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Currently submitted to: JMIR mHealth and uHealth

Date Submitted: May 12, 2026
Open Peer Review Period: May 12, 2026 - Jul 7, 2026
(currently open for review)

Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.

Smartphone Keystroke Monitoring to Predict Progression Independent of Relapse in Multiple Sclerosis: A machine-learning-based evaluation

  • Juan Luis Chico-Garcia; 
  • Raquel Sainz-Amo; 
  • Enric Monreal; 
  • Susana Sainz de la Maza; 
  • Fernando Rodriguez-Jorge; 
  • Alberto Nogales; 
  • Jaime Masjuan; 
  • Lucienne Costa-Frossard; 
  • Luisa Maria Villar

ABSTRACT

Background:

Progression independent of relapse activity (PIRA) is a major driver of long-term disability in multiple sclerosis (MS), yet its diagnosis remains retrospective, delaying treatment adaptation. Objective, real-time tools to anticipate PIRA are lacking.

Objective:

This study aimed to identify the most effective machine-learning model for PIRA prediction using passively acquired smartphone data and to evaluate its diagnostic performance.

Methods:

We conducted a prospective observational cohort study at a single MS center (November 2021–January 2024). Adults (≥18 years) with confirmed MS, compatible smartphone use, and ≥12 months follow-up were included. A custom mobile application continuously captured typing dynamics, extracting tapping speed as a digital biomarker. Time-series were analyzed using mixed linear regression and ARIMA models. Longitudinal data were transformed into a supervised learning dataset by segmenting the time series into overlapping temporal windows, each treated as an independent sample. The dataset was split into training, validation, and test sets (70/15/15) to develop and evaluate machine-learning models (XGBoost, TimesNet, and Transformers). The primary outcome was prediction of a clinically confirmed PIRA event.

Results:

Ninety-nine patients (median age 47 years, 63% women, median Expanded Disability Status Scale 2.5) completed follow-up; 14 developed PIRA. Baseline characteristics were comparable between groups. Time-series decomposition revealed distinct dynamics (Akaike Information Criterion [AIC]: 69.7 vs 108.0) between patients who developed PIRA and those who did not. A total of 25,440 temporal windows were generated. Among all models, TimesNet achieved the best performance, with accuracy 99.7%, precision 97% (95% CI 94–99), sensitivity 100% (95% CI 95–100), specificity 100% (95% CI 96–100), and F1-score 98%.

Conclusions:

Passive smartphone monitoring enables continuous assessment of motor function in MS. TimesNet outperformed other models for early PIRA detection, supporting its potential as a digital biomarker of progression risk. These findings warrant prospective multicenter validation for individualized disease monitoring.


 Citation

Please cite as:

Chico-Garcia JL, Sainz-Amo R, Monreal E, Sainz de la Maza S, Rodriguez-Jorge F, Nogales A, Masjuan J, Costa-Frossard L, Villar LM

Smartphone Keystroke Monitoring to Predict Progression Independent of Relapse in Multiple Sclerosis: A machine-learning-based evaluation

JMIR Preprints. 12/05/2026:100014

DOI: 10.2196/preprints.100014

URL: https://preprints.jmir.org/preprint/100014

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