bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Ontogeny of Major Neurotransmitter Receptor Systems in the Mammalian Central Nervous System: Norepinephrine, Dopamine, Serotonin, Acetylcholine, and Glycine
Authors: Rho Jong M. , Storey Thomas W.
Published: January 2008

Neurotransmitter receptors are critical elements in intercellular signaling within the central nervous system and are divided into two major types based on their molecular structure and biophysical properties. The first are ionotropic receptors— ligand-gated ion channels that directly affect the membrane potential via passage of permeant ions (such as sodium and calcium) and mediate fast synaptic transmission. The second type are slower metabotropic receptors that are also ligand gated but depend on an interaction with guanine nucleotide-binding proteins and mediate signal transduction by activating second-messenger systems within the cell. In the past two decades, a wealth of information has emerged regarding the molecular biology and pharmacology of classic neurotransmitter receptors (including adrenergic, dopaminergic, serotonergic, cholinergic, glycine, γ-aminobutyric acid [GABAA], and glutamate receptors). Further, the distribution of subunits comprising these receptors has been extensively studied. This review focuses on the molecular ontogeny of several of the major neurotransmitter receptor systems in the mammalian central nervous system, highlighting the role that some of these may play during brain development and in certain pathologic states. ( J Child Neurol 2001;16:271-281).
Thrombolytic Therapy in an Adolescent Ischemic Stroke
Authors: Noser Elizabeth Anne , Felberg Robert A. , Alexandrov Andrei V.
Published: January 2008

We report the case of a 16-year-old Caucasian girl who developed acute onset of left hemiplegia, left hemisensory deficit, and dysarthria. After a negative computed tomographic scan of the brain, the patient was given intravenous recombinant tissue plasminogen activator according to established adult guidelines. The patient experienced a marked improvement within 24 hours. Stroke etiology was determined to be a paradoxical embolus via a patent foramen ovale associated with pelvic vein thrombosis. This case illustrates the importance of early recognition of stroke and the utility of thrombolytics in treating ischemic infarcts in the adolescent population. ( J Child Neurol 2001;16:286-288).
Cognition, Attention, and Behavior in Prader-Willi Syndrome
Authors: Gross-Tsur Varda , Landau Yael E. , Benarroch Fortu , Wertman-Elad Raaya , Shalev Ruth S.
Published: January 2008

We studied the academic, cognitive, and behavior profile of 18 patients with Prader-Willi syndrome. All had severe learning disabilities in arithmetic and writing, and the majority were also dyslexic. Their average Full-Scale IQ was 73.7 ± 8.9, which was 1 SD below normal range, whereas their performance on executive, memory, and visuospatial tasks ranged from 2.1 to 7.0 SD below the expected means. Behavioral problems were measured using the Child Behavior Checklist, on which the majority scored in the pathologic range for social and attention problems, delinquent and aggressive behavior, somatic complaints, and thought problems. Genotypes of the children did not predict cognitive or behavioral profile, nor could behavior be associated with parameters of weight or IQ. In summary, we found that patients with Prader-Willi syndrome have profound learning disabilities and cognitive deficits, greater than expected for their IQ. Behavioral problems, including attention-deficit hyperactivity disorder (ADHD), are also prevalent and impede the overall management of this group of patients. The genotypes were not helpful in predicting cognitive or behavioral patterns. ( J Child Neurol 2001;16:288-290).
Topical Review: La Crosse and Other Forms of California Encephalitis
Authors: Rust Robert S. , Thompson Wayne H. , Matthews Charles G. , Beaty Barry J. , Chun Raymond W.M.
Published: January 2008

The California serogroup viruses are mosquito viruses that cause human infections on five continents. They are maintained and amplified in nature by a wide variety of mosquito vectors and mammalian hosts; they thrive in a remarkably wide variety of microclimates (eg, tropical, coastal temperate marshland, lowland river valleys, alpine valleys and highlands, high boreal deserts, and arctic steppes). In 1993, California serogroup viruses caused 71% of all cases of arboviral illness in the United States, principally La Crosse encephalitis.1 The 30 to 180 annual cases of La Crosse encephalitis represent 8% to 30% of all cases of encephalitis, rendering this illness the most common and important endemic mosquito-borne illness in the USA. Subclinical or mild infections are much more common. Methods and results acquired from intense study of California serogroup viruses have been applied, with benefit, to the study of the ecology and pathogenesis of many more serious human arboviral illnesses. The evolutionary potential of viruses, with particular reference to the development of more virulent strains, has been studied more closely in the California serogroup viruses than in almost any other agent of human disease. ( J Child Neurol 1999;14:1-14).
Topical Review: Vigabatrin in the Treatment of Infantile Spasms in Tuberous Sclerosis: Literature Review
Authors: Hancock Eleanor , Osborne John P.
Published: January 2008

