bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on the Epidemiology and Prognosis of Pediatric Epilepsy
Authors: Shinnar Shlomo , Pellock John M.
Published: June 2007

Epilepsy is among the most common serious neurologic disorders in childhood. Epidemiologic studies over the past few decades have greatly increased current knowledge of the incidence and prognosis of seizures. Newer epidemiologic studies have used population- or community-based cohorts, and careful attention has been given to etiology and specific epilepsy syndromes, the two most important factors affecting prognosis. Risk of epilepsy is highest in patients with an associated serious neurologic abnormality, such as mental retardation or cerebral palsy. More than two thirds of patients with childhood-onset epilepsy ultimately achieve remission. Of those attaining remission on medications, approximately 70% remain seizure free when medications are discontinued. Mortality is increased in patients with epilepsy, but the increased mortality risk in childhood-onset epilepsy is primarily seen in patients with neurologic abnormalities or intractable epilepsy. Although long-term seizure outcomes are generally favorable, childhood-onset epilepsy is associated with adverse long-term psychosocial outcomes, even in patients attaining remission. This review summarizes recent data on the epidemiology and prognosis of pediatric epilepsy. (J Child Neurol 2002;17:S4—S17).
West's Syndrome
Authors: Shields W. Donald
Published: June 2007

West's syndrome (infantile spasms) can be considered the classic disorder of the catastrophic childhood epilepsies. Although West's syndrome was identified 160 years ago, it is still not fully understood today. Because of the multiple etiologies associated with West's syndrome, the evaluation and treatment of the disease are complex, and, to date, there are no drugs approved by the US Food and Drug Administration specifically for the treatment of infantile spasms. The multiple etiologies associated with infantile spasms require that physicians take a broad look at all therapeutic options. There are, however, logical sequences that physicians should pursue when trying to treat this disorder. This article reviews the etiologies associated with West's syndrome, antiepilepsy drug therapies currently being used to treat the syndrome, and other treatment options available to clinicians. (J Child Neurol 2002;17:S76—S79).
Autopsy Case of Multiple Anomalies With Hypoplastic Cerebrum, Eyes, and Endocrine Organs, Mimicking Micro Syndrome
Authors: Hamano Kimiko , Kumada Satoko , Nagata Jinroh , Kurata Kiyoko , Hayashi Masaharu , Kojima Hideaki
Published: June 2007

We report an autopsy case of multiple anomalies with severe micrencephaly, bilateral microphthalmos, and hypoplastic endocrine organs. We examined expressions of calcium-binding proteins and hypothalamic and pituitary hormones. A female proband presented with microcephaly, microphthalmia, and psychomotor development delay. At the age of 23 years, she died of cardiorespiratory failure. The endocrine organs demonstrated severe underdevelopment, and the hypoplastic eyeballs had remnant lens, vitreous hemorrhage, and retinal detachment. The brain weighed 260 g; the cerebrum, cerebellum, and brain stem were extremely small; and the tertiary sulci were absent in the cerebral surface. The cross-sectional area of cerebral cortex was reduced to about one third of those in the control, although six-layered lamination, density of pyramidal neurons, and expressions of calcium-binding proteins were comparatively preserved in the cerebral cortex. The third ventricle was hypoplastic, and the bilateral thalami appeared to be fused and the hippocampus was unrolled, whereas the corpus callosum was preserved. In the hypothalamus, the paraventricular nucleus was only identified, and the adenohypophysial somatotrophs were reduced. This may be the first autopsy report of Micro syndrome, which is characterized by microcephaly, brain malformations, optic atrophy, and hypogenitalism, although the case lacked agenesis of the corpus callosum. ( J Child Neurol 2003;18:54—57).
Postoperative Malnutrition in Duchenne Muscular Dystrophy
Authors: Iannaccone Susan T. , Owens Hollis , Scott Janice , Teitell Betsy
Published: June 2007

Dysphagia and aspiration seem to be rare in Duchenne muscular dystrophy, but cachexia can be associated with early death. Commonly, weight loss can be attributed to inadequate caloric intake caused by loss of ability to self-feed and/or fatigue. Our objective was to determine whether scoliosis repair is associated with malnutrition. A retrospective chart review was undertaken of patients with Duchenne muscular dystrophy, including those who underwent operative repair of scoliosis. We identified nine boys who lost > 5% body weight within 12 months of surgery. Eight patients who gained weight after surgery and eight patients of comparable age who had no surgery served as control subjects. All patients had no change in biceps strength after surgery, but those who lost weight were unable to self-feed. We found that weight loss after surgery was associated with loss of self-feeding. We conclude that pre- and postoperative management of patients with Duchenne muscular dystrophy should include feeding evaluation and determination of postural changes. ( J Child Neurol 2003; 18: 17—20).
Leigh Disease With Mitochondrial DNA A8344G Mutation: Case Report and Brief Review
Authors: Tsao Chang-Yong , Herman Gail , Boué Daniel R. , Prior Thomas W. , Lo Warren D. , Atkin Joan F. , Rusin Jerome
Published: June 2007

