to the parenchyma. because the vrs often have an extra membrane in gray matter, the ischemic caa response is often observed in white matter. it has been hypothesized that the structure of vrs in the cerebral cortex may contribute to the development of alzheimer’s disease. in contrast to vrs of the basal ganglia, vrs in the cerebral cortex are surrounded by only one layer of leptomeninges. as such, vrs in the cerebral cortex may drain β-amyloid in interstitial fluid less effectively than vrs in the basal ganglia. the less-effective drainage may lead to the development of the β-amyloid plaques that characterize alzheimer’s disease. in support of this hypothesis, studies have noted the greater frequency of β-amyloid plaques in the cerebral cortex than in the basal ganglia of alzheimer’s disease patients. stroke because dilated perivascular spaces are so closely correlated with cerebrovascular disease, there is much current research on their use as a diagnostic tool. in a recent study of 31 subjects, abnormal dilation, along with irregular csf pulsation, were correlated with those subjects having three or more risk factors for strokes. therefore, perivascular spaces are a possible novel biomarker for hemorrhagic strokes. cadasil syndrome (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome) is a hereditary stroke condition due to a notch 3 gene mutation on chromosome 19. studies have noted that in comparison to family members lacking the affected haplotype that leads to the condition, an increased number of dilated spaces is observed in individuals with cadasil. these perivascular spaces are localized primarily in the putamen and temporal subcortical white matter and they appear to correlate with age of the individual with the condition rather than severity of the disease itself. there has been a high risk of stroke associated with dilated perivascular spaces in the elderly according to the framingham stroke risk score. in contrast, other studies have concluded that the dilation of these spaces is a normal phenomenon in aging with no association with arterosclerosis. this remains, therefore, an important point of research in the field. multiple sclerosis similar to the research concerning a potential connection between perivascular spaces and alzheimer's, mri scans of people recently diagnosed with multiple sclerosis (ms) have been studied. larger, more prevalent spaces have been observed in those with ms. additional studies with similar findings have suggested that the inflammatory cells which contribute to the demyelination that characterizes ms also attack the perivascular spaces. studies using advanced mri techniques will be necessary to determine if the perivascular spaces can be implicated as a potential marker of the disease. autism dilated perivascular spaces are common among the elderly and uncommon in children. studies have noted the association between both developmental delay and non-syndromic autism and enlarged or dilated perivascular spaces. non-syndromic autism categorizes autistic patients for which there is no known cause. history the appearance of perivascular spaces was first noted in 1843 by durant-fardel. in 1851, rudolph virchow was the first to provide a detailed description of these microscopic spaces between the outer and inner/middle lamina of the brain vessels. charles-philippe robin confirmed these findings in 1859 and was the first to describe the perivascular spaces as channels that existed in normal anatomy. the spaces were called virchow-robin spaces and are still also known as such. the immunological significance was discovered by wilhelm his, sr. in 1865 based on his observations of the flow of interstitial fluid over the spaces to the lymphatic system. for many years after virchow-robin spaces were first described, it was thought that they were in free communication with the cerebrospinal fluid in the subarachnoid space. it was later shown with the use of electron microscopy that the pia mater serves as separation between the two. upon the application of mri, measurements of the differences of signal intensity between the perivascular spaces and cerebrospinal fluid supported these findings. as research technologies continued to expand, so too did information regarding their function, anatomy and clinical significance.