Effects of New-Generation Antiepileptic Drug Prophylaxis on Delayed Neurovascular Events After Aneurysmal Subarachnoid Hemorrhage

Abstract

Neuroelectric disruptions such as seizures and cortical spreading depolarization may contribute to the development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH).However, effects of antiepileptic drug prophylaxis on outcomes remain controversial in SAH. The authors investigated if prophylactic administration of new-generation antiepileptic drugs levetiracetam and perampanel was bene cial against delayed neurovascular events after SAH. This was a retrospective single-center cohort study of 121 consecutive SAH patients including 56 patients of admission World Federation of Neurological Surgeons grades IV−V who underwent aneurysmal obliteration within 72 hours post-SAH from 2013 to 2021. Prophylactic antiepileptic drugs differed depending on the study terms: none (2013−2015), levetiracetam for patients at high risks of seizures (2016−2019), and perampanel for all patients (2020−2021). The 3rd term had the lowest occurrence of delayed cerebral microinfarction on diffusion-weighted magnetic resonance imaging and the tendency of reduced DCI.Other outcome measures were similar among the 3 terms including incidences of angiographic vasospasm, computed tomography-detectable delayed cerebral infarction, seizures, and 3-month good outcomes (modi ed Rankin Scale 0−2). The present study suggests that prophylactic administration of levetiracetam and perampanel at least does not worsen outcomes, and that perampanel may have the potential to reduce DCI by preventing microcirculatory disturbances after SAH. Further studies are warranted to investigate anti-DCI effects of a selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist perampanel in SAH patients in a large-scale prospective study.

Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage

“…33 Although we identified no patients with thalamic, midbrain, or pons infarction, the latter 2 cannot be adequately assessed in CT imaging and it is possible MRI would yield different results. In a recent study by Suzuki et al, 34 the role of microvascular infarction was highlighted after performing routine MRI in patients with SAH on admission and at discharge. Congruous to ischemic stroke research, routine MRI in future prospective studies could allow for voxel-based lesion symptom mapping specific to DCI-related infarction.…”

Contemporary management of aneurysmal subarachnoid haemorrhage. An update for the intensivist

“…Phenytoin as ASM should be avoided since it may induce harm. In an underpowered, prospective, single-centre, randomized, open-label trial, the benefit from prolonged levetiracetam prophylaxis was greatest for those with imaging evidence of early brain injury [ 65 ] and others have suggested a possible benefit against DCI with newer ASMs (levetiracetam and perampanel) [ 66 ]. All clinical or electrographic seizures that are diagnosed should be treated for at least 7 days and for those with delayed seizures or those with risk factors for seizures, more prolonged treatment should be considered.…”

Acute-Phase Plasma Pigment Epithelium-Derived Factor Predicting Outcomes after Aneurysmal Subarachnoid Hemorrhage in the Elderly

“…Thus, PEDF may be upregulated in brain tissues by ischemic injuries associated with EBI [14,16]. The severity of EBI is known to be correlated with admission WFNS grades [34], and more severe EBI is more likely to lead to angiographic vasospasm-related DCI or vasospasm-unrelated DCI and poor outcomes [30,33,37]. In this study, because angiographic vasospasm was not associated with outcome, it is suggested that EBI itself or DCI unrelated to vasospasm may be more important for poor outcome in elderly SAH patients.…”