype of the patient. These findings should be taken into account in the diagnostic process of patients presenting with multiple congenital anomalies and/or mental retardation conditions.
Although the "face of the giant panda" sign on magnetic resonance imaging (MRI) is traditionally considered to be characteristic of Wilson disease, it has also been reported in other metabolic disorders. This study describes the characteristic "giant panda" sign on MRI in a child with Leigh disease. The diagnosis was based on the history of neurological regression; examination findings of oculomotor abnormalities, hypotonia, and dystonia; raised serum lactate levels; and characteristic brain stem and basal ganglia signal changes on MRI. The midbrain and pontine tegmental signal changes were consistent with the "face of the giant panda and her cub" sign. In addition to Wilson disease, metabolic disorders such as Leigh disease should also be considered in the differential diagnosis of this rare imaging finding.
Patients with Fukuyama-type congenital muscular dystrophy sometimes experience transient exacerbations of muscle weakness. We took care of a 9-year-old boy with Fukuyama-type congenital muscular dystrophy who presented with acute respiratory failure and decreased exercise ability with marked elevation of serum creatine kinase indicating rhabdomyolysis. At that time, his younger sister suffered from erythema infectiosum. Although he had no particular symptoms, he was tested and proven to have acute human parvovirus B19 infection based on detection of anti-B19 IgM and parvovirus B19 DNA in his serum. His acute rhabdomyolysis was possibly triggered by human parvovirus B19 infection.
This study aimed to identify the indications in which electroencephalography in the pediatric emergency department is most useful. We retrospectively reviewed the influence that the results of the emergent electroencephalogram had on the eventual disposition of patients at our pediatric emergency department. Sixty-eight children (mean age, 7.3 years; 32 males) underwent 70 emergent electroencephalograms. Fifty-seven emergent electroencephalograms were performed for the suspicion of ongoing seizures or status epilepticus. Thirteen of the 22 children (59.1%) discharged from the emergency department were sent home mainly based on the results of the emergent electroencephalogram, which prevented an admission. In particular, 11 of 38 children with frequent and recurrent paroxysmal events concerning for seizures and 2 of 19 children with suspected ongoing status epilepticus were discharged after excluding an epileptic disturbance. The emergent electroencephalogram provided meaningful clinical information that influenced disposition, especially in patients with ongoing events in which the clinical picture was clarified by a rapidly acquired electroencephalogram.
Hemiplegic migraine is a rare subtype of migraine that is differentiated by motor weakness in the aura phase. The purpose of this case series was to examine the magnetic resonance angiogram findings of patients suffering from suspected acute hemiplegic migraine. This was a retrospective institutional board review protocol study of 8 patients. All patients received full brain magnetic resonance imaging under a 1.5-T magnet. The scans were subsequently evaluated by a neuroradiologist and 2 neurologists who were blinded to the study. The magnetic resonance angiogram findings of this study showed the presence of vasospasm within the intracranial vasculature during suspected acute hemiplegic migraine. This case series suggests that routine use of magnetic resonance angiography might be beneficial in both managing patients with acute hemiplegic migraine and helping to further understand the pathophysiology of this complicated disease process.
This study examined clinical findings and magnetic resonance imaging (MRI) characteristics in 114 patients with cortical dysplasia and corpus callosum and posterior fossa abnormalities to determine the clinical findings with the extent of the lesions on MRI. The age of patients was between 1 day and 15 years. Group 1 included 74 patients with corpus callosum abnormalities and/or cortical dysplasias and group 2 included 40 patients with posterior fossa abnormalities, which were isolated and/or associated with cortical dysplasia and/or corpus callosum abnormalities. Although associated congenital abnormality apart from central nervous system abnormalities, syndrome, or systemic disorder were more common in group 2 than group 1 patients (P < .05), we did not find a difference between the groups for psychomotor retardation and epilepsy (P > .05).
This population-based study assesses the long-term impact of childhood stroke on function and independence in young adults. We undertook a cross-sectional outcome study of patients with arterial ischemic stroke and cerebral sinovenous thrombosis, beyond 18 years of age. We studied 26 patients; 21 arterial stroke, 5 cerebral sinovenous thrombosis, with 16 females. Mean age at assessment was 21.5 years, and mean follow-up time was 10.8 years. According to the modified Rankin Scale, final outcomes were 37% normal, 42% mild, 8% moderate, and 15% severe deficits. Risk factors for abnormal functional outcome included arterial ischemic stroke, presence of arteriopathy, and 1-year poststroke Pediatric Stroke Outcome Measure score ≥ 2 (P < .05). Most (77-84%) were independent in driving, relationships, and employment. Functional status at 1 year poststroke strongly predicts long-term outcome. Mental illness in one-quarter of young adults surviving childhood stroke represents an important direction for research.
Stroke affects 2.7 children per 100,000 annually, leaving many of them with lifelong residual impairments despite intensive rehabilitation. In the present study the authors evaluated the effectiveness of 48 hours of transcutaneous functional electrical stimulation therapy for retraining voluntary reaching and grasping in 4 severe chronic pediatric stroke participants. Participants were assessed using the Rehabilitation Engineering Laboratory Hand Function Test, Quality of Upper Extremity Skills Test, Pediatric Evaluation of Disability Inventory, and Assisting Hand Assessment. All participants improved on all measures. The average change scores on selected Rehabilitation Engineering Laboratory Hand Function Test components were 14.5 for object manipulation (P = .042), 0.78 Nm for instrumented cylinder (P = .068), and 14 for wooden blocks (P = .068) and on the grasp component of Quality of Upper Extremity Skills Test was 25.93 (P = .068). These results provide preliminary evidence that functional electrical stimulation therapy has the potential to improve upper limb function in severe chronic pediatric stroke patients.
We assessed the impact of videotape analysis on scoring of the Hypertonia Assessment Tool (HAT) that discriminates between hypertonia subtypes. The HAT was administered to 28 children with cerebral palsy (mean age 9 years, range 4-17 years, 61% male). HAT examinations were videotaped; scores were assigned before and after videotape review. Neurological examination provided the gold standard diagnosis. Interrater reliability, criterion validity and individual item validation were assessed using prevalence and bias-adjusted kappa (PABAK). Videotape review did not significantly change the HAT item scores or diagnoses. Item validation eliminated 1 dystonia item. Interrater reliability was moderate for dystonia (PABAK = 0.43) and excellent for spasticity and rigidity (PABAK = 0.86-1.0). Criterion validity was substantial for spasticity (PABAK = 0.71), moderate for dystonia (PABAK = 0.43-0.57) and excellent for the absence of rigidity (PABAK = 1.0). The HAT can be administered without videotape review. Dystonia item 1 did not change the HAT hypertonia diagnosis and will be removed from the HAT.
Infantile spasms constitute a severe epileptic encephalopathy of infancy with poor long-term developmental outcome. Many diverse etiologies have been associated with infantile spasms, but the pathophysiological process is still not fully understood. We describe 2 cases of previously healthy 1- and 3-month-old infants who suffered a nonaccidental head injury with extensive cerebral lesions. Both presented with acute focal seizures rapidly controlled with phenobarbital. Nevertheless, they developed infantile spasms after a latency period of 3-4 months. Spasms were rapidly controlled with vigabatrin. Both children manifested with developmental delay, either exacerbated (case 1) or elicited (case 2) by infantile spasms. Our report highlights nonaccidental head injury as a risk factor for developing infantile spasms following a seizure-free latency period. A better understanding of the pathophysiology linking accidental brain trauma with infantile spasms could lead to more effective neuroprotective strategies. In the meantime, increased awareness and follow-up are warranted.
Intracranial hemorrhage has been rarely reported during the course of polyarteritis nodosa. We describe a 6-year-old boy who presented with fever, altered sensorium, skin rash, hypertension, and catastrophic intracranial hemorrhage. After surgical evacuation of the intracranial hematoma, he underwent a computerized tomography angiogram that showed narrowing of the right anterior cerebral artery. Skin biopsy showed small vessel vasculitis. Nerve conduction studies were suggestive of mononeuritis multiplex. He was diagnosed as polyarteritis nodosa and managed with immunosuppressants, to which he responded favorably. The most interesting aspect of the child’s presentation was the catastrophic onset of altered sensorium with raised intracranial pressure, which was a diagnostic challenge. The mechanisms of intracranial hemorrhage in polyarteritis nodosa and a review of the literature are discussed. The authors emphasize that it is important to recognize intracranial hemorrhage as a life-threatening complication in children with polyarteritis nodosa to institute timely therapy.
Using vignettes of real cases and the SimulConsult diagnostic decision support software, neurologists listed a differential diagnosis and workup before and after using the decision support. Using the software, there was a significant reduction in error, up to 75% for diagnosis and 56% for workup. This error reduction occurred despite the baseline being one in which testers were allowed to use narrative resources and Web searching. A key factor that improved performance was taking enough time (>2 minutes) to enter clinical findings into the software accurately. Under these conditions and for instances in which the diagnoses changed based on using the software, diagnostic accuracy improved in 96% of instances. There was a 6% decrease in the number of workup items accompanied by a 34% increase in relevance. The authors conclude that decision support for a neurological diagnosis can reduce errors and save on unnecessary testing.
The authors examined the preliminary psychometrics of a depression screening tool for youth with epilepsy. Development involved content analysis, cognitive interviewing, and qualitative analysis. Ninety-three youths with epilepsy aged 10 to 17 years completed the Neurological Disorders Depression Inventory for Epilepsy–Youth and the depression module of a standardized clinical interview. Caregivers rated seizure severity and completed the Pediatric Symptom Checklist. Results indicated strong reliability indices, including test-retest, value, and internal consistency for the Neurological Disorders Depression Inventory for Epilepsy–Youth. It was significantly associated with the other measures of depression and psychosocial functioning. Factor analyses revealed a 1-factor solution for 9 items, with 35.7% of the variance explained. An optimal cutoff score of 27 resulted in a sensitivity index of 0.80 and a specificity index of 0.71. The Neurological Disorders Depression Inventory for Epilepsy–Youth is a screening tool that can be utilized in routine epilepsy care, but further evaluation is necessary.
Fundoscopy is an important aspect of a neurological examination but can be challenging in uncooperative children. This study explored whether viewing a video during examination improves the success, duration, and ease of pediatric fundoscopy. This single-practitioner, randomized study involved 60 patients aged 1 to 8 years. Patients were randomized (by eye examined) to the treatment group (video-assisted) or control group (no video). A caregiver and the practitioner ranked the level of difficulty of each examination. There was a 28% improvement in the success rate of visualizing the optic disc (P < .001). Further analysis showed a 48% improvement in the success rate in children aged 1 to 4 years (P < .001) but no difference in children aged 5 to 8 years (P = .23). Time needed to visualize the optic disc also improved (16.3 s, P < .001). Improvement in the ease of examination (P < .001) was noted by both the practitioner and caregiver. This simple adjunct has the potential to improve the efficacy of this aspect of the pediatric neurological examination.
Peter Becker was a German neurologist who helped classify the muscular dystrophies, and described Becker muscular dystrophy and Becker myotonia. His involvement in National Socialism began in 1933, when he was compelled by his peers to join the SA (brown shirts). He later joined the Nazi party, the Nazi Doctors Association, and the Nazi Lecturers’ Association. He renewed his SA membership to maintain his position at a genetics institute. Colleagues stated postwar that he was not an active Nazi, and he was de-Nazified in 1947, able to continue his career. Later, Becker admitted to most, but not all, of his Nazi memberships in his autobiography, and wrote 2 books exploring the origins of Nazism and racial hygiene. The "neurologic court of opinion" must weigh in on how we should best remember Becker, and at the very least, we as neurologists must learn the dangers of career opportunism at any cost.
We report a 5-year-old girl who presented with fever, drooling, dysphagia, and anarthria. Moreover, voluntary facial movements were disturbed, but the emotional facial movements were completely normal. This clinical phenomenon is known as the anterior opercular syndrome. There was a positive polymerase chain reaction for herpes simplex in the cerebrospinal fluid. The diagnosis herpes simplex encephalitis was supported by both magnetic resonance images (MRI) as by electroencephalogram (EEG). Herpes simplex encephalitis is a rare, but severe, cause of the anterior opercular syndrome that demands treatment as soon as possible in order to prevent high morbidity or mortality. The phenomenon of autonomic-voluntary dissociation, associated with other clinical and radiologic findings related to an underlying neurologic disorder, alerts clinicians to the anterior opercular syndrome as a critical diagnostic observation with time-dependent therapeutic consequences.
Dystrophinopathies are diagnosed by genetic studies and muscle biopsy. Most centers have multiplex polymerase chain reaction facilities diagnosing 65% to 70% of dystrophinopathy cases. Muscle biopsy is a time-consuming, invasive procedure whereas skin biopsy is a simple procedure done under local anesthesia. The current study evaluated the diagnostic accuracy of skin biopsy in dystrophinopathy. Overall, 119 confirmed cases of muscular dystrophy (111 males and 8 females) were included in the final analysis, of which 100 (all males) were dystrophinopathy. Skin biopsy diagnosed dystrophinopathy in suspected muscular dystrophy patients with a sensitivity of 98% (92.3%-99.7%), specificity of 99% (93.7%-99.9%), positive predictive value of 94.7% (71.9%-99.7%), and negative predictive value of 90% (66.9%-98.2%). Skin biopsy can be used for screening dystrophinopathy in muscular dystrophy patients (high sensitivity and positive predictive value). It being a simple and minimally invasive procedure, histopathologic and molecular markers of disease progression and response to novel treatment options can be assessed serially.
We report a boy, referred at 25 months following a dramatic isolated language regression antedating autistic–like symptomatology. His sleep electroencephalogram (EEG) showed persistent focal epileptiform activity over the left parietal and vertex areas never associated with clinical seizures. He was started on adrenocorticotropic hormone (ACTH) with a significant improvement in language, behavior, and in EEG discharges in rapid eye movement (REM) sleep. Later course was characterized by fluctuations/regressions in language and behavior abilities, in phase with recrudescence of EEG abnormalities prompting additional ACTH courses that led to remarkable decrease in EEG abnormalities, improvement in language, and to a lesser degree, in autistic behavior. The timely documentation of regression episodes suggesting an "atypical" autistic regression, striking therapy-induced improvement, fluctuation of symptomatology over time could be ascribed to recurrent and persisting EEG abnormalities.
Congenital insensitivity to pain is a rare sensory neuropathy that manifests with multiple and recurrent injuries secondary to a lack of negative pain stimuli. When present with compulsive onychophagia, prompt recognition and behavioral management to prevent chronic digital infection or amputation is imperative. We present the case of two 7 year-old monozygotic twins that presented with congenital insensitivity to pain and compulsive onychophagia without directed parental counseling or behavioral modification strategies. The presenting child was noted to have an acute digital felon and osteomyelitis of several distal phalanges, and the sister had a similar history with distal phalangeal amputations. The occurrence of these overlapping disorders in monozygotic twins has not been previously reported, however, patient and parental education with behavioral modifications of injurious and compulsive behavior is the cornerstone of management. In addition, we have provided a review of the diagnosis for clinical differentiation.
Hirayama disease is characterized by asymmetrical focal weakness and atrophy of the distal upper limbs with onset in the teens and early 20s. This retrospective study aims to review clinical features of the children (onset before the age of 18 years) with Hirayama disease from mainland of China. Sixty-five children who fulfilled the clinical criteria for Hirayama disease were enrolled. The mean age of onset was 15.7 years, 3.3 years later than the peak age for the normal growth curve. Electrophysiology studies showed chronic denervation changes in C7-T1 segments with normal sensory nerve conduction. Flexion cervical magnetic resonance imaging (MRI) showed forward shifting of the posterior dural sac and engorgement of the posterior epidural venous plexus. Therapeutic intervention with cervical collar can induce a premature arrest of disease progression. Knowledge and awareness of Hirayama disease will facilitate diagnosis and therapeutic intervention in its early stages.
The purpose of the present study was to evaluate the relationship between headaches and physical and sexual abuse. A self-administered, anonymous questionnaire was presented to 2088 tenth grade students in Northern Israel. Participants were Jews and Arabs between the ages of 15 to 16 years. Arab adolescents comprised 55% of the analyzed sample and adolescent Jews 45%. With regard to gender, 56% of participants were females. Of the Arab participants, 18.6% reported having frequent headaches, less than that reported in the Jewish group (27.9%). Jewish girls who were physically abused during childhood had a higher prevalence of frequent headaches (55% vs 33% P < .001). Jewish students who reported being sexually abused had higher headache prevalence as well (44.4% vs 27.3% P = .05). In conclusion, adolescents who reported to have been physically or sexually abused report a higher prevalence of headache compared to their peers.