The purpose of this report is to review the efficacy and safety of vigabatrin in the treatment of infantile spasms in infants suffering from tuberous sclerosis complex. We reviewed all studies published in the English-language literature investigating the use of vigabatrin in the treatment of infantile spasms. Ten studies gave results for the efficacy of vigabatrin in infantile spasms for infants both with and without underlying diagnoses of tuberous sclerosis. Of the 313 patients without tuberous sclerosis complex, 170 (54%) had complete cessation of their infantile spasms; of the 77 patients with tuberous sclerosis complex, 73 (95%) had complete cessation of their seizures. We conclude that vigabatrin should be considered as first-line monotherapy for the treatment of infantile spasms in infants with either a confirmed diagnosis of tuberous sclerosis or those at high risk, ie, those with a first-degree relative with tuberous sclerosis complex. Paradoxically, in those without tuberous sclerosis complex, vigabatrin might be less efficacious than suggested by studies including patients with tuberous sclerosis complex. (J Child Neurol 1999;14:71-74).
Hemispheric Language Dominance in Children Demonstrated by Functional Magnetic Resonance Imaging
Authors: Lee Benjamin C. P. , Kuppusamy Karthikeyan , Grueneich Royal , El-Ghazzawy Omar , Gordon Rachael E. , Weili Lin  , Haacke E. Mark
Published: January 2008

The objective of this study was to demonstrate hemispheric language dominance in normal children. Fifteen normal children were evaluated with functional magnetic resonance imaging (MRI) using an age-related silent word spelling paradigm. The data were analyzed with the cross-correlation method, and lateralization indices were calculated in language regions as determined by Talairach coordinates. Activation foci were detected in the left inferior frontal area and were strongly lateralized, with language lateralization indices of 0.74 ± 0.21 (age 7-12 years, nine subjects), and 0.79 ± 0.18 (13-18 years, six subjects). The indices were similar to those for adults (0.83 ± 0.21, four subjects). Our study established that language is strongly lateralized to the left hemisphere in children as young as 7 years of age. (J Child Neurol 1999;14:78-82).
Clinical, Pathologic, and Neurochemical Studies of an Unusual Case of Neuronal Storage Disease With Lamellar Cytoplasmic Inclusions: A New Genetic Disorder?
Authors: Rose Arthur L. , Farmer Peter M. , Mitra Nirmala , Wisniewski Krystyna E. , Pullarkat Raju K.
Published: January 2008

A child of first-cousin Puerto Rican parents had global developmental delay, failure to thrive, and hypotonia since early infancy. At 1½ years of age, she developed clinical and electrophysiologic evidence of progressive motor and sensory neuropathy At 2½ years, she developed visual impairment and optic atrophy followed by gradual involvement of the 7th, 9th, 10th, and 12th cranial nerves. Uncontrollable myoclonic seizures began at 4 years and she died at 6 years of age. Motor nerve conduction velocities were initially normal and later became markedly slowed. Sensory distal latency responses were absent. Lysosomal enzyme activities in leukocytes and fibroblasts were normal. Sural nerve and two muscle biopsies showed only nondiagnostic abnormalities. Electron microscopy of lymphocytes, skin, and fibroblasts showed cytoplasmic inclusions. Light microscopy of frontal cortex biopsy showed neuronal storage material staining positively with Luxol fast blue, and electron microscopy showed cytoplasmic membranous bodies in neurons, suggesting an accumulation of a ganglioside. At autopsy, all organs were small but otherwise normal and without abnormal storage cells in the liver, spleen, or bone marrow. Anterior spinal nerve roots showed loss of large myelinated axons. The brain was small and atrophic; cortical neurons showed widespread accumulation of storage material, most marked in the pyramidal cell layer of the hippocampus. Subcortical white matter was gliotic with loss of axons and myelin sheaths. In cortical gray matter there was a 35% elevation of total gangliosides, with a 16-fold increase in G M3, a three- to four-fold increase in GM2 gangliosides, and a 15-fold elevation of lactosyl ceramide. GM3 sialidase activity was normal in gray matter at 3.1 nmols/mg protein per hour and lactosyl ceraminidase I and II activities were 70% to 80% of normal. In white matter, total myelin was reduced by 50% but its composition was normal. Phospholipid distribution and sphingomyelin content were normal in gray matter, white matter, and in the liver. These biochemical findings were interpreted as nonspecific abnormalities. The nature of the neuronal storage substance remains to be determined. (J Child Neurol 1999;14:123-129).
Congenital Hydranencephalic-Hydrocephalic Syndrome Associated With Mitochondrial Dysfunction
Authors: Castro-Gago Manuel , Alonso Adela , Pintos-Martinez Elena , Beiras-Iglesias Andrés , Campos Yolanda , Arenas Joaquin , Novo-Rodriguez Maria Inés , Eiris-Punal Jesus
Published: January 2008

We report the case of a 3-year-old girl, the only child of a nonconsanguineous couple without relevant antecedents, who was born with hydranencephalic-hydrocephalic syndrome diagnosed by ultrasonography at gestation week 28, and who was treated during the neonatal period by implantation of a ventriculoperitoneal shunt. She showed severe mental retardation, and died at age 4 years following an acute respiratory infection. Due to persistently high lactic acid levels in blood, muscle and skin biopsies were taken. Analysis of muscle biopsies revealed microscopic and ultrastructural alterations typical of mitochondrial disorders, and low levels of complexes III and IV of the mitochondrial respiratory chain. The enzymes of the pyruvate dehydrogenase complex showed normal activities in cultured skin fibroblasts. These findings raise the possibility that at least some cases of congenital hydranencephalic-hydrocephalic syndrome may be due to alterations in the mitochondrial respiratory chain. (J Child Neurol 1999; 14: 131-135).
Topical Review: Management of the Respiratory Complications of Neuromuscular Diseases in the Pediatric Intensive Care Unit
Authors: Birnkrant David J. , Pope John F. , Eiben Robert M.
Published: January 2008

