bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Basis of Canavan's Disease
Authors: Surendran Sankar , Matalon Kimberlee M. , Tyring Stephen K. , Matalon Reuben
Published: June 2007

Canavan's disease is an autosomal recessive disorder caused by aspartoacylase deficiency. The deficiency of aspartoacylase leads to increased concentration of N-acetylaspartic acid in brain and body fluids. The failure to hydrolyze N-acetylaspartic acid causes disruption of myelin, resulting in spongy degeneration of the white matter of the brain. The clinical features of the disease are hypotonia in early life, which changes to spasticity, macrocephaly, head lag, and progressive severe mental retardation. Although Canavan's disease is panethnic, it is most prevalent in the Ashkenazi Jewish population. Research at the molecular level led to the cloning of the gene for aspartoacylase and development of a knockout mouse for Canavan's disease. These developments have afforded new tools for research in the attempts to understand the pathophysiology of Canavan's disease, design new therapies, and explore methods for gene transfer to the central nervous system. ( J Child Neurol 2003;18:604—610).
Encephalocraniocutaneous Lipomatosis: Neurologic Manifestations
Authors: Valencia Ignacio , Carapeto Francisco J. , Ventura Purificación , Pilar Samper M. , Rodríguez Gerardo , Pérez-González José M. , Legido Agustín
Published: June 2007

We report a new case of encephalocraniocutaneous lipomatosis, a rare neurocutaneous syndrome of unknown etiology with involvement of tissues arising from the mesoderm and ectoderm: skin, eye, adipose tissue, and brain. We also review the neurologic manifestations of the syndrome, the most frequent of which include seizures, ventricular enlargement, calcifications, mental retardation, and cerebellopontine angle tumor. Our patient had an extensive extradural spinal cord lipomatous lesion, emphasizing the importance of screening for spinal abnormalities in asymptomatic patients with this condition. ( J Child Neurol 2003;18:725—729).
Alternative Therapy Use by Chinese-Canadian Children With Stroke and Cerebrovascular Disease
Authors: Golomb Meredith R. , Hune Selina , MacGregor Daune L. , deVeber Gabrielle A.
Published: June 2007

The use of alternative therapies in immigrant children with stroke and cerebrovascular diseases has not been reported. We identified immigrant and first-generation Chinese-Canadian children with stroke and cerebrovascular diseases in a pediatric stroke clinic and used standardized questionnaires to interview their parents about alternative therapy use. The chi-square test was used to assess the associations of parental educational level and foreign birth in the child with alternative therapy use. We identified 17 children, 9 boys and 8 girls. Six were immigrants to Canada and 11 were Canadian born. Nine of 17 families (53%) reported using alternative therapies. All 9 used Chinese herbs, but only 3 were able to report the names of specific preparations. Four families were using medications that had the potential to affect coagulation. Documentation of alternative therapy use was found in the medical charts of 3 of the 9 patients. Three families reported feeling uncomfortable discussing alternative therapy use with their physicians. We did not see an association between alternative therapy use and parental educational level or foreign birth in the child. Physicians should be aware that parents of children with stroke may be using alternative therapies to treat their children and may be unwilling or unable to report all therapies used. ( J Child Neurol 2003;18:714—717).
Neurobiology of Rett Syndrome
Authors: Johnston Michael V. , Mullaney Brendan , Blue Mary E.
Published: June 2007

Girls with Rett syndrome display signs of neuronal dysfunction including mental retardation, seizures, stereotyped movements, and abnormal breathing and autonomic control. Decelerating head growth during infancy might reflect a disorder in production or pruning of neuronal synapses or both. Recent immunocytochemical studies in rodent brain investigating development of MeCP2, the transcription factor mutated in Rett syndrome, suggest that expression is delayed until the time of synapse formation. These findings are consistent with other evidence that Rett syndrome disrupts genetic programs that establish and refine synaptic connections. ( J Child Neurol 2003;18:688—692).
Neurotrophic Factors in the Pathogenesis of Rett Syndrome
Authors: Riikonen Raili
Published: June 2007

Rett syndrome is characterized by disruption of a period of vigorous brain growth with synapse development. Neurotrophic factors are important regulators of neuronal growth, differentiation, and survival during early brain development. The aims of this study were to study the role of neurotrophic factors in Rett syndrome, specifically whether Rett syndrome has abnormal levels of specific neurotrophic factors in serum and cerebrospinal fluid and whether the changes differ from other neuropediatric patients, for example, those with infantile autism. Four neurotrophic factors were measured: nerve growth factor, brain-derived neurotrophic factor, glial cell line—derived neurotrophic factor, and insulin-like growth factor 1 from the frozen cerebrospinal fluid and from serum (except glial cell line—derived neurotrophic factor) by enzyme-linked immunosorbent assay and cerebrospinal fluid glutamate and aspartate by high-performance liquid chromatography (HPLC) method in patients with Rett syndrome. Insulin-like growth factor 1 was measured from the cerebrospinal fluid of patients with infantile autism. We found low concentrations of cerebrospinal fluid nerve growth factor in patients with Rett syndrome compared with control patients. The serum levels and other cerebrospinal fluid neurotrophic factor levels of the patients did not differ from the controls. Patients with Rett syndrome had high cerebrospinal fluid glutamate levels. Patients with infantile autism had low cerebrospinal fluid insulin-like growth factor 1 levels. Nerve growth factor acts especially on cholinergic neurons of the basal forebrain, whereas insulin-like growth factor 1 acts on cerebellar neurons. In Rett syndrome, the forebrain is more severely affected than the other cortical areas. In autism, many studies show hippocampal or cerebellar pathology. Our findings are in agreement with the different morphologic and neurochemical findings (brain growth, affected brain areas, neurotransmitter metabolism) in the two syndromes. Impairment in dendritic development in Rett syndrome could be the consequence of cholinergic deficiency and of neurotrophic factor/glutamate imbalance. Cholinergic gene expression might be influenced by the Rett syndrome gene directly or via the neurotrophic factor system. ( J Child Neurol 2003;18:693—697).
Functional Magnetic Resonance Imaging of Phonologic Processing in Neurofibromatosis 1
Authors: Billingsley Rebecca L. , Jackson Edward F. , Slopis John M. , Swank Paul R. , Mahankali Srikanth , Moore Bartlett D.
Published: June 2007

