Personalized prediction of rehabilitation outcomes in multiple sclerosis: a proof-of-concept using clinical data, digital health metrics, and machine learning

Background A personalized prediction of upper limb neurorehabilitation outcomes in persons with multiple sclerosis (pwMS) promises to optimize the allocation of therapy and to stratify individuals for resource-demanding clinical trials. Previous research identified predictors on a population level through linear models and clinical data, including conventional assessments describing sensorimotor impairments. The objective of this work was to explore the feasibility of providing an individualized and more accurate prediction of rehabilitation outcomes in pwMS by leveraging non-linear machine learning models, clinical data, and digital health metrics characterizing sensorimotor impairments. Methods Clinical data and digital health metrics were recorded from eleven pwMS undergoing neurorehabilitation. Machine learning models were trained on data recorded pre-intervention. The dependent variables indicated whether a considerable improvement on the activity level was observed across the intervention or not (binary classification), as defined by the Action Research Arm Test (ARAT), Box and Block Test (BBT), or Nine Hole Peg Test (NHPT). Results In a cross-validation, considerable improvements in ARAT or BBT could be accurately predicted (94% balanced accuracy) by only relying on patient master data. Considerable improvements in NHPT could be accurately predicted (89% balanced accuracy), but required knowledge about sensorimotor impairments. Assessing these with digital health metrics instead of conventional scales allowed increasing the balanced accuracy by +17% . Non-linear machine-learning models improved the predictive accuracy for the NHPT by +25% compared to linear models. Conclusions This work demonstrates the feasibility of a personalized prediction of upper limb neurorehabilitation outcomes in pwMS using multi-modal data collected before neurorehabilitation and machine learning. Information from digital health metrics about sensorimotor impairment was necessary to predict changes in dexterous hand control, thereby underlining their potential to provide a more sensitive and fine-grained assessment than conventional scales. Non-linear models outperformed ones, suggesting that the commonly assumed linearity of neurorehabilitation is oversimplified. clinicaltrials.gov registration number: NCT02688231

[1]  Ilse Lamers,et al.  Intensity-dependent clinical effects of an individualized technology-supported task-oriented upper limb training program in Multiple Sclerosis: A pilot randomized controlled trial. , 2019, Multiple sclerosis and related disorders.

[2]  Maura Casadio,et al.  Evaluating upper limb impairments in multiple sclerosis by exposure to different mechanical environments , 2018, Scientific Reports.

[3]  Olivier Lambercy,et al.  The Virtual Peg Insertion Test as an assessment of upper limb coordination in ARSACS patients: A pilot study , 2014, Journal of the Neurological Sciences.

[4]  Gitendra Uswatte,et al.  Phase II Randomized Controlled Trial of Constraint-Induced Movement Therapy in Multiple Sclerosis. Part 2: Effect on White Matter Integrity , 2018, Neurorehabilitation and neural repair.

[5]  D. Hamilton,et al.  Interpreting regression models in clinical outcome studies , 2015, Bone & joint research.

[6]  Stacy L Fritz,et al.  Minimal Detectable Change Scores for the Wolf Motor Function Test , 2009, Neurorehabilitation and neural repair.

[7]  Arja Virtanen,et al.  Effects of aerobic and strength exercise on motor fatigue in men and women with multiple sclerosis: a randomized controlled trial , 2004, Clinical rehabilitation.

[8]  Alan D. Lopez,et al.  The Global Burden of Disease Study , 2003 .

[9]  Leo Breiman,et al.  Classification and Regression Trees , 1984 .

[10]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[11]  Karin Coninx,et al.  The impact of robot-mediated adaptive I-TRAVLE training on impaired upper limb function in chronic stroke and multiple sclerosis , 2018, Disability and rehabilitation. Assistive technology.

[12]  Olivier Lambercy,et al.  Assessment of upper limb motor function in patients with multiple sclerosis using the Virtual Peg Insertion Test: A pilot study , 2013, 2013 IEEE 13th International Conference on Rehabilitation Robotics (ICORR).

