Seizure 2022, Vol 100, Editor’s Choice: Efficacy and safety of antiseizure medication in post-stroke epilepsy
While the number of medical treatment options in the epileptological toolbox continues to increase every year, treatments capable of affecting the course of epilepsy remain elusive. The ILAE recently recognised this continuing major gap in our therapeutic arsenal by encouraging clinicians and researchers to talk of the pharmaceuticals we routinely use to treat epilepsy as antiseizure medicines (ASMs) rather than antiepileptic drugs (AEDs). The abandonment of the term AED was not meant to indicate that truly “antiepileptic” medications would not be of interest. The opposite is true: The fact that we suddenly have no AEDs at our disposal at all should stimulate interest in the development of a new class of drugs with proven disease-modifying potential.
Unfortunately, there are many reasons for the lack of drugs with well-documented antiepileptic (or antiepileptogenic) properties. Epilepsy is a highly heterogeneous disease, and it is unlikely that a single antiepileptogenic mechanism would work in the context of the broad range of possible aetiologies. Similarly potential biomarkers of the development of epilepsy may only be predictive of the development of epilepsy in particular circumstances. In the absence of reliable biomarkers, studies of antiepileptogenic drugs have to be quite long – and capture the proportion of the treated population who ultimately develop epilepsy after a given insult (or in the presence of a particular risk factor).
Having said that, in animal studies of acquired epilepsies, several antiseizure drugs (including levetiracetam, brivaracetam, topiramate, gabapentin, pregabalin, vigabatrin and eslicarbazepine acetate) have shown antiepileptogenic or disease-modifying effects (1), and several studies designed to observe possible antiepileptic properties of drugs which can – to date – only be described as ASMs are currently in progress (2,3). These studies follow on from previous (unsuccessful) studies exploring possible antiepileptogenic effects of short courses of valproate or diazepam or of levetiracetam in the post stroke setting (4,5).
My Editor’s Choice from the current volume of Seizure is a retrospective study or poststroke epilepsy by Yaroslav Winter et al., which – while not proving the antiepileptogenic properties of any drugs studied – may generate hypotheses which future studies need to test. Their analysis of data from 207 patients with post stroke epilepsy who did not change their initial antiseizure monotherapy during 12 months of follow-up suggests that complete seizure control was more likely to be achieved by antiseizure medications acting via the slow inactivation of sodium channels, such as lacosamide and eslicarbazepine (6). While the focus of this study was on secondary prevention, it suggests that these medications would also be particularly interesting drugs to test in primary epilepsy prevention studies in the post-stroke setting.
(1) Klein P, Friedman A, Hameed MQ, et al. Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy? Epilepsia. 2020 Mar;61(3):359-386. doi: 10.1111/epi.16450
(2) Nicolo J, Chen Z, Moffat B, et al. Study protocol for a phase II randomised, double-blind, placebo-controlled trial of perampanel as an antiepileptogenic treatment following acute stroke. BMJ Open 2021;11:e043488. doi: 10.1136/bmjopen-2020-043488
(3) Prevention of epilepsy in stroke patients at high risk of developing unprovoked seizures: anti-epileptogenic effects of eslicarbazepine acetate, EurdraCT number: 2018-002747-29. https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-002747-29/SE.
(4) Chang RS, Leung WC, Vassallo M, Sykes L, Battersby Wood E, Kwan J. Antiepileptic drugs for the primary and secondary prevention of seizures after stroke. Cochrane Database Syst Rev. 2022 Feb 7;2(2):CD005398. doi: 10.1002/14651858.CD005398.
(5) van Tuijl JH, van Raak EP, de Krom MC, et al. Early treatment after stroke for the prevention of late epileptic seizures: a report on the problems performing a randomised placebo-controlled double-blind trial aimed at anti-epileptogenesis. Seizure. 2011 May;20(4):285-91. doi: 10.1016/j.seizure.2010.12.012.
(6) Winter Y, Uphaus T, Sandner K, Klimpe S, v. Stuckrad-Barre S, Groppa S. Efficacy and safety of antiseizure medication in post-stroke epilepsy, Seizure 2022;100:109-114.