Levetiracetam given via intravenous administration has been shown to be an effective alternative in adults with epilepsy when oral administration is not feasible. This study was a prospective single-arm, multicenter study to assess tolerability, safety, and pharmacokinetics of intravenous levetiracetam in children with epilepsy. Children with epilepsy ages 1 month to 16 years requiring intravenous levetiracetam were enrolled. Assessments included vital signs, electrocardiogram, hematology, chemistry, plasma concentrations of antiepileptic medications, weight, physical/neurological examinations, and pharmacokinetics. A total of 52 patients were enrolled. Mild to moderate treatment-emergent adverse events occurred in 63%, the most frequent being pyrexia and dry mouth. Most other treatment-emergent adverse events were considered unrelated to intravenous levetiracetam administration. Therefore, intravenous levetiracetam in the acute setting was overall well tolerated in children 1 month to 16 years.
The authors describe 2 patients with early infantile epileptic encephalopathy caused by 2 novel mutations involving the STXBP1 gene. The authors suggest that in spite of the rarity of STXBP1 mutations, molecular analysis of STXBP1 gene should be performed in patients with early infantile epileptic encephalopathy, after exclusion of ARX mutations in male patients and CDKL5 mutations in female patients. The potential mechanisms explaining the variable clinical phenotypes caused by STXBP1 mutations are discussed and the designation of early-onset epileptic encephalopathies, including an updated genetic classification, is proposed to encompass the epileptic encephalopathies beginning in the first 6 months of life.
Apneic neonatal seizures can present as apparent life-threatening events. We report a newborn with unexplained episodes of apnea associated with cyanosis and desaturation, starting on the first day postpartum. Biochemical tests were normal. Central nervous system infections as well as abnormalities of upper airways and cardiovascular system were excluded. Brain monitoring using amplitude-integrated electroencephalography (aEEG) was inconclusive. Continuous monitoring using video EEG revealed epileptic seizures originating from the left temporal region as the cause of the apneas. Magnetic resonance imaging (MRI) of the brain showed a developmental malformation of the left frontal and temporal lobes. The patient became seizure free after treatment with antiepileptic medication. This report illustrates that brain monitoring using amplitude-integrated EEG alone could miss focal neonatal seizures. When clinical suspicion of apneic seizures is high in infants with apparent life threatening events, multichannel polygraphic video-EEG monitoring is indicated. Prompt diagnosis and treatment can be life saving.
Levetiracetam is one of the new anticonvulsant drugs that has a high therapeutic index and potential antiepileptogenic effects. Herein, we report a patient with multidrug refractory epilepsy and Ohtahara syndrome who was accidentally administered 300 mg/kg/d for 35 days by her mother. To our knowledge, there are only a few cases of accidental overdose of levetiracetam in pediatric patients reported in the literature, and this case study is the first to report such a high and long-term dose in an infant who showed no adverse effects.
Immune-mediated limbic encephalitis affects both adults and children. Patients typically present with seizures, memory problems, and imaging changes in the medial temporal lobes. Both paraneoplastic and nonparaneoplastic forms have been described in which the antibody to the voltage-gated potassium channel-complex associated protein, leucine-rich glioma-inactivated 1, is most commonly reported. Elevated antithyroid antibodies have also been reported in a range of neurological syndromes with encephalopathy, such as limbic encephalitis, often collectively termed Hashimoto encephalopathy, a condition whereby corticosteroids responsiveness with a complete recovery is commonly observed. Here we describe 3 children presenting with limbic encephalitis with elevated thyroid antibodies that did not respond to corticosteroids alone and required more aggressive immunotherapy, mirroring the slower treatment response that is more frequently seen in other immune-mediated forms of limbic encephalitis.
Schizencephaly is a rare and severe congenital brain defect. Its etiology is not unequivocal and its clinical course differs with every case. The aim of the study was to analyze correlations between clinical and radiologic features of schizencephaly in Polish patients. The study group consisted of 25 children. Epileptic seizures were observed in 60% of cases and in 32% epilepsy was drug resistant. Generalized hypotonia was found in 24%, spastic diparesis in 48%, and spastic hemiparesis in 28% of cases. Seizures were more frequent in the bilateral than unilateral schizencephaly subgroup (72% vs 29%, P = .045). There was a correlation between the presence of the bilateral type II schizencephaly and the occurrence of seizures (P = .002, r = 0.578). There is a correlation between the type of schizencephaly and the presence of seizures in Polish pediatric patients. In most of the patients, schizencephaly leads to developmental retardation and epileptic seizures.
We report 3 previously normal children that presented for evaluation of new onset seizures. Case 1, a 7-year-old female, presented with refractory left frontal lobe seizures associated with right arm simple motor seizures refractory to 6 antiepileptic medications at sufficient doses and levels. Case 2, a 15-year-old female, presented with left frontotemporal lobe seizures and nonconvulsive seizures, associated with neuropsychiatric symptoms refractory to 5 antiepileptic medications. Both patients received intravenous steroids and intravenous immunoglobulin. Case 3, an 11-year-old male, presented with a generalized tonic clonic seizure and worsening hallucinations responding to intravenous corticosteroids and 1 antiepileptic medication. All 3 patients had extensive infectious and metabolic evaluation and were found to be serum immunoglobulin M positive for mycoplasma pneumoniae. Despite their prolonged severe symptoms, all patients had virtually complete recovery with excellent seizure control after aggressive seizure management with immunotherapy and antiepileptic medication.
Seven children (5 male, 2 female) were seen over the last 16 years with rigid spine syndrome. Six children had rigid spinal muscular dystrophy (selenoprotein N1–related myopathy [SEPN1RM]) and 1 had myopathy associated with rigid spine. The main presenting complaint in all was difficulty in bending the spine. The diagnosis was made on clinical features and imaging of the paraspinal muscles. Muscle histopathology revealed minimal myopathic changes to severe muscle degeneration. Genetic testing, which was only available for the last case, for selenoprotein was negative.
Baclofen is a -aminobutyric acid (GABA) agonist that is commonly prescribed for the treatment of spasticity in children. The clinical indications for baclofen use in the pediatric population have increased in recent years. Prescribing baclofen mandates education regarding abrupt withdrawal and overdose because of the severe clinical reactions this can precipitate. This report highlights the case of a patient who presented with acute onset of coma and a flaccid paralysis after baclofen overdose. We reviewed the presentation, clinical course, diagnostic studies, and outcome of this patient. A review of prior literature regarding baclofen overdose is included. Baclofen overdose is heralded by dose-related alteration in consciousness and weakness, progressing to coma and a flaccid paralysis. Screening for baclofen overdose is accomplished through high-power liquid chromatography. Baclofen overdose is treated with supportive care and antiepileptic medications as indicated. There is usually full spontaneous recovery with elimination of the medication.
We aimed to examine the effectiveness of combined neurofeedback therapy and imagery training in adolescent patients with refractory Tourette syndrome. Two patients, aged respectively 14 and 16 years, had been treated with haloperidol and tiapride; however, this medication was ineffective and accompanied by intolerable side effects. In this study, the patients completed 80 sessions of neurofeedback treatment followed by imagery training. The patients were assessed with behavior rating scales both before and after the treatment as well as during follow-up examinations to evaluate the effect of the combined therapy. Patients showed significant improvement in motor tic and vocal tic symptoms, exemplified by a reduction in the frequency and intensity of tics, indicating that neurofeedback, together with imagery training, has a positive therapeutic effect on adolescent patients with medication-refractory Tourette syndrome.
To evaluate the consistency of the Hammersmith Infant Neurological Examination scores of very-low-birth-weight infants at 6 and 12 months of age and its correlation to cranial ultrasonography findings, we designed a prospective study between January 2005 and January 2008, in the tertiary Neonatal Unit of Aristotle University of Thessaloniki, Greece. All infants enrolled had a cranial ultrasonography performed at term. Preterm infants born at <32 weeks gestation with a birth weight <1500 g were eligible for the study. One hundred seventy-four infants were finally enrolled; out of those, 46 (26%) had an optimal score at 6 and 76 (44%) at 12 months of age. Mean global scores were 61 and 69 at 6 and 12 months, respectively. The Hammersmith Infant Neurological Examination score significantly increased between 6 and 12 months, equally in all ultrasonography groups. The presence of cystic periventricular leukomalacia was associated to lower scores and neurologic impairment.
Childhood disintegrative disorder, a rare, relentlessly progressive neurologic disorder, first described by Heller in 1908, remains a condition of great interest. It has long been debated whether it is a discrete disorder or simply a late-onset variant of childhood autism. We have studied 6 cases of childhood disintegrative disorder, collected over 8 years, and followed for 2.5 to 22 years (mean 8.6 years). Childhood disintegrative disorder begins later in life than autism, and following a period of entirely normal development; the regression is more global and more severe than in autism; seizures are more frequent than in autism, yet demonstrable organicity in childhood disintegrative disorder is decidedly rare. Lastly, the prognosis is usually much worse than in autism, but in those cases with neither seizures nor epileptiform activity on electroencephalography (EEG), the outcome may be more favorable. Childhood disintegrative disorder should be viewed as a condition distinct from childhood autism.
This study examined whether motor-related participation could be assessed by global positioning systems in individuals with cerebral palsy. Global positioning systems monitoring devices were given to 2 adolescent girls (14-year-old with diplegic cerebral palsy and her 15-year-old healthy sister). Outcome measures were traveling distances, time spent outdoors, and Children’s Assessment of Participation and Enjoyment questionnaires. Global positioning systems documented that the girl with cerebral palsy did not visit nearby friends, spent less time outdoors and traveled shorter distances than her sister (P = .02). Participation questionnaire corroborated that the girl with cerebral palsy performed most activities at home alone. Lower outdoor activity of the girl with cerebral palsy measured by a global positioning system was 29% to 53% of that of her sibling similar to participation questionnaires (44%). Global positioning devices objectively documented low outdoor activity in an adolescent with cerebral palsy compared to her sibling reflecting participation reported by validated questionnaires. Global positioning systems can potentially quantify certain aspects of participation.
Foot drop is commonly caused by compromise of the peripheral nervous system. Unilateral foot drop as the first sign of a parasagittal brain tumor has been reported in the adult literature but never previously in the pediatric population. We report a child with a right parietal rhabdomyosarcoma in which foot drop was the only abnormal neurologic finding at initial presentation. Localization to the central nervous system should be included in children presenting with foot drop.
A 6-week-old male infant presented with 2 days of fever, emesis, and diarrhea, associated with episodic and chaotic rapid eye movements, determined to be opsoclonus. An electroencephalogram (EEG) obtained during the events was normal. He was treated empirically for meningitis, and an initial workup for neuroblastoma including urine homovanillic acid and vanillylmandelic acid levels, abdominal ultrasonography, and computed tomography (CT) of the chest, abdomen, and pelvis was negative. Stool and blood cultures were positive for Salmonella, and antibiotic regimen was adjusted appropriately. Over the next few days, his fever, emesis, and diarrhea subsided, and the opsoclonus resolved by hospital day 6. He was back to baseline by hospital day 9. Although there have been cases of parainfectious opsoclonus associated with Lyme disease, enterovirus, Streptococcus, and West Nile virus, this represents the first reported pediatric case of opsoclonus associated with salmonellosis. Only 2 such cases in adults have been reported in the literature.
The voltage-gated sodium channel genes and HOXD genes are clustered on chromosome 2q, and duplication of this region is associated with 2 clinical phenotypes: early-onset epilepsy and mesomelic dysplasia Kantaputra type, respectively. We report a case involving 2q24.3–2q32.1 duplication encompassing both the voltage-gated sodium channel and HOXD gene clusters, which were detected by a comparative genomic hybridization array. The associated clinical features were early-infantile-onset epilepsy, hypoplastic left heart syndrome, and global developmental delay. However, no features of mesomelic dysplasia were found. A fluorescent in situ hybridization study showed that the noncontiguous insertion of the duplicated chromosome 2q segment into chromosome 6q was inherited from the father, who has a balanced insertional translocation. The unique genotype–phenotype correlation in the present case suggests that dosage-sensitive effects might apply only to the voltage-gated sodium channel genes.
This event-related potential study focused on neural correlates of inhibitory affective control in attention-deficit hyperactivity disorder (ADHD). Sixteen boys with ADHD and 16 healthy boys underwent an emotional Go/NoGo task with pictures of facial expressions from the categories anger, sadness, happiness, and neutral. The participants were instructed to execute or withhold a motor response to specific emotions. Patients relative to controls displayed a severe impairment in response inhibition toward anger cues, which was accompanied by a reduced P300 amplitude (positive voltage deflection about 300 ms after picture onset). The control group showed a P300 differentiation of the affective categories that was absent in the ADHD group. The pronounced anger-processing deficit in ADHD patients might be linked to their interpersonal difficulties and should be addressed in psychotherapy.
A family with 2 siblings with severe spinal muscular atrophy with respiratory distress 1 (SMARD1) was genetically proved to be caused by mutations in IGHMBP2 gene. Both patients developed progressive muscular weakness and respiratory distress and died before 6 months of age. One novel deletion, c.780delG;p.(Gln260Hisfs*24), inherited from the father and a nonsense mutation, c.1488C>A;p.(Cys496*), inherited from the mother were detected. An attempt was made to correlate the genetic-clinical data available in the literature. The clinical case presented in this study might be considered as the most severe form of spinal muscular atrophy respiratory distress 1 reported so far, presumably because of the total absence of IGHMBP2 enzyme activity.
Central nervous system infections are significant causes of mortality and long-term neurologic complications in children. Survivors often require an extended period of rehabilitation. The authors carried out a retrospective analysis of 1158 children (aged 1 month to 16 years; 31 boys) treated in one pediatric intensive care unit in Warsaw between 2002 and 2010. Forty-three of 1158 (3.7%) children presented with neuroinfections. Nearly two-thirds of the children were younger than age 5 years. The majority of cases (62.8%) were vaccine-preventable bacterial infections. The most frequent complications were brain edema (30.2%), brain hemorrhage (27.9%), and secondary nosocomial pneumonia (25.6%). One-fifth of children developed late, long-term neurologic complications. The mortality rate was 20.9%. The study showed that central nervous system infections are significant causes of hospitalization in the pediatric intensive care unit and often result in death or long-term complications. These infections mainly affect children younger than age 5 years. The majority could be prevented with immunizations.
Varicella (chickenpox) is a common childhood infection caused by the varicella-zoster virus, which is often self-limiting and usually benign. Although uncommon, neurologic complications of varicella have been documented that include postinfectious cerebellar ataxia, meningoencephalitis, Reye syndrome, myelitis, optic neuritis, stroke, Guillain-Barré syndrome, seventh cranial nerve palsy, and Ramsay-Hunt syndrome. In this case study, the authors describe a 7-year-old girl who presented with varicella skin rash with unsteady gait and anarthria on day 2, and her condition was attributed to cerebellar mutism. To date, this complication has never been reported in a child with primary varicella infection. Therefore, this case study documents a rare but serious complication of childhood chickenpox.
Bilateral periventricular nodular heterotopia is a neuronal migration disorder characterized by gray matter cellular rests in the periventricular regions. Megalencephaly has not been reported in children with bilateral periventricular nodular heterotopia. No other disorder with a similar phenotype has been reported. Here we report the case of a 5-year-old Japanese boy with bilateral periventricular nodular heterotopia and megalencephaly. Relative macrocephaly was evident at birth, and bilateral periventricular nodular heterotopia and megalencephaly were noted on magnetic resonance imaging (MRI). However, no hydrocephalus or indication of cerebral cortical dysplasia was seen. A mild intellectual disability was present, but the patient had no history of seizures. Genetic analysis revealed no mutation on the capillary sequences for FLNA, and no pathogenic abnormalities were evident on array comparative genomic hybridization. This case could represent a new disease entity: bilateral periventricular nodular heterotopia with megalencephaly.
Certain drugs are known to cause metabolic changes resulting in altered metabolic profiles. We report here a case where a combination of antiepileptic drugs resulted in a profile that mimicked a metabolic disorder. A 16month-old female child on antiepileptic drugs (valproate and topiramate) was suspected to have the inherited metabolic disorder, dihydrolipoamide dehydrogenase deficiency, based on clinical symptoms and metabolic profile showing hyperalaninemia, elevated branched-chain amino acids, and lactate-pyruvate ratio. Suspecting that the observed metabolic changes could have also arised from medication, current medication was weaned off and replaced with levetiracetam, clonazepam, and levocarnitine (supportive therapy). Metabolic profiling conducted after 47 days showed normal alanine, branched-chain amino acids, ornithine, and lactate-pyruvate ratio, suggesting that the earlier abnormalities could have been medication induced. We stress that metabolic changes resulting from chronic medication should be considered while interpreting a positive result when investigating an inherited metabolic disorder.
