Most ischaemic strokes are thromboembolic in origin, with common sources of embolism being

large artery atherosclerosis and cardiac diseases, particularly atrial fibrillation. Other causes of
ischaemic stroke include small vessel disease, which is associated with elevated blood pressure and
diabetes mellitus and is particularly common in Asia. Less common overall, but proportionally more
prevalent in younger patients, are arterial dissection, vasculitis, patent foramen ovale (PFO) with
paradoxical embolism (that is, whereby venous thrombi enter the systemic and cerebral circulation)
and haematological disorders (Fig. 2; Table 1). The cause of ischaemic stroke is important as it can
guide therapeutic strategies for the prevention of recurrent stroke.

Atherosclerosis. One common cause of ischaemic stroke is an embolus in the cerebral vasculature
(Fig. 3) that originated from an ulcerated and typically stenotic atherosclerotic plaque in the aortic
arch, neck or intracranial vessels. In patients with atherosclerosis, throm

can form when the lipid core of atherosclerotic plaques is exposed to the bloodstream, which can be
caused by inflammation and ulceration of the fibrous cap of plaques. These thrombi can occlude the
atherosclerotic vessel or, more commonly in the large vessels relevant to stroke, can embolize
distally. In western populations, the most frequent location of atherosclerotic plaques that can cause
ischaemic stroke is the internal carotid artery, just after its bifurcation from the common carotid
artery. This is hypothesized to relate to reduced shear stress on the arterial wall at that site. Low
shear stress is associated with intimal thickening and reduced nitric oxide release that are thought to
mediate this susceptibility to cholesterol plaque development25. Although intracranial
atherosclerosis is sometimes observed in patients in western countries, usually in heavy smokers
and individuals with diabetes mellitus26, it is much more common in Asia27. Indeed, intracranial
atherosclerosis is reported to cause ~30–50% of ischaemic strokes in Asian patients compared with
5–10% of strokes in white patients28. This disorder presents a challenge for standard
thrombectomy, as it is associated with higher reocclusion rates after thrombectomy and has an
increased requirement for stenting, the latter carrying a greater risk of complications, particularly
bleeding related to the use of antiplatelet medications to maintain stent patency29.