Longitudinal Orthostatic Tremor Study (LOTS): a multi-centre, prospective cohort protocol for characterising orthostatic tremor and orthostatic myoclonus.

INTRODUCTION: Orthostatic tremor (OT) is a rare movement disorder defined by high-frequency tremor predominantly in the standing position, often causing mobility limitation and reduced quality of life. Its natural history, disease burden and treatment response remain poorly understood due to limited longitudinal evidence. The Longitudinal Orthostatic Tremor Study (LOTS) aims to characterise clinical, demographic and therapeutic trajectories in OT and orthostatic myoclonus over 5 years.

METHODS AND ANALYSIS: LOTS is a multicentre prospective cohort study expanding an initial retrospectively characterised cohort of 58 patients from a tertiary centre in India. Additional incident cases will be recruited across national and international sites over 2 years. Participants will undergo assessments at baseline, 6 months and annually for 5 years. Primary outcomes include the OT-10 scale and the novel OT Disease Burden Index. Secondary outcomes include electrophysiology (surface EMG), quality of life, OT Impact Profile and treatment response. Exploratory measures include neuroimaging, genetics, wearable-based metrics and gait analysis where feasible. Latent class analysis will identify subgroups with distinct trajectories, and mixed-effects models will assess longitudinal change and predictors of progression. Sensitivity analyses will account for differences between retrospective and prospective baselines. Anticipated limitations include attrition and variation in access to specialised electrophysiology.

TRIAL REGISTRATION NUMBER: This study has been registered with the Clinical Trials Registry-India (CTRI; Registration number: CTRI/2025/10/096248).