CADASIL RAPIDLY ACCELERATED BY HYPOTENSION POST-TRAUMA: AUTOPSY REVEALS IMPORTANT CONTRIBUTION OF BOTH ARTERIES AND VEINS IN WHITE MATTER PATHOLOGY

Abstract

Vascular reactivity of subcortical arteries is impaired in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This ‘earthen pipe’ state impairs autoregulation with dependency on blood pressure for brain perfusion. Chronic hypoperfusion can cause ischemic damage but less is known about the effects of acute hypotension. Additionally, the contribution of veins has been overlooked in conditions with leukoaraiosis, in general (including Alzheimer’s disease), and in CADASIL specifically. We describe the imaging and pathological findings of a case in whom CADASIL was dramatically accelerated following acute episodes of hypotension. Interestingly, venous collagenosis was demonstrated in the periventricular white matter regions. Case report with neuroimaging and pathological data. A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture, and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He expired within 5 weeks of the trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy, and multiple cavitations involving deep subcortical grey and white matter. Small arteries had thickened walls, disruption of the muscularis and intimal PAS-positive material (Fig 1A). Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis (Fig 1 B,C). There was no pathological evidence of global hypoxia or diffuse axonal injury. The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. Additionally, collagenosis of veins in the affected white matter regions is a novel finding not yet reported in CADASIL, to our knowledge. A few reports have suggested an integral role of collagenized veins in age-related leukoaraiosis and this may also apply to CADASIL. This case underscores the importance of blood pressure regulation in patients with CADASIL and highlights the potential importance of veins in white matter pathology. Cerebral arterial and venous pathology in white matter hyperintensities in CADASIL A. Arteriole containing PAS positive granular material within the media (arrow). B. Collagenosis of periventricular veins (arrows) highlighted by Masson's trichrome. C. The collagenized veins (arrows) do not contain the PAS positive material within their collagenized walls.