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.

Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage

“…In our study population, 42.7% patients had DCI, similar to previously reported rates (Karamchandani et al 2014). First, there is no significant difference between DCI and non-DCI groups in the time after SAH before EEG monitoring began (1.7±1.1 vs 1.7±1.2 days), or in the total duration of EEG monitoring (6.9±2.9 vs. 7.0±3.0) as measured by the two-sample KS test (p =0.001).…”

Prophylactic Antiepileptics and Seizure Incidence Following Subarachnoid Hemorrhage

“…18,19 However, Karamchandani et al found no significant difference in DIND between PHT vs. LEV treatment. 17 Surprisingly, adjusted analysis of our sample suggests LEV may actually be associated with the greatest risk of DIND- twice that of not receiving prophylactic AEDs. Although post hoc findings require cautious interpretation, they are nonetheless important given that current AHA/Stroke Guidelines state that the use of anticonvulsants is reasonable, without specifically recommending a particular anticonvulsant.…”

“…5,6,17–20 Rosengart et al analyzed 4 independent SAH trials and found patients who had received AEDs were 1.6 times more likely to have a poor outcome at 3 months, as well as being at increased risk for radiographic vasospasm, neurological deterioration, cerebral infarction, and elevated temperature during hospitalization. 5 Phenytoin, the first-line prophylactic AED traditionally used in SAH, has been shown to not only have a variety of adverse effects, but has also been correlated with poor neurologic recovery following SAH.…”

Seizures and Choice of Antiepileptic Drugs Following Subarachnoid Hemorrhage: A Review

“…For example, late seizures have been defined as occurring between 24 hours and 6 weeks of the initial hemorrhage, 13 more than 1 week following surgery for an SAH, 7 12 or more hours after hemorrhage but before surgical repair, 10 more than 14 days after the initial hemorrhage, 11,17 or as any seizures occurring after discharge. Alternatively, some have classified seizures in temporal relation to surgical repair, to the patient's hospital admission, or to initiation of AED therapy, 7,14,15,[18][19][20][21] whereas others have simply reported an overall incidence of any seizures that occurred during the patient's hospital stay. 9,[22][23][24][25][26][27][28] Furthermore, the definition of what constitutes a seizure was inconsistent among studies.…”

“…The overall reported rate of postadmission seizures in SAH have ranged from 0 to 31%. 7,[9][10][11]14,15,17,20,[24][25][26]28,29,[33][34][35][36][37] The highest reported rate (31%) was observed by Dennis et al 29 in patients with nonconvulsive seizures detected by electroencephalogram (EEG). On the other hand, the study that did not report any seizures excluded patients with onset seizures and included only patients with SAH Hunt-Hess grades of I to III.…”