Abstract 3643: Intimal Hyperplasia Of Leptomeningeal Arteries In CADASIL
Objective: CADASIL is associated with abnormalities of penetrating white matter arteries; but recent studies showing pathology in the gray matter and the increased incidence of migraine with aura suggest that leptomeningeal vessels may be affected in the disease. The pathology of leptomeningeal vessels has not been extensively characterized. This study tests the hypothesis that the intima and media of leptomeningeal small vessels are abnormal in CADASIL compared to age matched controls and the very old.
Methods: Samples analyzed included four genetically proven CADASIL brains (average age 61), four controls without symptoms of cerebrovascular disease (average age 68), and five very aged brains (average age 90). Temporal lobe brain sections (approximately 5-10 cm2) from autopsy material were stained with Movat’s pentachrome and immunohistochemistry (for smooth muscle actin, NOTCH3, and collagen). All leptomeningeal arteries < 150 um were digitally imaged (total number 190 [CADASIL], 171 [control], and 157 [aged]). We measured intimal, medial, and adventitial thickness, inner and outer diameter, and sclerotic index (SI).
Results: We first confirmed that pentachrome staining precisely delineates the intima, media, and adventitia of leptomeningeal arteries by comparing serial vessels stained using immunohistochemical markers. Pentachrome stained was then used to delineate three layers of each vessel. The intima of CADASIL arteries was significantly thickened compared to controls and the very aged (7.5+/-3.2; 1.3+/- 0.5; 1.85+/-0.69 um; p<0.0001). Medial thickness was lower in CADASIL compared to controls (but similar to the very aged) (3.5+/-3.2; 5.3+/-2.6; 3.3+/-2.6 um; p<0.0001). Inner diameters of CADASIL vessels were larger than controls and the very aged (41+/-21; 34+/-19; 33+/-17 um; p<0.005). Outer diameters of CADASIL vessels were larger than controls and the aged (75+/-33; 54+/-28; 55+/-25 um; p<0.0001). SI was significantly increased in CADASIL compared to other groups (0.46+/-0.12; 0.38+/-0.10; 0.41+/-0.10; p<0.05).
Conclusion: The leptomeningeal arteries in CADASIL undergo significant remodeling. The most obvious change is a dramatic increase in intimal thickness and vessel diameter. The significant loss of media in CADASIL was also seen in very aged brains. These pathological findings may underlie migraine with aura, which is seen at a higher frequency in CADASIL patients. In addition, leptomeningeal pathology could contribute to impairment of cerebral blood flow regulation in the white matter.
- © 2012 by American Heart Association, Inc.