bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurofibromatosis 2 in the Pediatric Population
Authors: Nunes Fabio , MacCollin Mia
Published: June 2007

Neurofibromatosis 2 is a severe autosomal dominant disorder characterized by the occurrence of bilateral vestibular schwannomas and other benign tumors of the nervous system. Excellent natural history studies exist for adults with neurofibromatosis 2, but limited outcome data are available for children with neurofibromatosis 2. In this study, we present clinical data on 12 patients with neurofibromatosis 2 and age at diagnosis before 18 years. Full record review included surgical reports, pathology reports, and imaging studies; all patients were personally examined by a single author. One third of the patients presented with hearing impairment and another third presented with other cranial nerve dysfunction. Tumor load was extensive, including cranial meningiomas in 75%, cranial schwannomas other than vestibular schwannomas in 83%, and spinal cord tumors in 75%. Family history was present in two thirds of the patients. Surgical removal of vestibular schwannomas was performed in 58%; none had full preservation of hearing postsurgery. Functionally, 75% of children had hearing loss, 83% had visual impairment, 25% had abnormal ambulation, and 25% were performing below grade level. In conclusion, increased clinical awareness, better imaging techniques, and molecular diagnostics have made pediatric diagnosis of neurofibromatosis 2 feasible, but outcomes appear to be worse than in adult patients. Further work is needed to determine optimal management of pediatric neurofibromatosis 2. ( J Child Neurol 2003;18:718—724).
Parental Satisfaction With Sumatriptan Nasal Spray in Childhood Migraine
Authors: Pakalnis Ann , Kring Donna , Paolicchi Juliann
Published: June 2007

Migraine headaches are a frequently encountered neurologic problem in children. The utility of the triptans has not been as clearly documented in this population, although it is well delineated in acute migraine attacks in adults. We conducted a retrospective chart review of our experience with using sumatriptan nasal spray in children aged 5 to 12 years from our headache clinic population with migraine headaches. The nasal spray formulation is used frequently in our clinic population with patients who have failed over-the-counter therapy with ibuprofen or acetaminophen. None of the triptans are approved by the US Food and Drug Administration for use in children or adolescents (12 years and older). One hundred of these patients were identified, and their parents or guardians completed a standardized questionnaire regarding their child's response to sumatriptan nasal spray in acute migraine. Fifty-seven of 100 families completed the questionnaire, and 44 of 57 families (77%) reported good to excellent relief of their child's migraine attacks with sumatriptan nasal spray. In our cohort of pediatric patients, sumatriptan nasal spray was effective and well tolerated when used for abortive therapy of acute migraine attacks. ( J Child Neurol 2003;18:772—775).
Epidemiology of Childhood Guillain-Barré Syndrome as a Cause of Acute Flaccid Paralysis in Honduras: 1989—1999
Authors: Molinero Marco R. , Varon Daniel , Holden Kenton R. , Sladky John T. , Molina Ida B. , Cleaves Francisco
Published: June 2007

The objective of this study was to investigate the incidence of acute flaccid paralysis in the pediatric population of Honduras over an 11-year period, determine what percentage of acute flaccid paralysis was Guillain-Barré syndrome, and identify the epidemiologic features of Guillain-Barré syndrome. There were 546 childhood cases of acute flaccid paralysis seen between January 1989 and December 1999 at the Hospital Escuela Materno-Infantil in Tegucigalpa, Honduras. Of these cases with acute flaccid paralysis, 394 (72.2%) were diagnosed with Guillain-Barré syndrome. Our incidence of Guillain-Barré syndrome in the Honduran pediatric population (1.37/100,000 per year) is higher than that shown in other studies. There was a significantly higher incidence of Guillain-Barré syndrome in younger children (ages 1—4 years), a significant preponderance of cases from rural areas, and a mild predominance in boys but a typical clinical presentation. The Honduran pediatric Guillain-Barré syndrome population had an increased mortality rate. Guillain-Barré syndrome has become the leading cause of childhood paralysis in Honduras. A better understanding of the population at highest risk and opportunities for earlier intervention with more effective therapeutic modalities may permit reducing the mortality among Honduran children who develop Guillain-Barré syndrome. ( J Child Neurol 2003; 18: 741—747).
Hemimegalencephaly: Part 2. Neuropathology Suggests a Disorder of Cellular Lineage
Authors: Flores-Sarnat Laura , Sarnat Harvey B. , Dávila-Gutiérrez Guillermo , Álvarez Antonio
Published: June 2007

