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. 2023 Nov 24:12:e49412.
doi: 10.2196/49412.

The Primary Prevention of Poststroke Epilepsy in Patients With Middle Cerebral Artery Infarct: Protocol for a Randomized Controlled Trial

Yu-Shiue Chen  1 , Pi-Shan Sung  1 , Ming-Chi Lai  2 , Chin-Wei Huang  1
Affiliations

The Primary Prevention of Poststroke Epilepsy in Patients With Middle Cerebral Artery Infarct: Protocol for a Randomized Controlled Trial

Yu-Shiue Chen et al. JMIR Res Protoc. .

Abstract

Background: Poststroke epilepsy poses a significant clinical challenge for individuals recovering from strokes, leading to a less favorable long-term outlook and increased mortality rates. Existing studies have primarily concentrated on administering antiseizure or anticonvulsant treatments only after the onset of late-onset seizures, without intervening during the epileptogenesis phase following a stroke.

Objective: This research protocol is designed to conduct a randomized controlled trial to assess whether the early, preventive introduction of low-dose antiepileptic drug therapy (levetiracetam [LEV] or perampanel [PER]) in patients who have experienced middle cerebral artery (MCA) infarction can reduce the risk of developing poststroke epilepsy (primary prevention).

Methods: Participants with MCA infarction, either with or without reperfusion treatments, will be recruited and promptly receive preventive intervention within 72 hours of the stroke occurrence. These participants will be randomly assigned to receive either PER (4 mg per day), LEV (1000 mg per day), or a placebo that matches the active drugs. This treatment will continue for 12 weeks after allocation. Brain magnetic resonance imaging will be used to confirm the presence of MCA territory infarction, and an electroencephalography will be used to ensure the absence of epileptiform discharges or electrographic seizures at the time of the stroke. All participants will undergo follow-up assessments for 72 weeks after allocation.

Results: The primary outcome under evaluation will be the incidence of poststroke epilepsy in the 3 groups following the 18-month study period. Secondary outcomes will encompass the time to the occurrence of the first seizure, the severity of seizures, any treatment-related adverse events, and the modified Rankin scale score at 3 and 18 months. Exploratory outcomes will involve comparing the effectiveness and safety of PER and LEV.

Conclusions: We anticipate that the intervention groups will experience a lower incidence and reduced severity of poststroke epilepsy compared to the control group after 18 months. We aim to establish evidence supporting the potential preventive effects of LEV and PER on poststroke seizures and epilepsy in patients with MCA infarction, as well as to explore the antiepileptogenic potential of both LEV and PER in patients with major ischemic strokes.

Trial registration: ClinicalTrials.gov NCT04858841; https://clinicaltrials.gov/study/NCT04858841.

International registered report identifier (irrid): DERR1-10.2196/49412.

Keywords: angina; cardiologist; cardiology; cardiovascular; development; drug therapy; efficacy; epilepsy; heart attack; middle cerebral artery infarct; mortality; poststroke epilepsy; prognosis; randomized control trial; seizure; seizure severity; stroke; stroke survivor.

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Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
Randomized controlled trial flow diagram. Tx: Treatment.
Figure 2
Figure 2
SPIRIT flow diagram: schedule of enrollment, interventions, and assessment procedures. EEG: electroencephalography; MRI: Magnetic Resonance Imaging; mRs: modified Rankin Scale; NIHSS: National Institute of Health Stroke Scale; SPIRIT: Standard Protocol Items: Recommendations for Interventional Trials; TEAE: treatment-emergent adverse event; **: primary outcome; *: secondary outcome.
Figure 3
Figure 3
A typical case with middle cerebral artery infarct enrolled in this study.
See this image and copyright information in PMC

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References

    1. Tanaka T, Ihara M. Post-stroke epilepsy. Neurochem Int. 2017 Jul 01;107:219–228. doi: 10.1016/j.neuint.2017.02.002.S0197-0186(16)30341-2 - DOI - PubMed
    1. Shetty AK. Prospects of levetiracetam as a neuroprotective drug against status epilepticus, traumatic brain injury, and stroke. Front Neurol. 2013;4:172. doi: 10.3389/fneur.2013.00172. https://europepmc.org/abstract/MED/24204362 - DOI - PMC - PubMed
    1. Zelano J, Holtkamp M, Agarwal N, Lattanzi S, Trinka E, Brigo F. How to diagnose and treat post-stroke seizures and epilepsy. Epileptic Disord. 2020;22(3):252–263. doi: 10.1684/epd.2020.1159. https://onlinelibrary.wiley.com/doi/10.1684/epd.2020.1159 epd.2020.1159 - DOI - DOI - PubMed
    1. Huang CW, Saposnik G, Fang J, Steven DA, Burneo JG. Influence of seizures on stroke outcomes: a large multicenter study. Neurology. 2014;82(9):768–776. doi: 10.1212/WNL.0000000000000166.WNL.0000000000000166 - DOI - PubMed
    1. Pitkänen A, Roivainen R, Lukasiuk K. Development of epilepsy after ischaemic stroke. Lancet Neurol. 2016;15(2):185–197. doi: 10.1016/S1474-4422(15)00248-3.S1474-4422(15)00248-3 - DOI - PubMed

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