Ankle sprain is only rarely reported as the cause of peroneal nerve palsy and occurs predominantly in adults. Peroneal nerve palsy following an ankle sprain is extremely rare in children. Furthermore, peroneal nerve palsy most commonly results from a severe ankle sprain with considerable pain and edema. Peroneal nerve palsy after minor ankle torsion without major clinical symptoms of ankle sprain is uncommon. Here, we report the case of a 9-year-old boy who developed right peroneal neuropathy, leading to foot drop, following minor ankle plantar flexion/inversion torsion. Electrophysiological findings confirmed a focal neuropathy around the fibular head. The neurologic symptoms resolved completely 4 months after the injury. This case emphasizes that peroneal neuropathy can occur after minor ankle torsion without evident ankle sprain symptoms. Moreover, electrophysiological evaluation is very helpful to confirm the diagnosis and is important for prognostic evaluation.
The goal of the International Classification of Functioning is to standardize the classification of health and function of children around the world. To facilitate the application of this classification, International Classification of Functioning–based tools like the "Core Sets" are being developed. We conducted an international survey of professional experts to identify the most relevant areas of functioning in children with cerebral palsy. The questionnaire covered each component of the classification. In total, 193 professionals completed the survey (response rate 78%). Overall, 9706 answers were linked to the classification (pediatric version) by 2 professionals. From the experts’ perspective, movement-related areas and social participation are the most relevant areas of functioning. Experts suggest a more comprehensive profile of functioning in particular in areas of personal capacity and social participation. The results of this survey will inform the development of the International Classification of Functioning Core Sets for children with cerebral palsy.
A patient with neurofibromatosis type 1 and the rare finding of concomitant meningioma and optic pathway glioma within the same optic nerve is presented. A 4-year-old boy was admitted to our hospital with right-sided proptosis. He also had numerous café-au-lait macules and axillary freckling on physical exam. According to National Institutes of Health (NIH) criteria, he met the diagnostic criteria for neurofibromatosis type 1. On magnetic resonance imaging (MRI), a mass originating from the right optic nerve sheath with normal appearance of the optic nerve was observed, which was consistent with optic nerve sheath meningioma. Another mass lesion was observed in the prechiasmatic region of the same optic nerve, which was consistent with optic nerve glioma. Two different types of optic pathway tumors in the same optic nerve is an extraordinary case. It is important to recognize imaging findings of these tumors and make correct diagnosis.
Implantation of an intrathecal baclofen pump is recommended for children with cerebral palsy as a means to improve care and comfort when other options fail to control severe hypertonia. Making an assessment of a child’s spasticity-related limitations in both routine care and activity is a necessary component of selection of intrathecal baclofen candidates. The Rehabilitation Institute of Chicago Care and Comfort Caregiver Questionnaire (RIC CareQ) is a validated, easy-to-use questionnaire that elicits information about the ease of daily activity and caregiving in patients with severe spasticity. Questionnaires completed by caregivers and patients at a pediatric physiatry spasticity clinic over an 11-year period were reviewed to evaluate whether the Rehabilitation Institute of Chicago Care and Comfort Caregiver Questionnaire captured improved caregiving and comfort of children with cerebral palsy and severe spasticity following intrathecal baclofen pump implantation. The Questionnaire scores showed improvement after intrathecal baclofen pump implantation, consistent with subjective reports of patient and caregiver satisfaction.
Fukutin-related protein (FKRP) is a putative glycosyltransferase that mediate O-linked glycosylation of the α-dystroglycan. Mutations in the FKRP gene cause a spectrum of diseases ranging from a limb girdle muscular dystrophy 2I (LGMD2I), to severe Walker-Warburg or muscle-eye-brain forms and a congenital muscular dystrophy (with or without mental retardation) termed MDC1C. This article reports on a Moroccan infant who presented at birth with moderate floppiness, high serum creatine kinase (CK) levels, and brain ultrasonograph suggestive of widening of the posterior fossa. Muscle biopsy displayed moderate dystrophic pattern with complete absence of α-distroglycan and genetic studies identified a homozygous missense variant in FKRP. Mutations in FKRP should be looked for in forms of neonatal-onset hyperCKaemia with floppiness and small cerebellum.
We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.
Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic and usually refractory epilepsy syndrome that occurs after a febrile illness in previously normal children. The pathogenesis of the syndrome is unknown, and the diagnosis is typically made by exclusion after an exhaustive negative workup for central nervous system infections and autoimmune or metabolic disorders. Magnetic resonance imaging of patients with this condition has previously shown hippocampal abnormalities, typically found several months or longer after initial seizures. We report a previously healthy 5-year-old child who developed hippocampal atrophy by day 37 of his illness. The development of early hippocampal atrophy in this epileptic encephalopathy may provide insight into pathogenesis and highlights the need for aggressive and effective interventions early in the disease process.
A 14-year-old male presented with paresthesias on the right upper and lower extremities, headache, and vomiting. In addition to worsening paresthesia and weakness on the right side of his body, blurred vision, fever, and skin lesions developed. He also had skin lesions characterized with 3-10 mm papules with a white atrophic center surrounded by pink rim mostly on the trunk and lower extremities. Brain magnetic resonance imaging showed chronic subdural effusion and encephalomalacia of the left cerebral hemisphere. Cerebrospinal fluid (CSF) examination revealed increased protein levels. Electromyography was consistent with diffuse polyradiculoneuropathy. Skin biopsy confirmed the diagnosis of a rare vasculopathy: Degos disease. A case presenting with chronic subdural effusion, encephalomalacia, elevated CSF protein, and polyradiculopathy should be carefully examined for skin lesions, which may suggest the diagnosis of Degos disease.
Time to treatment of seizures is critical to efficacy. We performed a quality initiative and evaluated time to treatment of inpatient seizure emergencies with first- and second-line medicines before and after implementation of a computerized, standard treatment protocol. Data from 125 patients revealed that 179 seizure episodes required first-line antiepileptic drugs, and the mean time to treatment was 7.72 minutes. In 87 episodes, patients (49%) received the drugs within 5 minutes. Forty-six episodes required second-line drugs. In 17 (37%), patients received them within 30 minutes (mean 49.48 minutes). After implementation of the protocol, the mean time to treatment with first-line drugs was 3.74 minutes, a reduction of >50% (P < .0001). The mean time to treatment with second-line drugs was 25.05 minutes, a reduction of ~50% (P < .0001). This effective model for reducing the time to treatment of seizure emergencies may be useful to similar institutions.
A 4-year-old boy presented with a history of tremor for 7 days. He also had recurrent diarrhea for the previous 1 year, and poor weight gain. Magnetic resonance of the brain was suggestive of central pontine myelinolysis. There was no evidence of electrolyte abnormalities. The serum tissue transglutaminase level was markedly elevated, and the duodenal biopsy revealed features of celiac disease. The patient was started on gluten-free diet. The tremor resolved within 3 months. Repeat imaging of the brain done 3 months after starting gluten-free diet showed complete resolution of the lesion. This case highlights the unusual presentation of central pontine myelinosis as tremor in a malnourished child with celiac disease.
Although genetic defects are the leading cause of central nervous system malformations including in the posterior fossa, specific malformative patterns should alert the clinician to consider rather a teratogenic etiology. We discuss the imaging features of 2 mid-hindbrain malformations consecutive to the intake of isotretinoin (Roaccuatane®; case 1) and misoprostol (Cytotec®; case 2) during pregnancy and review the pertinent literature. We correlate the morphological appearance of the mid-hindbrain malformation, as seen on high-resolution magnetic resonance imaging to possible drug-induced pathogenetical mechanisms. The recognition of characteristic imaging patterns enables diagnosis of and/or confirmation of suspected drug-induced hindbrain malformations. This has important medicolegal implications and also clinical significance to avoid unsuccessful and misleading genetic testing.
The use of complementary and alternative medicine by children with autism and the association of its use with child comorbid symptoms and parental stress was studied in an ethnically diverse population, in a cross-sectional study with structured interviews. The sample included 50 families of children with autism and 50 families of children with other developmental disabilities, matched by age/gender. Interview included the Complementary and Alternative Medicine Questionnaire, Gastrointestinal Questionnaire, Children’s Sleep Habits Questionnaire, Aberrant Behavior Checklist, and Parenting Stress Index. In this ethnically diverse sample, the use of complementary and alternative medicine was significantly higher for the autism group. In the autism group, use was significantly related to child’s irritability, hyperactivity, food allergies, and parental stress; in the developmental disabilities group, there was no association with child comorbid symptoms or parental stress. The results contribute information to health care providers about families of children with autism who are more likely to use complementary and alternative medicine.
SMART syndrome (stroke-like migraine attacks after radiation therapy) is a rare condition that involves complex migraines with focal neurologic findings in patients following cranial irradiation for central nervous system malignancies. Little is known about the mechanisms behind the disorder, making successful treatment challenging. We report 2 new cases of SMART syndrome in pediatric patients as well as review all documented cases of the syndrome. Each of our 2 pediatric patients suffered multiple episodes. Attacks were characterized by severe headache, visual disturbance, aphasia, and weakness. Recovery occurred over several days to weeks. The data from all documented reports of SMART syndrome indicate a greater prevalence for male gender. An age-dependent pattern of onset was also observed, with a greater variability of syndrome onset in patients who received cranial irradiation at a younger age. SMART appears to be a reversible, recurrent long-term complication of radiation therapy with possible age- and gender-related influences.
The aim of this study was to describe the association between pediatric pseudotumor cerebri and low serum vitamin A levels. We retrospectively reviewed the charts of 6 children (5 boys, 1 girl; mean age 8 years) with increased intracranial pressure and low serum vitamin A levels (mean 16.0 ± 8.8 µg/dL). The etiology of the vitamin A deficiency was a restricted diet (2 children), intestinal malabsorption caused by celiac disease (2 children), and undetermined cause (2 children). Only 1 child had ocular signs of xerosis. Poor visual acuity at presentation and lower serum vitamin A levels were associated with a poor visual outcome and development of optic atrophy. In conclusion, pseudotumor cerebri in children can be associated with vitamin A deficiency even when other manifestations of xerophthalmia do not exist. Early recognition of this condition and appropriate therapy can prevent blindness.
Sudden unexplained death in epilepsy (SUDEP) is associated with generalized tonic-clonic seizures and occurs most often when patients are in bed. There are several seizure detection monitors on the market, but little data are available on the sensitivity and specificity of these devices. We recently tested 2 models of seizure detection alarms with disappointing results. Here we tested the Emfit movement monitor on children with various seizure types who also had standard video electroencephalography (EEG), cardiopulmonary, and nursing monitoring. Video EEG records were reviewed to detect any seizures. In 45 patients, 78 seizures were recorded by video EEG. The Emfit movement monitor captured 23 seizure events (30%) in total, and 15 of the 28 (54%) that occurred during sleep. Most importantly, the alarm was activated with 11 of the 13 (85%) generalized tonic-clonic seizures that occurred in sleeping children. The Emfit movement monitor performed very well in comparison to previously tested devices.
Chronic inflammatory demyelinating polyneuropathy is a rare condition in children. In this article, we report our experience in the management of 10 cases of childhood chronic inflammatory demyelinating polyneuropathy in a single center, in the era of contrast-enhanced magnetic resonance imaging (MRI), genetic microarray, and chronic inflammatory demyelinating polyneuropathy disease activity status. Robust neurophysiologic abnormalities were present in all cases and both MRI and lumbar puncture were useful adjuncts in diagnosis. Genetic microarray is a simple technique useful in excluding the most common hereditary demyelinating neuropathy. Intravenous immunoglobulin was an effective first-line therapy in most cases, with refractory cases responding to corticosteroids and rituximab. We found the chronic inflammatory demyelinating polyneuropathy disease activity status useful for assessing outcome at final follow-up, whereas the modified Rankin score was better for assessing peak motor disability.
We describe a 13-year-old female with abrupt onset urinary retention progressing rapidly to pandysautonomia with symptoms of postural orthostatic tachycardia syndrome, gastroparesis, anhidrosis, pupillary dysfunction, and abdominal pain. Pandysautonomia has been reported frequently in adults, but is less commonly described in children. Autonomic nervous system dysfunction usually has a self-limiting course with gradual near-complete or complete recovery. Most patients with pure pandysautonomia produce an antibody targeted against the ganglionic nicotinic acetylcholine receptor and titers have been shown to correlate with symptom severity. The clinical presentation described in this report is consistent with a progressive form of acute autoimmune autonomic neuropathy, but she was initially seronegative for known autoantibodies. She responded promptly to plasmapheresis. This case report emphasizes the importance of recognizing features of autonomic nervous system dysfunction and discusses the medical evaluation and treatment options for pediatric patients based on symptom severity.
This study utilized diffusion tensor imaging fiber tractography to examine the miscrostructural integrity of limbic and paralimbic white matter tracts in 36 children (age M = 124 months) with histories of early deprivation, raised from birth in orphanages and subsequently adopted into the United States, compared to 16 age-matched typically developing children. We found increased mean diffusivity bilaterally in the arcuate fasciculus and increased mean diffusivity and reduced fractional anisotropy bilaterally in the uncinate fasciculus and cingulum in children with early deprivation. Microstructural integrity of the left arcuate fasciculus and right cingulum was related to language and behavioral functioning, respectively. White matter abnormalities were also associated with length of deprivation and time in the adoptive home. Our findings suggest that white matter pathways, connecting limbic and paralimbic brain regions is abnormal in children with histories of early deprivation, with some pathways appearing more susceptible to early deprivation than others.
Although levodopa is the main treatment for dystonia, its role in cerebral palsy has not been assessed. We hypothesized that levodopa will improve upper limb function in individuals with cerebral palsy. Nine participants (age 16.8 ± 5.6 years) with quadriplegic cerebral palsy and upper limb dystonia were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Function was assessed before and after 2 weeks of treatment of levodopa and placebo using box-and-blocks, 9-hole pegs, dynamometer recordings, and Quality of Upper Extremity Skills Test. No benefits for upper limb functional performance were found following levodopa (6.65 ± 1.66 mg/kg/d) treatment compared to placebo. No side effects were reported.
Nonketotic hyperglycinemia is an inborn error of glycine metabolism. It manifests mostly as an acute encephalopathy in the neonatal period, although later, atypical presentations have also been reported. Mutations in 3 different genes have been implicated in nonketotic hyperglycinemia. Here we report a novel mutation, c.2296G>T (p.Gly766Cys), in exon 19 of the glycine decarboxylase (GLDC) gene (Refseq accession number NM_000170.2) in a consanguineous Indian couple with a history of 4 neonatal deaths.
This study aimed to investigate any differences between the motor skills and sensory processing abilities of children between the ages of 4 and 8, who do and do not have an idiopathic toe walking gait. Children in each cohort were tested with a number of norm referenced assessments. A total of 60 children participated, 30 within each cohort. Those with an idiopathic toe walking gait were found to have different Sensory Profile quadrant scores (P = .002), poorer performance on the Bruininks–Oseretsky Test of Motor Proficiency (P ≤ .001), a lower vibration perception threshold (P = .001), and poorer performance on the Standing Walking Balance subtest of the Sensory Integration and Praxis Test (P = .047), compared with non–toe walking peers. Although this research does not give a causative factor for toe walking gait, it provides a number of theories as to why this gait may not be idiopathic in nature.
This study evaluated prevalence and risk factors for vitamin D deficiency among children with epilepsy on long-term antiepileptic drugs treated in South Queensland, Australia. Children with epilepsy seen in a tertiary neurology clinic were contacted requesting bone health blood tests during winter of 2011. Vitamin D deficiency was defined as 25-hydroxy vitamin D levels <20 ng/mL, and insufficiency between 21 and 29 ng/mL. One hundred thirty letters were sent, with 111 (85%) subsequently having blood tests performed. Vitamin D deficiency was identified in 24 (22%) of 111 and an additional 45 (41%) of 111 had vitamin D insufficiency. Multiple logistic regression analysis identified children on >2 antiepileptic drugs or with underlying genetic etiologies were more likely to have vitamin D deficiency. High proportion of children on long-term antiepileptic drugs in Queensland risk vitamin D deficiency and insufficiency despite living in the subtropics. Vitamin D monitoring and supplementation is important in the management of children on long-term antiepileptic drugs requiring tertiary care in Queensland.
