Advertisement

Effect of Primary Prophylactic Antiseizure Medication for Seizure Prevention Following Intracerebral Hemorrhage in the ERICH Study

      Abstract

      Objectives

      Intracerebral hemorrhage (ICH) has the highest morbidity and mortality rate of any stroke subtype and clinicians often administer prophylactic antiseizure medications (ASMs) as a means of preventing post-stroke seizures, particularly following lobar ICH. However, evidence for ASM efficacy in preventing seizures and reducing disability is lacking given limited randomized trials. Herein, we report analysis from a large prospective observational study that evaluates the effect of primary prophylactic ASM administration on seizure occurrence and disability following ICH.

      Materials and methods

      Primary analysis was performed on 1630 patients with ICH enrolled in the ERICH study. A propensity score for administration of prophylactic ASM was developed and patients were matched by the closest propensity score (difference < 0.1). McNemar's test was used to compare occurrence of in-hospital seizure and disability, defined by modified Rankin Score (mRS) ≥ 3 at 3 months post ICH.

      Results

      Of the 815 matched pairs of patients treated with primary prophylactic ASM, there was no significant difference in seizure occurrence (p = 0.4631) or disability (p = 0.4653). Subset analysis of 280 matched pairs of patients with primary lobar ICH similarly revealed no significant difference in seizure occurrence (p = 0.1011) or disability (p = 1.00) between prophylactically treated and untreated patients.

