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Exercise after Brain Injury: Evidence and Recommendations

Exercise after Brain Injury: Evidence and Recommendations. Speakers. Matthew Allen Puderbaugh DO Resident Physician, Department of Physical Medicine and Rehabilitation University of Minnesota Diane Schretzman Mortimer MD, MSN, FAAPMR

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Exercise after Brain Injury: Evidence and Recommendations

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  1. Exercise after Brain Injury: Evidence and Recommendations

  2. Speakers Matthew Allen Puderbaugh DO Resident Physician, Department of Physical Medicine and Rehabilitation University of Minnesota Diane Schretzman Mortimer MD, MSN, FAAPMR Medical Director, Inpatient TBI/ Polytrauma Rehabilitation Minneapolis VA Health Care System Beth Wittry, PT, DPT Neurologic Physical Therapy Resident Minneapolis VA Health Care System

  3. Disclosures We have no financial disclosures to report. We are not speaking on behalf of the VA or federal government.

  4. Objectives After participating in this presentation, participants will be able to: 1) Discuss at least two evidence-based potential benefits of exercise on neuroanatomical, neurochemical, and cellular/ molecular functions of the brain. 2) Describe at least two ways to assess and address vestibular dysfunction, weakness, cognitive impairment and other common barriers to exercise after brain injury. 3) State at least three recommendations for developing and implementing exercise programs after brain injury.

  5. Objective 1 Discuss at least two evidence-based potential benefits of exercise on neuroanatomical, neurochemical, and cellular/ molecular functions of the brain.

  6. Brain Injuries • At least 1.7 million TBIs per year in US. • Many more non-traumatic injuries. • 1 in 100 US civilians has some long-term or permanent disability from TBI. • Survivors have emotional, physical, cognitive distress, physical and social barriers. • Survivors are risk for secondary and chronic conditions.

  7. TBI Pathophysiology • TBI involves disruptions in ionic, metabolic, physiological homeostasis.

  8. Exercise It has been well-established that physical exercise plays a role in: • Maintenance of overall health • Cardiovascular health • Glucose control • Weight management • Bone density • Mental health

  9. Exercise There’s ample animal and growing human evidence that exercise can be beneficial for the brain. Exercise may: • Have positive effect on general memory and cognition. • Preserve cognitive function in older adults with and without dementia. • Improve function of prefrontal cortex leading to better attention, speed of information processing, global cognition, attention, and cognitive flexibility. • Lead to generalized cognitive benefits, including better motor learning and rapid sequence-specific learning.

  10. Exercise after TBI: Benefits • Fatigue • Depression and anxiety • Sleep • A randomized controlled trial of 76 people 6 months to 5 years following injury showed there was less depression and improved sleep, community participation and overall quality of life in people who recounted higher levels of exercise. Hoffman JM, Bell KR, Powell JM, et al. A randomized controlled trial of exercise to improve mood after traumatic brain injury. PM&R 2010: 2; 9-919.

  11. Exercise after TBI: Cognitive Effects After TBI, aerobic exercise can result in significant increases in cognition • Specifically, aerobic exercise may help with executive function, attention and working memory.

  12. Possible Mechanisms • Better fitness • Plasticity/ Neurogenesis • Cellular modulators • Angiogenesis • Growth factors • Endocrine factors • Neurotransmitters • Other neuromodulators • Molecular changes • Anti-inflammatory Kreber LA, Griesbach GS. The interplay between neuropathology and activity based rehabilitation after traumatic brain injury. Brain Research 2016: 158.

  13. Better Fitness Improved aerobic fitness leads to increased cerebral blood flow, oxygen extraction and glucose utilization. Of note, sedentary lifestyles are common after TBI.

  14. Plasticity • Exercise may improve neural plasticity. • That is, exercise can cause specific changes to the neurochemical mircroenvironment which lead to improved function.

  15. Plasticity/ Neurogenesis • In the human brain, the only place neurogenesis occurs is the hippocampus, in the , subventricular zone and subgranular zone of hippocampal dentate gyrus. • In animal studies, neurogenesis occurs there after activities like running and other voluntary exercise activities. • The cellular regeneration that occurs correlates with improved performance on temporospatial memory and learning tasks.