[13]  Fary Khan,et al.  Rehabilitation in Multiple Sclerosis: A Systematic Review of Systematic Reviews. , 2017, Archives of physical medicine and rehabilitation.

[14]  Derek K. Jones,et al.  Neuroplasticity and functional recovery in multiple sclerosis , 2012, Nature Reviews Neurology.

[15]  Etienne Burdet,et al.  On the analysis of movement smoothness , 2015, Journal of NeuroEngineering and Rehabilitation.

[16]  Annalisa Barla,et al.  Temporal prediction of multiple sclerosis evolution from patient-centered outcomes , 2017, MLHC.

[17]  C. Stinear,et al.  Prediction of recovery of motor function after stroke , 2010, The Lancet Neurology.

[18]  Daniel Castle,et al.  Using biomarkers to predict clinical outcomes in multiple sclerosis , 2019, Practical Neurology.

[19]  Thierry Keller,et al.  A Systematic Review of International Clinical Guidelines for Rehabilitation of People With Neurological Conditions: What Recommendations Are Made for Upper Limb Assessment? , 2019, Front. Neurol..

[20]  A. Geurts,et al.  Definition dependent properties of the cortical silent period in upper-extremity muscles, a methodological study , 2014, Journal of NeuroEngineering and Rehabilitation.

[21]  T. Platz,et al.  Reliability and validity of arm function assessment with standardized guidelines for the Fugl-Meyer Test, Action Research Arm Test and Box and Block Test: a multicentre study , 2005, Clinical rehabilitation.

[22]  Ilse Lamers,et al.  The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis , 2017, Multiple sclerosis.

[23]  A J Thompson,et al.  Multiple sclerosis: a preliminary study of selected variables affecting rehabilitation outcome , 1999, Multiple sclerosis.

[24]  V. Mathiowetz,et al.  Adult Norms for the Nine Hole Peg Test of Finger Dexterity , 1985 .

[25]  Z. Obermeyer,et al.  Predicting the Future - Big Data, Machine Learning, and Clinical Medicine. , 2016, The New England journal of medicine.

[26]  Anders Odén,et al.  Prediction of outcome in multiple sclerosis based on multivariate models , 1994, Journal of Neurology.

[27]  Marko Munih,et al.  Upper limb motion analysis using haptic interface , 2001 .

[28]  Peter Schuck,et al.  The ‘smallest real difference’ as a measure of sensitivity to change: a critical analysis , 2003, International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation.

[29]  E. Troisi,et al.  Prognostic factors in multidisciplinary rehabilitation treatment in multiple sclerosis: an outcome study , 2005, Multiple sclerosis.

[30]  M. Ferrarin,et al.  Robot Training of Upper Limb in Multiple Sclerosis: Comparing Protocols With or WithoutManipulative Task Components , 2012, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[31]  Joseph Finkelstein,et al.  Factors Affecting Adherence with Telerehabilitation in Patients with Multiple Sclerosis , 2019, ITCH.

[32]  Olivier Lambercy,et al.  A data-driven framework for the selection and validation of digital health metrics: use-case in neurological sensorimotor impairments , 2019 .

[33]  L Turner-Stokes,et al.  Multidisciplinary rehabilitation for adults with multiple sclerosis. , 2007, The Cochrane database of systematic reviews.

[34]  V de Groot,et al.  The usefulness of evaluative outcome measures in patients with multiple sclerosis. , 2006, Brain : a journal of neurology.

[35]  Valentina Squeri,et al.  Adaptive robot training for the treatment of incoordination in Multiple Sclerosis , 2010, Journal of NeuroEngineering and Rehabilitation.

[36]  Annalisa Barla,et al.  The hidden information in patient-reported outcomes and clinician-assessed outcomes: multiple sclerosis as a proof of concept of a machine learning approach , 2019, Neurological Sciences.

[37]  B. Lakhani,et al.  Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis , 2016, Behavioural Brain Research SreeTestContent1.

[38]  Maria Paola Canevini,et al.  Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes , 2019, Front. Neurol..

[39]  Valentina Tomassini,et al.  Neuroplasticity and Motor Rehabilitation in Multiple Sclerosis , 2015, Front. Neurol..