Neurofibromatosis 1 is associated with reading disabilities, but few associations between neuroanatomic abnormalities and reading problems have been found. We examined the neuronal bases for phonologic processing, a core component of learning to read, in 15 individuals with neurofibromatosis 1 and 15 controls using functional magnetic resonance imaging (MRI). Our results revealed differential use of inferior and dorsolateral prefrontal cortical areas relative to posterior (temporal, parietal, and occipital) cortices for participants with neurofibromatosis 1 compared with controls during phonologic (rhyme) decisions. In addition, similar to previous brain imaging studies of reading deficits in the general population, poorer performance on one of the phonologic decision tasks was associated with increased signal change in the right superior temporal gyrus for the neurofibromatosis 1 group. Behavioral performance on the functional MRI tasks was related to academic reading measures for the neurofibromatosis 1 group. The differential patterns of functional connectivity observed here lend support to previous morphologic studies that suggested inferior frontal and superior temporal areas to be important mediators of reading and language development in neurofibromatosis 1. ( J Child Neurol 2003;18:731—740).
Periodic Lateralized Epileptiform Discharges in Children
Authors: Yoshikawa Hideto , Abe Tokinari
Published: June 2007

Thirteen children in whom electroencephalography revealed periodic lateralized epileptiform discharges in the acute phase of cerebral involvement were included in this study. Four were diagnosed as having influenza-associated encephalopathy, two nonherpetic limbic encephalitis, two theophylline-associated seizures, one Mycoplasma pneumoniae encephalitis, one acute encephalopathy, and one bacterial meningitis. All patients developed seizures; six developed hemiconvulsions. As to prognosis, two died, six had some neurologic sequelae, and five had no neurologic sequelae. Although periodic lateralized epileptiform discharges are not disease specific, the importance of these disorders had not been focused on as a cause of periodic lateralized epileptiform discharges. ( J Child Neurol 2003;18:803—805).
Toxic Pediatric Parkinsonism: Report of a Child With Metabolic Studies and Response to Treatment
Authors: Chutorian Abe M. , Bojko Aviva , Heier Linda , Frucht Steven , Nygaard Toby , Edelberg David
Published: June 2007

We successfully treated a child with parkinsonism secondary to cytosine arabinoside with levodopa/carbidopa and attempted to elucidate the pathogenesis of the disorder by sequential analysis of cerebrospinal fluid biogenic amines, sequential magnetic resonance imaging, and fluorodopa positron emission tomography, which revealed both permanent and reversible biochemical and structural alterations. The parkinsonian disorder resolved in 9 months. Metabolic changes and structural abnormalities on imaging studies were chronologically correlated with the clinical course. ( J Child Neurol 2003;18:812—815).
Infantile Spasms in an Infant With Cytomegalovirus Infection Treated With Ganciclovir
Authors: Voudris Konstantinos A. , Vagiakou Eleni A. , Mastroyianni Sotiria , Dimitriou Yboni , Skardoutsou Angeliki
Published: June 2007

A 3-month-old male infant with cytomegalovirus infection and intractable partial seizures was treated with ganciclovir for 6 weeks. The drug was well tolerated, and virus shedding in the cerebrospinal fluid and urine was eliminated, although infantile spasms at the age of 6 months appeared. At the age of 12 months, intractable seizures persisted, and the psychomotor development of the infant was markedly delayed. To our knowledge, no previous similar case has been reported. These findings suggest that treatment with ganciclovir of infants with cytomegalovirus infection results only in cessation of virus shedding in the cerebrospinal fluid and urine without having a preventive effect on the future appearance of infantile spasms. This may be due to the irreversibility of previous brain damage from the cytomegalovirus infection and the virostatic nature of the drug. ( J Child Neurol 2004;19:50—53).
Study of Multimodal Evoked Potentials in Patients With Type 1 Gaucher's Disease
Authors: Perretti Anna , Parenti Giancarlo , Balbi Pietro , Titomanlio Luigi , Marcantonio Lucia , Iapoce Mariangela , Frascogna Anna Rita , Andria Generoso , Santoro Lucio
Published: June 2007

