Exercise Intolerance After Mild Traumatic Brain Injury Occurs in All Subtypes in the Adult Population.

Thematically grouped symptom clusters are present during the acute timeline of post-mild traumatic brain injuries (mTBI), representing clinical profiles called subtypes. Exercise intolerance has not been evaluated within the subtype classifications and, because guidelines support early submaximal aerobic exercise, further knowledge is required in regard to the exercise capabilities among the concussion subtypes. This cross-sectional study (n = 78) aimed to characterize the presence of exercise intolerance within the clinical subtypes and to explore performance on the Buffalo Concussion Treadmill Test (BCTT) in the adult subacute (2-12 weeks post-injury) mTBI population. All participants were evaluated using the BCTT to determine exercise tolerance. We first used the Neurobehavioral Symptom Inventory (NSI) questionnaire to assign each participant a primary subtype(s). To further explore all five subtypes (headache, cognitive, vestibular, ocular motor, and mood), participants were assessed using a multitude of thematically grouped assessments including self-reported questionnaires, clinical tests of vestibular and ocular motor function, balance function, and computerized cognitive testing. Thirty-seven (47%) subjects were exercise tolerant and 41 (53%) were exercise intolerant. There was no difference in the distribution of primary subtypes between the exercise tolerant and exercise intolerant groups. In addition, no significant differences were found between the exercise tolerant and exercise intolerant groups on other thematically grouped subtype assessments. The exercise intolerant group had a significantly higher resting heart rate (HR), lower percentage of age-predicted maximum HR achieved, lower Borg Rate of Perceived Exertion (RPE), and could walk on the treadmill for less time (lower duration) compared with the exercise tolerant group. The current findings suggest that exercise intolerance is common and pervasive across all five mTBI subtypes. A comprehensive mTBI assessment should include evaluation for exercise intolerance regardless of the primary clustering of symptoms and across patient populations. Therefore, early referral to physical therapists, athletic trainers, or medical clinics that can perform the BCTT may be helpful to initiate appropriate exercise prescriptions for patients with mTBI.

Assessing the Effects of Mild Traumatic Brain Injury on Vestibular Home Exercise Performance with Wearable Sensors.

After a mild traumatic brain injury (mTBI), dizziness and balance problems are frequently reported, affecting individuals' daily lives and functioning. Vestibular rehabilitation is a standard treatment approach for addressing these issues, but its efficacy in this population remains inconclusive. A potential reason for suboptimal outcomes is the lack of objective monitoring of exercise performance, which is crucial for therapeutic success. This study utilized wearable inertial measurement units (IMUs) to quantify exercise performance in individuals with mTBI during home-based vestibular rehabilitation exercises. Seventy-three people with mTBI and fifty healthy controls were enrolled. Vestibular exercises were performed, and IMUs measured forehead and sternum velocities and range of motions. The mTBI group demonstrated a slower forehead peak angular velocity in all exercises, which may be a compensatory strategy to manage balance issues or symptom exacerbation. Additionally, the mTBI group exhibited a larger forehead range of motion during specific exercises, potentially linked to proprioceptive deficits. These findings emphasize the usefulness of utilizing IMUs to monitor the quality of home-based vestibular exercises for individuals with mTBI and the potential for IMUs improving rehabilitation outcomes.

Balance telerehabilitation and wearable technology for people with Parkinson's disease (TelePD trial).