Pediatric neuromuscular diseases such as Duchenne muscular dystrophy and spinal muscular atrophy cause pulmonary compromise. In severely affected patients, upper respiratory tract infections exacerbate lower respiratory tract secretion retention, with the potential for pneumonia, pulmonary atelectasis, and respiratory failure. In the pediatric intensive care unit, effective treatment includes noninvasive positive pressure ventilation and manual and mechanical mucus clearance techniques. A practical approach to commonly encountered respiratory complications in pediatric neuromuscular diseases is presented in this review. (J Child Neurol 1999; 14:139-143).
Neuropsychologic and Adaptive Functioning in Adolescents and Young Adults Shunted for Congenital Hydrocephalus
Authors: Hommet Caroline , Billard Catherine , Gillet Patrice , Barthez Marie Anne , Lourmiere Josette Maheut , Santini Jean Jacques , de Toffol Bertrand , Corcia Philippe , Autret Alain
Published: January 2008

The major aim of this study was to assess whether the syndrome of nonverbal learning disabilities described in hydrocephalic children is observed in adulthood. Eleven adults shunted for congenital hydrocephalus related to spina bifida and eight adults shunted for hydrocephalus related to aqueductal stenosis were administered an extensive neuropsychologic battery to investigate discrepancies between verbal and visuospatial cognition, verbal and visuospatial long-term memory, and psycho-social adaptive abilities. The results showed no discrepancies between Wechsler Performance IQ or Verbal IQ in either hydrocephalic group. Nevertheless, the subjects with spina bifida appeared more cognitively impaired than the subjects with aqueductal stenosis, who performed normally on the Wechsler Adult Intelligence Scale-Revised. Memory assessment using Signoret's Memory Battery revealed no discrepancy between verbal and visuospatial memory in the hydrocephalic group. Nevertheless, the subjects with spina bifida had poorer verbal and visuospatial memory performance than the subjects with aqueductal stenosis. There were no differences on the Vineland Adaptive Behavioral Scale between subjects with spina bifida and those with aqueductal stenosis in autonomy, socialization, and daily living skills. These results suggest that shunted congenital hydrocephalus is not characterized by nonverbal learning disabilities syndrome in adolescence or in adulthood. (J Child NeuroL 1999;14:144-150).
Differing Risk Factors for Cerebral Palsy in the Presence of Mental Retardation and Epilepsy
Authors: Arpino Carla , Curatolo Paolo , Stazi Maria Antonietta , Pellegri Alda , Vlahov David
Published: January 2008

Whether the combined diagnosis of cerebral palsy with mental retardation or with mental retardation and epilepsy reflects more severe manifestations of the spectrum of cerebral palsy, or whether these conditions reflect overlapping outcomes related to different exposure, remains an open question. At two centers, in Rome and Conegliano, Italy, 51 children with combined cerebral palsy, mental retardation, and epilepsy, 31 children with both cerebral palsy and mental retardation, and 48 with cerebral palsy alone were identified and examined, and their mothers interviewed. The triple diagnosis group was significantly more likely than the other two groups to have a history of neonatal convulsions and a history of epilepsy in first-degree relatives, but less likely to have a mother's age at delivery greater than 33 years, a birthweight less than 1500 g, or gestational age less than 32 weeks. The dual diagnosis group was more likely than the other two groups to have maternal education of less than 8 years. These data suggest the possibility of different etiopathogenetic pathways for various presentations of cerebral palsy. (J Child Neurol 1999;14:151-155).
Association of the 677C→T Mutation on the Methylenetetrahydrofolate Reductase Gene in Turkish Patients With Neural Tube Defects
Authors: Boduroglu Koray , Alikaşifoğlu Mehmet , Anar Burcu , Tunçbilek Ergul
Published: January 2008

We report the analysis of the 677C→T mutation on the 5,10-methylenetetrahydrofolate reductase gene in Turkish controls and cases of neural tube defects. Mutation analysis of 91 patients with neural tube defects, 72 mothers, 63 fathers, and 93 healthy controls has been made by polymerase chain reaction and allele specific restriction digestion with Hinf I. We did not find a significant difference in the 677C→T allele and genotype distribution among the patients with neural tube defects, their parents, and the control group. This result suggests that another mutation in the folate-related enzyme genes could be responsible for neural tube defects in Turkey. None of the mothers of patients with neural tube defects was advised to use folic acid as recommended to prevent neural tube defects. An immediate attempt to establish an education program for healthcare providers and women of childbearing age is crucial in Turkey. Furthermore, fortification of foods with folate would be a better approach. (J Child Neurol 1999;14:159-161).
Rett Syndrome: Randomized Controlled Trial of L-Carnitine
Authors: Ellaway Carolyn , Williams Katrina , Leonard Helen , Higgins Gwen , Christodoulou John
Published: January 2008

