Statin use and the risk of post-stroke seizures: A meta-analysis

Xu, Tao; Wang, You; Yuan, Jinxian; Chen, Yangmei; Luo, Haiyan

doi:10.1016/j.seizure.2020.10.004

Cited by 12 publications

(10 citation statements)

References 32 publications

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“…The lower incidence of PSE in stroke patients with dyslipidemia can be explained by the seizure-protective effects of lipid-lowering agents, statin used for this condition. Previous investigations have indicated that administering statins can decrease poststroke seizure occurrence and PSE ( 49 , 51 , 52 ). Therefore, we further evaluated the association between PSE and statin treatment in this study.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan

et al. 2022

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BackgroundThe incidence of ischemic stroke has been increasing in the young population over the past 20 years. Poststroke epilepsy (PSE) is a common complication after stroke. However, few population-based studies with sufficient follow-up have investigated factors associated with PSE, especially factors related to comorbidities and unhealthy lifestyles in the modern young population. Accordingly, this study aimed to determine the long-term incidence and these risk factors for PSE young adults.MethodsThis cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) from 2002 to 2018. All patients aged between 19 and 44 years and diagnosed with ischemic stroke from 2002 to 2015 were retrospectively enrolled with a follow-up of at least 3 years. Multivariable Cox regression models were performed to identify predictors of PSE, including patients' demographics, baseline conditions, stroke severity, etiologies, comorbidities, and unhealthy behaviors.ResultsAmong 6,512 ischemic stroke patients, 402 cases (6.2%) developed PSE who were with a mean follow-up period of 8.3 years (SD = 4.3 years). During the overall follow-up, stroke severity and manifestations were associated with PSE, including National Institutes of Health Stroke Scale (NIHSS) score ≥10 (aHR, 1.98; 95% CI, 1.50–2.61), seizure at first stroke admission [adjusted hazard ratio (aHR), 57.39; 95% confidence interval (CI), 43.02–76.55], length of hospital stay ≥14 days (aHR, 1.60; 95% CI, 1.26–2.02), recurrent stroke (aHR, 2.32; 95% CI, 1.85–2.90), aphasia (aHR, 1.77; 95% CI, 1.20–2.60), and malignancy (aHR, 2.05; 95% CI, 1.30–3.24). Furthermore, stroke patients with drug abuse were 2.90 times more likely to develop PSE than those without (aHR, 2.90; 95% CI, 1.53–5.50). By contrast, statin use (aHR, 0.62; 95% CI, 0.48–0.80) was associated with a lower risk of PSE. The risk factors at 1-year and 5-year PSE were similar to that of an overall follow-up.ConclusionsStroke severity, aphasia, malignancy, and drug abuse were associated increased risk of PSE and statin use may protect against PSE in young adults. Reducing the severity of stroke, statin use and controlling unhealthy behaviors might be able to decrease the development of PSE. Since PSE is associated with poor outcomes, early identification or intervention of PSE based on the risk factors might reduce the harmful effects of PSE.

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Section: Discussionmentioning

confidence: 99%

Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan

et al. 2022

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“…First investigations on blood biomarkers in PSE have recently been published and underline the fact, that inflammatory processes might be involved in the pathomechanism of PSE (Abraira et al, 2020 ). Furthermore, the recently published meta-analyses on the beneficial effect of statins on the development of PSE point towards a pro-inflammatory origin of RSS (Guo et al, 2015 ; Xu et al, 2020 ; Fang et al, 2021 ). As clinical research on PSE is very laborious and time-consuming, translational research would be very useful to understand the basic pathomechanisms.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

“…The importance of BBB leakage with respect to the development of PSE is further underlined by the fact that statins reduce the risk for hospitalization for epilepsy after stroke in a dose-dependent manner. Their effect is mainly ascribed to their anti-inflammatory and protective action on the BBB (Xu et al, 2020 ; Fang et al, 2021 ; Guo et al, 2021 ).…”

Section: Post-stroke Epilepsymentioning

confidence: 99%

Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-stroke Epilepsy

Tröscher

Gruber

Wagner

et al. 2021

Front. Aging Neurosci.

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Post-stroke Epilepsy (PSE) is one of the most common forms of acquired epilepsy, especially in the elderly population. As people get increasingly older, the number of stroke patients is expected to rise and concomitantly the number of people with PSE. Although many patients are affected by post-ischemic epileptogenesis, not much is known about the underlying pathomechanisms resulting in the development of chronic seizures. A common hypothesis is that persistent neuroinflammation and glial scar formation cause aberrant neuronal firing. Here, we summarize the clinical features of PSE and describe in detail the inflammatory changes after an ischemic stroke as well as the chronic changes reported in epilepsy. Moreover, we discuss alterations and disturbances in blood-brain-barrier leakage, astrogliosis, and extracellular matrix changes in both, stroke and epilepsy. In the end, we provide an overview of commonalities of inflammatory reactions and cellular processes in the post-ischemic environment and epileptic brain and discuss how these research questions should be addressed in the future.

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“…Secondary Prophylaxis . The current literature does not support the prophylactic use of antiepileptic drugs (AEDs) to prevent early- and late-onset seizures following a stroke, as they have not been found to reduce the risk of occurrence [ 49 ]. However, once a diagnosis of PSE is established, AEDs help establish seizure control with secondary prophylaxis.…”

Section: Review Outlinementioning

confidence: 99%

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

Phan

Ramos

Soares

et al. 2022

Oxidative Medicine and Cellular Longevity

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Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65 age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca2+ accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.

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Statin use and the risk of post-stroke seizures: A meta-analysis

Cited by 12 publications

References 32 publications

Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan

Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan

Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-stroke Epilepsy

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

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