Abstract

Recent studies have identified that peripheral stimulation in Parkinson’s disease (PD) is effective in tremor reduction, indicating that a peripheral feedback loop plays an important role in the tremor reset mechanism. This was an open-label, quasi-experimental, pre- and post-test design, single-blind, single-group study involving 20 tremor-dominant PD patients. The objective of this study is to explore the effect of electrical muscle stimulation (EMS) as an adjunctive treatment for resting tremor during “on” period and to identify the best machine learning model to predict the suitable stimulation level that will yield the longest period of tremor reduction or tremor reset time. In this study, we used a Parkinson’s glove to evaluate, stimulate, and quantify the tremors of PD patients. This adjustable glove incorporates a 3-axis gyroscope to measure tremor signals and an EMS to provide an on-demand muscle stimulation to suppress tremors. Machine learning models were applied to identify the suitable pulse amplitude (stimulation level) in five classes that led to the longest tremor reset time. The study was registered at the www.clinicaltrials.gov under the name “The Study of Rest Tremor Suppression by Using Electrical Muscle Stimulation” (NCT02370108). Twenty tremor-dominant PD patients were recruited. After applying an average pulse amplitude of 6.25 (SD 2.84) mA and stimulation period of 440.7 (SD 560.82) seconds, the total time of tremor reduction, or tremor reset time, was 329.90 (SD 340.91) seconds. A significant reduction in tremor parameters during stimulation was demonstrated by a reduction of Unified Parkinson’s Disease Rating Scale (UPDRS) scores, and objectively, with a reduction of gyroscopic data (p < 0.05, each). None of the subjects reported any serious adverse events. We also compared gyroscopic data with five machine learning techniques: Logistic Regression, Random Forest, Support Vector Machine (SVM), Neural Network (NN), and Long-Short-Term-Memory (LSTM). The machine learning model that gave the highest accuracy was LSTM, which obtained: accuracy = 0.865 and macro-F1 = 0.736. This study confirms the efficacy of EMS in the reduction of resting tremors in PD. LSTM was identified as the most effective model for predicting pulse amplitude that would elicit the longest tremor reset time. Our study provides further insight on the tremor reset mechanism in PD.

Highlights

  • Tremor is found in 70% of patients with Parkinson’s disease (PD), usually occurring at rest (Hughes et al, 1993; Deuschl et al, 1998)

  • Significant correlations between average pulse amplitude and the following stimulation parameters were identified: max pulse amplitude (r = 0.787, p < 0.001), duration of continuing tremor reduction after the withdrawal of electrical muscle stimulation (EMS) until the tremor reemerged to the pre-stimulation level (r = 0.474, p = 0.035), and tremor reset time (r = 0.495, p = 0.027)

  • Based on the conclusions provided by the model, a higher average pulse amplitude and a greater stimulation time results in a longer tremor reset time

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Summary

Introduction

Tremor is found in 70% of patients with Parkinson’s disease (PD), usually occurring at rest (Hughes et al, 1993; Deuschl et al, 1998). The standard treatment of parkinsonian tremors are dopaminergic and anticholinergic medications, but the outcomes are often unreliable when compared to treatment outcomes for other cardinal motor symptoms, such as bradykinesia and rigidity (Jimenez and Vingerhoets, 2012). There are no evidence-based therapeutic guidelines that provide the efficacy of specific dopaminergic medications for parkinsonian tremors (Ferreira et al, 2013; Connolly and Lang, 2014). There is a real need to identify a new efficacious treatment, with fewer adverse events, for this symptom

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