Cerebral tissue from hemispherectomy in three children (two 4-month-old girls and one 4-year-old boy) with hemimegalencephaly was studied using histochemical and immunocytochemical markers of neuronal and glial maturation and identity. Histologic abnormalities of cellular growth and cytomorphology, including “balloon cells,” were present in both gray and white matter, in addition to disorganized tissue architecture. Cells in the mitotic cycle were absent. Many hypertrophic, atypical cells with enlarged processes exhibited mixed or ambiguous lineage, with immunoreactivity for both glial (glial fibrillary acidic protein [GFAP]; S-100β) and neuronal proteins (microtubule-associated protein 2 [MAP2], neuronal nuclear antigen, chromogranin A, and neurofilament protein [NFP]). Strong vimentin reactivity was present in neurons, as well as glial cells and cells of mixed lineage, suggesting incomplete maturation. Synaptophysin-reactive axons terminated on a minority of balloon cells and on most heterotopic single neurons in white matter, confirmed by electron microscopy, demonstrating that single heterotopic neurons are not synaptically “isolated,” as they may appear; thus, they are capable of contributing to epilepsy. Oligodendrocytes are the least affected cells, at least in some cases. The findings are reminiscent of the hamartomas of tuberous sclerosis. We conclude that hemimegalencephaly is a primary disorder of neuroepithelial lineage and cellular growth. A migratory disturbance contributes to disorderly tissue architecture but is secondary. No pathologic difference is detected between isolated and syndromic forms of hemimegalencephaly. ( J Child Neurol 2003;18:776—785).
Poor Outcome for Neonatal-Type Nonketotic Hyperglycinemia Treated With High-Dose Sodium Benzoate and Dextromethorphan
Authors: Chien Yin-Hsiu , Hsu Chia-Chi , Huang Aichu , Chou Shi-Ping , Lu Frank-Li , Lee Wang-Tso , Hwu Wuh-Liang
Published: June 2007

Neonatal-type nonketotic hyperglycinemia treatment remains unsatisfactory, even if started early. A review of six patients who underwent treatment for neonatal-type nonketotic hyperglycinemia in our hospital is presented. All patients were treated with a standardized protocol. Medical histories were retrieved from case notes. All six patients had elevated cerebrospinal fluid plasma glycine levels initially. All but one had received sodium benzoate and dextromethorphan from 1 month of age. All suffered from intractable seizures and severe mental retardation, and only two patients remain alive. One patient died at 5 days of age. No resuscitation was attempted in accordance with the family's wish after genetic counseling. The prognosis of neonatal nonketotic hyperglycinemia remains poor with current treatment. Genetic counseling helps parents cope with this devastating genetic disease. ( J Child Neurol 2004;19:39—42).
Wilms' Tumor in a Case With Möbius' Syndrome Associated With Arthrogryposis and Mega Cisterna Magna
Authors: Yaris Nilgun , Aynaci F. Müjgan , Kalyoncu Mukaddes , Ödemiş Ender , Okten Aysenur
Published: June 2007

Möbius' syndrome is a rare congenital anomaly characterized by paralysis of the 7th and other cranial nerves and musculoskeletal abnormalities. We report a patient with Möbius' syndrome associated with arthrogryposis and mega cisterna magna in addition to the classic components of this syndrome. The case is interesting because she developed Wilms' tumor at 21 months of age. To our knowledge, this is the first case of this association reported in the literature. ( J Child Neurol 2004;19:67—70).
Radial Nerve Palsy Owing to Localized Hypertrophic Neuropathy (Intraneural Perineurioma) in Early Childhood
Authors: Isaac Sherif , Athanasou Nicholas A. , Pike Michael , Burge Peter D.
Published: June 2007

Localized hypertrophic neuropathy, also termed intraneural perineurioma, is a rare disorder of unknown etiology that produces a slowly progressive painless focal lesion of a peripheral nerve. It is characterized histologically by concentric whorls (“onion bulbs”) of epithelial membrane antigen-reactive, S-100 protein-negative perineurial cells surrounding nerve fibers. We report a radial nerve palsy in a child aged 2 years in whom the diagnosis of localized hypertrophic neuropathy was made by biopsy. Resection of the affected nerve segment and sural nerve grafting produced no useful recovery after 3 years, probably because of the long duration of denervation. When this mononeuropathy presents in early childhood, uncertainty over the time of onset can lead to difficulty in distinguishing this potentially treatable lesion from congenital and other causes of nerve palsy. ( J Child Neurol 2004;19:71—75).
Pyridoxine-Dependent Seizures: Magnetic Resonance Spectroscopy Findings
Authors: Alkan Alpay , Kutlu Ramazan , Aslan Mehmet , Sigirci Ahmet , Orkan Ismet , Yakinci Cengiz
Published: June 2007

Pyridoxine-dependent seizures are an extremely rare genetic disorder. Early diagnosis and treatment are important for the prevention of permanent brain damage. Elevated levels of glutamate and decreased levels of γ-aminobutyric acid (GABA) in the frontal and parietal cortices are among the characteristic features of this disorder. These metabolic abnormalities eventually lead to seizures and neuronal loss. In this case report, we present magnetic resonance spectroscopy findings of a 9-year-old girl with pyridoxine-dependent seizures with mental retardation. The N-acetyl-aspartate-to-creatine ratio was found to be decreased in the frontal and parieto-occipital cortices, which could indicate neuronal loss. Magnetic resonance spectroscopy could be a useful tool in the neuroimaging evaluation for assessment of parenchymal changes despite a normal-appearing brain magnetic resonance image in patients with pyridoxine-dependent seizures. ( J Child Neurol 2004;19:75—78).
Cognitive Deficits in Children With Sickle Cell Disease
Authors: Steen R. Grant , Fineberg-Buchner Charlotte , Hankins Gisele , Weiss Larry , Prifitera Aurelio , Mulhern Raymond K.
Published: June 2007

