title: Incidence of delayed seizures, delayed cerebral ischemia and poor outcome with the use of levetiracetam versus phenytoin after aneurysmal subarachnoid hemorrhage.
abstract: Current guidelines recommend against the use of phenytoin following aneurysmal subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as levetiracetam, acceptable. Our objective was to evaluate the risk of poor functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH patients treated with levetiracetam versus phenytoin. Medical records of patients with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome measure was poor functional outcome, defined as modified Rankin Scale (mRS) score >3 at first recorded follow-up. Secondary outcomes measures included DCI and the incidence of delayed seizures. The association between the use of levetiracetam and phenytoin and the outcomes of interest was studied using logistic regression. Medical records of 564 aSAH patients were reviewed and 259 included in the analysis after application of inclusion/exclusion criteria. Phenytoin was used exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%) patients were switched from phenytoin to levetiracetam. Six (2%) patients had delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow-up. On multivariate analysis, only modified Fisher grade and seizure before anticonvulsant administration were associated with DCI while age, Hunt-Hess grade and presence of intraparenchymal hematoma were associated with mRS score >3. Choice of anticonvulsant was not associated with any of the outcomes of interest. There was no difference in the rate of delayed seizures, DCI or poor functional outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high rate of crossover from phenytoin suggests that levetiracetam may be better tolerated.
authors.affiliation: Department of Neurology, The University of Texas Health Science Center at Houston Medical School, Houston, TX, USA.
authors.forename: Rahul Ramesh
authors.initials: RR
authors.lastname: Karamchandani
authors.affiliation: Departments of Neurosurgery and Neurology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jeffrey James
authors.initials: JJ
authors.lastname: Fletcher
authors.affiliation: Department of Neurosurgery, University of Michigan Heath System, 3552 Taubman Health Care Center, SPC 5338, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Aditya Swarup
authors.initials: AS
authors.lastname: Pandey
authors.affiliation: Department of Neurosurgery, University of Michigan Heath System, 3552 Taubman Health Care Center, SPC 5338, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address: vrajajee@yahoo.com.
authors.forename: Venkatakrishna
authors.initials: V
authors.lastname: Rajajee
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006406:Hematoma / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000627:therapeutic use*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012640:Seizures / Q000453:epidemiology*; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010672:Phenytoin; D010889:Piracetam
keywords: Anticonvulsants; Brain ischemia; Intracranial vasospasm; Levetiracetam; Phenytoin; Seizures; Subarachnoid hemorrhage