Digital biomarkers can highlight subtle clinical differences in radiologically isolated syndrome compared to healthy con
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Digital biomarkers can highlight subtle clinical differences in radiologically isolated syndrome compared to healthy controls Mikael Cohen1 · Lydiane Mondot2 · Salim Fakir1 · Cassandre Landes1 · Christine Lebrun1 Received: 26 June 2020 / Revised: 12 October 2020 / Accepted: 13 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Objective To explore the use of digital biomarkers to distinguish healthy controls (HC) from subjects with a radiologically isolated syndrome (RIS). Methods We developed a smartphone application called MS Screen Test (MSST) to explore several dimensions of the neurological exam such as finger tapping speed, agility, hand synchronization, low contrast vision and cognition during a short evaluation. This app was tested on a cohort of healthy volunteers including a subset of subjects who underwent two evaluations on the same day to assess reproducibility. In a second step, the app was tested on a cohort of RIS subjects. Performances of RIS subjects were compared with age and genre-matched HC. Results HC underwent two consecutive evaluations on MSST. The analysis showed good reproducibility for all measures. Then 21 RIS subjects were compared to 32 matched HC. Compared to HC, we found that RIS subjects had a lower finger tapping speed on the dominant hand (5.6 versus 6.5 taps per second; p = 0.005), a longer inter hand interval during the hand synchronization task (14.4 versus 11.3 ms; p = 0.03) and significantly poorer scores on the low contrast vision and cognition tests. Conclusion MSST only requires a smartphone to obtain digital biomarkers relative to several dimensions of the neurological examination. Our results highlighted subtle differences between HC and RIS subjects. We plan to evaluate this tool in MS patients, which will allow us to get a much larger sample of subjects, to determine whether digital biomarkers can predict disease course. Keywords RIS · Multiple sclerosis · Digital biomarkers
Introduction Radiologically isolated syndrome (RIS) is a rare entity that is defined by the incidental finding of lesions suggestive of multiple sclerosis (MS) on brain MRI in subjects who required a scan for another reason such as headaches or traumatic brain injury.
* Mikael Cohen cohen.m@chu‑nice.fr 1
Service de Neurologie, CRC SEP, Unité de Recherche Clinique Cote D’Azur (UR2CA-URRIS), Centre Hospitalier Universitaire Pasteur 2, 30 Voie Romaine, 06002 Nice, Cedex, France
Service de Radiologie, Unité de Recherche Clinique Cote D’Azur (UR2CA - URRIS), Centre Hospitalier Universitaire Pasteur 2, 30 Voie Romaine, 06002 Nice, Cedex, France
2
The first cohort was reported in 2008 [1] and diagnostic criteria were proposed in 2009 by Okuda and al [2]. Confirmation of RIS implies that the individual never had any history consistent with central nervous system demyelination. The neurological exam has to be normal and MRI needs to fulfill dissemination in space criteria derived from lesions size, shape, and location. Follow-up of
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