BACKGROUND: Balance impairments, that lead to falls, are one of the main symptoms of Parkinson's disease (PD). Telerehabilitation is becoming more common for people with PD; however, balance is particularly challenging to assess and treat virtually. The feasibility and efficacy of virtual assessment and virtual treatment of balance in people with PD are unknown. The present study protocol has three aims: I) to determine if a virtual balance and gait assessment (instrumented L-shape mobility test) with wearable sensors can predict a gold-standard, in-person clinical assessment of balance, the Mini Balance Evaluation Systems Test (Mini-BESTest); II) to explore the effects of 12 sessions of balance telerehabilitation and unsupervised home exercises on balance, gait, executive function, and clinical scales; and III) to explore if improvements after balance telerehabilitation transfer to daily-life mobility, as measured by instrumented socks with inertial sensors worn for 7 days. METHODS: The TelePD Trial is a prospective, single-center, parallel-group, single-blind, pilot, randomized, controlled trial. This trial will enroll 80 eligible people with PD. Participants will be randomized at a 1:1 ratio into receiving home-based balance exercises in either: 1) balance telerehabilitation (experimental group, n = 40) or 2) unsupervised exercises (control group, n = 40). Both groups will perform 12 sessions of exercise at home that are 60 min long. The primary outcome will be Mini-BESTest. The secondary outcomes will be upper and lower body gait metrics from a prescribed task (instrumented L-shape mobility test); daily-life mobility measures over 7 days with wearable sensors in socks, instrumented executive function tests, and clinical scales. Baseline testing and 7 days of daily-life mobility measurement will occur before and after the intervention period. CONCLUSION: The TelePD Trial will be the first to explore the usefulness of using wearable sensor-based measures of balance and gait remotely to assess balance, the feasibility and efficacy of balance telerehabilitation in people with PD, and the translation of balance improvements after telerehabilitation to daily-life mobility. These results will help to develop a more effective home-based balance telerehabilitation and virtual assessment that can be used remotely in people with balance impairments. TRIAL REGISTRATION: This trial was prospectively registered on ClinicalTrials.gov (NCT05680597).

Assessment of balance in people with mild traumatic brain injury using a balance systems model approach.

PURPOSE: Measuring persistent imbalance after mTBI is challenging and may include subjective symptom-reporting as well as clinical scales. Clinical assessments for quantifying balance following mTBI have focused on sensory orientation. It is theorized that balance control goes beyond sensory orientation and also includes subdomains of anticipatory postural adjustments, reactive postural control, and dynamic gait. The Mini Balance Evaluation Systems Test (Mini-BESTest) is a validated balance test that measures balance according to these subdomains for a more comprehensive assessment. The purpose of this study was to compare Mini-BESTest total and subdomain scores after subacute mTBI with healthy controls. METHODS: Symptomatic mTBI (n = 90, 20 % male, age=36.0 ± 12.0, 46.3.4 ± 22.1 days since injury) and healthy control (n = 45, 20 % male, age=35.4 ± 12.5) participants completed the Mini-BESTest for balance. Mini-BESTest between-group differences were evaluated using Wilcoxon rank-sum tests. RESULTS: The mTBI group (Median[minimum,maximum]) had a significantly worse Mini-BESTest total score than the healthy controls (24[18,28] vs 27[23-28], p < 0.001). The mTBI group performed significantly worse in 3 of the 4 subdomains compared to the healthy controls: reactive postural control: 5[2-6] vs 6[3-6], p = 0.003; sensory orientation: 6[5,6] vs 6[6], p = 0.005; dynamic gait: 8[5-10] vs 9[8-10], p < 0.001. There was no significance difference between groups in the anticipatory postural adjustments domain (5[3-6] vs 5[3-6], p = 0.12). CONCLUSIONS: The Mini-BESTest identified deficits in people with subacute mTBI in the total score and 3 out of 4 subdomains, suggesting it may be helpful to use in the clinic to identify balance subdomain deficits in the subacute mTBI population. In combination with self-reported assessments, the mini-BESTest may identify balance domain deficits in the subacute mTBI population and help guide treatment for this population.

The effects of augmenting traditional rehabilitation with audio biofeedback in people with persistent imbalance following mild traumatic brain injury.

Complaints of non-resolving imbalance are common in individuals with chronic mild traumatic brain injury (mTBI). Vestibular rehabilitation therapy may be beneficial for this population. Additionally, wearable sensors can enable biofeedback, specifically audio biofeedback (ABF), and aid in retraining balance control mechanisms in people with balance impairments. In this study, we described the effectiveness of vestibular rehabilitation therapy with and without ABF to improve balance in people with chronic mTBI. Participants (n = 31; females = 22; mean age = 40.9 ± 11 y) with chronic (>3 months) mTBI symptoms of self-reported imbalance were randomized into vestibular rehabilitation with ABF (n = 16) or without ABF (n = 15). The intervention was a standard vestibular rehabilitation, with or without ABF, for 45 min biweekly for 6 weeks. The ABF intervention involved a smartphone that provided auditory feedback when postural sway was outside of predetermined equilibrium parameters. Participant's completed the Post-Concussion Symptom Scale (PCSS). Balance was assessed with the sensory organization test (SOT) and the Central Sensorimotor Integration test which measured sensory weighting, motor activation, and time delay with sway evoked by surface and/or visual surround tilts. Effect sizes (Hedge's G) were calculated on the change between pre-and post-rehabilitation scores. Both groups demonstrated similar medium effect-sized decreases in PCSS and large increases in SOT composite scores after rehabilitation. Effect sizes were minimal for increasing sensory weighting for both groups. The with ABF group showed a trend of larger effect sizes in increasing motor activation (with ABF = 0.75, without ABF = 0.22) and in decreasing time delay (with ABF = -0.77, without ABF = -0.52) relative to the without ABF group. Current clinical practice focuses primarily on sensory weighting. However, the evaluation and utilization of motor activation factors in vestibular rehabilitation, potentially with ABF, may provide a more complete assessment of recovery and improve outcomes.