Rett syndrome is a severe neurodevelopmental disorder of unknown etiology, occurring almost exclusively in female patients. The etiology and functional significance of plasma carnitine deficiency seen in some patients with Rett syndrome is unknown. To investigate whether L-carnitine might be of benefit in Rett syndrome, a randomized, placebo-controlled, double-blind crossover trial of L-carnitine has been completed in 35 subjects. Eight-week treatment phases were completed for both a placebo and L-carnitine. Outcome was measured by parents/caregivers and at medical follow-up using three established tools: the Rett Syndrome Motor Behavioral Assessment, the Hand Apraxia Scale, and the Patient Well-Being Index. Analysis comparing change between baseline and week 8 of treatment for L-carnitine and the placebo showed that both parents/caregivers and medical follow-up detected improvements in the subjects' well-being. In addition, medical review showed an improvement on the Hand Apraxia Scale for a higher proportion of girls on L-carnitine. Identification of predictors of clinical improvement has been limited by the power of the study. These findings suggest that L-carnitine is of benefit in some patients with Rett syndrome. While L-carnitine did not lead to major functional changes in ability, the type of changes reported could still have a substantial impact on the girls and their families. Information is still needed, however, to determine if only subgroups of girls with the disorder are responsive to L-carnitine and the appropriate duration of therapy. ( J Child Neurol 1999;14:162-167).
Clinical Trials in Motor Neuron Diseases
Authors: Miller Robert G.
Published: January 2008

Although there is no truly effective disease-specific therapy for any of the motor neuron diseases, rapid progress in our understanding of the pathophysiology of some of these disorders is being made. In addition to progress in neuroscience, clinical trials of agents that appear to slow the progress of at least one of these diseases, amyotrophic lateral sclerosis, are beginning to show promising results. The first clinical trials in spinal muscular atrophy are currently underway. A number of other developments have raised the quality of clinical trials, which should improve their productivity and efficiency in the future. (J Child Neurol 1999;14:173-179).
Genetic Susceptibility to Neurodevelopmental Disorders
Authors: Ryan Stephen G.
Published: January 2008

A large body of evidence suggests that genetic factors influence liability to many common neurodevelopmental disorders. Examples include Tourette syndrome, attention-deficit hyperactivity disorder, autism, and dyslexia. Characterization of the genetic component of susceptibility to these conditions at a molecular level should improve classification, elucidate fundamental neurobiologic mechanisms of disease, and suggest novel approaches to treatment. Susceptibility loci for complex traits could be identified by detecting linkage to a well-mapped genetic marker or by detecting association with a putative high-risk allele at a candidate locus. This article reviews the principles underlying these complementary approaches, and notes recent progress in specific conditions. As the molecular epidemiology of susceptibility to common neurodevelopmental disorders emerges, it might be increasingly possible to identify "high-risk" and "low-risk" genotypes. Clinicians should understand the nature of this kind of information in order to appreciate its power as well as its limitations. (J Child Neurol 1999; 14:187-195).
Slow Progression of Juvenile Metachromatic Leukodystrophy 6 Years After Bone Marrow Transplantation
Authors: Kapaun Petra , Dittmann Ralf W. , Granitzny Barbara , Eickhoff Wilhelm , Wulbrand Henning , Neumaier-Probst Eva , Zander Axel , Kohlschüetter Alfried
Published: January 2008

Metachromatic leukodystrophy refers to a group of genetic neurologic diseases caused by deficiencies of the enzyme arylsulfatase A and the resulting accumulation of sulfatides in white matter. Bone marrow transplantation has been advocated as a treatment in an attempt to correct the enzyme deficiency. Such a transplant was performed in 1991 in a 16-year-old girl with a form of late juvenile metachromatic leukodystrophy caused by a homozygous P426L mutation in the arylsulfatase A gene. Engraftment was prompt and resulted in constant enzymatic normalization of circulating lymphocytes. The elevated urinary excretion of sulfatides remained unaffected. Clinical findings up until transplantation consisted of gait disturbances, impairment of cognitive functioning, and deterioration in school performance over several years. During a 6-year follow-up period, the patient's condition was subject to major fluctuations but, on the whole, findings showed slow neurologic and neurophysiologic deterioration. The clinical course observed after bone marrow transplantation probably more or less reflects the natural course expected in this form of late-onset metachromatic leukodystrophy. (J Child Neurol 1999; 14:222-228).
Clinical Utility of the Judgment of Line Orientation Test and Facial Recognition Test in Children With Acquired Unilateral Cerebral Lesions
Authors: Paquier Philippe F. , van Mourik Marijke , Van Dongen Hugo R. , Catsman-Berrevoets Coriene E. , Creten Wouter L. , Stronks Dik L.
Published: January 2008

In unselected adult patients with brain damage, the Judgment of Line Orientation Test and the Facial Recognition Test are considered valid instruments for detecting right cerebral hemisphere lesions. It is unknown, however, whether this applies to children as well. Performance levels on the Judgment of Line Orientation Test and the Facial Recognition Test of 18 children with acquired left cerebral lesions and 14 children with acquired right cerebral lesions were reviewed. Subjects were unselected for age, sex, or etiology. Age-related norms were obtained in 81 normal controls, aged 7 to 14 years. Judgment of Line Orientation Test and Facial Recognition Test performance levels did not predict the presence of cerebral pathology per se in our unselected groups with demonstrated unilateral cerebral lesions, nor did they contribute to the prediction of the side of the lesion within the two groups with cerebral lesions. These results cast serious doubt on an important aspect of the clinical utility of both tests in children, namely their discriminative validity in the assessment of etiologically unselected populations with brain damage. (J Child Neurol 1999;14:243-248).
Marin-Amat Syndrome: Case Report and Review of the Literature
Authors: Pavone Piero , Garozzo Rosaria , Trifiletti Rosario R. , Parano Enrico
Published: January 2008

