Showing papers in "Journal of Child Neurology in 2000"
TL;DR: Poor outcome in children after ischemic stroke is therefore frequent and more likely in the presence of arterial stroke, rehabilitation therapy, and associated neurologic disorders, which justifies clinical trials of treatment strategies in childhood isChemic stroke.
Abstract: Ischemic stroke during infancy and childhood has the potential for life-long morbidity. Information on the neurologic outcome of children who survive ischemic stroke is lacking. Children surviving ischemic stroke between January 1, 1995 and July 1, 1999 were prospectively followed. Neurologic deficit severity was based on the Pediatric Stroke Outcome Measure (PSOM) developed in this study and parental response to two recovery questions. Predictor variables for poor outcome were tested. One-hundred twenty-three children with arterial ischemic stroke and 38 with sinovenous thrombosis were followed for a mean of 2.1 years (range, 0.8 to 6.6 years). The primary outcome based on PSOM assessment was: normal, 37%; mild deficit, 20%; moderate deficit, 26%; and severe deficit, 16%. The secondary outcome was full recovery in 45% of patients, based on parental response. The primary and secondary outcome measures were moderately correlated (P < .001; K = 0.5). In bivariate analysis, arterial stroke type, male gender,...
585 citations
TL;DR: It is speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology.
Abstract: In most cases symptoms of autism begin in early infancy. However, a subset of children appears to develop normally until a clear deterioration is observed. Many parents of children with "regressive"-onset autism have noted antecedent antibiotic exposure followed by chronic diarrhea. We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology. To help test this hypothesis, 11 children with regressive-onset autism were recruited for an intervention trial using a minimally absorbed oral antibiotic. Entry criteria included antecedent broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea, deterioration of previously acquired skills, and then autistic features. Short-term improvement was noted using multiple pre- and post-therapy evaluations. These included coded, paired videotapes scored by a clinical psychologist blinded to treatment status; these noted improvement in 8 of 10 children studied. Unfortunately, these gains had largely waned at follow-up. Although the protocol used is not suggested as useful therapy, these results indicate that a possible gut flora-brain connection warrants further investigation, as it might lead to greater pathophysiologic insight and meaningful prevention or treatment in a subset of children with autism.
555 citations
TL;DR: This is the first report concerning an effect of thrombocytosis and showing that silent stroke alone is not a factor of cognitive deficit when not associated with low hematocrit or throm bocytotic.
Abstract: After obtaining familial informed consent, between January 1996 and July 1997, 173 children (5 to 15 years old) with sickle cell disease were enrolled in a prospective multicenter study using blood screening, transcranial Doppler ultrasonography (n = 143), cerebral magnetic resonance imaging (n = 144), and neuropsychologic performance evaluation (n = 156) (Wechsler Intelligence tests WISC-III, WIPPSI-R), which were also performed in 76 sibling controls (5 to 15 years old). Among the 173 patients with sickle cell disease (155 homozygous for hemoglobin SS, 8 sickle cell β0 thalassemia, 3 sickle cell β + thalassemia, 7 sickle cell hemoglobin C disease SC), 12 (6.9%) had a history of overt stroke, and the incidence of abnormal transcranial Doppler ultrasonography (defined as mean middle cerebral artery velocity > 200 cm/sec or absent) was 8.4% in the overall study population and 9.6% in patients with homozygous sickle cell anemia. The silent stroke rate was 15%. Significantly impaired cognitive functioning wa...
238 citations
TL;DR: Spasticity in patients with cerebral palsy can be treated effectively by continuous intrathecal baclofen, and adverse events, although common, were manageable.
Abstract: Intrathecal baclofen infusion has demonstrated effectiveness in decreasing spasticity of spinal origin. Oral antispasticity medication is minimally effective or not well tolerated in cerebral palsy. This study assessed the effectiveness of intrathecal baclofen in reducing spasticity in cerebral palsy. Candidates were screened by randomized, double-blind, intrathecal injections of baclofen and placebo. Responders were defined as those who experienced an average reduction of 1.0 in the lower extremities on the Ashworth Scale for spasticity. Responders received intrathecal baclofen via the SynchroMed System and were followed for up to 43 months. Fifty-one patients completed screening and 44 entered open-label trials. Lower-extremity spasticity decreased from an average baseline score of 3.64 to 1.90 at 39 months. A decrease in upper extremity spasticity was evidenced over the same study period. Forty-two patients reported adverse events. Most common reports were hypotonia, seizures (no new onset), somnolence, and nausea or vomiting. Fifty-nine percent of the patients experienced procedural or system-related events. Spasticity in patients with cerebral palsy can be treated effectively by continuous intrathecal baclofen. Adverse events, although common, were manageable.