Leigh disease, subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder often seen in infancy or childhood but rarely reported in adults. Genetic heterogeneity is well recognized, and the associated etiologies include both mitochondrial and nuclear DNA defects. We describe an infant presenting with developmental delay and then progressive multisystem disorder and neuroradiologic features of Leigh disease. He and his maternal relatives all have the A8344G mitochondrial DNA mutation. However, only minor clinical features are seen in his maternal relatives, with migraine being the most common problem. Additionally, the A8344G mitochondrial DNA mutation is associated with spinocerebellar degeneration, other nonspecific mitochondrial encephalomyopathies, atypical Charcot-Marie-Tooth disease, and progressive external ophthalmoplegia. The A8344G mitochondrial DNA mutation may present with Leigh disease or other different atypical clinical features without myoclonic epilepsy and ragged red fibers. ( J Child Neurol 2003; 18: 62—64).
Andermann Syndrome in a Turkish Patient
Authors: Demir Ercan , Irobi Joy , Erdem Sevim , Demirci Mehmet , Tan Ersin , Timmerman Vincent , De Jonghe Peter , Topaloglu Haluk
Published: June 2007

Agenesis of the corpus callosum with peripheral neuropathy or Andermann syndrome is an autosomal recessive disorder rarely found outside certain regions of the province of Quebec, Canada. We report a 5-year-old Turkish patient with Andermann syndrome born to consanguineous parents. She presented with diffuse hypo-tonic weakness, predominantly in the distal extremities, and mild mental retardation. Electromyography showed axonal-demyelinating sensorimotor neuropathy. Sural nerve biopsy was compatible with demyelinating neuropathy. Cranial magnetic resonance imaging revealed total agenesis of the corpus callosum, dilatation of the interhemispheric fissure, and enlargement of the cisterna magna. The molecular genetic analysis using microsatellite DNA markers covering the agenesis of the corpus callosum with peripheral neuropathy locus on chromosome 15q13—q15 showed that the patient is homozygous for the whole region. Our findings confirm that Andermann syndrome is a genetically homogeneous disorder. ( J Child Neurol 2003; 18: 76—79).
Combined Treatment With Subcutaneous Interferon-α, Oral Isoprinosine, and Lamivudine for Subacute Sclerosing Panencephalitis
Authors: Aydin Ömer Faruk , Şenbil Nesrin , Kuyucu Necdet , Gürer Y.K. Yavuz
Published: June 2007

We compared patients with subacute sclerosing panencephalitis who received treatment according to our protocol for at least 6 months (19 patients) with the patients who could not receive any treatment (13 patients). The treatment protocol consisted of oral isoprinosine (100 mg/kg/day), subcutaneous interferon alpha-2a (10 mU/m2/three times a week), and oral lamivudine (10 mg/kg/day). There were no statistical differences between the two groups according to Neurological Deficit Index, clinical stage, and average age on admission and also on the final evaluation after treatment. The mortality rates of both groups were similar: 3 (15.7%) for the treatment group and 6 (46%) for controls. The remission rates for the treatment and control groups were 7 of 19 (36.8%) and 0 of 13 (0%), respectively, and the difference was statistically significant ( P = .036). The mean survival period of the treatment group was significantly longer than that of the control group ( P = .01). In conclusion, this combination treatment protocol resulted in higher remission rates and longer survival periods when compared with controls, as well as a remission rate that was better than the spontaneous remission rate of 5%. For this reason, and as well as because interferon-α therapy has an easier route of application and a higher family compliance, we have considered this an alternative protocol for patients with subacute sclerosing panencephalitis. ( J Child Neurol 2003; 18:104—108).
Familial Spastic Paraplegia as the Presenting Manifestation in Patients With Purine Nucleoside Phosphorylase Deficiency
Authors: Tabarki Brahim , Yacoub Moncef , Tlili Kalthoum , Trabelsi Anouar , Dogui Mohamed , Essoussi Ahmed S.
Published: June 2007

We report two siblings with purine nucleoside phosphorylase deficiency revealed by isolated spastic paraplegia, whereas symptoms of immune deficiency did not become apparent until 3 years of age. As the concurrence of immunodeficiency and neurologic problems strongly suggests the diagnosis of purine nucleoside phosphorylase deficiency, special attention should be paid to counts of lymphocytes in any infant with spastic paraplegia. ( J Child Neurol 2003;18:140—141).
Do Not Overlook Acute Isoniazid Poisoning in Children With Status Epilepticus
Authors: Çaksen Hüseyin , Odabas Dursun , Erol Mehmet , Anlar Ömer , Tuncer Oguz , Atas Bülent
Published: June 2007

A previously healthy 2-year-old girl was admitted with generalized convulsive status epilepticus. She was in a stupor and could respond only to painful stimuli. She also had severe metabolic acidosis. Although initial liver function tests were normal, they were found to be moderately high on the fifth day of admission; however, they dropped to their normal ranges on the twelfth day of admission. Initially, the patient was diagnosed as having idiopathic status epilepticus, and classic anticonvulsant agents, including diazepam, phenytoin, and then phenobarbital, were given. However, her seizures did not subside, and diazepam infusion was initiated. After initiation of diazepam infusion, the seizures were completely controlled. On the fourth day of admission, her parents said that she had accidentally received 20 tablets (a total dose of 2000 mg) of isoniazid just before admission to our hospital. Later, we injected 200 mg of pyridoxine intravenously. During follow-up, her general condition improved, and anticonvulsant agents were discontinued because an electroencephalogram was found to be normal. She was discharged from the hospital on the twelfth day of admission. At the fourth month of follow-up, she was seizure free. Because of this case, we would like to re-emphasize that acute isoniazid poisoning should also be considered in a child with unexplained status epilepticus. ( J Child Neurol 2003; 18: 142—143).
Auditory Processing Studied Prospectively in Two Hemidecorticectomy Patients
Authors: Boatman Dana , Vining Eileen P. , Freeman John , Carson Benjamin
Published: June 2007

