Treatment of status epilepticus with zonisamide: A multicenter cohort study of 34 patients and review of literature.

INTRODUCTION: We present a summary of clinical cases of oral zonisamide (ZNS) used to treat refractory and super-refractory episodes of status epilepticus (SE). METHODS: Zonisamide administration in SE was identified in the clinical records of patients treated in Frankfurt and Marburg between 2011 and 2017. RESULTS: Zonisamide was administered during a total of 37 SE episodes in 34 patients with a mean age of 58.7 ±â€¯17.8 years, 21 of them were female (61.7%). The median latency from the onset of SE to administration of ZNS was 6.3 days. Patients had already undergone unsuccessful treatment with a median of three other antiseizure drugs (ASDs). The median initial dose of ZNS was 100 mg/d, titrated to a median maintenance dose of 400 mg/d. Patients underwent ZNS treatment for a median period of 7 days. Zonisamide was the final drug administered in 9 of 37 (24.3%) episodes, with a clinical effect attributed to ZNS observed in 6 of 37 (16.2%) episodes. An effect attributed to ZNS was observed in 5 out of 30 episodes of refractory SE (RSE) and in one out of 7 episodes of super-refractory SE (SRSE). Possible negative side effects of ZNS were observed in two patients (one patient each with ataxia and skin rash). The mortality rate in hospitalized patients was 10.4% (n = 4). CONCLUSION: The rate of SE resolution attributed to ZNS treatment (16.2%) can be considered relevant, particularly since ZNS treatment tends to be administered only after several other options have been tried, and has a treatment latency of over six days. Zonisamide may therefore be considered as an alternative oral treatment option in RSE and SRSE.

Treatment of refractory and superrefractory status epilepticus with topiramate: A cohort study of 106 patients and a review of the literature.

OBJECTIVE: Novel treatments are needed to control treatment-resistant status epilepticus (SE). We present a summary of clinical cases where oral topiramate (TPM) was used in refractory SE (RSE) and superrefractory SE (SRSE). METHODS: A review of medical records was carried out to detect TPM administration in SE patients treated in Frankfurt and Marburg between 2011 and 2016. The primary outcome question concerned SE resolution after TPM initiation. RESULTS: In total, TPM was used in 106 of 854 patients having a mean age of 67.4 ± 18.1 years, 61 of whom were female (57.5%). The median latency from SE onset to TPM initiation was 8.5 days. Patients with SE had previously failed a median of five other antiepileptic drugs. The median initial TPM dose was 100 mg/d, which was uptitrated to a median maintenance dose of 400 mg/d. Treatment with TPM was continued for a median time of 12 days. TPM was the last drug provided to 42 of 106 (39.6%) patients, with a resultant response attributed to TPM observed in 29 of 106 (27.4%) patients. A response was attributed to TPM in 21 (31.8%) of 66 RSE cases and eight (20%) of 40 SRSE cases. Treatment-emergent adverse events were attributed to TPM usage in two patients, one each with pancreatitis and hyperchloremic acidosis, and in 38 patients (35.8%), hyperammonemia was seen. Thirty-four of these patients received a combination of TPM and valproate and/or phenobarbital. The intrahospital mortality rate was 22.6% (n = 24). SIGNIFICANCE: The rate of SE cessation attributed to TPM treatment (27.4%) represents a relevant response given the late treatment position of TPM and the treatment latency of more than 8 days. Based on these results and in line with the findings of other case series, TPM can be considered an alternative option for treating RSE and SRSE.

Costs and cost-driving factors for acute treatment of adults with status epilepticus: A multicenter cohort study from Germany.

OBJECTIVE: To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). METHODS: In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. RESULTS: We evaluated 341 admissions in 316 patients (65.7 ± [standard deviation]18.2 years; 135 male) treated for SE. Mean costs of hospital treatment were €14,946 (median €5,278, range €776-€152,911, €787 per treatment day) per patient per admission, with a mean length of stay (LOS) of 19.0 days (median 14.0, range 1-118). Course of SE had a significant impact on mean costs, with €8,314 in NSE (n = 137, median €4,597, €687 per treatment day, 22.3% of total inpatient costs due to SE), €13,399 in RSE (n = 171, median €7,203, €638/day, 45.0% of total costs, p < 0.001), and €50,488 in SRSE (n = 33, median €46,223, €1,365/day, 32.7% of total costs, p < 0.001). Independent cost-driving factors were SRSE, ventilation, and LOS of >14 days. Overall mortality at discharge was 14.4% and significantly higher in RSE/SRSE (20.1%) than in NSE (5.8%). SIGNIFICANCE: Acute treatment of SE, and particularly SRSE and ventilation, are associated with high hospital costs and prolonged LOS. Extrapolation to the whole of Germany indicates that SE causes hospital costs of >€200 million per year. Along with the demographic change, incidence of SE will increase and costs for hospital treatment and sequelae of SE will rise.