Multiple system atrophy with autonomic failure: clinical, histological and neurochemical observations on four cases

Four cases of progressive autonomic failure are described, in all of which there were additional non-autonomic neurological abnormalities, including pyramidal, extra-pyramidal and cerebellar features. Histological examination revealed cell degeneration in the substantia nigra, putamen and intermediolateral columns of the spinal cord as a common pathological finding. In addition, 3 cases showed loss of Purkinje cells in the cerebellum and degeneration of pontine nuclei and inferior olivary nuclei. In one case there was cell loss from the locus coeruleus, caudate nucleus, vestibular nuclei and dorsal vagal nuclei. These were, therefore, cases of multiple system atrophy. Neurochemically, a common feature was a profound depletion in dopamine and noradrenaline from brain regions which are normally rich in these catecholamines. Central cholinergic systems appeared to be involved also, but to a variable degree.