Auditory processing of speech and nonspeech sounds was studied prospectively in two hemidecorticectomy patients (ages 10—11 years) with Rasmussen's syndrome. We tested auditory word recognition under four listening conditions: in quiet, in noise, after acoustic filtering, and dichotically. Recognition of environmental sounds and discrimination of tones and digitized syllables were also tested. Presurgical testing confirmed normal processing of speech and nonspeech, for both patients, under all listening conditions. One year after surgery, both patients demonstrated intact recognition of words and environmental sounds in quiet but impaired word recognition in noise. The left hemidecorticectomy patient also demonstrated impaired recognition of low-pass filtered words. These findings suggest that either hemisphere can process speech or nonspeech sounds in quiet, whereas both hemispheres are needed to process speech in background noise. Hemispheric contributions to processing speech in noise appear to differ, with the left hemisphere compensating for loss of phonologic information and the right hemisphere compensating for increased attention demands. ( J Child Neurol 2003; 18: 228—232).
Prevalence of Neuromuscular Diseases in Chinese Children: A Study in Southern China
Authors: Chung Brian , Wong Virginia , Ip Patrick
Published: June 2007

Our objective was to study the prevalence of neuromuscular diseases in Chinese children. A prospective study of neuromuscular diseases in Chinese children was conducted from 1985 to 2001 in Hong Kong, which is a city in southern China. The population census of June 30, 2001, was used to calculate the prevalence of neuromuscular diseases in Chinese children. Altogether, 332 children aged < 19 years at first assessment with neuromuscular diseases confirmed by using electromyography, muscle biopsy, and/or molecular genetic study were included in the study. Of these, 228 (68%) had inherited and 104 (32%) had noninherited neuromuscular diseases. Of the inherited neuromuscular diseases, the most common were the dystrophinopathies, including Duchenne muscular dystrophy ( n = 66) and Becker muscular dystrophy ( n = 8). Spinal muscular atrophy was the second most common ( n = 61). Of the noninherited neuromuscular disorders, myasthenia gravis was the most common ( n = 62, 60%). Nearly 88% of the cases of myasthenia gravis were ocular type. The prevalence rate of neuromuscular diseases in June 2001 ( n= 291 surviving) is estimated to be 214 × 10—6. The estimated prevalence rate of neuromuscular diseases in our Chinese children is 1 in 4669. ( J Child Neurol 2003; 18: 217—219).
Rhombencephalosynapsis Associated With Cutaneous Pretibial Hemangioma in an Infant
Authors: Odemis Ender , Çakir Murat , Aynaci Fatma Müjgan
Published: June 2007

Rhombencephalosynapsis is a rare congenital abnormality characterized by noncleavage of the cerebellar hemispheres and dentate nuclei with agenesis or severe hypoplasia of the cerebellar vermis. We report an 8-month-old boy with hypotonia, mental and motor retardation, and capillary hemangiomas on his pretibial region. Cranial magnetic resonance imaging revealed vermian hypoplasia with fused cerebellar hemispheres called rhombencephalosynapsis. Other cerebellar and cerebral structures were normal. With this constellation of findings, we attempt to identify the pathogenesis of this posterior fossa malformation. We also discuss cerebellar embryogenesis to differentiate this condition from other posterior fossa malformations such as Dandy-Walker malformation and Joubert's syndrome. ( J Child Neurol 2003; 18: 225—228).
Central Pontine and Extrapontine Myelinolysis Owing to Disequilibrium Syndrome
Authors: Aydin Ömer Faruk , Üner Çiğ dem , Şenbil Nesrin , Bek Kenan , Erdoğan Özlem , Yavuz Gürer Y.K.
Published: June 2007

Neurologic disorders can be seen in patients with end-stage renal failure owing to complications of hemodialysis or peritoneal dialysis. The disequilibrium syndrome can be seen, usually soon after or toward the end of dialysis. We report a patient with central pontine and extrapontine myelinolysis owing to disequilibrium syndrome. The patient had depressed consciousness, agitation, tremor, stupor, and hyperactive deep tendon reflexes toward the end of the second peritoneal dialysis. A brain computed tomographic (CT) scan showed hypodense lesions in pontine and extrapontine locations without radiocontrast medium enhancement. After 2 days, the patient had only minimal memory deficits. A control brain CT scan 1 week later showed a decrease of the lesions in central pontine and extrapontine locations. Central pontine and extrapontine myelinolysis should be suspected and investigated in the acute neurologic disorders of dialysis patients. ( J Child Neurol 2003;18:292—296).
Childhood Epilepsy: What Is the Evidence for What We Think and What We Do?
Authors: Camfield Peter , Camfield Carol
Published: June 2007

