Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term "stroke" is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

An Updated Definition of Stroke for the 21st Century A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Objectives To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death.

Design Systematic review and meta-analysis.

Data sources PubMed from 1966 to 23 November 2009.

Study selection Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death.

Data extraction Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome.

Data synthesis 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested.

Conclusion White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

https://www.bmj.com/content/bmj/341/bmj.c3666.full.pdf

The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis

http://directory.umm.ac.id/Data%20Elmu/jurnal/B/Biological%20Psichatry/Vol48.Issue8.2000/6889.pdf

Neuroimaging studies of mood disorders.

Background Changes in the cerebral hemispheric white matter, detectable with increasing frequency by modern neuroimaging methods, are associated with aging and conceivably may contribute to the development of specific cognitive deficits. The pathogenesis of these cerebral white matter abnormalities (sometimes described as leukoaraiosis) is unknown. This review evaluates the available evidence in support of the hypothesis that the etiology of leukoaraiosis is related to a specific type of cerebral ischemia and highlights mechanisms by which ischemic injury to the brain may induce selected structural alterations limited to the cerebral white matter. Summary of Review The review is based on the critical analysis of over 100 publications (most appearing in the last decade) dealing with the anatomy and physiology of the arterial circulation to the cerebral white matter and with the pathogenesis of leukoaraiosis. Conclusions A significant number of clues support the hypothesis that some types of leukoaraiosis m...

https://air.unimi.it/bitstream/2434/579412/2/Pantoni%20-%20Stroke%201997-%20Pathogenesis%20of%20Leukoaraiosis-1.pdf

Pathogenesis of Leukoaraiosis A Review

The term cerebral small vessel disease (SVD) describes a range of neuroimaging, pathological, and associated clinical features. Clinical features range from none, to discrete focal neurological symptoms (eg, stroke), to insidious global neurological dysfunction and dementia. The burden on public health is substantial. The pathogenesis of SVD is largely unknown. Although the pathological processes leading to the arteriolar disease are associated with vascular risk factors and are believed to result from an intrinsic cerebral arteriolar occlusive disease, little is known about how these processes result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms, and the association with risk factors. Pathology often shows end-stage disease, which makes identification of the earliest stages difficult. Neuroimaging provides considerable insights; although the small vessels are not easily seen themselves, the effects of their malfunction on the brain can be tracked with detailed brain imaging. We discuss potential mechanisms, detectable with neuroimaging, that might better fit the available evidence and provide testable hypotheses for future study.

/pdf/mechanisms-of-sporadic-cerebral-small-vessel-disease-24mg5j0ptv.pdf

Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging

We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

R. Kleinert

Papers

Pathologic correlates of incidental MRI white matter signal hyperintensities