222 citations
TL;DR: A linkage study of moyamoya disease using markers on chromosome 6, where the HLA gene is located, identified an allele with possible linkage to moyAMoya disease, and sharing of the allele among affected members in 19 families was investigated, considering the haplotype.
Abstract: Genetic factors have been suggested to contribute to the etiology of moyamoya disease. The authors have previously reported an association between moyamoya disease and several alleles for human leukocyte antigens (HLA). To further specify the genetic component of moyamoya disease, a linkage study of moyamoya disease using markers on chromosome 6, where the HLA gene is located, was performed. The 15 microsatellite markers of chromosome 6 were studied in 20 affected sibling pairs. From an identical-by-descent analysis of these markers, an allele with possible linkage to moyamoya disease was identified. Sharing of the allele among affected members in 19 families was investigated, considering the haplotype. The marker, D6S441, might be linked to moyamoya disease. Considering the haplotype, the allele was shared among the affected members in 16 (82%) of the 19 families, but not in two others. In one family, sharing of the allele could not be determined because of low heterozygosity. Further studies are necessary to clarify multiple genetic factors that are definitely linked with moyamoya disease.
206 citations
TL;DR: The Tuberous Sclerosis Complex 1998 Consensus Conference clinical criteria represent an important advance in the diagnosis of tuberous sclerosis complex and physicians should be alerted as to the frequency of the criteria in different stages of children.
Abstract: The Tuberous Sclerosis Complex 1998 Consensus Conference clinical criteria represent an important advance in the diagnosis of tuberous sclerosis complex. Since many findings regarded as highly specific for tuberous sclerosis complex are not apparent until late childhood or adulthood, refinements by age may prove of value. We have stratified 106 children into five age groups (0 to 2 years of age, above 2 to 5 years, above 5 to 9 years, above 9 to 14 years, and above 14 to 18 years). Physicians should be alerted as to the frequency of the criteria in different stages of children.
202 citations
TL;DR: It is concluded that it is important to determine the mechanism of childhood stroke, because it strongly influences outcome, the recurrence risk, and treatment choice.
Abstract: This paper describes 59 patients, 3 months to 16 years of age, who were seen consecutively in the same center for cerebral arterial infarction. It focuses on the mechanism of stroke. The pathophysiologic process could be established for 78% of the children. Arteriopathic stroke (31 patients, or 53%) was the most common. The arteriopathies were either progressive (moyamoya in 4 patients, or 7%) or nonprogressive (27 patients, or 46%). The latter form occurred in two patterns: dissection of cervicocephalic arteries (12 patients, or 20%) and transient cerebral arteriopathy of unknown origin but probably angiitis (15 patients, or 25%). Cardiac or transcardiac embolic stroke occurred in 12% of the series and systemic diseases in 14%. There was a favorable outcome in 70% of patients having stroke due to nonprogressive arterial disease and stroke due to unidentified mechanisms. In contrast, only 26% of patients with embolic stroke, systemic disease, or moyamoya had a favorable outcome. Recurrences were more frequent and severe in this latter group. It is concluded that it is important to determine the mechanism of childhood stroke, because it strongly influences outcome, the recurrence risk, and treatment choice.
186 citations
TL;DR: Three to four plus urine ketones are necessary, but not necessarily sufficient, to achieve optimal seizure control in children on the ketogenic diet, and is more likely when blood β-hydroxybutyrate levels are greater than 4 mmol/L.
Abstract: The objective of this study was to determine the relationship between beta-hydroxybutyrate levels and seizure control in children on the ketogenic diet. Seventy-four children on the ketogenic diet presenting for routine follow-up visits had blood levels of beta-hydroxybutyrate correlated with their seizure control. Forty-two children admitted for initiation of the ketogenic diet had urine ketones measured by dipstick and correlated with simultaneous blood levels of beta-hydroxybutyrate. Blood beta-hydroxybutyrate levels statistically correlated with seizure control (P = .003). Children with blood beta-hydroxybutyrate levels greater than 4 mmol/L were significantly more likely to have a decrease in seizure frequency than those with levels less than 4 mmol/L. Urine ketones of 4+ (160 mmol/L) were found on dipstick when blood beta-hydroxybutyrate levels exceeded 2 mmol/L. Seizure control correlates with blood beta-hydroxybutyrate levels and is more likely when blood beta-hydroxybutyrate levels are greater than 4 mmo/L. The traditional measurement of urine ketones by dipsticks in children on the ketogenic diet provides a less than optimal assessment of the degree of blood ketosis. Three to four plus (80-160 mmol/L) urine ketones are necessary, but not necessarily sufficient, to achieve optimal seizure control in children on the ketogenic diet. At present, however, urine ketones are the only readily available inexpensive approach to ketone assessment.
172 citations
TL;DR: Certain mitochondrial point mutations could be the basis for autism in some individuals, according to a family with a heterogeneous group of neurologic disorders associated with the mitochondrial DNA G8363A transfer ribonucleic acid (RNA)Lys mutation.