We report a 10-year-old girl with Marin-Amat syndrome, a rare facial synkinesis sometimes referred to as the inverted Marcus Gunn phenomenon. Symptoms were apparent 6 months following unilateral peripheral facial nerve palsy Her facial synkinesis failed to improve, despite improvement in her facial palsy consistent with an aberrant regeneration of the facial nerve. The clinical features of the reported cases of Marin-Amat syndrome are briefly reviewed. To our knowledge, this is the first documented report of Marin-Amat syndrome in a child. ( J Child Neurol 1999; 14:266-267).
Moyamoya Syndrome in a Patient With Congenital Human Immunodeficiency Virus Infection
Authors: Hsiung Ging-Yuek R. , Marcio Sotero de Menezes
Published: January 2008

A 10-year-old boy with congenital human immunodeficiency virus (HIV) infection developed recurrent episodes of left hemiparesis at age 7 years. The progression of his disease was followed by computed tomography, magnetic resonance imaging, magnetic resonance angiography, and cerebral angiography. The series of images showed progressive stenosis of both carotid arteries at the suprasellar origin with involvement of his anterior and middle cerebral arteries, while prominent collateral vessels developed from his external carotid supply through ophthalmic and middle meningeal arteries. The pattern of cerebrovascular disease is consistent with moyamoya syndrome. We suggest that further studies on the pathophysiology of cerebrovascular disease in patients with HIV could be helpful in understanding the cause of moyamoya disease as well. Also, with the various advances in treatment of HIV, neurovascular complications could be seen more frequently as the long-term survival in these patients improves. ( J Child Neurol 1999; 14:268-270).
Topical Review: Hypertensive Encephalopathy, Reversible Occipitoparietal Encephalopathy, or Reversible Posterior Leukoencephalopathy: Three Names for an Old Syndrome
Authors: Pavlakis Steven G. , Frank Yitzchak , Chusid Rebecca
Published: January 2008

Children with hypertension, seizures, lethargy, encephalopathy, headache, and occipital blindness are reviewed. After undergoing antihypertensive therapy, most children improve. Some patients have a similar syndrome associated with chemotherapy, transplantation, transfusion, or human immunodeficiency virus-1 (HIV-1) infection. These latter children can develop symptoms with only minimal or no discernible elevations in blood pressure and improve, in the case of cancer-associated encephalopathy, after discontinuing chemotherapy. The reported children with this distinctive clinical condition are compared to adults with reversible posterior leukoencephalopathy syndrome. Since both gray and white matter are involved, we had suggested previously that the name be changed to (reversible) occipitoparietal encephalopathy syndrome. However, reversible posterior leukoencephalopathy has been used in the adult population and probably should be employed in children for the sake of uniformity, since both children and adults have the same clinical presentation and presumably a similar pathophysiology for the encephalopathy syndrome. The diagnosis is confirmed by reversible posterior abnormalities seen on T2-weighted brain magnetic resonance imaging, and by the presence of either headache, altered mental status, seizures, or visual disturbances. ( J Child Neurol 1999;14:277-281).
Evaluation of Gross and Fine Motor Functions in Children With Hemidecortication: Predictors of Outcomes and Timing of Surgery
Authors: Graveline Chantal , Hwang Paul , Bone Gillian , Shikolka Carey , Wade Shawna , Crawley Adrian , Mikulis David
Published: January 2008

The purpose of this study is three-fold: First, to determine the levels of gross and fine motor functions in children before and after hemidecortication, using standardized measurement tools; second, to investigate if predictors of these outcomes can be characterized; and third, to explore if both clinical measures and functional magnetic resonance imaging (MRI) potentially can identify optimal timing of surgery. The Gross Motor Function Measure and the Quality of Upper Extremity Skills Test are shown to be comprehensive, standardized outcome measures of movement performance in affected children. Age at surgery and interval between age at seizure onset and age at surgery could be the most reliable predictors of clinical outcomes. Functional MRI studies are valuable in exploring the potential of the cortical reorganization that sustains residual sensorimotor function. The combination of clinical measures with functional MRI is a promising method of inquiry into developmental and plasticity processes. (J Child Neurol 1999;14:304-315).
Topical Review: Molecular Heterogeneity in Medulloblastoma With Implications for Differing Tumor Biology
Authors: Adesma Adekunle M.
Published: January 2008

Medulloblastomas and related primitive neuroectodermal tumors are the second most common malignant tumors of childhood. In spite of improvements in cancer therapy, these tumors are still associated with significant morbidity and mortality. Although these tumors share similar histologic features, recent molecular studies suggest that they could represent a genetically mixed group of tumors. The genetic events that might play a role in the biology of these tumors also could allow a molecular subtyping of medulloblastomas. Such molecular subtyping of medulloblastomas could allow for the use of newer therapeutic techniques, such as gene therapy, for selective targeting of critical genetic events in subsets of medulloblastomas. It is becoming increasingly clear that in medulloblastomas, the morphologic similarity of "small blue" cells does not imply similar or shared molecular characteristics, with implications for differing tumor biology. (J Child Neurol 1999;14:411-417).
Extrapontine Myelinolysis With Involvement of the Hippocampus in Three Children With Severe Hypernatremia
Authors: Brown William D. , Caruso June M.
Published: January 2008

