Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study.

Background: Alternating hemiplegia of childhood (AHC) is a rare neurological disorder characterised by early-onset episodes of hemiplegia, dystonia, various paroxysmal symptoms, and developmental impairment. Almost all cases of AHC are sporadic but AHC concordance in monozygotic twins and dominant transmission in a family with a milder phenotype have been reported. Thus, we aimed to identify de-novo mutations associated with this disease.

[Repetitive peripheral magnetic stimulation. Treatment option for spasticity?].

Background: In an open study the effect of repetitive peripheral magnetic stimulation (RPMS) on the spastic talipes equinus of various origins, degree and duration was evaluated in 53 children and adolescents.

Study Design And Methods: Clinical and electrophysiological investigations were designed to measure the RMPS effect on the spasticity and the functional capabilities of the spastic talipes equines. Moreover, the duration of the effect of one RPMS session should be established.

The LAM-SAFE Study: lamotrigine versus carbamazepine or valproic acid in newly diagnosed focal and generalised epilepsies in adolescents and adults.

Objective: To investigate efficacy and safety of lamotrigine (LTG) versus carbamazepine (CBZ) or valproic acid (VPA) in newly diagnosed focal (FE) and idiopathic generalised (GE) epilepsies in adolescents and adults.

Methods: Open-label randomised comparative multicentre 24-week monotherapy trial in newly diagnosed epilepsy patients of >or=12 years of age. Patients with FE were treated with LTG or CBZ, those with GE received LTG or VPA.

[Optimizing epilepsy therapy in children and adolescents with lamotrigine].

Lamotrigine is a broadly effective antiepileptic drug in mono- and add-on therapy for children and adolescents with focal and generalized epilepsies. Some epileptologists consider lamotrigine as the drug of primary choice in older school children and adolescents because of its good tolerability (no increase of body weight, no impairment of cognitive functions, due to new data probably no teratogenic properties). Lamotrigine can be used with good efficacy in numerable epilepsy diseases, such as tuberous sclerosis, juvenile neuronal lipofuscinosis and Rett syndrome.

[Recommendations for blood studies and clinical monitoring in early detection of valproate-associated liver failure. Results of a consensus conferences 9 May - 11 May 1997 in Berlin].

Valproate is a frequently used antiepileptic drug. It is associated with rare but serious adverse effects like liver failure. The first symptom is impairment of the patient's well being.

Long-term follow-up study of vigabatrin in pretreated children with West syndrome.

A multicentre, long-term, open-label, add-on study of vigabatrin was undertaken in 23 pretreated children with infantile spasms. After 3 months of vigabatrin therapy 11 of the 23 patients had become seizure-free. At this time two-thirds of these 11 children still received other antiepileptic drugs (AEDs) in addition to vigabatrin (mostly valproic acid and/or dexamethasone).

Quantification of cerebrospinal fluid proteins in children by high-resolution agarose gel electrophoresis.

Physiologic alterations in cerebrospinal fluid proteins occur inter alia with aging. Agarose gel electrophoresis discriminates many cerebrospinal fluid proteins and in addition quantifies concentration alterations. This study aimed to investigate the time course of these alterations in children and to establish normative values for cerebrospinal fluid protein properties.

[Long-term monitoring of therapy-induced computerized tomographic cranial changes in children with acute lymphoblastic leukemia].

Purpose: Long-term follow-up of cranial CT scans of children with acute lymphoblastic leukemia and evaluation of the influence of chemo- and radiotherapy on the CCT changes.

Patients And Methods: CCT scans of 68 children with non-B-ALL were analyzed retrospectively for signs of atrophy and changes in density. Patients were treated between 1981 and 1990 at the St.

Otorhinolaryngological complications of progressive facial hemiatrophy (Romberg's disease).

Progressive facial hemiatrophy (PFH) is characterized by slowly progressive atrophy of subcutaneous tissue. Bone, muscles, nerves, the eye, and the brain may be affected by atrophy. Four patients suffering from various otorhinolaryngological complications of PFH or Romberg's disease are reported.

Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities.

Since our last report on valproate (VPA)-related hepatotoxicity in 1988, 8 other children have died of VPA-associated liver failure in Germany and Switzerland. We compared the clinical course of these children with that of 6 children with a reversible outcome of severe hepatotoxicity related to VPA. Thirty-five percent of patients with fatal liver failure were normally developed, 23.

Single-photon emission computed tomography investigations of alternating hemiplegia of childhood.

Alterations in regional cerebral blood-flow, as determined by single-photon emission computed tomography (SPECT) using technetium [99mTc] hexamethyl propylenamine oxime, were studied in two children presenting with alternating hemiplegia of childhood. Both experienced hemiplegic episodes several times per month, despite marked improvement on flunarizine therapy. SPECT images of both patients revealed focal areas of decreased uptake of the radiotracer, representing impaired regional cerebral blood-flow during, as well as between, seizures.

Valproate (VPA) metabolites in various clinical conditions of probable VPA-associated hepatotoxicity.

Of a cohort of 470 epileptic patients in whom valproate (VPA) serum metabolites had been measured, 170 subjects without symptoms or signs of hepatic side effects were chosen as a reference group to establish the usual metabolic pattern. A wide interindividual variation of VPA metabolite concentrations was noted. Infants receiving VPA monotherapy and comedication with other antiepileptic drugs (AEDs) showed lower concentrations of the potential hepatotoxin 4-ene-VPA than did older children.