Abstract: We report a family with a heterogeneous group of neurologic disorders associated with the mitochondrial DNA G8363A transfer ribonucleic acid (RNA)Lys mutation. The phenotype of one child in the family was consistent with autism. During his second year of life, he lost previously acquired language skills and developed marked hyperactivity with toe-walking, abnormal reciprocal social interaction, stereotyped mannerisms, restricted interests, self-injurious behavior, and seizures. Brain magnetic resonance imaging (MRI) and repeated serum lactate studies were normal. His older sister developed signs of Leigh syndrome with progressive ataxia, myoclonus, seizures, and cognitive regression. Her laboratory studies revealed increased MRI T2-weighted signal in the putamen and posterior medulla, elevated lactate in serum and cerebrospinal fluid, and absence of cytochrome c oxidase staining in muscle histochemistry. Molecular analysis in her revealed the G8363A mutation of the mitochondrial transfer RNA(Lys) gene in blood (82% mutant mitochondrial DNA) and muscle (86%). The proportions of mutant mitochondrial DNA from her brother with autism were lower (blood 60%, muscle 61%). It is likely that the origin of his autism phenotype is the pathogenic G8363A mitochondrial DNA mutation. This observation suggests that certain mitochondrial point mutations could be the basis for autism in some individuals.
151 citations
TL;DR: The clinical and radiographic findings of 68 children and adolescents with nontraumatic intraparenchymal brain hemorrhage were analyzed retrospectively and it was found that the likelihood of establishing the cause of bleeding was greater when evaluation included cerebral angiography.
Abstract: The clinical and radiographic findings of 68 children and adolescents with nontraumatic intraparenchymal brain hemorrhage were analyzed retrospectively. There were 43 boys and 25 girls, and the average age was 7.1 years (range, 3 months to 18 years). The most common presenting symptom was a combination of headache or vomiting (40 cases, or 58.8%). Hemiparesis was the major presenting sign in 11 (16.2%) of the children, seizures occurred in 25 (36.8%) patients, and 6 (8.8%) children were irritable. Only 2 (2.9%) children were comatose at presentation. One or more risk factors for hemorrhage were found in 61 (89.7%) of 68 children. A third (23 cases, or 33.8%) had an arteriovenous malformation or fistula; altogether 29 (42.6%) children had some type of congenital vascular anomaly. Hematologic or coagulation disorders were present in 22 (32.4%) patients, and 9 (13.2%) patients had brain tumors. Hemorrhage could not be attributed to systemic hypertension in any child. The likelihood of establishing the cause ...
133 citations
TL;DR: The literature on congenital, genetic, and acquired risk factors for stroke in childhood is reviewed, and includes data from the large series of patients seen at Great Ormond Street Hospital over the past 10 years, which suggests genetic predisposition, trauma, infection, and nutritional deficiencies appear to be important.
Abstract: Since early recurrence occurs in at least 10% of patients presenting with their first stroke in childhood in the reported series, the search for modifiable risk factors should be a priority. Risk factors for stroke in adults include hypertension, diabetes, and smoking, as well as cardiac disease and sickle cell anemia; asymptomatic cerebrovascular disease and transient ischemic events may predict stroke in this age group. The investigation of a child with a stroke has traditionally focused on finding a single cause rather than looking for risk factors to which the patient may be exposed life long. Approximately half of children presenting with stroke have a known predisposing condition, but some have unexpected pathologies such as primary cerebrovascular disease associated with congenital heart anomalies, or may have modifiable risk factors such as hypertension associated with sickle cell disease. The literature on children presenting with initially unexplained (cryptogenic) stroke suggests that there is a daunting list of possible causes, but since the series have mainly been small, it has been difficult to evaluate the relative importance of the reported associations. This paper reviews the literature on congenital, genetic, and acquired risk factors for stroke in childhood, and includes data from the large series of patients seen at Great Ormond Street Hospital over the past 10 years. The majority have arteriographic abnormalities and there is little evidence for asymptomatic cardiac disease. Genetic predisposition, trauma, infection, and nutritional deficiencies appear to be important, although case-control studies will be required to prove causation. Appropriate screening for modifiable risk factors may lead to prevention of recurrence in some patients. In the long term, an understanding of the multiple etiologies of childhood cerebrovascular disease and ischemic stroke may lead to primary prevention in this age group, and perhaps in adults.
TL;DR: The data indicate that partial seizures and single parenchymal cysts are the most frequent clinical and neuroradiographic manifestations of neurocysticercosis in children and albendazole therapy should be considered.
