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Showing papers in "Journal of Child Neurology in 2002"


Journal ArticleDOI
TL;DR: It is concluded that Williams syndrome is not an uncommon cause of mental retardation, with a prevalence of approximately 6% of patients with genetic etiology.
Abstract: There are limited population-based data on the occurrence of Williams syndrome. We estimated its prevalence combining data from two investigations. One was an epidemiologic study originally designed to assess the prevalence and etiology of mental retardation among 30,037 Norwegian children born between 1980 and 1985 and living in Akershus County on January 1, 1993. The other investigation was a national survey of Williams syndrome. In the first study, 213 children were referred for evaluation, whereas the second study comprised 57 cases with Williams syndrome born between 1970 and 1992, who were referred for evaluation from all Norwegian counties. The epidemiologic study revealed three children with Williams syndrome, whereas one additional case complying with our demographic criteria was identified in the national survey, thus giving a prevalence of 1 in 7500. In all cases, a typical chromosome 7q11.23 deletion was detected. We also conclude that Williams syndrome is not an uncommon cause of mental retardation, with a prevalence of approximately 6% of patients with genetic etiology.

680 citations


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

241 citations


Journal ArticleDOI
TL;DR: It is concluded that it is feasible to conduct large-scale functional MRI studies of children as young as 5 years old and can be used by other research groups to guide study design and plans for recruitment of young subjects.
Abstract: The potential benefits of functional magnetic resonance imaging (MRI) for the investigation of normal development have been limited by difficulties in its use with children. We describe the practical aspects, including failure rates, involved in conducting large-scale functional MRI studies with normal children. Two hundred and nine healthy children between the ages of 5 and 18 years participated in a functional MRI study of language development. Reliable activation maps were obtained across the age range. Younger children had significantly higher failure rates than older children and adolescents. It is concluded that it is feasible to conduct large-scale functional MRI studies of children as young as 5 years old. These findings can be used by other research groups to guide study design and plans for recruitment of young subjects.

201 citations


Journal ArticleDOI
TL;DR: After 8 weeks on L-carnosine, children showed statistically significant improvements on the Gilliam Autism Rating Scale and the Receptive One-Word Picture Vocabulary test (all P < .05).
Abstract: L-Carnosine, a dipeptide, can enhance frontal lobe function or be neuroprotective. It can also correlate with γ-aminobutyric acid (GABA)-homocarnosine interaction, with possible anticonvulsive effects. We investigated 31 children with autistic spectrum disorders in an 8-week, double-blinded study to determine if 800 mg L-carnosine daily would result in observable changes versus placebo. Outcome measures were the Childhood Autism Rating Scale, the Gilliam Autism Rating Scale, the Expressive and Receptive One-Word Picture Vocabulary tests, and Clinical Global Impressions of Change. Children on placebo did not show statistically significant changes. After 8 weeks on L-carnosine, children showed statistically significant improvements on the Gilliam Autism Rating Scale (total score and the Behavior, Socialization, and Communication subscales) and the Receptive One-Word Picture Vocabulary test (all P < .05). Improved trends were noted on other outcome measures. Although the mechanism of action of L-carnosine is...

196 citations


Journal ArticleDOI
TL;DR: Hemimegalencephaly is a rare hamartomatous malformation of the brain, remarkable for its extreme asymmetry, which can be isolated or associated with several neurocutaneous syndromes; less frequently, it also involves the brain stem and cerebellum.
Abstract: Hemimegalencephaly is a rare hamartomatous malformation of the brain, remarkable for its extreme asymmetry. It can be isolated or associated with several neurocutaneous syndromes; less frequently, it also involves the brain stem and cerebellum. Traditionally, hemimegalencephaly has been considered a primary neuroblast migratory disturbance. At present, genetic theories of pathogenesis and modern histopathology provide a basis for this complex malformation as a primary disturbance in cellular lineage, differentiation, and proliferation, interacting with a disturbance in gene expression of body symmetry, with earlier onset than radial neuroblast migration. From my personal experience with 10 patients with hemimegalencephaly and review of the literature, I have found the same clinical neurologic, neuroimaging, and neuropathologic features in isolated and syndromic hemimegalencephaly. Magnetic resonance imaging (MRI) reveals abnormal gyration, ventriculomegaly, colpocephaly, an "occipital sign" (displacement of the occipital lobe across the midline), and increased volume and T2 signal of white matter, in addition to the overall increased size of the involved hemisphere. Mild, moderate, and severe grades of severity can be recognized, providing a functional neurologic prognosis and therapeutic plan. Early diagnosis is crucial because despite neuroimaging and pathologic evidence, hemimegalencephaly sometimes still is unrecognized. Also, misdiagnosis of obstructive hydrocephalus or cerebral neoplasm can lead to unnecessary surgical procedures. Although hemispherectomy has a high morbidity, it is recommended early for patients with severe, intractable epilepsy. The mildest forms of hemimegalencephaly are infrequent and the least recognized.

