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 termlacunewas 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 termlipohyalinosis. Since that time, few attempts have been made to reconcile this pathologic description with modern mechanisms of cerebral small vessel disease (CSVD). During the past 6 years, progress has been made in understanding the clinical mechanisms, imaging characteristics, and genetic basis of LS. Conclusions and Relevance Questions persist regarding the order of events related to the initiation and progression of CSVD, how LS is related to other sequelae of CSVD, and whether LS is part of a systemic disease process. The relative roles of aging, oxidative stress, mechanical stress, genetic predisposition, and other vascular risk factors should be further studied, especially in the era of widespread antihypertensive use. Although understanding of endothelial dysfunction has increased, future work on the role of media and adventitial dysfunction should be explored. Recent advances in mapping the brain vasculome may generate new hypotheses. The investigation of new therapeutic targets, aimed at reversing CSVD processes and promoting neural repair after LS, depends upon further understanding these basic mechanisms.

Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter.

The basilar artery (BA) is the largest artery in the posterior circulation and forms the central core of this vascular territory. It is most commonly affected by atherosclerosis, and necropsy studies have found it to be one of the first and most severely involved of all intracranial arteries.¹ The BA is also affected by embolism, dissections, aneurysms, migraine, and inflammatory conditions.² Despite the wide range of underlying pathologic features, BA occlusive disease is an uncommon cause of stroke. Most reports have retrospectively described isolated cases or small series of patients.^3-10 Early reports were based on necropsy studies that emphasized clinicoanatomical correlations rather than the underlying vascular lesion, correlating focal brain lesions with symptoms and signs found during life.^4-6,11 Until recently, premortem diagnosis of posterior circulation vascular lesions required invasive techniques, such as catheter angiography, a procedure often not performed because it was considered risky and unnecessary to guide therapy. Consequently, many series included only select patients and did not reflect the true spectrum of disease.^7-10 Now new treatment options, such as thrombolysis and angioplasty and noninvasive diagnostic imaging techniques promote premortem diagnosis of BA occlusive disease. However, still few prospective studies are available,^12-15 and disparities remain regarding the natural history, underlying stroke mechanisms, vascular features, and prognosis of BA occlusive disease. We herein report an analysis of patients with moderate to severe stenosis or occlusion of the BA in the New England Medical Center Posterior Circulation Registry (NEMC-PCR), the largest prospective series of consecutively collected patients with posterior circulation ischemia to date.

Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEI) are effective in prevention of ischemic stroke, as measured by reduced stroke incidence. We aimed to compare stroke severity between stroke patients who were taking ACEI before their stroke onset and those who were not, to examine the effects of pretreatment with ACEI on ischemic stroke severity. We retrospectively studied 126 consecutive patients presenting within 24 hours of ischemic stroke onset, as confirmed by diffusion-weighted magnetic resonance imaging (DWI). We calculated the NIHSS score at presentation, as the primary measure of clinical stroke severity, and categorized stroke severity as mild (NIHSS [less than or equal to] 7), moderate (NIHSS 8-13) or severe (NIHSS [greater than or equal to] 14). We analyzed demographic data, risk-factor profile, blood pressure (BP) and medications on admissions, and determined stroke mechanism according to TOAST criteria. We also measured the volumes of admission diffusion- and perfusion-weighted (DWI /PWI) magnetic resonance imaging lesions, as a secondary measure of ischemic tissue volume. We compared these variables among patients on ACEI and those who were not. Thirty- three patients (26%) were on ACE-inhibitors. The overall median baseline NIHSS score was 5.5 (range 2-21) among ACEI-treated patients vs. 9 (range 1-36) in non-ACEI patients (p = 0.036). Patients on ACEI prior to their stroke had more mild and less severe strokes, and smaller DWI and PWI lesion volumes compared to non-ACEI treated patients. However, none of these differences were significant. Predictably, a higher percentage of patients on ACEI had a history of heart failure (p = 0.03). Age, time-to-imaging or neurological evaluation, risk-factor profile, concomitant therapy with lipid lowering, other antihypertensives or antithrombotic agents, or admission BP were comparable between the two groups. Our results suggest that ACE-inhibitors may reduce the clinical severity of stroke, as measured by NIHSS score. Further, larger-scale, prospective studies are needed to validate our findings, and to elucidate the mechanism(s) of ACEImediated benefits in patients with ischemic stroke.