[40]  Lynn D. Hudson,et al.  Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis , 2017, Multiple sclerosis.

[41]  V. Mathiowetz,et al.  Adult norms for the Box and Block Test of manual dexterity. , 1985, The American journal of occupational therapy : official publication of the American Occupational Therapy Association.

[42]  Allen Walter Heinemann,et al.  Prediction of adolescent injury risk awareness , 1994 .

[43]  Roger Tam,et al.  Machine learning in secondary progressive multiple sclerosis: an improved predictive model for short-term disability progression , 2019, Multiple sclerosis journal - experimental, translational and clinical.

[44]  Doina Precup,et al.  Prediction of Disease Progression in Multiple Sclerosis Patients using Deep Learning Analysis of MRI Data , 2019, MIDL.

[45]  Ilse Lamers,et al.  Upper limb assessment in multiple sclerosis: a systematic review of outcome measures and their psychometric properties. , 2014, Archives of physical medicine and rehabilitation.

[46]  K. Borgwardt,et al.  Machine Learning in Medicine , 2015, Mach. Learn. under Resour. Constraints Vol. 3.

[47]  Dagmar Sternad,et al.  Sensitivity of Smoothness Measures to Movement Duration, Amplitude, and Arrests , 2009, Journal of motor behavior.

[48]  R. Gassert,et al.  Upper limb assessment using a Virtual Peg Insertion Test , 2011, 2011 IEEE International Conference on Rehabilitation Robotics.

[49]  K. Roy,et al.  Be aware of error measures. Further studies on validation of predictive QSAR models , 2016 .

[50]  W. Byblow,et al.  Functional potential in chronic stroke patients depends on corticospinal tract integrity. , 2006, Brain : a journal of neurology.

[51]  Kimatha Oxford Grice,et al.  Adult norms for a commercially available Nine Hole Peg Test for finger dexterity. , 2003, The American journal of occupational therapy : official publication of the American Occupational Therapy Association.

[52]  W. Byblow,et al.  Prediction Tools for Stroke Rehabilitation. , 2019, Stroke.

[53]  J M Linacre,et al.  Prediction of rehabilitation outcomes with disability measures. , 1994, Archives of physical medicine and rehabilitation.

[54]  G. Demeurisse,et al.  [Motor evaluation in vascular hemiplegia]. , 1979, Bruxelles medical.

[55]  Alan J. Thompson,et al.  Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity , 2014, Neurology.

[56]  Olivier Lambercy,et al.  Systematic Review on Kinematic Assessments of Upper Limb Movements After Stroke , 2019, Stroke.

[57]  Matthew Petoe,et al.  The PREP algorithm predicts potential for upper limb recovery after stroke. , 2012, Brain : a journal of neurology.

[58]  J. Krakauer,et al.  Computational neurorehabilitation: modeling plasticity and learning to predict recovery , 2016, Journal of NeuroEngineering and Rehabilitation.

[59]  N. Yozbatiran,et al.  Motor assessment of upper extremity function and its relation with fatigue, cognitive function and quality of life in multiple sclerosis patients , 2006, Journal of the Neurological Sciences.

[60]  J. Bell-Krotoski,et al.  The repeatability of testing with Semmes-Weinstein monofilaments. , 1987, The Journal of hand surgery.

[61]  Fary Khan,et al.  Rehabilitation interventions in multiple sclerosis: an overview , 2012, Journal of Neurology.

[62]  Robert C Reiner,et al.  Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 , 2019, The Lancet Neurology.

[63]  Ilaria Carpinella,et al.  Quantitative assessment of upper limb motor function in Multiple Sclerosis using an instrumented Action Research Arm Test , 2014, Journal of NeuroEngineering and Rehabilitation.

[64]  Jaana Paltamaa,et al.  Measuring Deterioration in International Classification of Functioning Domains of People With Multiple Sclerosis Who Are Ambulatory , 2008, Physical Therapy.

[65]  Guigang Zhang,et al.  Deep Learning , 2016, Int. J. Semantic Comput..