Prognostic value of histopathological findings in aneurysmal subarachnoid hemorrhage

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Aneurysmal subarachnoid hemorrhage (SAH) carries a severe prognosis, which is often related to the development of cerebral vasospasm. Even though several clinical and radiological predictors of vasospasm and functional outcome have been established, the prognostic value of histopathological findings remains unclear.


Histopathological findings in resected distal aneurysm walls were examined, as were the clinical and radiological factors in a series of 91 patients who had been neurosurgically treated for aneurysmal SAH. The impact of the histological, clinical, and radiological factors on the occurrence of vasospasm and functional outcome at discharge was analyzed.


Histopathological findings frequently included lymphocytic infiltrates (60%), fibrosis (60%), and necrosis (50%) of the resected aneurysm wall. On univariate analysis, clinical (Hunt and Hess grade) and radiological (aneurysm size) factors as well as histopathological features—namely, lymphocytic infiltrates and necrosis of the aneurysm wall—were significantly associated with the occurrence of vasospasm. On multivariate analysis, lymphocytic infiltrates (OR 6.35, 95% CI 2.32–17.36, p = 0.0001) and aneurysm size (OR 1.22, 95% CI 1.05–1.42, p = 0.009) remained the only factors predicting the development of vasospasm. A poor functional outcome at discharge was significantly associated with vasospasm, other clinical factors (Hunt and Hess grade, alcohol consumption, hyperglycemia, and elevated white blood cell count [WBC] at admission), and radiological factors (Fisher grade and aneurysm size), as well as with histopathological features (lymphocytic infiltrates [p = 0.0001] and necrosis of the aneurysm wall [p = 0.0015]). On multivariate analysis taking into account all clinical, radiological, and histological factors; vasospasm (OR 9.82, 95% CI 1.83–52.82, p = 0.008), Hunt and Hess grade (OR 5.61, 95% CI 2.29–13.74, p = 0.0001), patient age (OR 1.09, 95% CI 1.02–1.16, p = 0.0013), elevated WBC (OR 1.29, 95% CI 1.01–1.64, p = 0.04), and Fisher grade (OR 4.35, 95% CI 1.25–15.07, p = 0.015) best predicted functional outcome at discharge.


The demonstration of lymphocytic infiltrates in the resected aneurysm wall is of independent prognostic value for the development of vasospasm in patients with neurosurgically treated aneurysmal SAH. Thus, histopathology might complement other clinical and radiological factors in the identification of patients at risk.

Abbreviations used in this paper: BMI = body mass index; GOS = Glasgow Outcome Scale; SAH = subarachnoid hemorrhage; SMC = smooth-muscle cell; WBC = white blood cell count.

Article Information

Address correspondence to: Martin Hasselblatt, M.D., Institute of Neuropathology, University Hospital Münster, Domagkstrasse 19, 48149 Münster, Germany. email:

*Drs. Holling and Jeibmann contributed equally to this study.

© AANS, except where prohibited by US copyright law.



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    Photomicrographs showing lymphocytic infiltrates (A), necrosis (B), fibrosis (C), SMC hyperplasia (D), and hemosiderin (E) within the aneurysm wall as well as periadvential vessels in the vicinity of the aneurysm wall (F). H & E (A, D, E, and F) and van Gieson (B and C). Original magnification × 200 and × 400 (insets).

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    Graph depicting the relationship between lymphocytic infiltrates and the timing of surgery. The extent of lymphocytic infiltrates in the aneurysm wall (0 = absent, 1 = weak, 2 = strong) and the timing of surgery are not correlated (p = 0.402, Spearman rank correlation coefficient).



Bowman GBonneau RHChinchilli VMTracey KJCockroft KM: A novel inhibitor of inflammatory cytokine production (CNI-1493) reduces rodent post-hemorrhagic vasospasm. Neurocrit Care 5:2222292006


Chyatte DBruno GDesai STodor DR: Inflammation and intracranial aneurysms. Neurosurgery 45:113711461999


Dhar RDiringer MN: The burden of the systemic inflammatory response predicts vasospasm and outcome after subarachnoid hemorrhage. Neurocrit Care 8:4044122008


Dumont ASDumont RJChow MMLin CLCalisaneller TLey KF: Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 53:123 1252003


Fergusen SMacdonald RL: Predictors of cerebral infarction in patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 60:6586672007


Frösen JPiippo APaetau AKangasniemi MNiemela MHernesniemi J: Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35:2287 22932004


Hansen-Schwartz JVajkoczy PMacdonald RLPluta RMZhang JH: Cerebral vasospasm: looking beyond vasoconstriction. Trends Pharmacol Sci 28:2522562007


Hijdra Avan Gijn JNagelkerke NJVermeulen Mvan Crevel H: Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage. Stroke 19:125012561988


Hoh BLTopcuoglu MASinghal ABPryor JCRabinov JDRordorf GA: Effect of clipping, craniotomy, or intravascular coiling on cerebral vasospasm and patient outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery 55:7797862004


Jamous MANagahiro SKitazato KTTamura TAziz HAShono M: Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats. J Neurosurg 107:4054112007


Kataoka KTaneda MAsai TKinoshita AIto MKuroda R: Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke 30:139614011999


Lagares AGomez PALobato RDAlen JFAlday RCampollo J: Prognostic factors on hospital admission after spontaneous subarachnoid haemorrhage. Acta Neurochir (Wien) 143:6656722001


Macdonald RLRosengart AHuo DKarrison T: Factors associated with the development of vasospasm after planned surgical treatment of aneurysmal subarachnoid hemorrhage. J Neurosurg 99:6446522003


Niskanen MMHernesniemi JAVapalahti MPKari A: Oneyear outcome in early aneurysm surgery: prediction of outcome. Acta Neurochir (Wien) 123:25321993


Rosengart AJSchultheiss KETolentino JMacdonald RL: Prognostic factors for outcome in patients with aneurysmal subarachnoid hemorrhage. Stroke 38:231523212007


Salary MQuigley MRWilberger JE Jr: Relation among aneurysm size, amount of subarachnoid blood, and clinical outcome. J Neurosurg 107:13172007


Schoch BRegel JPWichert MGasser TVolbracht LStolke D: Analysis of intrathecal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage. Neurosurgery 60:8288362007


Solenski NJHaley EC JrKassell NFKongable GGermanson TTruskowski L: Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Participants of the Multicenter Cooperative Aneurysm Study. Crit Care Med 23:100710171995


Suarez JI: Treatment of ruptured cerebral aneurysms and vasospasm after subarachnoid hemorrhage. Neurosurg Clin N Am 17:Suppl 157692006


van Gijn JRinkel GJ: Subarachnoid haemorrhage: diagnosis, causes and management. Brain 124:2492782001




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