[Repetitive peripheral magnetic stimulation. Treatment option for spasticity?]. / Repetitive periphere Magnetstimulation. Therapieoption bei Spastik?

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 magnetic stimulation comprising 10 series of 10 s duration was applied over the first sacral radix using a frequency of 20 Hz and a 1.2-fold intensity above the motoric threshold. RESULTS: The RPMS significantly reduced the tonus of the spastic talipes equines and this effect lasted for 1 week. No significant changes of electrophysiological parameters measuring the F-wave, H-reflex und ASR tendon reflex could be observed. CONCLUSION: The RPMS could prove to be an effective option for the treatment of spasticity. However, this method needs further evaluation by evidence-based studies.

Low CSF GABA concentration in children with febrile convulsions, untreated epilepsy, and meningitis.

In 14 children with epilepsy, 51 with febrile convulsions and 22 with meningitis gamma-aminobutyric acid (GABA) concentrations in lumbar CSF were determined. While the mean for CSF GABA concentrations for all epileptic children was unchanged [144 (range: 73-285) pmol/ml; controls: 148 (range: 90-243) pmol/ml] extraordinarily high GABA levels were found in the CSF of two children on valproate (525 and 557 pmol/ml) and remarkably low GABA concentrations in hitherto untreated epileptic children [109 (range: 67-176) pmol/ml]. Children with febrile convulsions [103 (range: 63-170) pmol/ml] and acute meningitis [105 (range: 65-171) pmol/ml] had significantly decreased CSF GABA concentrations (P less than 0.001 and P less than 0.02 compared with controls). The data indicate that valproate intake increases dramatically the GABA concentrations in the CSF of epileptic children. Furthermore, the study supports the concept that low GABAergic activity within the CNS may be one cause for an increased seizure frequency.

Oligoclonal gamma-globulin banding of cerebrospinal fluid in patients with subacute sclerosing panencephalitis. Comparison of the electrophoretic pattern with that in multiple sclerosis and congenital infections.

Lumbar cerebrospinal fluid (CSF) of 8 patients with subacute sclerosing panencephalitis (SSPE) was examined by agarose gel electrophoresis. In comparison with normal controls and children with different neurological diseases (including infections, tumours and degenerative diseases) the quantitative evaluation of the pherograms by an analog computer revealed an extreme change of the gamma-globulin profile. All cases showed 6-7 abnormal subfractions consisting of 2-4 tall, markedly protruding spikes and several small intermediate fractions. The oligoclonal gamma-globulin contributed 20.1-42.5% to total protein. This particular gamma-globulin profile seems to be highly indicative of the diagnosis of SSPE. It can be distinguished from the oligoclonal pattern in patients suffering from multiple sclerosis (MS) and congenital infections. The CSF protein profile of 13 patients with MS was different from that in SSPE in that it showed 1-5 monoclonal gamma-fractions in every case with none or only one peak protuding more markedly. The percentage of all subfractions amounted to 4.5-23.8% of total protein. As in MS, the aspect of oligoclonality in 9 children with congenital infections (cytomegalic inclusion body disease, toxoplasmosis and rubella) was quite variable, as again 1-5 abnormal subfractions were detected. Their relative concentrations, on the whole ranging from 0.6-12% of total protein, was considerably lower than in SSPE.

Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism.

Gamma-hydroxybutyric aciduria is a disorder of gamma-aminobutyric acid metabolism in which a compound of known neuropharmacologic activity accumulates. We have studied two patients in whom high levels of gamma-hydroxybutyric acid were found in blood, urine and cerebrospinal fluid. A coupled assay has been developed which estimates succinic semialdehyde dehydrogenase activity in isolated human lymphocytes. The mean activity of succinic semialdehyde dehydrogenase in a control and the four parents and two healthy siblings of these patients was 8.8 +/- 1.9 pmol . min-1 . mg-1 protein. In the patients the activities were 0.8 and 1.1 pmol . min-1 . mg-1 protein, approximately 9-13% of control. In the presence of saturating amounts of NAD+, lymphocyte sonicates, derived from the patients accumulated a significant amount of 14C-succinic semialdehyde from 14C-gamma aminobutyric acid, whereas none could be detected in controls. The data suggest a deficiency of succinic semialdehyde dehydrogenase in these patients, the first documented defect of the metabolism of gamma-aminobutyric acid in man.

