Progression and prognosis in multiple system atrophy. An analysis of 230 Japanese patients

• Published in: Brain (London, England : 1878) England : 1878), 2002-05, Vol.125 (Pt 5), p.1070-1083
• Main Authors: WATANABE, Hirohisa, SAITO, Yufuko, HIRAYAMA, Masaaki, SOBUE, Gen, TERAO, Shinichi, ANDO, Tetsuo, KACHI, Teruhiko, MUKAI, Eiichiro, AIBA, Ikuko, ABE, Yuji, TAMAKOSHI, Akiko, DOYU, Manabu
• Format: Article
• Language: English
• Subjects: Activities of Daily Living; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Humans; Longitudinal Studies; Medical sciences; Multiple System Atrophy - diagnosis; Multiple System Atrophy - mortality; Multiple System Atrophy - pathology; Neurology; Prognosis; Risk Factors; Survival Analysis
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awf117

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