Brain, Vol. 117, No. 4, 835-845, 1994
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Clinical features and natural history of multiple system atrophy
An analysis of 100 cases
1Institute of Neurology London, UK 2Department of Epidemiology and Public Health, University College London 3Parkinson's Disease Society Brain Bank London, UK
Correspondence to:
0Correspondence to: Dr N. P. Quinn, University Department of Clinical Neurology, Institute of Neurology, Queen Square, London WC1N 3BG, UK
The clinical features and natural history of 100 patients diagnosed as probable multiple system atrophy (MSA) are described. In all 14 (of 41 deceased) cases who underwent post-mortem examination of the brain, the diagnosis was confirmed pathologically, providing some validation of the clinical diagnostic criteria used. There were 67 men and 33 women. Median age at onset (at time of first reported symptom) was 53 (range 33–76) years. Autonomic symptoms were the initial feature in 41% of the patients, but had subsequently developed in 97% at latest follow-up. The most frequent autonomic symptom in men was impotence, and in women was urinary incontinence. Symptomatic orthostatic hypotension, although present in 68%, was severe in only 15% of patients. Parkinsonism was the initial feature in 46%, but had subsequently developed in 91% of subjects at latest follow-up. It was the predominant motor disorder [striatonigral degeneration (SND) type] in 82% of the patients, and was usually asymmetric (74%). Although akinesia and rigidity predominated, tremor was present at rest in 29% of patients, but in only 9% had a classical pill-rolling parkinsonian rest tremor been recorded. Twenty-nine percent of MSA patients had a good or excellent levodopa response at some stage. However, only 13% maintained this response. Prominent orofacial dyskinesias and dystonias occurred in a quarter of treated patients with MSA. Early onset (before age 49 years) MSA patients tended to have a good levodopa response. Cerebellar symptoms or signs were the only initial feature in 5%. Although subsequently developing in a further 47% of cases, in only 18% was a cerebellar syndrome the only (9%) or predominant (9%) motor disorder [olivopontocerebellar (OPCA) type]. Pyramidal involvement at latest follow-up was noted in 61 % of all cases. In a further seven patients the initial features involved more than one system, and one other had presented as a parasomnia. Multiple system atrophy of the OPCA type most commonly presented with gait ataxia. Tremor, pyramidal signs and myoclonus were less common than in MSA of the SND type. Cerebellar signs were present in 42% of patients with MSA of the SND type and parkinsonian signs in 50% of patients with MSA of the OPCA type. Disease progression was faster than in idiopathic Parkinson's disease, so that >40% of patients were markedly disabled or wheelchair bound within 5 years of onset of motor disturbance. Median survival of the whole group as calculated by Kaplan-Meier analysis was 9.5 years. Total disease duration from first symptom was longer in males, especially if presenting before age 49 years and at Hoehn and Yahr stage I or 11. However, there was no sex difference in survival from first motor symptom.
multiple system atrophy; olivopontocerebellar atrophy; striatonigral degeneration; Shy-Drager syndrome
Received October 22, 1993. Revised February 25, 1994. Accepted March 18, 1994.
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