bluuebunny/crossref_metadata_2025 huggingface dataset:
Topical Review: Fetal and Neonatal Neurologic Case Histories: Assessment of Brain Disorders in the Context of Fetal-Maternal-Placental Disease
Authors: Scher Mark S.
Published: June 2007

The more conventional role of the pediatric neurologist involves the evaluation of the child after birth. Although the pediatric neurologist rarely attends the delivery of the neonate, consultation by the neurologist should begin immediately following stabilization by the neonatal resuscitation team. Four interrelated aspects of the neurologist's clinical assessment will be discussed in the context of reaching a consultative opinion, which must incorporate knowledge of chronologic events before as well as during labor and delivery. This evaluation encompasses an assessment of levels of arousal, increased or decreased muscle tone, presence of seizures, and effects of systemic diseases on the central nervous system, which are the essential elements of a complete neurologic examination. Documentation of the neonate's neurologic condition, together with knowledge of maternal, fetal, and placental diseases, will help anticipate neuroresuscitative decisions, as well as subsequent neurologic deficits. ( J Child Neurol 2003; 18: 155—164).
Characteristics of Prolonged Afterdischarges in Children With Malformations of Cortical Development
Authors: Chitoku Shiro , Otsubo Hiroshi , Harada Yu , Jay Venita , Rutka James T. , Weiss Shelly K. , Elliott Irene , Ochi Ayako , Kitayama Masaomi , Carter Snead O.
Published: June 2007

We investigated aberrant cortical excitability in malformations of cortical development. From subdural electrodes, we recorded afterdischarges lasting ≥ 6 seconds in 12 of 13 patients with malformations of cortical development and 6 of 10 pediatric patients with nonmalformations of cortical development and reviewed amperage thresholds, distribution of afterdischarges, and motor responses. In patients with malformation of cortical development, motor response thresholds were high; afterdischarge and motor response thresholds, which essentially overlapped, inversely correlated with age ( P < .01); afterdischarge thresholds declined with age; and 8 patients showed afterdischarges in remote sites. In nonmalformation of cortical development, afterdischarge thresholds did not significantly correlate with age; motor response thresholds tended to decline with age; and 2 patients had remote afterdischarges. Adolescent patients with malformations of cortical development had lower afterdischarge thresholds than adolescents with nonmalformation of cortical development ( P < .05). From their high afterdischarge (and motor response) thresholds, we concluded that preadolescent patients with malformation of cortical development have less excitable, immature cortices, whereas adolescent patients with malformation of cortical development with low afterdischarge thresholds have hyperexcitable cortices. Remote afterdischarges over focal dysplastic cortex suggest aberrant cortical excitability and neural circuits.( J Child Neurol 2003;18:247—253).
Optic Pathway Gliomas in Children With and Without Neurofibromatosis 1
Authors: Czyzyk Elzbieta , Jóźwiak Sergiusz , Roszkowski Marcin , Schwartz Robert A.
Published: June 2007

Optic pathway gliomas represent 2 to 5% of brain tumors in children. Frequently asymptomatic, sometimes they demonstrate rapid growth, causing considerable visual dysfunction, neurologic deficits, and endocrine disturbances. Most optic pathway gliomas are diagnosed in patients with neurofibromatosis 1. Little is known about their natural course; therefore, there are no clear and widely accepted guidelines for their treatment. This study compared the clinical manifestations and natural history of sporadic and neurofibromatosis 1—associated optic pathway gliomas with regard to age at diagnosis, gender, and findings on neurologic, ophthalmologic, and neuroradiologic examinations in 83 children with optic pathway gliomas: 51 children with neurofibromatosis 1 and 32 children without any symptoms or signs of neurofibromatosis 1. A prospective study was performed in 21 patients with neurofibromatosis 1. In the rest of the patients with neurofibromatosis 1 and in 32 children with sporadic tumors, the analysis was carried out retrospectively. There was an increased incidence of females in the group of patients with neurofibromatosis 1 with optic pathway gliomas compared with the entire group of patients with neurofibromatosis 1 remaining for follow-up ( P = .013). All optic pathway gliomas were found in children below 10 years of age, slightly earlier in the group without neurofibromatosis 1 (median age 4.6 vs 4.8 years). Children with optic pathway gliomas associated with neurofibromatosis 1 had predominantly multifocal lesions ( P = .0001), whereas in the group without neurofibromatosis 1, isolated chiasmal involvement was more common ( P = .002). Children with sporadic gliomas had significantly more frequently increased intracranial pressure, decreased visual acuity, and abnormalities of fundus of the eye at the time of diagnosis. The radiologic progression, visual deterioration, and endocrinologic complications were documented on follow-up more commonly in children with sporadic tumors. Our findings support the concept that there is an earlier and more severe clinical presentation of optic pathway gliomas in children with sporadic tumors than in those associated with neurofibromatosis 1. ( J Child Neurol 2003;18:471—478).
Specificity of Cerebellar Vermian Abnormalities in Autism: A Quantitative Magnetic Resonance Imaging Study
Authors: Kaufmann Walter E. , Cooper Karen L. , Mostofsky Stewart H. , Capone George T. , Kates Wendy R. , Newschaffer Craig J. , Bukelis Irena , Stump Mariah H. , Jann Adelene E. , Lanham Diane C.
Published: June 2007

