Progression and prognosis in multiple system atrophy

Abstract

We investigated the disease progression and survival in 230 Japanese patients with multiple system atrophy (MSA; 131 men, 99 women; 208 probable MSA, 22 definite; mean age at onset, 55.4 years). Cerebellar dysfunction (multiple system atrophy-cerebellar; MSA-C) predominated in 155 patients, and parkinsonism (multiple system atrophy-parkinsonian; MSA-P) in 75. The median time from initial symptom to combined motor and autonomic dysfunction was 2 years (range 1-10). Median intervals from onset to aid-requiring walking, confinement to a wheelchair, a bedridden state and death were 3, 5, 8 and 9 years, respectively. Patients manifesting combined motor and autonomic involvement within 3 years of onset had a significantly increased risk of not only developing advanced disease stage but also shorter survival (P < 0.01). MSA-P patients had more rapid functional deterioration than MSA-C patients (aid-requiring walking, P = 0.03; confinement to a wheelchair, P < 0.01; bedridden state, P < 0.01), but showed similar survival. Onset in older individuals showed increased risk of confinement to a wheelchair (P < 0.05), bedridden state (P = 0.03) and death (P < 0.01). Patients initially complaining of motor symptoms had accelerated risk of aid-requiring walking (P < 0.01) and confinement to a wheelchair (P < 0.01) compared with those initially complaining of autonomic symptoms, while the time until confinement to a bedridden state and survival were no worse. Gender was not associated with differences in worsening of function or survival. On MRI, a hyperintense rim at the lateral edge of the dorsolateral putamen was seen in 34.5% of cases, and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%. These putaminal and pontine abnormalities became more prominent as MSA-P and MSA-C features advanced. The atrophy of the cerebellar vermis and PB showed a significant correlation particularly with the interval following the appearance of cerebellar symptoms in MSA-C (r = 0.71, P < 0.01, r = 0.76 and P < 0.01, respectively), but the relationship between atrophy and functional status was highly variable among the individuals, suggesting that other factors influenced the functional deterioration. Atrophy of the corpus callosum was seen in a subpopulation of MSA, suggesting hemispheric involvement in a subgroup of MSA patients. The present study suggested that many factors are involved in the progression of MSA but, most importantly, the interval from initial symptom to combined motor and autonomic dysfunction can predict functional deterioration and survival in MSA.

Comparison of Different Symptom Assessment Scales for Multiple System Atrophy

“…The patients in this study were a good representation of the Asian and Japanese MSA population and were consistent with the previous studies [35][36][37]. Our study patients were in the relatively early stages of MSA and consequently had good ADL, but the average onset age was slightly high.…”

“…The former groups were graded to have a rapid progression. The poor prognosis of MSA-P and rapid progression of early-stage MSA patients were previously mentioned [17,35], but it was not indicated that early-onset MSA would rapidly progress.…”

Norepinephrine Transporter Blockade With Atomoxetine Induces Hypertension in Patients With Impaired Autonomic Function

“…On average, MSA patients have reduced life expectancy, with death occurring within 9 years of disease. 26 In contrast, patients with peripheral autonomic failure syndromes have a better prognosis. A neurological examination is paramount in the differentiation of these conditions.…”

Adult onset sporadic ataxias: a diagnostic challenge

“…Autonomic dysfunction may be mild or absent in the beginning of the ataxia symptoms, and appear in the course of the disease progression. Response to levodopa is poor in MSA-C 37,38 . Typical neuroimaging features in MSA-C include hyperintense signal in cerebellar peduncles, olivopontocerebellar atrophy (cerebellum and brainstem), and "hot cross bun" sign, which indicates degeneration of the pons fibers (Figure 2) 1,37…”