Motor Dysfunction in REM Sleep Behavior Disorder: A Rehabilitation Framework for Prodromal Synucleinopathy

Abstract

Parkinson disease (PD) and other related diseases with α-synuclein pathology are associated with a long prodromal or preclinical stage of disease. Predictive models based on diagnosis of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) make it possible to identify people in the prodromal stage of synucleinopathy who have a high probability of future disease and provide an opportunity to implement neuroprotective therapies. However, rehabilitation providers may be unaware of iRBD and the motor abnormalities that indicate early motor system dysfunction related to α-synuclein pathology. Furthermore, there is no existing rehabilitation framework to guide early interventions for people with iRBD. The purpose of this work is to (1) review extrapyramidal signs of motor system dysfunction in people with iRBD and (2) propose a framework for early protective or preventive therapies in prodromal synucleinopathy using iRBD as a predictive marker. Longitudinal and cross-sectional studies indicate that the earliest emerging motor deficits in iRBD are bradykinesia, deficits performing activities of daily living, and abnormalities in speech, gait, and posture. These deficits may emerge up to 12 years before a diagnosis of synucleinopathy. The proposed rehabilitation framework for iRBD includes early exercise-based interventions of aerobic exercise, progressive resistance training, and multimodal exercise with rehabilitation consultations to address exercise prescription, progression, and monitoring. This rehabilitation framework may be used to implement neuroprotective, multidisciplinary, and proactive clinical care in people with a high likelihood of conversion to PD, dementia with Lewy bodies, or multiple systems atrophy.

Keywords: Parkinson disease; exercise; prodromal; rehabilitation; sleep disorders; α-synuclein.

Figure 1.

Estimated lead time of prodromal markers. Lead times for non-motor and motor signs are approximated from data found in Postuma 2012 and Fereshtehnejad et al. 2019. Limb bradykinesia lead time marked using quantitative data. Time in years refers to the prodromal stage with time point zero being the time of phenoconversion to an overt alpha-synucleinopathy such as Parkinson’s disease, dementia with Lewy bodies or multiple systems atrophy.