Journal of Child Neurology

Generalized whole brain volume loss is well documented in moderate to severe traumatic brain injury. Whether this atrophy occurs in the thalamus and brainstem has not been systematically studied in children. Magnetic resonance imaging (MRI) quantitative analysis was used to investigate brain volume loss in the thalamus and brainstem in 16 traumatic brain injury subjects (age range 9-16 years) compared with 16 age and demo-graphically matched controls. Based on multiple analysis of covariance, controlling for age and head size, reduced volume in the thalamus and the midbrain region of the brainstem were found. General linear model analyses revealed a relation between processing speed on a working memory task and midbrain and brain stem volumes. Reduced volume in thalamic and brainstem structures were associated with traumatic brain injury. Reduction in midbrain and thalamic volume is probably a reflection of the secondary effects of diffuse axonal injury and reduction in cortical volume from brain injury.

Four cases of pediatric sciatic neuropathies due to unusual vascular mechanisms are reported. Pediatric sciatic neuropathies were seen after umbilical artery catheterization, embolization of arteriovenous malformation, meningococcemia, and hypereosinophilic vasculitis. Electrophysiologic studies demonstrated abnormalities in motor studies of peroneal and tibial nerves. Sensory studies demonstrated abnormalities of sural and superficial peroneal nerves. Results of needle electromyography were abnormal in sciatic-innervated muscles. Prognosis was variable and depended on the severity of the initial nerve injury.

This study evaluates the neurologic profiles of infants with deformational plagiocephaly. Forty-nine infants with deformational plagiocephaly between the ages of 4 and 13 months (mean age, 8.1 months) are evaluated, along with 50 age-matched control subjects (mean age, 8.1 months). A modified version of the Hammersmith infant neurologic assessment was performed on each infant. A caregiver completed a questionnaire regarding the infant's prematurity, development, and health to date. Results are analyzed using t test. There is a statistically significant difference in overall neurologic assessment scores of infants with deformational plagiocephaly vs their healthy peers (P = .002). This difference is predominately in tone, whereby infants with deformational plagiocephaly have significantly more abnormal tone than nonplagiocephalic infants (P = .003). This abnormality is not one of decreased tone but one of variable tone, deflecting abnormally high and low tone. Infants with deformational plagiocephaly are more likely to have altered tone but not exclusively decreased tone.

This study tested the hypothesis that gamma-glutamyl transferase (GGT) can be used as a reliable biomarker to distinguish skeletal muscle from liver damage. Twenty-eight Duchenne muscular dystrophy subjects with proven dystrophin gene mutations were enrolled. Included were 14 ambulatory and 14 nonambulatory patients with approximately half of each cohort taking corticosteroids. Twenty normal males served as controls. Initial blood samples for serum GGT and creatine kinase were taken between 8AM and 9AM and redrawn 8 hours later to test for variability. Between blood draws, subjects resumed normal activities in a play environment or could leave the clinic. Not a single duchenne muscular dystrophy patient showed a GGT outside the control range at any time point, while creatine kinase levels were 14 to 200 times normal. Validation of this finding is essential for management of patients with muscle disorders exposed to potentially hepatotoxic drugs for clinical management or monitoring subjects participating in clinical trials.

Few cases of simultaneous acute demyelination of the peripheral and central nervous systems are reported. Four patients diagnosed as having Guillain-Barré syndrome and acute disseminated encephalomyelitis during the same hospitalization are described herein. Two patients manifest an atypical form of Guillain-Barré syndrome, with magnetic resonance imaging of the head showing acute disseminated encephalomyelitis. A third patient has acute disseminated encephalomyelitis and develops Guillain-Barré syndrome during his hospitalization. A fourth patient demonstrates transverse myelitis that evolves into Guillain-Barré syndrome, with demyelination seen on brain magnetic resonance imaging. All patients are treated with intravenous immunoglobulins or corticosteroids. Three patients have a favorable outcome; 1 patient has a chronic inflammatory demyelinating polyradiculoneuropathy. Guillain-Barré syndrome and acute disseminated encephalomyelitis can occur simultaneously in the pediatric population. This may be explained by a shared epitope between peripheral and central nervous system myelin. Further research is necessary to better describe this entity and its prognosis.

A prospective study was performed of all children started on the ketogenic diet at our institution for intractable epilepsy from January 2003 to March 2007 (n = 137), examining for baseline and follow-up total cholesterol and triglyceride levels. Interventions for dyslipidemia were analyzed for their effectiveness. At baseline, 25% of children had hypercholesterolemia (>200 mg/dL), which increased to 60% for those receiving the ketogenic diet. Children receiving a solely formula-based ketogenic diet were less likely to have hypercholesterolemia than those eating solid food after adjusting for age and initial ketogenic ratio (P < .001). Only a slightly higher likelihood of a 20% decrease in cholesterol occurred for those children in whom a dietary intervention was made compared with observation alone (60% vs 41%; P = .11). Hypercholesterolemia occurs in most children receiving a solid food based ketogenic diet but improved in approximately half, even without interventions.