Abstract: Neurocysticercosis is a major cause of neurologic illness worldwide. Its manifestations are variable, and somewhat different when it occurs in children. Controversy exists regarding anticysticercal therapy. The clinical, laboratory, and radiographic features of 500 consecutive children with neurocysticercosis were studied; the children were then followed prospectively and their response to albendazole therapy was analyzed. Diagnosis of neurocysticercosis was based primarily on neuroimaging. Computed tomographic (CT) scans, neurocysticercosis serology, chest radiographs, and Mantoux tests were done in all children, and magnetic resonance imaging scans in 10%. All children with multiple lesions, and some randomly allocated children with single, small, enhancing CT lesions received albendazole. CT scans were repeated after 3 to 6 months. There were 272 boys and 228 girls, age range 1 6/12 to 12 6/12 years. Seizures were present in 94.8% of cases; 83.7% had focal seizures. Features of raised intracranial pressure were seen in 30% of patients and focal neurodeficit in 4%. Single lesions were seen in 76% of the children, with perilesional edema in 57.4%. Thirty-four children who had multiple cysts and received albendazole underwent serial CT evaluation. Four showed disappearance of lesions and 22 had reductions in the size or number, to give an overall improvement rate of 76%. Serial CT studies were available on 176 children with single lesions, 90 of whom received albendazole. Improvement (disappearance or reduction in the size of lesions) was observed in 91% (82 of 90) of albendazole-treated children versus 85% (73 of 86) of untreated children. This difference was not significant. No significant side-effects of albendazole were reported. These data indicate that partial seizures and single parenchymal cysts are the most frequent clinical and neuroradiographic manifestations of neurocysticercosis in children. Although albendazole therapy should be considered, especially in children with multiple lesions, many children with isolated neurocysticercosis will improve without antiparasitic therapy.
TL;DR: The clinical and pathologic features of these Guillain-Barré syndrome subtypes are reviewed, and the role of antecedent infections, particularly Campylobacter jejuni gastroenteritis, and of antiganglioside antibody responses are reviewed with respect to pathogenesis.
Abstract: Guillain-Barre syndrome is an acute autoimmune polyradiculoneuropathy with a clinical presentation of flaccid paralysis with areflexia, variable sensory disturbance, and elevated cerebrospinal fluid protein without pleocytosis Although Guillain-Barre syndrome previously had been viewed as a unitary disorder with variations, it currently is viewed as a group of syndromes with several distinctive subtypes These include the principal subtype prevalent in the Western world (acute inflammatory demyelinating polyradiculoneuropathy, and others, each with distinctive electrodiagnostic and pathologic features, including acute motor axonal neuropathy), acute motor-sensory axonal neuropathy, Miller Fisher syndrome, and perhaps others The clinical and pathologic features of these Guillain-Barre syndrome subtypes are reviewed, and the role of antecedent infections, particularly Campylobacter jejuni gastroenteritis, and the role of antiganglioside antibody responses are reviewed with respect to pathogenesis Treatment of Guillain-Barre syndrome includes both important supportive measures and immunotherapies, specifically high-dose intravenous immunoglobulin and plasma exchange
TL;DR: It is hypothesized that their locations within the neurotransmitter-specific circuitry of the basal ganglia motor loop are important and might make the globus pallidus more vulnerable to less intense, subacute oxidative stresses from mitochondrial toxins such as bilirubin or from genetic mitochondrial disorders.
Abstract: Magnetic resonance imaging and neuropathologic studies have demonstrated remarkably selective patterns of injury to subregions of the basal ganglia in children. Examples are kernicterus and certain mitochondrial encephalopathies, which cause selective injury to the globus pallidus, and near-total perinatal asphyxia, which causes lesions in the putamen and thalamus. To explain the differential vulnerability of nuclei within millimeters of each other, we hypothesize that their locations within the neurotransmitter-specific circuitry of the basal ganglia motor loop are important. In severe hypoxic-ischemic encephalopathy, excitatory glutamatergic pathways into the putamen and thalamus are overactive, but the globus pallidus might be protected because its activity is silenced by inhibitory neuronal activity. In contrast, the relatively high resting neuronal activity in the globus pallidus might make it more vulnerable to less intense, subacute oxidative stresses from mitochondrial toxins such as bilirubin or from genetic mitochondrial disorders. This hypothesis has implications for designing neuroprotective therapies and for treating associated chronic movement disorders.
TL;DR: A Clinical Alert, issued by the National Heart, Lung, and Blood Institute, recommending screening and consideration of treatment in children with sickle cell disease and 2 to 16 years of age who are at risk based on transcranial Doppler ultrasonography, and who have not had stroke.
