Seizure control and educational outcome in childhood-onset epilepsy.

Patients with epilepsy are more prone to have learning disabilities. This study investigated the therapeutic and educational outcome of 102 epileptic children. Analyzed data included age at onset, etiology, presence of underlying brain lesions, seizure type, and electroencephalographic (EEG) patterns. Cryptogenic seizures, remote symptomatic seizures, and underlying brain lesions were found in 29, 26, and 14 patients, respectively, whereas 47 patients had idiopathic seizures. Eighty-three patients achieved seizure control (46 remained seizure free), and 19 patients remained poorly controlled. Sixty-five patients were in regular schools, and 37 required special education (17 with mental retardation). Predictors for poor seizure control were remote symptomatic seizures, underlying brain lesions, and (when grouped together) hypsarrhythmia and mixed EEG patterns (P < .001). Predictors for special education needs were young age at onset, remote symptomatic seizures, underlying brain lesions, hypsarrhythmia and mixed EEG patterns, and poor seizure control (P < .001). We conclude that in childhood epilepsy, the need for special education is substantial and more common than treatment failure.

Clinical manifestations of psychiatric patients who are carriers of tay-sachs disease. Possible role of psychotropic drugs.

Patients with late-onset Tay-Sachs disease (TSD) may manifest with neuropsychiatric features. We hypothesized that the prevalence of TSD carriers in psychiatric patients is higher than in the general population and their clinical profile is different from that of their noncarrier counterparts. Among 500 Ashkenazi-Jewish psychiatric patients, 19 were found to be TSD carriers. Their prevalence in the study population is proportional to that in the general Ashkenazi population. However, abnormal neurological findings, especially cognitive impairment, were commoner among TSD carriers (47.4 vs. 26.2%, p = 0.04). It is possible that chronic use of some psychotropic drugs plays a role in this phenomenon.

Sleep patterns in autistic children.

Sleep disturbances are regarded as a common clinical feature in autistic children. This concept is based primarily on informal observations or studies conducted with questionnaires. In this study we compared data obtained by questionnaires to that obtained with actigraphy. Among 22 autistic children, 12 were reported as having sleep problems and 8 patients completed 72 hours actigraphy. While the employment of questionnaires disclosed that autistic children had an earlier morning awakening time and multiple and early night arousals, actigraphic monitoring showed that with the exception of an earlier morning arousal time (p = .045), sleep patterns of autistic children were similar to that of normal children. Parental oversensitivity to sleep disturbances of the autistic children may explain this phenomenon.

The role of botulinum toxin in the treatment of lower limb spasticity in children with cerebral palsy--a pilot study.

The use of botulinum toxin in cerebral palsy is still experimental. We conducted a pilot clinical trial with botulinum toxin injections on 14 children with spastic cerebral palsy. All patients were mobile with dynamic contractures of the gastrocnemius-soleus muscles. The injections were monophasic in 9 patients and biphasic in 5 patients. Improvement in dorsiflexion, quality of gait and grade of independence were achieved in 3 patients; improvement in dorsilflexion and quality of gait were achieved in 6 patients. There was no significant change in quality of gait in 4 patients. The beneficial effect lasted 4-9 months (mean 6.7 months). A combined functional score given by the physicians, therapists and parents showed a marked improvement in 6 patients (42.9%), a mild improvement in 3 patients (21.4%) and no improvement in 5 patients (35.7%). Biphasic injections were slightly more effective than monophasic injections (p < 0.02). Adverse effects were usually mild. We conclude that botulinum toxin may be used for the reduction of spasticity in patients with cerebral palsy who have dynamic deformities of the ankle joints.

Congenital pontocerebellar atrophy in three patients: clinical, radiologic and etiologic considerations.

We report three patients with severe pontocerebellar atrophy (PCA) associated with a variable degree of cerebral atrophy. The clinical features consisted of progressive microcephaly, central hypotonia, visual impairment, abnormal eye movements and delayed psychomotor development. These are similar but not identical to the features of pontocerebellar hypoplasia type 2 described by Barth. The picture also differs from the classical form of autosomal dominant olivopontocerebellar atrophy. While in two patients the disease seemed to be genetic with highly suspicious autosomal recessive inheritance, the etiology in the third patient was probably nongenetic. We suggest that PCA is a morphologic entity with distinct radiologic features but variable clinical, pathophysiologic and etiologic backgrounds.

Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene.

Late-onset GM2 gangliosidosis is a variant form of Tay-Sachs disease characterized by onset of symptoms and signs in adolescence or in early adult life. The deficiency of beta-hexosaminidase A (Hex A) in this form of GM2 gangliosidosis has been invariably associated with the presence of the Gly269-->Ser substitution in the alpha-chain. We found two siblings of Ashkenazi Jewish descent diagnosed with late-onset GM2 gangliosidosis who were negative for the Gly269-->Ser mutation. Analysis of the HEXA gene showed that they were compound heterozygotes for the functionally silent 4-bp insertion in exon 11, typical of the infantile form of the disease and for a novel mutation, T538-->C, resulting in the missense Tyr180-->His. Expression studies in COS-7 cells suggested that the effect of this mutation was to decrease the stability of the alpha-chain at physiologic temperatures and therefore to indirectly affect the formation of mature Hex A.

Mitochondrial encephalomyopathies presenting with features of autonomic and visceral dysfunction.

Three children are reported with mitochondrial encephalomyopathy who presented with autonomic dysfunction. Autonomic dysfunction included gastrointestinal dysmotility, apnea, cardiac arrhythmias, decreased lacrimation, supersensitivity to metacholine, altered sweating, and postural hypotension. These patients illustrate that in some mitochondrial encephalomyopathies autonomic features may be prominent and can mimic the clinical features associated with hereditary sensory and autonomic neuropathies.

Neurologic complications in pediatric solid tumors.

The cases of 61 children, consecutively diagnosed during 1986-1990 as having malignant solid tumors (but excluding those with brain tumors and lymphoproliferative diseases), were reviewed. Neurologic complications occurred in 19 (31%), most often in association with neuroblastomas and sarcomas. Complications observed in order of frequency were: brain metastases in 6 children, spinal cord compression in 5, peripheral or cranial neuropathies in 4, and seizures in the remaining 4. Early recognition of neurologic compromise and rapid initiation of treatment are mandatory in order to prevent permanent disability.

Congenital toxoplasmosis: a significant cause of neurological morbidity in Israel?

The incidence of congenital toxoplasmosis in Israel is largely unknown, as is the impact of this condition on the neurological diseases of childhood. We examined the association between toxoplasmosis and three neurological disorders: epilepsy, cerebral palsy, and nerve deafness. Ninety-five children 1-15 years of age who had one of these three diagnoses but who had not had perinatal meningitis or anoxia and had no genetic predisposition for the documented neurological disorder were eligible for the study; 109 children hospitalized for elective surgery served as age-matched controls. Demographic and serological data were analyzed by logistic regression. The prevalences of serum antibodies to Toxoplasma gondii in the study and control groups were 22% and 9%, respectively. Children with one of the three neurological disorders were significantly more likely to have IgG antibodies to T. gondii (relative risk, 2.5; P = .03). The relative risk of seropositivity was remarkably high (7.1) among children with nerve deafness (P = .01). Large-scale prospective cohort studies of pregnant women are needed to substantiate the impact of congenital toxoplasmosis on the neurological diseases of childhood in Israel.

Reduced carnitine and antiepileptic drugs: cause relationship or co-existence?

Serum carnitine was measured longitudinally before and after therapy in 15 patients receiving valproic acid, 14 patients receiving carbamazepine and 8 patients receiving phenobarbital. The patients who received valproic acid showed a significant reduction in free (and total) serum carnitine (mean (SE) 37.6 (6.2) mumol/l without valproic acid, 29.1 (1.6) mumol/l with valproic acid (p < 0.001)). Such an effect was not found in patients receiving carbamazepine or phenobarbital.

Developmental disabilities among children between birth and 3 years old in the Haifa district: a population study.

The incidence of major neurodevelopmental deficits among children between birth and 3 years of age in the Haifa district was evaluated. Routine standardized developmental screening at the well-baby clinics was employed. The records of all children referred to the only two child developmental centers in the district during a period of 4 years were analyzed. The overall incidence was 31 per 1000 and was lower than expected. The age at diagnosis and associated disorders are discussed. In 30% of the cohort the diagnosis was inaccurate, and a 22% false positive referral rate was noted. A more thorough training in the early diagnosis of psychomotor developmental problems in childhood in the well-baby clinics is indicated.