We tested a hypothesis that children with sickle cell disease who are completely normal by magnetic resonance imaging can still be cognitively impaired, as predicted by a model of diffuse brain injury. Fifty-four patients with hemoglobin SS (average age 10.9 years ± 2.9 years SD) were examined with the Wechsler Intelligence Scale for Children-III (WISC-III) and were randomly matched by age, race, and gender with healthy children from the Wechsler normative database. Patients were also imaged at 1.5 Tesla with standard imaging sequences. Among 30 patients who were normal by magnetic resonance imaging, there were substantial deficits in Wechsler Full-Scale IQ, Verbal IQ, and Performance IQ (all P < .01) compared with African-American controls. The patient Wechsler Full-Scale IQ was 12.9 points lower than that of controls and decreased as a function of age (probability = .014). The findings suggest that there is diffuse brain injury in patients and that patient deficits increase with age. ( J Child Neurol 2005;20:102—107).
ThOMAs: The Other Means of Assessment
Authors: Williams Andrew N. , Debelle Geoffrey D. , Davies Paul , Barrett Tim G.
Published: June 2007

We describe a pilot study to investigate whether drawing “Thomas the Tank Engine” could be as effective a measure of developmental progress as the Goodenough-Harris Draw A Man test against the ThOMAs test (The Other Means of Assessment), with internal validation. The study included 95 children aged between 3 and 11 years of age, including a subgroup of 13 children with registered special needs from community and general pediatric clinics within Birmingham, UK, as a means of validation. There was no significant evidence that ThOMAS was either culturally or sex biased. Using regression analysis, nine items were found to correlate highly with actual age, and their total score gave a correlation of 0.563 with age. Adding further items did not increase this. After being converted into age-standardized scores, ThOMAS was as sensitive and specific as the Draw A Man test, and more so above a defined age-standardized threshold. This pilot study suggests that drawing Thomas the Tank Engine would appear to be as sensitive and specific a means of identifying children with special needs as the Goodenough-Harris Draw A Man test. The relatively small sample size means that further research is necessary to further define the age standardizations and to refine the ThOMAs test. ( J Child Neurol 2005;20:108—111).
Add-On Melatonin Improves Sleep Behavior in Children With Epilepsy: Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Gupta Madhur , Aneja Satinder , Kohli Kamlesh
Published: June 2007

This double-blind, randomized, placebo-controlled study in epileptic children, aged 3 to 12 years, evaluated the effect of add-on melatonin on the sleep behavior of these children on sodium valproate monotherapy using a parental questionnaire. Of the 31 patients, 16 randomly received add-on melatonin, whereas 15 received add-on placebo. The questionnaire showed good internal consistency in our patient population (Cronbach's α = .83). The percentage decrease in the median total sleep score was 24.4 (range 0.0—34.9) in the valproate + melatonin group compared with 14.0 (range —2.2—18.8) in the valproate + placebo group, the difference being statistically significant ( P < .05). The median percentage decrease in the parasomnias score was 60 (range 0.0—70.8) in the valproate + melatonin group compared with 36.4 (range 0.0—63.2) in the valproate + placebo group, the difference being statistically significant ( P < .05). There was no significant difference between the percentage decrease in the daytime drowsiness scores and sleep fragmentation scores. Parent-child interaction subscale scores were not significantly different between age groups. The age at onset of seizures and the type of seizures did not correlate significantly to the total sleep scores. Given that sleep problems are known to complicate epilepsy, add-on melatonin, which has a wide safety window, can be of promise in the pharmacotherapy of pediatric epilepsy. ( J Child Neurol 2005;20:112—115).
Childhood Acute Disseminated Encephalomyelitis Presenting as Foix-Chavany-Marie Syndrome
Authors: RamachandranNair Rajesh , Manoj P. , Rafeequ Mohammed , Girija A.S.
Published: June 2007

A 10-year-old boy presented with anarthria and bilateral central faciolinguovelopharyngeomasticatory paralysis with “automatic voluntary dissociation” suggestive of Foix-Chavany-Marie syndrome or anterior opercular syndrome following a nonspecific upper respiratory infection. Brain magnetic resonance imaging revealed bilateral subcortical perisylvian demyelination in addition to multiple subcortical white-matter demyelination. The clinicoradiologic picture suggested acute disseminated encephalomyelitis. The child recovered completely following intravenous methylprednisolone and intravenous immunoglobulin therapy. This is the first report of anterior opercular syndrome in childhood acute disseminated encephalomyelitis. ( J Child Neurol 2004;19:163—165).
Paroxysmal Tonic Upgaze and Partial Tetrasomy of Chromosome 15: A Novel Genetic Association
Authors: Joseph Kevin , Avallone John , Difazio Marc
Published: June 2007

Paroxysmal tonic upgaze of childhood is an eye movement abnormality characterized by periodic episodes of conjugate upward eye deviation. Although the spectrum of paroxysmal tonic upgaze has broadened considerably, a specific pathophysiology has not been elucidated. We report an infant with paroxysmal tonic upgaze who presented to his pediatrician with associated hypotonia and gross motor delay. High-resolution chromosome analysis demonstrated a supernumerary dicentric bisatellited marker chromosome. Analysis revealed partial tetrasomy of 15q. Given the significant amount of euchromatin demonstrated, it is likely that the chromosomal abnormalities are causative for the constellation of manifestations in this patient. To date, a specific genetic abnormality has not been associated with paroxysmal tonic upgaze. The finding of a genetic association with paroxysmal tonic upgaze might help characterize the substrate for ophthalmologic manifestations. Further study in this chromosomal region in patients with paroxysmal tonic upgaze is warranted. ( J Child Neurol 2005;20:165—168).
Postural Headache in a Child With Marfan Syndrome
Authors: Rosser Tena , Finkel Julie , Vezina Gilbert , Majd Massoud
Published: June 2007

