What causes lacunar stroke?

The mechanism underlying, and the long term consequences of, lacunar ischaemic stroke, the cause of a quarter of all ischaemic strokes, are poorly understood, but are not benign. Evidence supports the hypothesis that, in most lacunar strokes, the vascular abnormality is pathologically diffuse, even if the clinical manifestations are focal, and result from small vessel endothelial damage, subtle increase in blood-brain barrier permeability, and leakage of substances toxic to the brain into the perivascular tissue. As originally proposed in the lacunar hypothesis, only a small proportion of lacunar stroke appears to result from artery to artery or cardiogenic emboli or intracranial large artery stenoses. These latter embolic/stenotic lesions may be recognisable by their size (being larger). It might be questioned how this presumably gradual process could produce a sudden lacunar infarct. In fact, lacunar stroke symptoms (more than other stroke subtypes) not uncommonly progress after onset. Perhaps the interstitial fluid composition eventually reaches a critically abnormal point where the axons cease to transmit signals, or the vessel wall thickening narrows the lumen and reduces blood flow, or fails to allow nutrients out and waste products of metabolism back into the circulation. This diffuse endothelial failure might also account for additional asymptomatic lacunar infarcts observed at presentation with, or during follow up after, a symptomatic lacunar infarct with no underlying embolic source. These asymptomatic lesions, gradually multiplying, could be the source of the WMLs. Neurones can switch off suddenly, even when the underlying process is gradual; for example, neurones switch off electrical activity (manifest as a stroke) as cerebral blood flow falls below about 25 ml/100 g brain/min, thus the fall in blood flow may have been gradual but the symptoms are sudden. An important target for new therapeutic approaches to prevent or treat a common form of ischaemic stroke and cognitive decline may have been over-looked. It is important to understand this process better, not simply in order to reduce the burden of lacunar stroke, but because the same mechanism may also underlie WMLs and consequent cognitive decline to dementia. Lacunar ischaemic stroke has for too long been simply lumped together with other stroke subtypes; while it is likely that many older stroke patients will share common vascular risk factors, this tendency has hindered understanding of what appears to be an importantly different stroke subtype that may require different acute treatment and prevention. For example, the association with microhaemorrhages, a possible risk factor for intracerebral haemorrhage, is worrying, and may increase the risk of haemorrhage complicating anti-thrombotic drug treatment compared with their use in cortical ischaemic stroke. Further studies, using detailed, accurate, and unbiased patient classification, are needed to examine risk factors for lacunar stroke including blood-brain barrier function (now possible with detailed MRI), how to identify those lacunar strokes that are due to embolism, and clarify long term outcomes. Study of small arteriolar abnormalities in other vascular beds (for example the retina, where the arterioles can be directly observed) and systemic endothelial abnormalities will help both in understanding the mechanisms of lacunar ischaemic stroke and in identifying diagnostic and prognostic markers.