Clinical, laboratory, and radiographic predictors of the occurrence of seizures following aneurysmal subarachnoid hemorrhage

Clinical article

Restricted access


At present, the administration of prophylactic antiepileptic medication following aneurysmal subarachnoid hemorrhage (SAH) is controversial, and the practice is heterogeneous. Here, the authors sought to inform clinical decision making by identifying factors associated with the occurrence of seizures following aneurysm rupture.


Exploratory analysis was performed on 413 patients enrolled in CONSCIOUS-1 (Clazosentan to Overcome Neurological Ischemia and Infarction Occurring after Subarachnoid Hemorrhage), a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm. The association among clinical, laboratory, and radiographic covariates and the occurrence of seizures following SAH were determined. Covariates with a significance level of p < 0.20 on univariate analysis were entered into a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis was used to define optimal predictive thresholds.


Of the 413 patients enrolled in the study, 57 (13.8%) had at least 1 seizure following SAH. On univariate analysis, a World Federation of Neurosurgical Societies grade of IV–V, a greater subarachnoid clot burden, and the presence of midline shift and subdural hematomas were associated with seizure activity. On multivariate analysis, only a subarachnoid clot burden (OR 2.76, 95% CI 1.39–5.49) and subdural hematoma (OR 5.67, 95% CI 1.56–20.57) were associated with seizures following SAH. Using ROC curve analysis, the optimal predictive cutoff for subarachnoid clot burden was determined to be 21 (of a possible 30) on the Hijdra scale (area under the curve 0.63).


A greater subarachnoid clot burden and subdural hematoma are associated with the occurrence of seizures after aneurysm rupture. These findings may help to identify patients at greatest risk for seizures and guide informed decisions regarding the prescription of prophylactic anticonvulsive therapy. Clinical trial registration no.: NCT00111085 (

Abbreviations used in this paper:ACA = anterior cerebral artery; AED = antiepileptic drug; AUC = area under the curve; CONSCIOUS-1 = Clazosentan to Overcome Neurological Ischemia and Infarction Occurring after Subarachnoid Hemorrhage; ICA = internal carotid artery; MCA = middle cerebral artery; ROC = receiver operating characteristic; SAH = subarachnoid hemorrhage; WFNS = World Federation of Neurosurgical Societies.

Article Information

Address correspondence to: R. Loch Macdonald, M.D., Ph.D., St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8. email:

Please include this information when citing this paper: published online April 12, 2013; DOI: 10.3171/2013.3.JNS122097.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Receiver operating characteristic curve analysis of the Hijdra score. Left: An ROC curve analysis demonstrating an AUC of 0.63, significantly better than chance at identifying patients with posthemorrhagic seizures. Right: Optimal sensitivity and specificity of ROC curve analysis for diagnosis of posthemorrhagic seizures in SAH patients is a Hijdra score of 21 (possible maximum of 30).



Adelöw CAndersson TAhlbom ATomson T: Prior hospitalization for stroke, diabetes, myocardial infarction, and subsequent risk of unprovoked seizures. Epilepsia 52:3013072011


Arboix AMartí-Vilalta JL: Predictive clinical factors of very early in-hospital mortality in subarachnoid hemorrhage. Clin Neurol Neurosurg 101:1001051999


Baker CJPrestigiacomo CJSolomon RA: Short-term perioperative anticonvulsant prophylaxis for the surgical treatment of low-risk patients with intracranial aneurysms. Neurosurgery 37:8638711995


Bederson JBConnolly ES JrBatjer HHDacey RGDion JEDiringer MN: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 40:99410252009


Berger ARLipton RBLesser MLLantos GPortenoy RK: Early seizures following intracerebral hemorrhage: implications for therapy. Neurology 38:136313651988


Brawley BWStrandness DE JrKelly WA: The biphasic response of cerebral vasospasm in experimental subarachnoid hemorrhage. J Neurosurg 28:181968


Butzkueven HEvans AHPitman ALeopold CJolley DJKaye AH: Onset seizures independently predict poor outcome after subarachnoid hemorrhage. Neurology 55:131513202000


Byrne JVBoardman PIoannidis IAdcock JTraill Z: Seizures after aneurysmal subarachnoid hemorrhage treated with coil embolization. Neurosurgery 52:5455522003


Cabral RJKing TTScott DF: Epilepsy after two different neurosurgical approaches to the treatment of ruptured intracranial aneurysm. J Neurol Neurosurg Psychiatry 39:105210561976


Choi KSChun HJYi HJKo YKim YSKim JM: Seizures and epilepsy following aneurysmal subarachnoid hemorrhage: incidence and risk factors. J Korean Neurosurg Soc 46:93982009


Claassen JPeery SKreiter KTHirsch LJDu EYConnolly ES: Predictors and clinical impact of epilepsy after subarachnoid hemorrhage. Neurology 60:2082142003


Connolly ES JrRabinstein AACarhuapoma JRDerdeyn CPDion JHigashida RT: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43:171117372012


De Reuck JGoethals MVonck KVan Maele G: Clinical predictors of late-onset seizures and epilepsy in patients with cerebrovascular disease. Eur Neurol 54:68722005