The case of a 10-year-old female with Marfan syndrome and postural headache secondary to spontaneous intracranial hypotension is described. The patient was found to have multiple dural ectasias and a cerebrospinal fluid leak at the left cervicothoracic junction. Her presentation, diagnostic work-up, and management are reviewed, and the relevant literature is discussed. Spontaneous intracranial hypotension secondary to cerebrospinal fluid leaks from dural ectasia should be recognized as a potential complication in children with Marfan syndrome and other connective tissue diseases. ( J Child Neurol 2005;20:153—155).
Severe Epilepsy and Pachygyria Associated With Peculiar Facial Traits Characterize Fryns-Aftimos Syndrome
Authors: Valente Kette D. , de Vincentiis Silvia , Thomé-Souza Sigride , Valente Marcelo
Published: June 2007

We describe an 18-year-old boy with a frontofacial syndrome. The presence of severe epilepsy led to a neuroimaging investigation, which revealed a diffuse pachygyric (normal thickness and simplified folding) cortex that was bilateral and affected all supra-tentorial regions, sparing the medial and inferior aspects of the frontal lobe plus the posterior occipital region. In addition, an unusual skull base presentation with small posterior fossa, narrowed foramen magnum, and low torcular and tentorial insertions was documented. Dysmorphic ventricles and enlarged cavi of the septi pellucidum, vergae, and velum interpositum were also noted. This case shares many similarities with two patients formerly described by Fryns and Aftimos, who were previously classified as having mental retardation and multiple congenital anomalies syndrome. The existence of a new case corroborates the idea of a distinct condition with particular characteristic dysmorphic facial features and the presence of a specific malformation of cortical development associated with severe epilepsy. We believe that epilepsy and pachygyria play a central role in distinguishing this syndrome from others classified as frontofacial or cerebrofrontofacial syndromes, and we propose the term “Fryns-Aftimos syndrome” to name it. ( J Child Neurol 2005;20:160—163).
Topical Review: Neuronal Migration in Developmental Disorders
Authors: McManus Matthew F. , Golden Jeffrey A.
Published: June 2007

Normal central nervous system development is dependent on extensive cell migration. Cells born in the proliferative ventricular zone migrate radially along specialized glial processes to their final locations. In contrast, most inhibitory interneurons found in the adult mammalian cerebral cortex and some other structures migrate along a nonradial pathway and on substrates only recently defined. Defects in radial cell migration have been implicated in several distinct human syndromes in which patients often present with epilepsy and mental retardation and have characteristic cerebral abnormalities. The identification of several genes responsible for human neural cell migration defects has led to a better understanding of the cellular and molecular interactions necessary for normal migration and the pathogenesis of these disorders. The prototypic cell migration disorder in humans is type I lissencephaly. Although type 1 lissencephaly is clearly a defect in radial cell migration, recent data from two model systems ( Lis1 and ARX mutant mice) indicate that a defect in non—radial cell migration also exists. Thus, the result of a LIS1 mutation appears to have broader implications than a radial cell migration defect alone. Furthermore, it is likely that the observed defect in non—radial cell migration contributes to the clinical phenotype observed in these patients. Herein we discuss the role of normal non—radial cell migration in cortical development, as well as how perturbations in both radial and nonradial migration result in developmental anomalies. ( J Child Neurol 2005;20:280—286).
Topical Review: Genotype-Phenotype Correlation in Lissencephaly and Subcortical Band Heterotopia: The Key Questions Answered
Authors: Leventer Richard Jacob
Published: June 2007

Lissencephaly and subcortical band heterotopia are closely related cortical malformations and are true disorders of neuronal migration. The genetic basis of approximately 70% of classic lissencephaly and 80% of typical subcortical band heterotopia is known. Most are due to abnormalities within the LIS1 or DCX genes, with abnormalities ranging from single basepair substitutions to contiguous gene deletions. Understanding the genetic basis of these disorders has led to the elucidation of the molecular and developmental mechanisms that are adversely affected. There is a robust correlation between many of the clinical aspects of lissencephaly or subcortical band heterotopia and the type and location of mutations in the affected gene. Using this knowledge, the clinician can predict with some accuracy which gene is likely to be affected based on the clinical and imaging features. This review answers some of the key questions regarding the genotype-phenotype correlation for lissencephaly and subcortical band heterotopia. ( J Child Neurol 2005;20:307—312).
Clinical Application of Experimental Cortical Dysplasia in Rats
Authors: Tanaka Tatsuya , Tsuda Hiroshige , Hashizume Kiyotaka , Sakurai Juro , Hodozuka Akira , Nakai Hirofumi
Published: June 2007