To gain insight into the specificity of cerebellar vermian abnormalities reported in autism, we conducted a magnetic resonance imaging (MRI) study of boys with either of two conditions associated with autism, Down syndrome and fragile X syndrome, compared with boys with idiopathic autism and controls. The subjects, ranging in age from 3 to 9 years, included 16 boys with Down syndrome + autism and 11 boys with Down syndrome only; 13 boys with fragile X syndrome + autism and 9 boys with fragile X syndrome only; 10 boys with idiopathic autism; and 22 controls. Diagnosis of autism was based on DSM-IV criteria, confirmed primarily by the Autism Diagnostic Interview. T1-weighted midsagittal MRIs were used to measure midline structures. Intracranial area, reflecting brain size, was significantly smaller in subjects with Down syndrome. Therefore, all vermian measures were expressed as ratios to intracranial area. Analysis of covariance (covarying for age and IQ) demonstrated that posterior vermi (lobules VI—VII and VIII—X) were markedly smaller in both Down syndrome groups and those with fragile X syndrome only, whereas only lobules VI—VII were reduced in idiopathic autism. Factorial analyses of variance tested interactions between autism factor and the diagnosis of Down syndrome or fragile X syndrome. The size of lobules VI—VII/intracranial area was dependent on autism status only in fragile X syndrome, with ratios significantly larger in fragile X syndrome with autism with respect to fragile X syndrome only. We conclude that selective posterior vermis hypoplasia is seen not only in idiopathic autism but also in Down syndrome and some individuals with fragile X syndrome. However, reductions in vermian lobules VI and VII appear to be specific to idiopathic autism, whereas increased size of lobules VI and VII is associated with autism in fragile X syndrome. The latter results are consistent with MRI studies showing lobules VI—VII hyperplasia in a subset of subjects with idiopathic autism and cerebral and hippocampal enlargements in fragile X syndrome. ( J Child Neurol 2003;18:463—470).
Role of Gabapentin in Spinal Muscular Atrophy
Authors: Merlini Luciano , Solari Alessandra , Vita Giuseppe , Bertini Enrico , Minetti Carlo , Mongini Tiziana , Mazzoni Elena , Angelini Corrado , Morandi Lucia
Published: June 2007

Recent studies suggest that gabapentin has a neuroprotective effect in experimental models of motoneuron disease. We carried out a multicenter, randomized, controlled trial of gabapentin versus no treatment in 120 patients with type II or III spinal muscular atrophy for 12 months. We assessed maximum voluntary isometric contraction with a handheld myometer and calculated an arm megascore (summing elbow flexion, hand grip, and three-point pinch scores), and a leg megascore (summing knee flexion, knee extension, and foot extension scores). Forced vital capacity and timed tasks were also evaluated. Arm megascore improved by at least 30% in 24.6% of treated and 16.9% of untreated patients (relative risk = 1.45; 95% confidence interval = 0.71—2.97). The leg megascore improved by at least 30% in 37.7% of treated and 20.3% of untreated patients (relative risk = 1.85; 95% confidence interval = 1.02—3.37). We conclude that gabapentin produced a significant improvement in leg megascore at 6 months, which was more evident at 12 months, with a trend for improvement in arm megascore at 12 months. The treatment had no effect on forced vital capacity or timed functional tests. ( J Child Neurol 2003;18:537—541).
Topical Review: Pathophysiology of Sturge-Weber Syndrome
Authors: Comi Anne M.
Published: June 2007

Sturge-Weber syndrome is a neurocutaneous disorder classically presenting with a facial port-wine stain, vascular eye abnormalities, and an ipsilateral occipital leptomeningeal angioma. Children with Sturge-Weber syndrome often develop progressive neurologic problems. Data on the pathophysiology of Sturge-Weber syndrome are briefly reviewed. The embryologic, genetic, and pathologic considerations are discussed, as are theories regarding the mechanisms of the degenerative brain changes. Sturge-Weber syndrome likely results from an early embryologic malformation of vascular development affecting the development of the nearby skin, eye, and brain structures. Studies suggest that complex molecular interactions contribute to the abnormal development and function of blood vessels in Sturge-Weber syndrome. Neurologic deterioration in Sturge-Weber syndrome is likely secondary to impaired blood flow to the brain and is worsened by the presence of seizures. Insights from related areas are discussed, and future research studies are suggested. ( J Child Neurol 2003;18:509—516).
Independent Walking After Neonatal Arterial Ischemic Stroke and Sinovenous Thrombosis
Authors: Golomb Meredith R. , deVeber Gabrielle A. , MacGregor Daune L. , Domi Trish , Whyte Hilary , Stephens Derek , Dick Paul T.
Published: June 2007

Few studies have examined walking after neonatal arterial ischemic stroke and sinovenous thrombosis. We looked at the development of walking in a retrospective and consecutive cohort study of 88 term and near-term neonates. We used Kaplan-Meier survival curves and Cox proportional hazards models to assess (1) sex, (2) stroke type (arterial ischemic stroke or sinovenous thrombosis), (3) number of cerebral hemispheres with infarction, and (4) presence of neonatal comorbidity as predictors of the probability over time of starting to walk independently. These variables were assessed as predictors of parent-reported gait normality using the chi-square test on 2 × 2 contingency tables. Seventy-five of 83 survivors (90.4%, 95% confidence interval = 81.9—95.7) walked with a median time of first steps at 13 months of age (95% confidence interval = 12—14). Only bilateral strokes were associated with a lower probability over time of initiating independent walking (hazard ratio = 0.41, P = .04). Parents reported normal gait for 58 of 75 walkers (77.3%, 95% confidence interval = 67.8—86.8). No variables predicted parent-reported gait normality. Our findings suggest that most survivors of neonatal arterial ischemic stroke and sinovenous thrombosis walk with a gait that appears normal to parents, but bilateral infarctions decrease the probability over time of starting to walk independently. (J Child Neurol 2003;18:530—536).
Cerebrotendinous Xanthomatosis
Authors: Federico Antonio , Dotti Maria Teresa
Published: June 2007

