An Item Response Theory analysis of the Unified Multiple System Atrophy Rating Scale

Highlights

• The majority of UMSARS item scores progressed with disease duration and disability.

• 70% of the scale information was carried by only 11/26 items.

• These 11 items reflect patient-centered outcomes.

• A shortened scale based on these items may be useful for future clinical trials.

• Improvements seem necessary regarding items assessing dysautonomia.

Abstract

Introduction

The Unified Multiple System Atrophy Rating Scale (UMSARS) has four subscales that have been specifically designed for the clinical assessment of MSA patients. UMSARS I (activities of daily living) and II (motor examination) subscales are regularly used as primary endpoints in treatment trials. The main objective of this study was to identify UMSARS I and II subscale items that best describe progression over time.

Methods

All MSA patients seen at the French Reference Centre for MSA from 2007 to 2020 were included in a prospective cohort with an annual follow-up assessment including UMSARS. The repeated measures of the 26 UMSARS I and II items were analyzed using a longitudinal Item Response Theory model to identify the most informative items for each of the five UMSARS IV disease stages. Sample size estimates were further calculated for the most informative items as a group.

Results

A total of 557 MSA patients were included with a mean follow-up of 2.3 years. The majority of items progressed with disease duration or across the different UMSARS IV disability stages, with the exception of those related to dysautonomia. Roughly 70% of the scale information was carried by only 11/26 items, many reflecting the patient perspective. These yielded similar sample size estimates than UMSARS I + II items.

Conclusion

This study provides important information about the progression of UMSARS I and II subscale items. Improvements seem particularly necessary regarding those assessing dysautonomia. A shortened scale may be useful as outcome for future clinical trials.

Introduction

Multiple system atrophy (MSA) is a rare progressive neurodegenerative synucleinopathy characterised by various combinations of autonomic failure, parkinsonism and cerebellar ataxia. Depending on the predominance of the symptoms, two forms are distinguished, i.e. MSA-P with predominant parkinsonism and MSA-C with predominant cerebellar impairment. The prognosis is poor with a median survival between 6 and 10 years [1,2].

The Unified Multiple System Atrophy Rating Scale (UMSARS) was developed in 2004 for the quantitative assessment of disease severity in MSA patients [3]. The scale is composed of four sub-scales: UMSARS I is a functional score based on 12 questions that evaluate activities of daily living. Each question is scored from 0 to 4, with a higher score indicating a lower functional status; UMSARS II is a motor examination comprising 14 questions also scored from 0 to 4; UMSARS III consists of the measurement of supine and standing blood pressure; UMSARS IV is a disability scale which ranges from 1 (no disability) to 5 (severe disability). UMSARS I and II were used to describe disease progression in natural history studies in MSA and as primary endpoints in treatment trials [1].

Despite the use of this scale in MSA for almost 20 years, some essential aspects are still unknown such as the contribution of the different items to the total score and their progression during different disease stages [4]. Hence, the main objective of this study was to identify UMSARS I and II subscale items that best describe MSA progression over time. We also estimated the minimum sample size required for treatment trials according to these items.