Protracted clinical course for patients with Canavan disease.

Before the establishment of N-acetylaspartic aciduria due to aspartoacylase deficiency as the cause of Canavan disease, diagnosis was based on the characteristic clinical features and spongiform encephalopathy, a pathological response shared by a number of other unrelated conditions. Thus confusion exists in the literature about the phenotype of spongiform encephalopathy (Canavan disease), with reports of 'juvenile' and 'congenital' forms, as well as the classical infantile type. In this report, six of 22 patients with infantile-onset Canavan disease survived beyond six years of age. This phenotypical pattern might be the result of better medical management and care, rather than evidence of genetic heterogeneity.

Is eye cosmetic a source of lead poisoning?

Kohl is a lead-containing eye cosmetic applied to many infants in Israel and in other countries in the Middle East. Seven samples of kohl used in our region contained 17.3%-79.5% lead. We assessed 24 kohl users and 30 non-kohl users, aged 6-16 months, for blood lead, zinc protoporphyrin, hemoglobin, mean corpuscular volume (MCV), serum iron and calcium. Blood lead levels were significantly higher in the infants to whom kohl was applied (11.2 vs. 4.3 micrograms/dl, P less than 0.001) and were greater than 20 micrograms/dl in three of them. In the non-kohl users, blood lead levels were significantly higher in infants whose mothers used kohl (5.2 vs. 2.8 micrograms/dl, P less than 0.02). No significant differences were found in the other parameters. The kohl-using infants were significantly shorter at 3-5 weeks of age (P less than 0.005) but not at the time of the study. No significant differences were found in weight and head circumference at birth or at the time of the study between kohl-using infants and controls. Regression analysis showed that among the analyzed variables the infant's blood lead level was related only to the use of kohl. We conclude that application of kohl to the infant's or mother's eyes is associated with a significant increase in the infant's blood lead levels and in the minority of cases with asymptomatic lead poisoning.

Ataxia-telangiectasia: linkage analysis in highly inbred Arab and Druze families and differentiation from an ataxia-microcephaly-cataract syndrome.

Ataxia-telangiectasia (A-T) is a progressive autosomal recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation sensitivity and a highly increased proneness to cancer. A-T is ethnically widespread and genetically heterogeneous, as indicated by the existence of four complementation groups in this disease. Several "A-T-like" genetic diseases share various clinical and cellular characteristics with A-T. By using linkage analysis to study North American and Turkish A-T families, the ATA (A-T, complementation group A) gene has been mapped to chromosome 11q23. A number of Israeli Arab A-T patients coming from large, highly inbred families were assigned to group A. In one of these families, an additional autosomal recessive disease was identified, characterized by ataxia, hypotonia, microcephaly and bilateral congenital cataracts. In two patients with this syndrome, normal levels of serum immunoglobulins and alpha-fetoprotein, chromosomal stability in peripheral blood lymphocytes and skin fibroblasts, and normal cellular response to treatments with X-rays and the radiomimetic drug neocarzinostatin indicated that this disease does not share, with A-T, any additional features other than ataxia. These tests also showed that another patient in this family, who is also mentally retarded, is affected with both disorders. This conclusion was further supported by linkage analysis with 11q23 markers. Lod scores between A-T and these markers, cumulated over three large Arab families, were significant and confirmed the localization of the ATA gene to 11q23. However, another Druze family unassigned to a specific complementation group, showed several recombinants between A-T and the same markers, leaving the localization of the A-T gene in this family open.

[Early developmental aspects of Tourette syndrome].

Tourette syndrome is a neuropsychiatric disorder characterized by a combination of multiple motor and vocal tics. It is frequently associated with other manifestations which are typical, though not obligatory for the diagnosis. Some of these manifestations may appear in early childhood and cause developmental disorders. Our observations in 2 families, in which an early developmental symptom was later found to be an associated manifestation of Tourette syndrome, led us to investigate our other patients with this syndrome. In all, 16 patients were studied. Early developmental disabilities, such as speech and language disorder, learning disabilities, attention deficit hyperactivity disorder, motor clumsiness or behavioral problems were found in 8. An epidemiological survey is needed to determine the prevalence of the association of Tourette syndrome with developmental manifestations in early childhood.