This article reviews the strength of the evidence that underlies the current approach to the management of childhood epilepsy. The authors reviewed published, peer-reviewed English literature accessed through PubMed and Cochrane reviews with evidence rated as Class 1 (strongest) to Class 4 (weakest). There is considerable inaccuracy in the diagnosis of seizures and epilepsy syndromes. Sound information supports the consensus that the diagnosis of epilepsy should await two unprovoked seizures. Population-based studies indicate that remission from childhood onset epilepsy occurs in at least 50% of children. It is easier to predict a good seizure outcome than a poor one. Absence of concomitant neurologic handicap and onset before about 12 years of age are the most consistent predictors of remission. Intractability is poorly defined and difficult to predict until several antiepilepsy drugs have been used and failed to control the seizures. Most epilepsy syndrome diagnoses do not yield an accurate prognosis. Social outcome appears unsatisfactory in about 50% of cases without intellectual handicap. Death is rare in childhood epilepsy. Those without severe neurologic handicaps have the same mortality as the general population. We identified only 27 published randomized trials of antiepilepsy drugs in children that compare the efficacy of antiepilepsy drugs, offer treatment of syndromes currently without successful treatment, or have negative effects. There is a pressing need for better definitions of seizures and epilepsy syndromes. The causes of poor social outcome are unclear. Intractability needs a clear definition and randomized trials comparing treatment regimes are sadly lacking. ( J Child Neurol 2003; 18:272-287).
Transient Lesion in the Splenium of the Corpus Callosum in Acute Cerebellitis
Authors: Kato Zenichiro , Kozawa Ryo , Kondo Naomi , Hashimoto Kazuyuki
Published: June 2007

We report the reversible magnetic resonance imaging (MRI) findings in a 2-year-old girl with acute cerebellitis. The high signal intensity in the cerebellum was obvious on diffusion-weighted images, and the splenium of the corpus callosum also showed high signal intensity on T2-weighted images and on diffusion-weighted images. The lesion in the splenium quickly returned to normal 72 hours later, whereas the hyperintensity in the cerebellum persisted for 1 week until clinical improvement was achieved. The findings in our patient suggested the particular vulnerability of the splenium of the corpus callosum compared to other regions and the importance of the MRI examinations including diffusion-weighted images in the early stage of encephalitis. ( J Child Neurol 2003;18:291—292).
Hydatid Disease of the Spine in South African Children
Authors: Ndondo Alvin P. , Fieggen Graham , Wilmshurst Jo M.
Published: June 2007

We present three patients with neurologic complications of the spine from hydatid disease. The first was a 6-year-old girl with lower limb paralysis evolving over 2 weeks. Neuroimaging revealed a cystic mass compressing the spinal cord at the level of T8 and extending from the vertebral body. She underwent surgical decompression. Histopathologic examination confirmed hydatid disease. At 6-month follow-up, functional improvement had occurred with full ambulation. She continues on long-term albendazole therapy. Two other patients are described, one with primary spinal disease and the other with cerebral disease and secondary seeding to the spine. Spinal hydatid disease is a rarity, even more so in children. Although secondary disease, primarily affecting bone, carries a poorer long-term outlook, the first patient made a dramatic recovery and has raised therapeutic dilemmas as to the total duration of continuing albendazole therapy. The literature documents some 37 reports, mostly in adults. Considering the frequency of hydatid disease in South Africa, the incidence in our population could be under-recorded. Unless the clinician includes spinal hydatid disease, in endemic areas, as part of the differential list for paralysis and considers performing neuroimaging, this potentially treatable diagnosis will be missed. ( J Child Neurol 2003;18:343—346).
Epilepsy in Neurofibromatosis 1
Authors: Vivarelli Rossella , Grosso Salvatore , Calabrese Fulvia , Farnetani MariaAngela , Di Bartolo Rosanna , Morgese Guido , Balestri Paolo
Published: June 2007

Neurofibromatosis 1 is the most common neurocutaneous disease. Neurologic manifestations are mainly represented by tumors such as optic gliomas, focal areas of high T2-weighted signal known as unidentified bright objects, and mental retardation or learning disabilities. The prevalence of seizures has been reported to range from 3.8 to 6%. In the present study, we evaluated prevalence, type, and etiology of epilepsy in a neurofibromatosis 1 population. A retrospective analysis of 198 patients affected by neurofibromatosis 1 was performed. Fourteen patients (7%) were found to be epileptic. Every patient underwent electroencephalographic examination and neuroimaging investigations. Thirteen were submitted to magnetic resonance imaging (MRI) study and one to computed tomographic (CT) scanning. Single-photon emission computed tomographic and positron emission tomographic studies were performed in a few selected cases. Seizures were partial in 12 of these (85%) and generalized in 2 (15%). In nine (64%), epilepsy was secondary to brain lesions: five of these had cerebral tumors (three with epilepsy as the first symptom), three had cortical malformation, and one had mesial temporal sclerosis. Seizures were controlled rapidly in eight (57%) and drug resistant in four (29%). Two patients were lost at follow-up. All patients with uncontrolled seizures had severe mental retardation, and three of these had malformations of cortical development. Our observations and our re-evaluation of the literature indicate that patients with neurofibromatosis 1 have an increased risk of epilepsy related to intracranial masses and cytoarchitectural abnormalities, and seizures can represent the first symptom of a tumor or cortical malformation. Brain MRI and, in selected cases, functional studies appear to be useful in patients with neurofibromatosis 1 who present with seizures, especially if associated with mental retardation. ( J Child Neurol 2003;18:338—342).
Acute Painful Neuropathy (Insulin Neuritis) in a Boy Following Rapid Glycemic Control for Type 1 Diabetes Mellitus
Authors: Wilson Jennifer L. , Sokol Deborah K. , Smith Lisa H. , Snook Riley J. , Waguespack Steven G. , Kincaid John C.
Published: June 2007