Glucose transporter protein type 1 deficiency syndrome is a metabolic disorder manifesting as cognitive impairment, acquired microcephaly, epilepsy, and/or movement disorder caused by mutations in the SLC2A1 gene. We describe a cohort of isolated and familial cases of glucose transporter protein type 1 deficiency syndrome, emphasizing seizure semiology, electroencephalographic (EEG) features, treatment response and mutation pathogenicity. SLC2A1 mutations were detected in 3 sporadic and 4 familial cases. In addition, mutations were identified in 9 clinically unaffected family members in 2 families. The phenotypic spectrum of glucose transporter protein type 1 deficiency is wider than previously recognized, with considerable intra-familial variation. Diagnosis requires either hypoglycorrachia followed by SLC2A1 sequencing or direct gene sequencing. A ketogenic diet should be the first line of treatment, but more flexible diets, like the Atkins modified diet, can also be followed. Carbonic anhydrase inhibitors, such as acetazolamide or zonisamide, can be effective for seizure control.
Developmental delay and brain anomalies leading to significant morbidity and mortality are frequently caused by chromosomal rearrangements. We report on a familial unbalanced translocation resulting in distal monosomy 5p15.3-pter with trisomy 12q24.2-qter in 2 half siblings with cerebral dysgenesis, severe intellectual disability, dysmorphic features, progressive weakness, and atrophy of muscles.
The hypothesis that the presence of macrocephaly might vary with the specific growth chart used was tested by using the Nellahus, CDC, and recent Rollins et al revision head circumference charts to plot the head circumferences of 253 children with neurodevelopmental disorders and with ages between 12 to 36 months; of these children, 59 had a diagnosis of autism spectrum disorder. The CDC and Rollins et al head circumference charts identified more cases of macrocephaly and fewer cases of microcephaly than did the older Nellhaus chart but did not significantly differ in their identification of macrocephaly in children with autism.
Embryonal tumor with abundant neuropil and true rosettes has been recently defined as a distinct central nervous system embryonal neoplasm, although it was initially regarded as a subtype of central nervous system primitive neuroectodermal tumor. To date 70 cases have been reported. We have performed a literature review and we present 2 new cases. Analysis of the reported data revealed that radiotherapy, tumor excision and high-dose adjuvant chemotherapy with sequential autologous hematopoietic stem cell rescue have a prognostic significance.
Children with type I spinal muscular atrophy commonly demonstrate reduced bone mineral density. Our objectives were to evaluate and assess adequacy of vitamin D intake, serum levels, and association with bone mineral density. Assessments were completed using 3-day food records and dual energy x-ray absorptiometry scans. The spinal muscular atrophy type I cohort included 22 males and 18 females (N = 40), with a mean age of 18.6 months. Data collection occurred from 2001 to 2011. Seventy-five percent of patients had inadequate intake of vitamin D at the initial visit. Using mixed-effects analyses, vitamin D and calcium intakes correlated positively with bone mineral density (r = 0.31 and r = 0.53, respectively). Increased vitamin D and calcium consumption were associated with an increase in bone mineral density (P = .04 and P = .01, respectively). Vitamin D intake correlated positively with serum levels (r = 0.65). Further study is needed to determine optimal intakes of vitamin D and calcium in the spinal muscular atrophy type I population.
Idiopathic photosensitive occipital lobe epilepsy is a reflex, age- and localization-related syndrome. We describe the clinical and electroencephalographic features, therapy, and outcome of 16 children/adolescents with this syndrome. The cohort included 2 sets of siblings and 7 patients with other first- or second-degree relatives with a seizure history. All patients had occipital onset seizures and 15 had secondarily generalized tonic-clonic seizures. Seizure frequency was relatively low in all patients but one. Myoclonic seizures later developed in 2 patients with juvenile myoclonic epilepsy. Eight patients achieved full seizure control with monotherapy, and 5 required a second drug; 3 patients had rare seizures and were not treated with antiepileptics. Seven patients required special education or developmental assistance. This interesting syndrome sheds light on the pathophysiology and genetic etiology of common phenomena such as photosensitivity and headache. Further large prospective studies are required to better define this unique syndrome and its implications.
Tics are the most frequent movement disorder in children and they are most prevalent during the school-age years. Most tics are transitory; however, certain tics can be chronic, causing negative repercussions at school, within the family, and socially. In some cases, tics are associated with obsessive compulsive disorder, attention-deficit hyperactivity disorder (ADHD) and other conditions that require diagnosis and prompt treatment. In South America, there are no indexed studies determining the prevalence of tics in school-age children. The aim of this study was to establish the prevalence of tics in schoolchildren aged 6 to 12 years. From 16 000 students aged 6 to 12 years who were enrolled in first to fifth grade, a sample of 346 school-aged children was chosen via a multistage sampling process that randomized the educational systems in terms of proportional size and the stratification between public and private schools and adjusted for the design effect. The students were screened and those who were positive for tics underwent clinical evaluations and semistructured interviews by the researchers to determine the prevalence of the disease. The parents and teachers of 323 students returned our surveys (93.3%). One hundred thirty-eight students (42.7%) were considered positive for tics based on parents’ and teachers’ reports. The clinical evaluation established a 17.97% prevalence of tics (58 students), and 25 students (43.2%) also met diagnostic criteria for ADHD. Of the students with tics, 27.6% presented with transitory tics, and 72.4% presented with chronic tics. Gilles de la Tourette syndrome was detected in 11 of the children (3.4%). The average age of child with tics was 9 ± 1.5 years, and the majority of the children with tics attended third grade at a basic primary school. Children from public and private schools were equally likely to present with tics. Tics are noteworthy in our field and are associated with other neurobehavioral disorders, such as ADHD. Both tic disorders and ADHD require diagnosis and prompt treatment to promote social and school performance.
The opsoclonus-myoclonus syndrome is a distinct disorder characterized by opsoclonus, myoclonus, and ataxia, along with marked irritability and behavioral changes. Worldwide, data on its epidemiology, clinical features, and outcome are scarce. The aim of the study was to determine the clinical profile and outcome of children with this disorder. A retrospective study of all children admitted with a diagnosis of opsoclonus-myoclonus from 2000 to 2012 was done. Outcome was assessed on follow-up by direct assessment and by telephonic interview. Eleven patients with a diagnosis of opsoclonus-myoclonus were admitted over a 12-year period. Of the 11, 4 had paraneoplastic etiology. Children with paraneoplastic opsoclonus had more relapses and a poor outcome as compared to an idiopathic group. Paraneoplastic opsoclonus had a poor outcome in our experience.
Alpha-mannosidosis is a rare lysosomal storage disorder with a heterogeneous clinical presentation. We describe a set of siblings with alpha-mannosidosis. The older child presented with a severe phenotype with multisystem involvement and had progressive deterioration in her motor and cognitive functioning. She had a poor outcome. The second child has a less severe disease course. He is being managed symptomatically only because of the family’s poor socioeconomic circumstances. Therapeutic options in this condition are limited to bone marrow transplant early in the disease course. These disorders, although rare, should be considered in the approach to a child with dysmorphism, developmental delay, skeletal deformities, and visceromegaly.
Among adults, wakefulness and rapid eye movement (REM) sleep, compared to non-REM sleep, require higher overall brain metabolism, but in neonates analogous data are not available. Behavioral states with higher metabolic demand could increase vulnerability to hypoperfusion or hypoxia in the compromised neonatal brain. Using cerebral oximetry (near-infrared spectroscopy), and simultaneous polysomnography, we evaluated whether brain oxygen metabolism varies by sleep-wake state among critically ill newborns. For each of 10 infants, sleep-wake cycling was detectable and cerebral oximetry varied (P < .0001) across behavioral states, but the patterns differed among subjects. We conclude that cerebral oxygen metabolism varies with sleep-wake states in high-risk newborns. The direction and degree of these changes are variable and subject-specific in this initial sample, but could reflect or affect brain injury and vulnerability.
4H syndrome is a rare and distinct leukodystrophy characterized by hypomyelination, hypogonadotropic hypogonadism, and hypodontia. Detecting signs of pubertal growth failure and abnormal dentition offer the clues to the diagnosis. We present an Indian boy with this novel syndrome with previously unreported feature of bilateral undescended testes. We also provide a brief overview of all published cases.
Data were collected parenting stress, adaptive behavior, pain, and health issues from the caregivers of 35 girls and women with Rett syndrome (mean age = 20.3). A majority (60%) of parents reported stress in the clinical range on at least 1 subscale of the Parenting Stress Index–Short Form. Seizures and uncertainty about their daughter’s gastrointestinal pain experience were significantly associated with higher levels of parenting stress. No other child factors (adaptive behavior, age, residential status) were significantly related to parenting stress. Factors related to chronic health concerns (seizures, ambiguous pain presentation) may be important when considering family stress issues in relation to general outcomes for girls with Rett syndrome and related developmental disorders.
Childhood-onset cluster headache is an excruciatingly painful and distressing condition. A retrospective study was conducted on charts of patients referring to our Headache Center. Those diagnosed as cluster headache were selected. We identified 11 children (6 males and 5 females). The mean age of cluster headache onset was 10 years (range: 5-16). All children had episodic cluster headache. All children had unilateral orbital pain; 7 patients had throbbing pain, whereas 4 children complained stabbing pain. The mean duration of the attack was 86 minutes (ranging from 30 to 180 minutes). The frequency of episodes was between 1 and 4 per day. All children had the typical cluster headache autonomic features, such as lacrimation, conjunctival injection, ptosis, and nostril rhinorrhea. Steroids showed a good clinical efficacy in interrupting cluster headache recurrence. As symptomatic drugs, acetaminophen as well as ibuprofen were ineffective; indomethacin was effective in 1 case.
Pontocerebellar hypoplasias represent a group of neurodegenerative autosomal recessive disorders characterized by hypoplasia/atrophy of the cerebellum, hypoplastic ventral pons, and microcephaly and associated with various clinical features. Pontocerebellar hypolasia type 2 is the most common form, and different mutations in genes encoding subunits of the transfer ribonucleic acid (RNA)–splicing endonuclease (TSEN) complex were identified in patients. The authors report clinical, imaging, and molecular studies in 2 unrelated patients with different clinical pictures of the pontocerebellar hypoplasia type 2 spectrum and novel mutations in TSEN54, aiming to further define the clinical spectrum of the disease and possible indicators of more favorable progression. They identified a novel missense mutation c.355T>G/p.Y119D in compound heterozygosity with the "common" c.919G>T/p.A307S (patient 1) and a novel homozygous c.7ins6(CCGGAG)/p.E2-P3insPE variant (patient 2). An expanded array of mutations might contribute in defining possible differences in severity and phenotype-genotype correlations.
In Tourette syndrome, motor and phonic tics are associated with a spectrum of psychiatric disorders. As proxy report instruments are commonly used to assess children with Tourette syndrome, we investigated the relationship between child and mother ratings of behavioral problems. We enrolled 28 children with Tourette syndrome (25 males; mean age, 13.9 years) and 61 gender- and age-matched healthy controls (55 males; mean age, 14.7 years). Clinicians completed measures of tic severity, and all children completed the Youth Self-Report version of the Child Behavior Checklist, while their mothers completed the Child Behavior Checklist. In the clinical group, Youth Self-Report scores were significantly lower than mothers’ Child Behavior Checklist scores across the majority of subscales (especially affect and somatization). In contrast, for the control group, mother and child ratings only differed for the externalizing behavior subscales. Clinicians should be aware of these differences between self and mother ratings for specific behavioral problems in Tourette syndrome.
Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome (ROHHADS) is a rare, but potentially lethal, pediatric disorder. To date, nearly 80 patients have been reported in the literature; however, the etiopathogenesis is still unclear and debated. Both genetic and paraneoplastic or immune-mediated causes have been supposed to be involved in this syndrome. Nonetheless, at this time, a diagnostic biomarker is not available and diagnosis is based exclusively on clinical criteria. Aiming to establish the immune-mediated pathogenesis, we report 2 children with a clinical picture consistent with ROHHADS and whose cerebrospinal fluid analysis disclosed an intrathecal synthesis of oligoclonal bands. Even if many aspects remain to be explained, this finding suggests that ROHHADS could share similar pathogenetic mechanisms with other immune-mediated central nervous system disorders, and even more important, it might pave the way to a therapeutic chance for these patients by means of immunotherapy.
Congenital myasthenic syndromes are inherited disorders caused by various defects in neuromuscular transmission. Although the typical presentation is fatigable weakness with prominent cranial involvement, neonates can lack these hallmark manifestations, and in those with choline acetyltransferase gene mutations, basal electrophysiological testing can yield negative findings. The authors report the case of a male infant presenting at birth with oculomotor and bulbofacial weakness, hypotonia, clubfoot, and severe respiratory insufficiency. Electromyography showed myogenic signs, and basal repetitive nerve stimulation yielded negative findings. Since age 6 months, the infant had progressively improved, acquiring autonomous respiration. Prolonged subtetanic repetitive nerve stimulation disclosed a marked decremental response compatible with suspected congenital myasthenic syndrome with episodic apnea. Genetic testing identified 2 novel choline acetyltransferase mutations (R470X, F580C). Keeping a high clinical suspicion of this rare condition and undertaking early comprehensive electrophysiological assessments including prolonged repetitive nerve stimulation (10 Hz for 5 minutes) can expedite the diagnosis.
Acute cerebellar ataxia is the most common cause of childhood ataxia, usually resulting from infections or vaccinations. Cases of acute cerebellar ataxia have been reported as a consequence of several viral and bacterial infections as well as immunizing agents, such as varicella, influenza, hepatitis B, and diphtheria-pertussis-tetanus vaccines. Although immunization with meningococcal group C conjugate vaccines has been associated with several neurological side effects, acute cerebellar ataxia has not been previously reported. The authors describe a case of a 12-year-old girl exhibiting acute cerebellar ataxia following meningococcal group C conjugate vaccination. In this patient, cerebellar symptoms started within 24 hours from the vaccination, and infective causes have been ruled out by serum and liquoral analyses. Magnetic resonance imaging findings were normal. Progressive clinical improvement was obtained after corticosteroid treatment. This case increases the small number of postvaccinal ataxias and contributes to further clarifying the complex pathogenesis of this disorder.
We to report clinical biological and radiologic features of rubella encephalitis in childhood and assess its prognostic impact. Our retrospective study was conducted in an intensive care unit of a university hospital in Sfax, Tunisia. Twenty-one children (age range, 1-15 years) were included. Median age was 9 years (lower and upper quartiles, 7-11 years). On admission, generalized maculopapular eruption was found in 17 cases (81%). Median Glasgow Coma Scale score was 7 (lower and upper quartiles, 7-8). Twenty patients (95.2%) experienced at least 1 episode of seizures. Sixteen patients (76.2%) developed a status epilepticus. The result for enzyme-linked immunosorbent assay detecting anti-rubella immunoglobulin (M) was positive in the serum and in the cerebrospinal fluid samples for all our patients. Magnetic resonance imaging (MRI) of the brain was performed on admission for 3 patients (14.3%) and within a median of 4 days (lower and upper quartiles, 2-6 days) for 8 patients. The test was normal in 6 cases. Two deaths were recorded (9.5%). Survivors had no neurological sequelae 6 months after intensive care unit discharge.
The objective was to investigate the prevalence of attention-deficit hyperactivity disorder (ADHD) in children with frontal lobe epilepsy and related factors. The medical records of 190 children diagnosed with frontal lobe epilepsy at Qilu Hospital of Shandong University between 2006 and 2011 were retrospectively collected, and a follow-up analysis of the prevalence of ADHD in these children was conducted. Of the 161 children with an effective follow-up, 59.0% (95/161) with frontal lobe epilepsy suffered from ADHD as well. Analysis of epilepsy and ADHD-related factors indicated that the incidence of ADHD was 89.4% (76/85) in children with abnormal electroencephalogram (EEG) discharges on the most recent EEG, which was significantly higher than the ADHD incidence of 25% (19/76) in children with normal readings on the most recent EEG (P < .01). Children with frontal lobe epilepsy have a high incidence of ADHD. Sustained abnormal discharge on the electroencephalogram is associated with increased comorbidity of ADHD with frontal lobe epilepsy.
Our objective was to examine the association of attention deficit and disorganization in boys with and without specific developmental disorder of motor function. Four groups of boys between the age of 7 and 12 years—(1) Disorganization + coordination disorder (n = 30); (2) Coordination disorder (n = 33); (3) Disorganization (n = 28); and (4) Control (n = 29)—were included. Teachers completed the Questionnaire for Assessing the Students’ Organizational Abilities for the Teacher and the Conners’ Teachers Rating Scale–Revised. The Movement Assessment Battery for Children and 2 subscales of an intelligence test (vocabulary and similarities) were administered. A significantly increased rate of attention deficit in children with organizational deficit was identified. Attention deficit in children with specific motor disorder was exclusively associated with an organizational deficit. Organizational deficit in childhood is highly associated with attention deficit, and this association is particularly relevant in children with specific coordination disorder.
