Personalised profiling to identify clinically relevant changes in tremor due to multiple sclerosis

Background: There is growing interest in sensor-based assessment of upper limb tremor in multiple sclerosis and other movement disorders. However, previously such assessments have not been found to offer any improvement over conventional clinical observation in identifying clinically relevant changes in an individual's tremor symptoms, due to poor test-retest repeatability. Method: We hypothesised that this barrier could be overcome by constructing a tremor change metric that is customised to each individual's tremor characteristics, such that random variability can be distinguished from clinically relevant changes in symptoms. In a cohort of 24 people with tremor due to multiple sclerosis, the newly proposed metrics were compared against conventional clinical and sensor-based metrics. Each metric was evaluated based on Spearman rank correlation with two reference metrics extracted from the Fahn-Tolosa-Marin Tremor Rating Scale: a task-based measure of functional disability (FTMTRS B) and the subject's self-assessment of the impact of tremor on their activities of daily living (FTMTRS C). Results: Unlike the conventional sensor-based and clinical metrics, the newly proposed ’change in scale’ metrics presented statistically significant correlations with changes in self-assessed impact of tremor (max R2>0.5,p< 0.05 after correction for false discovery rate control). They also outperformed all other metrics in terms of correlations with changes in task-based functional performance (R2=0.25 vs. R2=0.15 for conventional clinical observation, both p< 0.05).Conclusions: The proposed metrics achieve an elusive goal of sensor-based tremor assessment: improving on conventional visual observation in terms of sensitivity to change. Further refinement and evaluation of the proposed techniques is required, but our core findings imply that the main barrier to translational impact for this application can be overcome. Sensor-based tremor assessments may improve personalised treatment selection and the efficiency of clinical trials for new treatments by enabling greater standardisation and sensitivity to clinically relevant changes in symptoms

A Wearable Mechatronic Device for Hand Tremor Monitoring and Suppression: Development and Evaluation

Tremor, one of the most disabling symptoms of Parkinson\u27s disease (PD), significantly affects the quality of life of the individuals who suffer from it. These people live with difficulties with fine motor tasks, such as eating and writing, and suffer from social embarrassment. Traditional medicines are often ineffective, and surgery is highly invasive and risky. The emergence of wearable technology facilitates an externally worn mechatronic tremor suppression device as a potential alternative approach for tremor management. However, no device has been developed for the suppression of finger tremor that has been validated on a human. It has been reported in the literature that tremor can be selectively suppressed by mechanical loading. Therefore, the objectives of this thesis were to develop a wearable tremor suppression device that can suppress tremor at the wrist and the fingers, and to evaluate it on individuals with PD in a pre-clinical trial. To address these objectives, several experiments were performed to quantify hand tremor; an enhanced high-order tremor estimator was developed and evaluated for tremor estimation; and a wearable tremor suppression glove (WTSG) was developed to suppress tremor in the index finger metacarpophalangeal (MCP) joint, the thumb MCP joint, and the wrist. A total of 18 individuals with PD were recruited for characterizing tremor. The frequencies and magnitudes of the linear acceleration, angular velocity, and angular displacement of tremor in the index finger MCP joint, the thumb MCP joint, and the wrist were quantified. The results showed that parkinsonian tremor consists of multiple harmonics, and that the second and third harmonics cannot be ignored. With the knowledge of the tremor characteristics, an enhanced high-order tremor estimator was developed to acquire better tremor estimation accuracy than its lower-order counterpart. In addition, the evaluation of the WTSG was conducted on both a physical tremor simulator and on one individual with PD. The results of the simulation study proved the feasibility of using the WTSG to suppress tremor; and the results of the evaluation on a human subject showed that the WTSG can suppress tremor motion while allowing the user to perform voluntary motions. The WTSG developed as a result of this work has demonstrated the feasibility of managing hand tremor with a mechatronic device, and its validation on a human subject has provided useful insights from the user\u27s perspectives, which facilitate the transition of the WTSG from the lab to the clinic, and eventually to commercial use. Lastly, an evaluation studying the impact of suppressed tremor on unrestricted joints was conducted on 14 individuals with PD. The results showed a significant increase in tremor magnitude in the unrestricted distal joints when the motions of the proximal joints were restricted. The average increase of the tremor magnitude of the index finger MCP joint, the thumb MCP joint, the wrist and the elbow are 54%, 96%, 124%, and 98% for resting tremor, and 50%, 102%, 49%, and 107% for postural tremor, respectively. Such a result provided additional clinical justification for the significance of the development of a wearable mechatronic device for hand tremor management. Although the focus of this thesis is on hand tremor management, the development and evaluation of a full upper-limb tremor suppression device is required as a future step, in order to advance the use of wearable mechatronic devices as one of the valid tremor treatment approaches