In this report, we review the clinical, biochemical, pathophysiologic, and therapeutic aspects of cerebrotendinous xanthomatosis. We stress the importance of early diagnosis and treatment. In addition, we describe our experience in treating patients with chenodeoxycholic acid, an essential drug for this disorder that is no longer available. ( J Child Neurol 2003;18:633—638).
Leukoencephalopathy With Vanishing White Matter: From Magnetic Resonance Imaging Pattern to Five Genes
Authors: Leegwater Peter A. J. , Pronk Jan C. , van der Knaap Marjo S.
Published: June 2007

Leukoencephalopathy with vanishing white matter can be diagnosed on the basis of distinct clinical and magnetic resonance imaging (MRI) findings. It is a recessively inherited disorder, most often presenting in young children. The clinical symptoms include a slowly progressive cerebellar ataxia, spasticity, variable optic atrophy, and relatively preserved mental capacities. In addition, there are episodes of rapid and major deterioration following infections with fever and minor head trauma. These episodes can end in unexplained coma. MRI findings suggest that over time there is a progressive vanishing of the abnormal white matter, which is replaced by cerebrospinal fluid. We performed a genome-wide search and localized a gene for vanishing white matter on chromosome 3q27. We demonstrated that mutations in the gene EIF2B5 cause the disease. This gene encodes one of the five subunits of the translation factor eIF2B. Patients without mutations in the EIF2B5 gene were found to be mutated in one of the other genes that encode eIF2B subunits: EIF2B1 to EIF2B4. ( J Child Neurol 2003;18:639—645).
InterRett and RettBASE: International Rett Syndrome Association Databases for Rett Syndrome
Authors: Fyfe Susan , Cream Angela , de Klerk Nick , Christodoulou John , Leonard Helen
Published: June 2007

In 2001, the International Rett Syndrome Association funded the establishment of a World Wide Web—based database to collect and display the genetic data of children and adults with Rett syndrome from around the world. RettBASE () encompasses both published and unpublished data; includes pathogenic mutations, benign polymorphisms, and sequence variations of uncertain significance; and has a range of query capabilities, allowing for simple or complex interrogation of the database. To undertake genotype—phenotype correlations and to identify the likely subtle differences in phenotype, detailed phenotype data on large samples will be provided by the International Rett Syndrome Association International Phenotype database InterRett. InterRett is under development by the Australian Rett syndrome study group at the Telethon Institute for Child Health Research in Perth, Western Australia. It will collect data from clinicians and families and provide deidentified, collated data on the Internet (). Data records will be linked with RettBASE through a common unique identifier. An international reference panel is advising on the development of the database. Data collection procedures from families and clinicians are currently being piloted. Full data collection from both groups began in the second half of 2003. Concurrently, the output database will be developed to provide deidentified individual records and collated data for clinicians and researchers and collated data for families and the general public. This Web-based database will be an invaluable resource for understanding the nature of the disorder and managing children and adults with Rett syndrome. ( J Child Neurol 2003;18:709—713).
Survey of MeCP2 in the Rett Syndrome and the Non—Rett Syndrome Brain
Authors: Duncan Armstrong Dawna , Deguchi Kimiko , Antallfy Bobbie
Published: June 2007

The clinical and neuropathologic aspects of Rett syndrome suggest that an arrest of brain development produces the phenotype, but it is not understood how the gene implicated in Rett syndrome, methyl-CpG protein 2 (MeCP2), is regulated during brain development. In this study, the ontogeny of MeCP2 is examined in the developing human brain and in the female Rett syndrome brain to evaluate the relationship between MeCP2 expression and brain development in health and disease, respectively. Immunocytochemistry using an antibody to the C-terminal region of the protein was performed in paraffin sections of the developing brain to define the age and the sites of MeCP2 protein expression. In development, there is no MeCP2 expression in the germinal matrix or in the progenitor cells. At 10 to 14 weeks' gestation, the neurons of the brain stem and the Cajal-Retzius and subplate neurons of the cortex express MeCP2. By midgestation, some neurons of the basal ganglia express MeCP2, and at late gestation, the most mature cortical neurons in the lower cortical layers are positive. The postnatal cortex continues to increase its expression of neuronal MeCP2. In the Rett syndrome brain, fewer neurons express MeCP2 than in the normal brain. This reduction is most apparent in the brain stem and thalamus. The neurons of the cerebral cortex show the least reduction. We conclude that the regulation of MeCP2 abundance is related to human brain development, being expressed in neurons when they appear mature. In Rett syndrome, however, the expression pattern of MeCP2 does not completely resemble that of the normal immature brain, suggesting that the maintenance of MeCP2 might be determined in specific neurons by factors other than those controlling maturation. In the developing brain, synaptic activity and plasticity could be necessary to maintain MeCP2 in selected neuronal populations. ( J Child Neurol 2003;18:683—687).
Sleep Organization in Children With Partial Refractory Epilepsy
Authors: Lahorgue Nunes Magda , Ferri Raffaele , Arzimanoglou Alexis , Curzi Lilia , Appel Carla C. , Costa da Costa Jaderson
Published: June 2007

