Medullary microvessel degeneration in multiple system atrophy

Multiple system atrophy (MSA) is a rare and fatal early-onset autonomic disorder which is characterised by Parkinsonism and orthostatic hypotension (OH). The pathophysiology of MSA is not fully understood but key features include the depletion of medullary autonomic neurons and presence of glial cellular inclusions. We hypothesise that the degeneration of medullary autonomic microvessels is an additional finding in MSA. Using digital pathology we quantified basement membrane collagen (Coll IV), smooth muscle actin (α-actin) and endothelial glucose transporter (Glut 1) expression in medullary autonomic nuclei of 8 MSA and 8 OH cases, compared with 12 controls with no autonomic dysfunction. We found decreased Coll IV (p = 0.000) and Glut 1 (p = 0.000) but not α-actin expression, in medullary autonomic nuclei of MSA, but not OH cases compared with control subjects. Medullary microvessel degeneration in MSA may be secondary to the primary neuro-glial pathogenesis of the disorder, and could accelerate its ageing-related progression.