Quantifying the effect of amyotrophic lateral sclerosis on the neural and non-neural properties of the wrist

Abstract

Amyotrophic lateral sclerosis (ALS) is themost frequent form of motor neuron diseases (MND). This neurodegenerativedisease progresses relentlessly quick. The characteristic feature of ALS is theconcurrent degeneration of the upper and lower motoneurons (UMN & LMN) inthe central and peripheral nervous system. Symptomatic behavior in ALS is theresult of complex symptom interplay, as well as symptom counteraction. Therefore,adequate examination of motor function in ALS requires an examination techniquethat quantifies disease symptoms at their origin, rather than at their point ofexpression. The goal of this study was to quantify and explore the effect ofALS on intrinsic and reflexive properties of the limbs of the patients underpassive and active conditions. To the best of our knowledge, this study was thefirst to assess a MND within this particular framework. A group of10 ALS patients and 9 controls were recruited for participation in an extensiveprotocol, comprising of several motor tasks and maximal voluntary contractionmeasurements. The tasks were performed on a single-axis wrist manipulator,which produced multisine torque perturbations. A linear system identificationand parameter estimation procedure was implemented to estimate the parametersof a neuromuscular model with 5 task-dependent (2 intrinsic, 3 reflexive) and 8task-independent parameters. Allparticipants were able to fully comply with the study protocol and indicatedthat the effort required for the tasks was easily maintained. Variance of theintrinsic parameters was generally increased in the patient group, with atendency towards a reduced median. The median of the reflexive parameter musclespindle position dependence was significantly increased in ALS patients during arelax task. Additionally, reflexive and intrinsic parameters of individual patientswere frequently found to be responsive to the patients respective clinicalstate. Muscle stiffness during the relax task was strongly correlated to thesummed average EMG in ALS patients (r = 0.75, p = 0.013). During active tasks,three main control strategies were derived from the intrinsic and reflexiveparameters in patients. We showthat our study protocol is viable for examination of ALS patients within alarge range of physical capacity. The use of quantitative parameters allowed usto disentangle fundamentally overlapping UMN and LMN symptoms. The derivedparameters were shown to enhance clinical scores within their respective clinicaldefinitions. Lastly, our results offer new insights beyond the current clinicalknowledge of motor function under active conditions in ALS.