In this study, we examined whether topologic network analysis, using resting state functional magnetic resonance imaging (MRI), can detect abnormalities of functional brain connectivity in children with unilateral brain injury due to Sturge-Weber syndrome. Three children with Sturge-Weber syndrome (ages 1, 3, and 10 years) underwent structural and resting state functional MRI, glucose metabolism positron emission tomography (PET), and neurocognitive evaluation. Eight different resting state networks were compared between the affected and unaffected hemispheres by quantitatively accessing communication efficiency measures. Significantly reduced efficiency values were found in all 3 patients. Visual network deficiency was present in both children with a visual field defect; frontal network abnormalities were associated with fine motor impairment. Location of network abnormalities corresponded to and, in some cases, extended beyond structural MRI and glucose PET abnormalities. The presented approach can detect early functional abnormalities of specific brain networks in children with Sturge-Weber syndrome.
Aspartylglucosaminuria is a rare autosomal recessive lysosomal storage disorder leading early to a progressive intellectual disability. Monozygous Qatari twins presented with an unusual perinatal manifestation characterized by severe muscular hypotonia, scarce spontaneous movements, multiple contractures, and respiratory insufficiency. Biochemical investigations suggested aspartylglucosaminuria, and a novel homozygous mutation c.439T>C (p.S147P) was found in the aspartylglucosaminidase gene. However, it cannot be excluded that the unusual neonatal presentation is due to an additional autosomal recessive disease in this multiply consanguineous family. The classical aspartylglucosaminuria phenotype (progressive speech delay, psychomotor retardation, and behavioral abnormalities) was observed in 3 Turkish siblings. Although aspartylglucosaminuria was suspected early, the definite diagnosis was not confirmed until the age of 18 years. A novel homozygous mutation c.346C>T (p.R116W) was found. These 5 cases emphasize that aspartylglucosaminuria is panethnic and may possibly present with prenatal manifestation. Screening for aspartylglucosaminuria should be done in all patients with unexplained psychomotor retardation.
Hemiplegia-hemiconvulsion-epilepsy syndrome is characterized by prolonged unilateral clonic seizures in a child followed by the development of hemiplegia. Focal status epilepticus results in unilateral cerebral edema of the epileptic hemisphere in the acute phase followed by cerebral hemiatrophy. Literature in the last 5 years does not describe malignant cerebral edema or resultant death. We report a case of a 3-year-old girl with hemiplegia-hemiconvulsion-epilepsy syndrome who died due to malignant cerebral edema and temporal lobe herniation. The first indication of worsening of clinical status after being seizure free was voltage suppression on continuous electroencephalography (EEG). We describe neuroimaging, EEG findings, and neuropathologic findings at autopsy and review pertinent literature. We also evaluate the evolving role of continuous EEG monitoring in the pediatric intensive care unit.
Rotavirus infection disturbs cellular Ca2+ homeostasis by triggering an increase in Ca2+ permeation. A theoretical link between Ca2+ dysregulation and seizures in patients with rotavirus gastroenteritis has been suggested, but no prior studies have investigated this relationship. To test our hypothesis that patients with rotavirus-associated seizures have greater Ca2+ homeostasis disruption than those without seizures, we compared clinical and laboratory data—including corrected total serum Ca2+ levels—between the 2 groups. Age, gender, maximum body temperature, day of admission, levels of electrolytes except Ca2+, blood pH, and urine ketone levels were not related to seizure occurrence. Significantly lower Ca2+ levels were found among the seizure (+) group (9.22 ± 0.50 vs 9.66 ± 0.46 mg/dL, P = .01). Although Ca2+ levels were within normal ranges and did not directly cause the seizures, our results provide preliminary evidence for a relationship between Ca2+ homeostasis disruption and seizures in rotavirus patients.
Neonatal neurology is a growing subspecialty area. Given the considerable amount of neurologic problems present in the neonatal intensive care unit, a neurologist with expertise in neonates is becoming more important. We sought to evaluate the change in neurologic care in the neonatal intensive care unit at our tertiary care hospital by having a dedicated neonatal neurologist. The period post–neonatal neurologist showed a greater number of neurology consultations (P<.001), number of neurology encounters per patient (P<.001), a wider variety of diagnoses seen, and an increase in the use of video electroencephalography (P=.022), compared to the period pre–neonatal neurologist. The neonatologists expressed appreciation for having a dedicated neurologist available. Standardized protocols for treating hypoxic-ischemic encephalopathy and neonatal seizures were also developed. Overall, by having a neonatal neurologist, neurology became part of the multidisciplinary team providing focused neurologic care to newborns.
A male infant with trisomy 21 simultaneously showed clinical features of hypomelanosis of Ito and hemimegalencephaly, with related intractable epileptic seizures. The epileptic seizures were refractory to conventional antiepileptic drugs and persisted until the patient underwent functional hemispherotomy. It is well known that patients with hypomelanosis of Ito may also have cortical dysplasia and hemimegalencephaly and that approximately half of these patients have chromosomal abnormalities. However, to our knowledge, there is no previous report of a patient with trisomy 21 associated with hemimegalencephaly. Here, we describe a rare case of coexisting trisomy 21 and hypomelanosis of Ito, associated with hemimegalencephaly.
A 6-year-old boy presented with weakness of the right upper and lower limbs, noted since infancy. Magnetic resonance imaging of the brain revealed periventricular nodular heterotopia lining the trigone and occipital horns of bilateral lateral ventricles along with herniation of the cerebellar tonsils below the foramen magnum suggestive of Chiari type 1 malformation. The association of periventricular nodular heterotopia with Chiari type 1 malformation has not been described earlier in children.
To determine the range of neurodevelopmental diagnoses associated with intermediate (45-54 repeats) and premutation (55-200 repeats) range cytosine-guanine-guanine fragile X expansions, the medical records of children with intermediate or premutation range expansions were retrospectively reviewed, and all neurodevelopmental diagnoses were abstracted. Twenty-nine children (9 female, 20 male; age, 13 months to 17 years) with intermediate (n = 25) or premutation (n = 4) range expansions were identified with neurodevelopmental diagnoses, including global developmental delay/intellectual disability (n = 15), language and learning disorders (n = 9), attention-deficit hyperactivity disorder (n = 5), epilepsy (n = 5), and motor disorders (n = 12), including 2 boys younger than 4 years of age with tremor and ataxia. Thus, children with intermediate or premutation range fragile X cytosine-guanine-guanine expansions may be more susceptible than children without such expansions to other processes, both genetic and environmental, that contribute to neurodevelopmental disability.
Pitt-Hopkins syndrome is characterized by mental retardation, hyperventilation, and dysmorphic features due to TCF4 mutations. We report a case of Pitt-Hopkins syndrome in a 21/2-year-old boy presenting with psychomotor retardation, recurrent respiratory tract infections, and dysmorphic features with absence of hyperventilation or other breathing abnormalities. Comparative genomic hybridization and quantitative real-time polymerase chain reaction were used to confirm TCF4 haploinsufficiency. Pitt-Hopkins syndrome is a rare debilitating disease that should be in the differential diagnosis of other neurodevelopmental disorders characterized by mental retardation and hypotonicity despite the absence of hyperapnea and seizures. Quantitative real-time polymerase chain reaction is another method to identify TCF4 and to confirm Pitt-Hopkins syndrome diagnosis.
Giant axonal neuropathy is a rare autosomal recessive disorder, which typically involves both central and peripheral nervous system. Yet the phenotypic-genotypic correlation remains obscure. We report a novel compound heterozygous mutation with the c. 805C>T in exon 4(Arg545His missense mutation) and the c. 1634G>A in exon 11(Arg269Trp missense mutation) in an 11-year-old Chinese giant axonal neuropathy case. This patient had an atypical giant axonal neuropathy phenotype rather similar to Charcot-Marie-Tooth disease, without tightly curled hair and mental retardation. The patient had a slowly progressive sensory motor neuropathy since age 3 years, and she also had nystagmus, feet deformities, scoliosis, and cerebellar tonsillar protrusion. Electrophysiological studies indicated a predominantly axonal sensory-motor neuropathy. The diagnosis was confirmed by sural nerve biopsy and direct sequencing of all the 11 gigaxonin exons. The proband’s parents are heterozygotes of the disease without symptoms. Our findings extend the number of gigaxonin mutations that cause giant axonal neuropathy.
Executive dysfunction occurs in sickle cell anemia, but there are few early data. Infants with sickle cell anemia (n = 14) and controls (n = 14) performed the "A-not-B" and Object Retrieval search tasks, measuring precursors of executive function at 9 and 12 months. Significant group differences were not found. However, for the A-not-B task, 7 of 11 sickle cell anemia infants scored in the lower 2 performance categories at 9 months, but only 1 at 12 months (P = .024); controls obtained scores at 12 months that were statistically comparable to the scores they had already obtained at 9 months. On the Object Retrieval task, 9- and 12-month controls showed comparable scores, whereas infants with sickle cell anemia continued to improve (P = .027); at 9 months, those with lower hemoglobin oxygen saturation passed fewer trials (Rs = 0.670, P = .024) and took longer to obtain the toy (Rs = –0.664, P = .013). Subtle delays in acquiring developmental skills may underlie abnormal executive function in childhood.
Autoimmune myasthenia gravis is rarely seen during infancy. Similar to adults, 85% to 90% of generalized pediatric myasthenia gravis cases have acetylcholine receptor antibodies. Approximately 30% of the remaining cases have antibodies against muscle-specific kinase. Information on the clinical course, treatment alternatives, and prognosis of pediatric muscle-specific kinase antibody–positive myasthenia gravis is limited because of the small number of cases. Here, we present a 14-month-old girl with muscle-specific kinase antibody–positive myasthenia gravis as one of the youngest patients described so far in the literature.
Biotinidase deficiency is a treatable cause of infantile epilepsy and the presentation can be nonspecific. The seizures are difficult to differentiate from other causes of epileptic encephalopathy, which generally have a poor prognosis. We report 2 infants who presented with seizures, and whose low cerebrospinal fluid glucose and high cerebrospinal lactate caused a diagnostic dilemma. Subsequent urine organic acids pointed to the correct diagnosis and avoided invasive investigation. The children had a good clinical outcome with resolution of their seizures on biotin treatment.
Mutations in the conserved telomere maintenance component 1 (CTC1) gene were recently described in Coats plus syndrome and in cerebroretinal microangiopathy with calcifications and cysts. Norrie disease protein (NDP) gene was found mutated in Norrie disease, in Familial Exudative Vitreoretinopathy, and in Coats syndrome. Here we describe a boy affected by Norrie disease who developed typical features of cerebroretinal microangiopathy with calcifications and cysts. Direct sequencing of the CTC1 and NDP genes in this patient shows the presence of compound heterozygosity for 2 mutations in CTC1 (c.775G>A, pV259M and a novel microdeletion c.1213delG) and a missense mutation in the NDP gene (c.182T>C, p.L61P). Based on these genetic findings and on the expression of both genes in endothelial cells, we postulate that microangiopathy might be a primary underlying pathologic abnormality in cerebroretinal microangiopathy with calcifications and cysts. This hypothesis is further supported by magnetic resonance imaging (MRI) data showing multiple minute calcifications in the deep gray nuclei and in terminal arteriolar zones.
A 14-year-old boy presented with acute visual loss due to cortical blindness. Two weeks after the visual symptoms, the patient developed behavioral abnormalities. Brain magnetic resonance imaging (MRI) revealed hyperintense lesions at parieto-occipital lobes on T2-weighted and fluid attenuated inversion recovery images. Sleep and awake electroencephalography (EEG) were normal, but diazepam administration revealed bilateral periodic synchronous complexes occurring every 20 to 30 seconds. Elevated measles antibody titers in cerebrospinal fluid confirmed the diagnosis of subacute sclerosing panencephalitis. We conclude that visual loss due to cortical blindness is an important finding of subacute sclerosing panencephalitis. Diazepam administration during EEG should be a part of investigation in cases with unexplained cortical blindness.
The acronym PHACE describes the association of facial hemangioma with anomalies of the posterior fossa, cerebral arteries, and cardiovascular and ocular alterations. This study presents a case of diagnostic suspicion based on fetal MRI. We report the case of a pregnant woman whose 26-week MRI revealed a female fetus with hypoplasia of the right cerebellar hemisphere and right microphthalmia, leading to the suspicion of PHACE syndrome. The diagnosis was confirmed at birth, together with other criteria: facial hemangioma, absent posterior inferior cerebellar artery, and dysplasia of the right internal carotid artery. To our knowledge, this is the first live case described prenatally with both ocular and cerebellar findings on fetal MRI that suggest PHACE syndrome. The prenatal presence of 2 PHACE criteria led to the suspicion of this syndrome, and prenatal diagnostic criteria might be developed to improve information regarding the prognosis of cerebellar malformations.
Central sleep apnea is not uncommon in children with neurologic disorders. The mechanisms include increased ventilatory chemosensitivity to carbon dioxide level. Conventional treatments include oxygen, noninvasive ventilation, and in patients with heart failure, improving cardiac output. Here, we present a case of a 9-year-old male with Angelman syndrome, epilepsy, insomnia, and central sleep apnea. The patient was initially evaluated for nighttime awakenings and pauses in breathing. Sustained-release melatonin was used to improve his nighttime awakenings. A polysomnography confirmed central sleep apnea. We saw a reduction in arousals and improvement in insomnia with sustained-release melatonin. On a repeat study, central sleep apnea was improved. We hypothesize that sustained-release melatonin, by improving sleep continuity and reducing arousals, might improve central sleep apnea. Studies are needed to test the hypothesis.
Polyarteritis nodosa is a systemic necrotizing vasculitis involving medium-sized muscular arteries. Polyneuropathy is the only neurologic manifestation included in the pediatric classification schema. Central nervous system manifestations include infarction, hemorrhage, and encephalitis. We report on a 13-year-old female whose initial presentation of polyarteritis nodosa included hypertension, seizures, and neuroimaging findings of vasogenic edema and posterior reversible encephalopathy syndrome. Posterior reversible encephalopathy syndrome has been reported in association with renal disease, transplantation, autoimmunity, and cytotoxic medications. Posterior reversible encephalopathy syndrome outcomes are usually favorable with supportive care and treatment of the underlying etiology. The patient’s neurologic condition improved after treatment of hypertension. Hypertension, posterior reversible encephalopathy syndrome, and abdominal pain led to a diagnostic workup. A systemic vasculitis was confirmed after detection of a perinephric hematoma and intrarenal aneurysms. This is a novel case of posterior reversible encephalopathy syndrome as an initial manifestation of pediatric polyarteritis nodosa.
Coma-induced blisters is a rare condition associated with prolonged impairment of conscious level, which is relatively well-known in adults following overdose with barbiturates. However, it has been very rarely described in children. A case of coma-bullae occurring in an 11-year-old child with meningoencephalitis is herein reported. The bullous lesions occurred on the limbs and trunks, and evolved into necrotic ulcers in a few days. No correlation with any drug overdosage was found. A skin biopsy revealed epidermal and eccrine sweat gland necrosis with abundant neutrophils, and thrombosis of the vessels in the lower dermis. A comprehensive review of the literature showed that only 5 cases of coma-bullae in children have been published so far. Coma blistering resolves spontaneously within days or weeks. Diagnosis of coma-bullae may require careful clinical-pathologic correlation to exclude other blistering diseases in children.
The authors report the case of a 4-year-old boy who developed progressive unilateral weakness and developmental delays prior to his diagnosis of classical homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse white matter changes, raising the concern for a secondary diagnosis causing leukoencephalopathy, since classical homocystinuria is not typically associated with these changes. Other inborn errors of the transsulfuration pathway have been reported as causing these changes. Once begun on therapy for his homocystinuria, his neurologic deficits resolved and his delays rapidly improved. Repeat MRI performed one year after instating therapy showed resolution of his white matter abnormalities. This case illustrates the need to consider homocystinuria and other amino acidopathies in the differential diagnosis of childhood white matter diseases and lends weight to the hypothesis that hypermethioninemia may induce white matter changes.