[Irreversible valproate-associated liver failure].

A very severely retarded infant with a Dandy-Walker malformation was treated with valproate since the age of 6 months on account of infantile spasms. Three weeks after start of therapy dexamethasone was applied additionally because valproate was ineffective. Seventy-six days after initiation of valproate therapy the infant died with the clinical signs of fulminant valproate-associated hepatotoxicity despite the discontinuation of valproate.

Detection by HPLC-ICP of metallothionein in serum of an epileptic child with valproate-associated hepatotoxicity.

A patient who developed valproate-associated hepatotoxicity had significantly lower serum levels of total protein, albumin and selenium than the controls. This study shows that with the beginning of the hepatic coma metallothionein (MT) appeared in the serum mainly in the form of Zn-thionein, which altered the Zn distribution pattern of the serum in a characteristic manner. HPLC-ICP3 was successfully applied to the simultaneous speciation of elements and characterization of MT by the use of one gel permeation column.

Differentiation between valproate-induced anticonvulsant effect, teratogenicity and hepatotoxicity. Aspects of species variation, pharmacokinetics, metabolism and implications of structural specificity for the development of alternative antiepileptic agents such as delta 2-valproate.

Valproate is metabolized into a large number of compounds via various metabolic routes. Metabolic profiles depend on species and age. Hepatotoxicity may be correlated with abnormal metabolism, especially in young age.

[New aspects in prevention of febrile convulsions].

In general, febrile convulsions have a good prognosis. The risk of death or neurologic and mental handicap is low. Though the risk of epilepsy is increased, there is no evidence that anticonvulsant treatment can prevent occurrence of later epilepsy.

Valproate metabolites in serum and urine during antiepileptic therapy in children with infantile spasms: abnormal metabolite pattern associated with reversible hepatotoxicity.

The purpose of this study was to identify abnormal metabolite patterns of valproate (VPA) as possible early indicators of VPA-induced liver toxicity. In a prospective study, we determined serum and urine levels of VPA metabolites by gas chromatography-mass spectrometry (GC-MS) during the course of therapy in 25 children treated for infantile spasms with high VPA doses (less than or equal to 100 mg/kg body weight/day). Most patients had similar metabolite profiles: The main metabolites in serum were the beta-oxidation products (2-en-VPA and 3-keto-VPA) and the major diunsaturated metabolite 2,3'-dien-VPA.

[Valproate-associated hepatotoxicity--pathogenesis, clinical aspects, therapy and prevention].

The potential hepatotoxicity resulting in fatal liver failure is of major concern in treating patients with valproate (VPA). Until now there is no relevant laboratory parameter allowing early detection of impending liver failure. The major routes of VPA biotransformation are glucuronidation and beta-oxidation.

[Benign familial neonatal seizures].

Benign familial neonatal seizures are a rare cause of newborn seizures which can be easily detected by the family history because of their autosomal dominant inheritance. Based on 20 patients documented in the literature and one patient admitted to our clinic, the clinical picture can be characterized as follows: Only newborns at term are affected. Seizure types include multifocal-clonic, focal-clonic and subtle, beginning mostly on the 3rd day after birth (range: 1-8 day), the frequency can reach 40 per day.

Therapy of infantile spasms with valproate: results of a prospective study.

In a prospective study, 22 children with recently manifested infantile spasms (18 patients with symptomatic and 4 with idiopathic infantile spasms) were treated with sodium valproate (VPA). Before VPA was instituted, a loading test was performed to exclude abnormal patterns of VPA metabolites by gas chromatography and mass spectroscopy of serum and urine. This test was repeated during VPA therapy; an abnormal pattern of VPA metabolites was not observed.

[Alternating hemiplegia in childhood. Clinical report and single photon emission computed tomography study].

From 6 months of age on this girl experienced frequent episodes of hemiplegia involving both sides of the body and lasting up to 8 days. The attacks were often precipitated by tonic deviation of the head and/or the eyes to one side and nystagmus. At this stage the girl used to cry.

Increased concentration of prostaglandin E-2 in cerebrospinal fluid of children with febrile convulsions.

Concentrations of prostaglandins (PGs) in the central nervous system are known to increase during and after experimentally induced seizures. In the present study, concentrations of PGE-2 were determined by radioimmunoassay in lumbar cerebrospinal fluid (CSF) of 17 children shortly after a febrile convulsion. PGE-2 data of these children were compared with those determined in afebrile children and febrile children without convulsions.

Penetration of valproate and its active metabolites into cerebrospinal fluid of children with epilepsy.

Levels of the antiepileptic drug valproate (VPA) and five of its active metabolites (2-en-VPA, 3-keto-VPA, and 3-,4-, and 5-hydroxy-VPA) were determined by gas chromatography-mass spectrometry in cerebrospinal fluid (CSF) of 15 epileptic children undergoing chronic treatment with VPA. In eight of these children, total and free drug and metabolite concentrations in plasma were also measured. All VPA metabolites present in plasma could also be detected in CSF, although concentrations were substantially lower than those of the parent compound.

[Leigh's subacute necrotizing encephalomyelopathy due to decreased activity of the pyruvate dehydrogenase complex].

A new patient with Leigh's syndrome (subacute necrotizing encephalomyelopathy due to pyruvate dehydrogenase complex deficiency) is presented. A Turkish boy of consanguinously married healthy parents developed progressive muscle weakness since infancy. At the age of 3 years he was unable to sit, stand or walk.