Lacosamide as treatment for partial epilepsy: mechanisms of action, pharmacology, effects, and safety

Lacosamide (LCM) is a novel agent that has been developed as an antiepileptic drug. In vitro studies suggest that LCM modulates voltage-gated sodium channels by enhancing their slow inactivation. In addition, LCM seems to interact with collapsin-response mediator protein 2 and thus may mediate neuronal plasticity. LCM has an elimination half-life of 13 hours, no relevant protein binding, and does not induce or inhibit enzymes of the cytochrome P450 system. No clinically significant drug–drug interactions have been discovered as yet. Experimental data suggest anticonvulsant as well as analgesic effects. Large clinical studies have demonstrated its efficacy for treatment of patients with partial seizures. LCM is well tolerated, and the most common adverse events are unspecific central nervous system and gastrointestinal effects such as dizziness, vertigo, nausea, and headache. LCM is approved for treatment of partial seizures with or without secondary generalization in the United States and the European Union within a dose range of 200 to 400 mg per day, administered twice daily. In addition to the oral formulations, an intravenous infusion solution is available

Repeated Intracarotid Amobarbital Tests

Rationale:Our goal was to determine the frequency of repeated intracarotid amobarbital test (IAT) at our center and to estimate the retest reliability of the IAT for both language and memory lateralization. Methods: A total of 1,249 consecutive IATs on 1,190 patients were retrospectively reviewed for repeat tests. Results: In 4% of patients the IAT was repeated in order to deliver satisfactory information on either language or memory lateralization. Reasons for repetition included obtundation and inability to test for memory lateralization, inability to test for language lateralization, no hemiparesis during first test, no aphasia during first test, atypical vessel filling, and bleeding complications from the catheter insertion site. Language lateralization was reproduced in all but one patient. Repeated memory test results were less consistent across tests, and memory lateralization was unreliable in 63% of the patients. Discussion: In spite of test limitations by a varying dose of amobarbital, crossover of amobarbital from one side to the other, testing of both hemispheres on the same day, practice effects, unblinded observers, fluctuating cooperation of the patients, and a biased sample of patients language lateralization was reproduced in all but one patient. In contrast, repeated memory test results were frequently contradictory. Memory results on IAT therefore seem much less robust than the results of language testing. Gain of reliable information versus the risks of complications and failed tests has to be considered when a patient is subjected to an IAT

Tools of market researches on the internet

In article the offline and on-line tools of carrying out market researches on the Internet are discussed. The author has emphasized advantages and shortcomings of each of tools, and also has proved need of their use

Pregabalin-associated acute psychosis and epileptiform EEG-changes

SummaryPregabalin is a novel anticonvulsive and analgesic drug that has been marketed in Europe for more than a year. The typical side effects are dizziness, somnolence and weight gain. We present a patient who, after unintended rapid up-titration of pregabalin, experienced psychotic symptoms associated with rhythmic EEG-changes resolving completely after discontinuation of pregabalin and benzodiazepine administration

Making SENSE--Sustained Effort Network for treatment of Status Epilepticus as a multicenter prospective registry.

BACKGROUND: Evidence regarding the different treatment options of status epilepticus (SE) in adults is scarce. Large randomized trials cover only one treatment at early stage and suggest the superiority of benzodiazepines over placebo, of intravenous lorazepam over intravenous diazepam or over intravenous phenytoin alone, and of intramuscular midazolam over intravenous lorazepam. However, many patients will not be treated successfully with the first treatment step. A large randomized trial covering the treatment of established status (ESETT) has just been funded recently by the NIH and will not start before 2015, with expected results in 2018; a trial on the treatment of refractory status with general anesthetics was terminated early due to insufficient recruitment. Therefore, a prospective multicenter observational registry was set up; this may help in clinical decision-making until results from randomized trials are available. METHODS/DESIGN: SENSE is a prospective, multicenter registry for patients treated for SE. The primary objective is to document patient characteristics, treatment modalities and in-house outcome of consecutive adults admitted for SE treatment in each of the participating centres and to identify predictors of outcome. Pre-treatment, treatment-related and outcome variables are documented systematically. To allow for meaningful multivariate analysis in the patient subgroups with refractory SE, a cohort size of 1000 patients is targeted. DISCUSSION: The results of the study will provide information about risks and benefits of specific treatment steps in different patient groups with SE at different points of time. Thus, it will support clinical decision-making and, furthermore, it will be helpful in the planning of treatment trials. TRIAL REGISTRATION: DRKS00000725

Вдосконалення антикризового управління бізнесом ресторанів та закладів мобільного харчування

Пояснювальна записка: 77 стор., 12 рис., 7 табл., 30 джерел, додатки, презентація PowerPoint. Об’єкт дослідження: процес управління бізнесом в сфері діяльності ресторанів та закладів мобільного харчування. Мета роботи: теоретичне обґрунтування інструментарію підвищення ефективності функціонування ресторанів і закладів мобільного харчування в невизначених умовах всесвітньої кризи. В роботі розроблена вдосконалена модель бізнесу для ресторанів та закладів мобільного харчування адаптована до умов кризи. У першому розділі проаналізовані напрямки вдосконалення антикризового управління бізнесом спираючись на досвід українських підприємців та праці науковців, визначені завдання магістерського дослідження. У другому розділі здійснена оцінка фактичного впливу кризи (КОВІД-19) на бізнес ресторанів та закладів мобільного харчування на національному рівні, визначено характер антикризових заходів суб’єктів регуляторної діяльності та їх впливу на перспективи бізнесу, розроблено сценаріїв розвитку кризової ситуації та типових антикризових рішень. У третьому розділі проаналізовано традиційну модель бізнесу ресторанів та закладів мобільного харчування та вдосконалено під умови кризових обмежень, визначено ключові чинники ефективності антикризового управління в умовах КОВІД-19

Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).

To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432

Frequency of seizures and epilepsy in neurological HIV-infected patients

SummaryBackgroundInfection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy.MethodsThe database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined.ResultsOf 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on anticonvulsant therapy (gabapentin: 14 patients, carbamazepine: 9 patients, valproate: 2 patients, phenytoin: 1 patient, lamotrigine: 1 patient). Patients with only provoked seizures had no epilepsy risk factors except HIV infection, and were less likely to be infected via intravenous drug abuse.ConclusionsSeizures are a relevant neurological symptom during the course of HIV infection. Although in some patients seizures only occur provoked by acute disease processes, the majority of patients with new onset seizures eventually develops epilepsy and require anticonvulsant therapy. Intravenous drug abuse and the presence of non-HIV-associated risk factors for epilepsy seem to be associated with the development of chronic seizures in this patient group

Wada Test Reliability (Response to Haber et al.)

Response piece