We report a case of acute, painful polyneuropathy in a boy with newly diagnosed type 1 diabetes mellitus associated with a precipitous drop in hemoglobin A1c. After initiation of insulin, the patient's hemoglobin A1c dropped from 14.1 to 7.6%, and he developed severe pain in his feet, which prevented him from walking. Nerve conduction studies were consistent with mild to moderate sensorimotor peripheral neuropathy. Initially, he required opiate analgesics for pain control. Three months after presentation, the patient showed dramatic improvement and regained his ability to walk. Although not well described in the pediatric literature, this case represents insulin neuritis, one of the few diabetic neuropathies that has a favorable outcome. ( J Child Neurol 2003;18:365—367).
Neurofibromatosis 1: A Novel NF1 Mutation in an 11-Year-Old Girl With a Giant Cell Granuloma
Authors: Krammer Uta , Wimmer Katharina , Wiesbauer Peter , Rasse Michael , Lang Susanna , Müllner-Eidenböck Andrea , Frisch Herwig
Published: June 2007

We report an 11-year-old girl who presented with a painless unilateral enlargement of the nasal bridge. Because of multiple café-aulait spots and a positive family history, neurofibromatosis 1 was diagnosed. On a computed tomographic scan, a unilocular radiolucency measuring 1.2 × 2 cm was seen in the anterior wall of the maxillary sinus, which was surgically removed. Histology revealed a central giant cell granuloma. Hyperparathyroidism, which can present with an osseous tumor and similar histology, was excluded. Molecular analysis uncovered a novel splice mutation (A4268G) in this neurofibromatosis 1 family, affecting our patient as well as her mother and brother. This article focuses on the variability of the neurofibromatosis 1 phenotype in this family and the possible relationship between central giant cell granuloma and neurofibromatosis 1. ( J Child Neurol 2003;18:371—373).
Unusual Side Effects of Lamotrigine Therapy
Authors: Das Krishna B. , Harris Chris , Smyth Diane P. L. , Cross J. Helen
Published: June 2007

An 8-year-old boy developed tremor, unsteadiness, chorea, and eye movement abnormalities on starting lamotrigine for myoclonic jerks. Investigations for a neurodegenerative disorder were negative. Symptoms and signs resolved on stopping lamotrigine. He was well and asymptomatic on follow-up after 4 years. Another 7-year-old boy who started on lamotrigine for suspected absence seizures developed abnormalities of eye movement with associated cognitive decline, which also resolved on discontinuing the medication. Eye movement abnormalities, involuntary movements, and behavioral changes appear to be unusual side effects of lamotrigine therapy. ( J Child Neurol 2003;18:479—480).
Neurologic Aspects of 49,XXXXY Syndrome
Authors: Galasso Cinzia , Arpino Carla , Fabbri Francesca , Curatolo Paolo
Published: June 2007

49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome characterized by mental retardation, severe speech impairment, craniofacial abnormalities, multiple skeletal defects, and genital abnormalities. We describe a 13-year-old boy with 49,XXXXY syndrome, language impairment, seizures, and left-hemisphere magnetic resonance imaging abnormalities and review the distinctive neurologic, cognitive, and behavioral phenotypes associa t e d w i t h t h i s d i s o r d e r. F i n a l l y, w e d i s c u s s testosterone supplementation in the treatment of this syndrome. ( J Child Neurol 2003;18:501—504).
Folinic Acid—Responsive Seizures Presenting as Breakthrough Seizures in a 3-Month-Old Boy
Authors: Frye Richard E. , Donner Elizabeth , Golja Annamaria , Rooney Cynthia M.
Published: June 2007

Neonatal seizures associated with white-matter changes on neuroimaging suggest an etiology of hypoxic-ischemic encephalopathy. Metabolic and idiopathic etiologies are also considerations but are less likely. Despite the fact that two disorders associated with neonatal seizures are diagnosed by cerebrospinal fluid neurotransmitter analysis, such an analysis is not standard in the work-up for idiopathic neonatal seizures. We describe an infant who had a prolonged delivery, seizures on the first day of life, and white-matter changes on neuroimaging. A progressive seizure disorder that was refractory to standard antiepilepsy medications developed at 2 months of age. Analysis of cerebrospinal fluid neurotransmitters at that time demonstrated a pattern consistent with folinic acid—responsive seizures. Seizures ceased 24 hours after starting folinic acid. Serial neuroimaging, electroencephalograms, and metabolic changes from this patient are presented. This case illustrates the importance of cerebrospinal fluid neurotransmitter analysis as part of the work-up for idiopathic neonatal seizures. ( J Child Neurol 2003;18:562—569).
The Attention-Deficit Hyperactivity Disorder Paradox: 2. Phenotypic Variability in Prevalence and Cost of Comorbidity
Authors: Burd Larry , Klug Marilyn G. , Coumbe Matthew J. , Kerbeshian Jacob
Published: June 2007

The objective of this study was to use population-based data to estimate the cost and phenotypic variation of conditions comorbid with attention-deficit hyperactivity disorder (ADHD). The North Dakota Department of Health's Claims Database was used to estimate the administrative prevalence, rates of comorbidity, and cost of care for subjects with ADHD. The case population was 7745 children. We then examined the 10 most frequent comorbidities for a defined condition in the International Classification of Diseases-9th edition ( ICD-9). The observed prevalence of general health conditions was 12 to 70% less than expected. The presence of a comorbid condition resulted in increases in costs of care of $381 to $731 per case per year. The observed prevalence of comorbid mental health conditions was 97 to 5286% higher than expected. The prevalence of conditions comorbid with ADHD varies widely, with rates of general medical conditions decreased and rates of most mental disorders increased. The costs for comorbidity with general health conditions were offset by large decreases in prevalence rates compared with controls. We identified an ADHD paradox: decreased rates of comorbid general health conditions and increased rates of comorbid mental disorders. Further research on comorbidity in ADHD is required. ( J Child Neurol 2003; 18:653-660).
Metabolic Changes in the Knockout Mouse for Canavan's Disease
Authors: Surendran Sankar , Matalon Kimberlee M. , Szucs Sylvia , Tyring Stephen K. , Matalon Reuben
Published: June 2007