To detect early subclinical nervous dysfunction in Gaucher's disease type 1, we carried out motor, brainstem auditory, visual, and somatosensory evoked potentials in 17 patients with Gaucher's disease type 1. Central motor evoked potential abnormalities were found in nine patients (69.2%), consisting of an increased motor threshold in all, with prolonged central motor conduction time in two patients. Brainstem auditory evoked potentials were abnormal in five patients (31.2%), and the most frequent abnormality was a bilateral increased I—III interpeak latency. Visual evoked potentials showed a delayed latency of the P100 wave in four patients (25%). Somatosensory evoked potential abnormalities were found in three patients (18.7%), consisting of an increased N13—N20 interval in two patients and a not reproducible N13 wave in one patient. Our findings suggest that the multimodal evoked potential approach provides information about nervous subclinical damage in Gaucher's disease type 1; transcranial magnetic stimulation proved to be the most sensitive tool. Early detection of subclinical neurologic dysfunction can be useful in view of more effective therapeutic strategies. ( J Child Neurol 2005;20:124—128).
Cerebellar Injury in the Extremely Premature Infant: Newly Recognized but Relatively Common Outcome
Authors: Bodensteiner John B. , Johnsen Stanley D.
Published: June 2007

Severe injury to the cerebellum as a complication of extreme prematurity with extremely low birthweight was recently described in 13 children with the clinical diagnosis of cerebral palsy. We report another 10 cases of this syndrome. The clinical features include striking motor impairment and variable degrees of ataxia and athetosis or dystonia, which represent a distinct clinical type of cerebral palsy. Most are severely damaged, with cognitive, language, and motor delays. All are microcephalic, except one with hydrocephalus. Neuroimaging studies demonstrate the absence of major portions of the cerebellum involving both the inferior vermis and hemispheres. Most also have injury of a less severe nature in the cerebrum. This report indicates that this is not an uncommon outcome of extremely low birthweight infants, and we hope to encourage further investigations into the relative frequency and likely etiologies of the condition. ( J Child Neurol 2004;19:139—142).
Topical Review: Neuronal Migration Disorders, Genetics, and Epileptogenesis
Authors: Guerrini Renzo , Filippi Tiziana
Published: June 2007

Several malformation syndromes with abnormal cortical development have been recognized. Specific causative gene defects and characteristic electroclinical patterns have been identified for some. X-linked periventricular nodular heterotopia is mainly seen in female patients and is often associated with focal epilepsy. FLN1 mutations have been reported in all familial cases and in about 25% of sporadic patients. A rare recessive form of periventricular nodular heterotopia owing to ARGEF2 gene mutations has also been reported in children with microcephaly, severe delay, and early-onset seizures. Lissencephaly-pachygyria and subcortical band heterotopia represent a malformative spectrum resulting from mutations of either the LIS1 or the DCX ( XLIS) gene. LIS1 mutations cause a more severe malformation posteriorly. Most children have severe developmental delay and infantile spasms, but milder phenotypes are on record, including posterior subcortical band heterotopia owing to mosaic mutations of LIS1. DCX mutations usually cause anteriorly predominant lissencephaly in male patients and subcortical band heterotopia in female patients. Mutations of the coding region of DCX were found in all reported pedigrees and in about 50% of sporadic female patients with subcortical band heterotopia. Mutations of XLIS have also been found in male patients with anterior subcortical band heterotopia and in female patients with normal brain magnetic resonance imaging. The thickness of the band and the severity of pachygyria correlate with the likelihood of developing severe epilepsy. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the reelin ( RELN) gene. X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia in genotypic males is associated with mutations of the ARX gene. Affected boys have severe delay and infantile spasms with suppression-burst electroencephalograms. Early death is frequent. Carrier female patients can have isolated corpus callosum agenesis. Schizencephaly has a wide anatomoclinical spectrum, including focal epilepsy in most patients. Familial occurrence is rare. Initial reports of heterozygous mutations in the EMX2 gene have not been confirmed. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to chromosome Xq28 in some pedigrees, autosomal dominant or recessive inheritance in others, and an association with chromosome 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy. Recessive bilateral frontoparietal polymicrogyria has been associated with mutations of the GPR56 gene. ( J Child Neurol 2005;20:287—299).
Topical Review: Molecular and Neurologic Findings of Peroxisome Biogenesis Disorders
Authors: Shimozawa Nobuyuki , Nagase Tomoko , Takemoto Yasuhiko , Funato Michinori , Kondo Naomi , Suzuki Yasuyuki
Published: June 2007

Peroxisomal disorders, an expanding group of genetic disorders in humans, can be grouped into three categories: peroxisome biogenesis disorders, single peroxisomal enzyme deficiencies, and contiguous gene syndrome. At present, 13 complementation groups of peroxisome biogenesis disorders and their responsible genes have been identified, including our newly identified group with a PEX14 defect. We describe neuronal abnormalities related to deficiencies in peroxisomes and the phenotype-genotype relationship in peroxisome biogenesis disorders. We also identified 32 Japanese patients with peroxisome biogenesis disorders, subdivided into six complementation groups. Our institution acts as the only diagnostic center for studies on peroxisomal disorders in Japan. ( J Child Neurol 2005;20:326—329).
Electroencephalographic Recordings of Focal Seizures in Patients Affected by Periventricular Nodular Heterotopia: Role of the Heterotopic Nodules in the Genesis of Epileptic Discharges
Authors: Battaglia Giorgio , Franceschetti Silvana , Chiapparini Luisa , Freri Elena , Bassanini Stefania , Giavazzi Alessio , Finardi Adele , Taroni Franco , Granata Tiziana
Published: June 2007

