Gerd Kurlemann

Levetiracetam in children with refractory epilepsy: A multicenter open label study in Germany

PURPOSE To evaluate the efficacy and tolerability of Levetiracetam (LEV) in a large pediatric cohort with drug-resistant epilepsy from a prospective multicenter observational study. METHODS We report the results of a multicenter observational survey of a cohort of 285 pediatric patients (mean: 9.9 years, range: 0; 6-17; 11) with refractory generalized and focal epilepsy who received Levetiracetam as an add-on open label treatment trial. The average duration of epilepsy was 6.0 years and the patients were treated with a mean of 7.0 antiepileptic drugs (AED) before LEV was introduced. RESULTS No serious persistent adverse events were reported. Reversible colitis and an apnoea syndrome in a child with phosphorylase-A-kinase-deficiency were noted. Mild to moderate side effects were reported in 128 patients (44.9%), consisting most frequently of somnolence (23.9%), general behavioral changes (15.4%), aggression (10.5%) and sleep disturbances (3.2%). In 209 patients, efficacy was analyzed over a treatment period of at least 12 weeks compared to a baseline of 2 weeks. Thirteen patients (6.2%) became seizure free, 39 (18.7%) responded with a seizure reduction of more than 50% following introduction of LEV. No response to LEV was reported in 65.1% (n=136). A decrease of initial treatment effect was seen in 37 patients (17.8%) while in 6.7% the seizure frequency doubled to the baseline (n=14). In seven patients (3.3%), the effect of LEV on seizure frequency could not be evaluated. A positive psychotropic effect was observed in 18 patients (8.6%). Mental retardation was associated with poor response and associated with more side effects and earlier discontinuation of LEV therapy. CONCLUSION LEV is a well-tolerated new AED that may effectively improve seizure control as an add-on drug in resistant epilepsy in childhood with good tolerability. However, neurologically handicapped children appear at increased risk for reversible neurocognitive side effects and have a poorer treatment response.

Event-related potentials (P300) in primary headache in childhood and adolescence.

There is strong evidence for a loss of habituation during cognitive processing in migraine as measured by P300 and contingent negative variation in adults. Event-related potentials evoked by an oddball paradigm have not yet been studied in children and adolescents suffering from different primary headache types. We recorded visually evoked event-related potentials (two consecutive trials, 200 stimuli each) in 48 children and adolescents suffering from migraine without or with aura, from episodic tension-type headache, and from ergotamine-induced headache and analyzed the latencies, amplitudes, and reaction times. No statistically significant differences were noted between all headache types and healthy controls analyzing the averaged parameters for the whole measurement. However, a highly significant loss of cortical habituation as measured by P300 amplitude and latency could be observed in migraine without and with aura by analyzing the first and the second trial of measurement separately. This phenomenon increased with age and could not be seen in healthy controls, or patients with tension-type headache or ergotamine-induced headache. Our data suggest a specific cognitive processing in migraine even in children and adolescents. Measurement of the habituation effect in P300 latency and amplitude provides a specific method to differentiate between primary headache types in childhood and adolescence. (J Child Neurol 1998;13:322-326).

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. The primary efficacy variable was the number of seizure-free patients during study weeks 17 and 24. RESULTS Two hundred and thirty-nine patients were included. One hundred and seventy-six patients suffered from FE and 63 from GE. In the FE group, 88 patients each were treated with CBZ or LTG. Ninety-four percent of the CBZ patients and 89% of the LTG patients became seizure-free according to an intent-to-treat analysis (not statistically different). The rate of patients discontinuing treatment due to adverse events or a lack of efficacy was 19% with CBZ compared to 9% with LTG (not statistically different). In the GE group, 30 patients received VPA and 33 LTG. During study weeks 17 and 24, 61% of the LTG patients and 84% of the VPA patients had become seizure-free (not statistically significant). The drop-out rate due to lack of efficacy or adverse events was 12% with LTG and 3% with VPA (not statistically different). CONCLUSIONS This study indicates that the effectiveness of LTG in focal and generalised epilepsy syndromes as initial monotherapy in patients >or=12 years is in the range of standard first-line antiepileptic drugs.

High uptake of L-3-[123I]iodo-α-methyl tyrosine in pilocytic astrocytomas

Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of malignancy on various neuroimaging modalities. This retrospective analysis was conducted to determine whether scintigraphic features of malignancy are also found on single-photon emission tomography (SPET) using L-3-[123I]iodo-α-methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas were retrospectively selected from a large series of patients referred for the evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16 patients, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was available in 10 of the patients and SPET using technetium-99m tetrofosmin or thallium-201 had been performed in 11. Image analysis was performed using standard protocols to determine how many patients exceeded the respective thresholds of malignancy. Features of malignancy were found in 7/16 IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET investigations. A significant correlation of tumour size and IMT uptake in primary pilocytic astrocytomas indicated partial volume effects to partly account for the differential uptake behaviour (n=10, r=0.87, P<0.05). Differences in IMT uptake in primaries (1.7±0.6, n=10) and in recurrent tumours (2.3±0.7, n=6) did not attain statistical significance. IMT SPET results indicative of malignancy are regularly found in pilocytic astrocytomas, despite their good prognosis. No uptake may be detected in largely cystic or in small tumours.

Vigabatrin in Metachromatic Leucodystrophy; Positive Influence on Spasticity

reported the positive use of vigabatrin for two children with metachromatic leucodystrophy (MLD), with decreased GABA levels in the CSF, which normalized during vigabatrin therapy2. A t the same time, a clear reduction in spasticity was observed. We diagnosed MLD in a two-year-old boy, who is now 2% years old. Clinically there was marked spasticity in the legs, nystagmus and marked mental retardation. There was no measurable reduction of arylsulfatase A in leucocytes and fibroblasts. Because of the report by Jaeken and colleagues and our own unpublished observations of decreased muscle tone in multiply disabled children during treatment with vigabatrin for therapy-resistant epilepsy, we started this boy on vigabatrin 2 x 25Omg/day.

Ceasing of movement-disorder attacks immediately after the onset of pregnancy: possible effect of human chorionic gonadotropin.

In a woman with paroxysmal kinesiogenic choreoathetosis, attacks ceased within a few days after conception. An effect of human chorionic gonadotrophin is assumed, since this hormone decreased sodium currents and excessive action potential generation in an experimental approach.