This report details clinical and experimental studies of focal cortical dysplasia. The first part deals with 14 surgical cases of children with intractable epilepsy. At surgery, intraoperative electrocorticography was performed to localize the epileptic foci under neuroleptanalgesia. Thirteen patients showed epileptiform discharges on this preresection electrocorticography. All foci in noneloquent areas were resected. Patients who had undergone total lesionectomy with complete focus resection showed the most favorable postoperative results. However, the positive correlation between the intraoperative electrocorticographic findings and the pathologic classification of cortical dysplasia was not found in the present study. Nine patients have been seizure free with reduced medication and two patients have achieved worthwhile improvement. We conclude that intraoperative electrocorticography can improve the surgical outcome for intractable epilepsy by localizing epileptic foci for resection. The second part describes a kainic acid—induced experimental model of focal cortical dysplasia, which demonstrated not only the epileptic properties of the dysplasia but also the perilesional epileptogenicity. The findings supported the surgical results for the patients with focal cortical dysplasia. ( J Child Neurol 2005;20:351—356).
Neurophysiologic Findings of Neuronal Migration Disorders: Intrinsic Epileptogenicity of Focal Cortical Dysplasia on Electroencephalography, Electrocorticography, and Magnetoencephalography
Authors: Otsubo Hiroshi , Iida Koji , Oishi Makoto , Okuda Chiyuki , Ochi Ayako , Pang Elizabeth , Weiss Shelly K. , Rutka James T. , Chuang Sylvester H. , Snead O. Carter
Published: June 2007

We define specific neurophysiologic characteristics for focal cortical dysplasia, a neuronal migration disorder. We reviewed data from published reports and our patients with focal cortical dysplasia. Our patients underwent preoperative scalp video-electroencephalography (EEG), magnetic resonance imaging (MRI), magnetoencephalography, and intraoperative or extraoperative electrocorticography monitoring. Scalp EEG showed trains of rhythmic epileptiform spike or sharp waves. Positive spikes correlated with early seizure onset, MRI lesion around the rolandic fissure, hemiparesis, and a less favorable outcome. Interictal electrocorticography showed continuous epileptogenic discharges: repetitive electrographic seizures and bursting discharges or continuous or quasicontinuous rhythmic spiking. Ictal electrocorticography showed paroxysmal fast and/or repetitive spiking. Magnetoencephalography showed clustered spike sources within and extending from the lesion. Cortical stimulation gave more frequent, lower-threshold afterdischarges and higher-threshold primary motor function. Focal cortical dysplasias are highly and intrinsically epileptogenic. For surgical seizure control, EEG, electrocorticography, and magnetoencephalography must delineate the intrinsic epileptogenic zone within and extending from the focal cortical dysplasia identified by MRI. ( J Child Neurol 2005;20:357—363).
Certification in Child Neurology: New Directions for the Twenty-First Century
Authors: Percy K. , Juul Dorthea , Scheiber Stephen C. , Janda Pat
Published: June 2007

The American Board of Psychiatry and Neurology was formed in 1934, and the first certifying examination was administered in 1935. It was not until 1969 that the American Board of Psychiatry and Neurology began conducting certifying examinations in child neurology. Since then, 10 child neurologists have served as American Board of Psychiatry and Neurology directors and nearly 1500 child neurologists have been certified, more than 200 of whom have also attained certification in the subspecialties of clinical neurophysiology, neurodevelopmental disabilities, and pain medicine. This article describes the evolution of the certification process as the Board has endeavored to use the best testing methodologies to fulfill its commitment to the public and to its constituents in psychiatry and neurology. Training pathways in child neurology are also reviewed as they have evolved in response to evident staff shortages and to promote entry into academic careers. ( J Child Neurol 2005;20:644—647).
Ante- and Perinatal Factors for Cerebral Palsy: Case-Control Study in Estonia
Authors: Stelmach Tiina , Pisarev Heti , Talvik Tiina
Published: June 2007

Establishing consistency between cerebral palsy registries in reporting of new cases enables more effective collaboration in terms of researching predisposing factors. To identify antenatal and intrapartum risk factors for cerebral palsy in the Estonian population, we undertook a matched case-control study of 153 children with cerebral palsy, ascertained from a population-based survey. One hundred two maternal, antenatal, and intrapartum variables were initially retrieved from medical records. Main outcome measures were the odds ratio estimates of relative risk of cerebral palsy. As a result of the study, and considering the whole spectrum of severity, the relevant risk factors during pregnancy were bleeding after 20 weeks, anemia in the second half of pregnancy, pregnancy-induced hypertension in the second half of pregnancy, and preeclampsia. The most important intrapartum factors were premature birth, placental abruption, an acute hypoxic event during delivery, and any fetal presentation other than vertex. Predisposing factors related to neonatal condition were an Apgar score ≤ 7 at the first and fifth minutes of life, hypoxic-ischemic encephalopathy, and assisted ventilation. Our findings suggest that intrapartum factors, including those hypothetically realized through hypoxic-ischemic pathways, are not of low importance in the etiology of cerebral palsy. ( J Child Neurol 2005;20:654—661).
Factors Predicting the Efficacy of Botulinum Toxin-A Treatment of the Lower Limb in Children With Cerebral Palsy
Authors: Fazzi Elisa , Maraucci Ilaria , Torrielli Simona , Motta Francesco , Lanzi Giovanni
Published: June 2007