Extension of community healthcare outcomes in Parkinson disease (Parkinson ECHO): A feasibility study.

Background: Parkinson's disease is the second most common neurodegenerative disorder and presents with a heterogeneous group of symptoms. Managing these symptoms requires coordinated care from a neurology specialist and a primary care provider. Access to neurology care is limited for those patients with Parkinson's disease who reside in rural areas given financial and mobility constraints along with the rarity of specialty providers. Methods: To close this gap, we developed and implemented a telehealth-based Project ECHO® (Extension for Community Healthcare Outcomes) program, "Parkinson ECHO," to provide education and support for rural clinicians and allied health members. The sessions focused on a topic within Parkinson's disease diagnosis or management followed by case discussions. We assessed the feasibility of this tele-mentoring educational offering, the favorability of this approach, and the effect it had on clinician confidence in diagnosing and treating Parkinson's disease using Likert-based surveys. Results: Thirty-three unique participants from 13 Oregon counties and one county in the state of Washington, of whom 70 % served rural and/or medically underserved communities, participated in Parkinson ECHO. There was a 52 % dropout rate based on survey response, though session attendance was higher. Participants were overall satisfied with the format and content of Parkinson ECHO. There were improvements in knowledge and confidence in diagnosing and treating Parkinson's disease which persisted 6 months following the conclusion of the program. Unexpectedly, two participants reported convening a multidisciplinary group to discuss improvements to PD care. Conclusion: The COVID-19 pandemic was an unexpected obstacle, but the teleconference nature permitted us to complete the program to positive effect. We found Parkinson ECHO did significantly increase participant confidence levels in diagnosing and managing Parkinson's disease.

Exploring Age and Sex Patterns for Rehabilitation Referrals After a Concussion: A Retrospective Analysis.

Objective: To explore patterns of postconcussion care at a level 1 trauma center. Design: Retrospective cohort study. Setting: U.S. level 1 trauma center and local satellite units. Participants: Patients of any age with a concussion diagnosis that reported to level 1 trauma center and local satellite units between 2016 and 2018 (N=2417). Intervention: Not applicable. Main Outcome Measures: Age, sex, point of entry, rehabilitation referrals, and pre-existing comorbidity diagnosis. Results: Patient age (mean [SD]) significantly differed among points of entry, from youngest to oldest: 26.0 (14.0) years in sports medicine, 29.3 (23.0) years in the emergency department, 34.6 (23.6) years at primary care providers, and 46.0 (19.7) years at specialty care departments. Sex also significantly differed among points of entry; emergency departments reported more men (55.6%), whereas the other points of entry reported more women (59.3%-65.6%). Patients were more likely to receive a referral from sports medicine (odds ratio [OR]unadjusted=75.05, P<.001), primary care providers (ORunadjusted=7.98, P<.001), and specialty care departments (ORunadjusted=7.62, P<.001) than from the emergency department. Women were more likely to receive a referral (ORunadjusted=1.92, P<.0001), regardless of point of entry. Lastly, patients with a preexisting comorbidity were more likely (ORadjusted=2.12, P<.001) to get a rehabilitation referral than patients without a comorbidity. Conclusions: Point of entry, age, sex, and preexisting comorbidities are associated with postconcussion care rehabilitation referral patterns. Improving concussion education dissemination across all entry points of a level 1 trauma center may standardize the postconcussion rehabilitation referral patterns, potentially improving the time to recovery from a concussion.

