Assessment of Upper Extremity Function in Multiple Sclerosis: Feasibility of a Digital Pinching Test

Background The development of touchscreen-based assessments of upper extremity function could benefit people with multiple sclerosis (MS) by allowing convenient, quantitative assessment of their condition. The Pinching Test forms a part of the Floodlight smartphone app (F. Hoffmann-La Roche Ltd, Basel, Switzerland) for people with MS and was designed to capture upper extremity function. Objective This study aimed to evaluate the Pinching Test as a tool for remotely assessing upper extremity function in people with MS. Methods Using data from the 24-week, prospective feasibility study investigating the Floodlight Proof-of-Concept app for remotely assessing MS, we examined 13 pinching, 11 inertial measurement unit (IMU)–based, and 13 fatigability features of the Pinching Test. We assessed the test-retest reliability using intraclass correlation coefficients [second model, first type; ICC(2,1)], age- and sex-adjusted cross-sectional Spearman rank correlation, and known-groups validity (data aggregation: median [all features], SD [fatigability features]). Results We evaluated data from 67 people with MS (mean Expanded Disability Status Scale [EDSS]: 2.4 [SD 1.4]) and 18 healthy controls. In this cohort of early MS, pinching features were reliable [ICC(2,1)=0.54-0.81]; correlated with standard clinical assessments, including the Nine-Hole Peg Test (9HPT) (|r|=0.26-0.54; 10/13 features), EDSS (|r|=0.25-0.36; 7/13 features), and the arm items of the 29-item Multiple Sclerosis Impact Scale (MSIS-29) (|r|=0.31-0.52; 7/13 features); and differentiated people with MS-Normal from people with MS-Abnormal (area under the curve: 0.68-0.78; 8/13 features). IMU-based features showed similar test-retest reliability [ICC(2,1)=0.47-0.84] but showed little correlations with standard clinical assessments. In contrast, fatigability features (SD aggregation) correlated with 9HPT time (|r|=0.26-0.61; 10/13 features), EDSS (|r|=0.26-0.41; 8/13 features), and MSIS-29 arm items (|r|=0.32-0.46; 7/13 features). Conclusions The Pinching Test provides a remote, objective, and granular assessment of upper extremity function in people with MS that can potentially complement standard clinical evaluation. Future studies will validate it in more advanced MS. Trial Registration ClinicalTrials.gov NCT02952911; https://clinicaltrials.gov/study/NCT02952911


Tables
Table S1.Definitions of Pinching Test features derived from the Pinching Test.

Figure S2 .Figure S3 .
Figure S2.EDSS scores and 9HPT time at baseline and week 24 in PwMS.EDSS scores and 9HPT times were stable throughout the study period.(A) Histogram depicting the change in EDSS from baseline to week 24 (end of study).(B) Scatter plot depicting the EDSS scores at baseline and week 24.For most PwMS (number of PwMS indicated by the size of the "Counts" dot), the change was within 1 point on the EDSS scale (indicated by the red

Figure S4 .Figure S5 .
Figure S4.Cross-sectional Spearman's rank correlations between Pinching Test features and cerebellar as well as pyramidal FSS in PwMS.(A) pinching, (B) IMU-based, and (C-D) fatigability features were correlated against cerebellar and pyramidal FSSs after adjusting for age and sex.Error

Figure S6 .
Figure S6.Relationship between the Pinching Test features.(A) Repeated-measures correlation analysis shows that the Pinching Test features within a single test run are not strongly correlated with each other.
principal component analysis revealed that 6 principal components are necessary to explain approximately 90% of the variance of the pinching features.(C) The loading matrix of the factor analysis further corroborates the notion that the individual pinching features all capture different aspects of upper extremity impairment.Comp.: Component.

(
pinches = number of pinch attempts during the 30 secs of the test Number of successful pinches = number of pinch attempts during the 30 secs of the test that resulted in a successfully pinched tomato shape 2 +z 2 , where x, y, and z are the accelerometer signal in the x, y, and z axis, respectively.The accelerometer magnitude is computed for each time stamp and aggregated for either the entire test SD x 2 +y 2 +z 2 , where x, y, and z are the accelerometer signal in the x, y, and z axis, respectively, and SD is the standard deviation.The accelerometer magnitude is computed for each time stamp and aggregated for either the entire test duration, during the pinching, or during pinch gaps. Kurtosis accelerometer magnitude (entire test/pinch duration/pinch gap) Kurtosis x 2 +y 2 +z 2 , where x, y, and z are the accelerometer signal in the x, y, and z axis, respectively.The accelerometer magnitude is computed for each time stamp and aggregated for either the entire test duration, during the pinching, or during pinch gaps. 2 , where x, y, and z are the accelerometer signal in the x, y, and z axis, respectively, computed for each time stamp.2, where x, y, and z are the accelerometer signal in the x, y, and z axis, respectively, computed for each time stamp, and SD is the standard deviation.IMU: inertial measurement unit; SD: standard deviation.

Table S2 .
Ability of dominant-and nondominant-handed pinching features to differentiate between PwMS with no-to-minimal disability from PwMS with at least mild disability on the cerebellar functional system.a Mann-Whitney U test with FDR correction adjusted for age and sex.
b AUC: area under the curve; FDR: false discovery rate; FSS: functional system score; HC: healthy controls; PwMS: people with multiple sclerosis.

Table S3 .
Ability of dominant-and nondominant-handed pinching features to differentiate between PwMS with no-to-minimal disability from PwMS with at least mild disability on the pyramidal functional system.a This analysis included 18 HC, 53 PwMS with no-to-minimal disability on the pyramidal functional system (pyramidal FSS: ≤2), and 14 PwMS with at least mild disability on the pyramidal functional system (pyramidal FSS: ≥3).b Mann-Whitney U test with FDR correction adjusted for age and sex.AUC: area under the curve; FDR: false discovery rate; FSS: functional system score; HC: healthy controls; PwMS: people with multiple sclerosis. a

Table S4 .
Ability of fatigability features (aggregated by median) to differentiate between PwMS withoutvs PwMS with at least mild levels of fatigue.a a This analysis included 17 PwMS without (FSMC total score <43) and 50 PwMS with at least mild levels of fatigue (FSMC total score ≥43).b Mann-Whitney U test with FDR correction adjusted for age and sex.AUC: area under the curve; FDR: false discovery rate; FSMC: Fatigue Scale for Motor and Cognitive Function; PwMS: people with multiple sclerosis.

Table S5 .
Ability of fatigability features (aggregated by SD) to differentiate between PwMS without vs PwMS with at least mild levels of fatigue.a Mann-Whitney U test with FDR correction adjusted for age and sex.Green background highlights a statistically significant P value at <.05.AUC: area under the curve; FDR: false discovery rate; FSMC: Fatigue Scale for Motor and Cognitive Function; PwMS: people with multiple sclerosis; SD: standard deviation.
a This analysis included 17 PwMS without (FSMC total score <43) and 50 PwMS with at least mild levels of fatigue (FSMC total score ≥43).b

Table S6 .
Overview of test-retest reliability, agreement with standard clinical measures, and ability to differentiate and distinguish PwMS subgroups.