Multiple system atrophies: A neuropathological and neurochemical study

Abstract

The 5 familial cases which are reported here, showed a similar clinical course characterized by an early onset and a very long duration provided adequate nursing care was available. The main features were a very prominent pyramidal syndrome, less pronounced or partially masked cerebellar, myoclonic and extrapyramidal syndromes and preterminal sphincter disturbances which accounted for feeding difficulties, malnutrition and infections. Epilepsy was not infrequent but its management was possible with modest does of antiepileptic drugs. Investigations during life are helpful in ruling out some lipidoses such as metachromatic leucodystrophy, but they did not give any useful evidence as to pathogenesis. If one accepts an autosomal recessive inheritance (this is not completely certain), it is clear that neither clinical examination nor investigations are at present helpful in the detection of heterozygotes. The main pathological findings were multiple system atrophies and leucodystrophy. The system atrophies were qualitatively similar to those found in the classical spinocerebellar degenerations but they were much more widespread above the spinal level. The constellation of optic, thalamic, pontine, olivary, pyramidal and other long-tract lesions, among which the thalamic degeneration was unusually pronounced, appears to be unique among the abiotrophic processes. The second major pathological feature which contributes to the specificity of the syndrome, is the diffuse sclerosis of the white matter. If one attempts to classify these lesions into the conventional group of leucodystrophies, then they belong to the very large and ill-defined group of orthochromatic leucodystrophies (for a review, see Peiffer 1970b). Lipid analyses of postmortem brain tissue in 2 patients revealed a decrease in the lipid content of the white matter. No such effect was noted in grey matter. This drastic reduction - true for neutral lipids, glycolipids and phospholipids - could be interpreted as the chemical manifestation of demyelination. HFA deficiency occurring both in white and grey matter was the striking biochemical feature in our patients. This finding is rather unique and could perhaps be regarded as a primary event in this disease. A deficiency of the α-hydroxylating system is the most likely cause of this familial disorder.