Implementation and Adoption of Telerehabilitation for Treating Mild Traumatic Brain Injury.

BACKGROUND AND PURPOSE: Multimodal physical therapy for mild traumatic brain injury (mTBI) has been shown to improve recovery. Due to the coronavirus disease-2019 (COVID-19) pandemic, a clinical trial assessing the timing of multimodal intervention was adapted for telerehabilitation. This pilot study explored feasibility and adoption of an in-person rehabilitation program for subacute mTBI delivered through telerehabilitation. METHODS: Fifty-six in-person participants-9 males; mean (SD) age 34.3 (12.2); 67 (31) days post-injury-and 17 telerehabilitation participants-8 males; age 38.3 (12.7); 61 (37) days post-injury-with subacute mTBI (between 2 and 12 weeks from injury) were enrolled. Intervention included 8, 60-minute visits over 6 weeks and included subcategories that targeted cervical spine, cardiovascular, static balance, and dynamic balance impairments. Telerehabilitation was modified to be safely performed at home with minimal equipment. Outcome measures included feasibility (the number that withdrew from the study, session attendance, home exercise program adherence, adverse events, telerehabilitation satisfaction, and progression of exercises performed), and changes in mTBI symptoms pre- and post-rehabilitation were estimated with Hedges' g effect sizes. RESULTS: In-person and telerehabilitation had a similar study withdrawal rate (13% vs 12%), high session attendance (92% vs 97%), and no adverse events. The telerehabilitation group found the program easy to use (4.2/5), were satisfied with care (4.7/5), and thought it helped recovery (4.7/5). The telerehabilitation intervention was adapted by removing manual therapy and cardiovascular portions and decreasing dynamic balance exercises compared with the in-person group. The in-person group had a large effect size (-0.94) in decreases in symptoms following rehabilitation, while the telerehabilitation group had a moderate effect size (-0.73). DISCUSSION AND CONCLUSIONS: Telerehabilitation may be feasible for subacute mTBI. Limited ability to address cervical spine, cardiovascular, and dynamic balance domains along with underdosage of exercise progression may explain group differences in symptom resolution.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A392 ).

Best Practices in the Clinical Management of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Consensus Statement of the CurePSP Centers of Care.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.

The Sensor Technology and Rehabilitative Timing (START) Protocol: A Randomized Controlled Trial for the Rehabilitation of Mild Traumatic Brain Injury.

BACKGROUND: Clinical practice for rehabilitation after mild traumatic brain injury (mTBI) is variable, and guidance on when to initiate physical therapy is lacking. Wearable sensor technology may aid clinical assessment, performance monitoring, and exercise adherence, potentially improving rehabilitation outcomes during unsupervised home exercise programs. OBJECTIVE: The objectives of this study were to: (1) determine whether initiating rehabilitation earlier than typical will improve outcomes after mTBI, and (2) examine whether using wearable sensors during a home-exercise program will improve outcomes in participants with mTBI. DESIGN: This was a randomized controlled trial. SETTING: This study will take place within an academic hospital setting at Oregon Health & Science University and Veterans Affairs Portland Health Care System, and in the home environment. PARTICIPANTS: This study will include 160 individuals with mTBI. INTERVENTION: The early intervention group (n = 80) will receive one-on-one physical therapy 8 times over 6 weeks and complete daily home exercises. The standard care group (n = 80) will complete the same intervention after a 6- to 8-week wait period. One-half of each group will receive wearable sensors for therapist monitoring of patient adherence and quality of movements during their home exercise program. MEASUREMENTS: The primary outcome measure will be the Dizziness Handicap Inventory score. Secondary outcome measures will include symptomatology, static and dynamic postural control, central sensorimotor integration posturography, and vestibular-ocular-motor function. LIMITATIONS: Potential limitations include variable onset of care, a wide range of ages, possible low adherence and/or withdrawal from the study in the standard of care group, and low Dizziness Handicap Inventory scores effecting ceiling for change after rehabilitation. CONCLUSIONS: If initiating rehabilitation earlier improves primary and secondary outcomes post-mTBI, this could help shape current clinical care guidelines for rehabilitation. Additionally, using wearable sensors to monitor performance and adherence may improve home exercise outcomes.

