Dystonia in multiple system atrophy. (Paper).

Objective: To delineate the frequency and nature of dystonia in multiple system atrophy (MSA).

Methods: a cohort of 24 patients with clinically probable MSA over the past 10 years were prospectively followed up. Motor features were either dominated by parkinsonism (MSA-P subtype, n=18) or cerebellar ataxia (MSA-C, n=6). Classification of dystonic features and their changes with time was based on clinical observation during 6-12 monthly follow up visits. Parkinsonian features and complications of drug therapy were assessed. Most patients (22/24) died during the observation period. Neuropathological examination was confirmatory in all of the five necropsied patients.

Results: At first neurological visit dystonia was present in 11 (46%) patients all of whom had been levodopa naive at this time point. Six patients (25%) exhibited cervical dystonia (antecollis) (MSA-P n=4, MSA-C n=2), five patients (21%) showed unilateral limb dystonia (MSA-P n=4; MSA-C n=1). A definite initial response to levodopa treatment was seen in 15/18 patients with MSA-P, but in none of the six patients with MSA-C. A subgroup of 12 patients with MSA-P developed levodopa induced dyskinesias 2.3 years (range 0.5-4) after initiation of levodopa therapy. Most patients had peak dose craniocervical dystonia; however, some patients experienced limb or generalised dystonia. Isolated peak dose limb chorea occurred in only one patient.

Conclusion: The prospective clinical study suggests that dystonia is common in untreated MSA-P. This finding may reflect younger age at disease onset and putaminal pathology in MSA-P. Levodopa induced dyskinesias were almost exclusively dystonic affecting predominantly craniocervical musculature. Future studies are required to elucidate the underlying pathophysiology of dystonia in MSA.

Clinical features and natural history of multiple system atrophy (MSA) have been established in four recent series. (1-4) Multiple system atrophy is usually defined by the predominance of parkinsonian (MSA-P type) or cerebellar (MSA-C type) features. (5,6) According to a recent literature review dystonia is rare in postmortem confirmed MSA. (7) We therefore prospectively investigated the frequency of dystonia and its relation to levodopa treatment in a group of 24 patients with MSA.

PATIENTS AND METHODS

Clinical studies

Twenty four consecutive patients with probable MSA according to the criteria of Quinn and Gilman were included in the study. (5,6) Seventeen patients were women, and seven were men (ratio 2.4:1). Mean age at disease onset was 59 (SD 7.6) years (range 45-72 years) and mean disease duration defined as onset of symptoms to last follow up (n=2) or death (n=22) was 5.7 (SD 2.3) years (range 3-13 years). Eighteen out of 24 patients with MSA were classified as MSA-P type (75%); the remaining six patients fulfilled the criteria of the MSA-C variant (25%). Patients were repeatedly followed up at 6 to 12 monthly intervals for up to 10 years and the following clinical features were recorded:

(1) Presence of dystonia, its topographical distribution and clinical pattern (tonic versus phasic movements), and onset in relation to initiation of levodopa therapy (before levodopa v after levodopa).

(2) Levodopa dose and motor response to levodopa using the following rating scale: nil to …