Multiple system atrophy in Hokkaido, Japan: a prospective registry study of natural history and symptom assessment scales followed for 5 years

Abstract

Objectives: Multiple system atrophy (MSA) is a refractory neurodegenerative disease, but novel treatments are anticipated. An accurate natural history of MSA is important for clinical trials, but is insufficient. This regional registry was launched to complement clinical information on MSA.

Setting: Patient recruitment started in November 2014 and is ongoing at the time of submission. The number of participating facilities was 66. Postal surveys were sent to medical facilities and patients with MSA in Hokkaido, Japan.

Participants: After obtaining written consent from 196 participants, 184 overview surveys and 115 detailed surveys were conducted.

Primary and secondary outcome measures: An overview survey evaluated conformity to diagnostic criteria and a detailed survey implemented an annual assessment based on the Unified Multiple System Atrophy Rating Scale (UMSARS).

Results: At the time of registration, 58.2% of patients were diagnosed with cerebellar symptoms predominant type MSA (MSA-C) and 29.9% were diagnosed with parkinsonism predominant type MSA (MSA-P). UMSARS Part Ⅳ score of 4 or 5 accounted for 53.8% of participants. The higher the UMSARS Part Ⅳ score, the higher the proportion of MSA-P. At baseline, levodopa was used by 69 patients (37.5%) and the average levodopa dose was 406.7 mg/day. The frequency of levodopa use increased over time. Eleven cases changed from MSA-C to MSA-P during the study, but the opposite was not observed. Information about survival and causes of death was collected on 54 cases. Half of deaths were respiratory-related. Sudden death was recorded even in the group with UMSARS Part Ⅳ score of 1.

Conclusions: This study is the first large-scale prospective MSA cohort study in Asia. MSA-C was dominant, but the use of antiparkinsonian drugs increased over the study period. Changes from MSA-C to MSA-P occurred, but not vice versa.

Keywords: epidemiology; geriatric medicine; neurology.

Figure 1

Flow diagram of the study. (A) Overview of registration. (B) New overview surveys and deaths each year from the start of the study. Solid line: cumulative new overviewed participants; dotted line: cumulative deaths. MSA, multiple system atrophy.

Figure 2

Disease type percentages stratified by UMSARS Part Ⅳ score at the time of registration. The number in parentheses refers to the number of patients. MSA, multiple system atrophy; MSA-C, cerebellar symptoms predominant type MSA; MSA-C=P, cerebellar ataxia and parkinsonian symptoms equally; MSA-P, parkinsonism predominant type MSA; UMSARS, Unified Multiple System Atrophy Rating Scale.

Figure 3

Changes in various scales over 4–5 years and standardised response mean of scale scores. (A) Changes in 16 cases that could be followed continuously up to the fourth evaluation. Black solid line: ICLEMSA; grey line: UMSARS Part Ⅱ (UMSARS2); dotted line: MSA-QoL motor score (MSA-QoLm). (B–D) Score changes in UMSARS Part Ⅱ (B), MSA-QoL motor score (C) and ICLEMSA (D) in 16 cases, MSA-C and MSA-P. Grey solid line: all 16 cases; dotted line: MSA-C; black line: MSA-P. Each data marker suggests the average and 95% CI. (E) Standardised response mean of scale scores. (F) UMSARS Part Ⅱ score changes by drug use. Each bar shows the average score of each evaluation and the error bar indicates the SD. Shaded bars indicate levodopa use, and grey bars indicate levodopa non-use. The table shows the number of patients using levodopa who could be evaluated by the UMSARS. BMI, body mass index; ICLEMSA, Items That Change Largely in the Early-Stage Multiple System Atrophy; MSA, multiple system atrophy; MSA-C, cerebellar symptoms predominant type MSA; MSA-P, parkinsonism predominant type MSA; MSA-QoL, Multiple System Atrophy Health-Related Quality of Life scale; UMSARS, Unified Multiple System Atrophy Rating Scale.

Figure 4

Causes of death and Kaplan-Meier curves. (A) Causes of death (when known); (B) Kaplan-Meier curve by UMSARS Part Ⅳ at the time of registration; and (C) Kaplan-Meier curve by MSA-C and MSA-P at the time of registration. MSA, multiple system atrophy; MSA-C, cerebellar symptoms predominant type MSA; MSA-P, parkinsonism predominant type MSA; UMSARS, Unified Multiple System Atrophy Rating Scale.