Autonomic dysfunction and exercise intolerance in concussion: a scoping review.

PURPOSE: Concussion commonly results in exercise intolerance, often limiting return to activities. Improved understanding of the underlying mechanisms of post-concussive exercise intolerance could help guide mechanism-directed rehabilitation approaches. Signs of altered cardiovascular autonomic regulation-a potential contributor to exercise intolerance-have been reported following concussion, although it is not clear how these findings inform underlying mechanisms of post-concussive symptoms. Systematic summarization and synthesis of prior work is needed to best understand current evidence, allowing identification of common themes and gaps requiring further study. The purpose of this review was to (1) summarize published data linking exercise intolerance to autonomic dysfunction, and (2) summarize key findings, highlighting opportunities for future investigation. METHODS: The protocol was developed a priori, and conducted in five stages; results were collated, summarized, and reported according to PRISMA guidelines. Studies including injuries classified as mild traumatic brain injury (mTBI)/concussion, regardless of mechanism of injury, were included. Studies were required to include both autonomic and exercise intolerance testing. Exclusion criteria included confounding central or peripheral nervous system dysfunction beyond those stemming from the concussion, animal model studies, and case reports. RESULTS: A total of 3116 publications were screened; 17 were included in the final review. CONCLUSION: There was wide variability in approach to autonomic/exercise tolerance testing, as well as inclusion criteria/testing timelines, which limited comparisons across studies. The reviewed studies support current clinical suspicion of autonomic dysfunction as an important component of exercise intolerance. However, the specific mechanisms of impairment and relationship to symptoms and recovery require additional investigation.

Use of a Home-Based, Commercial Exercise Platform to Remotely Monitor Aerobic Exercise Adherence and Intensity in People With Parkinson Disease.

OBJECTIVE: Physical therapists are well-positioned to prescribe exercise outside of a clinical setting to promote positive health behaviors in people with Parkinson disease (PD). Traditionally, a barrier to precise exercise prescription has been reliance on participant self-reported exercise adherence and intensity. Home-based, commercially available exercise platforms offer an opportunity to remotely monitor exercise behavior and facilitate adherence based on objective performance metrics. The primary aim of this project was to characterize the feasibility and processes of remote aerobic exercise data monitoring from a home-based, commercially available platform in individuals participating in the 12-month Cyclical Lower Extremity Exercise for PD II (CYCLE-II) randomized clinical trial. Secondary aims focused on using exercise behavior to classify the cohort into exercise archetypes and describing a shared decision-making process to facilitate exercise adherence. METHODS: Data from each exercise session were extracted, visualized, and filtered to ensure ride integrity. Weekly exercise frequency was used to determine exercise archetypes: Adherent (2-4 exercise sessions per week), Over-adherent (>4 exercise sessions per week), and Under-adherent (<2 exercise sessions per week). RESULTS: A total of 123 people with PD completed 22,000+ exercise sessions. Analysis of exercise frequency indicated that 79% of participants were adherent; 8% were over-adherent; and 13% were under-adherent. Three case reports illustrate how shared decision-making with the use of exercise performance data points guided exercise prescription. CONCLUSIONS: The number of exercise sessions and completeness of the data indicate that people with PD were able to utilize a commercial, home-based exercise platform to successfully engage in long-term aerobic exercise. Physical therapists can use objective data as a part of a shared decision-making process to facilitate exercise adherence. IMPACT: Commercially available exercise platforms offer a unique approach for physical therapists to monitor exercise behavior outside of a clinical setting. The methods used in this project can serve as a roadmap to utilizing data from consumer-based platforms.

Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease.

BACKGROUND: An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD. OBJECTIVE: To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications. METHODS: We performed secondary analyses of heart rate and blood pressure data from the Study in Parkinson's Disease of Exercise (SPARX). RESULTS: 128 individuals were enrolled into SPARX (63.7±9.3 years; 57.0% male, 0.4 years since diagnosis [median]). 103 individuals were not taking chronotropic medications, of which 90 had a normal maximal heart rate response to exercise testing (155.3±14.0 bpm; PDnon-chrono) and 13 showed evidence of chronotropic incompetence (121.3±11.3 bpm; PDchrono, p < 0.05). PDchrono had decreased VO2peak compared to PDnon-chrono (19.7±4.5 mL/kg/min and 24.3±5.8 mL/kg/min, respectively, p = 0.027). There was a positive correlation between peak heart rate during exercise and the change in systolic blood pressure from supine to standing (r = 0.365, p < 0.001). CONCLUSIONS: A subgroup of individuals with early PD not on dopaminergic medication had chronotropic incompetence and decreased VO2peak, which may be related to autonomic dysfunction. Evaluation of both heart rate responses to incremental exercise and orthostatic vital signs may serve as biomarkers of early autonomic impairment and guide treatment. Further studies should investigate whether cardiovascular autonomic dysfunction affects the ability to exercise and whether exercise training improves autonomic dysfunction.

Study in Parkinson's disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial.

BACKGROUND: To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline. METHODS: This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60-65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80-85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity. DISCUSSION: SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health. TRIAL REGISTRATION: ClinicalTrials.gov NCT04284436 . Registered on February 25, 2020.

Effectiveness of a Long-Term, Home-Based Aerobic Exercise Intervention on Slowing the Progression of Parkinson Disease: Design of the Cyclical Lower Extremity Exercise for Parkinson Disease II (CYCLE-II) Study.

OBJECTIVE: Previous short duration studies have demonstrated that high-intensity aerobic exercise improves aspects of motor and non-motor function in people with Parkinson disease (PwPD); however, the effectiveness of a long-term exercise intervention on slowing disease progression is unknown. The primary aim of this study is to determine the disease-altering effects of high-intensity aerobic exercise, administered on an upright stationary cycle, on the progression of PD. A secondary aim is to develop a prognostic model for 12-month changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) of PwPD undergoing an aerobic exercise intervention. METHODS: This pragmatic, multisite, single-rater blinded, randomized controlled trial will recruit PwPD from 2 large, urban, academic medical centers. Participants (N = 250 PwPD) will be randomized to (1) home-based aerobic exercise or (2) usual and customary care. Those in the aerobic exercise arm will be asked to complete in-home aerobic exercise sessions at 60% to 80% of heart rate reserve 3 times per week for 12 months utilizing a commercially available upright exercise cycle. The usual and customary care group will continue normal activity levels. Daily activity will be monitored for both groups throughout the 12-month study period. The primary outcome, both to assess disease-modifying response to aerobic exercise and for prognostic modeling in the aerobic exercise arm, is 12-month rate of change in the MDS-UPDRS III. Clinical and biomechanical measures will also be used to assess upper and lower extremity motor function as well as non-motor functions. IMPACT: Should long-term aerobic exercise demonstrate disease-modifying capability, this study will provide evidence that "Exercise is Medicine" for PwPD. Further, the derived prognostic model will inform a patient-specific exercise prescription for PwPD and expected effects on PD progression.