Central pontine myelinolysis is a disorder of unknown etiology linked to overly aggressive correction of hyponatremia. In addition to the typical location of demyelination with preservation of neurons and axon cylinders in the basis pontis, similar lesions have been described in extrapontine locations. Central pontine myelinolysis and extrapontine myelinolysis usually occur together, and are identified at autopsy rather than in life because symptoms of extrapontine myelinolysis are often masked in the critically ill patient. Central pontine myelinolysis is described in children, usually in the clinical setting of hyponatremic dehydration. Extrapontine myelinolysis has not been described in children previously. We report three children with severe hypernatremia and extrapontine myelinolysis involving various combinations of thalamus, basal ganglia, external and extreme capsules, and cerebellar vermis. All three had additional involvement of the hippocampus seen on T2-weighted magnetic resonance imaging. None of the three had detectable pontine lesions. Clinical features of the three cases were dehydration in a 28-month-old girl, respiratory syncytial virus bronchiolitis in a 14-month-old girl, and acute respiratory failure due to anaphylaxis after consumption of walnuts in a 3-year-old boy. Peak sodium values in each child were 195, 168, and 177 mmol/L, respectively; each received aggressive treatment for hypernatremia. We believe this to be the first report of extrapontine myelinolysis in children, the first report of extrapontine myelinolysis without central pontine myelinolysis in children, and the first report in children of hippocampal formation involvement. The pathogenesis of the central and extrapontine myelinolysis complex in children is more complicated than previously believed, and might differ significantly from that of adults. (J Child Neurol 1999;14:428-433).
Seizures in Chiari I Malformation: A Clinical and Electroencephalographic Study
Authors: Elia Maurizio , Biondi Roberto , Sofia Vito , Musumeci Sebastiano A. , Ferri Raffaele , Capovilla Giuseppe , Curatolo Paolo
Published: January 2008

Seven subjects with Chiari I malformations and seizures (four males, three females; age range 11 years, 7 months to 36 years; mean, 22.28 ± 7.58 years; median, 21) were identified in four different centers from among a group of 10 patients. Our aim was to analyze clinical and electroencephalographic characteristics of seizures in this etiologically homogeneous group of patients. Most of the seizures were of the complex partial type, and paroxysmal abnormalities were mainly localized over the frontal and temporal regions. The course of the epilepsy was rather benign, with complete control of seizures in four patients and an important reduction in frequency in the remaining three subjects. Other cortical alterations are not usually associated with the typical abnormalities of the posterior fossa in Chiari I malformation; thus, it is possible to hypothesize that cerebral microdysgenesis or, alternatively, a cerebellar dysfunction could underlie epileptogenesis in these patients. (J Child Neurol 1999;14:446-450).
Ischemic Stroke and Migraine in Childhood: Coincidence or Causal Relation?
Authors: Ebinger Friedrich , Boor Rainer , Gawehn Joachim , Reitter Bernd
Published: January 2008

Although migraine is an accepted cause of cerebral infarction in adults, this association is less well recognized in children. We present two children with migraine and cerebral infarction, which we regard as migrainous stroke, though neither patient fulfills all criteria of the International Headache Society for the diagnosis of migrainous infarction. Review of the literature concerning examples of migraine-associated stroke in childhood suggests that these criteria are too restrictive to comprise the majority of migrainous strokes, especially in this age group. (J Child Neurol 1999; 14:451-455).
Congenital Intramedullary Tumor With Neonatal Manifestations
Authors: Nunes Magda Lahorgue , Barbosa Coutinho Ligia Maria , Janisch Clauber , Camera Ehlers João Arthur
Published: January 2008

The authors report on a 45-day-old boy with a congenital intramedullary tumor with clinical manifestations since birth. Neurologic examination disclosed severe bilateral lower-limb hypotonia and diplegia, with exacerbated deep tendon reflexes and clonus associated with severe pain at manipulation. Further evaluation of this patient included screening for infections, computed tomographic scan, myelography, and somatosensory evoked potentials. The definite diagnosis was a solid holocord astrocytoma. This report discusses a rare disorder in the neonatal period and makes other medical practitioners aware of this diagnosis. Previously published literature is also reviewed. ( J Child Neurol 1999; 14:467-469).
Medication Cost Reduction in Children on the Ketogenic Diet: Data From a Prospective Study
Authors: Gilbert Donald L. , Pyzik Paula L. , Vining Eileen P.G. , Freeman John M.
Published: January 2008

In a prospective study of the efficacy of the ketogenic diet in children with severe, refractory epilepsy, data were collected on medication changes over 1 year. Cost reductions in medications were calculated over the first year and estimated for a second year. Fifty-seven percent of the children stayed on the diet for 1 year, and 74% of these children had their number of medications reduced. Forty-eight percent of children who stayed on the diet were on no medications at 12 months follow-up. Daily medication costs were reduced by nearly 70%. (J Child Neurol 1999;14:469-471).
Expression of the Myotonic Dystrophy Locus-Associated Homeodomain Protein in Congenital Myotonic Dystrophy
Authors: Tachi Nobutada , Ohya Kazuhiro , Chiba Shunnzo
Published: January 2008

DM locus-associated homeodomain protein (DMAHP), a newly recognized homeodomain protein, is a candidate flanking gene and expressed in various tissues. We examined the expression of the DMAHP in tissues from a congenital myotonic dystrophy patient in comparison to that of control tissues by using semiquantitative reverse transcriptase-polymerase chain reaction. Reduced expression of DMAHP was observed in tissues from the patient with congenital myotonic dystrophy. This finding supports that reduced expression of DMAHP is related to the CTG repeat expansion. (J Child Neurol 1999;14:471-473).
Anomalous Ependyma Inducing Split Cord and Meningomyelocele?
Authors: Flitman Howard P. , Stanek Jerzy , Hsu Helen W. , de Courten-Myers Gabrielle M.
Published: January 2008