Abstract: Stroke is generally uncommon in children, but sickle cell disease is associated with a high risk of stroke in the early years of childhood. Large cerebral arteries, especially the middle cerebral and intracranial internal carotid, develop stenosis that predisposes to ischemic stroke. Noninvasive prediction of risk using transcranial Doppler ultrasonography made it possible to test primary stroke prevention in a clinical trial comparing chronic blood transfusion with standard care. A consortium of 14 clinical centers conducted a randomized clinical trial (Stroke Prevention in Sickle Cell Anemia--the "STOP" study) to test a strategy to prevent first stroke in children with sickle cell disease. Over 2000 children were screened with transcranial Doppler ultrasonography and of these, 130 with elevated blood velocity indicating high risk were enrolled in the trial. Regular red cell transfusions sufficient to reduce the percentage of Hb S gene product from over 90 to less than 30 of total hemoglobin was associated with a marked reduction in stroke. The untreated risk of 10% per year was reduced over 90% with treatment, an effect sufficient to cause early termination of the trial. Although treatment was unblinded, the design included blinded adjudication of possible stroke by a panel of neurologists remote from the study sites. The study led to a Clinical Alert, issued by the National Heart, Lung, and Blood Institute, recommending screening and consideration of treatment in children with sickle cell disease and 2 to 16 years of age who are at risk based on transcranial Doppler ultrasonography, and who have not had stroke.
TL;DR: Vagus nerve stimulation could be an effective and safe adjunct therapy for the treatment of Lennox-Gastaut syndrome and side effects, including hoarseness, coughing, and pain in the throat, were transient and tolerable.
Abstract: Lennox-Gastaut syndrome is a severe age-specific epilepsy syndrome that presents with medication-resistant seizures in childhood. Antiepileptic drugs are the mainstay of treatment. Nonpharmacologic treatments include corpus callosum section and the ketogenic diet. However, no single treatment is safe and effective. We treated 13 patients with Lennox-Gastaut syndrome between the ages of 4 and 44 years (mean, 16.7 years) with vagus nerve stimulation. During the first 6 months of treatment, vagus nerve stimulation produced a median seizure rate reduction of 52% (range, 0% to 93%; P = .04). At 6 months of follow-up, three patients had a greater than 90% reduction in seizures, two had a greater than 75% reduction, one had a greater than 50% reduction, and six had at least a 25% reduction. One patient did not improve. No patient worsened after initial improvement. Side effects, including hoarseness, coughing, and pain in the throat, were transient and tolerable. No patient discontinued vagus nerve stimulation. ...
TL;DR: This series confirms the wide range of clinical manifestations in Asperger's syndrome and autism, including tics and other features of Tourette syndrome, and suggests that sensory deprivation contributes to the development of adventitious movements in this population.
Abstract: Asperger's syndrome is a condition in the autistic spectrum in which language development is normal. Patients with Asperger's syndrome frequently exhibit repetitive movements (stereotypies), and can have motor and phonic tics in addition to other behavioral abnormalities. We present 12 patients with autistic spectrum disorders who were referred to our Movement Disorders Clinic for evaluation of tics. Eight of the 12 had normal language development and therefore met criteria for Asperger's syndrome. All patients exhibited stereotypic movements; in addition, seven had tics and six of these met diagnostic criteria for Tourette syndrome. Of the six patients with clinical features of both Asperger's syndrome and Tourette syndrome, three had severe congenital sensory deficits. The autistic patients in our series were clinically heterogeneous and though tics were clearly present, other aberrant movements demonstrated by them were harder to classify. Our series confirms the wide range of clinical manifestations in Asperger's syndrome and autism, including tics and other features of Tourette syndrome. Furthermore, it suggests that sensory deprivation contributes to the development of adventitious movements in this population.
TL;DR: This proposal is a first attempt to incorporate the recent molecular genetic data that explain programming of development etiologically into traditional schemes of classifying nervous system malformations.
Abstract: Traditional schemes of classifying nervous system malformations are based on descriptive morphogenesis of anatomic processes of ontogenesis, such as neurulation, neuroblast migration, and axonal pathfinding. This proposal is a first attempt to incorporate the recent molecular genetic data that explain programming of development etiologically. A scheme based purely on genetic mutations would not be practical, in part because only in a few dysgeneses are the specific defects known, but also because several genes might be involved sequentially and many genes inhibit or augment the expression of others. The same genes serve different functions at different stages and are involved in multiple organ systems. Some complex malformations, such as holoprosencephaly, result from several unrelated defective genes. Finally, a pure genetic classification would be too inflexible to incorporate some anatomic criteria. The basis for the proposed scheme is, therefore, disturbances in patterns of genetic expression; polarity gradients of the axes of the neural tube (eg, upregulation or downregulation of genetic influences); segmentation (eg, deletions of specific neuromeres, ectopic expression); mutations that cause change in cell lineage (eg, dysplastic gangliocytoma of cerebellum, myofiber differentiation within brain); and specific genes or molecules that mediate neuroblast migration in its early (eg, filamin-1), middle (eg, LIS1, double-cortin), or late course (eg, reelin, L1-CAM). The proposed scheme undoubtedly will undergo many future revisions, but it provides a starting point using currently available data.