Although it is currently known that sleep can influence epilepsy and epilepsy can influence sleep organization, few data have been published on this mutual interaction concerning the pediatric population. The objective of this study was to verify the eventual presence of sleep alterations in children with partial refractory epilepsy. Seventeen patients with partial refractory epilepsy were submitted to whole-night polysomnography as part of their epilepsy investigation. Polysomnographic recordings were performed on a digital video-electroencephalography (EEG) system and consisted of the registration of EEG (24 channels), electro-oculogram, electromyogram, electrocardiogram, and nasal airflow and abdominal respiratory movements. Sleep stages were visually scored following standard criteria, and ictal events were classified according to the international classification of seizures. The patients were also subdivided into two subgroups based on the presence or absence of ictal episodes during the recording night. The results concerning sleep organization were compared with those obtained from a normal control group. The analysis of the sleep parameters showed a reduction of total time in bed and total sleep time in both subgroups of epileptic children; there was a higher number of stage shifts per hour in the control group than in both epileptic subgroups. The percentage of stage 2 shifts is significantly reduced in patients with epilepsy and seizures during the night and the percentage of stage 3 to 4 shifts is increased. Nonsignificant differences are evident for the number of awakenings per hour and the percentage of stage 1 shifts. The percentage of rapid eye movement (REM) sleep is reduced, and first REM latency is increased in both epileptic subgroups, compared with normal controls, without statistical significance. Nine of 17 patients had seizures during the polysomnographic recording; nocturnal ictal events occurred mostly during non-REM sleep stage 2. Our results show that patients with partial refractory epilepsies have only mild sleep structure abnormalities, and this can be considered as an effect of the epileptic syndrome per se or as a result of the chronic antiepilepsy drug treatment. ( J Child Neurol 2003;18:763—766).
Vermian Hypoplasia and Arrested Cerebral Myelination in Two Sisters: Variant of Joubert's Syndrome or a New Syndrome?
Authors: DeMyer William , Espay Alberto , Walsh Laurence , Benes Susan , Edwards-Brown Mary
Published: June 2007

Two adult sisters have vermian hypoplasia, ataxia, nystagmus, pontine divergence insufficiency, and mild to moderate intellectual disability, with an arrest of cerebral myelination resembling the pattern of a 4-month-old infant. Other abnormalities include high myopia, optic nerve hypoplasia, decreased bone density, hypoplasia of the secondary teeth, and amenorrhea. We did not find matching patients described in the literature. The sisters could represent a variant of one of the described syndromes of the cerebellocerebro-oculorenal spectrum, such as a variant of Joubert's syndrome, or a disorder sui generis within the spectrum. ( J Child Neurol 2003;18:755—762).
Impact of the Journal of Child Neurology: 2002 Data
Authors: Brumback Roger A.
Published: June 2007

The Journal of Child Neurology ( JCN) began in 1986 as a quarterly publication focused on child neurology and the related clinical pediatric neuroscience areas of pediatric neurosurgery, child psychiatry, pediatric neuroradiology, and developmental and behavioral pediatrics. As submitted material increased, JCN expanded in publication frequency and now appears monthly. Article quality has always been high and many articles have been frequently cited. Over the years, the ratings produced for the ISI Journal Citation Reports® have identified JCN as a high-ranking pediatric journal based upon the impact factor value. Currently (year 2002 figures), JCN (with its impact factor of 1.338) ranks 24th out of 68 pediatric journals. ( J Child Neurol 2003;18:795—797).
Hydrogen Peroxide Neurotoxicity in Childhood: Case Report With Unique Magnetic Resonance Imaging Features
Authors: Cannon George , Caravati E. Martin , Filloux Francis M.
Published: June 2007

Concentrated hydrogen peroxide (H2O2) intoxication is relatively rare in children. Serious irreversible neurotoxicity generally results. The case of an 11-year-old boy who inadvertently drank a concentrated (35%) H2O2 solution is described. He exhibited signs of an acute encephalopathy with cortical visual impairment. Extensive cerebrocortical diffusion restriction with apparent gyral edema was evident at 3 days following ingestion, particularly in the parieto-occipital regions bilaterally. Spontaneous neurologic improvement quickly followed, and nearly full clinical resolution was evident 1 month later. The pattern of imaging abnormalities closely resembles that of reversible posterior leukoencephalopathy. Concentrated H2O2 neurotoxicity in children can exhibit unique patterns (a reversible posterior leukoencephalopathy) and a better than expected outcome. ( J Child Neurol 2003;18:805—808).
Speech and Language Deterioration in Benign Rolandic Epilepsy
Authors: Berroya Anna G. , McIntyre Jenny , Webster Richard , Lah Suncica , Lawson John , Bleasel Andrew F. , Bye Ann M. E.
Published: June 2007

