Validation of a precision tremor measurement system for multiple sclerosis

Thushara Perera, Wee Lih Lee, Shivanthan A.C. Yohanandan, Ai Lan Nguyen, Belinda Cruse, Frederique M.C. Boonstra, Gustavo Noffs, Adam P. Vogel, Scott C. Kolbe, Helmut Butzkueven, Andrew Evans, Anneke van der Walt

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Tremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy. New Method: We present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 samples of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers. Results: Velocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84% of its initial measurement compared to 91% for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p = 0.002) in healthy subjects. Comparison with Existing Methods: Subjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended. Conclusions: TREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability.

Original languageEnglish
Pages (from-to)377-384
Number of pages8
JournalJournal of Neuroscience Methods
Volume311
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Multiple sclerosis
  • Objective monitoring
  • Quantification
  • Tremor

Cite this

Perera, T., Lee, W. L., Yohanandan, S. A. C., Nguyen, A. L., Cruse, B., Boonstra, F. M. C., ... van der Walt, A. (2019). Validation of a precision tremor measurement system for multiple sclerosis. Journal of Neuroscience Methods, 311, 377-384. https://doi.org/10.1016/j.jneumeth.2018.09.022
Perera, Thushara ; Lee, Wee Lih ; Yohanandan, Shivanthan A.C. ; Nguyen, Ai Lan ; Cruse, Belinda ; Boonstra, Frederique M.C. ; Noffs, Gustavo ; Vogel, Adam P. ; Kolbe, Scott C. ; Butzkueven, Helmut ; Evans, Andrew ; van der Walt, Anneke. / Validation of a precision tremor measurement system for multiple sclerosis. In: Journal of Neuroscience Methods. 2019 ; Vol. 311. pp. 377-384.
@article{d2f98eff66304d45ba3baf11fe696df7,
title = "Validation of a precision tremor measurement system for multiple sclerosis",
abstract = "Background: Tremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy. New Method: We present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 samples of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers. Results: Velocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84{\%} of its initial measurement compared to 91{\%} for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p = 0.002) in healthy subjects. Comparison with Existing Methods: Subjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended. Conclusions: TREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability.",
keywords = "Multiple sclerosis, Objective monitoring, Quantification, Tremor",
author = "Thushara Perera and Lee, {Wee Lih} and Yohanandan, {Shivanthan A.C.} and Nguyen, {Ai Lan} and Belinda Cruse and Boonstra, {Frederique M.C.} and Gustavo Noffs and Vogel, {Adam P.} and Kolbe, {Scott C.} and Helmut Butzkueven and Andrew Evans and {van der Walt}, Anneke",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jneumeth.2018.09.022",
language = "English",
volume = "311",
pages = "377--384",
journal = "Journal of Neuroscience Methods",
issn = "0165-0270",
publisher = "Elsevier",

}

Perera, T, Lee, WL, Yohanandan, SAC, Nguyen, AL, Cruse, B, Boonstra, FMC, Noffs, G, Vogel, AP, Kolbe, SC, Butzkueven, H, Evans, A & van der Walt, A 2019, 'Validation of a precision tremor measurement system for multiple sclerosis' Journal of Neuroscience Methods, vol. 311, pp. 377-384. https://doi.org/10.1016/j.jneumeth.2018.09.022

Validation of a precision tremor measurement system for multiple sclerosis. / Perera, Thushara; Lee, Wee Lih; Yohanandan, Shivanthan A.C.; Nguyen, Ai Lan; Cruse, Belinda; Boonstra, Frederique M.C.; Noffs, Gustavo; Vogel, Adam P.; Kolbe, Scott C.; Butzkueven, Helmut; Evans, Andrew; van der Walt, Anneke.

In: Journal of Neuroscience Methods, Vol. 311, 01.01.2019, p. 377-384.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Validation of a precision tremor measurement system for multiple sclerosis

AU - Perera, Thushara

AU - Lee, Wee Lih

AU - Yohanandan, Shivanthan A.C.

AU - Nguyen, Ai Lan

AU - Cruse, Belinda

AU - Boonstra, Frederique M.C.

AU - Noffs, Gustavo

AU - Vogel, Adam P.

AU - Kolbe, Scott C.

AU - Butzkueven, Helmut

AU - Evans, Andrew

AU - van der Walt, Anneke

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Tremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy. New Method: We present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 samples of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers. Results: Velocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84% of its initial measurement compared to 91% for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p = 0.002) in healthy subjects. Comparison with Existing Methods: Subjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended. Conclusions: TREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability.

AB - Background: Tremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy. New Method: We present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 samples of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers. Results: Velocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84% of its initial measurement compared to 91% for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p = 0.002) in healthy subjects. Comparison with Existing Methods: Subjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended. Conclusions: TREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability.

KW - Multiple sclerosis

KW - Objective monitoring

KW - Quantification

KW - Tremor

UR - http://www.scopus.com/inward/record.url?scp=85053819109&partnerID=8YFLogxK

U2 - 10.1016/j.jneumeth.2018.09.022

DO - 10.1016/j.jneumeth.2018.09.022

M3 - Article

VL - 311

SP - 377

EP - 384

JO - Journal of Neuroscience Methods

JF - Journal of Neuroscience Methods

SN - 0165-0270

ER -

Perera T, Lee WL, Yohanandan SAC, Nguyen AL, Cruse B, Boonstra FMC et al. Validation of a precision tremor measurement system for multiple sclerosis. Journal of Neuroscience Methods. 2019 Jan 1;311:377-384. https://doi.org/10.1016/j.jneumeth.2018.09.022