Evidence of persistent blood-brain barrier abnormalities in chronic-progressive multiple sclerosis.

Abstract

Brain capillaries were analyzed morphometrically for alterations in organelle distribution and density in biopsy samples of central nervous system tissue from seven patients diagnosed as having chronic progressive multiple sclerosis. Data were expressed as percentage of endothelial cytoplasm occupied by the respective organelles. The density of pinocytotic vesicles in endothelium ranged from 0.53% within normal-appearing parenchyma to 1.2% in gliotic areas. For mitochondria the values ranged from 10.87% in normal areas to 4.72% in the same respective samples. Thus, an inverse correlation between vesicular and mitochondrial content was observed. These findings suggest that endothelial cells in gliotic areas are similar to endothelial cells of the systemic circulation in their mitochondrial content and pinocytotic activity. Interendothelial junctions in capillaries of all areas examined appeared normal. Additional evidence for a continuous blood-brain barrier anomaly in multiple sclerosis was the accumulation of perivascular fibrin, suggesting an increase in microvascular permeability. Perivascular collagen deposits, degenerative changes in pericytes and astrocytic swelling were also indicators of an increase in blood-brain barrier permeability. Taken together with previous data from experimental autoimmune encephalomyelitis, the present findings in chronic silent multiple sclerosis lesions suggest that central nervous system endothelial cells show persistent abnormalities of the blood-brain barrier, even in the absence of active inflammation.