Given the 2010 position statement issued by the American Academy of Neurology that neurologists be consulted on return-to-play decisions following a concussion, we surveyed members of the Child Neurology Society to asses clinical practice management of concussion among child neurologists. Among the 239 respondents, the majority continued to rely on the American Academy of Neurology’s 1997 Practice Parameter to guide their decision-making process. Although the 2008 consensus statement from the Third International Conference on Concussion in Sport (Zurich Guidelines) is currently considered the most up-to-date guideline, few respondents relied exclusively on this guideline. More respondents who completed continuing medical education on concussion reported making clinical decisions based on the Zurich guidelines. The finding that child neurologists who completed continuing medical education had a greater familiarity with the more recently proposed consensus-based concussion guidelines supports the development of additional education in sports concussion at all levels of child neurology training.
The pathogenesis of acute encephalitis is divided into either direct infection or by immune-mediated inflammation, but the cause is still unknown. This retrospective study aimed to screen antineuronal antibodies in children with severe acute encephalitis. Thirty-four children (22 boys and 12 girls) underwent assessments such as antineuronal antibodies survey for autoimmune encephalitis and polymerase chain reaction/viral culture and antibody assays for all commonly recognized causes of infectious encephalitis. Sixteen (47.1%) were positive for autoantibodies, including antiglutamic acid decarboxylase antibodies in 16 and voltage-gated potassium channel complex antibodies in 1. Sixteen patients (47.1%) had presumed infectious etiologies, including 6 with influenza, 6 with Mycoplasma pneumoniae, 3 with enterovirus, and 1 with herpes simplex virus. In this study, influenza and Mycoplasma pneumoniae infection are the main presumed causes of severe acute encephalitis in children, although an immune-mediated mechanism may also play a role.
Lacosamide is a US Food and Drug Administration (FDA)–approved antiepileptic drug for patients 17 years or older with partial epilepsy. There are sparse data on children. The objective of our study was to evaluate its efficacy/safety in children with refractory epilepsy. Forty children (mean age 14.3 years) were treated with lacosamide at our institution (adjunctive therapy in 36, monotherapy in 4). Fifteen patients had symptomatic focal epilepsy, 2 had cryptogenic focal epilepsy, 20 had symptomatic generalized epilepsy, and 3 had cryptogenic generalized epilepsy. Two had juvenile myoclonic epilepsy and 5 had Lennox-Gastaut syndrome. Forty-two percent had at least >50% reduction in seizure frequency, and 6 became seizure free. Average dose was 7 mg/kg/d and average follow-up was 9.2 months. Responders had a 76.5% mean decrease in seizures. Fifteen children experienced an adverse reaction and 7 discontinued lacosamide (4: Ineffective, I: insurance denial, 1: tremor, 1: behavior). Lacosamide is effective and well-tolerated in children with refractory epilepsy.
Pelizaeus-Merzbacher–like disease is an autosomal recessive disorder characterized by neonatal nystagmus, ataxia, progressive spasticity, and development delay and is rarely caused by GJC2 mutations. We report 7 patients from a large consanguineous family who had variable severity of Pelizaeus-Merzbacher–like disease. The 3 youngest of branch A were bedridden by their first year because of permanent scissoring of their legs and had severe frontal lobe epilepsy. The single patient from branch B was the least affected, being able to walk until 12 years of age and had no epilepsy. Brain magnetic resonance imaging (MRI) showed hypomyelination. The patients had a novel canonical splicing GJC2 c.-20+1G>C mutation with a predicted loss of the coding connexin 47 protein. The exceptionally large number of patients in this unique family enabled to describe the intrafamilial variability of Pelizaeus-Merzbacher–like disease. The predicted functional loss of connexin 47 might be associated with a severe form of Pelizaeus-Merzbacher–like disease.
This study compares primary stereotypies (repetitive, self-stimulating, and seemingly nonsensical movements that can occur within typically developing children) and secondary stereotypies (those occurring within autistic or mentally retarded children). Utilizing a retrospective chart review from 1995 to 2010, the current study compares primary and secondary stereotypies by the application of a classification system that organizes the movement by its type (motor only, phonic only, mixed) and complexity. In addition, it investigates other parameters associated with the movements such as duration, frequency, age, functional impairment, and progression. The sample group consisted of 28 primary and 28 secondary cases. Primary stereotypies were predominantly motor, simple, of shorter duration, and of less frequency, whereas secondary stereotypies had more vocalization, complexity, longer durations, and higher frequencies. Moreover, functional impairment due to stereotypies was noted in 3 primary and 7 secondary cases, and worsening of stereotypies was noted in 70% of primary versus 44% of secondary cases.
The goal of this project was to promote bicycle helmet use via an inpatient educational program. We hypothesized that this program would increase bicycle helmet use. One hundred twenty inpatients with history of regular (>1 time per week) bicycle riding (mean age 10.0 ± 3.6 years; 67 males, 53 females; 57 whites, 59 blacks, 4 other) were randomized to treatment (n = 58) or control (n = 62) groups. All participants received a bicycle helmet. At 1 month, 50 (92.6%) of the intervention group and 48 (82.8%) of the control group wore a helmet every bike ride (P < .07). At 3 months, 50 (96.2%) of the intervention group and 44 (80%) of the controls wore a helmet with every bike ride (P < .03). The study proved feasible, requiring trained personnel to deliver the intervention. Providing a helmet without the intervention was effective in 80% to 83% of cases with respect to parental report of helmet wearing compliance.
Post-stroke seizures and epilepsy in children are a common but understudied complication. In this retrospective cohort study, the medical records of 65 children aged 0 to 18 years were analyzed to assess the risk of post-stroke seizures, detect the prevalence of post-stroke epilepsy, and ascertain which risk factors are associated with this condition in children. Forty-two patients (64.6%) had epileptic seizures following stroke (35 early, 7 late-onset), with most (78.5%) occurring in the first 24 hours. Nineteen children (29.2%) developed post-stroke epilepsy, which was significantly more common among patients with late-onset seizures (P = .034). There was a significant association between cortical involvement and development of epilepsy (P = .01). After Poisson regression, the relative risk of epilepsy was calculated as 2.4 in children with late-onset post-stroke seizures (95% confidence interval, 1.4-3.9; P = .001) and 3.7 in children with cortical involvement (95% confidence interval, 1.4-9.7; P = .009).
Leigh syndrome, due to a dysfunction of mitochondrial energy metabolism, is a genetically heterogeneous and progressive neurologic disorder that usually occurs in infancy and childhood. Its clinical presentation and neuroimaging findings can be variable, especially early in the course of the disease. This report presents a patient with infantile Leigh syndrome who had atypical radiologic findings on serial neuroimaging studies with early and severe involvement of the cervical spinal cord and brainstem and injury to the thalami and basal ganglia occurring only late in the clinical course. Postmortem microscopic examination supported this timing of injury within the central nervous system. In addition, mitochondrial deoxyribonucleic acid sequencing showed a novel homoplasmic variant that could be responsible for this unique lethal form of Leigh syndrome.
Early infantile epileptic encephalopathy or Ohtahara syndrome is the earliest form of the age-dependent epileptic encephalopathies. Its manifestations include tonic spasms, focal motor seizures, suppression burst pattern, pharmaco-resistance, and dismal prognosis. The purpose of this study was to evaluate the effectiveness of epilepsy surgery in selected infants. We identified 11 patients, 9 from the literature and 2 from our institution that fulfilled diagnostic criteria of Ohtahara syndrome and had undergone epilepsy surgery in infancy. Seven of the 11 infants have remained seizure free (Engel class IA) and four are reportedly having rare to infrequent seizures (Engel class IIB). All patients experienced "catch up" development. In contrast to Ohtahara's15 pharmacotherapy managed patients, who had a mortality rate of approximately fifty percent, and those that survived continued to have seizures and were severely impaired, the outcome of selected surgically managed patients is much more favorable.
Niemann–Pick disease type C is a rare neurodegenerative disorder with autosomal recessive inheritance that can be broadly categorized into different forms dependent on age at disease onset: pre-/perinatal, early infantile, late infantile, juvenile, and adolescent/adult. This study was conducted to define the age at onset, clinical manifestations, neuroimaging findings and response to treatment in 21 patients diagnosed with Niemann–Pick disease type C and managed in the neurology departments of hospitals in Tehran, Iran. The effects of miglustat on patient ambulation, fine and gross motor function, swallowing, hearing, speech, seizures, psychomotor development, and ocular movements were evaluated for up to 26 months of treatment. Ambulation, fine and gross motor movements, swallowing, speech, and supranuclear gaze palsy were generally stabilized during therapy, and psychomotor delay appeared to be improved in early- and late-infantile onset patients. However, miglustat had no effect on organomegaly or other systemic manifestations of the disease. Miglustat was well tolerated.
Craniopharyngioma frequently involves intracranial pain-sensitive structures. We retrospectively studied prevalence, associated risk factors, and outcome of headaches in children with craniopharyngioma. Fisher exact test and multivariate analysis were used to study association of study variables. Of the 51 craniopharyngioma patients treated at our institution from January 1994 to December 2005, 40 (78%) reported headaches (35 [68%] before tumor diagnosis). Migraine headaches were diagnosed in 32 (63%) and tension-type headaches in 11 patients (22%). The median follow-up period was 2.7 years. At the last follow-up, 38 (75%) were headache free. Presence of hydrocephalus, distortion of circle of Willis, and large tumor volume were associated with headache, and the last 2 variables were also associated with more severe and frequent headaches. Radiation treatment and insertion of Ommaya reservoir were associated with reduced headache frequency. In conclusion, headaches are common in patients with craniopharyngioma and are likely related to tumor size and volume. In most patients, headaches improve with successful tumor treatment.
Cognitive dysfunction is common in pediatric-onset multiple sclerosis, but long-term data on cognitive maturation in these patients are sparse. We report the clinical features and cognitive trajectories in 4 pediatric-onset multiple sclerosis patients who were 10 years or younger at first attack and were followed between 1998 and 2010. Relapses in all 4 patients were frequent early in the disease and became infrequent or absent over time. Declines on neuropsychological testing were most pronounced on measures of processing speed, specifically visuomotor speed, and executive control requiring mental sequencing and set shifting, whereas global intellectual ability and phonemic fluency remained stable or improved over time. These case studies demonstrate a negative impact of multiple sclerosis on cognitive development in the long term and suggest that continued observation into adulthood is required to appreciate the vocational consequences of pediatric-onset multiple sclerosis.
Acute disseminated encephalomyelitis has an acute onset followed by improvement over several weeks. However, some cases require more time for a definitive diagnosis after protracted psychiatric or nonspecific symptoms. The authors investigated the time from onset to definitive diagnosis, subsequent course of treatment, and outcomes in 7 children with acute disseminated encephalomyelitis treated at the authors’ hospital. The mean duration of illness before definitive diagnosis was 20.7 days (range: 2-50 days). Steroid pulse therapy was performed in all cases, and rapid improvements were observed; the mean duration from treatment initiation to hospital discharge was 8.6 days (range: 4-14 days). None of the cases showed neurological sequelae. Although this study investigated a small number of patients, its results suggest that time to diagnosis is often longer in children than in adults, and even in cases of delayed treatment, response to steroid pulse therapy is good and outcomes may not necessarily be affected.
There is a high incidence of autism in tuberous sclerosis complex. Given the evidence of impaired face processing in autism, the authors sought to investigate electrophysiological markers of face processing in children with tuberous sclerosis complex. The authors studied 19 children with tuberous sclerosis complex under age 4, and 20 age-matched controls, using a familiar–unfamiliar faces paradigm. Of the children, 6 with tuberous sclerosis complex (32%) had autism. Children with tuberous sclerosis complex showed a longer N290 latency than controls (276 ms vs 259 ms, P = .05) and also failed to show the expected hemispheric differences in face processing. The longest N290 latency was seen in (1) children with autism and tuberous sclerosis complex and (2) children with temporal lobe tubers. This study is the first to quantify atypical face processing in children with tuberous sclerosis complex. This functional impairment may provide insight into a mechanism underlying a pathway to autism in tuberous sclerosis complex.
To document the impact of Tourette syndrome on the health care needs of children and access to health care among youth with Tourette syndrome, parent-reported data from the 2007-2008 National Survey of Children’s Health were analyzed. Children with Tourette syndrome had more co-occurring mental disorders than children with asthma or children without Tourette syndrome or asthma and had health care needs that were equal to or greater than children with asthma (no Tourette syndrome) or children with neither asthma nor Tourette syndrome. Health care needs were greatest among children with Tourette syndrome and co-occurring mental disorders, and these children were least likely to receive effective care coordination. Addressing co-occurring conditions may improve the health and well-being of children with Tourette syndrome. Strategies such as integration of behavioral health and primary care may be needed to improve care coordination.
Hyperekplexia is a rare neurologic disorder, characterized by excessive startle response to unexpected stimuli. There are 3 cardinal features: generalized stiffness immediately after birth that normalizes during the first year of life; excessive startle reflex to unexpected (particularly auditory) stimuli; and a short period of generalized stiffness following the startle response while patient cannot elicit voluntary movements. Awareness of this condition will avoid misdiagnosis of disorders like epilepsy. Clonazepam is an effective medical treatment. We report a patient whose frequent falls triggered by sudden noise or tactile stimuli was initially misdiagnosed as epilepsy. The clinical diagnosis was subsequently revised to hyperekplexia and confirmed by mutation analysis of the GLRA1 gene, which showed c.497G>C (p.Cys166Ser) and c.526delG (p.Asp176Metfs*16). Both of them are novel mutations. His response to clonazepam is dramatic and has been able to engage in sports and social activities.
To see if the systemic inflammation profile of 123 infants born before the 28th week of gestation who had intraventricular hemorrhage without white matter injury differed from that of 68 peers who had both lesions, we compared both groups to 677 peers who had neither. Cranial ultrasound scans were read independently by multiple readers until concordance. The concentrations of 25 proteins were measured with multiplex arrays using an electrochemiluminescence system. Infants who had both hemorrhage and white matter injury were more likely than others to have elevated concentrations of C-reactive protein and interleukin 8 on days 1, 7, and 14, and elevated concentrations of serum amyloid A and tumor necrosis factor–α on 2 of these days. Intraventricular hemorrhage should probably be viewed as 2 entities: hemorrhage alone and hemorrhage with white matter injury. Each entity is associated with inflammation, but the combination has a stronger inflammatory signal than hemorrhage alone.
A retrospective cohort study was conducted to describe the relationship between gross motor function and manual ability in children with cerebral palsy and explore differences between cerebral palsy subtypes and associated comorbidities. Children with cerebral palsy born between 1999 and 2008 were included from the Registre de la Paralyse Cérébrale de Québec identifying 332 children. The overall agreement between Gross Motor Function Classification System and Manual Ability Classification Scale Levels was moderate (kappa 0.457, standard error 0.034) with a strong positive correlation (Spearman rho of 0.820, standard error 0.023). This agreement was moderate among children with spastic quadriparesis and dysketic cerebral palsy, fair in children with spastic diplegia, and poor in children with spastic hemiplegia. Children with cognitive impairment showed a higher correlation than those without cognitive impairment. The correlation between gross motor function and manual ability in children with CP varies based on neurologic subtype and cognitive level.
Panayiotopoulos syndrome is an idiopathic epilepsy syndrome presenting with a large variety of autonomic symptoms. The mechanism of autonomic symptoms is still not well understood. A neurologically normal 13-month-old boy presented on 2 occasions with complex partial status epilepticus that included significant ictal priapism. Inpatient brain magnetic resonance imaging (MRI) scan showed restricted diffusion-weighted imaging within his left temporal lobe and electroencephalograms (EEGs) left temporal slowing only. An outpatient EEG 6 months later showed abundant multifocal, predominantly posterior, as well as irregular generalized spike-and-slow-wave discharges on normal background consistent with the diagnosis of Panayiotopoulos syndrome. Ictal priapism is a previously undescribed phenomenon that is consistent with parasympathetic manifestations noted in this young boy. Acute postictal MRI and EEG findings suggest that this undeniably fascinating seizure semiological sign may be localized to the left temporal region.
Insomnia is prevalent in pediatrics, particularly in those with neurodevelopmental disorders. Gabapentin has shown promise in treating insomnia in adults. The purpose of our study was to review our experience with using gabapentin to treat insomnia in children. We identified 23 children, seen by the authors in our Pediatric Sleep Clinic from January 2009 to March 2012. The mean age was 7.2 years and 70% were male. The majority (87%) had been given diagnoses of neurodevelopmental or neuropsychiatric disorders. All parents received education in sleep behavioral interventions. The majority of children (70%) had both sleep-onset and sleep maintenance insomnia. The average starting dose of gabapentin was 5 mg/kg every bedtime and the maximal dose was 15 mg/kg every bedtime. At follow-up, improved sleep was noted in 78% of children. Adverse effects were noted in 6 children.