Inertial Sensors Reveal Subtle Motor Deficits When Walking With Horizontal Head Turns After Concussion.

OBJECTIVE: To examine whether horizontal head turns while seated or while walking, when instrumented with inertial sensors, were sensitive to the acute effects of concussion and whether horizontal head turns had utility for concussion management. SETTING: Applied field setting, athletic training room. PARTICIPANTS: Twenty-four collegiate athletes with sports-related concussion and 25 healthy control athletes. DESIGN: Case-control; longitudinal. MAIN MEASURES: Peak head angular velocity and peak head angle (range of motion) when performing head turns toward an auditory cue while seated or walking. Gait speed when walking with and without head turns. RESULTS: Athletes with acute sports-related concussion turned their head slower than healthy control subjects initially (group ß = -49.47; SE = 16.33; P = .003) and gradually recovered to healthy control levels within 10 days postconcussion (group × time ß = 4.80; SE = 1.41; P < .001). Peak head velocity had fair diagnostic accuracy in differentiating subjects with acute concussion compared with controls (areas under the receiver operating characteristic curve [AUC] = 0.71-0.73). Peak head angle (P = .17) and gait speed (P = .64) were not different between groups and showed poor diagnostic utility (AUC = 0.57-0.62). CONCLUSION: Inertial sensors can improve traditional clinical assessments by quantifying subtle, nonobservable deficits in people following sports-related concussion.

Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

OBJECTIVE: To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. METHODS: DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an "off"-levodopa Unified Parkinson's Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency. RESULTS: Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in "on" time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index (p = 0.004) and subscores for cognition (p = 0.011) and communication (p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 ± 4.3 points vs -6.31 ± 9.7 points (p = 0.0012) and phonemic fluency (+1.0 ± 8.2 points vs -5.5 ± 9.6 points, p = 0.038). CONCLUSIONS: Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. CLINICALTRIALSGOV IDENTIFIER: NCT01703598. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging-guided implantation is not significantly different from awake microelectrode recording-guided implantation in improving motor outcomes at 6 months.

Estrogen signaling is necessary for exercise-mediated enhancement of motoneuron participation in axon regeneration after peripheral nerve injury in mice.

Thousands of people each year suffer from peripheral nerve injury. Treatment options are limited, and recovery is often incomplete. Treadmill exercise can enhance nerve regeneration; however, this appears to occur in a sex-dependent manner. Females respond best to short duration, high speed interval training; whereas, males respond best to slower, continuous training. Previous studies have shown a role for testosterone in this process, but the role of estrogen is unknown. To evaluate the role of estrogen signaling in treadmill exercise, we blocked estrogen receptor (ER) signaling during treadmill exercise in males and female wild type mice. The right common fibular (CF) branch of the sciatic nerve was cut and repaired with fibrin glue that contained the ER antagonist ICI 182,780. Estradiol-filled or blank Silastic capsules were implanted subcutaneously at the time of nerve transection. Starting three days post-transection, exercised mice received treadmill training using the paradigm appropriate to their sex 5 days a week for 2 weeks. Fourteen days after the initial nerve transection, motoneurons whose axons had regenerated at least 1.5 mm distal to the original cut sites were labeled with a retrograde tracer. Regeneration was quantified by counting the number of fluorescent labeled motoneurons in the lumbar region of the spinal cord. Both treadmill training and estradiol administration increased the number of motoneurons participating in axon regeneration, but these effects were blocked by ER antagonist treatment. Estrogen signaling is important for the enhancing effects of treadmill exercise on motoneuron participation after peripheral nerve cut. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1133-1143, 2017.

Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation) that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2), we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2) to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555) was greater in mice that received optical treatment. Thus, the acute (1 hour), one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-). We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons.