Patients affected by periventricular nodular heterotopia are frequently characterized by focal drug-resistant epilepsy. To investigate the role of periventricular nodules in the genesis of seizures, we analyzed the electroencephalographic (EEG) features of focal seizures recorded by means of video-EEG in 10 patients affected by different types of periventricular nodular heterotopia and followed for prolonged periods of time at the epilepsy center of our institute. The ictal EEG recordings with surface electrodes revealed common features in all patients: all seizures originated from the brain regions where the periventricular nodular heterotopia were located; EEG patterns recorded on the leads exploring the periventricular nodular heterotopia were very similar both at the onset and immediately after the seizure's end in all patients. Our data suggest that seizures are generated by abnormal anatomic circuitries, including the heterotopic nodules and adjacent cortical areas. The major role of heterotopic neurons in the genesis and propagation of epileptic discharges must be taken into account when planning surgery for epilepsy in patients with periventricular nodular heterotopia. ( J Child Neurol 2005;20:369—377).
Recurrent Intractable Seizures in Children With Cortical Dysplasia Adjacent to Dysembryoplastic Neuroepithelial Tumor
Authors: Sakuta Ryoichi , Otsubo Hiroshi , Nolan Melinda A. , Weiss Shelly K. , Hawkins Cynthia , Rutka James T. , Chuang Nathaniel A. , Chuang Sylvester H. , Snead O. Carter
Published: June 2007

The purpose of this study was to identify the pathologic features that predict postoperative outcome in children with cortical dysplasia adjacent to dysembryoplastic neuroepithelial tumors. We reviewed the records of children with dysembryoplastic neuroepithelial tumor who underwent epilepsy surgery and who had at least 1 year of surgical follow-up. We divided the dysembryoplastic neuroepithelial tumors into three pathology classes (simple, complex, and nonspecific), categorized adjunctive cortical dysplasia into four types, and compared histopathology with seizure outcomes. We identified 26 children with dysembryoplastic neuroepithelial tumors. Dysembryoplastic neuroepithelial tumors were complex in 19 patients (73%), simple in 6 (23%), and nonspecific in 1 (4%). Cortical dysplasia was adjacent to dysembryoplastic neuroepithelial tumors in 18 patients. Six patients had type IA cortical dysplasia, 5 had type IB, 3 had type IIA, and 1 had type IIB. The 3 remaining patients had repeated surgeries; of these, 2 patients had cortical dysplasias of type IA/IB and 1 was type IIA/IIB. Eight (39%) of 18 patients with dysembryoplastic neuroepithelial tumors and cortical dysplasia required further surgery for recurrent intractable seizures ( P < .05), whereas none of 8 patients without cortical dysplasia required additional surgery. Of 13 patients with type I cortical dysplasia, only 4 had a poor seizure outcome, whereas all 5 patients with type II had a poor seizure outcome postoperatively ( P < .05). Children with dysembryoplastic neuroepithelial tumor and cortical dysplasia often had recurrent intractable seizures postoperatively and required further epilepsy surgery. Cortical dysplasia adjacent to dysembryoplastic neuroepithelial tumor can play a role in the epileptogenicity of dysembryoplastic neuroepithelial tumor. Complete resection of a dysembryoplastic neuroepithelial tumor and its adjacent cortical dysplasia should be considered. ( J Child Neurol 2005;20:377—384).
Multivoxel Magnetic Resonance Spectroscopy in a Rhizomelic Chondrodysplasia Punctata Case
Authors: Siğirci Ahmet , Alkan Alpay , Kutlu Ramazan , Gülcan Hande
Published: June 2007

A case of a 5-day-old newborn with rhizomelic chondrodysplasia punctata was investigated with multivoxel magnetic resonance spectroscopy, including chemical shift imaging maps, which disclosed a decrease in the choline peak and the choline signal intensity, respectively, in the right cerebral hemisphere. This is the second report of multivoxel magnetic resonance spectroscopy examination of the brain associated with rhizomelic chondrodysplasia punctata in the literature. Multivoxel magnetic resonance spectroscopy with chemical shift imaging maps has the advantage of obtaining more information in a short period of time, which shortens the duration of anesthesia and its associated risks and complications. We suggest that future efforts be directed to evaluating such patients with multivoxel magnetic resonance spectroscopy instead of single-voxel magnetic resonance spectroscopy. ( J Child Neurol 2005;20:698—701).
The Human Secretin Gene in Children With Autistic Spectrum Disorder: Screening for Polymorphisms and Mutations
Authors: Ng Samuel S.M. , Chow Billy K.C. , Wong Virginia C.N.
Published: June 2007

We screened 29 children with autism for mutation in the human secretin gene using single-strand conformation polymorphism. No mutation was detected in exon 2, 3, or 4. Polymerase chain reaction and DNA sequence of 5' variable number of tandem repeats showed two polymorphisms with deletion or duplication of a repeat unit that failed to show any gene expression with transient transfection assay. We did not find evidence of a relationship between human secretin gene mutation and autism. ( J Child Neurol 2005;20:701—704).
Rett Syndrome: Model of Neurodevelopmental Disorders
Authors: Percy Alan K. , Lane Jane B.
Published: June 2007