      Conclusions

      Although current guidelines do not recommend primary prophylactic ASM following ICH, clinical use remains widespread. Data from the ERICH study did not find an association between administering primary prophylactic ASM and preventing seizures or reducing disability following ICH, thus providing evidence to influence clinical practice and patient care.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • DeHerdt V.
        • Dumont F.
        • Henon H.
        • et al.
        Early seizures in intracerebral hemorrhage: incidence, associated factors, and outcome.
        Neurology. 2011; 77: 1794-1800
        • Claassen J.
        • Jette N.
        • Chum F.
        • et al.
        Electrographic seizures and periodic discharges after intracerebral hemorrhage.
        Neurology. 2007; 69: 1356-1365
        • Vespa P.M.
        • O'Phelan K.
        • Shah M.
        • et al.
        Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome.
        Neurology. 2003; 60: 1441-1446
        • Arntz R.M.
        • Maaijwee N.A.
        • Rutten-Jacobs L.C.
        • et al.
        Epilepsy after TIA or stroke in young patients impairs long-term functional outcome: the FUTURE Study.
        Neurology. 2013; 81: 1907-1913
        • Battey T.W.
        • Falcone G.J.
        • Sheth K.N.
        • et al.
        Authors' reply: confounding by indication in retrospective studies of intracerebral hemorrhage: antiepileptic treatment and mortality.
        Neurocrit Care. 2013; 18: 287-288
        • Naidech A.M.
        • Beaumont J.
        • Jahromi B.
        • et al.
        Evolving use of seizure medications after intracerebral hemorrhage: a multicenter study.
        Neurology. 2017; 88: 52-56
        • Reddig R.T.
        • Nixdorf K.E.
        • Jensen M.B.
        The prophylactic use of an antiepileptic drug in intracerebral hemorrhage.
        Clin Neurol Neurosurg. 2011; 113: 895-897
        • Sheth K.N.
        • Martini S.R.
        • Moomaw C.J.
        • et al.
        Prophylactic antiepileptic drug use and outcome in the ethnic/racial variations of intracerebral hemorrhage study.
        Stroke. 2015; 46: 3532-3535
        • Messe S.R.
        • Sansing L.H.
        • Cucchiara B.L.
        • et al.
        Prophylactic antiepileptic drug use is associated with poor outcome following ICH.
        Neurocrit Care. 2009; 11: 38-44
        • Garrett M.C.
        • Komotar R.J.
        • Starke R.M.
        • et al.
        Predictors of seizure onset after intracerebral hemorrhage and the role of long-term antiepileptic therapy.
        J Crit Care. 2009; 24: 335-339
        • Alberti A.
        • Paciaroni M.
        • Caso V.
        • et al.
        Early seizures in patients with acute stroke: frequency, predictive factors, and effect on clinical outcome.
        Vasc Health Risk Manag. 2008; 4: 715-720
        • Beghi E.
        • D'Alessandro R.
        • Beretta S.
        • et al.
        Incidence and predictors of acute symptomatic seizures after stroke.
        Neurology. 2011; 77: 1785-1793
        • Berger A.R.
        • Lipton R.B.
        • Lesser M.L.
        • et al.
        Early seizures following intracerebral hemorrhage: implications for therapy.
        Neurology. 1988; 38: 1363-1365
        • Bladin C.F.
        • Alexandrov A.V.
        • Bellavance A.
        • et al.
        Seizures after stroke: a prospective multicenter study.
        Arch Neurol. 2000; 57: 1617-1622
        • DeReuck J.
        • Hemelsoet D.
        • VanMaele G.
        Seizures and epilepsy in patients with a spontaneous intracerebral haematoma.
        Clin Neurol Neurosurg. 2007; 109: 501-504
        • Passero S.
        • Rocchi R.
        • Rossi S.
        • et al.
        Seizures after spontaneous supratentorial intracerebral hemorrhage.
        Epilepsia. 2002; 43: 1175-1180
        • Woo K.M.
        • Yang S.Y.
        • Cho K.T.
        Seizures after spontaneous intracerebral hemorrhage.
        J Korean Neurosurg Soc. 2012; 52: 312-319
        • Yang T.M.
        • Lin W.C.
        • Chang W.N.
        • et al.
        Predictors and outcome of seizures after spontaneous intracerebral hemorrhage. Clinical article.
        J Neurosurg. 2009; 111: 87-93
        • Kammersgaard L.P.
        • Olsen T.S.
        Poststroke epilepsy in the Copenhagen stroke study: incidence and predictors.
        J Stroke Cerebrovasc Dis. 2005; 14: 210-214
        • Okuda S.
        • Takano S.
        • Ueno M.
        • et al.
        Clinical features of late-onset poststroke seizures.
        J Stroke Cerebrovasc Dis. 2012; 21: 583-586
        • Foy P.M.
        • Copeland G.P.
        • Shaw M.D.
        The natural history of postoperative seizures.
        Acta Neurochir. 1981; 57 (Wien): 15-22
        • Foy P.M.
        • Copeland G.P.
        • Shaw MD.
        The incidence of postoperative seizures.
        Acta Neurochir. 1981; 55 (Wien): 253-264
        • Gilmore E.J.
        • Maciel C.B.
        • Hirsch L.J.
        • et al.
        Review of the utility of prophylactic anticonvulsant use in critically Ill patients with intracerebral hemorrhage.
        Stroke. 2016; 47: 2666-2672
        • Krakow K.
        • Sitzer M.
        • Rosenow F.
        • et al.
        Predictors of acute post stroke seizures.
        Cerebrovasc Dis. 2010; 30: 584-589
        • Naidech A.M.
        • Garg R.K.
        • Liebling S.
        • et al.
        Anticonvulsant use and outcomes after intracerebral hemorrhage.
