Shaping the Future of Neurological Wilson’s Disease Assessment and Monitoring with Novel Digital Biomarkers
Michaela Pernon1, Chloé Laurencin2, Grégoire Lafay3, Loïc Carment3, Kenza Drareni3, Clémence Faulcon3, Arthur Feyt3, Clarissa Gorin3, Saad Zinaï3, Emilie Guilpain3, Aurélia Poujois1
1Department of Neurology, Rothschild Foundation Hospital, Paris, France, National Reference Center for Wilson's Disease and Other Copper-Related Rare Diseases, Rothschild Foundation Hospital, Paris, France, 2Department of Neurology, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France, National Reference Center for Wilson's Disease and Other Copper-Related Rare Diseases, Femme Mère Enfant Hospital (HFME-GHE), Hospices Civils de Lyon, Bron, France, 3Ad Scientiam, Paris, France
Objective:
Defining new digital biomarkers (dBMKs) allowing a comprehensive assessment and monitoring of neurological Wilson’s disease (NWD) to bridge the existing practice gaps.
Background:
Neurological features of Wilson’s disease include dysarthria, tremor, gait, balance and postural control impairments. Patients often experience concomitant manifestations that may change over time, hampering their assessment and management. Accurate assessment of the phenotypic presentation of NWD and treatment response is crucial for appropriate care management. Current evaluation using the Unified Wilson's Disease Rating Scale is primarily qualitative, time-consuming and exhibits several limitations necessitating objective measurements of patients' neurological functional status. Other neurological scales inadequately capture the broad-spectrum of NWD symptoms.
Design/Methods:
A double-diamond methodology was used to narrow down the key health concepts to be addressed in NWD and identify their related candidate dBMKs, captured using smartphone’s sensors. To support this approach, an extensive literature review and 19 research sessions with Wilson’s disease experts were conducted.
Results:
Dysarthria, tremor and gait & balance impairments were identified as key health concepts to objectively track and monitor; 50 candidate dBMKs were specified accordingly. Breaking down dysarthria into six dimensions, namely: vocal quality, pneumo-phonatory control, articulatory precision, prosody, hypernasality and intelligibility, seemed critical to pinpoint possible predominant subtypes. DBMKs were specified to characterize each dimension.
DBMKs were also identified to objectively typify action, rest and postural tremor.
Finally, dBMKs were defined for the comprehensive and objective characterization of gait and balance impairments (parkinsonian/ dystonic/ ataxic gait, falls, balance weakness and impaired postural control).
Conclusions:
Initial results showed that using dBMKs for accurate phenotypic classification and longitudinal monitoring of NWD, is both feasible and of medical interest. Clinical validation is needed to establish dBMKs as the future gold standards for NWD assessment and monitoring, overcoming neurological scales limitations.