PMID- 34719076 OWN - NLM STAT- MEDLINE DCOM- 20220404 LR - 20220731 IS - 1468-1331 (Electronic) IS - 1351-5101 (Print) IS - 1351-5101 (Linking) VI - 29 IP - 2 DP - 2022 Feb TI - Smartphone-derived keystroke dynamics are sensitive to relevant changes in multiple sclerosis. PG - 522-534 LID - 10.1111/ene.15162 [doi] AB - BACKGROUND: To investigate smartphone keystroke dynamics (KD), derived from regular typing, on sensitivity to relevant change in disease activity, fatigue, and clinical disability in multiple sclerosis (MS). METHODS: Preplanned interim analysis of a cohort study with 102 MS patients assessed at baseline and 3-month follow-up for gadolinium-enhancing lesions on magnetic resonance imaging, relapses, fatigue and clinical disability outcomes. Keyboard interactions were unobtrusively collected during typing using the Neurokeys App. From these interactions 15 keystroke features were derived and aggregated using 16 summary and time series statistics. Responsiveness of KD to clinical anchor-based change was assessed by calculating the area under the receiver operating characteristic curve (AUC). The optimal cut-point was used to determine the minimal clinically important difference (MCID) and compared to the smallest real change (SRC). Commonly used clinical measures were analyzed for comparison. RESULTS: A total of 94 patients completed the follow-up. The five best performing keystroke features had AUC-values in the range 0.72-0.78 for change in gadolinium-enhancing lesions, 0.67-0.70 for the Checklist Individual Strength Fatigue subscale, 0.66-0.79 for the Expanded Disability Status Scale, 0.69-0.73 for the Ambulation Functional System, and 0.72-0.75 for Arm function in MS Questionnaire. The MCID of these features exceeded the SRC on group level. KD had higher AUC-values than comparative clinical measures for the study outcomes, aside from ambulatory function. CONCLUSIONS: Keystroke dynamics demonstrated good responsiveness to changes in disease activity, fatigue, and clinical disability in MS, and detected important change beyond measurement error on group level. Responsiveness of KD was better than commonly used clinical measures. CI - (c) 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. FAU - Lam, Ka-Hoo AU - Lam KH AUID- ORCID: 0000-0003-0926-1445 AD - Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. FAU - Twose, James AU - Twose J AD - Neurocast B.V., Amsterdam, The Netherlands. FAU - McConchie, Hannah AU - McConchie H AUID- ORCID: 0000-0002-6422-4447 AD - Neurocast B.V., Amsterdam, The Netherlands. FAU - Licitra, Giovanni AU - Licitra G AD - Neurocast B.V., Amsterdam, The Netherlands. FAU - Meijer, Kim AU - Meijer K AD - Neurocast B.V., Amsterdam, The Netherlands. FAU - de Ruiter, Lodewijk AU - de Ruiter L AD - Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. FAU - van Lierop, Zoe AU - van Lierop Z AD - Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. FAU - Moraal, Bastiaan AU - Moraal B AD - Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. FAU - Barkhof, Frederik AU - Barkhof F AD - Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. AD - Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, UK. FAU - Uitdehaag, Bernard AU - Uitdehaag B AD - Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. FAU - de Groot, Vincent AU - de Groot V AD - Department of Rehabilitation Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. FAU - Killestein, Joep AU - Killestein J AD - Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211114 PL - England TA - Eur J Neurol JT - European journal of neurology JID - 9506311 SB - IM MH - Cohort Studies MH - Disability Evaluation MH - Humans MH - Minimal Clinically Important Difference MH - *Multiple Sclerosis/diagnostic imaging MH - ROC Curve MH - Smartphone PMC - PMC9299491 OTO - NOTNLM OT - ROC curve OT - biometry OT - multiple sclerosis OT - pattern recognition OT - physiological OT - smartphone COIS- K.H. Lam has no conflicts of interest. J. Twose, H. McConchie, G. Licitra, and K.A. Meijer are employees of Neurocast B.V. (industry partner). L.R.J. de Ruiter, Z.Y.G.J. van Lierop, and B. Moraal have no conflicts of interest. F. Barkhof acts as a consultant to Biogen-Idec, Bayer-Schering, Merck-Serono, Roche, Novartis, IXICO, and Combinostics. He has received sponsorship from EU-H2020, NWO, SMSR, EU-FP7, Novartis, and GE Healthcare. He is on the editorial boards of Radiology, Neuroradiology, Multiple Sclerosis Journal, and Neurology. He is supported by the NIHR Biomedical Research Center at UCLH. B.M.J. Uitdehaag received consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, and Teva. V. de Groot has no conflicts of interest. J. Killestein has accepted speaker and consultancy fees from Merck, Biogen, Teva, Genzyme, Roche, and Novartis. EDAT- 2021/11/01 06:00 MHDA- 2022/04/05 06:00 PMCR- 2022/07/20 CRDT- 2021/10/31 21:31 PHST- 2021/09/25 00:00 [received] PHST- 2021/10/24 00:00 [accepted] PHST- 2021/11/01 06:00 [pubmed] PHST- 2022/04/05 06:00 [medline] PHST- 2021/10/31 21:31 [entrez] PHST- 2022/07/20 00:00 [pmc-release] AID - ENE15162 [pii] AID - 10.1111/ene.15162 [doi] PST - ppublish SO - Eur J Neurol. 2022 Feb;29(2):522-534. doi: 10.1111/ene.15162. Epub 2021 Nov 14.