The case is that of a female fetus of 17 to 18 weeks' gestation with major defects of the central nervous system: (1) The thoracic vertebrae demonstrated rachischisis, with segmental diplomyelia; the duplicated cords were dissimilar in size and lay side by side within a single meningeal sheath lacking a dividing septum or spur. Cranially to the divided cord lay an unsplit segment of "open cord" lacking the posterior elements and exposing the centrally placed ependyma of the central canal flanked by glial and epidermal lining, respectively; it could be regarded as an example of a meningomyelocele. (2) Heterotopic massed ependymal cells, some of which were actively proliferating, were associated with the choroid plexus in the brain. Minor anomalies included cerebellar heterotopia and the malpositioning of dorsal root ganglia outside the meningeal sheath. Because the ependyma is such a powerful inducer of the development of neighboring tissue, the findings could be united by a common pathogenic theme, viz problematic ependymal development and migration within both the brain and spinal cord. The causative agent responsible for these abnormalities remains unidentified, but the balance of evidence suggests that its effect was felt during the second week of postconceptual age. (J Child Neurol 1999;14:473-477).
Restricted Unilateral Sydenham's Chorea: Reversible Contralateral Striatal Hypermetabolism Demonstrated on Single Photon Emission Computed Tomographic Scanning
Authors: Dilenge Marie-Emmanuelle , Shevell Michael I. , Dinh Laurent
Published: January 2008

Sydenham's chorea results from group A streptococcus infection and subsequent generation of antineuronal antibodies directed at the caudate nucleus and putamen. Predominantly bilateral, in up to 30% of cases the chorea can be unilaterally restricted. Imaging studies, both structural (magnetic resonance imaging) and functional (positron emission tomography), in patients with bilateral Sydenham's chorea have suggested reversible striatal abnormalities. Two patients with unilateral Sydenham's chorea are presented. Computed tomographic and magnetic resonance imaging were normal in both. However, hexamethylpropylenamine oxime single photon emission tomographic (HMPAO SPECT) studies demonstrated hypermetabolism in the contralateral basal ganglia. Resolution of symptoms in one of the patients coincided with normalization of the SPECT scan. Thus, unilateral striatal hypermetabolism appears to underlie the contralateral chorea observed. ASPECT scan probably should be included in the work-up of new-onset chorea. (J Child Neurol 1999;14:509-513).
Plantar Response Profile of High-Risk Infants at One Year of Life
Authors: Zafeiriou Dimitrios I. , Tsikoulas Ioannis G. , Kremenopoulos Georgios M. , Kontopoulos Eleftherios E.
Published: January 2008

To clarify the plantar reflex profile at 1 year of life in different categories of neurodevelopmental abnormalities, plantar responses were examined prospectively in 204 high-risk infants, of whom 58 developed cerebral palsy, 22 had developmental retardation without motor disturbance, and 124 were normal at a follow-up examination at 3 years of age. The plantar response was extensor in 82.3% of infants subsequently found to be neurologically normal at the first month of life, becoming flexor at the age of 9 and 11 months in 68.5% and 86.3%, respectively. Twenty-one (42.9%) of 49 patients with various types of spastic cerebral palsy demonstrated a combined extensor response (ie, dorsiflexion of the great toe with fanning of the remaining toes) as early as the first month of life. Children with spastic quadriplegia and hemiplegia more frequently demonstrated a combined extensor response compared to diplegic patients. The combined extensor plantar response remains a reliable prognostic clinical tool that contributes to an earlier diagnosis of spastic cerebral palsy as early as the first month of life. (J Child Neurol 1999;14:514-517).
Flow Cytometric Evaluation of Defects of the Mitochondrial Respiratory Chain
Authors: Williams Andrew J. , Coakley John C. , Christodoulou John
Published: January 2008

Cultured human skin fibroblasts from 12 patients with a variety of mitochondrial respiratory chain defects were examined for their capacity to oxidize dihydrorhodamine-123 to the fluorescent molecule rhodamine-123 using a flow cytometer. We found that cells from patients with functional defects in respiratory chain enzymes were less able to oxidize dihydrorhodamine-123 than those of healthy controls. Ten of the cell strains had reduced activity in at least one of the respiratory chain complexes and also showed significantly reduced fluorescence when compared to the mean of eight normal control cell strains. One patient had mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (with the A3243G mutation) and reduced respiratory chain activities in muscle and liver. Molecular analysis did not show the mutation in cultured skin fibroblasts, and had correspondingly normal fluorescence. The 12th cell strain showed reduced fluorescence but did not reach statistical significance. This strategy could be of use in helping direct further investigations in patients, and in studying the biochemical pathogenesis of mitochondrial DNA mutations in cybrid studies. (J Child Neurol 1999;14:518-523).
Electroencephalographic Findings in Ornithine Transcarbamylase Deficiency
Authors: Brunquell Philip , Tezcan Kamir , DiMario Francis J.
Published: January 2008