A 5-year-old boy presented with typical clinical and electrophysiologic features of benign rolandic epilepsy. His neurodevelopment, language, and behavior prior to the onset of epilepsy were appropriately normal. He demonstrated marked deterioration of language and cognitive function during the course to a mild and then a moderate disability range. Serial sleep electroencephalographic recordings initially showed continuous and bilateral rolandic discharges with evolution to localized left rolandic spikes. Language and cognitive improvements were subsequently seen. Educational support and evolution of the electroencephalogram to a localized focus could have been contributory. It is anticipated, however, that he will have significant long-term problems in complex language. ( J Child Neurol 2004;19:53—58).
Acute Necrotizing Encephalopathy of Childhood Associated With Influenza Type B Virus Infection in a 3-Year-Old Girl
Authors: Huang Shih-Ming , Chen Chu-Chin , Chiu Pao-Chin , Cheng Ming-Fang , Lai Ping-Hong , Hsieh Kai-Sheng
Published: June 2007

Acute necrotizing encephalopathy of childhood represents a novel entity of acute encephalophathy, predominantly affecting infants and young children living in Taiwan and Japan. It manifests with symptoms of coma, convulsions, and hyperpyrexia after 2 to 4 days of respiratory tract infections in previously healthy children. The hallmark of acute necrotizing encephalopathy of childhood consists of multifocal and symmetric brain lesions affecting the bilateral thalami, brainstem tegmentum, cerebral periventricular white matter, or cerebellar medulla. The etiology and pathogenesis of this kind of acute encephalopathy remain unknown, and there is no specific therapy or prevention. The prognosis is usually poor, and less than 10% of patients recover completely. We report a 3-year-old previously healthy girl presenting with acute necrotizing encephalopathy of childhood associated with influenza type B virus infection, which resulted in severe neurologic sequelae. We also review the current knowledge of the clinical, neuroimaging, and pathologic aspects of acute necrotizing encephalopathy of childhood. ( J Child Neurol 2004;19:64—67).
Topical Review: Levetiracetam in Pediatrics
Authors: Vigevano Federico
Published: June 2007

Levetiracetam is a new antiepileptic drug whose efficacy and tolerability are already well known in adults. Few studies are available in children. This review, based on the international literature, aims to identify and make known the possible indications for levetiracetam in childhood. Most studies suggest that levetiracetam is effective against partial and generalized epilepsy. In resistant partial epilepsy, the percentage of responders reaches 64%, with 8 to 23% seizure free. Levetiracetam is used to treat symptomatic and idiopathic epilepsies. The drug has also proven effective against photosensitivity and epileptic and nonepileptic myoclonus. The most frequent side effects involve the behavioral sphere and manifest mostly in patients with a history of behavioral problems. In some patients, levetiracetam increases the number of seizures, but this adverse reaction can be partially avoided with slow titration. Doses for children should be 130 to 140% of those advised for adults. Levetiracetam seems to have a broad spectrum of action and is, on the whole, well tolerated. Its efficacy against generalized epilepsy is particularly promising in childhood. ( J Child Neurol 2005;20:87—93).
Episodic Hyponatremia in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Strokelike Episodes (MELAS)
Authors: Kubota Hiroaki , Tanabe Yuzo , Takanashi Jun-ichi , Kohno Yoichi
Published: June 2007

Various organ involvements and endocrinologic abnormalities associated with electrolyte imbalance, including hyponatremia, are seen in patients with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS); however, the clinical significance of hyponatremia in these patients is rarely reported. We analyzed the serum sodium concentration profiles and clinical and laboratory data of seven patients with MELAS. We found that hyponatremia occurred episodically in four of the seven patients from an early stage of the disease. We identified excessive sodium loss in urine to be associated with the hyponatremic episodes and the causes of hyponatremia in two patients as relative adrenal insufficiency, acute renal failure, and serious paralytic ileus. However, even extensive examinations failed to reveal the cause in other patients. Because severe hyponatremia can cause serious complications, clinicians should pay attention to serum sodium levels and maintain them properly in patients with MELAS. ( J Child Neurol 2005;20:116—120).
Cognitive Changes in Children Treated for Acute Lymphoblastic Leukemia With Chemotherapy Only According to the Pediatric Oncology Group 9605 Protocol
Authors: Montour-Proulx Isabelle , Kuehn Sally M. , Keene Daniel L. , Barrowman Nicholas J. , Hsu Elizabeth , Matzinger Mary-Ann , Dunlap Hal , Halton Jacqueline M.
Published: June 2007

The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Children's Hospital of Eastern Ontario. Mean age at diagnosis was 4.88 ± 2.54 years. The mean ( n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 ± 15.69 and 84.83 ± 19.11, respectively). Mean ( n = 20) Verbal and Visual Memory Indexes of 82.95 ± 15.46 and 88.30± 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity. ( J Child Neurol 2005;20:129—133).
Molybdenum Cofactor Deficiency Presenting With Severe Metabolic Acidosis and Intracranial Hemorrhage
Authors: Teksam Ozlem , Yurdakok Murat , Coskun Turgay
Published: June 2007

Molybdenum cofactor deficiency leads to combined deficiency of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase enzyme activities. The major clinic symptom is intractable seizures seen soon after birth. No definite therapy is available. We report here a newborn with molybdenum cofactor deficiency—associated Dandy-Walker malformation who presented with severe lactic acidosis and intracranial hemorrhage. ( J Child Neurol 2004; 19:155—157).
Valproate-Induced Eosinophilia in Children With Epilepsy: Role of Interleukin-5
Authors: Makis Alexandros C. , Tzoufi Meropi , Kateri Maria D. , Bourantas Konstantinos I. , Papadopoulou Zoe L.
Published: June 2007