Rett syndrome is a neurodevelopmental disorder that primarily affects girls, most of whom have mutations in the transcription regulatory gene MECP2. However, mutations in MECP2 also have been identified in normal carrier female individuals, female individuals with mild learning disabilities and features of Angelman syndrome, and male individuals with Klinefelter syndrome or Rett syndrome—like features, fatal neonatal encephalopathy, and familial X-linked mental retardation with or without motor abnormalities. Therefore, molecular testing should be considered for a wide spectrum of individuals. As such, Rett syndrome remains a clinical diagnosis. In this article, we also discuss three recent developments: (1) the recognition of significant gallbladder dysfunction, especially in those 20 years of age or younger; (2) a clinical trial of folate and betaine, which produced no objective improvement but did yield a subjective increase in attention and interaction; and (3) measurement of cerebrospinal fluid folate levels in a large cohort, which yielded normal values, indicating no need for supplementation. ( J Child Neurol 2005;20:718—721).
Dissecting MECP2 Function in the Central Nervous System
Authors: Kishi Noriyuki , Macklis Jeffrey D.
Published: June 2007

Rett syndrome is a neurodevelopmental disorder and an important cause of mental retardation and autistic behavior in girls and in a small group of boys. In 1999, mutation of the methyl-CpG binding protein 2 ( MECP2) gene encoding a transcriptional repressor on the X chromosome was found to cause Rett syndrome. Since this discovery, significant research has focused on the elucidation of its specific role in the central nervous system. Recent studies revealed that MECP2 is expressed in more differentiated neurons rather than in less differentiated neuroblasts and that MECP2 is involved in the maturation and maintenance of neurons, including dendritic arborization and axonal projections, rather than in early cell fate decisions in the mammalian brain. In this review, we summarize recent findings regarding regional, temporal, and cell type—specific MECP2 expression in the central nervous system; neurobiologic abnormalities in MECP2 -mutant mice; and MECP2 target genes in the central nervous system. ( J Child Neurol 2005;20:753—759).
Natural History of Rett Syndrome
Authors: Nomura Yoshiko , Segawa Masaya
Published: June 2007

Rett syndrome is a unique neurodevelopmental disorder, with onset of hypotonia, autistic tendency, and abnormalities of fine finger movements and gross movements of the arms in early infancy. Clinical features include specific age-dependent symptoms. Studies of early and late signs correlated locomotive dysfunction to language disability and stereotypy to regression of higher cortical functions. Studies of sleep parameters revealed early hypofunction of brainstem aminergic neurons and late occurrence of hypofunction of dopaminergic neurons, followed by receptor supersensitivity. The syndrome's pathophysiology suggests that early hypofunction of aminergic neurons interferes with the development of higher neuronal systems. Particular symptoms surface at different ages throughout the natural course of Rett syndrome, with regressional and static periods. ( J Child Neurol 2005;20:764—768).
Video and CD-ROM as a Training Tool for Performing Neurologic Examinations of 1-Year-Old Children in a Multicenter Epidemiologic Study
Authors: Kuban Karl C. K. , O'Shea Michael , Allred Elizabeth , Leviton Alan , Gilmore Herbert , DuPlessis Adré , Krishnamoorthy Kalpathy , Hahn Cecil , Soul Janet , O'Connor Sunila E. , Miller Karen , Church Paige T. , Keller Cecilia , Bream Richard , Adair Robin , Miller Alice , Romano Elaine , Bassan Haim , Kerkering Kathy , Engelke Steve , Marshall Diane , Milowic Kristy , Wereszczak Janice , Hubbard Carol , Washburn Lisa , Dillard Robert , Heller Cherrie , Burdo-Hartman Wendy , Fagerman Lynn , Sutton Dinah , Karna Padu , Olomu Nick , Caldarelli Leslie , Oca Melisa , Lohr Kim , Scheiner Albert
Published: June 2007

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals. ( J Child Neurol 2005;20:829—831).
Case of Aicardi-Goutières Syndrome With Long-lasting Increase of Cerebrospinal Interferon-α
Authors: Dimova Petia S. , Mikova Olya A.
Published: June 2007

Aicardi-Goutières syndrome is a rare progressive encephalopathy characterized by a typical clinical picture, bilateral basal ganglia calcifications, leukodystrophy and brain atrophy, lymphocytosis, and elevated interferon-α in the cerebrospinal fluid. Among the cases described to date, variability in the clinical expression or in the cerebrospinal fluid abnormalities has been reported. We present a case with a delayed diagnosis at the age of 8 years, when brain computed tomography was done because there was no first image from the age of 8 months, when the disease started. Symmetric basal ganglia calcifications were visualized and led to purposeful investigation of the cerebrospinal fluid. It revealed an interferon-α titer of 103 IU/mL, which, together with the progressive brain damage and disease course, was crucial for the diagnosis. This rare finding of long-term highly elevated interferon-α in the cerebrospinal fluid is discussed with respect to the clinical course. ( J Child Neurol 2005;20:915—920).
Hypomelanosis of Ito and Moyamoya Disease
Authors: Rafay Mubeen F. , Al-Futaisi Amna , Weiss Shelly , Armstrong Derek
Published: June 2007

