Small vessel disease.

As the name suggests, small vessel disease affects the smaller arteries and
arterioles of the brain. Small vessel disease can manifest in several ways, including lacunar stroke,
leukoaraiosis (white matter changes that can be observed as T2-hyperintensities on MRI or
hypodensities on CT), cerebral microbleeds and intracerebral haemorrhage. Deep subcortical and
brainstem structures are supplied by small-calibre perforating arteries that arise from much larger
arteries of the circle of Willis, exposing the small vessels to high pressure that could predispose to
lipohyalinosis (narrowing of the small cerebral vessels). Lipohyalinosis is not the only cause of small
subcortical infarcts, and traditional clinical patterns defined as lacunar syndromes have limited
specificity for small vessel disease-related stroke. Atherosclerosis of the parent artery with occlusion
of the perforating vessel origin is another important mechanism of lacunar clinical syndromes30. In
rare cases, monogenic disorders can cause small vessel disease, for example, CADASIL, which
typically presents with migraine followed by lacunar infarcts and then dementia.

Arterial dissection. A dissection or tear in the intimal layer of an artery with intramural thrombus is
an important cause of stroke, particularly in younger patients. Most dissections that cause ischaemic
stroke are in the extracranial carotid and vertebral arteries and can occlude the artery at the site of
dissection or cause thrombus formation and distal embolism. Although varying degrees of cervical
trauma can cause dissection, it is often quite minor; for some individuals, forceful coughing or
sneezing may be sufficient to cause dissection. Furthermore, dissections are often spontaneous.
Some collagen and connective tissue diseases can predispose to arterial dissections, although, aside
from fibromuscular dysplasia and Ehlers–Danlos syndrome, these disorders are rarely identifiable
with currently available tests and limited genetic contributions to dissection risk have been
discovered to date31. As a result, testing for an underlying connective tissue disorder is not routine.