Clinical Neurology and Neurosurgery 117 (2014) 120–121

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Letters to the Editor Distinguishing clinical outcomes aneurysmal versus nonaneurysmal subarachnoid hemorrhage

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Dear Sir, I have read, with great interest, a recently published article in Clinical Neurology and Neurosurgery by Tsermoulas et al. titled ‘Immediate coma and poor outcome in subarachnoid hemorrhage are independently associated with an aneurysmal origin’ [1]. The authors analyzed 421 patients with nontraumatic subarachnoid hemorrhage (SAH) including 359 patients with aneurysms (aSAH) and 62 patients without aneurysms (naSAH). The authors defined the amount of SAH by a semiquantitative method, the clinical grade at presentation, and the short term functional outcome for each patient [2]. Not surprisingly, significantly more patients were comatose in the aSAH cohort compared to the naSAH cohort (p < 0.001). However, the crucial finding from this study was the independent effect of aneurysmal origin on poor outcome (p < 0.001). I believe that the impact of this study’s most important finding was partially attenuated by comparing the naSAH to all patients with aSAH rather than performing a matched analysis. As expected, the aSAH patients had, on average, higher quantities of intracranial blood than the naSAH patients. The difference in outcomes between the aSAH and naSAH patients would have been further emphasized if the two cohorts were matched such that the blood loads of the aSAH and naSAH patients were equally distributed. Given the inclusion of all aSAH patients, it would have been interesting to know if the size or location of an aneurysm affected the patient’s presentation and outcome. A proportion of the aSAH patients were intervened upon, but the impact of intervention, either positive or negative, was not addressed. Neither surgical clipping nor endovascular coil embolization of ruptured aneurysms is without risk [3]. While it is unlikely any procedural complications would have dramatically affected the difference in outcomes between the aSAH and naSAH cohorts, any influence of intervention on the clinical outcomes of the aSAH group may have affected the statistical analysis. In summary, the authors should be congratulated for addressing the effect of aneurysmal origin on SAH outcomes. In addition to the pathophysiological mechanisms proposed by the authors as a possible explanation for the poorer outcomes in patients harboring aneurysms, biomolecular changes implicated in the pathogenesis of cerebral aneurysms, such as the promotion of vascular smooth muscle cell phenotypic modulation by pro-inflammatory cytokines, may also be linked to clinical manifestations [4]. Ultimately, this study has potentially far-reaching implications for animal models of cerebral aneurysms, SAH, and vasospasm [5].

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References [1] Tsermoulas G, Flett L, Gregson B, Mitchell P. Immediate coma and poor outcome in subarachnoid haemorrhage are independently associated with an aneurysmal origin. Clin Neurol Neurosurg 2013;115(8):1362–5. [2] Hijdra A, Brouwers PJ, Vermeulen M, van Gijn J. Grading the amount of blood on computed tomograms after subarachnoid hemorrhage. Stroke 1990;21(8):1156–61. [3] Molyneux A, Kerr R, Stratton I, Sandercock P, Clarke M, Shrimpton J, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002;360(9342):1267–74. [4] Ali MS, Starke RM, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, et al. TNF-alpha induces phenotypic modulation in cerebral vascular smooth muscle cells: implications for cerebral aneurysm pathology. J Cereb Blood Flow Metab 2013;33(10):1564–73. [5] Nuki Y, Tsou TL, Kurihara C, Kanematsu M, Kanematsu Y, Hashimoto T. Elastase-induced intracranial aneurysms in hypertensive mice. Hypertension 2009;54(6):1337–44.

Dale Ding ∗ University of Virginia Department of Neurosurgery, Charlottesville 22908, USA ∗ Correspondence to: University of Virginia, Department of Neurosurgery, P.O. Box 800212, Charlottesville 22908, USA. Tel.: +1 434 924 2203; fax: +1 434 982 5753. E-mail address: [email protected]

30 July 2013 Available online 18 December 2013 http://dx.doi.org/10.1016/j.clineuro.2013.08.034

Response Keywords: Aneurysm Coma Intracranial pressure Subarachnoid haemorrhage

Dear Sir, We thank Dr. Ding for his comments. The pathophysiologic mechanism that leads to coma in the acute phase of spontaneous subarachnoid haemorrhage (SAH) is not well understood. We showed that aneurysmal origin of SAH is a determinant of coma and outcome independent of the amount of blood spilled in the subarachnoid space. We agree that possible explanations for the difference in outcomes include changes related to the pathogenesis of aneurysms.

Distinguishing clinical outcomes between aneurysmal versus nonaneurysmal subarachnoid hemorrhage.

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