Intravenous lacosamide in status epilepticus: Correlation between loading dose, serum levels, and clinical response.

INTRODUCTION: Intravenous lacosamide (LCM) is increasingly used in the treatment of status epilepticus (SE), but optimal loading dose and target serum levels are unclear. We analysed the correlation between LCM serum levels after intravenous loading dose and clinical response. MATERIALS AND METHODS: Retrospective study in two centres from December 2014 to May 2016 including consecutive SE patients treated with LCM, in which trough serum levels after intravenous loading dose were available. Trough levels were correlated with the loading dose and the clinical response, defined as LCM introduction terminating SE without the need of further treatment. Correlations were adjusted for other SE characteristics. RESULTS: Among 40 patients, 16 (40%) responded to LCM. LCM serum concentrations within the reference interval (10-20mg/l) were associated with loading doses of >9mg/kg (p=0.003; χ2). However, we observed no difference between LCM serum levels in responders (median 10.4mg/l) versus non-responders (median 9.5mg/l; p=0.36; U test), even after adjusting for other predictors of clinical outcome (SE severity, aetiology, and number of previous treatment). DISCUSSION: High intravenous LCM loading doses (>9mg/kg) were associated with serum levels within the reference interval, there was however no correlation with the clinical response. Prospective studies are needed to evaluate the benefit of increasing the LCM loading dose in SE.

New ILAE versus previous clinical status epilepticus semiologic classification: Analysis of a hospital-based cohort.

OBJECTIVES: In 2015, the International League Against Epilepsy (ILAE) issued a new status epilepticus (SE) classification, including a detailed semiologic axis. This study assesses frequencies of SE forms in a cohort of adult patients, and explores differences and practical implications as compared to a seizure-type-bound classification. METHODS: The prospective adult SE registry of the Lausanne University Hospital (CHUV) was considered over 5 years (2011-2015); each SE episode was retrospectively reclassified for its semiology according to the new ILAE scheme. Mortality rates were retrieved for each subgroup of SE. RESULTS: Among 488 SE episodes, according to the seizure-type-bound classification, 230 (47%) had a generalized convulsive, and 29 (6%) had a nonconvulsive SE in coma; both categories overlapped almost perfectly between the two classifications. However, the 84 episodes with focal SE without consciousness impairment and the 141 episodes with consciousness impairment were each translated into two major (and five sub-) categories of the new ILAE classification, having markedly different mortality rates. In addition, of 140 episodes labeled as focal motor SE according to the new classification, 54% had concomitant consciousness impairment, whereas 46% did not; again, mortality rates were heterogeneous. SIGNIFICANCE: Although generalized convulsive and nonconvulsive SE in coma show an almost perfect correspondence across SE semiologic classifications, focal SE is markedly heterogeneous and appears to be better reflected in the new classification, offering more clinically relevant subdivisions, also differing in mortality rates. This refined knowledge may allow the development of clinical prognostic scores that are more precise than existing tools, and should be taken into account for epidemiologic studies.

Status epilepticus: impact of therapeutic coma on outcome.

OBJECTIVES: Therapeutic coma is advocated in guidelines for management of refractory status epilepticus; this is, however, based on weak evidence. We here address the specific impact of therapeutic coma on status epilepticus outcome. DESIGN: Retrospective assessment of a prospectively collected cohort. SETTING: Academic hospital. PATIENTS: Consecutive adults with incident status epilepticus lasting greater than or equal to 30 minutes, admitted between 2006 and 2013. MEASUREMENTS AND MAIN RESULTS: We recorded prospectively demographics, clinical status epilepticus features, treatment, and outcome at discharge and retrospectively medical comorbidities, hospital stay, and infectious complications. Associations between potential predictors and clinical outcome were analyzed using multinomial logistic regressions. Of 467 patients with incident status epilepticus, 238 returned to baseline (51.1%), 162 had new disability (34.6%), and 67 died (14.3%); 50 subjects (10.7%) were managed with therapeutic coma. Therapeutic coma was associated with poorer outcome in the whole cohort (relative risk ratio for new disability, 6.86; 95% CI, 2.84-16.56; for mortality, 9.10; 95% CI, 3.17-26.16); the effect was more important in patients with complex partial compared with generalized convulsive or nonconvulsive status epilepticus in coma. Prevalence of infections was higher (odds ratio, 3.81; 95% CI, 1.66-8.75), and median hospital stay in patients discharged alive was longer (16 d [range, 2-240 d] vs 9 d [range, 1-57 d]; p < 0.001) in subjects managed with therapeutic coma. CONCLUSIONS: This study provides class III evidence that therapeutic coma is associated with poorer outcome after status epilepticus; furthermore, it portends higher infection rates and longer hospitalizations. These data suggest caution in the straightforward use of this approach, especially in patients with complex partial status epilepticus.