187 citations


Journal ArticleDOI
TL;DR: The cell minicolumn is a self-contained ecosystem of connectivity linking afferent, efferent, and inerneuronal connections as discussed by the authors, which has been found to be abnormal in patients with autism.
Abstract: All subcortical arrangements are primarily nuclear in type. The cortex has been the first part of the brain to evolve a radial and laminar arrangement of cells. The resultant modular arrangement is based on the cell minicolumn: a self-contained ecosystem of connectivity linking afferent, efferent, and inerneuronal connections. Recently, the cell minicolumn has been found to be abnormal in patients with autism. This article relates different aspects of the cell minicolumn and larger-scale neuronal assemblies to potential research techniques and their application to clinical practice.

174 citations


Journal ArticleDOI
TL;DR: The State Trait Anxiety Inventory and Children's Depression Inventory may be used as a tool to provide information to clinicians and among the epilepsy-related factors, whereas epilepsy duration, seizure frequency, and polytherapy were determined to increase anxiety and depression, age of seizure onset, seizure type, and electroencephalographic findings were not related to Anxiety and depression.
Abstract: Cognitive and behavioral impairments are found more often among epileptic children than among their peers. In this study, we evaluated the anxiety and depression in epileptic children to compare their results with that of a healthy control group and to determine the relationship of anxiety and depression scores to epilepsy-related factors. The State Trait Anxiety Inventory (STAI) and Children's Depression Inventory (CDI) were applied to 35 patients with epilepsy aged 9 to 18 years (mean age 12.9 +/- 2.52 years) and to 35 healthy children who served as the control group. Both study and control groups were divided into two age groups (9 to 11 and 12 to 18 years) to exclude the effect of puberty on anxiety and depression scores. Significant depression and suicidal ideation were determined in the study group. The mean trait anxiety score was significantly higher in the 9- to 11-year age group of epileptic patients than the corresponding control group (35.90 +/- 6.90 and 29.33 +/- 2.84, P < .05). The mean state anxiety score (33.90 +/- 3.90 and 30.40 +/- 6.02, P < .05), trait anxiety score (38.20 +/- 6.84 and 32.20 +/- 3.90, P < .05), and depression score (16.65 +/- 8.32 and 8.15 +/- 3.15, P < .05) were significantly higher in the 12- to 18-year age group of epileptic children than in the control group. Among the epilepsy-related factors, whereas epilepsy duration, seizure frequency, and polytherapy were determined to increase anxiety and depression, age of seizure onset, seizure type, and electroencephalographic findings were not related to anxiety and depression. Symptoms of anxiety and depression are common among epileptic children, especially during puberty. The State Trait Anxiety Inventory and Children's Depression Inventory may be used as a tool to provide information to clinicians.

163 citations


Journal ArticleDOI
TL;DR: In this paper, the authors performed nocturnal polysomnography on 11 children with autism who had symptoms of disrupted sleep and wakefulness and identified rapid eye movement (REM) sleep behavior disorder in 5 of these 11 patients.
Abstract: We performed nocturnal polysomnography on 11 children with autism who had symptoms of disrupted sleep and nocturnal awakenings. We identified rapid eye movement (REM) sleep behavior disorder in 5 of these 11 patients. Since REM sleep behavior disorder typically affects elderly males with neurodegenerative diseases, the identification of this phenomenon in autistic children could have profound implications for our understanding of the neurochemical and neurophysiologic bases of autism. Further, accurate diagnosis of REM sleep behavior disorder would enable specific treatment with clonazepam and help the family and the child consolidate sleep and improve daytime performance.

147 citations


Journal ArticleDOI
TL;DR: The natural history and some important clinical manifestations of neurofibromatosis 1 are reviewed, with emphasis on features that constitute the standard diagnostic criteria and the pathogenic implications of these clinical manifestations are considered.
Abstract: Neurofibromatosis 1 occurs in 2 to 3 people per 10,000. The most frequent clinical features are cafe-au-Iait macules, neurofibromas, intertriginous freckling, Lisch nodules, and learning disabiliti...

