Kellinghaus C, Berning S, Immisch I, Larch J, Rosenow F, Rossetti AO, Tilz C, Trinka E. Intravenous lacosamide for treatment of status epilepticus.
Acta Neurol Scand: 2011: 123: 137–141.
© 2010 John Wiley & Sons A/S. Objectives –  Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first‐line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment. Methods –  We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM. Results –  Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200–400 mg), which was administered at 40–80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented. Conclusions –  Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.

Objective: To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. Methods: 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. Results: 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. Interpretation: 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.

SUMMARYLacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE. KEY WORDS: Convulsive status epilepticus, Refractory convulsive status epilepticus, Lacosamide.Status epilepticus (SE), consisting of convulsive type (CSE) and nonconvulsive type (NCSE), is a clinical emergency and a potentially life-threatening condition. The incidence of SE in Germany, Switzerland, Italy, and in the white U.S. population has been reported to be 10-20/ 100,000, which is even higher in the developing countries, especially in the children and older age group (Jallon et al., 1999;Coeytaux et al., 2000;Knake et al., 2001;Wu et al., 2002;Vignatelli et al., 2005;DeLorenzo, 2006). The reported mortality varies from 1.9-40% (Rosenow et al., 2007). CSE is the most often encountered type in clinical practice and needs to be interrupted rapidly to avoid death and neurologic sequelae. Refractory CSE (RCSE) is defined as SE not responding to the first and second treatment effort. It is associated with prolonged intensive care and a poor outcome.Therefore, more effective substances and treatment strategies for SE are needed. Lacosamide (Vimpat) is a novel antiepileptic substance recently licensed for adjunctive therapy for partial-onset seizures. Herein we report the first clinical case of successful treatment of RSCE with lacosamide. Methods and ResultsA 38-year-old male patient had epileptic seizures due to perinatal hypoxia with resulting infantile cerebral palsy. The seizure semiology was as follows: sudden simple partial seizures with versive movement of the head to the left, myoclonic jerks of the left extremities, followed by complex partial seizures with disturbance of consciousness, and, most often, secondarily generalized tonic-clonic seizures. The mean seizure frequency was around 5-7 per month with duration of 2-3 min. The antiepileptic regimen prior to admission was levetiracetam 2 · 1,500 mg (serum concentration 68 lmol/L), clonazepam 2 mg, and topiramate 200 mg (serum concentration 10 mg/ml). The patient was severely physically disabled with spastic tetrapareses, and a percutaneous gastri...

Summary:Purpose: Overexpression of the multiple drug resistance gene 1 (MDR1) was quantified in brain tissue from Coriaria lactone (CL)-kindled Sprague-Dawley (SD) rats after treatment with lamotrigine (LTG) or topiramate (TPM) and compared with that found in rats treated with carbamazepine (CBZ) and valproate (VPA).Methods: Twenty-five CL-kindled SD rats were randomized into five groups (n = 5 for each group) to receive once-daily feeding of CBZ, VPA, TPM, and LTG as the monotherapy equivalent of maximum human adult dosage, or normal saline (NS control) for 1 month. The expression of P-gp in brain tissues of all rats was quantified by using an image analysis and measuring system (Image Pro-plus 4.0). Mean area and mean integrated optical density (mean IOD) of P-gp expression were calculated.In addition, the changes in seizure severity were analyzed via video-camera monitoring.Results: A significant decrease in the number and duration of seizures with antiepileptic drug (AED) treatment was observed in the TPM and LTG groups. The mean area and mean IOD of P-gp expression were highest in the CBZ group and next highest in the VPA group; much lower values were measured in the TPM and LTG groups, and the lowest in the NS control group (p < 0.05).Conclusions: TPM and LTG significantly inhibited seizures in this CL model. The expression of P-gp was not significantly increased by TPM or LTG treatment in this study.

Ictal onset localization is feasible with MEG. Both interical and ictal MEG contribute valuable information to the presurgical assessment of epilepsy patients.

Epilepsy surgery candidates with extratemporal foci represent a particular diagnostic and therapeutic challenge, because of anatomic and functional features of the pertaining areas. In the last decade, novel developments in the field of electrophysiological techniques have offered new approaches to detailed localization of specific epileptic discharges as well as eloquent regions. Magnetoencephalography, in combination with neuroimaging data and simultaneously recorded EEG, yields promising results to clarify centers of epileptic activity and their relationship to structural abnormalites and functionally significant areas. Examples are given to illustrate the range of applications of this method as a contribution to routine presurgical evaluation.

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Background and objectives:Refractory status epilepticus (RSE) bear significant morbidity and mortality. Therapy escalation and in some cases intubation are recommended. Most existing studies are retrospective and focus on ICUs. We aimed to describe routine-care management, and analyze determinants of RSE development and outcomes in a large multicenter cohort.Methods:We performed post hoc analysis of an observational, cohort study, who prospectively registered all consecutive adults with SE at 9 centers from 3 German-speaking countries. Only incident episodes were included. Ongoing SE despite 2 anti-seizure medications was defined as RSE. Patients intubated during first- or second-line treatments were excluded. Variables investigated included demographics, severity (Status Epilepticus Severity Score), etiology, and guideline-compliant treatment (defined as fixed minimum doses). Outcome parameters included survival and mRS at baseline and discharge (good: 0–2 or absence of worsening compared with pre-hospitalization).Results:Among 1179 SE episodes from 1049 adults, 996 patients were eligible (median age: 70 years, 52% female), of which 545 (54.7%) developed RSE. RSE was associated with higher baseline mRS (p<0.001) and treatment deviation from guidelines (p<0.001, OR 0.09; 95%CI 0.06-0.1). Good outcomes were observed in 52.7% of refractory patients, correlating with lower status epilepticus severity (p<0.001), absence of acute etiology (p<0.001, OR 0.5 95%CI 0.3-0.7), adequate first-line benzodiazepine dose (p<0.001, OR 2.5 95%CI 1.6-4.0), shorter durations of SE and hospitalization (both p<0.001), and lack of intubation (p<0.001, OR 0.4 95%CI 0.3-0.6). Most (71.7%) refractory patients were not intubated. Intubation was associated with younger age (p=0.006), more severe consciousness disturbances (p<0.001, OR 3.2 95%CI 2.1-4.8), more severe SE types (p<0.001), higher severity score (p=0.009), acute etiologies (p=0.01, OR 1.6 95%CI 1.1-2.4), more anti-seizure medications (p<0.001), initial treatment after shorter latency (p=0.01), worse outcomes (p<0.001, OR 0.4 95%CI 0.4-0.6), and longer hospitalizations (p<0.001).Discussion:Variables associated with RSE were identified, some potentially preventable. More than 70% of RSE were treated without intubation, suggesting that focal RSE without deep impairment of consciousness, in older patients, may be successfully treated outside ICUs.Trial Registration:Original cohort study registered at the German Clinical Trials Register (DRKS00000725).