Effects of Group, Individual, and Home Exercise in Persons With Parkinson Disease: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Comparative studies of exercise interventions for people with Parkinson disease (PD) rarely considered how one should deliver the intervention. The objective of this study was to compare the success of exercise when administered by (1) home exercise program, (2) individualized physical therapy, or (3) a group class. We examined if common comorbidities associated with PD impacted success of each intervention. METHODS: Fifty-eight people (age = 63.9 ± 8 years) with PD participated. People were randomized into (1) home exercise program, (2) individual physical therapy, or (3) group class intervention. All arms were standardized and based on the Agility Boot Camp exercise program for PD, 3 times per week for 4 weeks. The primary outcome measure was the 7-item Physical Performance Test. Other measures of balance, gait, mobility, quality of life, balance confidence, depressions, apathy, self-efficacy and UPDRS-Motor, and activity of daily living scores were included. RESULTS: Only the individual group significantly improved in the Physical Performance Test. The individual exercise showed the most improvements in functional and balance measures, whereas the group class showed the most improvements in gait. The home exercise program improved the least across all outcomes. Several factors effected success, particularly for the home group. DISCUSSION AND CONCLUSIONS: An unsupervised, home exercise program is the least effective way to deliver exercise to people with PD, and individual and group exercises have differing benefits. Furthermore, people with PD who also have other comorbidities did better in a program directly supervised by a physical therapist.Video Abstract available for additional insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A112).

Neuronal BDNF signaling is necessary for the effects of treadmill exercise on synaptic stripping of axotomized motoneurons.

The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells.

Exercise, neurotrophins, and axon regeneration in the PNS.

Electrical stimulation and exercise are treatments to enhance recovery from peripheral nerve injuries. Brain-derived neurotrophic factor and androgen receptor signaling are requirements for the effectiveness of these treatments. Increased neuronal activity is adequate to promote regeneration in injured nerves, but the dosing of activity and its relationship to neurotrophins and sex steroid hormones is less clear. Translation of these therapies will require principles associated with their cellular mechanisms.

Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration.

After peripheral nerve injury, neurotrophins play a key role in the regeneration of damaged axons that can be augmented by exercise, although the distinct roles played by neurons and Schwann cells are unclear. In this study, we evaluated the requirement for the neurotrophin, brain-derived neurotrophic factor (BDNF), in neurons and Schwann cells for the regeneration of peripheral axons after injury. Common fibular or tibial nerves in thy-1-YFP-H mice were cut bilaterally and repaired using a graft of the same nerve from transgenic mice lacking BDNF in Schwann cells (BDNF(-/-)) or wild-type mice (WT). Two weeks postrepair, axonal regeneration into BDNF(-/-) grafts was markedly less than WT grafts, emphasizing the importance of Schwann cell BDNF. Nerve regeneration was enhanced by treadmill training posttransection, regardless of the BDNF content of the nerve graft. We further tested the hypothesis that training-induced increases in BDNF in neurons allow regenerating axons to overcome a lack of BDNF expression in cells in the pathway through which they regenerate. Nerves in mice lacking BDNF in YFP(+) neurons (SLICK) were cut and repaired with BDNF(-/-) and WT nerves. SLICK axons lacking BDNF did not regenerate into grafts lacking Schwann cell BDNF. Treadmill training could not rescue the regeneration into BDNF(-/-) grafts if the neurons also lacked BDNF. Both Schwann cell- and neuron-derived BDNF are thus important for axon regeneration in cut peripheral nerves.

Sex differences in the effectiveness of treadmill training in enhancing axon regeneration in injured peripheral nerves.

Exercise in the form of daily treadmill training results in significant enhancement of axon regeneration following peripheral nerve injury. Because androgens are also linked to enhanced axon regeneration, we wanted to investigate whether sex differences in the effect of treadmill training might exist. The common fibular nerves of thy-1-YFP-H mice were cut and repaired with a graft of the same nerve from a strain-matched wild-type donor mouse. Animals were treated with one of two daily treadmill training paradigms: slow continuous walking for 1 h or four higher intensity intervals of 2 min duration separated by 5-min rest periods. Training was begun on the third day following nerve injury and continued 5 days per week for 2 weeks. Effects on regeneration were evaluated by measuring regenerating axon profile lengths in optical sections through the repair sites and grafts at the end of the training period. No sex differences were found in untrained control mice. Continuous training resulted in significant enhancement of axon regeneration only in males. No effect was found in females or in castrated males. Interval training was effective in enhancing axon regeneration only in females and not in intact males or castrated males. Untrained females treated with the aromatase inhibitor, anastrozole, had significant enhancement of axon regeneration without increasing serum testosterone levels. Two different mechanisms exist to promote axon regeneration in a sex-dependent manner. In males treadmill training uses testicular androgens. In females, a different cellular mechanism for the effect of treadmill training must exist.