146 citations


Journal ArticleDOI
TL;DR: In this study, the effects and side effects of rectal diazepam and intranasal midazolam were compared in the treatment of acute convulsions in children to develop a practical and safe treatment protocol and it is concluded that as an antiepileptic agent, intran asal midrazolam is more effective than rectaldiazepam.
Abstract: In this study, the effects and side effects of rectal diazepam and intranasal midazolam were compared in the treatment of acute convulsions in children to develop a practical and safe treatment protocol. In the diazepam group, the seizures of 13 (60%) patients terminated in 10 minutes; however, 9 (40%) patients did not respond. In the midazolam group, 20 (87%) patients responded in 10 minutes, but 3 (13%) patients did not respond. Regarding the anticonvulsant effect, midazolam was found to be more effective than diazepam, and the difference was statistically significant (P < .05). The necessity of a second drug for the seizures that did not stop with the first drug was higher in the diazepam group than the midazolam group, and the difference was statistically significant (P < .05). We conclude that as an antiepileptic agent, intranasal midazolam is more effective than rectal diazepam. After administration, we did not observe any serious complications. Further investigations are necessary; however, intranasal administration is easy, so if the nasal drop and spray forms used in some European countries and the United States are available worldwide, it will be very useful for physicians in the emergency room.

142 citations


Journal ArticleDOI
TL;DR: The efficacy of an imagery intervention designed specifically to train the forward modeling of purposive actions was examined, and it was shown to be equally effective to perceptual-motor training in facilitating the development of motor skill in the referred children.
Abstract: Children with impaired motor coordination (or developmental coordination disorder) have difficulty representing internally the visuospatial coordinates of intended movements. We have proposed that this deficit reflects impairment in the generation of forward models of the efference copy of intended movements-the efference-copy-deficit hypothesis. In this study, we challenged this hypothesis by examining the efficacy of an imagery intervention designed specifically to train the forward modeling of purposive actions. A pre-post design was adopted. Fifty-four children referred with motor coordination problems were assigned randomly to one of three groups: imagery training, traditional perceptual-motor training, and wait-list control. The imagery protocol-delivered by an interactive CD-ROM-was shown to be equally effective to perceptual-motor training in facilitating the development of motor skill in the referred children. These results support the efference-copy-deficit hypothesis in explaining the cause of motor clumsiness in most children. Directions for future intervention studies and remediation in the field of developmental clumsiness are discussed.

Journal ArticleDOI
TL;DR: The findings suggest that mitochondrial dysfunction, including extensive abnormalities in specific enzyme activities, mitochondrial structure, and mitochondrial DNA integrity, may be present in children with a clinical constellation including hypotonia, epileptic seizures, autism, and developmental delay.
Abstract: A group of 12 children clinically presenting with hypotonia, intractable epilepsy, autism, and developmental delay, who did not fall into previously described categories of mitochondrial encephalomyopathy, were evaluated for mitochondrial respiratory enzyme activity levels, mitochondrial DNA, and mitochondrial structural abnormalities. Reduced levels in specific respiratory activities were found solely in enzymes with subunits encoded by mitochondrial DNA in seven of eight biopsied skeletal muscle specimens evaluated. Five cases exhibited increased levels of large-scale mitochondrial DNA deletions, whereas pathogenic point mutations previously described in association with mitochondrial encephalomyopathies were not found. Mitochondrial structural abnormalities were present in three of four patients examined. Our findings suggest that mitochondrial dysfunction, including extensive abnormalities in specific enzyme activities, mitochondrial structure, and mitochondrial DNA integrity, may be present in children with a clinical constellation including hypotonia, epileptic seizures, autism, and developmental delay. The acronym HEADD is presented here to facilitate pursuit of mitochondrial defects in patients with this clinical constellation after other causes have been excluded.

Journal ArticleDOI
TL;DR: Knowing the molecular basis of the variable expression of clinical manifestations of neurofibromatosis could provide better anticipatory guidance and more effective management of the medical complications that are associated with this condition.
Abstract: Neurofibromatosis 1 serves as a paradigm for understanding the principles of human genetics. The concepts of gene mutation, penetrance of the condition, variable clinical expressivity, mosaicism, age-dependent expression of clinical manifestations, and pleiotropy are evident in this autosomal dominant condition. The lack of genotype-phenotype correlation, except the whole-gene deletion phenotype, leads to speculation on modifiers of the haploinsufficient state of the NF1 gene product neurofibromin. The variant form of neurofibromatosis, neurofibromatosis Noonan's syndrome, suggests potential interaction of independent biochemical pathways. Identification of the NF1 gene led to the discovery of its role in ras signal transduction. Neurofibromin is a negative regulator of intracellular ras signaling. This observation now provides the framework for the development of rational medical therapies. In addition, knowledge of the molecular basis of the variable expression of clinical manifestations could provide better anticipatory guidance and more effective management of the medical complications that are associated with this condition.