TL;DR: It is suggested that hypomelanosis of Ito is not a single condition but rather a nonspecific manifestation of chromosomal mosaicism and that this term should now be dropped.
Abstract: The term hypomelanosis of Ito is applied to individuals with skin hypopigmentation along the lines of Blaschko. Even though originally described as a purely cutaneous disease, subsequent reports have included a 33% to 94% association with multiple extracutaneous manifestations mostly of the central nervous and musculoskeletal systems leading to frequent characterization as a neurocutaneous disorder. A number of reports claimed familial occurrence and supported single gene inheritance for hypomelanosis of Ito, but none has been proved. Miscellaneous chromosomal mosaicisms have been demonstrated in some but not all affected individuals. Thus, it has been suggested that hypomelanosis of Ito is not a single condition but rather a nonspecific manifestation (ie, a phenotype) of chromosomal mosaicism and that this term should now be dropped. In this article, we review these developments focusing on the neurologic and genetic aspects of hypomelanosis of Ito. Our personal experience with 41 hypomelanosis of Ito pa...
TL;DR: Dengue virus can cause acute encephalopathy with fever and can masquerade as other types of acute viral encephalitis, however, its clinical course and prognosis are usually favorable and its clinical courses and laboratory findings compatible with typical dengue infection.
Abstract: The objective of this study was to investigate the possibility of dengue virus infection causing an abnormal neurologic presentation. Between 1996 and 1998, all pediatric patients with clinical man...
TL;DR: The study confirms the wide clinical spectrum and the difficulties encountered in diagnosis of idiopathic intracranial hypertension and suggests a wide variety of etiologic associations should be investigated to provide definitive therapy.
Abstract: We studied prospectively the etiology, clinical presentation, and outcome of idiopathic intracranial hypertension in 36 patients (20 boys and 16 girls) aged 3.5 months to 14 years. The etiology was identified in 28 (77.7%) patients. The most common predisposing factor was middle-ear infection, followed by obesity. Of the 36 cases seen, 26 presented with the classic picture of headaches, papilledema, and elevated cerebrospinal fluid pressure; 8 children had intracranial hypertension in the absence of papilledema and 2 had fundoscopic evidence of papilledema with normal cerebrospinal fluid pressure initially. In four children resolution of intracranial hypertension occurred with removal of the causative agent or appropriate treatment of the underlying condition. In 8 of 17 patients intracranial hypertension resolved with acetazolamide therapy and in 22 of 24 patients it resolved with corticosteroids in combination with acetazolamide. Subnormal visual acuity, narrowing of visual fields, or both were present on the initial examination in 10 patients; 2 of them, who presented with loss of vision, have permanent visual impairment. Four additional patients presented a transient, mild impairment of visual acuity during treatment. Our study confirms the wide clinical spectrum and the difficulties encountered in diagnosis of idiopathic intracranial hypertension. A wide variety of etiologic associations should be investigated to provide definitive therapy. Loss of visual function is the only serious complication.
TL;DR: Control treatment trials with venlafaxine are warranted in autism spectrum disorders after improvement was noted in repetitive behaviors and restricted interests, social deficits, communication and language function, inattention, and hyperactivity.
Abstract: Autism is characterized by social deficits, communication and language impairments, narrow restricted interests, repetitive behaviors, inattention, and hyperactivity. While selective serotonin reuptake inhibitors have demonstrated efficacy in treating core symptoms of autism, norepinephrine reuptake inhibitors have demonstrated efficacy in symptoms of attention-deficit hyperactivity disorder (ADHD). An open, retrospective clinical study with venlafaxine evaluated its effect on core symptoms of autism as well as associated features of ADHD. Ten consecutive subjects meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for an autism spectrum disorder were treated with venlafaxine, initiated at 12.5 mg per day and adjusted on a flexible basis. Six of 10 completers were judged to be sustained treatment responders, by scoring 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions improvement scale. Venlafaxine was effective in low dosages (mean, 2...
TL;DR: A specific profile of difficulties in coordination, lateralization, spatial and graphomotor skills, and abundance of associated movements is typical of the children with intrauterine growth retardation and hints at possible later learning disabilities.