        Stroke. 2009; 40: 3810-3815
        • Taylor S.
        • Heinrichs R.J.
        • Janzen J.M.
        • et al.
        Levetiracetam is associated with improved cognitive outcome for patients with intracranial hemorrhage.
        Neurocrit Care. 2011; 15: 80-84
        • Woo D.
        • Rosand J.
        • Kidwell C.
        • et al.
        The ethnic/racial variations of intracerebral hemorrhage (ERICH) study protocol.
        Stroke. 2013; 44: e120-e125
        • Walsh K.B.
        • Sekar P.
        • Langefeld C.D.
        • et al.
        Monocyte count and 30-day case fatality in intracerebral hemorrhage.
        Stroke. 2015; 46: 2302-2304
        • Flibotte J.J.
        • Hagan N.
        • O'Donnell J.
        • et al.
        Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage.
        Neurology. 2004; 63: 1059-1064
        • Goldstein J.N.
        • Fazen L.E.
        • Snider R.
        • et al.
        Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage.
        Neurology. 2007; 68: 889-894
        • Kumar M.A.
        • Rost N.S.
        • Snider R.W.
        • et al.
        Anemia and hematoma volume in acute intracerebral hemorrhage.
        Crit Care Med. 2009; 37: 1442-1447
        • Berges S.
        • Moulin T.
        • Berger E.
        • et al.
        Seizures and epilepsy following strokes: recurrence factors.
        Eur Neurol. 2000; 43: 3-8
        • Conrad J.
        • Pawlowski M.
        • Dogan M.
        • et al.
        Seizures after cerebrovascular events: risk factors and clinical features.
        Seizure. 2013; 22: 275-282
        • Goswami R.P.
        • Karmakar P.S.
        • Ghosh A.
        Early seizures in first-ever acute stroke patients in India: incidence, predictive factors and impact on early outcome.
        Eur J Neurol. 2012; 19: 1361-1366
        • Hundozi Z.
        • Shala A.
        • Boshnjaku D.
        • et al.
        Hypertension on admission is associated with a lower risk of early seizures after stroke.
        Seizure. 2016; 36: 40-43
        • Labovitz D.L.
        • Hauser W.A.
        • Sacco RL.
        Prevalence and predictors of early seizure and status epilepticus after first stroke.
        Neurology. 2001; 57: 200-206
        • Mecarelli O.
        • Pro S.
        • Randi F.
        • et al.
        EEG patterns and epileptic seizures in acute phase stroke.
        Cerebrovasc Dis. 2011; 31: 191-198
        • Serafini A.
        • Gigli G.L.
        • Gregoraci G.
        • et al.
        Are early seizures predictive of epilepsy after a stroke? Results of a population-based study.
        Neuroepidemiology. 2015; 45: 50-58
        • Wang G.
        • Jia H.
        • Chen C.
        • et al.
        Analysis of risk factors for first seizure after stroke in Chinese patients.
        Biomed Res Int. 2013; 2013702871
        • Gilad R.
        • Boaz M.
        • Dabby R.
        • et al.
        Are post intracerebral hemorrhage seizures prevented by anti-epileptic treatment?.
        Epilepsy Res. 2011; 95: 227-231
        • Neshige S.
        • Kuriyama M.
        • Yoshimoto T.
        • et al.
        Seizures after intracerebral hemorrhage; risk factor, recurrence, efficacy of antiepileptic drug.
        J Neurol Sci. 2015; 359: 318-322
        • Rossi C.
        • DeHerdt V.
        • Dequatre-Ponchelle N.
        • et al.
        Incidence and predictors of late seizures in intracerebral hemorrhages.
        Stroke. 2013; 44: 1723-1725
        • Haapaniemi E.
        • Strbian D.
        • Rossi C.
        • et al.
        The CAVE score for predicting late seizures after intracerebral hemorrhage.
        Stroke. 2014; 45: 1971-1976
        • Kwon S.Y.
        • Obeidat A.Z.
        • Sekar P.
        • et al.
        Risk factors for seizures after intracerebral hemorrhage: ethnic/racial variations of intracerebral hemorrhage (ERICH) study.
        Clin Neurol Neurosurg. 2020; 192105731
        • Naidech A.M.
        • Beaumont J.
        • Muldoon K.
        • et al.
        Prophylactic seizure medication and health-related quality of life after intracerebral hemorrhage.
        Crit Care Med. 2018; 46: 1480-1485
        • Cella D.
        • Lai J.S.
        • Nowinski C.J.
        • et al.
        Neuro-QOL: brief measures of health-related quality of life for clinical research in neurology.
        Neurology. 2012; 78: 1860-1867
        • Broderick J.P.
        • Adams H.P.
        • Barsan W.
        • et al.
        Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the stroke council, American heart association.
        Stroke. 1999; 30: 905-915
        • Adams H.P.
        • delZoppo G.
        • Alberts M.J.
        • et al.
        Guidelines for the early management of adults with ischemic stroke: a guideline from the American heart association/American stroke association stroke council, clinical cardiology council, cardiovascular radiology and intervention council, and the atherosclerotic peripheral vascular disease and quality of care outcomes in research interdisciplinary working groups: the American academy of neurology affirms the value of this guideline as an educational tool for neurologists.
        Stroke. 2007; 38: 1655-1711
        • Hemphill J.C.
        • Greenberg S.M.
        • Anderson C.S.
        • et al.
        Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the american heart association/American stroke association.
        Stroke. 2015; 46: 2032-2060