Pharmacological treatment of post-stroke epilepsy: still more questions than answers
Francesco Brigo, MD
– Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
– Division of Neurology, “Franz Tappeiner” Hospital, Merano, Italy
Johan Zelano, MD PhD
– Sahlgrenska academy and Sahlgrenska university hospital, Gothenburg, Sweden
Both organizers of the Seizures & stroke congress February 20-22 2019, Gothenburg
Cerebrovascular disease is the most commonly identified cause of acquired epilepsy,1 and stroke represents the underlying cause in 11% of all epilepsies in adults.2 Early post-stroke seizures occurring within one week from the stroke are not suggestive of an enduring predisposition of the brain to generate epileptic seizures;3 they do not entail a diagnosis of epilepsy, and considering the low risk of recurrence4 do not necessarily require a long-term treatment with antiepileptic drugs.5 Conversely, late post-stroke seizures are associated with a risk of recurrence over the following 10 year as high as 71.5% (95% CI: 59.7–81.9%).4 Hence, the occurrence of even a single late post-stroke seizure implies a diagnosis of epilepsy.6
We have recently performed a systematic review of the literature to assess the available evidence on the efficacy and tolerability of antiepileptic drugs for the treatment of post-stroke epilepsy.7 Only two randomized controlled trials were identified through a comprehensive and systematic search of the literature. One trial compared levetiracetam (LEV) with controlled-release carbamazepine (CR-CBZ)8 and the other compared lamotrigine (LTG) with CR-CBZ.9 No significant difference in terms of seizure freedom was found between either LEV or LTG and CR-CBZ, whereas LEV and LTG had lower occurrence of adverse events. The lack of statistical difference in efficacy between LEV or LTG and CR-CBZ was likely the consequence of the small number of patients included in each trial, with a high risk of false negative results due to inadequate statistical power. Furthermore, both studies were affected by unclear or high risk of bias and differed for stroke etiology and inclusion of early post-stroke seizures.
In a network meta-analysis we also indirectly compared the efficacy and tolerability of LEV and LTG using CR-CBZ as common comparator. Not surprisingly, we found no difference between LEV and LTG for seizure freedom, whereas adverse events occurred more frequently with LEV than with LTG (odds ratio 6.87; 95%CI: 1.15-41.1), with a trend towards higher withdrawal rates due to poor tolerability in patients receiving LEV.
Overall, the evidence supporting the use of specific antiepileptic drugs for the treatment of post-stroke epilepsy is scarce and based on low-quality studies. Hence, it is insufficient to provide strong recommendations to inform clinical practice. However, LEV and LTG appear interesting options, particularly for their better tolerability compared to CR-CBZ. However, data on CR-CBZ are also insufficient to discourage its use, although the risk of pharmacological interactions and negative effects on lipid levels10 should be carefully considered before choosing this drug for treating post-stroke epilepsy.
Based on the available evidence, the choice of the antiepileptic drug for post-stroke seizures should take into consideration not only the efficacy and tolerability profile, but also the pharmacokinetic properties, ease of use, patient´s preferences, and the effects on cognition, behavior and motor functions.7,11 It is astonishing that, despite the high prevalence of cerebrovascular disease among the underlying causes of epilepsy in adults and elderly, only two trials have been conducted so far to assess the role of antiepileptic drugs in post-stroke epilepsy. There is an urgent need for further studies to provide robust data on antiepileptic treatment of this common condition.
This and other unresolved issues will be extensively discussed in Seizures & Stroke, the first International Congress on Epilepsy in Cerebrovascular Disease, which will be held in Gothenburg, Sweden, from 20th to 22nd February 2019. The congress will gather experts in the field for scientific discussions and state-of-the art updates on management of seizures in the context of cerebrovascular disease. Strategies and opportunities for cooperative studies on pharmacological treatment of post-stroke seizures will be one of the main object of discussion among participants.
Undoubtedly, in this field there is a lot of work to be done. Let´s start doing it. Together.
- Menon B, Shorvon SD. Ischaemic stroke in adults and epilepsy. Epilepsy Res 2009;87:1–11.
- Camilo O, Goldstein LB. Seizures and epilepsy after ischaemic stroke. Stroke 2004;35:1769–75.
- Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia 2010;51:671–5.
- Hesdorffer DC, Benn EK, Cascino GD, Hauser WA. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia 2009;50:1102–8.
- Ryvlin P, Montavont A, Nighoghossian N. Optimizing therapy of seizures in stroke patients. Neurology. 2006;67:S3-9.
- Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014;55:475–82.
- Brigo F, Lattanzi S, Zelano J, et al. Randomized controlled trials of antiepileptic drugs for the treatment of post-stroke seizures: A systematic review with network meta-analysis. Seizure. 2018;61:57-62.
- Gilad R, Sadeh M, Rapoport A, et al. Monotherapy of lamotrigine versus carbamazepine in patients with poststroke seizure. Clin Neuropharmacol 2007;30:189–95.
- Consoli D, Bosco D, Postorino P, et al. Levetiracetam versus carbamazepine in patients with late poststroke seizures: a multicenter prospective randomized open-label study (EpIC Project). Cerebrovasc Dis 2012;34:282–9.
- Mintzer S, Trinka E, Kraemer G, Chervoneva I, Werhahn KJ. Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid-lowering agents in the elderly. Epilepsia. 2018 Sep 3. doi: 10.1111/epi.14554.
- Zelano J. Poststroke epilepsy: update and future directions. Ther Adv Neurol Disord 2016;9:424–35.