Microatherosclerosis is a common but often overlooked cause of ischemic stroke

Background Fisher described several distinct vascular pathologies underlying lacunar infarction. However, subsequent literature and clinical practice have often misattributed symptomatic lacunar stroke primarily to lipohyalinosis and intracranial branch ostial atherosclerosis. Classic neuropathologic studies indicate that many lacunar strokes are instead caused by microatherosclerosis - small atheromatous plaque within penetrating arteries. This study aims to quantify the proportion of symptomatic lacunar infarcts in clinical practice attributable to microatherosclerosis. Methods Three systematic meta-analyses, per PRISMA guidelines were performed of large clinical series to delineate: (1) the proportion of ischemic strokes due to lacunar infarcts; (2) among lacunar events, the relative frequencies of pure motor hemiparesis (PMH), pure sensory stroke (PSS), dysarthria-clumsy hand (DCH), ataxic hemiparesis (AH); and (3) proportional contribution of microatherosclerosis, lipohyalinosis, intracranial branch-origin atherosclerosis and embolism to symptomatic lacunar stroke. Results The neuropathology systematic review showed: PMH caused by microatherosclerosis-64%, lipohyalinosis-14%, embolism-14% and intracranial branch-artery atherosclerosis-7%; PSS caused by lipohyalinosis-100%: and DCH and AH each caused by microatherosclerosis-33%, intracranial branch-artery atherosclerosis-33%, and embolism-33%. The first clinical series meta-analysis showed, among 24 large ischemic stroke series enrolling 32,169 patients, lacunar infarct frequency was 17.8%. The second showed, among 7 large series enrolling 1,646 lacunar infarct patients, subtype frequencies were: PMH-47%, PSS-10.6%, DCH-7.7% and AH-11.2% (with the remainder sensorimotor stroke and less common lacunar syndromes). Quantitative synthesis indicated that: microatherosclerosis is estimated to be the most common cause of lacunar strokes, accounting for 43%, followed by lipohyalinosis-20%, embolism-20%, and intracranial branch-origin atherosclerosis-17%; and that microatherosclerosis is the estimated cause of 7.7% of all ischemic strokes. Conclusion Microatherosclerotic plaque within a penetrating artery is a common cause of cerebral ischemia, accounting for an estimated 1 in 13 of all ischemic strokes. This substantial burden of microatherosclerosis may be an important pathophysiologic basis for the benefits of thrombolytic and statin therapy in select patients with lacunar ischemic strokes.