Advances in Understanding the Pathophysiology of Lacunar Stroke

Abstract

troke is the second leading cause of death in the world and the leading cause of disability in the United States. 1 Among ischemic strokes, there are different subtypes, including large artery atherosclerosis, cardioembolism, and cerebral small vessel disease (CSVD). Although CSVD has several clinical and radiographic manifestations, lacunar stroke (LS) is prototypical and accounts for 20% to 30% of ischemic strokes. 2,3 Clinically, LS can manifest with several syndromes depending on lesion location. 4 Silent LSs are found in 20% to 50% of healthy elderly people. 5 Lacunar strokes are particularly burdensome, with a 20% recurrence rate, 25% fiveyear mortality, and associated morbidities, such as vascular cognitive impairment. 3 Lacunar strokes, appropriately named given their propensity to form cavities (lacunes), were first described in 1838 (Figure 1). 3 More recently, the Standards for Reporting Vascular Changes on Neuroimaging definitions were developed to standardize terms that describe the appearance of sequelae of CSVD, including recent small subcortical infarcts, lacunes, white matter hyperintensities (WMHs), perivascular spaces, microbleeds, and brain atrophy, on imaging. 6 Lacunar strokes primarily encompass 2 terms: recent small subcortical infarcts, defined as recent infarctions in the territory of 1 perforating arteriole with imaging features or clinical symptoms consistent with occurrence in the previous few weeks, and lacunes, defined as round or ovoid, subcortical, fluid-filled cavities 3 to 15 mm in diameter, consistent with previous acute small subcortical infarcts or hemorrhages in the territory of 1 perforating arteriole. 6 Although this review focuses on LS, other abnormalities that result from CSVD are relevant because there are interrelated mechanisms and treatment implications. For example, recent small subcortical infarcts can also contribute to WMH, 3 and many intracerebral hemorrhages (ICHs) likely result from similar vessel abnormalities. 7 This suggests that patients with LS may have an increased risk for bleeding when taking antithrombotic medications. IMPORTANCE Stroke is the second leading cause of death in the world, and nearly one-third of ischemic strokes are lacunar strokes (LSs) or small subcortical infarcts. Although smaller in size, they create large problems, leaving many patients with intellectual and physical disabilities. Because there are limitations in understanding the underlying pathophysiology of LS, the development of novel therapies has been slow.OBSERVATIONS When the term lacune was described in the 1800s, its underlying pathophysiological basis was obscure. In the 1960s, C. Miller Fisher, MD, performed autopsy studies that showed that vessels supplying lacunes displayed segmental arteriolar disorganization, characterized by vessel enlargement, hemorrhage, and fibrinoid deposition. For these pathologic changes, he coined the term lipohyalinosis. Since that time, few attempts have been made to reconcile this pathologic description with modern mechanisms of cerebr...

Periodontitis is associated with systemic inflammation and vascular endothelial dysfunction in patients with lacunar infarct

“…Lacunar infarct (LI), which is a small cerebral subcortical infarct, causes ≈ 25% of the cases of ischemic stroke . Atheroma in the middle cerebral artery is responsible for almost 20% of LI cases . Evidence regarding embolism as a common cause for LI is limited (< 10% of LI cases) .…”

“…Atheroma in the middle cerebral artery is responsible for almost 20% of LI cases . Evidence regarding embolism as a common cause for LI is limited (< 10% of LI cases) . Although the exact mechanism remains unclear, intrinsic cerebral small vessel disease such as lipohyalinosis (referred to hyaline deposition in the perforating arteries together with diffuse arteriopathy) is considered as the most common cause of LI .…”

“…Evidence regarding embolism as a common cause for LI is limited (< 10% of LI cases) . Although the exact mechanism remains unclear, intrinsic cerebral small vessel disease such as lipohyalinosis (referred to hyaline deposition in the perforating arteries together with diffuse arteriopathy) is considered as the most common cause of LI . It has been demonstrated that endothelial dysfunction by amyloid beta (Aβ) deposition has been related to LIs and leukoaraiosis (white matter hyperintensities) .…”

“…diffuse arteriopathy) is considered as the most common cause of LI. 2 It has been demonstrated that endothelial dysfunction by amyloid beta (A ) deposition has been related to LIs and leukoaraiosis (white matter hyperintensities). 3,4 In this sense, A was found to be involved in the disruption of the endothelial vascular function in patients with LI.…”

Increased platelet procoagulant potential predicts recurrent stroke and TIA after lacunar infarction

“…Mechanisms leading to stroke recurrence in lacunar strokes are not well defined, although endothelial dysfunction and blood brain barrier disruption play a critical role in the pathophysiology leading to infarction . The presence of atheroma or cardioembolism, common etiologies for non‐lacunar stroke, has not been associated with most small subcortical strokes .…”