Journal ArticleDOI
TL;DR: Continuous midazolam and diazepam infusions were equally effective for control of refractory status epilepticus, however, midrazolam was associated with more seizure recurrence and higher mortality in refractors predominantly caused by central nervous system infections.
Abstract: The objective of this study was to compare the efficacy of continuous midazolam and diazepam infusion for the control of refractory status epilepticus. An open-label, randomized control study was undertaken at the Pediatric Emergency and Intensive Care Service of a multidisciplinary teaching and referral hospital. Subjects included 40 children, 2 to 12 years of age, with refractory status epilepticus (motor seizures uncontrolled after two doses of diazepam, 0.3 mg/kg per dose, and phenytoin infusion, 20 mg/kg). Either continuous midazolam (n = 21) or diazepam infusion (n = 19) in incremental doses was administered. The primary outcome measure was the proportion of children in each group with successful control of refractory status epilepticus. The secondary outcome measure was the time to control seizure activity, recurrence of seizure after initial control, if any, the frequency of hypotension, and the need for ventilation. The two groups were similar in age (mean +/- SD = 4.9 +/- 43.6 months) and etiology. Twenty-three (57.5%) patients had acute central nervous system infection. Refractory status epilepticus was controlled in 18 (86%) and 17 (89%) patients in the midazolam and diazepam groups, respectively (P = not significant). The median time to seizure control was 16 minutes in both groups, but in the midazolam group, seizures recurred in more children (57% versus 16% in diazepam group; P .05). Continuous midazolam and diazepam infusions were equally effective for control of refractory status epilepticus. However, midazolam was associated with more seizure recurrence and higher mortality in refractory status epilepticus predominantly caused by central nervous system infections.

Journal ArticleDOI
TL;DR: The Gray Level Index is defined as the ratio of the area covered by Nissl-stained elements to unstained area in postmortem samples, which indicates the possible presence of increased cell-packing density in subcortical structures in autistic individuals.
Abstract: Although neuropathologic studies have centered on small samples, it is accepted that brains of autistic individuals tend to be large, on average. Knowledge regarding the cause of this macrocephaly is limited. Postmortem studies reveal little in terms of cortical dysplasia. Some of these studies suggest increased cell-packing density in subcortical structures. These neuronomorphometric studies have been subjective or based their conclusions on measures of neuronal density. Our study sought the possible presence of increased cell-packing density by using the Gray Level Index. The Gray Level Index is defined as the ratio of the area covered by Nissl-stained elements to unstained area in postmortem samples. Analyzed images included Brodmann's cortical areas 9, 21, and 22 of 9 autistic patients (7 males, 2 females; mean age of 12 years, with a range of 5 to 28 years) and 11 normal controls (7 males, 4 females; mean age of 14 years, with a range of 3 to 25 years). The overall multivariate test revealed significant differences both between autistic patients and controls (P = .001) and between hemispheres (P = .025). Follow-up univariate tests showed significant diagnosis-dependent effects in feature distance (P = .005), the standard deviation in distance (P = .016), and feature amplitude (P = .001). The overall mean Gray Level Index was 19.4% in controls and 18.7% in autism (P = .724). In autism, an increased number of minicolumns, combined with fewer cells per column (or their greater dispersion), results in no global difference in neuronal density.

