Seizure 2021, Vol 88, Editor’s Choice: Effects of double-dose statin therapy for the prevention of post-stroke epilepsy: A prospective clinical study
I retain vague memories of a period in my pre-clinical studies when pharmacology seemed relatively straightforward. Anticonvulsants were used to treat seizures, antidepressant drugs for depression, antihypertensives to control high blood pressure and statin therapy to reduce the levels of cholesterol. Lowering levels of cholesterol made good sense because of its contribution to atherosclerosis and the risk of myocardial infarction or stroke. This period of relative bliss was initially challenged when I found out about “good” (HDL) and “bad” (LDL) cholesterol and the importance of the HDL/LDL ratio. However, since then, it has become clear that the effects of statins extend well beyond the regulation of cholesterol metabolism and that their benefits in the primary and secondary prevention of complications of vascular disease are not exclusively mediated by cholesterol levels or ratios, but also by decreasing oxidative stress and inflammation, and by antithrombotic actions (1).
Statins exert their beneficial effects on cholesterol metabolism by inhibiting the rate-limiting enzyme of the L-mevalonate pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. This pharmacological effect reduces inflammation through effects on downstream metabolites of the same pathway. These metabolites play critical roles in different steps of the body’s immune response including immune cell activation, migration, cytokine production, immune metabolism and cell survival (2).
Importantly, a number of studies suggest that these effects are not only pharmacologically demonstrable but also of clinical significance. The clinical benefits of statin therapy may include antiseizure and antiepileptogenic effects, especially in the context of post stroke epilepsy (3, 4). My editor’s choice from the current volume of Seizure, an observational study in 1,033 patients followed up after experiencing stroke by Yanmei Zhu et al. adds to this evidence (5). In this study the incidence of post stroke epilepsy was 0.4% among the 245 patients who received double dose statin therapy and 2.5% in the 788 patients treated with a standard dose. These findings strengthen the rationale for large prospective studies of intensive statin therapy in patients with stroke and in older individuals with probable cerebrovascular disease presenting with a first seizure.
(1) Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005;45:89-118.
(2) Zeiser R. Immune modulatory effects of statins. Immunology 2018; 154:69-75.
(3) Etminan M, Samii A, Brophy J M. Statin use and risk of epilepsy: a nested case-control study. Neurology 2010; 75:1496-500.
(4) Guo J, Guo J, Li J. Statin treatment reduces the risk of poststroke seizures. Neurology2015; 85:701-7.
(5) Yanmei Zhu et al. Effects of double-dose statin therapy for the prevention of post-stroke epilepsy: A prospective clinical study. Seizure 202188:138-142.