Metaplasticity refers to the activity-dependent modification of the ability of synapses to undergo subsequent potentiation or depression, and is thought to maintain homeostasis of cortical excitability. Continuous magnetic theta-burst stimulation (cTBS; 50 Hz-bursts of 3 subthreshold magnetic stimuli repeated at 5 Hz) is a novel repetitive magnetic stimulation protocol used to model changes of synaptic efficacy in human motor cortex. Here we examined the influence of prior activity on the effects induced by cTBS. Without prior voluntary motor activation, application of cTBS for a duration of 20 s (cTBS300) facilitated subsequently evoked motor potentials (MEP) recorded from APB muscle. In contrast, MEP-size was depressed, when cTBS300 was preceded by voluntary activity of sufficient duration. Remarkably, even without prior voluntary activation, depression of MEP-size was induced when cTBS was extended over 40 s. These findings provide in vivo evidence for extremely rapid metaplasticity reversing potentiation of corticospinal excitability to depression. Polarity-reversing metaplasticity adds considerable complexity to the brain's response toward new experiences. Conditional dependence of cTBS-induced depression of corticospinal excitability on prior neuronal activation suggests that the TBS-model of synaptic plasticity may be closer to synaptic mechanisms than previously thought.
The influence of smoking on lamotrigine (LTG) serum levels in 44 patients with epilepsy treated with LTG in monotherapy was examined. Fifteen patients were smokers (range: three cigarettes per month -- three packages per day) and 29 were non-smokers. Analyzing 204 samples, smokers had a significantly lower serum level-to-dose ratio than non-smokers (0.0657mmolmg/l (smokers) vs. 0.0785mmolmg/l (non-smokers)) (p=0.0014). Analyzing only male patients, the same relationship with an almost equally high level of significance could be demonstrated (p=0.008). Our data indicate that the demonstrated effect of smoking on LTG metabolism is likely to be mediated via UDPGT2B7, as LTG is not a substrate of cytochrome P450 isoenzymes and UDPGT1A4 activity may not be affected by nicotine, but the exact mechanism underlying the demonstrated effect remains uncertain. These findings are likely to be independent from hormonal changes, as they could also be reproduced in the group of male patients. Therefore, the effect of smoking on blood levels of LTG has to be taken into account in the evaluation of treatment with this drug.
pilepsy is a common neurological disorders with a lifetime prevalence of 7.6 per 1000 persons (e1). In addition to recurrent seizures, epilepsy is also associated with comorbidities such as cognitive and psychological problems, as well as social difficulties (e2). Despite the known positive effects of sports and physical activity on quality of life and general disease prevention (e3), patients with epilepsy have long been discouraged from participating in sports activities (e4). This recommendation is likely based on the fear that sporting activity may cause injuries, potentially induce seizures, and have a negative effect on disease course. However, over the past few decades, studies have shown that sports-related injuries are not more common in these patients compared to the general population (e5). Therefore, the questions arise as to whether patients with epilepsy avoid sports and take less physical exercise than the general population on the basis of unverifiable rationales and prejudices (e6) and whether this leads to further disadvantages for this group. In 2016, the International League Against Epilepsy (ILAE) published a consensus paper that recommends safe sports participation for patients with epilepsy (e7). It is unclear which positive effects of sports on actual disease activity these patients are being deprived of. Therefore, the aim of this systematic review is to answer the following questions: • Are patients with epilepsy less physically active and less fit than the general population? • What effect does physical activity have on comorbidities in epilepsy? • What effect does physical activity have on the frequency of seizures? Methods The literature search was conducted on 31 January 2019, in the PubMed (Medline/PubMed Central) and Web of Science databases. The following search terms were used: (epilepsy OR "AED" OR seizure OR antiepileptic OR epileptic) AND (exercise OR "physical activity" OR sport OR training OR "physical effort" OR "physical therapy"). Longitudinal and crosssectional human studies, as well as case studies, were included. Diagnosed epilepsy and endpoints on Summary Background: For many years, people with epilepsy were advised not to engage in sports. In this systematic review, we investigated whether persons with epilepsy exercise less than the general population, and what effect physical activity has on epilepsy. Methods: A literature search was carried out in PubMed and the Web of Science, and 14 269 studies were entered into the selection process. The selected studies were assessed for their methodological quality and accordingly assigned an evidence level. Results: 42 studies were included in the review; 10 were classified as evidence level 3, 27 as evidence level 2-, 2 as evidence level 2+, and 3 as evidence level 1-. Persons with epilepsy are less physically active and less physically fit than the general population. Reduced physical activity is associated with a higher frequency of comorbidities and lower quality of life. Physical interventions can improve quality of lif...
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