Canavan's disease is an autosomal recessive disorder caused by aspartoacylase deficiency, which leads to accumulation of N-acetylaspartic acid in the brain and blood and an elevated level of N-acetylaspartic acid in the urine. The brain of patients with Canavan's disease shows spongy degeneration. How the enzyme deficiency and elevated N-acetylaspartic acid cause the pathophysiology observed in Canavan's disease is not obvious. The creation of a knockout mouse for Canavan's disease is being used as a tool to investigate metabolic pathways in the mouse and correlate them with the patients with Canavan's disease. The level of glutamate is lower in the knockout mouse brain than in the wild-type mouse brain, similar to what we have found in children with Canavan's disease, and so are the levels of γ-aminobutyric acid (GABA). The level of aspartate is higher in the Canavan's disease mouse brain. The activity of aspartate aminotransferase, an enzyme involved in the malate-aspartate shuttle, is lower in the Canavan's disease mouse brain. The lower weight of the Canavan's disease mouse was in direct proportion to low total-body fat and bone mineral density. These changes might be similar to what is seen in patients with Canavan's disease and could have therapeutic implications. ( J Child Neurol 2003;18:611—615).
Pelizaeus-Merzbacher Disease and Spastic Paraplegia Type 2
Authors: Hudson Lynn D.
Published: June 2007

Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2 are two sides of the same coin. Both arise from mutations in the gene encoding myelin proteolipid protein. The disease spectrum for Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of Pelizaeus-Merzbacher disease featuring hypotonia, respiratory distress, stridor, nystagmus, and profound myelin loss. The diverse disease spectrum is mirrored by the underlying pathogenesis, in which a blockade at any stage of myelin proteolipid protein synthesis and assembly into myelin spawns a unique phenotype. The continuing definition of pathogenetic mechanisms operative in Pelizaeus-Merzbacher disease and spastic paraplegia type 2, together with advances in neural cell transplant therapy, augurs well for future treatment of the severe forms of Pelizaeus-Merzbacher disease. ( J Child Neurol 2003;18:616—624).
Alexander's Disease
Authors: Johnson Anne B. , Brenner Michael
Published: June 2007

Alexander's disease, a rare and fatal disorder of the central nervous system, most commonly affects infants and young children but can also occur in older children and sometimes adults. In infants and young children, it causes developmental delay, psychomotor retardation, paraparesis, feeding problems, usually megalencephaly, often seizures, and sometimes hydrocephalus. Juvenile cases often do not have megalencephaly and tend to have predominant pseudobulbar and bulbar signs. In both groups, characteristic magnetic resonance imaging findings have been described. In adult cases, the signs are variable, can resemble multiple sclerosis, and might include palatal myoclonus. In all cases, the examination of brain tissue shows the presence of widely distributed Rosenthal fibers. Almost all cases have recently been found to have a heterozygous, missense, point mutation in the gene for glial fibrillary acidic protein, which provides a new diagnostic tool. In most cases, the mutation appears to occur de novo, not being present in either parent, but some adult cases are familial. ( J Child Neurol 2003;18:625—632).
Ten-Year Prospective Study (Clinical Spectrum) of Childhood Guillain-Barré Syndrome in the Arabian Peninsula: Comparison of Outcome in Patients in the Pre— and Post—Intravenous Immunoglobulin Eras
Authors: Koul Roshan , Chacko Alexander , Ahmed Riaz , Varghese Thomas , Javed Hashim , Al-Lamki Zakia
Published: June 2007

A prospective study of Guillain-Barré syndrome from January 1992 to December 2001 was undertaken. Intravenous immunoglobulins were used in all patients. All patients were followed up until complete recovery. Various parameters, such as onset of weakness, duration of hospital stay, ventilation requirement, residual deficit, and mortality, were recorded. Acute relapses and fluctuations were also noted. The pattern of this group was compared with patients before 1992, who were not given intravenous immunoglobulins in the Sultanate of Oman. Our data were compared with a few studies prior to 1992 from the medical literature. Our study revealed a definite benefit with intravenous immunoglobulins. The disease course and hospital stay were shortened. Fewer patients needed ventilation. There was no mortality, and the residual deficit was less than 5%. Occasional relapses at a later stage in the course of illness have been noted in acute Guillain-Barré syndrome. However, acute relapse, a new phenomenon that was not seen in the pre—intravenous immunoglobulin era, stood at 11.9%. Intravenous immunoglobulins have made a significant difference in the outcome of Guillain-Barré syndrome, but one has to be aware of acute relapses, which usually occur in the first 2 to 3 weeks after administration. ( J Child Neurol 2003;18:767—771).
Mild Elevation of N-Acetylaspartic Acid and Macrocephaly: Diagnostic Problem
Authors: Surendran Sankar , Bamforth Fiona J. , Chan Alicia , Tyring Stephen K. , Goodman Stephen I. , Matalon Reuben
Published: June 2007