Journal ArticleDOI
TL;DR: This exploratory study suggests that both children who have had a stroke and their parents have significant and wide-ranging health needs.
Abstract: The aim of this study was to describe the functional consequences of childhood stroke in terms of activity limitation and to explore the relationship between extent of brain damage, impairment, and functional sequelae. A further aim was to describe the health of the parents of these children. Seventeen children and adolescents with cerebral infarction in the territory of the middle cerebral artery were enrolled in the study. A new activity limitation measure with a 4-point Likert scale (the Paediatric Stroke Activity Limitation Measure) was designed to examine the degree of difficulty experienced by the children in daily activities. The relationship between activity limitation scores, standardized health-related quality of life assessment (Child Health Questionnaire), extent of brain damage, and results of a comprehensive neurologic examination (Pediatric Stroke Outcome Measure) were investigated. Parent health was assessed using the Short-Form 36 General Health Survey. Activity limitation was evident in the domains of education, self-care, and motor skills. There was very good interobserver agreement using the new activity limitation scale between the occupational therapist and pediatric neurologist (Cohen's kappa = 0.88). In comparison with population norms, the subjects scored below average in both physical and psychologic health. There was a clear relationship between radiologically apparent extent of brain damage, degree of impairment, and functional outcome. Parental health also rated generally lower than expected. This exploratory study suggests that both children who have had a stroke and their parents have significant and wide-ranging health needs.

Journal ArticleDOI
TL;DR: It is shown that Lennox-Gastaut syndrome is one of the most difficult epilepsy syndromes to treat and is frequently resistant to treatment with standard antiepilepsy drugs.
Abstract: Lennox-Gastaut syndrome is a type of childhood epilepsy that has enormous detrimental effects on the patient's physical and developmental health and can also take a dramatic toll on the well-being of the patient's family. Lennox-Gastaut syndrome is characterized by variable etiology, multiple types of intractable seizures, and cognitive impairment in most patients. It is one of the most difficult epilepsy syndromes to treat and is frequently resistant to treatment with standard antiepilepsy drugs. This article reviews the etiology of Lennox-Gastaut syndrome, characteristics of predominant seizure types, methods of evaluating patients for Lennox-Gastaut syndrome, and available treatments including antiepilepsy drug therapy, ketogenic diet, and surgical options.

Journal ArticleDOI
TL;DR: The results support the view that clinical ADHD is the extreme of a behavioral continuum that extends into the normal population.
Abstract: Clinical diagnosis of attention-deficit hyperactivity disorder (ADHD) is based on evaluation of behavioral functioning in three domains: inattentiveness, hyperactivity, and impulsivity. Caudate and frontal lobe function figures prominently in several neuroanatomic models of attentional functioning. Studies comparing children with and without ADHD have found differences in the size and symmetry of the caudate nuclei. Using multiple regression, we tested the hypothesis that caudate volume symmetry (log left minus log right caudate volume) measured from serial sagittal magnetic resonance images in a sample of nonreferred children (12 girls/15 boys, 7.0 to 16.6 years, 81 to 129 IQ) would predict the cumulative severity of parent-reported ADHD diagnostic behaviors beyond variance predicted by age, sex, and level of internalizing problems as measured by the Child Behavior Checklist. No child had been previously diagnosed with ADHD, although one child was found to meet diagnostic criteria based on the rating scale used for the study. The degree of caudate asymmetry significantly predicted cumulative severity ratings of inattentive behaviors (P = .015), uniquely accounting for 17.1% of the variance in inattention symptomatology over demographic variables and internalizing problems, which collectively predicted 28.9% of the variance. Caudate asymmetry uniquely accounted for only 4.3% of the variance in cumulative severity ratings of hyperactive/impulsive symptomatology over demographic variables and internalizing problems that collectively predicted 21.2% of the variance. A greater degree of right to left caudate volume asymmetry predicted subclinical inattentive behaviors in a sample of nonreferred children. This finding is congruent with neuroanatomic models of attention emphasizing lateralized alteration in prefrontal/striatal systems. The results support the view that clinical ADHD is the extreme of a behavioral continuum that extends into the normal population.

Journal ArticleDOI
TL;DR: There is a slight increase in the frequency of mental retardation in children with neurofibromatosis 1, but the mean Full-Scale IQ for the patient group is within 1 SD of the population mean.
Abstract: Cognitive deficits and academic learning difficulties are the most common neurologic "complication" of neurofibromatosis 1 in childhood and can be responsible for significant lifetime morbidity. There is a slight increase in the frequency of mental retardation (Wechsler Full-Scale IQ < 70) in children with neurofibromatosis 1, but the mean Full-Scale IQ for the patient group is within 1 SD of the population mean. Academic difficulties are common, as are specific deficits in visuospatial ability, executive function, expressive and receptive language, and attentional skills. Behavioral and psychosocial problems have a major impact on quality of life, although there are few objective studies in this area Current research is focusing on the pathogenesis of the disorder. Clinical studies have identified possible radiologic and pathologic markers for cognitive deficits in neurofibromatosis 1, which can now be explored in animal models.