Botulinum toxin A is widely used for spasticity management in children with cerebral palsy, although outcomes are unpredictable. The aim of this study was to identify criteria for selecting patients most likely to benefit from botulinum toxin A treatment. Fifty-five subjects, aged 2.5 to 18 years, were recruited. The assessment covered measures of spasticity (Modified Ashworth Scale), function (using the Gross Motor Function Measure and the Physician's Rating Scale), selective motor control, static range of motion at the ankle with knee extended and flexed, range of motion of the knee flexors, central and peripheral vision, and cognitive ability. Outcomes at 3 months were compared with baseline values. All of the scales showed significant differences between pre- and postinjection values. Significantly increased Gross Motor Function Measure scores were found in children aged 48 months or under and in those able to walk with support. Greater improvements in selective motor control and Physician's Rating Scale were seen in those with a less severe pattern of paralysis, lower levels of impairment, the ability to walk (with or without support), normal visual acuity, and normal or borderline cognition. We identified factors that mark out patients as most likely to achieve functional gains: young age, hemiplegia or diplegia, slight to moderate disability, walking with support, normal or borderline cognition, and normal or borderline visual acuity. ( J Child Neurol 2005;20:661—666).
Unusual Clinical Presentations in Four Cases of Leigh Disease, Cytochrome C Oxidase Deficiency, and SURF1 Gene Mutations
Authors: Tay Stacey K.H. , Sacconi Sabrina , Ohran Akman H. , Morales Judith F. , Morales Augusto , De Vivo Darryl C. , Shanske Sara , Bonilla Eduardo , DiMauro Salvatore
Published: June 2007

Mutations in the SURF1 gene are the most frequent causes of Leigh disease with cytochrome c oxidase deficiency. We describe four children with novel SURF1 mutations and unusual features: three had prominent renal symptoms and one had ragged red fibers in the muscle biopsy. We identified five pathogenic mutations in SURF1: two mutations were novel, an in-frame nonsense mutation (834G→A) and an out-of-frame duplication (820-824dupTACAT). Although renal manifestations have not been described in association with SURF1 mutations, they can be part of the clinical presentation. Likewise, mitochondrial proliferation in muscle (with ragged red fibers) is most unusual in Leigh disease but might be part of an emerging phenotype. ( J Child Neurol 2005;20:670—674). for publication December 7, 2004.
Hallermann-Streiff Syndrome Associated With Complete Agenesis of the Corpus Callosum
Authors: Siğirci Ahmet , Alkan Alpay , Biçak Uğur , Yakinci Cengiz
Published: June 2007

Hallermann-Streiff syndrome is a rare clinical entity with unknown etiology characterized by a birdlike face, microphthalmia, a beaked nose, hypotrichosis, and proportional small stature. We present a 4-year-old boy in whom magnetic resonance imaging showed complete agenesis of the corpus callosum, which has not been presented in the literature. ( J Child Neurol 2005;20:691—693).
Focal Status Epilepticus as Atypical Presentation of Pyridoxine-Dependent Epilepsy
Authors: Yoshii Akira , Takeoka Masanori , Kelly Peter J. , Krishnamoorthy Kalpathy S.
Published: June 2007

Pyridoxine-dependent epilepsy usually presents in the neonatal period or even in utero, is refractory to antiepileptic medications, and is treatable with lifelong administration of pyridoxine. The seizures are typically generalized tonic-clonic, although myoclonic seizures or infantile spasms have been described. We report an infant who presented at 5 months of age with a right-sided clonic seizure with fever. Subsequently, she had recurrent right focal or generalized seizures despite sequential treatment with various antiepileptic medications. At 7 months, she was hospitalized with status epilepticus, which was finally controlled with pyridoxine. After she became seizure free, she continued to have a strong left arm preference with mild weakness of the right arm and delayed language skill. Eventually, she outgrew these symptoms. This case illustrates that pyridoxine-dependent epilepsy, although rare, must be included in the differential diagnosis of focal seizures, especially when the seizures are refractory to traditional antiepileptic drugs. ( J Child Neurol 2005;20:696—698).
Rett Syndrome: Pathogenesis, Diagnosis, Strategies, Therapies, and Future Research Directions
Authors: Deidrick Kathleen M. , Percy Alan K. , Schanen N. Carolyn , Mamounas Laura , Maria Bernard L.
Published: June 2007

Rett syndrome is a progressive neurodevelopmental disorder characterized by cognitive impairment, deficits in communication, stereotypic movements, and growth failure. On October 13, 2004, we held a symposium to determine how research findings enhance clinical practice for practitioners working with persons who have Rett syndrome and to identify the research needed to improve diagnostic accuracy and develop safe, effective therapies. Participants described diagnostic strategies, pathogenesis, therapies, and clinical trials and defined future research directions. This article summarizes their presentations and includes the verbatim edited transcript of question-and-answer sessions.
MeCP2 Dysfunction in Humans and Mice
Authors: Zoghbi Huda Y.
Published: June 2007

Rett syndrome is a leading cause of postnatal neurodevelopmental regression. Rett syndrome is caused by mutations in MECP2, the gene encoding methyl-CpG binding protein 2. In up to 96% of all classic cases, Rett syndrome cases are caused by mutations or deletions in MECP2. The phenotypic spectrum of MECP2 mutations is broad and includes mental retardation with or without seizures, Angelman syndrome—like phenotype, and autism. Mecp308/Y mice carry a truncating mutation and display many of the features seen in Rett syndrome. Social behavior abnormalities and impaired social interactions in Mecp308/Y mice suggest that MeCP2 plays a role in modulating the activity of genes and neurons important for social interactions. Mice that overexpress MeCP2 at twice the endogenous levels develop a progressive neurologic disorder, demonstrating that MeCP2 levels are tightly regulated and raising the possibility that duplications or gain-of-function mutations of MECP2 might underlie some cases of neurodevelopmental X-linked disorders. ( J Child Neurol 2005;20:736—740).
Rett Syndrome and Neuronal Development
Authors: Johnston Michael V. , Blue Mary E. , Naidu Sakkubai
Published: June 2007