The feasibility and clinical utility of early electroencephalogram (within 48 hours) was studied in 127 children (age, 1 month-17 years) referred for a “first seizure.” The electroencephalogram was considered late after 48 hours. Electroencephalogram abnormalities were classified as nonepileptiform or epileptiform. Children were classified as having an “epileptic” or “nonepileptic” event. An early electroencephalogram was obtained in 23 (18%). Late referral (n = 36), weekend event (n = 23), difficulty contacting families (n = 11), parental schedules (n = 9), and laboratory scheduling (n = 11) resulted in late electroencephalograms. All 94 children with an epileptic event had an electroencephalogram, 19 (20%) within 48 hours. Results were abnormal in 9 (47%) early (7 epileptiform, 2 nonepileptiform) and 35 (44%) late (30 epileptiform, 5 nonepileptiform). Increased abnormalities were not seen with early electroencephalography (P = .50). Early electroencephalograms may not be feasible in the pediatric population and did not show a higher yield of abnormalities.

This study assessed metabolic functioning of regional brain areas to address whether there is a neurometabolic profile reflecting the underlying neuropathology in individuals with autism spectrum disorders, and if varied profiles correlate with the clinical subtypes. Thirteen children (7-16 years) with autism spectrum disorders and 8 typically developing children were compared on ¹H-magnetic resonance spectroscopy data collected from hippocampus-amygdala and cerebellar regions. The autism spectrum disorder group had significantly lower N-acetyl-aspartate/creatine ratios bilaterally in the hippocampus-amygdala but not cerebellum, whereas myo-inositol/creatine was significantly increased in all measured regions. Choline/creatine was also significantly elevated in the left hippocampus-amygdala and cerebellar regions of children with autism spectrum disorder. Comparisons within the autism spectrum disorder group when clinically subdivided by history of speech delay revealed significant metabolic ratio differences. Magnetic resonance spectroscopy can provide important information regarding abnormal brain metabolism and clinical classification in autism spectrum disorders.

Objective: To examine the evidence for and against the classification of attention-deficit hyperactivity disorder (ADHD) as a valid disease entity, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV ), criteria. Data Sources: Sources included but were not limited to published literature on ADHD accessed via PubMed (http://www.ncbi.nlm.nih.gov/PubMed/). Study Selection: Peer-reviewed research, review articles, consensus statements, “white papers,” and proceedings of professional meetings were used. Data Extraction: Focused on evidence base and scientific validity of conclusions. Data Synthesis: Evidence for a genetic or neuroanatomic cause of ADHD is insufficient. Experimental work shows that executive function deficits do not explain ADHD. The psychometric properties of widely used ADHD rating scales do not meet standards expected for disease identification. Conclusions: ADHD is unlikely to exist as an identifiable disease. Inattention, hyperactivity, and impulsivity are symptoms of many underlying treatable medical, emotional, and psychosocial conditions affecting children.

Benign childhood epilepsy with centrotemporal spikes is the most common epileptic syndrome in childhood. Atypical forms of benign childhood epilepsy with centrotemporal spikes are common. The different atypical forms of the condition are believed to represent a continuum of the same underlying genetic mechanism. The atypical forms of benign childhood epilepsy with centrotemporal spikes include electrical status epilepticus in slow waves sleep, Landau-Kleffner syndrome, status epilepticus of benign childhood epilepsy with centrotemporal spikes, “classic” atypical form, and others. This review delineates the different forms with emphasis on the cognitive hazards of the more malignant types.

Functional magnetic resonance imaging (fMRI) represents a useful tool for studying brain functions and the neural basis of cognition in healthy children and in those in disease states. Functional magnetic resonance imaging is a relatively new use of existing magnetic resonance imaging technology that allows scientists and practitioners to observe the brain at work. It is based on the observation that local increases in blood flow are related to neural activity. This review considers principles of functional magnetic resonance imaging, issues relevant to imaging children, and research using functional magnetic resonance imaging to examine cognitive processing in pediatric populations. The focus is specifically on language studies to review strengths, limitations, and practical applications of this technology with children. Future directions for functional magnetic resonance imaging are presented.

Terminal deletion of the long arm of chromosome 2 is a rare chromosomal disorder characterized by low birth weight, delayed somatic and mental development, craniofacial defects, short neck, heart and lung congenital defects, and autistic features. We report on a girl with 46,XX.ish del(2)(q37.1) de novo karyotype, mental retardation, dysmorphic features, gastrointestinal anomalies, and autistic traits and compare her clinical manifestations with patients with the same deletion previously described in literature.

