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Lookup NU author(s): Yumi Yamamoto, Dr Masafumi Ihara, Carina Tham, Janet Slade, Arthur Oakley, Dr Tuomo Polvikoski, Professor Raj KalariaORCiD
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Background and Purpose-White matter (WM) hyperintensities on MRI or leukoaraiosis is characteristic of stroke syndromes. Increased MRI signals in the anterior temporal pole are suggested to be diagnostic for cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), with 90% sensitivity and 100% specificity. The structural correlates of these specific WM hyperintensities seen on T2-weighted and FLAIR sequences in the temporal pole of CADASIL are unclear. We assessed pathological changes in postmortem tissue from the temporal pole to reveal the cause of CADASIL-specific WM hyperintensities. Methods-A combination of tinctorial and immunostaining approaches and in vitro imaging methods were used to quantify the extent of perivascular space (PVS), arteriosclerosis determined as the sclerotic index, WM myelination as the myelin index, and damage within the WM as accumulated degraded myelin basic protein in samples of the anterior temporal pole from 9 CADASIL and 8 sporadic subcortical ischemic vascular dementia cases, and 5 similarly aged (young) and 5 older controls. Luxol fast blue-stained serial sections from a CADASIL case were also used to reconstruct the temporal pole, which was then compared to the MR images. Results-Luxol fast blue sections used to reconstruct the temporal pole revealed an abundance of enlarged PVS in the WM that topographically appeared as indistinct opaque regions. The mean and total areas of the PVS per WM area (%PVS) were significantly greater in CADASIL compared to the controls. The myelin index was severely reduced in CADASIL in relation to the subcortical ischemic vascular dementia and control sample that was consistent with increased immunoreactivity of degraded myelin basic protein, indicating myelin degeneration. Cerebral microvessels associated with the PVS exhibited a 4.5-fold greater number of basophilic (hyalinized) vessels and a 57% increase in the sclerotic index values in CADASIL subjects compared to young controls. A significant correlation between the quantity of hyalinized vessels and sclerotic index values was also apparent (P
Author(s): Yamamoto Y, Ihara M, Tham C, Low RWC, Slade JY, Moss T, Oakley AE, Polvikoski T, Kalaria RN
Publication type: Article
Publication status: Published
Journal: Stroke
Year: 2009
Volume: 40
Issue: 6
Pages: 2004-2011
ISSN (print): 0039-2499
ISSN (electronic): 1524-4628
Publisher: Lippincott Williams & Wilkins
URL: http://dx.doi.org/10.1161/STROKEAHA.108.528299
DOI: 10.1161/STROKEAHA.108.528299
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