Journal ArticleDOI
TL;DR: The data support the hypothesis that increased production of interleukin-1β in the central nervous system or increased diffusion of inter Leukin 1β through the blood-brain barrier is involved in the pathogenesis of febrile seizures.
Abstract: Proinflammatory cytokines (such as interleukin-1β, tumor necrosis factor-α) and nitric oxide are known to have both direct and indirect modulating effects on neurons and neurotoxic neurotransmitters released during excitation or inflammation. We measured interleukin-1β, tumor necrosis factor-α, and nitrite levels in the peripheral blood and cerebrospinal fluid of children with febrile seizures and compared our results with those of children with febrile illnesses without seizures. Twenty-nine children with febrile seizure and 15 controls were studied. The mean concentrations of interleukin-1β and nitrite were significantly increased in the cerebrospinal fluid (P < .01) of the children with febrile seizure. There were no significant changes in serum interleukin-1β, tumor necrosis factor-α, nitrite, and cerebrospinal fluid tumor necrosis factorα levels. Our data support the hypothesis that increased production of interleukin-1β in the central nervous system or increased diffusion of interleukin-1β through t...

Journal ArticleDOI
TL;DR: The cerebellum is part of a distributed system for motor control as discussed by the authors, which can be seen as a set of interval-type timers rather than as a single clock with pacemaker or oscillatory properties.
Abstract: Converging evidence from different research studies supports a role for the cerebellum in timing neural processes. The cerebellum is part of a distributed system for motor control. The timing hypothesis provides a specific functional role for the unique contribution of the cerebellum. The timing capabilities of the cerebellum appear to extend beyond motor control into tasks focusing on perceptual processing that require the precise representation of temporal information and sensorimotor learning. Behavioral and modeling studies suggest that the cerebellar timing system is best characterized as providing a near-infinite set of interval-type timers rather than as a single clock with pacemaker or oscillatory properties, but this is controversial. In addition to learning precisely timed motor responses, the cerebellum is involved in on-line processing using feed-forward systems for which sensory input is used prior to movement execution to improve movement accuracy. This would be a mechanism for triggering accurate "time." The cerebellum continues to fascinate scientists, and although survival is possible without the cerebellum, the resultant quality of life is significantly compromised with clumsiness, ataxia, hypotonia, dysarthria, slowing of various cognitive perceptual processes, and impaired fine motor and ocular-motor coordination. The last three decades have seen the development of research that has focused on how the cerebellum functions. Further neurophysiologic research in cerebellar cortical neurotransmission is likely to further our understanding of the cerebellar contribution to timing sensorimotor processes.

Journal ArticleDOI
TL;DR: It is clear that until a definitive treatment for Duchenne muscular dystrophy is available, the use of deflazacort and prednisone with judicious dietary control and close clinical monitoring for side effects seems the best intervention for interim preservation of function in such a common devastating disorder of young growing boys.
Abstract: Duchenne muscular dystrophy is the most common and most severe form of childhood muscular dystrophies, resulting in early loss of ambulation between the ages of 7 and 13 years and death in the teens and twenties. Despite the phenomenal advances made in the understanding of the molecular genetics of the disease, no definitive cure has been found. Of all of the therapeutic drugs studied in Duchenne muscular dystrophy, only prednisone seems to have the potential for providing interim functional improvement for boys with Duchenne muscular dystrophy while they wait for a cure with gene or cell therapy. There is still no consensus regarding recommending corticosteroids as standard therapy for boys. This is an evidence-based review of all of the studies of corticosteroids (prednisone, deflazacort, and oxandrolone) in Duchenne muscular dystrophy. From this review, it is clear that until a definitive treatment for Duchenne muscular dystrophy is available, the use of deflazacort and prednisone with judicious dietary control and close clinical monitoring for side effects seems the best intervention for interim preservation of function in such a common devastating disorder of young growing boys.