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. In 202 children without diseases known to alter cerebrospinal fluid, normative protein properties were quantified using nephelometry, ultrafiltration, high-resolution electrophoresis, and Gaussian curve fit densitometry. Total protein and protein concentrations (albumin and gamma-globulins) decreased from birth until 7 months age, and, from then on, increased slightly (transthyretin, albumin, and alpha2-proteins) or strongly (gamma-globulins). Protein proportions (transthyretin and transferrin) increased until about 3 years of age and decreased from then on. These normative values for children as quantified by high-resolution agarose gel electrophoresis are presented in a significance-structured percentile table. The time courses of these cerebrospinal fluid properties reflect physiologic alterations of the blood-brain barrier function during childhood.

[Pelvic bone angiomas]. / Pelvine Knochenangiome.

Three patients were seen with angiomas of the pelvic bones; the radiological and clinical features are described and the literature reviewed. The patients had been observed for four to six years. The differential diagnosis includes infiltrating mesenchymal neoplasms and the histologically similar, but rare, Gorham-Stout syndrome. Recommended treatment is irradiation, which is effective up to a point.

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). After a mean follow-up time of 5 1/4 years (range: 4 1/4-6 1/2) 72% of 18 evaluable patients (two children died, three were lost to follow-up) revealed seizure freedom for at least 1 year. The mean duration of vigabatrin therapy had been 2 1/2 years (range: 2 weeks to 4 3/4 years). Two-thirds of the 18 children continued to take AEDs, three of them undergoing vigabatrin monotherapy. Relapses of infantile spasms had occurred in 14% of the children. The rate of vigabatrin side effects (10%) was low. At follow-up, the EEG of 13 and the 18 patients demonstrated focal or multifocal epileptic discharges. Fifty-five percent had developed another epilepsy (focal epilepsy, secondary generalized epilepsy or myoclonic-astatic epilepsy). With respect to mental functions, three children were normal or slightly retarded, four showed moderate retardation and 11 revealed severe or very severe retardation. This long-term result is comparable to that in ACTH studies with unselected patients. The conclusions are: (1) vigabatrin is an effective drug for the short-term and long-term treatment of refractory infantile spasms; (2) the relapse rate is low; (3) vigabatrin is well tolerated; (4) with respect to secondary epilepsies and mental functions the long-term outcome in these pretreated children is similar to that in earlier studies with ACTH or corticosteroids.

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. Unilateral hearing loss could be located in the inner ear of one patient by audiologic examination. Localized bone destruction and disintegration of a portion of the anterior wall of the frontal sinus were observed in a patient after more than three decades. Marked shrinking of the homolateral parotid gland and homolateral masticatory spasm are reported as further otorhinolaryngological manifestations. The various complications of PFH call for close interdisciplinary cooperation.

[Optimizing epilepsy therapy in children and adolescents with lamotrigine]. / Optimierung der Epilepsietherapie von Kindern und Jugendlichen mit Lamotrigin.

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. The first studies show that lamotrigine is also effective in children under 2 years of age. For therapy of difficult-to-treat epilepsies the combination of lamotrigine with valproate has proved as especially useful. This clinical observation is supported by new results of animal experiments. The dose-dependant and typical CNS side effects vertigo, ataxia, nausea, tremor and diplopia are found most frequently. The rate of allergic skin rashes which was very high before 1998 has decreased markedly by new dosage guidelines and is now as low as in older antiepileptic drugs. Lamotrigine does not impair cognitive functions, especially not memory and language. It has mood-stabilizing features and may improve quality of life. In animal experiments lamotrigine shows antiepileptogenic and neuroprotective effects.

[Mitochondrial myopathies and encephalomyopathies. Neuromuscular and central nervous system diseases caused by defects in mitochondrial oxidative metabolism]. / Mitochondriale Myopathien und Enzephalomyopathien. Neuromuskuläre und zentralnervöse Erkrankungen infolge von Defekten des mitochondrialen oxydativen Stoffwechsels.

In this review the clinical data and biochemical findings of disorders of oxidative metabolism in the mitochondria are summarized. Defects in pyruvate metabolism, the citric acid circle, the respiratory chain and less well defined disorders of energy transfer are discussed.

[Benign familial neonatal seizures]. / Benigne familiäre neonatale Krampfanfälle.