Interleukin-5 contributes both in eosinophilopoiesis and neural development. Serum interleukin-5 levels were measured with enzyme-linked immunosorbent assay technique in 68 children with epilepsy receiving sodium valproate monotherapy and compared with the levels of 60 healthy controls and 14 children with epilepsy receiving carbamazepine. Eosinophilia was observed in 35.3% of children receiving valproate. Interleukin-5 in valproate users was significantly higher compared with children receiving carbamazepine and controls. Valproate users who exhibited eosinophilia had higher interleukin-5 levels compared with those without eosinophilia. However, the interleukin-5 level was also elevated, although to a lesser degree, in children without eosinophilia. The majority of valproate responders had high interleukin-5 levels. A positive correlation between interleukin-5 levels and the eosinophil count was also noted. We postulate that valproate contributes to the pathogenesis of eosinophilia, probably inducing interleukin-5 production. The finding that serum interleukin-5 was significantly elevated in valproate responders and even in valproate users without eosinophilia suggests that the increase in interleukin-5 might represent one of valproate's antiepileptic mechanisms. ( J Child Neurol 2005;20:150—152).
Clinical and Genetic Features in Two Families With MELAS and the T3271C Mutation in Mitochondrial DNA
Authors: Tay Stacey K. H. , Shanske Sara , Crowe Carol , Shanske Alan , Schafer Irwin , Pancrudo Jacklyn , Jiesheng Lu  , Bonilla Eduardo , DiMauro Salvatore
Published: June 2007

The majority of patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) have the A3243G point mutation. The much rarer T3271C mutation has been reported predominantly in Japanese subjects. Our objective was to better define the clinical phenotype and mutation load in patients with MELAS and the T3271C mutation in mitochondrial DNA. We present clinical and molecular genetic data in two pedigrees with the T3271C mutation. The age at onset was 8 years in one proband and 14 years in the other. Both patients had migrainelike headache, seizures, and strokelike episodes. Mutation loads were quantified in multiple tissues from the patients and from family members by polymerase chain reaction—restriction fragment length polymorphism analysis. The symptoms in both probands were typical of MELAS, and, contrary to previous reports, onset was early. Hearing loss was less common than in typical MELAS, and ragged red fibers were absent. The proportion of mutant genomes was consistently and markedly greater in DNA from urinary sediment than from blood. In the mother of one proband, mutant genomes were detected only in DNA from hair follicles and cheek mucosa. The phenotype of patients with the T3271C mutation might not be as distinct as that of the A3243G mutation, as previously described. Our data also suggest that urine is a better source of DNA than blood for diagnosis and that multiple tissues should be studied in maternal relatives, especially when the mutation cannot be detected in blood. ( J Child Neurol 2005;20:142—146).
Topical Review: Neuronal Migration in Cortical Development
Authors: Kanatani Shigeaki , Tabata Hidenori , Nakajima Kazunori
Published: June 2007

Cortical formation in the developing brain is a highly complicated process involving neuronal production (through symmetric or asymmetric cell division) interaction of radial glia with neuronal migration, and multiple modes of neuronal migration. It has been convincingly demonstrated by numerous studies that radial glial cells are neural stem cells. However, the processes by which neurons arise from radial glia and migrate to their final destinations in vivo are not yet fully understood. Recent studies using time-lapse imaging of neuronal migration are giving investigators an increasingly more detailed understanding of the mitotic behavior of radial glia and the migrating behavior of their daughter cells. In this review, we describe recent progress in elucidating neuronal migration in brain formation and how neuronal migration is disturbed by mutations in genes that control this process. ( J Child Neurol 2005;20:274—279).
Topical Review: Cortical Malformation and Pediatric Epilepsy: A Molecular Genetic Approach
Authors: Mochida Ganeshwaran H.
Published: June 2007

Genetic malformations of the cerebral cortex are important causes of neurologic morbidity in children because they are often associated with developmental delay, motor disturbances (cerebral palsy), and epilepsy. Primary autosomal recessive microcephaly is a cortical malformation with a low incidence of epilepsy. One of its causative genes, ASPM, might play an important role in regulating proliferation of neuronal progenitor cells. Mutations in ASPM do not seem to affect later stages of cortical development, such as neuronal migration, and this might be responsible for the low epileptogenicity of this malformation. ASPM might also have played an important role in the evolutionary expansion of the human brain. Bilateral frontoparietal polymicrogyria, on the other hand, is a highly epileptogenic malformation. Its causative gene, GPR56 , is also expressed in the neurogenic regions of the cortex, but its primary function might be in the determination of cell fate and/or cortical patterning. Further studies of these genes will likely lead to a better understanding of human brain development and epilepsy. ( J Child Neurol 2005;20:300—303).
Topical Review: Schizencephaly: Clinical Spectrum, Epilepsy, and Pathogenesis
Authors: Granata Tiziana , Freri Elena , Caccia Claudio , Setola Veronica , Taroni Franco , Battaglia Giorgio
Published: June 2007