Moyamoya disease is a cerebrovascular disease characterized by stenosis and occlusion of the arteries of the circle of Willis, with abnormal telangiectatic collateral circulation at the base of the brain. An association between moyamoya disease and neurofibromatosis 1, a neurocutanoeus disorder, is well established in the literature. However, its association with other neurocutaneous syndromes is infrequently reported. Hypomelanosis of Ito, another neurocutaneous syndrome, is characterized by macular hypopigmented skin whorls and variable neurologic involvement. Only one case study of an association between hypomelanosis of Ito and moyamoya disease has been reported in the English literature. We report a 17-year-old girl with both hypomelanosis of Ito and angiographic moyamoya disease. She presented with intractable seizures, progressive left hemiparesis, and skin manifestations of hypomelanosis of Ito. Although one might consider a coincidental association, this second case points to an association between the two disorders. Detailed neuroimaging, in particular angiography, should be considered in children with hypomelanosis of Ito and abnormal neurologic findings. ( J Child Neurol 2005;20:924—926).
Hippocampal Dysgenesis Associated With Temporal Lobe Hypoplasia and Arachnoid Cyst of the Middle Cranial Fossa
Authors: Sztriha Laszlo , Gururaj Aithala
Published: June 2007

We describe two children with left hippocampal dysgenesis in association with temporal lobe hypoplasia and arachnoid cyst of the middle cranial fossa. The hippocampus showed an abnormal globular shape and blurred internal structure in both patients. One of the patients had juvenile myoclonic epilepsy without evidence of seizure onset in the abnormal temporal region. The other patient did not have epilepsy; however, he showed developmental language disorder with a probable relationship to the left temporal abnormalities. ( J Child Neurol 2005;20:926—930).
Answer to Hypotonia: A Simple Hemogram
Authors: Kanra Güler , Cetin Mualla , Unal Sule , Haliloglu Goknur , Akça Tulay , Akalan Nejat , Kara Ates
Published: June 2007

A 1-year-old boy with weight loss, decreased activity, and psychomotor regression is presented. He was subjected to an extremely detailed evaluation, including electroencephalography (EEG) and magnetic resonance imaging (MRI), until a simple hemogram in our center revealed that he had macrocytic anemia with megaloblastic changes in the bone marrow. His history revealed that he had been exclusively breast-fed by his vegetarian mother. Further investigations showed low serum vitamin B12 concentration, methylmalonic aciduria, and homocysteinemia, indicating that the macrocytic anemia was due to vitamin B12 deficiency. This boy represents a case of macrocytic anemia and hypotonia owing to vitamin B12 deficiency that developed because of exclusive breast-feeding by a vegetarian mother. ( J Child Neurol 2005;20:930—931).
Patterns of Cerebral Injury in a Primate Model of Preterm Birth and Neonatal Intensive Care
Authors: Inder Terrie , Neil Jeffrey , Yoder Bradley , Rees Sandra
Published: June 2007

Very preterm birth is associated with significant neurodevelopmental morbidity, with 10% to 15% of these infants later developing cerebral palsy and up to 50% experiencing learning disabilities. The nature of the cerebral lesion predisposing these infants to such impairments is not fully understood but is likely related to both cerebral injury and alterations in cerebral development associated with neonatal intensive care. To study the impact of both preterm birth and neonatal intensive care on the immature brain, we are studying a preterm primate model delivered at 125 days of a 184-day gestational period and cared for in a neonatal intensive care unit for 2 to 4 weeks in a fashion highly similar to that for human preterm infants. The most common neuropathology in this model is white-matter damage manifested by reactive astrogliosis or activated microglia and enlarged ventricular size. Subarachnoid, germinal matrix, and intraventricular hemorrhages are also common. These preliminary results support the similarity of this model to both the alterations in cerebral developmental and the pattern of cerebral injury found in human preterm infants. We are now investigating the impact of randomized respiratory therapies on the pattern of cerebral injury. The prematurely born baboon appears to be an accurate and relevant model for the study of preterm human birth. ( J Child Neurol 2005;20:965—967).
What Is Attention-Deficit Hyperactivity Disorder (ADHD)?
Authors: Furman Lydia
Published: June 2007

