Journal of Child Neurology

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.

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.

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.

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.

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.

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.

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.

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).

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 Child Neurology Society/American Academy of Neurology practice parameter has recommended adrenocorticotropic hormone or vigabatrin in the short-term treatment of infantile spasms. When vigabatrin is unavailable or ineffective and adrenocorticotropic hormone is not a treatment option because of the prohibitive cost, other forms of corticosteroids have been considered in the treatment of infantile spasms. This retrospective study reviewed the Hospital for Sick Children’s experience with the short-term effectiveness of prednisolone versus adrenocorticotropic hormone in patients with infantile spasms who have failed vigabatrin. The results showed that while adrenocorticotropic hormone was more likely to lead to short-term spasm freedom, there was no difference in the likelihood of longer-term spasm resolution without relapse. These findings can guide clinicians in the treatment of infantile spasms post vigabatrin failure.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.