After almost 60 years since the original description, we have reviewed the results of the more recent studies on schizencephaly in an attempt to delineate its imaging and clinical spectra of presentation and to point out the still unsettled controversies on its pathogenesis. The clinical picture is mainly based on the presence of motor deficits and mental retardation, but the severity of the clinical picture is extremely variable, mainly related to the size and location of the clefts and to the presence of associated cerebral malformations. By contrast, the outcome of epilepsy, which is present in about half of the cases and drug resistant in a third, is not strictly related to the severity of the malformation. Some clinical and functional magnetic resonance imaging studies have suggested that, beside the features of the anatomic damage, the functional reorganization of a malformed and unaffected cortex is most likely crucial in determining the clinical outcome. Review of the genetic studies and the more recent personal data suggests that the role of the EMX2 gene in schizencephaly, if any, is restricted to a minority of cases, leaving the etiopathogenesis of this brain malformation still a matter of study and debate. ( J Child Neurol 2005;20:313—318).
Topical Review: Intractable Seizures in Tuberous Sclerosis Complex: From Molecular Pathogenesis to the Rationale for Treatment
Authors: Curatolo Paolo , Bombardieri Roberta , Verdecchia Magda , Seri Stefano
Published: June 2007

Tuberous sclerosis complex is a multisystem autosomal dominant genetic disorder resulting from mutations in one of two genes, TSC1 and TSC2. Pathologically, tuberous sclerosis complex is characterized by abnormal cellular differentiation and proliferation, as well as abnormal neuronal migration. Epilepsy occurs in about 90% of patients, with onset frequently in the first year of life. In a sizable proportion of individuals, seizures tend to be refractory to antiepileptic drug treatment. This article reviews the progress in understanding drug-resistant seizures in tuberous sclerosis complex, from molecular pathogenesis to the pathophysiologic mechanisms of epileptogenesis, and the rationale for appropriate medical and surgical treatment. ( J Child Neurol 2005;20:318—325).
Molecular Pathogenesis of Focal Cortical Dysplasia and Hemimegalencephaly
Authors: Crino Peter B.
Published: June 2007

My laboratory recently demonstrated that there is selective expression of phosphoribosomal S6 protein in balloon cells in focal cortical dysplasia and hemimegalencephaly but no expression of the upstream kinase, phospho-p70S6 kinase. Two proteins activated by phospho-p70S6 kinase, phospho-STAT3 and phospho-4EBP1, were not detected in balloon cells. Using complementary DNA arrays in hemimegalencephaly specimens, we found increased expression of cyclin D1 and c-myc messenger ribonucleic acids (RNAs). Expression of cyclin D1 and c-myc genes is transcriptionally activated by βcatenin. Western analysis demonstrated increased levels of nonphosphorylated β-catenin in hemimegalencephalic cortex. Reduced levels of Ser33, Ser37, and Thr41 phospho-β-catenin, sites known to be phosphorylated by glycogen synthase kinase 3 and to be essential for β-catenin inactivation, were detected in hemimegalencephaly. Enhanced transcription of cyclin D1 and c-myc messenger RNAs, increased transcriptionally active β-catenin, and decreased Ser33/Ser37/Thr41 phospho-β-catenin suggest activation of the Wnt-1/β-catenin cascade in hemimegalencephaly, which can lead to aberrant cell proliferation and hemispheric enlargement during brain development. Enhanced activation of phospho-S6 and β-catenin suggests two converging cell pathways that can be pivotal in the pathogenesis of focal cortical dysplasia and hemimegalencephaly. ( J Child Neurol 2005;20:330—336).
Clinical Aspects of Hemimegalencephaly by Means of a Nationwide Survey
Authors: Sasaki Masayuki , Hashimoto Toshiaki , Furushima Wakana , Okada Mari , Kinoshita Satoru , Fujikawa Yoshinao , Sugai Kenji
Published: June 2007

We surveyed Japanese patients with hemimegalencephaly by means of a questionnaire. Clinical findings, including intellectual and motor function levels and epileptic symptoms, were investigated. All 44 patients (28 males and 16 females) with hemimegalencephaly were sporadic. Sixteen patients had underlying neurocutaneous syndromes. The number of patients with right-sided hemimegalencephaly ( n = 29) was almost twice that of patients with left-sided hemimegalencephaly ( n = 15). Forty-one patients had mental retardation and hemiparesis and 14 patients were bedridden. All patients had epileptic seizures, which first appeared within a month in 18 cases and within 6 months in 11 cases. In 42 patients, magnetic resonance imaging revealed both cortical and white-matter abnormalities in the affected hemisphere. Antiepileptic drugs were not very effective. Fifteen patients were surgically treated. Eleven patients underwent functional hemispherectomy, which resulted in fairly good seizure control and improved development. There is a correlation between the onset of epilepsy and the degree of clinical severity of motor deficit and intellectual level. Neither underlying disorders nor laterality of the affected side was related to the degree of clinical severity. ( J Child Neurol 2005;20:337—341).
Pathologic Features of Dysplasia and Accompanying Alterations Observed in Surgical Specimens From Patients With Intractable Epilepsy
Authors: Kakita Akiyoshi , Kameyama Shigeki , Hayashi Shintaro , Masuda Hiroshi , Takahashi Hitoshi
Published: June 2007

