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      Blood Pressure Gradients in the Brain: Their Importance to Understanding Pathogenesis of Cerebral Small Vessel Disease

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          Abstract

          The term “lacunar infarction” referred to small infarctions in the basal ganglia, internal capsule, thalamus, and brainstem, due to hypertensive small vessel disease. However, it has become common to refer to all small infarctions as lacunar. It is important to understand that true lacunes occur in a phylogenetically ancient part of the brain, the “vascular centrencephalon”, where short straight arteries with few branches transmit high blood pressure straight through to end-arterioles. The cortex is supplied by long arteries with many branches, so there is a very large blood pressure gradient in the brain. When blood pressure in the brachial artery is 117/75 mmHg, the pressure in the lenticulostriate artery would be 113/73, and the pressure in small parietal arterioles would be only 59/38 mmHg. Recent studies have reported that patients with a pulse pressure >60 mmHg and diastolic pressure <60 mmHg have a doubling of coronary risk and a 5.85-fold increase in stroke risk. This means that new low systolic targets being proposed will probably decrease the incidence of true lacunes, but increase small subcortical infarctions in the hemispheres. The pathogenesis of small vessel disease should be interpreted in the light of these blood pressure gradients.

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          Most cited references23

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          Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

          To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. Convents in the Midwestern, Eastern, and Southern United States. A total of 102 college-educated women aged 76 to 100 years. Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
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            Lacunar strokes and infarcts: a review.

            C M Fisher (1982)
            At least 20 different lacunar syndromes have been described and can be recognized by characteristic clinical features. Almost all occur in patients with hypertension. Small lacunes are usually due to lipohyalinosis, larger ones to atheromatous or embolic occlusion of a penetrating vessel. The concept of the "lacunar state" is examined in the light of recent knowledge with the conclusion that the clinical deficit is primarily related to unrecognized normal pressure hydrocephalus rather than to the presence of a few lacunes. The notion that lacunes occur haphazardly is criticized because the first or only lacune tends to be symptomatic. The incidence of cerebral lacunes has declined since the introduction of antihypertensive therapy, an indication that therapy is effective.
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              Understanding white matter disease: imaging-pathological correlations in vascular cognitive impairment.

              Most strokes are covert and observed incidentally on brain scans, but their presence increases risk of overt stroke and dementia. Amyloid angiopathy, associated with Alzheimer Disease (AD) causes stroke, and when even small strokes coexist with AD, they lower the threshold for dementia. Diffuse ischemic white matter disease impairs executive functioning, information processing speed, and gait. Neuroimaging techniques, such as tissue segmentation, Diffusion Tensor Imaging, MR Spectroscopy, functional MRI and amyloid PET, probe microstructural integrity, molecular biology, and activation patterns, providing new insights into brain-behavior relationships. MR-pathological studies of periventricular hyperintensity (leukoaraiosis) in aging and dementia reveal arteriolar tortuosity, reduced vessel density, and occlusive venous collagenosis which causes venous insufficiency and vasogenic edema. Activated microglia, oligodendroglial apoptosis, clasmatodendritic astrocytosis, and upregulated hypoxia-markers are seen on immunohistochemistry. Further research is needed to understand and treat this chronic subcortical vascular disease, which is epidemic in our aging population.
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                Author and article information

                Journal
                Brain Sci
                Brain Sci
                brainsci
                Brain Sciences
                MDPI
                2076-3425
                23 January 2019
                February 2019
                : 9
                : 2
                : 21
                Affiliations
                Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, 1400 Western Road, London, ON N6G 2V4, Canada; dspence@ 123456robarts.ca ; Tel.: +1-519-931-5731; Fax: +1-519-931-5737
                Author information
                https://orcid.org/0000-0001-7478-1098
                Article
                brainsci-09-00021
                10.3390/brainsci9020021
                6406272
                30678095
                916c19b0-c4c1-455d-b77b-44b092459ba4
                © 2019 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 December 2018
                : 22 January 2019
                Categories
                Review

                small vessel disease,lacunar infarction,hypertension,cerebral autoregulation,blood pressure gradients,vascular centrencephalon

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