Background Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy.Methods A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher's exact test, alpha.=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged >= 12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed.Results The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07).Conclusions There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm.

ZusammenfassungRotigotin transdermales System wurde als erstes Wirkstoffpflaster zur kontinuierlichen Behandlung des mittelschweren bis schweren idiopathischen Restless-legs-Syndroms (RLS) bei Erwachsenen zugelassen. Es enthält den nicht ergolinen Dopaminagonisten Rotigotin, der kontinuierlich über 24 Stunden in die Blutbahn abgegeben wird. Dies ermöglicht eine Beherrschung der klinischen Symptome über den Tag und könnte durch die kontinuierliche dopaminerge Stimulation über die Pflasterapplikation im Vergleich zu bisher verfügbaren Therapien mit einer geringeren Augmentationsrate verbunden sein. Ziel dieser Übersichtsarbeit ist es, die publizierten Studiendaten vorzustellen und mögliche Vorteile der neuen Therapieoption für die klinische Praxis herauszuarbeiten.

Rotigotine transdermal system is the first transdermal system that was launched fort the treatment of moderate to severe idiopathic restless legs syndrome (RLS) in adults. The patch releases continuously the non-ergoline dopamine agonist rotigotine over a period of 24 hours. The continuous dopaminergic stimulation leads to a control of daytime symptoms and could result in a lower augmentation rate in comparison to orally delivered drug. Purpose of this review was to summarize results of the clinical trials and to point out potential benefits of transdermal treatment in RLS for daily routine.

Depressive Störungen sind eine häufige Komorbidität beim Restless-legs-Syndrom (RLS). Vergleichbare Prävalenzraten von Begleitdepressionen finden sich zwar auch bei anderen Erkrankungen, die Assoziation zwischen RLS und Depression ist jedoch durch die RLS-bedingten erheblichen Schlafstörungen besonders komplex. Klinisch von Bedeutung ist zudem, dass verfügbare Daten, überwiegend aus Fallberichten, zeigen, dass eine Vielzahl antidepressiver Medikamente die RLS-Symptomatik verstärken kann. Eine komorbide Depression beeinflusst den Therapieerfolg der Grunderkrankung und sollte deshalb berücksichtigt werden. Bislang gibt es keine systematischen Untersuchungen und daher keine evidenzbasierten Empfehlungen zur pharmakologischen Therapie von depressiven Symptomen bei RLS. In der vorliegenden Übersicht werden die klinische Relevanz von depressiven Störungen bei RLS und die Auswirkung einer antidepressiven Behandlung auf die RLS-Symptomatik diskutiert sowie ein Therapiealgorithmus (Evidenzklasse C) zur Behandlung einer komorbiden Depression bei RLS vorgestellt.

Depressive disorders are a prevalent comorbidity in restless legs syndrome (RLS). Although similar prevalence rates of comorbid depression can be found in other diseases, the association between RLS and depression is particularly complex due to the RLS-related sleep disorders. It is also clinically important that according to findings derived mainly from case studies many antidepressant agents can aggravate RLS symptoms. The presence of comorbid depression influences therapy outcome in general and should therefore be taken into account. So far, there is no evidence-based systematic research concerning diagnosis and treatment process, and no recommendations exist for the treatment of affective disorders in RLS. In the present work, the clinical relevance of depression in RLS and antidepressive treatment in RLS symptoms is discussed and a therapeutic algorithm (evidence level C) for the treatment of depression in RLS is provided.

Objectives: To evaluate the effectiveness of pramipexole on RLS symptom severity and the impact on quality of life in patients with primary Restless Legs Syndrome (RLS) in routine clinical practice.

Sixty percent of the patients with restless legs syndrome (RLS) report a positive family history. To date five loci have been mapped on chromosome 12q, 14q, 9p, 2q, and 20p (RLSI-5) but no gene has been identified so far. To identify Genes related to RLS, we performed a three-stage association study (explorative study, replication study, high-density mapping) in two Caucasian RLS case-control samples of altogether 91 independent cases and controls. In the explorative study (367 cases and controls, respectively), we screened 1536 SNPs in 366 genes in a 21 Mb region encompassing the RLS I critical region on chromosome 12. Armitage trend test revealed three genomic regions that were significant (P < 0.05). In the replication study (551 cases and controls, respectively) we genotyped the most significant SNPs of Stage 1. After correction for multiple testing. association was observed with SNP rs7977109 (P-nominal = 0-00 175, PWestfall-Young = 0.04895, OR = 0.76228, 95% CI 0.64310-0.90355), which is in the neuronal nitric oxide synthase (NOS]) gene. High-density mapping using altogether 34 tagging and coding SNPs of the NOS] gene in both case-control samples further confirmed the significant association results to NOS]. Ten more SNPs revealed significance with nominal P-values from 0.0001 to 0.0482 (genotypic test and Armitage test). Altogether, this study provides evidence for an association of variants in the NOS] gene and RLS, and suggests the involvement of the NO/arginine pathway in the pathogenesis of RLS. Potential usage of NO modulating agents as new treatment options for RLS have become a challenging aspect for future research of this disorder. (c) 2007 Movement Disorder Society.

Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.

Gutachterliche Fragestellungen bei Patienten mit einem Restless-Legs-Syndrom (RLS) nehmen stetig zu. Darum hat die “AG Motorik und Schlaf” der DGSM erstmals Empfehlungen zur Begutachtung und sozialmedizinischen Einschätzung des RLS erarbeitet. Im Folgenden werden die spezifischen Empfehlungen zur Beurteilung des RLS im Rahmen gutachterlicher Verfahren zusammengefasst (aus [5]). Diese Konsensusleitlinie soll eine Grundlage zur Vereinheitlichung und Qualitätssicherung in der Begutachtung des RLS darstellen und nicht in individuelle Begutachtungen eingreifen.

Ictal heart rate was investigated in otherwise subclinical epileptic seizures to test the hypothesis as to whether ictal tachycardia is physiological and not a physical or psychological stress response. In addition, we aimed to evaluate the localizing significance of pure ictal tachycardia. We included 21 epilepsy patients, who showed an ictal EEG seizure pattern during 22, otherwise subclinical seizures. All patients underwent ictal video-EEG recordings to evaluate the possibility of resective epilepsy surgery. The changes in heart rate in these patients were investigated in order to determine their relationship to localization and duration of EEG seizure patterns. Ictal tachycardia was observed in 41% of the otherwise subclinical seizures (nine out of 22), and significantly more often in seizures arising from the temporal lobe than from extratemporal regions (62% versus 11%, p < 0.0018). The seizure duration as defined by EEG was significantly positively correlated with an increase of heart rate (p = 0.043). Ictal heart rate can increase as a result of epileptic activation of autonomic cortex, reflecting a temporal lobe autonomic influence. Thus, measurement of heart rate should be included in the evaluation of otherwise subclinical epileptic seizures, because of its localizing value.