Children with neurofibromatosis type 1 exhibit a variety of developmental delays. However, there is little information about the progression of these deficits over the course of development. Using the Parents’ Evaluation of Developmental Status measurement tool, we assessed 124 infants (0-2 years of age), preschool-age children (3-5 years of age), and school-age children (6-8 years of age) with neurofibromatosis type 1 to define the natural history of delays. School-age children exhibited significantly more areas of delay than infants or preschool-age children. Delays in math, reading, gross motor, fine motor, and self-help development were observed more frequently in older than younger children. Finally, analysis of 43 subjects for whom longitudinal assessments were available revealed that children often migrated between delayed and nondelayed groups in all areas except gross motor development. Based on these findings, we advocate early developmental screening and intervention for this at-risk pediatric population, especially in the area of gross motor function.
Niemann-Pick type C is an autosomal recessive lipid storage disease caused by mutations in the NPC1 or NPC2 gene. In childhood-onset Niemann-Pick type C, the usual course is slowly progressive, with normal cerebral magnetic resonance at onset. Here the authors present the case of a patient carrying 2 compound heterozygous NPC1 mutations: the known nonsense mutation (p.Trp833X) in exon 16 and a novel missense mutation (p.Ile609Phe) in exon 12. At onset, the patient presented ataxia, cognitive decline, and epilepsy, with early cerebral atrophy and marked cerebellar vermis atrophy. The course of the disease was rapid, and the patient died within 1-2 years of onset. A possible phenotype-genotype correlation is discussed. This case further expands the clinical spectrum and the genetic heterogeneity of Niemann-Pick type C due to NPC1 mutations.
Asymmetric face flushing, known as harlequin syndrome, is an autonomic disorder that occurs with other dysfunctions or in isolation. It may be secondary to organic causes or unknown in origin. The latter, which is uncommon in childhood, is considered benign. We report on a boy who first showed this anomaly at 4 years of age, followed up for 6 years. During this time, we saw an increase in the frequency and duration of the episodes of asymmetric face flushing. In the past months, the episodes were associated with a wider involvement of autonomic symptoms, consisting of severe localized headache, lack of coordination, asymmetric sweating, and a loss of strength that lasted about 30 minutes. A review list of young patients affected by this condition is reported.
Hereditary sensory and autonomic neuropathy type IV is an autosomal recessive disorder characterized by severe mental retardation and self-mutilation-related complications. Recently, we investigated a 16-year-old Korean boy with normal intelligence. He had preserved pain sensation but was suspected of having hereditary sensory and autonomic neuropathy type IV because of the recurrent bone fractures and painless joint destruction in the absence of any predisposing medical conditions. Genetic analysis of the NTRK1 gene revealed compound heterozygous mutations including c.851-33T>A and c.2303C>T (p.Pro768Leu) in the NTRK1 gene. The p.Pro768Leu mutation has been identified in 2 Japanese patients with a mild phenotype. Therefore, although it is rare, hereditary sensory and autonomic neuropathy type IV should be considered in patients with recurrent bone fractures and painless joint destruction who do not have any predisposing conditions even when they do not have typical clinical features such as mental retardation or pain insensitivity.
Epilepsy is a very uncommon first manifestation of a neuroblastoma. A 5-month-old healthy infant presented with acute onset seizures and developmental regression. Extensive investigation was remarkable for urinary vanillylmandelic acid and homovanillic acid peaks. Abdominopelvic magnetic resonance imaging (MRI) disclosed a presacral unresectable pelvic neuroblastoma. Chemotherapy and monthly dexamethasone pulses were administrated. Seizures stopped 3 days after the first pulse of dexamethasone. At 3-year follow-up, the patient is asymptomatic and has normal neurologic and developmental examinations. This case illustrates an impressive clinical and electroencephalographic (EEG) improvement on corticosteroid therapy, raising several hypotheses, including the possibility of a nonclassic paraneoplastic neurologic syndrome.
Birth asphyxia is one of the multiple causes of neonatal encephalopathy. The objective of this study was to evaluate neurodevelopmental outcomes of newborn term infants with definitive asphyxia. Thirty infants met study criteria for asphyxia. The 5-year incidence of asphyxia was estimated to be 5.5 in 1000. According to the Age and Stage Questionnaire, 10.5% of 6-month-old infants, 14.3% of 12- and 18-month-old infants, and 5.3% of 24-month-old infants had neurodevelopmental delay in gross motor function in the absence of cerebral palsy. In 7.3% of 18-month-old infants, neurodevelopmental delay in problem-solving ability was observed. Higher values of Apgar score and bicarbonate levels were associated with higher Age and Stage Questionnaire total score. Delivery type, maternal age, gravidity of mother, and existence of mother disease during pregnancy were also associated with lower Age and Stage Questionnaire total score in different stages of life.
Error/correct-related negativities, response-locked components of the evoked response potential, and N100, a stimulus-locked component, were used to compare error detection monitoring in skilled readers and in compensated and noncompensated dyslexic adolescent readers during a lexical decision task. Results showed a general increase in N100 amplitudes prior to error commission in all groups; a significant decrease in error/correct-related negativity amplitudes in the noncompensated dyslexics compared with the other 2 groups; and smaller error-related negativity correlated with a higher number of decoding errors, lower working memory scores, and lower speed of processing in the neuropsychological battery. Based on the hypothesis in previous studies that the error detection mechanism is a subcomponent of executive functions, the possibility that poor executive ability underlies poor reading skills in the noncompensated dyslexic readers is discussed. These findings can be used as a platform for executive-based diagnosis and training for individuals with reading disabilities.
For parents of children with epilepsy, seizures occurring in sleep are a major concern. Risk factors for sudden unexplained death in epilepsy patients include being in bed and generalized tonic-clonic seizures. A device for detecting nocturnal seizure activity would be valuable. Children with various seizure types undergoing evaluation had standard video electroencephalography (EEG), cardiopulmonary and nursing monitoring, and 1 of 2 models (ST-2 and MP5) of a Medpage bed alarm. The video EEG record was reviewed to detect any seizures missed by the bed alarms or caregivers. The ability of the bed alarms to detect motor seizures in general and specific seizure types was tested. In 15 patients, 69 seizures were recorded by video EEG. The ST-2 did not detect any nocturnal seizures. The MP5 alarm detected 1 of 15 in sleeping patients: a generalized tonic-clonic seizure. The Medpage seizure alarms do not appear to adequately detect nocturnal seizures.
Children with the neurofibromatosis type 1 (NF1) inherited tumor predisposition syndrome are at risk for the development of brain tumors. In addition, children with neurofibromatosis type 1 often exhibit low tone (hypotonia). In this study, the authors explored the hypothesis that hypotonia could be a clinical indicator of glioma in children with neurofibromatosis type 1. A total of 56 children between 1 and 7 years of age with a confirmed diagnosis of neurofibromatosis type 1 were evaluated. Brain magnetic resonance imaging (MRI) was available for 19 of these children. Chi-square analysis demonstrated a statistically significant correlation between hypotonia and glioma in children with neurofibromatosis type 1 (90% sensitivity and 78% specificity). These results suggest that hypotonia might be a clinically useful indicator of brain tumor in this at-risk population.
Glucose metabolism of children with drug-resistant epilepsy, controlled by antiepileptic drugs epilepsy, and first-time nonfebrile seizures was studied through the performance of an oral glucose tolerance test and through insulin, C-peptide, and glycosylated hemoglobin measurements. In the refractory epilepsy group, there were more abnormal oral glucose tolerance test results (62.07%) in comparison to the controlled epilepsy group (25%) and the group of first-time seizures (21.21%). There was a significant difference between the group of refractory epilepsy and every other group concerning the abnormality of the oral glucose tolerance test (P < .05). The mean values of insulin, HbA1c, and C-peptide levels were normal for all groups. The results of the present study suggest that there is a distinction of refractory epilepsies from the drug-controlled ones and the first-induced seizures relating to their metabolic profile, regardless of the type of seizures.
The syndrome of transient headache and neurologic deficits associated with cerebrospinal fluid lymphocytosis (HaNDL) is characterized by 1 or more episodes of severe headache, transient neurologic deficits, and lymphocytic pleocytosis in the cerebrospinal fluid. It is a benign and self limited disorder seldom reported in pediatric age. We report the case of a 14-year-old girl who suffered from 2 episodes of headache with transient focal neurologic deficits and pleocytosis consistent with the syndrome of HaNDL. This entity should be taken into account as a differential diagnosis in otherwise healthy children presenting with recurrent headache and acute neurologic deficits. Repeated use of invasive and expensive laboratory and imaging investigations can be avoided when the diagnosis of the syndrome of HaNDL is correctly established.
Studies suggest that dystonia is associated with increased motor cortex excitability. Cathodal transcranial direct current stimulation can temporarily reduce motor cortex excitability. To test whether stimulation of the motor cortex can reduce dystonic symptoms in children, we measured tracking performance and muscle overflow using an electromyogram tracking task before and after stimulation. Of 10 participants, 3 showed a significant reduction in overflow, and a fourth showed a significant reduction in tracking error. Overflow decreased more when the hand contralateral to the cathode performed the task than when the hand ipsilateral to the cathode performed the task. Averaged over all participants, the results did not reach statistical significance. These results suggest that cathodal stimulation may allow a subset of children to control muscles or reduce involuntary overflow activity. Further testing is needed to confirm these results in a blinded trial and identify the subset of children who are likely to respond.
Anthropometric development and growth were assessed in 2 groups of 6- to 9-year-olds: children with autism spectrum disorders and typically developing children. In a case-control study conducted in Valencia, Spain, we compared the body mass index (kg/m2) of 40 children with autism spectrum disorders (cases) and 113 typically developing children (controls) from the same area of residence. The sex- and age-adjusted odds ratios for being underweight in cases was 2.41 compared to controls. Furthermore, the body mass index distribution of the cases was significantly offset to lower values with respect to that of the controls (P = .024). In particular, 20% of the cases had a body mass index below the fifth percentile versus just 8.85% of the controls. Our data suggest that the anthropometric development of children with autism spectrum disorders should be monitored as part of routine care.
Previous work has shown that medication errors related to anticonvulsants are common during the transition into the hospital for pediatric patients. The purpose of this work was to evaluate whether children with epilepsy admitted for reasons other than epilepsy experience nonoptimal care in anticonvulsant medication management preceding the occurrence of seizures. Using a retrospective cohort of children with epilepsy admitted for reasons other than epilepsy, we created timelines from data in the medical record for the children who experienced seizures. These timelines included the timing and concentration of anticonvulsant administration and seizure occurrence. Three child neurologists independently identified whether nonoptimal care preceded the occurrence of seizures and potentially contributed to the occurrence of the seizure. Of 120 children, 18 experienced seizures and 12 experienced nonoptimal care in anticonvulsant management preceding seizure occurrence. Nonoptimal care that occurred during the transition into the hospital included missed doses of anticonvulsants, delays in administration during which seizures occurred, and patients inadvertently not receiving their home dosing of medication. Anticonvulsant medication errors are known to occur during the transition into the hospital. Here we present a case series of children who experienced nonoptimal care in anticonvulsant medication management who subsequently experienced seizures. Further work to identify how likely the outcome of seizures is following anticonvulsant medication errors, specifically focusing on timing as well as interventions to change the system issues that lead to these errors, is indicated.
Spinal muscular atrophy is an autosomal recessive neurodegenerative disease caused by homozygous mutation to the survival motor neuron 1 (SMN1) gene. Historically, spinal muscular atrophy has been considered to almost exclusively affect the function and survival of alpha motor neurons of the spinal cord and brainstem. With the development of animal models of spinal muscular atrophy, the presence of widespread systemic abnormalities affecting the brain, heart, and pancreas has been repeatedly noted among animals with diminished survival motor neuron protein expression. While these observations suggest similar possible effects in humans, reports of primary systemic disease manifestations among humans affected by spinal muscular atrophy are strikingly lacking. Here we report a case of a 29-year-old man with genetically confirmed spinal muscular atrophy type II who presented with new onset diabetes mellitus and diabetic ketoacidosis.
The authors report a case of hyperekplexia presenting in the neonatal period resistant to clonazepam that responded subsequently to levetiracetam. Hyperekplexia is often misdiagnosed as epilepsy and can be difficult to manage with a particular concern over neonatal apnea and an increased risk of sudden infant death syndrome. The mainstay of therapy to date has been with clonazepam. The authors describe the salient features of their case, clinical diagnosis, and issues pertaining to management. The authors believe this is the first reported case of the use of levetiracetam for effectively treating hyperekplexia within the neonatal and infant period.
This study sought to characterize the optic disc morphology, particularly the cup-to-disc ratio of the optic nerve head in children with idiopathic intracranial hypertension. The medical charts and digital optic disc photos of children with confirmed diagnosis of idiopathic intracranial hypertension were reviewed retrospectively. The optic disc area, cup area, and cup-to-disc ratio were measured digitally using VISUPAC software, and the mean values of those parameters were compared to the published norms. Of children with idiopathic intracranial hypertension, 83% had absence of the physiological cup of the optic disc, compared to 10% of children in the general population of the same age. The median disc area was 2.2 mm2, and median cup area was 0.0mm2, compared to the published norms of 2.69 mm2 and 0.44 mm2, respectively. There is very significantly high prevalence of small optic disc cups in children with idiopathic intracranial hypertension, with the cup being absent on majority of cases in our patient cohort. This may signal an underlying systemic predisposition to the development of intracranial hypertension.
Acute ataxia is not an uncommon childhood complaint. It most commonly occurs in young patients secondary to a postinfectious cerebellitis, which is typically associated with a very good prognosis and recovery. In adolescence, acute cerebellar ataxia is more often the product of an etiology likely to progress into a chronic disorder without recovery to preillness baseline. In the present case, the authors describe a 15-year-old girl with subacute cerebellar ataxia of presumed immune-mediated etiology that advanced into a chronic cerebellar ataxia. Due to a family history, celiac disease was suspected as the origin of the ataxia; biopsy ruled out enteropathy, and the severe, abrupt radiological changes to the patient’s cerebellum are inconsistent with the reported sequelae of gluten ataxia. This case serves as a discussion for diagnostic challenges in adolescent patients with acute cerebellar ataxia with long-term sequelae as well as providing an adjunct discussion on the neurological complications of celiac disease.
The most typical symptom of Chiari malformation type I in children is headache. The authors describe a 14-year-old girl who presented with a 3-year history of gait decline and no headache, which is very unusual. After surgery to correct the Chiari I malformation, the patient’s gait improved; however, she went on to develop decreased hand use with joint deformities. She was diagnosed with a probable connective tissue disorder. Patients with connective tissue disorders are at increased risk for developing Chiari I malformation. The authors discuss the possible reasons for the unusual presentation of the Chiari I malformation and possible mechanisms. The unusual presentation of Chiari I delayed this young patient’s diagnosis and treatment.
The mitochondrial DNA m.13513G>A mutation in the ND5 subunit gene is a frequent cause of Leigh syndrome. Patients harboring this mutation typically present with ptosis and cardiac conduction abnormalities, particularly Wolff-Parkinson-White syndrome, and have a late clinical onset, which contrasts with the typical infantile form. The authors describe a patient presenting with intrauterine growth retardation and visual impairment at 3 months of age, followed by infantile spasms, severe gastrointestinal dysmotility, and neurological regression. The patient had hyperlactacidemia and bilateral basal ganglia and brainstem lesions on MRI. Although he did not present cardiac conduction abnormalities, his mother had been diagnosed with Wolff-Parkinson-White syndrome. The m.13513G>A mutation was found in the patient’s muscle and in several tissues of his mother. The present results expand the phenotype of Leigh syndrome associated with the m.13513G>A mutation, which should be suspected in patients with early-onset mitochondrial encephalopathy with infantile spasms or prominent gastrointestinal smooth muscle involvement.
Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase, which results in accumulation of fatty aldehydes and alcohols and is characterized by ichthyosis, intellectual disability, and spastic diplegia/quadriplegia. The authors describe 2 unrelated Honduran patients who carried the same novel homozygous nonsense mutation (c.1309A>T, p.K437X) and ALDH3A2 DNA haplotype, but widely differed in disease severity. One patient exhibited spastic quadriplegia with unusual neuroregression, whereas the other patient had the usual static form of spastic diplegia with neurodevelopmental disabilities. Biochemical analyses showed a similar profound deficiency of fatty aldehyde dehydrogenase activity and impaired fatty alcohol metabolism in both patients’ cultured fibroblasts. These results indicate that variation in the neurologic phenotype of Sjögren-Larsson syndrome is not strictly determined by the ALDH3A2 mutation or the biochemical defect as expressed in cultured fibroblasts, but by unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms.
