Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy.

Shy and Drager (1960), on the basis of some 40 published case reports, described a clinical syndrome to which their names have subsequently been attached. The complete syndrome includes orthostatic hypotension, anhidrosis, urinary and faecal incontinence, sexual impotence, Parkinsonian signs, external ocular palsies, amyotrophy, and iris atrophy. A detailed post-mortem examination of one of their cases showed neuronal degeneration at many sites, including the intermediolateral columns of the spinal cord. They did not comment on the relation of this finding to the autonomic features of their patient's disorder. In 1965, Fichefet, Sternon, Franken, Demanet, and Vanderhaeghen described a case presenting with orthostatic hypotension, with subsequent development of Parkinsonism. The pathology was that of idiopathic paralysis agitans, with Lewy-type cytoplasmic inclusions and loss of pigmented nerve cells. In addition, the authors observed some cell loss in the anterior and lateral horns of the spinal cord. In 1966, Johnson, Lee, Oppenheimer, and Spalding described the clinical, physiological, and pathological findings in two cases of orthostatic hypotension. In the first of these, the only associated disturbances were sexual impotence and loss of sweating. Lewy-type inclusions were found in the pigmented nuclei and elsewhere, but there was no detectable loss of pigmented cells. Cell loss in the intermediolateral columns was estimated at nearly 90%. In the second case, the autonomic disorder was followed, after a few years, by a progressive disorder of motor and cerebellar function. The lesions were those of olivo-ponto-cerebellar atrophy; in addition, there was cell loss, estimated at about 75 %, in the intermediolateral columns. Since then, there have been four reports on cases that have gone to necropsy-that of Nick, Contamin, Escourolle, Guillard, and Marcantoni (1967) and the two cases of Schwarz (1967)-all of which showed neuronal degeneration at various sites, including the inter28 mediolateral columns; and the case of Martin, Travis, and van den Noort (1968), which showed no relevant CNS pathology. The case reported here showed certain features of the Shy-Drager syndrome, including orthostatic hypotension, impotence, and incontinence. The patient also suffered from a cerebellar type of ataxia, which was temporarily made very much worse by smoking a cigarette. This type of sensitivity to nicotine has been reported by Spillane (1955) in patients with spino-cerebellar disease, but not, hitherto, in association with the Shy-Drager syndrome. The object of this paper is to provide evidence that (1) in this, as in other cases of the Shy-Drager syndrome, the basic disease is a primary atrophy of a selection of neurones in the CNS; (2) the features of sympathetic failure, including orthostatic hypotension, are attributable to cell loss in the intermediolateral columns; (3) nicotine sensitivity is associated with cerebellar system disorders, which are present in some cases of the Shy-Drager syndrome. There does not appear to be a direct connection between nicotine sensitivity and autonomic failure.