Dreier JPMajor SPannek HWWoitzik JScheel MWiesenthal D: Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex. Brain 135:2592752012


Echlin F: Experimental vasospasm, acute and chronic, due to blood in the subarachnoid space. J Neurosurg 35:6466561971


Graeb DARobertson WDLapointe JSNugent RAHarrison PB: Computed tomographic diagnosis of intraventricular hemorrhage. Etiology and prognosis. Radiology 143:91961982


Hart RGByer JASlaughter JRHewett JEEaston JD: Occurrence and implications of seizures in subarachnoid hemorrhage due to ruptured intracranial aneurysms. Neurosurgery 8:4174211981


Hart YSneade MBirks JRischmiller JKerr RMolyneux A: Epilepsy after subarachnoid hemorrhage: the frequency of seizures after clip occlusion or coil embolization of a ruptured cerebral aneurysm: results from the International Subarachnoid Aneurysm Trial. Clinical article. J Neurosurg 115:115911682011


Hasan DSchonck RSAvezaat CJTanghe HLvan Gijn Jvan der Lugt PJ: Epileptic seizures after subarachnoid hemorrhage. Ann Neurol 33:2862911993


Hijdra ABrouwers PJVermeulen Mvan Gijn J: Grading the amount of blood on computed tomograms after subarachnoid hemorrhage. Stroke 21:115611611990


Hoh BLNathoo SChi YYMocco JBarker FG II: Incidence of seizures or epilepsy after clipping or coiling of ruptured and unruptured cerebral aneurysms in the nationwide inpatient sample database: 2002–2007. Neurosurgery 69:6446502011


Huff JSPerron AD: Onset seizures independently predict poor outcome after subarachnoid hemorrhage. Neurology 56:142314242001


Ibrahim GMWeidauer SMacdonald RL: Interobserver variability in the interpretation of computed tomography following aneurysmal subarachnoid hemorrhage. Clinical article. J Neurosurg 115:119111962011


Kotila MWaltimo O: Epilepsy after stroke. Epilepsia 33:4954981992


Kvam DALoftus CMCopeland BQuest DO: Seizures during the immediate postoperative period. Neurosurgery 12:14171983


Lanzino GD'Urso PISuarez J: Seizures and anticonvulsants after aneurysmal subarachnoid hemorrhage. Neurocrit Care 15:2472562011


LeRoux PDHaglund MMNewell DWGrady MSWinn HR: Intraventricular hemorrhage in blunt head trauma: an analysis of 43 cases. Neurosurgery 31:6786851992


Lin CLDumont ASLieu ASYen CPHwang SLKwan AL: Characterization of perioperative seizures and epilepsy following aneurysmal subarachnoid hemorrhage. J Neurosurg 99:9789852003


Macdonald RLKassell NFMayer SRuefenacht DSchmiedek PWeidauer S: Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke 39:301530212008


Molyneux AJKerr RSYu LMClarke MSneade MYarnold JA: International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 366:8098172005


Naidech AMKreiter KTJanjua NOstapkovich NParra ACommichau C: Phenytoin exposure is associated with functional and cognitive disability after subarachnoid hemorrhage. Stroke 36:5835872005


Ohman J: Hypertension as a risk factor for epilepsy after aneurysmal subarachnoid hemorrhage and surgery. Neurosurgery 27:5785811990


Pinto ANCanhao PFerro JM: Seizures at the onset of subarachnoid haemorrhage. J Neurol 243:1611641996


Rhoney DHTipps LBMurry KRBasham MCMichael DBCoplin WM: Anticonvulsant prophylaxis and timing of seizures after aneurysmal subarachnoid hemorrhage. Neurology 55:2582652000


Rose FCSarner M: Epilepsy after ruptured intracranial aneurysm. BMJ 1:18211965


Rosengart AJHuo JDTolentino JNovakovic RLFrank JIGoldenberg FD: Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs. J Neurosurg 107:2532602007


Shah DHusain AM: Utility of levetiracetam in patients with subarachnoid hemorrhage. Seizure 18:6766792009


Sundaram MBChow F: Seizures associated with spontaneous subarachnoid hemorrhage. Can J Neurol Sci 13:2292311986


Szaflarski JPSangha KSLindsell CJShutter LA: Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care 12:1651722010


Teasdale GMDrake CGHunt WKassell NSano KPertuiset B: A universal subarachnoid hemorrhage scale: report of a committee of the World Federation of Neurosurgical Societies. J Neurol Neurosurg Psychiatry 51:14571988


Ukkola VHeikkinen ER: Epilepsy after operative treatment of ruptured cerebral aneurysms. Acta Neurochir (Wien) 106:1151181990


Zubkov AYWijdicks EF: Antiepileptic drugs in aneurysmal subarachnoid hemorrhage. Rev Neurol Dis 5:1781812008




All Time Past Year Past 30 Days
Abstract Views 50 50 23
Full Text Views 150 150 22
PDF Downloads 98 98 10
EPUB Downloads 0 0 0


Google Scholar