Abstract: This prospective study was designed to characterize the neurodevelopmental and cognitive difficulties specific to children with intrauterine growth retardation and to detect early clinical predictors of these difficulties. Eighty-one children with intrauterine growth retardation were monitored up to 6 to 7 years of age using biometric parameters, perinatal risk questionnaires, and detailed neurodevelopmental and cognitive assessments. Forty-one children served as age-matched, appropriate for gestational age controls. A significant difference in growth parameters (P < .001), neurodevelopmental score (P < .05), and IQ (P < .05) was found between the children with intrauterine growth retardation and controls. A specific profile of difficulties in coordination, lateralization, spatial and graphomotor skills, and abundance of associated movements is typical of the children with intrauterine growth retardation and hints at possible later learning disabilities. The clinical parameters best predicting neurodevelopmental outcome were the neonatal risk score (P < .05) and the weight and height at 6 years of age (P < .05). The children with intrauterine growth retardation with neonatal complications had lower neurodevelopmental scores than the controls but no difference in IQ. Intrauterine growth retardation children diagnosed prenatally had the same neurodevelopmental and IQ scores as those diagnosed at birth, probably due to the careful perinatal and obstetric care provided. Children with intrauterine growth retardation demonstrate a specific profile of neurodevelopmental disabilities at preschool age. Early diagnosis and intervention could probably reduce these difficulties to a minimum.
TL;DR: The results suggest that some features of ADHD in children with neurofibromatosis could be linked to quantifiable differences in brain morphology, but the nature of the genetic mutation in neuro fibrom atosis suggests that neurochemical effects also could be important.
Abstract: Neurofibromatosis-1 is a common autosomal-dominant genetic disorder associated with numerous physical anomalies and an increased incidence of attention-deficit hyperactivity disorder (ADHD). Studies of children with idiopathic ADHD have suggested a link between corpus callosum size and symptom severity. This study examines the contribution of corpus callosum morphology to symptoms of ADHD in children with neurofibromatosis. Eighteen control subjects and 36 children with neurofibromatosis underwent magnetic resonance imaging of the brain. Twelve subjects with neurofibromatosis had evidence of ADHD and 24 did not. Subjects with neurofibromatosis had significantly larger total corpus callosum area and significantly larger regional measurements in three of seven areas. However, there were no differences between the neurofibromatosis alone and neurofibromatosis plus ADHD groups. Increased severity of attention problems was associated with smaller total callosal areas. These results suggest that some features of ADHD in children with neurofibromatosis could be linked to quantifiable differences in brain morphology, but the nature of the genetic mutation in neurofibromatosis suggests that neurochemical effects also could be important.
TL;DR: Analysis of intelligence quotient results obtained from 38 children in an ongoing study of unilateral middle cerebral artery ischemic stroke indicates that, after stroke, mean IQ falls significantly below the population mean but remains within the average range.
Abstract: Review of published clinical and neuropsychologic outcome studies reveals limited information about intellectual functioning after childhood stroke. The extant data are supplemented here by analysis of intelligence quotient (IQ) results obtained from 38 children in an ongoing study of unilateral middle cerebral artery ischemic stroke. Evidence so far indicates that, after stroke, mean IQ falls significantly below the population mean but remains within the average range. There is no significant difference between hemispheric side of injury; the Verbal and Performance IQ lateralization profile widely recognized in adults with unilateral injury is not apparent in younger children, and there is only a trend toward this profile in older children. The effects of a number of other variables, including sex, site of stroke, and longitudinal assessment, are also considered. Although the generally minor effect of stroke on IQ is encouraging, a number of children do require extra help on return to school. Some suggestions for future research are highlighted in order to encourage further consideration of the issues raised here.
TL;DR: Heterotopic ossification was diagnosed in 32 patients with average time of onset of 4 months after traumatic brain injury, near drowning, strangulation, cerebral hemorrhage, hydrocephalus, or spinal cord injury and, in contrast to what has been found in adult studies, serum alkaline phosphatase was not elevated during heterotopicOssification formation.
Abstract: Heterotopic ossification, or myositis ossificans, denotes true bone in an abnormal place. The pathogenic mechanism is still unclear. A total of 643 patients (mean age, 9.1 years) admitted for neuropediatric rehabilitation were analyzed retrospectively with respect to the existence of neurogenic heterotopic ossification. The purpose of this study was to obtain information about incidence, etiology, clinical aspect, and consequences for diagnosis and therapy of this condition in childhood and adolescence. Heterotopic ossification was diagnosed in 32 patients (mean age, 14.8 years) with average time of onset of 4 months after traumatic brain injury, near drowning, strangulation, cerebral hemorrhage, hydrocephalus, or spinal cord injury. The sex ratio was not significant. In contrast to what has been found in adult studies, serum alkaline phosphatase was not elevated during heterotopic ossification formation. A persistent vegetative state for longer than 30 days proved to be a significant risk factor for heterotopic ossification. The incidence of neurogenic heterotopic ossification in children seems to be lower than in adults. A genetic predisposition to heterotopic ossification is suspected but not proven. As a prophylactic regimen against heterotopic ossification we use salicylates for those patients in a coma or persistent vegetative state with warm and painful swelling of a joint and consider continuous intrathecal baclofen infusion and botulinum toxin injection for those patients with severe spasticity. We prefer to wait at least 1 year after trauma before excision of heterotopic ossification.
TL;DR: A higher prevalence of hyperhomocysteinemia and the 677 C→T polymorphism were observed in children with stroke, but were not always associated.
