Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke worldwide and represents a significant health problem. The pathogenesis and natural history of ICAD are poorly understood, and rigorous treatment paradigms do not exist as they do for extracranial atherosclerosis. Currently, the best treatment for ICAD remains aspirin therapy, but many patients who are placed on aspirin continue to experience recurrent strokes. As microsurgical and endovascular techniques continue to evolve, the role of extracranial to intracranial bypass operations and stenting are increasingly being reconsidered. We performed a PubMed review of the English literature with a particular focus on treatment options for ICAD and present evidence-based data for the role of surgery and stenting in ICAD against medical therapy alone. 1. Introduction Intracranial atherosclerotic disease (ICAD) is the process by which atherosclerotic plaques affect large intracranial arteries. Intracranial stenosis represents the most advanced stage of ICAD and is a precursor to ischemic stroke. ICAD is the leading cause of stroke among patients of Asian ancestry , and Hispanics and Africans also appear to be more prone to  intracranial as opposed to extracranial atherosclerosis. Whites, on the other hand, are less affected, but ICAD is still thought to account for almost 10% of ischemic strokes in this subpopulation . Thus, worldwide, ICAD may be the leading the cause of ischemic stroke. Atherosclerotic lesions, as elsewhere in the body, develop silently and insidiously over years prior to becoming suddenly symptomatic in the form of a stroke. Symptomatic ICAD is burdened with an unacceptably high recurrence rate, such that among patients with symptomatic ICAD and >70% stenosis, approximately 23% will have a recurrent stroke over the ensuing 12 months , and nearly half of these recurrent strokes tend to be disabling. The prevalence and natural history of asymptomatic ICAD are much less understood, particularly in people of European descent. Due to this lack of insight, rigorous treatment paradigms do not exist for ICAD as they do for extracranial atherosclerotic disease. The treatment strategies for ICAD include optimal medical management, surgical, and endovascular options. In this paper, we aim to define the optimal treatment strategies for this devastating disease. 2. Methods MEDLINE and PubMed searches of the English literature were performed with the following keywords: intracranial atherosclerosis, extracranial-intracranial bypass, intracranial stenting, Wingspan,
R. L. Sacco, D. E. Kargman, Q. Gu, and M. C. Zamanillo, “Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction: the Northern Manhattan stroke study,” Stroke, vol. 26, no. 1, pp. 14–20, 1995.
M. I. Chimowitz, M. J. Lynn, H. Howlett-Smith et al., “Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis,” New England Journal of Medicine, vol. 352, no. 13, pp. 1305–1316, 2005.
K. S. L. Wong, C. Chen, J. Fu et al., “Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open-label, blinded-endpoint trial,” The Lancet Neurology, vol. 9, no. 5, pp. 489–497, 2010.
T. N. Turan, G. Cotsonis, M. J. Lynn, S. Chaturvedi, and M. Chimowitz, “Relationship between blood pressure and stroke recurrence in patients with intracranial arterial stenosis,” Circulation, vol. 115, no. 23, pp. 2969–2975, 2007.
P. Amarenco, L. B. Goldstein, M. Szarek et al., “Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial,” Stroke, vol. 38, no. 12, pp. 3198–3204, 2007.
The EC/IC Bypass Study Group, “Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial,” New England Journal of Medicine, vol. 313, no. 19, pp. 1191–1200, 1985.
C. P. Derdeyn, T. O. Videen, R. L. Grubb, and W. J. Powers, “Comparison of PET oxygen extraction fraction methods for the prediction of stroke risk,” Journal of Nuclear Medicine, vol. 42, no. 8, pp. 1195–1197, 2001.
R. L. Grubb Jr. and W. J. Powers, “Risks of stroke and current indications for cerebral revascularization in patients with carotid occlusion,” Neurosurgery Clinics of North America, vol. 12, no. 3, pp. 473–487, 2001.
D. J. Langer, A. Van Der Zwan, P. Vajkoczy, L. Kivipelto, T. P. Van Doormaal, and C. A. F. Tulleken, “Excimer laser-assisted nonocclusive anastomosis: an emerging technology for use in the creation of intracranial-intracranial and extracranial-intracranial cerebral bypass,” Neurosurgical Focus, vol. 24, no. 2, article no. E6, 2008.
T. Terada, M. Tsuura, H. Matsumoto et al., “Endovascular therapy for stenosis of the petrous or cavernous portion of the internal carotid artery: percutaneous transluminal angioplasty compared with stent placement,” Journal of Neurosurgery, vol. 98, no. 3, pp. 491–497, 2003.
A. Abou-Chebl, Q. Bashir, and J. S. Yadav, “Drug-eluting stents for the treatment of intracranial atherosclerosis: initial experience and midterm angiographic follow-up,” Stroke, vol. 36, no. 12, pp. e165–e168, 2005.
W. Kurre, J. Berkefeld, M. Sitzer, T. Neumann-Haefelin, and R. Du Mesnil De Rochemont, “Treatment of symptomatic high-grade intracranial stenoses with the balloon-expandable Pharos stent: initial experience,” Neuroradiology, vol. 50, no. 8, pp. 701–708, 2008.
D. Fiorella, E. I. Levy, A. S. Turk et al., “US multicenter experience with the Wingspan stent system for the treatment of intracranial atheromatous disease: periprocedural results,” Stroke, vol. 38, no. 3, pp. 881–887, 2007.