The clinical signs of Rett syndrome, as well as neuropathology and brain imaging, suggest that the disorder disrupts neuronal circuits. Studies using receptor autoradiography demonstrate abnormalities in the density of excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) synaptic receptors in postmortem brain from young female subjects with Rett syndrome. MeCP2, the protein that is abnormal in most female individuals with Rett syndrome, is expressed predominantly in neurons and appears during development at the time of synapse formation. Studies of nasal epithelium from patients with Rett syndrome show that the maturation of olfactory receptor neurons is impeded prior to the time of synapse formation. Recent reports indicate that MeCP2 controls the expression of brain-derived neurotrophic factor and the DNA-binding homeobox protein Dlx5. Brain-derived neurotrophic factor enhances glutamate neurotransmission at excitatory synapses, whereas Dlx5 is expressed in most GABAergic neurons and stimulates the synthesis of GABA. Taken together, this information supports the hypothesis that Rett syndrome is a genetic disorder of synapse development, especially synapses that use glutamate and GABA as neurotransmitters. ( J Child Neurol 2005;20:759—763).
Does Genotype Predict Phenotype in Rett Syndrome?
Authors: Ham Andrea L. , Kumar Asmita , Deeter Rose , Schanen N. Carolyn
Published: June 2007

Mutations in the X-linked gene encoding the methyl-CpG binding protein MeCP2 are the primary cause of classic and atypical Rett syndrome and have recently been shown to contribute to other neurodevelopmental disorders of varying severity. To determine whether there are molecular correlates to the phenotypic heterogeneity, numerous groups have performed genotype-phenotype correlation studies. These studies have yielded conflicting results, in part because they used different criteria for determining severity and classifying mutations. Evolution of the phenotype with age and variable expressivity arising from individual variability in X-chromosome inactivation patterns are among other reasons the findings varied. Nonetheless, evidence of differences in the phenotypic consequences of specific types of mutations is emerging. This review analyzes the available literature and makes recommendations for future studies. ( J Child Neurol 2005;20:768—778).
Serial Headache Drawings by Children With Migraine: Correlation With Clinical Headache Status
Authors: Stafstrom Carl E. , Goldenholz Shira R. , Dulli Douglas A.
Published: June 2007

Children's artistic self-depictions of headache provide valuable insights into their experience of pain and aid in the diagnostic differentiation of headache types. In a previous study, we compared the clinical diagnosis (gold standard) and artistic diagnosis of headaches in 226 children. In approximately 90% of cases, the drawing predicted the clinical diagnosis of migraine versus nonmigraine headache correctly. In the present study, we explored whether headache drawings correlate with clinical improvement after treatment in children with migraine headaches followed longitudinally. Children seen in the Pediatric Neurology Clinic with the chief complaint of headache were asked to draw a picture of what their headache feels like. On subsequent clinic visits, children with the clinical diagnosis of migraine were asked to draw another picture depicting their current headache. The two drawings were compared to assess whether there was improvement; this “artistic response” was then correlated with the child's clinical status (ie, whether the headaches were improved clinically). One hundred eleven children (66 girls, 45 boys) participated in the study, with a mean interval of 5.3 ± 2.3 (standard error of the mean) months between the first and second visits. The mean age at the first visit was 11.6 ± 3.1 years. The raters agreed that serial drawings were both improved or both not improved in 99 of the 111 cases (89%; interrater reliability kappa score of 0.767). Fifty-three children had improvements in their headaches and drawings, 3 children had an improved drawing but no clinical headache improvement, 32 children had no improvement in either their drawing or clinical headaches, and 11 children had improved headaches but no improvement in their drawing. The sensitivity of the drawings for clinical improvement was 0.83, and the specificity was 0.91. The predictive value of an improved headache drawing for an improved clinical response was 0.946. There was no correlation between specific treatment modality and artistic response. We concluded that children's headache drawings are a useful adjunct for the diagnosis of headache type and provide valuable insights into their experience of pain. The present data show that headache drawings can be used longitudinally to provide additional information about the clinical course. The technique is simple, inexpensive, and enjoyable for children and can be applied in a variety of clinical settings. ( J Child Neurol 2005;20:809—813).
Krabbe Disease: Severe Neonatal Presentation With a Family History of Multiple Sclerosis
Authors: Sahai Inderneel , Baris Hagit , Kimonis Virginia , Levy Harvey L.
Published: June 2007

Krabbe disease, also known as globoid cell leukodystrophy, is a rare autosomal recessive disorder caused by a deficiency of a lysosomal enzyme, galactocerebrosidase. This defect prevents normal turnover of the galactolipids and results in progressive demyelination. In the infantile form, symptoms typically present at 3 to 6 months of age with subsequent neurologic deterioration. We report a case with presentation on day 7 of life and rapid progression culminating in death at 10 weeks. Galactocerebrosidase activity was absent in the leukocytes, and a 30 kb deletion in the GALC gene was found. To our knowledge, this is the earliest reported death from Krabbe disease. Several family members have multiple sclerosis, which is also a demyelinating disorder. We propose that the neonatal expression could be an example of complementary gene interaction in which coinheritance of a predisposition to multiple sclerosis led to the unusual early manifestation and rapid course of Krabbe disease in this infant. ( J Child Neurol 2005;20:826—828).
Sydenham's Chorea: Positron Emission Tomographic (PET) Scan Studies
Authors: Aron Alan M.
Published: June 2007