Attention-deficit hyperactivity disorder (ADHD) is described as the most common neurobehavioral condition of childhood. We raise the concern that ADHD is not a disease per se but rather a group of symptoms representing a final common behavioral pathway for a gamut of emotional, psychological, and/or learning problems. Increasing numbers of children, especially boys, are diagnosed with ADHD and treated with stimulant medications according to a simplified approach. Methodical review of the literature, however, raised concerning issues. “Core” ADHD symptoms of inattentiveness, hyperactivity and impulsivity are not unique to ADHD. Rates of “comorbid” psychiatric and learning problems, including depression and anxiety, range from 12 to 60%, with significant symptom overlap with ADHD, difficulties in diagnosis, and evidence-based treatment methods that do not include stimulant medications. No neuropsychologic test result is pathognomic for ADHD, and structural and functional neuroimaging studies have not identified a unique etiology for ADHD. No genetic marker has been consistently identified, and heritability studies are confounded by familial environmental factors. The validity of the Conners' Rating Scale-Revised has been seriously questioned, and parent and teacher “ratings” of school children are frequently discrepant, suggesting that use of subjective informant data via scale or interview does not form an objective basis for diagnosis of ADHD. Empiric diagnostic trials of stimulant medication that produce a behavioral response have been shown not to distinguish between children with and without “ADHD.” In summary, the working dogma that ADHD is a disease or neurobehavioral condition does not at this time hold up to scrutiny of evidence. Thorough evaluation of symptomatic children should be individualized, and include assessment of educational, psychologic, psychiatric, and family needs. ( J Child Neurol 2005;20:994—1002).
Aphasia Owing to Subcortical Brain Infarcts in Childhood
Authors: Gout Ariel , Seibel Nathalie , Rouvière Constance , Husson Béatrice , Hermans Brigitte , Laporte Nicole , Kadhim Hazim , Grandin Cécile , Landrieu Pierre , Sébire Guillaume
Published: June 2007

The aim of this study was to further define the clinical features of subcortical aphasia in children with deep brain infarcts and to define the sequelae associated with childhood strokes. We retrospectively studied nine children with left subcortical brain infarcts who presented with acquired language disorder and underwent language investigations based on standardized tests. Stroke in these patients involved the left internal capsule, lenticular or thalamic nuclei, or a combination of these. Early aphasic manifestations following the deep cerebral infarcts affected language expression. These included mutism, nonfluent speech, word finding difficulties, and phonemic and semantic paraphasia. Speech comprehension was generally more preserved. All patients subsequently improved, although variably; sequelae such as dysfluency, word finding difficulties, and written language learning impairment could be detected through standardized tests in six of them (all younger than 6 years at the time of the infarct). Two of the three remaining patients (both older than 6 years at the time of the infarct) had a full recovery. Our study confirms the concept of childhood subcortical aphasia, depicts the linguistic profile in these patients, and sustains the indication of systematic formal language assessment during the follow-up of all children with subcortical infarct involving the dominant hemisphere. ( J Child Neurol 2005;20:1003—1008).
Radiographic Predictors of Neurocognitive Functioning in Pediatric Sickle Cell Disease
Authors: Kral Mary C. , Brown Ronald T. , Curé Joel K. , Besenski Nada , Jackson Sherron M. , Abboud Miguel R.
Published: June 2007

We compared magnetic resonance imaging (MRI), magnetic resonance angiography, and transcranial Doppler ultrasonography as predictors of specific neurocognitive functions in children with sickle cell disease. Participants were 27 children with sickle cell anemia (hemoglobin SS) who were participants in the Stroke Prevention Trial in Sickle Cell Anemia (STOP) and had no documented history of stroke. Children's MRIs were classified as normal or silent infarct, and their magnetic resonance angiograms were classified as normal or abnormal. The highest time-averaged mean flow velocity on transcranial Doppler ultrasonographic examination of the major cerebral arteries was analyzed. Age and hematocrit also were analyzed as predictor variables. The battery of neurocognitive tests included measures of intellectual functioning, academic achievement, attention, memory, visual-motor integration, and executive functions. MRI, magnetic resonance angiography, transcranial Doppler ultrasonography, age, and hematocrit were analyzed as predictors of participants' performance on the various measures of neurocognitive functioning. Age and hematocrit were robust predictors of a number of global and specific neurocognitive functions. When age and hematocrit were controlled, transcranial Doppler ultrasonography was a significantly unique predictor of verbal memory. We found an association between low hemoglobin and neurocognitive impairment. We also found that abnormalities on transcranial Doppler ultrasonography can herald subtle neurocognitive deficits. ( J Child Neurol 2006;21:37—44).
Vigabatrin Caused Rapidly Progressive Deterioration in Two Cases With Early Myoclonic Encephalopathy Associated With Nonketotic Hyperglycinemia
Authors: Tekgul Hasan , Serdarolu Gul , Karapinar Bulent , Polat Muzaffer , Yurtsever Serap , Tosun Ayşe , Coker Mahmut , Gokben Sarenur
Published: June 2007

Vigabatrin, a structural analogue of γ-aminobutyric acid (GABA), is used for the treatment of generalized and partial seizures in infants. The drug inhibits the GABA transaminase and elevates the GABA concentration in the brain. Here we present the vigabatrin experience in two patients with early myoclonic encephalopathy owing to nonketotic hyperglycinemia (glycine encephalopathy). Both patients had early infantile seizures characterized by fragmentary myoclonic jerks associated with burst-suppression pattern on electroencephalography. Nonketotic hyperglycinemia was diagnosed with elevated cerebrospinal fluid and plasma glycine levels. The seizures were initially thought to be infantile spasms, and vigabatrin (50 mg /kg/day) was started for the treatment of seizures. Rapidly progressive deterioration was noticed after a few days. Acute encephalopathy associated with sleepiness and respiratory failure developed. Vigabatrin produced acute encephalopathy, which regressed in a few days after vigabatrin was stopped in the first patient. However, in the second case, despite the discontinuation of vigabatrin, there was no recovery of general conditions. Our observations in two cases indicate the risk of using vigabatrin in patients with nonketotic hyperglycinemia. The elevated GABA concentration in the brain can enhance the encephalopathy, together with the elevated levels of glycine. ( J Child Neurol 2006;21:82—84).
Increased Medial Thalamic Creatine-Phosphocreatine Found by Proton Magnetic Resonance Spectroscopy in Children With Obsessive-Compulsive Disorder Versus Major Depression and Healthy Controls
Authors: Mirza Yousha , O'Neill Joseph , Smith Ethan A. , Russell Aileen , Smith Janet M. , Banerjee S. Preeya , Bhandari Rashmi , Boyd Courtney , Rose Michelle , Ivey Jennifer , Renshaw Perry F. , Rosenberg David R.
Published: June 2007