Malformations caused by abnormalities of cortical development, or cortical dysplasias, were examined in surgical specimens from 108 patients with medically intractable epilepsy to determine the scope of histopathologic changes. The relevance of the clinical findings was also evaluated. Various types and degrees of dysplastic features were observed in various combinations, including architectural abnormalities, an increased number of neurons in the molecular layer and/or cortical layer II, neuronal clustering, an increased number of satellite oligodendrocytes, abnormal gyration, single and/or aggregates of heterotopic neurons in the white matter, and the appearance of cytologically abnormal cells, such as giant or dysmorphic neurons and balloon cells. In the temporal lobe specimens, microdysgenesis (corresponding to mild malformations caused by abnormalities of cortical development and type IA/B focal cortical dysplasias) was more frequently observed than Taylor-type focal cortical dysplasia (type IIA/B), whereas in the frontal lobe specimens, the frequency of occurrence of both types was even. The ages at seizure onset and surgery of patients with the latter type were significantly lower than those of patients with the former. On the other hand, prominent astrocytosis in the cortex and white matter was evident in all cases, and many corpora amylacea and neurofibrillary tangle—like inclusions were observed in a subset of cases. An ultrastructural investigation revealed dilatation of the postsynaptic dendritic spines and shafts in the cortex and features indicating the occurrence in the white matter of demyelination followed by remyelination. Thus, with regard to the epileptogenic lesions, although dysplastic changes constitute the pathogenetic basis, the overlapping subsequent degenerative processes involving synapses, dendrites, and axons might contribute to the development of epileptogenic processes. Astrocytes might also actively participate in the development of the pathogenesis of epilepsy. ( J Child Neurol 2005;20:341—350).
Developmental and Functional Outcomes at School Age of Preschool Children With Global Developmental Delay
Authors: Shevell Michael , Majnemer Annette , Platt Robert W. , Webster Richard , Birnbaum Rena
Published: June 2007

The later developmental trajectory of young children diagnosed early with global developmental delay was determined. Using a prospective study, preschool children diagnosed with global developmental delay were systematically reassessed during the early school years with standardized developmental and functional outcome measures (Battelle Developmental Inventory and Vineland Adaptive Behavior Scale). Of an original cohort of 99 children assessed and diagnosed at a mean age of 3.4 ± 1.1 years, 48 were reassessed at a mean age of 7.3 ± 0.9 years. Group performance on the Battelle Developmental Inventory overall was 66.4 ± 4.3 (mean 100 ± 15). Between 75% and 100% of the cohort performed at least 1.5 SD below the normative mean on the individual domains of the Battelle Developmental Inventory. Similarly, the group mean on the Vineland Adaptive Behavior Scale overall was 63.5 ± 20.8 (mean 100 ± 15), with between 61% and 76% of the cohort scoring more than 1.5 SD below the mean on each of the domains. Univariate and multivariate analyses on potential predictor variables identified a lack of an underlying etiology as predictive of poorer performance on the Battelle Developmental Inventory fine motor and motor domains and increasing severity of initial delay as predictive of poorer performance on the Vineland Adaptive Behavior Scale communication domain and overall score. Similarly, maternal employment and paternal postsecondary education improved Vineland Adaptive Behavior Scale communication scores, whereas paternal postsecondary education alone predicted better socialization and total scores on the Vineland Adaptive Behavior Scale. Children with early global developmental delay demonstrate persistent and consistently poor performance across all developmental and functional domains. Few variables are apparent at intake to predict later performance. ( J Child Neurol 2005;20:648—654).
Efficacy and Tolerability of Topiramate in Children Younger Than 2 Years Old
Authors: Valencia Ignacio , Fons Carmen , Kothare Sanjeev V. , Khurana Divya S. , Yum Sabrina , Hardison H. Huntley , Legido Agustin
Published: June 2007

To evaluate the efficacy and tolerability of topiramate in children with epilepsy younger than 2 years of age, we retrospectively reviewed the records of patients treated at our institution between 2001 and 2003. Thirteen children ages 5 to 23 months, five boys and eight girls, were identified. Seizure types were partial (five), generalized tonic-clonic (three), myoclonic (one), and infantile spasms (four). The mean age at seizure onset was 9.7 months. Topiramate was started at a mean age of 11.4 months (4—23 months). The number of antiepileptic drugs prior to topiramate therapy ranged from zero to four. One patient had been on the ketogenic diet. Topiramate was used as monotherapy in seven children and as poly-therapy in six children. Mean follow-up was 14 months. The mean dose of topiramate was 8.8 mg/kg/day (2.5—18 mg/kg/day). The degree of seizure reduction was as follows: > 75% in five (38.5%) children, 50% to 75% in three (23%) children, and 0 to 25% in five (38.5%) children. Three of four (75%) patients with infantile spasms had a > 75% reduction in seizures. Adverse effects occurred in two children, including lethargy, hyperthermia, and anorexia. In children younger than 2 years of age, for whom the antiepileptic drug armamentarium is limited, topiramate appears to be an efficacious and safe therapeutic alternative for a variety of seizure types. ( J Child Neurol 2005;20:667—670).
Intrapartum Complications Associated With Malformations of Cortical Development
Authors: Montenegro Maria Augusta , Cendes Fernando , Saito Helena , Serra Jéssica G. , Lopes Camila F. , Piovesana Ana Maria S. , Milanez Helaine , Guerreiro Marilisa M.
Published: June 2007

Birth asphyxia can be an early sign of cerebral palsy, the effect of an antenatal anomaly rather than its cause. The objective of this study was to evaluate the occurrence of intrapartum complications in patients with malformation of cortical development. The data were retrospectively assessed and compared with a control group of children with idiopathic epilepsy. Intrapartum complications were reported in 22 (31.5%) patients, as opposed to only 2 in the control group ( p<0.001). Patients with cortical malformations frequently present intrapartum complications, which could lead to the misdiagnosis of hypoxic-ischemic encephalopathy. ( J Child Neurol 2005;20:675—678).