Two patients with Sydenham's chorea were evaluated with positron emission tomographic (PET) scans in the active phase of the disease. One patient had repeat scanning in the recovery phase. PET scans showed hypermetabolic changes of the caudate nuclei and putamen in the active phase of Sydenham's chorea. The scan reverted to normal in the recovery phase. These changes can afford a basis for comparing concurrent serum antibody studies in the acute and recovery phases of Sydenham's chorea. ( J Child Neurol 2005;20:832—833).
X-Linked MCT8 Gene Mutations: Characterization of the Pediatric Neurologic Phenotype
Authors: Holden Kenton R. , Zuñiga Oscar F. , May Melanie M. , Su Humberto , Molinero Marco R. , Rogers R. Curtis , Schwartz Charles E.
Published: June 2007

We report a family with X-linked mental retardation that has a novel mutation in the monocarboxylate transporter 8 ( MCT8) gene associated with a characteristic neurodevelopmental phenotype with early childhood hypotonia that progresses to spasticity and global developmental delays. Affected patients experience moderate to severe psychomotor delays and congenital hypotonia, develop a myopathic facies, have diminished muscle bulk and generalized muscle weakness, develop progressive spasticity and movement disorders, and have limited speech but alert, affable personalities. Acquired microcephaly and abnormal myelination on brain magnetic resonance imaging can be present. Normal monocarboxylate transporter 8 gene functioning appears to be necessary for normal thyroid-associated metabolism in neurons. Abnormal thyroid function tests appear to be a consistent finding in the absence of typical signs of thyroid dysfunction. Although the phenotype appears to be consistent, and although the neurotoxic effects of abnormal central and peripheral neuromuscular system thyroid metabolism might be partly or wholly responsible for the neurologic phenotype reported, the exact mechanism remains unclear. ( J Child Neurol 2005;20:852—857).
Diagnostic Approach to Cerebellar Disease in Children
Authors: D'Arrigo Stefano , Viganò Lucia , Bruzzone Maria Grazia , Marzaroli Michela , Nikas Ioannis , Riva Daria , Pantaleoni Chiara
Published: June 2007

We reviewed the clinical records of 51 extensively investigated pediatric patients with structural abnormalities of the cerebellum as revealed by magnetic resonance imaging (MRI). Ten had hypoplasia of the vermis, 21 had hypoplasia of the vermis and cerebellar hemispheres, 2 had pontocerebellar hypoplasia, and 18 had progressive cerebellar atrophy. A clear diagnosis was reached in 37 (72.5%). Initial characterization of the cerebellar alterations by MRI separated hypoplastic from atrophic cases and confirmed MRI as an essential preliminary means for distinguishing malformations from metabolic-degenerative conditions. However, the diagnostic possibilities are so numerous that it is not feasible to propose a standardized diagnostic protocol for pediatric patients with an altered cerebellum. Subsequent investigations should be suggested by the neuroradiologic and clinical peculiarities of each case. ( J Child Neurol 2005;20:859—866).
Efficacy and Safety of Topiramate in Refractory Epilepsy of Childhood
Authors: Grosso Salvatore , Franzoni Emilio , Iannetti Paola , Incorpora Gemma , Cardinali Cesare , Toldo Irene , Verrotti Alberto , Moscano Filomena Caterina , Lo Faro Valentina , Mazzone Luigi , Zamponi Nelia , Boniver Clementina , Spalice Alberto , Parisi Pasquale , Morgese Guido , Balestri Paolo
Published: June 2007

This study aimed to evaluate the long-term efficacy and safety of topiramate in treating children with drug-resistant epilepsy. A multicentric, retrospective, open-label, add-on study was undertaken of 277 children (mean age 8.4 years; range 12 months to 16 years) affected by drug-resistant epilepsy. The efficacy was rated according to the seizure types and epilepsy syndrome. After a mean period of 27.5 months of treatment (range 24—61 months), 11 patients (4%) were seizure free and 56 (20%) had more than 50% reduction in seizure frequency. The efficacy of topiramate treatment was noted in localization-related epilepsy and in generalized epilepsy. In addition, in a group of 114 patients, we compared the initial efficacy (evaluated after a mean of 9 months of follow-up) and the retention at a mean of 30 months of topiramate with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Fifty-five (48%) of 114 patients were initial responders. The retention at a mean of 30 months was 23 of 114 patients (20%), 4 of whom (3.5%) were still seizure free. A loss of efficacy occurred in 32 of the 55 initial responders (58%). It was prominent in patients with generalized epilepsy, such as symptomatic infantile spasms and Lennox-Gastaut syndrome, as well as in those with Dravet syndrome. By contrast, a well-sustained topiramate efficacy was noted among patients with localization-related epilepsy. Globally, adverse events were observed in 161 patients (58%) and were mainly represented by weight loss, hyperthermia, sedation, and nervousness, which, in most cases, disappeared after slowing titration or reducing the dosage of the drug. In conclusion, the present long-term study confirms that topiramate represents a useful drug effective in a wide range of seizures and epilepsy syndromes. Moreover, preliminary data seem to suggest that the efficacy of topiramate, when evaluated in the long-term perspective, is more sustained in localization-related epilepsy than in generalized epilepsy. ( J Child Neurol 2005;20:893—897).