Patients with slightly increased excretion of N-acetylaspartic acid in urine, together with macrocephaly, present a dignostic dilemma for Canavan's disease. We describe a 13-year-old male patient with macrocephaly, mild developmental delay, increased signal intensity in the basal ganglia bilaterally, partial cortical blindness, and retinitis pigmentosa. Although the clinical course and magnetic resonance imaging findings did not resemble typical Canavan's disease, N-acetylaspartic acid excretion in the patient's urine was slightly elevated, 99.90 ± 4.00 μg/mg creatinine, whereas the normal control range was < 83 μg/mg creatinine. Cultured skin fibroblasts from the patient showed no aspartoacylase activity. Cloning of genomic DNA isolated from the patient's fibroblasts showed an intronic mutation, specifically deletion of -2A and -3C at the acceptor site of exon 3 and disrupting the normal splicing of the gene. A second mutation was found in exon 6, 863 A→G in aspartoacylase complementary DNA, causing a tyrosine-to-cysteine (Y288C) amino acid substitution. Expression of the mutation on exon 6 showed normal aspartoacylase activity. These data suggest that expression of the mutation may help to understand the enzyme defect in a patient with slightly increased N-acetylaspartic acid excretion. ( J Child Neurol 2003;18:809—812).
Profound Infantile Neuroretinal Dysfunction in a Heterozygote for the CLN3 Genetic Defect
Authors: de los Reyes Emily , Dyken Paul Richard , Phillips Paul , Brodsky Michael , Bates Stephen , Glasier Charles , Mrak Robert E.
Published: June 2007

The neuronal ceroid-lipofuscinoses are a group of diseases that are characterized by progressive neuroretinal symptomatology, progressive accumulation of autofluorescing waxy lipopigments (ceroid-lipofuscin) within the brain and other tissues, and cerebral atrophy. Juvenile neuronal ceroid-lipofuscinosis, or Batten disease, is a form of neuronal ceroid-lipofuscinosis that is characterized by onset of neuroretinal symptoms between 4 and 10 years. Juvenile neuronal ceroid-lipofuscinosis is the most common type of neuronal ceroid-lipofuscinosis in the United States and Europe and is inherited as an autosomal recessive genetic disorder. Research in the last decade has led to the identification of the responsible gene for juvenile neuronal ceroid-lipofuscinosis, which is designated as CLN3. CLN3 is located on chromosome 16p11.2-12.1. The major mutation is a 1.02 kb deletion, which removes exons 7 and 8. Both homozygotic and heterozygotic deletions at the CLN3 gene site have been associated with the clinical syndromes of juvenile neuronal ceroid-lipofuscinosis. We report a possible atypical case of neuronal ceroid-lipofuscinosis, an infant, who presented at 5 months of age with a lack of developmental milestones, poor vision, severe retinopathy, intractable seizures, and progressive cerebral atrophy. Extensive laboratory investigations, including thorough metabolic evaluations, were unremarkable except for neuroimaging studies, electroencephalography, and electroretinography, all of which showed abnormalities confirming both cerebral and retinal degeneration. Although skin and conjunctival biopsies did not show classic fingerprint cytosomes by electron microscopic study, which characterize juvenile neuronal ceroid-lipofuscinosis, a diagnosis of an atypical form of juvenile neuronal ceroid-lipofuscinosis was suspected on the basis of the clinical picture. The retinal abnormalities, surprisingly, were those believed to be diagnostic of juvenile-onset neuronal ceroid-lipofuscinosis, or Batten disease. Subsequently, a heterozygous mutation for the common 1.02 kb deletion characteristic of juvenile neuronal ceroid-lipofuscinosis was established. ( J Child Neurol 2004;19:42—46).
Rectal Biopsy in the Diagnosis of Neuronal Intranuclear Hyaline Inclusion Disease
Authors: Kulikova-Schupak Romana , Knupp Kelly G. , Pascual Juan M. , Chin Steven S. , Kairam Ram , Patterson Marc C.
Published: June 2007

Neuronal intranuclear hyaline inclusion disease is a neurodegenerative disorder of childhood characterized by eosinophilic intranuclear inclusions and neuronal loss throughout the nervous system. Although most cases have been diagnosed postmortem, rectal biopsy may be diagnostic during life. We identified two patients: an 11-year-old boy (P1) with new-onset bulbar weakness and parkinsonism and a 15-year-old boy (P2) with severe cognitive and motor deterioration of uncertain etiology who presented at 4 years of age with a gait disturbance and motor slowing. Both patients had a history of behavioral problems marked by frequent temper tantrums. Both had nondiagnostic magnetic resonance imaging of the head and metabolic work-ups. Rectal biopsy was diagnostic 1 year (P1) and 11 years (P2) after the initial evaluation. Rectal biopsies should be considered in children presenting with otherwise unexplained multisystem degeneration, particularly in the presence of both upper and lower motoneuron signs accompanied by behavioral problems. ( J Child Neurol 2004; 19:59—62).
Benign Neonatal Sleep Myoclonus Mimicking Status Epilepticus
Authors: Turanli Güzide , Senbil Nesrin , Altunbasak Sakir , Topçu Meral
Published: June 2007

Benign neonatal sleep myoclonus is a self-limited movement disorder characterized by neonatal-onset myoclonic jerks only during sleep, abrupt and consistent cessation with arousal, and absence of concomitant electrographic changes suggestive of seizures. It has a good outcome and was included in the differential diagnosis of neonatal seizures. A presumed transient serotonin imbalance and genetic factors may play a role in the pathogenesis of this disorder. We report a case of benign neonatal sleep myoclonus mimicking status epilepticus in an infant with a family history of nocturnal myoclonus, tic disorder, and sleep disturbance. We suggest that this benign entity should be included in the differential diagnosis of status epilepticus during the newborn period. ( J Child Neurol 2004;19:62—63).
Congenital Myopathies in the New Millennium
Authors: Goebel Hans H.
Published: June 2007