Abstract: The aim of this study was to investigate a possible association among the thermolabile polymorphism, nucleotide 677 cytosine to thymidine point mutation (677 C-->T) of the methylenetetrahydrofolate reductase (MTHFR) gene, hyperhomocysteinemia, serum folate, vitamins B12 and B6, and stroke in children. Allele and genotype frequencies for the 677 C-->T polymorphism in 21 children with stroke and 28 healthy children of the same age were studied. No differences in allelic frequency were detected between the two populations. However, the prevalence of homozygous 677 C-->T was doubled in the stroke population (28.6%) compared to the healthy group (14.3%). Total plasma homocysteine (tHcy) levels were significantly increased in children aged 2 months to 15 years with stroke compared to reference values. No association was observed between the homozygous genotype (T/T) and hyperhomocysteinemia, nor between the T/T genotype and low folate levels (below the 95th percentile) in this group of patients. Vitamin concentrations in patients were not significantly different from reference values. Significant negative correlations were found between tHcy and folate and between tHcy and cobalamin, but not between tHcy and B6 concentrations. In summary, a higher prevalence of hyperhomocysteinemia and the 677 C-->T polymorphism were observed in children with stroke, but were not always associated. The systematic study of both abnormalities in children with stroke is recommended, so that hyperhomocysteinemia of any genetic origin can be corrected with vitamin supplementation. Moreover, the 677 C-->T genotype is a strong factor for predisposition to hyperhomocysteinemia and recurrent risk of stroke that might also be prevented with folate supplementation.
TL;DR: Treatment trials in spinal muscular atrophy should be designed with consideration of the natural history of strength and motor function in this disorder, as it is not clear from the results whether spinal muscularatrophy is a neurodegenerative disease.
Abstract: Spinal muscular atrophy is a genetic disorder of the motor neurons that causes profound hypotonia, severe weakness, and often fatal restrictive lung disease. Patients with spinal muscular atrophy present a spectrum of disease from the most severe infantile-onset type, called Werdnig-Hoffmann disease (type 1), associated with a mortality rate of up to 90%, to a late-onset mild form (type 3), wherein patients remain independently ambulatory throughout adult life. Although many clinicians agree that patients with spinal muscular atrophy lose motor abilities with age, it is unknown whether progressive weakness occurs in all patients with spinal muscular atrophy. We present here results of the first prospective study of muscle strength in patients with spinal muscular atrophy. There was no loss in muscle strength as determined by a quantitative muscle test during the observation period. However, motor function diminished dramatically in some patients with spinal muscular atrophy. Explanations for this loss of ...
TL;DR: Current treatment of childhood moyamoya disease in Japan, preoperative evaluation of perfusion reserve as a surgical indication, and the role of noninvasive follow-up by magnetic resonance angiography are reported.
Abstract: Early diagnosis and treatment of moyamoya disease in children is essential to minimize residual mental and physiologic deficits. Current treatment of childhood moyamoya disease in Japan, preoperative evaluation of perfusion reserve as a surgical indication, and the role of noninvasive follow-up by magnetic resonance angiography are reported. Approximately 20% of children with definite moyamoya disease were observed or treated medically. Among surgical procedures, single indirect bypass surgery was used in approximately 30% of all patients; combinations of direct and indirect bypass surgery, 20%; and multiple-indirect bypass surgery, 18%. Both adequate understanding of the primary condition and determination of optimal treatment, including specific operative procedures, required evaluation of cerebral circulation and metabolism. Surgical indications included reduced perfusion reserve in affected brain by positron emission tomography or single photon emission tomography with administration of acetazolamide or a CO2 load. Postoperative improvements of cerebral perfusion reserve show better correlation with disappearance of ischemic attacks than does angiographically demonstrated collateral formation. Follow-up evaluation with magnetic resonance angiography has advantages over conventional angiography because it is noninvasive and avoids general anesthesia.
TL;DR: The need to modify the treatment protocols when neurotoxicity appears is not fully established, and it is also unknown whether the use of sufficient amounts of leucovorin can overcome the toxic effects of the drug.
Abstract: Methotrexate can influence the central nervous system through several metabolic toxic pathways. These effects can be categorized as immediate, acute to subacute, or chronic neurologic syndromes. The acute to subacute syndrome occurs frequently in acute lymphoblastic leukemia treatment protocols, generally manifesting with focal neurologic signs and changes seen on magnetic resonance imaging and single photon emission computed tomography. While in some patients the neurotoxicity is transient and benign and allows for continuation of chemotherapy, in others it can be quite severe and debilitating, leading to permanent neurologic deficits. The need to modify the treatment protocols when neurotoxicity appears is not fully established. It is also unknown whether the use of sufficient amounts of leucovorin can overcome the toxic effects of the drug.