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. Interictally the patients are neurologically normal. As a rule, clinical, laboratory and neuroradiological investigations show no relevant deviations. The seizures usually disappear within 8 months. Nearly all children were treated with phenobarbital. After discontinuation of therapy, the seizures relapsed transiently in a few patients. Referring to about 140 patients described in the literature, the following conclusions can be drawn with regard to prognosis: Generally, mental development is normal, however, 4% of the patients later showed mental retardation. About 10% of the children developed epilepsy during childhood or adulthood. Two children died in the neonatal period. The fifth day fits must be separated from benign familial neonatal seizures, these are not genetically determined.

[New aspects in prevention of febrile convulsions]. / Neue Aspekte zur Prophylaxe von Fieberkrämpfen.

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. The aim of anticonvulsive prophylaxis is reduction of the rate of recurrences of febrile convulsions. Recent results point against the assumption that these can be prevented by long-term anticonvulsive treatment with phenobarbital or valproate. An alternative for longterm prophylaxis is intermittent short-term rectal application of diazepam suggested for children with a hightened risk of recurrences. Long-term prophylaxis with phenobarbital should only be considered in a small number of selective children.

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. The interictal finding of localized areas of reduced tracer uptake suggest that long-lasting hypoperfusion could be the pathophysiological mechanism by which the slowly resolving hemiplegia, and ultimately the permanent multifocal neurological deficits, are produced.

[Brain stem encephalitis (author's transl)]. / Hirnstammenzephalitis.

Basing on a case of brain stem encephalitis in a girl of 7 1/2 years of age, the features of this disease pattern are described. The initially found disturbance of the blood brain barrier provides a clue to the possible pathogenesis of the disease in association with the pattern of clinical signs, namely, an inflammatory-hyperergic reaction of the neurovascular system in the brain stem.

[Valproate-associated hepatotoxicity--pathogenesis, clinical aspects, therapy and prevention]. / Valproat-assoziierte Hepatotoxizität--Pathogenese, klinisches Spektrum, Therapie und Prophylaxe.

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. There are several other pathways of degradation with formation of mono- und di-unsaturated derivates. VPA dose, patients age, co-medication (anticonvulsants, aspirin), fasting and glucose supply influence the VPA metabolism. The clinical spectrum of VPA-associated hepatotoxicity reaches from slight increases of liver enzymes without clinical manifestations over reversible slight to severe liver dysfunction to fatal liver failure. With respect to pathogenesis attention has focused on depletion of beta-oxidation and change of biotransformation to other pathways with increased synthesis of toxic unsaturated VPA derivates. Several inborn errors of metabolism, acute infections and status epilepticus seem to predispose to liver failure. Another hypothesis lies in the possible VPA-induced depression of free radical scavenging enzyme activities. On this basis N-acetylcysteine has been used successfully in treating children with severe hepatotoxicity. In the presence of certain risk factors VPA should be avoided.

Cerebrospinal fluid gamma-aminobutyric acid levels in children with different types of epilepsy: effect of anticonvulsant treatment.

The mean gamma-aminobutyric acid (GABA) level in lumbar CSF of 31 children with epilepsy was not significantly different from that of 41 age-matched controls. However, when the epileptic children were subdivided into untreated patients and patients treated with antiepileptic drugs, the medication-free subgroup had a significantly lower mean CSF GABA level than nonepileptic children. Patients controlled by anticonvulsant therapy had significantly higher CSF GABA levels than untreated epileptic patients. A more detailed analysis of the children taking antiepileptic medication indicated that the only drug that significantly increased GABA in CSF was valproic acid. Analysis of CSF data with respect to the seizure type of the patients showed that, compared with controls, significantly reduced average GABA levels were present in children with infantile spasms (mostly untreated) and unmedicated generalized tonic-clonic seizures, whereas treated children with generalized tonic-clonic seizures and patients with partial epilepsy (mostly treated) did not significantly differ from controls. The data provide further evidence that impairment of the central GABA system may be involved in human epilepsy.

[Transient unilateral oculomotor paralysis]. / Passagere einseitige Okulomotoiusparese.

A three-year-old girl was admitted to the hospital one day after the acute onset of drooping of the left eyelid, associated with oculomotor external ophthalmoplegia. General neurological and physical examination was unremarkable. Results of serological tests as well as the clinical course of the disease (spontaneous recovery) show that the unilateral oculomotor neuropathy was most likely due to a self-limited enteroviral infection. The virus could not be cultured in the CSF. Echovirus type 11 as well as Coxsackie B4 virus might have caused the disease. During treatment with prednisone for 3 weeks in decreasing doses the girl recovered, by the seventh day she was able to raise her eyelid. 3 1/2 months later she had no evidence of residual ptosis and full range of ocular movements.