Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases.

[cadasil]

We quantified vascular changes in the frontal lobe and basal ganglia of four inherited small vessel diseases (SVDs ) including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL ), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL ), hereditary multi-infarct dementia of Swedish type (Swedish hMID ), and hereditary endotheliopathy with retinopathy , nephropathy , and stroke (HERNS ). Vascular pathology was most severe in CADASIL , and varied with marginally greater severity in the basal ganglia compared to the frontal lobe . The overall sclerotic index values in frontal lobe were in the order CADASIL ≥ HERNS > PADMAL > Swedish hMID > sporadic SVD , and in basal ganglia CADASIL > HERNS > Swedish hMID > PADMAL > sporadic SVD . The subcortical white matter was almost always more affected than any gray matter . We observed glucose transporter-1 (GLUT-1 ) protein immunoreactivities were most affected in the white matter indicating capillary degeneration whereas collagen IV (COL 4 ) immunostaining was increased in PADMAL cases in all regions and tissue types . Overall , GLUT-1 : COL 4 ratios were higher in the basal ganglia indicating modifications in capillary density compared to the frontal lobe . Our study shows that the extent of microvascular degeneration varies in these genetic disorders exhibiting common end-stage pathologies but is the most aggressive in CADASIL .