Journal ArticleDOI
TL;DR: It is demonstrated that basal hyperinsulinemia and insulin resistance can be present in patients who develop obesity during valproic acid treatment, and these obese patients could be exposed to the risks related to these metabolic abnormalities.
Abstract: Valproic acid is effective for treatment of many types of epilepsy, but its use in epileptic patients can be associated with an increase in body weight that could interfere with treatment compliance. The weight gain may result from different mechanisms, but the exact pathogenesis is still unknown. To evaluate insulin sensitivity in adolescents who gained weight during treatment with valproic acid, we studied 20 girls with different types of epilepsy: 15 patients had primary generalized seizures, including absence seizures (3 cases), and 5 patients had partial seizures. After 1 year of valproic acid treatment, the obese patients had serum insulin levels significantly higher than patients who did not gain weight (51.4 +/- 25.3 versus 28.2 +/- 12.9). Moreover, we observed that epileptic patients who gained weight were also insulin resistant in comparison with nonobese epileptic subjects. At the end of treatment, all patients showed normal levels of serum testosterone, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), and luteinizing hormone. We found no significant correlation between insulinemia and serum valproic acid concentrations in obese and nonobese patients treated with valproic acid. Our study demonstrates that basal hyperinsulinemia and insulin resistance can be present in patients who develop obesity during valproic acid treatment. Therefore, these obese patients could be exposed to the risks related to these metabolic abnormalities; if these data are confirmed in longer studies, these side effects may raise some concerns about the safety of valproic acid.

Journal Article
TL;DR: In this article, a 25- to 4-Hz spike-wave discharge in late infancy to early childhood was found to be the earliest signs of a brain energy failure syndrome associated with mutations of the GLUT1 gene.
Abstract: Glucose transporter 1 deficiency syndrome is emblematic of a brain energy failure syndrome Energy failure also results from other genetically determined metabolic disorders, such as hypoglycemic syndromes, hypoketonemic syndromes associated with fatty acid oxidation defects, glycolytic enzymopathies, and mitochondrial defects Glucose transporter 1 deficiency syndrome is particularly illustrative of this group of disorders and produces an infantile-onset epileptic encephalopathy that responds to a ketogenic diet The electroencephalographic correlate is distinctive and emerges as a 25- to 4-Hz spike-wave discharge in late infancy to early childhood Infantile apnea and oscillatory eye movements reminiscent of opsoclonus may be the earliest signs of this condition Mutations of the GLUT1 gene are causative and transmitted as an autosomal dominant trait Thioctic acid is a glucose transporter 1 activator, whereas barbiturates and methylxanthines are glucose transporter 1 inhibitors The ketogenic diet is effective treatment for glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency It also should benefit patients with neurologic symptoms resulting from a glycolytic enzymopathy

Journal ArticleDOI
TL;DR: The minicolumnar changes provide a possible link to receptive field abnormalities and a useful clinicopathologic correlate to Asperger's syndrome.
Abstract: Asperger's disorder or syndrome is characterized by impaired social interaction, normal intelligence, and adequate language skills in the areas of grammar and vocabulary. The symptoms are pervasive in nature and usually manifested in childhood. Despite the gravity and chronicity of the condition, the medical literature remains sparse and offers no information about possible neuropathologic underpinnings. The present study is a case report on two patients with Asperger's syndrome. Neuropathologic examination revealed no degenerative changes or gliosis. A more detailed assessment with computerized image analysis indicated abnormalities in the minicolumnar organization of the three areas examined (9, 21, 22) (P = .032). Specifically, minicolumns were smaller, and their component cells were more dispersed than normal. A similar neuropathology has recently been reported for autism and disputes the uniqueness of these findings. The minicolumnar changes provide a possible link to receptive field abnormalities and a useful clinicopathologic correlate to Asperger's syndrome.

Journal ArticleDOI
TL;DR: Levetiracetam, as add-on therapy, was effective in reducing seizure frequency in a variety of seizure types but was most effective for partial-onset seizures, and its apparent positive effects on cognition in some patients are encouraging.
Abstract: Levetiracetam, one of the newer-generation antiepilepsy drugs, is not currently approved for use in children. Given its favorable efficacy, pharmacokinetic, and, particularly, safety profile in adults, we felt that it may be a useful antiepilepsy drug for children with refractory epilepsy. We treated 39 patients (mean age 8.6 years) with open-label levetiracetam for up to 9 months. Seizure frequency, drug dosages, adverse events, and neurologic examinations were documented at baseline and routine follow-up visits. Levetiracetam, as add-on therapy, was effective in reducing seizure frequency in a variety of seizure types but was most effective for partial-onset seizures. Fourteen patients were discontinued for lack of efficacy or adverse events. Ten patients reported improvements in cognition or behavior. Levetiracetam was generally effective and well tolerated in this open-label study. Its apparent positive effects on cognition in some patients are encouraging. Large, well-controlled studies are needed to...