Few medical disciplines have benefited so enormously from the molecular revolution as myology. Whereas the congenital myopathies have flourished from enzyme histochemistry and electron microscopy, defining individual congenital myopathies by structural abnormalities, genetic research has only recently focused on congenital myopathies. However, a number of congenital myopathies have been molecularly elucidated: central and multiminicore diseases, nemaline myopathy, myotubular myopathy, and congenital myopathy marked by aggregation of proteins, giving rise to the concept of protein aggregate myopathies, to which now desminopathies, α-B crystallinopathies, selenoproteinopathy, myotilinopathy, actinopathies, and myosinopathies belong. Based on recent identification of mutations in respective genes, the principle “from morphology, that is, immunohistochemistry, to molecular analysis” through recognition of certain accrued proteins within muscle fibers and subsequent analysis of their respective genes has resulted in a wealth of genetic data and in reconsidering classification and nosologic interpretation of certain congenital myopathies. This heuristic principle needs to be further applied to other genetically still obscure congenital myopathies. ( J Child Neurol 2005;20:94—101).
Botulinum Toxin Injections for Children With Excessive Drooling
Authors: Hassin-Baer Sharon , Scheuer Esther , Buchman Aron S. , Jacobson Izhak , Ben-Zeev Bruria
Published: June 2007

The objective of this study was to evaluate the feasibility of ultrasonography-guided injections of botulinum toxin A into the parotid glands of children with severe drooling (sialorrhea). Excessive drooling is common in children with chronic neurologic disorders. Preliminary observations in adults suggest that injections of botulinum toxin A into the parotid glands can decrease drooling, but the optimal dose, sites of injection, and concomitant use of imaging during injections and its use for children have not been established. Ultrasonography was used to guide the injection of botulinum toxin (10—25 IU) into both parotid glands of nine children with excessive drooling. Subjective and objective measures of the severity of drooling were collected before and after botulinum toxin A injections. A booster injection was provided if the initial response was inadequate. Injections were well tolerated, and no adverse reactions were observed. Ultrasonography revealed that the parotid gland showed a variable depth, extent, and vascularization. Eight of nine patients needed a booster injection after 1 month. Objective measures of drooling severity were improved in seven of nine patients. However, subjective improvement was reported in only three of nine patients, and this improvement was functionally significant in only one patient. Although intraparotid injection of botulinum toxin A is safe and causes a reduction in saliva production in children, the doses used in this study did not result in functionally significant improvement. Higher doses of botulinum toxin A in the parotid glands or concomitant injections into the submandibular glands can increase the efficacy of these injections. Variability in size, depth, and vascular supply of the parotid gland suggests the importance of ultrasonography guidance for optimizing injections. These results underscore the need for further studies to establish the efficacy of this treatment in children. ( J Child Neurol 2005;20:120—123).
Topiramate-Valproate—Induced Hyperammonemic Encephalopathy Syndrome: Case Report
Authors: Cheung Eddie , Wong Virginia , Fung Cheuk-Wing
Published: June 2007

A 15-year-old boy with inverted duplication of chromosome 15 was admitted for acute onset of irritability, increasing sleepiness, and worsening of seizures. He had been on valproate and other anticonvulsants. However, he was found to have hyperammonemia within 2 weeks after the addition of low-dose topiramate to valproate. He recovered within 7 days after discontinuation of valproate. Topiramate was tailed off. The reintroduction of valproate monotherapy caused hyperammonemia again without clinical features of encephalopathy. He also developed anticonvulsant hypersensitivity syndrome following the use of phenytoin. We propose the term topiramate-valproate—induced hyperammonemic encephalopathy syndrome to include the following features: excessive sleepiness or somnolence, aggravation of seizures, hyperammonemia, and absence of triphasic waves on electroencephalography in any individual on simultaneous topiramate-valproate therapy. The ammonia level ranged from 1.5 to 2 times normal. The serum valproate level might be within the therapeutic range. The possible mechanism is topiramate-induced aggravation of all the known complications of valproate monotherapy. This condition is reversible with cessation of either valproate or topiramate. ( J Child Neurol 2004;19:157—160).
Type I Spinal Muscular Atrophy Can Mimic Sensory-Motor Axonal Neuropathy
Authors: Anagnostou Evdokia , Miller Steven P. , Guiot Marie-Christine , Karpati George , Simard Louise , Dilenge Marie-Emmanuelle , Shevell Michael I.
Published: June 2007

Spinal muscular atrophy is a group of allelic autosomal recessive disorders characterized by progressive motoneuron loss, symmetric weakness, and skeletal muscle atrophy. It is traditionally considered a pure lower motoneuron disorder, for which a current definitive diagnosis is now possible by molecular genetic testing. We report two newborns with a clinical phenotype consistent with that of spinal muscular atrophy type I and nerve conduction studies and electromyography suggesting more extensive sensory involvement than classically described with spinal muscular atrophy. Molecular testing confirmed spinal muscular atrophy in patient 1 but not in patient 2. Thus, in the setting of a suspected congenital axonal neuropathy, molecular testing might be necessary to distinguish spinal muscular atrophy type I from infantile polyneuropathy. ( J Child Neurol 2005;20:147—150).