Altered brain creatine-phosphocreatine levels might reflect changes in brain energy use and have been implicated in the pathogenesis of obsessive-compulsive disorder and major depressive disorder. We used proton magnetic resonance spectroscopy to measure absolute concentrations of creatine-phosphocreatine in the right and left medial thalami in 18 pediatric patients with major depressive disorder 9 to 17 years of age, 18 case-matched healthy controls, and 27 patients with obsessive-compulsive disorder 7 to 16 years old. The two patient groups were psychotropic drug naive and were not comorbid for the diagnosis of the comparison group. We found significantly increased left and right medial thalamic creatine-phosphocreatine concentrations in patients with obsessive-compulsive disorder compared with both healthy controls and patients with major depression. Creatine-phosphocreatine concentrations did not differ significantly between patients with major depression and healthy controls. Our data suggest that increased medial thalamic creatine-phosphocreatine concentrations in patients with untreated obsessive-compulsive disorder reflect altered energy use in the medial thalamus and might differentiate patients with obsessive-compulsive disorder from healthy controls and patients with major depression. Although these results must be considered preliminary, further study of the diagnostic specificity of creatine-phosphocreatine in obsessive-compulsive disorder is indicated. ( J Child Neurol 2006;21:106—111; DOI 10.2310/7010.2006.00016).
Diagnostic Strategy for the Detection of Dystrophin Gene Mutations in Asian Patients and Carriers Using Immortalized Cell Lines
Authors: Stacey Kiat Hong Tay  , Hwee Hoon Khng  , Poh Sim Low  , Poh San Lai
Published: June 2007

Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive diseases of muscle degeneration caused by mutations in the dystrophin gene. More than half of our local Asian patients have point mutations that cannot be detected by conventional multiplex polymerase chain reaction deletion screening. This study aimed to develop mutational screening and carrier detection for Duchenne and Becker muscular dystrophy using protein truncation analysis from Epstein-Barr virus—transformed lymphocyte cell lines. Messenger ribonucleic acid was extracted from fresh lymphocytes and Epstein-Barr virus—transformed lymphocyte cell lines of 14 patients. Reverse transcriptase polymerase chain reaction was performed in 11 overlapping segments, followed by in vitro protein translation and truncation analysis. DNA sequencing was carried out for the corresponding complementary DNA regions, which showed aberrant truncated protein products. Carrier studies using this method were also performed for two families. Half of the patients had frame-shifting deletions, and the remaining seven patients showed point mutations, of which four were novel. These mutations were detected in messenger ribonucleic acid extracted from both fresh lymphocytes and Epstein-Barr virus—transformed lymphocyte cell lines. Carrier status was confirmed in one family and was found to be negative in the other family studied. Protein truncation analysis is an efficient method of screening truncating point mutations from immortalized lymphocyte cell lines from patients. This approach not only serves to prove the pathogenicity of both deletion- and nondeletion-type mutations; it is also effective for carrier detection. The use of such cell lines obviates the need for repeated blood and muscle sampling in patients and offers a perpetual source of messenger ribonucleic acid that can be used long after the patient's demise. ( J Child Neurol 2006;21:150—155; DOI 10.2310/7010.2006.00029).
Topical Review: Epilepsy and Chromosomal Rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)]
Authors: Goldman Alica M. , Potocki Lorraine , Walz Katherina , Lynch Jennifer K. , Glaze Daniel G. , Lupski James R. , Noebels Jeffrey L.
Published: June 2007

Smith-Magenis syndrome is a multiple congenital anomalies/mental retardation syndrome associated with a heterozygous deletion of chromosome 17p11.2. Seizures have not been formally studied in this population. Our objectives were to estimate the prevalence of seizures and electroencephalographic (EEG) epileptiform abnormalities in patients with Smith-Magenis syndrome with defined chromosomal rearrangements and to describe the spectrum of abnormal EEG patterns. Prolonged video-EEGs were obtained in 60 patients. Eighteen percent of patients reported a seizure history; however, abnormal EEGs were identified in 31 of the 60 subjects and 27 of 31 were epileptiform. Generalized epileptiform patterns were the most common (73%). Most patients with either small or large deletions had an abnormal EEG (83%; 75%) in contrast to those with a common deletion (49%). Our results indicate that epileptiform EEG abnormalities are frequent in patients with Smith-Magenis syndrome. Considering that close to one third of individuals with Smith-Magenis syndrome with epileptiform abnormalities also had a history of clinical seizures, cortical hyperexcitability and epilepsy should be considered an important component of the Smith-Magenis syndrome clinical phenotype. ( J Child Neurol 2006;21:93—98; DOI 10.2310/7010.2006.00030).