Journal ArticleDOI
TL;DR: It is suggested that the learning disabilities associated with neurofibromatosis 1 are caused by excessive Ras activity that leads to increased γ-aminobutyric acid (GABAA) inhibition and to decreased long-term potentiation.
Abstract: Neurofibromatosis 1 is one of the most common single-gene disorders affecting neurologic function in humans. Mutations in the NF1 gene cause abnormalities in cell growth and differentiation and lead to a variety of learning disabilities. Neurofibromin has several biochemical functions, such as Ras-guanosine triphosphatase activity, adenylate cyclase modulation, and microtubule binding, all of which could be critical for brain function. We review how studies in mouse models are helping to unravel the molecular and cellular mechanisms underlying cognitive deficits in neurofibromatosis 1. These studies suggest that the learning disabilities associated with neurofibromatosis 1 are caused by excessive Ras activity that leads to increased gamma-aminobutyric acid (GABA(A)) inhibition and to decreased long-term potentiation. These findings have brought us closer than ever to the development of possible treatments for the learning disabilities associated with neurofibromatosis 1.

Journal ArticleDOI
TL;DR: In children with silent cerebral infarcts, large tissue loss is associated with lower Wechsler Full-Scale IQ and small tissue loss are associated with no apparent change in IQ compared with children with no cerebral infArcts.
Abstract: The effect of increased tissue injury in children with sickle cell disease and silent cerebral infarcts is not known. We determined the relationship between the extent of injury and IQ scores in children with silent cerebral infarcts. Participants were 27 children with sickle cell disease who had received magnetic resonance imaging. Children were divided into three groups: group 1, small lesion volume ( n = 9, 6.8 cm3); and group 3, no cerebral infarcts (n = 9). The Wechsler Full-Scale IQ was significantly lower for group 2 (mean = 76.1) when compared with group 1 (mean = 87.7) or group 3 (mean = 89.9). In children with silent cerebral infarcts, large tissue loss is associated with lower Wechsler Full-Scale IQ and small tissue loss is associated with no apparent change in IQ compared with children with no cerebral infarcts. The progressive accumulation of silent infarcts may lead to poorer intellectual functioning. (J Child Neurol 2002; 17: 890—894).

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TL;DR: It is revealed that the clinical manifestations in viable males vary from neonates with severe encephalopathy to adults with mental retardation and demonstrate genotype-phenotype correlations.
Abstract: Rett syndrome is a neurodevelopmental disorder characterized by cognitive and adaptive regression with autistic features, loss of acquired skills, and stereotypic hand movements that almost exclusively affects females. It is an X-linked dominant disorder, with presumed lethality in males. Nonetheless, there are a few descriptions of males suspected of having Rett syndrome. With the recent discovery that the MECP2 gene is responsible for most cases of Rett syndrome, it is possible to molecularly assess cases of affected males by direct sequencing analysis. We describe an Israeli family consisting of a female having classic Rett syndrome and a male sibling with severe neonatal encephalopathy. Molecular analysis revealed that both sister and brother have the same MECP2 gene mutation; however, their mother does not. This case, as well as other published studies of males with MECP2 mutations, reveals that the clinical manifestations in viable males vary from neonates with severe encephalopathy to adults with mental retardation and demonstrate genotype-phenotype correlations.

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TL;DR: It is concluded that there seems to be no correlation between the clinical stages and either the duration from the onset of subacute sclerosing panencephalitis or the MRI findings.
Abstract: We studied 36 patients (24 males, 12 females), all of whom had definite subacute sclerosing panencephalitis with typical periodic complexes in their electroencephalograms and increased titers of measles antibody in serum and cerebrospinal fluid. Their clinical and laboratory findings on admission were reviewed retrospectively. The age at onset of symptoms varied from 4 to 23 years. The average age at onset of disease was 13.1 +/- 4.18 years. The mean of the duration from the infection to the onset of subacute sclerosing panencephalitis was 9 years. Unusual symptoms, especially in the early periods of disease, included hemiparesis (7 patients), headache (3), generalized tonic-clonic seizures (6), absence seizure (1), nausea (3), and vomiting (3). Twenty-six cranial magnetic resonance imaging (MRI) and 12 computed tomography examinations were performed. Nine patients had normal MRI. In the early stages, lesions usually involved parieto-occipital corticosubcortical regions asymmetrically. In time, symmetric periventricular white-matter changes became more prominent. In addition to the common clinical findings in cases of subacute sclerosing panencephalitis reported in the literature, there were some different clinical features of the disease. Eventually, we concluded that there seems to be no correlation between the clinical stages and either the duration from the onset of subacute sclerosing panencephalitis or the MRI findings.