Basilar artery occlusion in children is rare. It has a high mortality and morbidity if recanalization is not achieved before extensive brainstem infarction has occurred. An 11-year-old boy presented with a clinical and radiological "top-of-the-basilar" syndrome. Intravenous tissue plasminogen activator was administered, and the patient was immediately referred to the regional stroke center. Subsequent mechanical thrombectomy using a Solitaire stent (Solitaire FR stent; ev3, Irvine, CA, USA) resulted in clot removal and recanalization of the basilar artery 4 hours after stroke onset. The patient made a full clinical recovery. To the authors’ knowledge this is the first report on basilar artery occlusion in a child treated with "bridging" therapy, the combination of intravenous thrombolysis and endovascular thrombectomy. If the diagnosis can be made within the time window for intravenous thrombolysis (4.5 hours), the present case suggests that bridging therapy in pediatric basilar artery occlusion can be safe and effective.
The ketogenic diet is an effective therapy for childhood epilepsy, but its important impacts on families could affect successful treatment. We assessed medical and psychosocial factors associated with successful ketogenic diet treatment. A total of 23 families of patients treated with ketogenic diet completed questionnaires (30% response), including inquiries about challenges to successful dietary treatments and validated family functioning scales. Of these, 14 were considered successful (diet discontinued once the child was seizure-free or continued as clinically indicated). Family-identified challenges were food preparation time (n = 11) and that the diet was too restrictive (n = 9). Neither Medicaid insurance nor family functioning scale scores were significantly associated with successful treatment. Lower seizure frequency prior to ketogenic diet initiation (P = .02) and postdiet seizure improvement (P = .01) were associated with increased odds of success. Effective ketogenic diet treatment is dictated both by psychosocial and epilepsy-related influences. A focus on understanding the psychosocial issues may help to improve families’ experiences and success with the ketogenic diet.
Cavernous haemangiomas, or cavernous malformations, have been reported during pregnancy, most of which have been either supratentorial or spinal lesions. We encountered a 15-year old pregnant patient with a rapidly progressive and haemorrhagic brainstem cavernous haemangioma. The case presented here describes the history and findings of this patient, as well as the less-commonly utilized technique we used to access the floor of the fourth ventricle via occipital craniotomy for complete macroscopic resection of this lesion, resulting in the gradual return of most of her neurological deficits.
Vanishing white matter disease is one of the most prevalent leukodystrophies in childhood. It is caused by mutations in any of the genes encoding the 5 subunits of the eukaryotic translation initiation factor 2B (eIF2B), EIF2B1 through EIF2B5. Phenotypic variation is wide and it may affect people of all ages. Here we present a child with vanishing white matter who had hepatomegaly and hypertriglyceridemia attacks along with neurologic deterioration episodes. He was found heterozygous for the 2 mutations c.817 A>C, p.Lys273Gln and c.939_948del, p.Asp314ProfsX23 in the gene EIF2B2. Until today, this association was not defined in the literature.
Anti–N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently recognized autoimmune neurologic disorder that presents with severe neuropsychiatric symptoms in previously healthy children. A 4-year-old Lebanese girl presented with new-onset behavioral changes, orofacial dyskinesias, fluctuation in consciousness, inability to walk, and mutism. Antibodies directed against NMDA receptors were detected in the patient’s serum and cerebrospinal fluid. Prompt treatment with a single course of intravenous immunoglobulin resulted in early complete recovery. This is the first case report of a Middle Eastern child affected with this condition.
Basal ganglia injury, accompanied by extrapyramidal signs, has been described in the setting of chronic tuberculous meningitis; however, such injury rarely occurs in acute bacterial meningitis and has never been reported with meningococcal meningitis. We report the case of a boy who developed tongue bradykinesia and dysarthria 1 week following presentation with meningococcal meningitis. Magnetic resonance imaging revealed bilateral basal ganglia lesions, suspected to result from cytotoxic edema secondary to infection. The patient subsequently developed general bradykinesia, choreoathetosis, and ataxia, which had improved but not completely subsided by the time of discharge, 8 weeks following initial presentation. The purpose of this report is to present basal ganglia injury with extrapyramidal signs as a possible complication of meningococcal meningitis. Furthermore, we emphasize the importance of suspecting parkinsonian signs as early indicators of basal ganglia involvement in the setting of meningitis, which may later develop into a full-blown movement disorder.
Gaucher’s disease is a rare lysosymal storage disorder characterized by deposition of glucocerebroside in cells of the macrophage monocyte system. Gaucher’s disease has 3 types—non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). It generally presents with delayed milestones, seizures, bony deformities, or massive organomegaly. The cute neuronoapthic variety is the rarer type that predominantly presents with neurological features. The authors present a case of the acute neuronopathic variety of Gaucher’s disease where the child presented with only abnormal head position.
Following unilateral cerebral injury, several patterns of cerebellar metabolism have been noted on positron emission tomography (PET); these changes have been attributed both to the distant diaschisis as well as to reorganizational changes within the cerebellum. We used diffusion tensor magnetic resonance imaging (MRI) to study 14 children who had undergone cerebral hemispherectomy because of intractable epilepsy and compared them with those from 17 controls. In 10 children who had preoperative and postoperative scans, a paired comparison was performed. Our findings showed significantly higher fractional anisotropy values in corticopontocerebellar pathways postoperatively compared to preoperatively. When compared to controls, we found a higher rate of age-related fractional anisotropy changes of corticopontocerebellar pathways in the postoperative scans. Our results indicate reorganizational changes in the contralateral (intact) corticopontocerebellar pathway and the cerebellar white matter. These changes likely contribute to the far better motor outcomes seen in children compared to adults sustaining such cortical injuries.
Phenytoin is a commonly prescribed anticonvulsant drug; however, there is evidence that long-term administration is related to cerebellar ataxia, cerebellar atrophy, loss of Purkinje cells, and hyperplasia of Bergman glia cells. The aim of the present study was to detect and describe any possible alterations of the Purkinje cells, and neurons of the dentate nucleus, as those can be seen with the use of silver impregnation techniques, such as Golgi and Nauta method. The study was performed on a 7-year-old boy who was under phenytoin treatment for more than 3.5 years and had clinical manifestations of cerebellar ataxia. Golgi silver impregnation technique revealed substantial loss of dendritic spines and tertiary dendritic branches, both on the Purkinje cells and the neurons of the dentate nucleus, whereas the Nauta method demonstrated swollen and degenerated axons of Purkinje cells.
We report 10 years’ follow-up of the previously described family with a novel mutation of the KCNA1 gene. The family consisted of 3 affected boys (first seen at ages 3, 11, and 12) and their affected mother and asymptomatic father and sister. They clinically presented with diffuse myokymia, muscle cramps, and lower limb spasticity without ataxia, but episodic ataxia developed later during adolescence and early adulthood. Long-term follow-ups of families with known KCNA1 gene mutation are rarely mentioned in the literature. Treatment with carbamazepine, 600 to 800 mg daily resulted in cessation of muscle cramps and marked improvement of lower leg symptoms. In the youngest child, after 2 years carbamazepine had to be changed to oxcarbazepine because of side effects. Carbamazepine and oxcarbazepine are both effective in treatment of symptoms related to KCNA1 gene mutation. Symptoms will reoccur if treatment is stopped and there is variability of symptom severity between family members.
Phenylketonuria is a treatable inborn error of amino acid metabolism caused by deficiency of the enzyme phenylalanine hydroxylase, responsible for converting phenylalanine to tyrosine. We report a 10-month-old boy with psychomotor regression and infantile spasms. He was diagnosed with classic phenylketonuria and West syndrome. Treatment was initiated with phenylalanine-restricted diet and vigabatrin. After 5 months of treatment, he persists with developmental delay, severe hypotonia, swallowing disorder, and drug-resistant epilepsy. Brain magnetic resonance imaging showed the typical abnormalities in supratentorial white matter and exceptional infratentorial and basal ganglia compromise. Severity of white matter abnormalities and neurologic symptoms correlates with blood levels of phenylalanine. Infratentorial changes occur in severe cases. Other mechanisms could take part in cases like this with atypical neuroimaging abnormalities of the basal ganglia.
Hereditary spastic paraplegias and related genetically heterogeneous disorders may be difficult to distinguish clinically. The FA2H gene has been associated with autosomal recessive neurodegenerative phenotypes encompassing spastic paraplegia with or without dystonia, and demyelinating leukodystrophy. To date, few individuals with mutations in the FA2H gene have been described. We report a 5-year-old girl of mixed Filipino and Vietnamese origin who presented with progressive lower limb spasticity and periventricular leukomalacia. The clinical diagnosis of FA2H-associated neurodegeneration was confirmed on the basis of 2 novel mutations in compound heterozygosity in the FA2H gene (p.S70L/p.P323L). This family highlights that FA2H-associated disorders may be underrecognized in children with neurodegeneration of many different ethnicities. Magnetic resonance imaging features play an important role as diagnostic clues in this and other hereditary spastic paraplegias. The consideration of this diagnosis is essential in providing families with important information on prognosis, as well as accurate genetic counseling.
Nemaline rods are the pathologic hallmark of nemaline myopathy, but they have also been described as a secondary phenomenon in a variety of other disorders. Nemaline rods have not been reported in pyruvate carboxylase deficiency before. Here we present a patient with pyruvate carboxylase deficiency and nemaline rods detected on muscle biopsy. The nemaline rods may be due to cellular energy shortage and altered energy metabolism in pyruvate carboxylase deficiency, similar to that in the previously reported patients. The mechanism of nemaline rod formation may be associated with the role of pyruvate carboxylase in cellular energy pathways.
Tourette syndrome is a neurodevelopmental disorder characterized by tics and comorbid behavioral problems. This study compared child- and parent-reported quality of life and everyday functioning. We assessed 75 children with Tourette syndrome, of which 42 (56%) had comorbid conditions (obsessive-compulsive disorder = 25; attention-deficit hyperactivity disorder = 6; both comorbidities = 4). All patients completed psychometric instruments, including the Gilles de la Tourette Syndrome–Quality of Life Scale for Children and Adolescents (child report) and the Child Tourette’s Syndrome Impairment Scale (parent report). Data were compared for patients with pure Tourette syndrome, Tourette syndrome + obsessive-compulsive disorder, Tourette syndrome + attention-deficit hyperactivity disorder, and Tourette syndrome + both comorbidities. There were no group differences in quality of life. However, there were differences for total, school, and home activities impairment scores. Children and parents may not share similar views about the impact of Tourette syndrome on functioning. The measurement of health-related quality of life in Tourette syndrome is more complex in children than adults.
We report a child presenting with intermittent ophthalmoplegia and fluctuating ptosis and facial weakness whose evaluation revealed no evidence of myasthenia gravis but did reveal hyperthyroidism secondary to Graves disease. Successful treatment of the child’s endocrinopathy resulted in complete resolution of his presenting symptoms. Children presenting with ophthalmoplegia and ptosis without proptosis should be evaluated for hyperthyroidism if no evidence of a myopathy or disorder of neuromuscular junction transmission is found.
Congenital muscular torticollis is a common condition, but long-term neurodevelopmental follow-up is lacking. This study reports on neurodevelopmental outcome of 68 children, aged 7 to 9 years, with a history of congenital muscular torticollis, excluding children with torticollis due to other conditions. Thirty-eight children were examined for presence of neurodevelopmental disorders. Telephone interview data were available for an additional 30 children. Of those examined, 22/38 (57.9%) had or were at risk for a developmental disorder (attention-deficit hyperactivity disorder (ADHD), developmental coordination disorder, language impairment, autistic spectrum disorder) on at least 1 of the assessments administered, 23/38 (60.5%) had received developmental treatment during childhood. One child, based on a telephone interview, had a history of developmental treatment. Therefore, 30/68 (44.1%) children of the total sample demonstrated a developmental delay/disorder, currently (22/68) or previously (8/68). Our findings suggest congenital muscular torticollis to be a significant risk factor for later neurodevelopmental conditions with disorders presenting at different stages of development.
Rett syndrome is a severe neurodevelopmental disorder, with hand stereotypies as a hallmark of the disease. Epilepsy is a frequent comorbidity and is accompanied by centrotemporal spikes on electroencephalogram, but stereotypic movements should not have epileptiform correlates. During routine video-electroencephalographic investigation in 5 Rett syndrome patients, we identified a peculiar type of unilateral, highly rhythmic hand tapping accompanied by contralateral synchronous centrotemporal spikes on electroencephalography. This phenomenon is not consistent with either reflex seizures or hand stereotypies and does not respond to antiepileptic drugs. The electroencephalographic activity probably represents evoked potentials, either somatosensory or motor, whereas the rhythmic activity raises the possibility of a subcortical pacemaker for a stereotypy variant. The phenomenon could be caused by abnormal circuitry among the hyperexcitable somatosensory cortex, motor cortex, and subcortical areas in Rett syndrome. Clinicians should be aware of the nonepileptic nature of this motor behavior and should not attempt to treat it.
Dominant spinocerebellar ataxias are a rare clinically and genetically heterogeneous group of neurodegenerative disorders. They are characterized by progressive cerebellar ataxia resulting in unsteady gait, clumsiness, dysarthria, and swallowing difficulty. The onset of symptoms is usually in the third or fourth decade of life; however, more subtle clinical manifestations can start in early childhood. Spinocerebellar ataxia type 5, a dominant spinocerebellar ataxia associated with mutations involving β-III spectrin (SPTBN2), has been described in 3 families. It typically consists of a slowly progressive spinocerebellar ataxia with onset in the third decade. The authors present the first case of infantile-onset spinocerebellar ataxia associated with a novel SPTBN2 mutation (transition C>T at nucleotide position 1438), the proband having a much more severe phenotype with global developmental delay, hypotonia, tremor, nystagmus, and facial myokymia.
The authors tested the hypothesis that de novo copy number variations (CNVs) implicated in known genomic disorders ("pathogenic CNVs") are significant predisposing factors of infantile spasms. The authors performed a genome-wide analysis of single-nucleotide polymorphism genotyping microarray data to identify the role of de novo/known pathogenic large CNVs in 13 trios of children affected by infantile spasms. A rare, large (4.8 Mb) de novo duplication was detected in the 15q11-13 region of 1 patient. In addition, 3 known pathogenic CNVs (present in the patient as well as 1 of the parents) were detected in total. In 1 patient, a known pathogenic deletion was detected in the region of 2q32.3. Similarly, in 1 other patient, 2 known pathogenic deletions in the regions of 16p11.2 and Xp22.13 (containing CDKL5) were detected. These findings suggest that some specific pathogenic CNVs predispose to infantile spasms and may be associated with different phenotypes.
Visual electrophysiological techniques represent excellent means for assessing retinal, optic pathways and visual cortex function. Electroretinograms, visual evoked potentials, and clinical records of 17 patients with mucopolysaccharidosis registered in the neurophysiological database of our institution were reviewed retrospectively. Ten patients were on enzyme replacement therapy, 2 underwent bone marrow transplantation, one also keratoplasty. Changes in the electroretinogram pointed to the diagnosis of retinal dystrophy type rod-cone in 8 patients. In patients in whom severe corneal clouding precluded fundus oculi inspection and at an early stage before typical fundus appearance diagnosis was possible only using the electroretinogram. Visual evoked potentials were useful to confirm the loss of visual function in patients difficult to test clinically. The authors suggest the use of electroretinogram and visual evoked potentials primarily as research tools to describe the natural history and ophthalmologic outcome in mucopolysaccharidoses, although they may have clinical utility in very selected cases.
Children with sickle cell disease have a very high risk of lifelong neurologic morbidity and mortality. Cerebrovascular accidents are a known complication in children with sickle cell disease. Posterior reversible encephalopathy syndrome is a constellation of acute neurologic findings increasingly recognized in pediatric critical care population with evidence of vasogenic edema on brain imaging possibly due to cerebral vascular endothelial cell dysfunction. This report, for the first time, describes a young adult with sickle cell disease who developed posterior reversible encephalopathy syndrome following blood transfusion.
Neurogenic pulmonary edema is a clinical syndrome that manifests as an acute onset of pulmonary edema in the setting of a central nervous system injury, without cardiac dysfunction. Neurogenic pulmonary edema is rare in children, and the mechanism is still not completely understood. The clinical pathology overlaps with acute lung injury and acute respiratory distress syndrome. The authors report a case of a 14-month-old previously healthy child who presented with febrile status epilepticus, fulminant neurogenic pulmonary edema, and acute respiratory distress syndrome. Neurogenic pulmonary edema should be considered in the differential diagnosis for the rapid progression of respiratory failure following an acute neurological injury such as status epilepticus in a child. Prompt respiratory support and treatment of the acute neurological insult can prevent further cerebral hypoxemic injury.