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

Abstract

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.

S2k-Leitlinie: Status Epilepticus im Erwachsenenalter

“…In einer systematischen Übersichtsarbeit wurden 10 Arbeiten mit 69 Episoden eines SE (bei 68 Patienten) analysiert [16]. [34].…”

“…6 Patienten hatten einen SRSE, bei 5 Patienten wurde Topiramat als letzte Substanz appliziert, bei 4 dieser Patienten wurde die Anfallsaktivität dadurch beendet. In einer Studie aus Frankfurt und Marburg wurden 40 Patienten mit SRSE mit Topiramat behandelt, bei 8 Patienten (20 %) konnte der SE durchbrochen werden [ 34 ].…”

Diagnosis and Treatment of Status Epilepticus

“…Ketamine, 45 megadose phenobarbital 46 therapy, and multiple combinations of various AEDs including high-dose oral AEDs can be considered. [47][48][49] Oral AEDs such as topiramate, oxcarbazepine, and perampanel can also be used with a loading or high dose (Table 6).…”

Polygonogram with isobolographic synergy for three-drug combinations of phenobarbital with second-generation antiepileptic drugs in the tonic–clonic seizure model in mice

“…Another limitation in this study is clinical application of PB that is currently used in pediatric population and rarely in adult patients [66,67]. Although its clinical application to humans is limited, in this study we chose PB because of its pharmacologic properties affecting directly GABAergic neurotransmission in the brain.…”