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Session: NeuroMuscular
Session starts: Thursday 26 January, 14:30
Presentation starts: 15:00
Room: Room 530

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Diederik Stikvoort (University Medical Center Utrecht)
Just Plouvier (Delft University of Technology)
Boudewijn Sleutjes (University Medical Center Utrecht)
Stephan Goedee (University Medical Center Utrecht)
Winfred Mugge (Delft University of Technology)
Alfred Schouten (Delft University of Technology)
Frans van der Helm (Delft University of Technology)
Leonard van den Berg (University Medical Center Utrecht)

Abstract:
Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disorder with ultimately fatal consequences. The expression of symptoms is highly heterogeneous, with large variation in degeneration rates of both upper and lower motor neurons (UMN, LMN)1. As a result, symptomatic motor behavior in ALS originates from a complex interplay of central and peripheral symptoms, including hyperreflexia, spasticity, rigidity and weakness2. UMN symptoms can be particularly hard to detect due to degeneration of all classes of motor neurons in the anterior horn of the spinal cord2. Secondary changes in muscles and connective tissue further alter the limb’s dynamics and the ensuing reflexive behavior3. Here, we present a protocol to quantify wrist neuromuscular control of ALS patients in order to explore their associations with the clinical manifestation of the disease. We plan to recruit 20 ALS patients, excluding participants with a muscle strength of the wrist muscles below an MRC of 3 (Medical Research Council scale, 0-5), presence of active psychiatric diseases such as frontotemporal dementia, concomitant neuropathy, history or presence of brain injury or other cerebral diseases. Reference data will be derived from age-gender matched controls. Wrist perturbations and closed-loop system-identification techniques will be employed to estimate the neuromuscular control of the wrist joint. Participants will perform multiple tasks while supplemented with unpredictable multisine torque perturbations, using a robotic manipulator, to elicit a wide range of neuromuscular control as previously described4¬. Parameterization of the wrist-dynamics using a neuromuscular model provides metrics describing the contribution of muscle- and reflex-dynamics to the observed motor behavior. Clinical metrics will be obtained, including muscle tone of the arm, reflex score of the examined arm, revised ALS Functional Rating Scale score (ALSFRS-R) and the fine motor function subscore (ALSFRS-R items 4-6). Comparable patterns of change in neuromuscular control will be identified through hierarchical clustering of the neuromuscular parameters. The clinical characteristics of these clusters will subsequently be compared. This study is the first to explore neuromuscular control in ALS with neuromuscular modeling and system-identification techniques. Quantifying changes related to UMN degeneration may be particularly useful for following disease progression in a clinical or clinical trial setting. 1. van Es MA, et al.. Amyotrophic lateral sclerosis. Lancet 2017;390(10107):2084-2098. 2. Swash M. Why are upper motor neuron signs difficult to elicit in amyotrophic lateral sclerosis? Journal of neurology, neurosurgery, and psychiatry 2012;83(6):659-662. 3. Kamper DG, Schmit BD, Rymer WZ. Effect of muscle biomechanics on the quantification of spasticity. Ann Biomed Eng 2001;29(12):1122-1134. 4. Mugge W, et al.. A rigorous model of reflex function indicates that position and force feedback are flexibly tuned to position and force tasks. Experimental Brain Research 2010;200(3-4):325-340.