The authors describe the case of an 8-year-old boy, otherwise healthy, who presented with symptoms consistent with attention-deficit hyperactivity disorder (ADHD) and was started on a trial of methylphenidate. Within 4 weeks, he experienced a rapid decline in fine motor skills, with dysarthria, intention tremor, motor impersistence, and diffusely increased tone. Symptoms persisted despite cessation of methylphenidate. At that time, a paternal history of Huntington disease was disclosed. Molecular analysis revealed an expansion in CAG repeats to 75 copies, within the range characteristic of juvenile Huntington disease. This report raises the possibility that use of dopaminergic agonists in patients with a family history of Huntington disease may lead to clinical exacerbation of motor symptoms and/or unwitting diagnosis in an unprepared family.

Catheter dysfunction is a common complication with ventriculoperitoneal shunts. Apart from infection, obstruction, and leakage, migration of the shunt tip may cause particular problems. Pleural effusion is easily classified as a shunt complication if a transdiaphragmatic migration of a shunt can be demonstrated. If, however, the tip of the shunt is found adjacent to the diaphragm, it is difficult to decide if the effusion is caused by the ventriculoperitoneal shunt. Different diagnostic methods can be used in this situation. Below we report a case of pleural effusion—without shunt migration—which was revealed to be a shunt complication by quantifying beta-trace protein in the effusion.

Nemaline myopathy is a clinically heterogeneous congenital myopathy caused by mutations in at least 6 genes related to thin filaments. Histologically, they show a characteristic if not homogeneous picture of nemaline rods, essential for the diagnosis. However, little is known regarding the development and progression of muscle histopathologic changes in nemaline myopathy. Results of muscle biopsies at 7 weeks of age and at 15 months of age from a child with nemaline myopathy due to a novel mutation in the ACTA1 gene are presented. The findings of the biopsies, separated by 13 months, demonstrate progression from vague cytoplasmic bodies in the first biopsy to typical nemaline rods in the second biopsy.

Selective dorsal rhizotomy at the lumbar level is a neurosurgical procedure, which reduces spasticity in the legs. Its effect has mainly been studied in children with spastic cerebral palsy. Little is known about the outcome of selective dorsal rhizotomy in patients with neurodegenerative disorders. We report the clinical course after selective dorsal rhizotomy in 2 patients with progressive spasticity. Leg spasticity was effectively and persistently reduced in both patients, facilitating care and improving sitting comfort. However, spasticity of the arms and other motor disturbances, such as spontaneous extension spasms and the ataxia, increased gradually in time. Selective dorsal rhizotomy leads to a disappearance of leg spasticity in patients with a neurodegenerative disease. Other motor signs are not influenced and may increase due to the progressive nature of the underlying disease.

Severe methylenetetrahydrofolate reductase deficiency is an autosomal recessive metabolic disorder of folate metabolism causing elevated plasma homocysteine levels and homocystinuria (MIM 236250). A developmentally delayed 10-year-old girl presented with symptoms of progressive ataxia, dysarthria, tremor, mental status changes, and white-matter changes on magnetic resonance imaging. These changes occurred during a 3- to 4-month time period, with an acceleration of symptoms during 2 to 3 weeks. The patient was found to have extremely high serum homocysteine and low—normal serum methionine. She received treatment with vitamin B12, folate, betaine, multivitamins, and aspirin, with subsequent improvement of her symptoms and reduction in her serum homocysteine level. This case emphasizes the need to include homocystinuria in the differential diagnosis of children with acute/subacute neurological changes, particularly in the context of developmental delay.

Increasing numbers of genetic origins are being reported for congenital muscle fiber-type disproportion. Most of these identified disorders are genetic myopathies. This is the first case report (to our knowledge) demonstrating congenital central hypoventilation syndrome due to PHOX2B mutations with congenital muscle fiber-type disproportion. The muscle histopathologic findings in the patient showed no changes of disuse atrophy and suggest that PHOX2B mutations may have an additional role in muscle development, contributing to respiratory failure in congenital central hypoventilation syndrome.

Glucose transporter type 1 (GLUT1) deficiency syndrome is a metabolic disorder characterized by a low cerebrospinal fluid glucose level caused by decreased activity of the glucose transporter protein. Of approximately 100 patients described with this syndrome in the published literature to date, only 3 patients have had intermittent ataxia as the initial manifestation. This case report describes a 13-year-old boy with a longstanding history of intermittent ataxia who was diagnosed as having GLUT1 deficiency syndrome after the onset of seizures at age 11 years. This case highlights the importance of a carefully organized lumbar puncture in the investigation and management of any child with neurodevelopmental delay and intermittent ataxia with or without seizures.