A 3-day-old infant presented with anorexia, irritability, hypotonia, and seizures. Blood ammonia was 2115 pmol/L and amino and organic acid analyses were consistent with ornithine transcarbamylase deficiency. Liver biopsy confirmed only 1% enzyme activity. The patient was treated with hemodialysis. An electroencephalogram (EEG) revealed multifocal independent spike-and-sharp-wave discharges. After initial stabilization he was placed on a low-protein diet with citrulline and phenylbutyrate. Conjugating agents (arginine, sodium benzoate, and sodium phenylacetate) have been added during periods of metabolic decompensation. Although developmentally delayed, the patient has shown signs of clinical improvement and EEG activity has likewise improved with only mild background slowing and no evidence of epileptogenic activity at 4 years of age. A second infant presented at 3 days of age with a similar history, blood ammonia of 1382 μmol/L, and metabolic studies indicative of ornithine transcarbamylase deficiency. EEG showed multifocal independent ictal and interictal discharges. Electrographic abnormalities persisted despite lowering of blood ammonia with hemodialysis and conjugating agents. The patient continued to decline clinically and died on the 7th hospital day. EEG changes parallel the clinical course of ornithine transcarbamylase deficiency and may serve as an objective marker of the effectiveness of therapeutic interventions. (J Child Neurol 1999;14:533-536).
Cerebral Glucose Metabolism in Type I α-N-Acetylgalactosaminidase Deficiency: An Infantile Neuroaxonal Dystrophy
Authors: Rudolf Jobst , Grond Martin , Planck Max , Schindler Detlev , Heiss Wolf-Dieter , Desnick Robert J.
Published: January 2008

Cerebral glucose metabolism was investigated in a 4.8-year-old boy with α- N-acetylgalactosaminidase deficiency using 2-[18F]fluoro-2-deoxy-D-glucose and positron emission tomography (PET). In comparison to normal values for age, the overall cerebral glucose metabolism was reduced and the regional cerebral glucose metabolism was decreased in proportion to the degree of atrophy. In the supratentorial cortical regions, the hypometabolism was asymmetric. However, the level of regional cerebral glucose metabolism in all cortical regions excluded a persistent vegetative state. In the lentiform nucleus and the head of the caudate, comparatively increased regional cerebral glucose metabolism was documented, similar to findings in neurodegenerative disorders with active epilepsy. In contrast, the infratentorial structures (cerebellar hemispheres, brain stem, mesencephalon, and hypothalamus), which are predominantly affected by the atrophic process, showed distinct and symmetric hypometabolism. Thus, the 2-[18F]-fluoro-2-deoxy-D-glucose PET scans provided additional insight into and correlation of the functional and structural disturbances in type I α- N-acetylgalactosaminidase deficiency, in addition to documenting the hypometabolism due to brain atrophy. (J Child Neurol 1999;14:543-547).
Rett Syndrome: Photographic Evidence of Rapid Regression
Authors: Fiumara Agata , Barone Rita , D'Asero Giuliana , Marzullo Elisabetta , Pavone Lorenzo
Published: January 2008

Rett Syndrome is known to occur in females, around the second year, with loss of hand use, onset of stereotypes and acquired microcephaly. Such regression is often very rapid, but this has never been documented. In one of our patients, photographs taken at different times clearly demonstrate the rapid progression of first symptoms. Moreover, in the present case, the occurrence of a febrile illness, which preceded the onset of the neurological picture, support the hypothesis that environmental factors may trigger the onset of Rett Syndrome in genetically predisposed subjects. (J Child Neurol 1999;14:550-552).
History of Joubert Syndrome and a 30-Year Follow-Up of the Original Proband
Authors: Andermann Frederick , Andermann Eva , Ptito Alain , Fontaine Suzanne , Joubert Marie
Published: January 2008

The 1960s were a period of great flowering in the recognition of neurologic disorders in children. The so-called ataxic cerebral palsies were an especially fertile field waiting for clarification. Congenital ataxia coupled with hyperpnea-apnea, abnormal eye movements, and retardation was identified as an autosomal-recessive syndrome eponimically associated with the senior author, Marie Joubert. The disorder, though rare, is increasingly recognized and a lay society dedicated to family support and research has been formed. In preparation for a recent symposium the original proband was re-examined 30 years later and the manifestations in adults clarified. Severe dysarthria was the most striking feature in this man, the hyperpnea-apnea had diminished, and the abnormal eye movements were less striking. Ataxia was still present but not severe. Poor judgment and borderline intelligence rounded out the clinical picture. Modem imaging has clarified, in part, the anatomic basis of this syndrome. (J Child Neurol 1999;14:565-569).
Neurogenetics of the Cerebellar System
Authors: Millen Kathleen J. , Millonig James H. , Wingate Richard J. T. , Alder Janet , Hatten Mary E.
Published: January 2008

The development of the cerebellum occurs in four basic steps. During the first epoch, genes that mark the cerebellar territory are expressed in a restricted pattern along the anterioposterior axis of the embryo. In the second, an embryonic region termed the rhombic lip generates precursors of the granule cell population of the cerebellar cortex, and the lateral pontine nucleus and olivary nucleus of the brain stem. In the third period, the program of neurogenesis of the granule neuron gives rise to the formation of the fundamental layers of the cerebellum and to the pattern of foliation. Concomitantly, programs of gene expression define the principal neuronal classes, the granule cell and Purkinje cell, that will establish the cerebellar circuitry in the postnatal period. Understanding the molecular mechanisms underlying these steps of development is likely to yield important insights into malformations such as Joubert syndrome. (J Child Neurol 1999;14:574-582).