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To: Journal of PRACTICAL NEUROLOGY Letters

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Papers: A M J MacLullich, J M Wardlaw, K J Ferguson, J M Starr, J R Seckl, and I J Deary Enlarged perivascular spaces are associated with cognitive function in healthy elderly men J Neurol Neurosurg Psychiatry 2004; 75: 1519-1523 [Abstract] [Full text] [PDF]

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Dialated Virchow-Robin spaces:They do matter

Alan Jackson, Anoop Varma, Tufail Patankar, David Neary, Julie Snowden   (29 November 2004)

Dialated Virchow-Robin spaces:They do matter 29 November 2004
Alan Jackson, Professor of Neuroradiology University of Manchester, Anoop Varma, Tufail Patankar, David Neary, Julie Snowden Send letter to journal: Re: Dialated Virchow-Robin spaces:They do matter alan.jackson{at}manchester.ac.uk Alan Jackson, et al.	Dear Editor, We noted with interest the findings of MacLullich et al [1] in a cohort of ageing healthy men, that increased numbers of enlarged perivascular spaces (EPVS; syn Virchow – Robin spaces (VRS)) are associated with worse non-verbal reasoning and, more generally, visuospatial cognitive ability after adjusting for prior intelligence. However, multiple linear regression showed that EPVS scores did not have a significant independent association with the visuospatial factor scores, whereas indices of white matter lesion load did. The authors conclude “The main implication of this finding is that MRI based assessments of changes in WM lesion scales should perhaps add a measure of EPVS. This will allow further exploration of whether EPVS are a form of relatively distinct pathological change seen in the ageing brain and in various disease states, or merely a benign manifestation of ageing” In an editorial “Dilated Virchow-Robin spaces: do they matter?” Barkhof comments that “Apparently, white matter damage may manifest itself as general atrophy (with ventricular widening), incomplete white matter infarction (with WML on MRI), and by virtue of widened VRS. What is particularly interesting is why some patients may develop extensive WML in the basal ganglia and diffusely widened VRS (so-called etat crible´) without significant atrophy (fig 2), while others develop only volume reduction (global atrophy)” [2]. Pathological studies have long recognised that dilation of perivascular spaces in ageing is most commonly a concomitant of arteriosclerosis of small cerebral vessels (microvascular angiopathy; MVA) occurring in moderate and severe (Grades 2 and 3) MVA [3]. This would suggest that EPVS may provide a more direct biomarker of MVA in disease states. To test this hypothesis we have recently completed a study of EPVS in patients with dementia (unpublished data). We used a locally developed scoring scheme for EPVS which is similar to that used by MacLullich et al [1] and which reflects the number of EPVS in the centrum semiovale and the basal ganglia. We applied the score, together with Shelten’s score of white matter lesion load [4] in a group of 75 patients with dementia (Alzheimer’s disease (AD; n=35), Vascular dementia (IVD; n=24), and Frontotemporal dementia (FTD; n=16)) and 35 normal volunteers (Norm). We also measured global cerebral atrophy (corrected for head size). This study demonstrated that white matter lesions were commoner in patients with IVD than in AD or normals (p<0.01) and that the basal ganglia EPVS score was significantly higher in vascular dementia than in normal volunteers (p<0.001), patients with AD (p<0.001) or patients with FTD (p<0.01). Centrum semi-ovale EPVS were commoner in FTD than AD (p<0.01) or normals (p<0.01). Basal ganglia EPVS score accounted 29% of the variance in a multiple logistic regression analysis regression model and the Schelten’s score of periventricular hyperintensity for only 2%. Interestingly there was no correlation between basal ganglia EPVS and global atrophy. However there was significant correlation between centrum- semiovale EPVS and atrophy in patients with FTD (who exhibited significantly greater atrophy than other groups). We would therefore support the view of Barkhof that EPVS in the centrum semiovale may largely reflect atrophy but that no such clear relationship exists for basal ganglia VRS. More importantly our observations support the hypothesis that EPVS in the basal ganglia may provide a useful biomarker of MVA and can have greater discriminative power than conventional scores of white matter lesion load. We strongly support the suggestions of MacLullich et al [1] that formal quantitative scores of EPVS should be included in future imaging studies where MVA may be suspected. References (1). MacLullich, A., et al., Enlarged perivascular spaces are associated with cognitive function in healthy elderly men. J Neurol Neurosurg Psychiatry, 2004. 75: p. 1519-1523 (2). Barkhof, F., Enlarged Virchow Robin spaces: do they matter? J Neurol Neurosurg Psychiatry, 2004. 75: p. 1516-1517 (3). Hommel, M. and F. Gray, Microvascular pathology, in Brain ischaemia: Basic concepts and clinical relevance, C. LR, Editor. 1995, Springer Verlag Berlin: New York. p. 215-223. (4). Scheltens, P., et al., A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci, 1993. 114(1): p. 7-12