Objective: To assess if MDS-UPDRS Part III tremor items may form a suitable subscale in early-stage PD.

Background: Symptoms of tremor are highly meaningful to people with PD [1]; evaluating the benefit of disease-modifying therapies on tremor is, therefore, an important clinical objective that requires sensitive measurement. The adequacy of an MDS-UPDRS Part III subscale, focused on bradykinesia and rigidity, was recently demonstrated [2]. This additional research reviews the option of a subscale focused on tremor items only.

Method: Data from the PPMI cohort and ORCHESTRA Phase II study (NCT04658186) in early-stage PD were analyzed. Exploratory Factor Analysis and psychometric models (Rasch Measurement Theory and Item Response Theory) were applied to identify relationships between MDS-UPDRS Part III items, their underlying concepts, and to assess psychometric properties at scale- and item-level.

Results: Analyses singled out items related to rest tremor of the limbs and of the lip/jaw, as well as postural and kinetic tremor of the hands from the other Part III items. Results also showed congruous inconsistencies between severity thresholds for all rest tremor items measured in participants at Baseline across both datasets and at the Month 36 visit in the PPMI cohort. When all Part III tremor items were combined, the resulting 10 items did not form a cohesive subscale; rest tremor items still displayed limited ability to define a continuum of severity for these early-stage PD patients. In contrast to rest tremor, postural and kinetic tremor items did not display major measurement issues; however, only the severity transition from ‘normal’ to ‘slight’ was relevant to the early PD population.

Conclusion: The analysis of the ORCHESTRA and PPMI data provided confirmatory evidence that rigidity/bradykinesia and tremor items should be considered separately when assessing change in PD severity [3–5]. In addition, a subscale encompassing the MDS-UPDRS Part III tremor items is not fit-for-purpose for assessing rest tremor, and potentially lacks granularity to accurately measure signs of action tremor in early-stage PD. Rest and action tremors have different prevalence and pathobiology from other motor symptoms and from each other [6,7]. Assessment of the impact of disease-modifying treatments on rest and action tremors is likely to require separate approaches, while accounting for PD phenotype.

References: 1. Morel T, Cleanthous S, Andrejack J et al. Patient experience in early-stage Parkinson’s disease: using a mixed methods analysis to identify which concepts are cardinal for clinical trial outcome assessment. Neurol Ther 2022;11(3):319–1340.
2. Key Prato M, Regnault A, Quéré S et al. Repurposing the MDS-UPDRS Part III for early-stage Parkinson’s disease: supportive evidence for a bradykinesia and rigidity specific sub-score (Abstract 75). Mov Disord 2023;38(Suppl 1).
3. Luo S, Zou H, Stebbins GT et al. Dissecting the domains of Parkinson’s disease: insights from longitudinal item response theory modeling. Mov Disord 2022;37(9):1904–1914.
4. Dirkx MF and Bologna M. The pathophysiology of Parkinson’s disease tremor. J Neurol Sci 2022;435:120196.
5. de Siqueira Tosin MH, Goetz CG, Luo S et al. Item response theory analysis of the MDS-UPDRS motor examination: tremor vs. nontremor items. Mov Disord 2020;35(9):1587–1595.
6. Lenka A and Jankovic J. Tremor syndromes: an updated review. Front Neurol 2021;12:684835.
7. Gupta DK, Marano M, Zweber C, et al. Prevalence and Relationship of Rest Tremor and Action Tremor in Parkinson’s Disease. Tremor Other Hyperkinet Mov (N Y). 2020;10:58.
Acknowledgement of data source: www.ppmi-info.org/access-data-specimens/download-data

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MDS Abstracts - https://www.mdsabstracts.org/abstract/time-to-rethink-the-measurement-of-tremor-in-early-stage-parkinsons-disease/