  16. How Might Neurogenesis Occur? • The regeneration appears related to local upregulation of numerous neurotrophins, such as BDNF, synapsin-1, and IGF-1 in hippocampus. • Voluntary exercise can upregulate proteins involved in signal transduction, synaptic trafficking, and transcriptional regulation. • Proteins associated with glycolysis, ATP synthase and transduction, and glutamate turnover are increased after a period of brief voluntary exercise in rats.

  17. Cellular Modulators Exercise increases production of array of proteins which are needed for neuroplasticity • Brain-derived neurotrophic factor (BDNF)- the one most widely assd with exercise. BDNF is produced both peripherally and in the brain, with high concentrations in the hippocampus. It increases with exercise in animal and human studies. Synaptic plasticity, via long-term potentiation, also increases with exercise induced increases in BDNF levels. • Insulin-like growth factor-1 (IGF-1), potent growth factor that his produced in liver and brain. Mediates exercise-induced angiogenesis and appears to play sig role in exercise-induced neurogenesis. IGF-1 stimulates BDNF upregulation during exercise. • Inhibiting hippocampal IGF-1 receptors during exercise modulates other proteins that likely contribute to enhancing neural function and cognitive performance. These include synapsin I, calcium calmodulin-dependent protein II (CAMKII) and mitogen activated protein kinase (MAPK).

  18. Cellular Modulators Fogelman D, Zafonte R. Exercise to enhance neurocognitive function after traumatic brain injury. PM&R 2012: 4: 909.

  19. Angiogenesis If more blood vessels are produced and/ or circulation through them improved, more blood can flow to an area. • Aerobic exercise promotes angiogenesis in brain regions related to locomotion, such as the cerebellum and primary motor cortex.

  20. Growth Factors Vascular endothelial growth factor (VEGF) has been associated with with neuronal proliferation and angiogenesis. • VEGF levels increase with exercise.

  21. Endocrine Factors Exercise positively affects functioning of the hypothalamic-pituitary-adrenal axis. • TBI can cause hypothalamic-pituitary dysfunction which can interfere with recovery. • Exercise may modulate that effect.

  22. Neurotransmitters Exercise affects neurotransmitters which are associated with mood and cognition.

  23. Other Neuromodulators Endogenous opioid may increase during exercise. • Endogenous opioids peptide families: • Beta endorphins • Enkephalins • Dynorphins • These are likely involved in pain modulation, reward, response to stress, and autonomic control mechanisms.

  24. Molecular Changes Exercise may lead to changes in gene expression. • Epigenetic modifications such as DNA methylation and histone acetylation occur with exercise. • These may contribute to neurologic benefits.

  25. Anti-inflammatory Exercise can modulate the inflammatory response to TBI. • TBI’s pathophysiological changes can lead to neuroinflammation and delayed cell death. • Much of that process occurs via cytokines, immune system messengers with pro- or anti- inflammatory properties. • Interleukin 6 (IL-6): proiflammatory AND anti-inflammatory (depending on environment it’s in) • Tumor necrosis factor alpha (TNF alpha): proinflammatory • Interleukin 1 beta (IL-1B): pro-inflammatory. • Exercise activates IL-6 which can help decrease rest of the inflammatory response.

  26. Timing Exercising within the first few days after injury does not have the same beneficial effect on the injured brain. • Early exercise can result in further metabolic demands when energy is already short and the brain is still metabolically compromised. • High levels of stress hormones at that point can be increased during exercise. • This can negatively affect brain healing by disrupting the endogenous mechanisms trying to restore homeostasis before neuroplasticity can be facilitated.

  27. Summary • Exercise can have a generalized positive impact on health, which is beneficial after the TBI. • Exercise may be an adjuvant to various pharmacological and non-pharmacological therapies for TBI. • Goal is to ensure that physical exercise programs promote adaptive neuroplasticity and brain recovery.

  28. References for part 1 • Basso JC, Suzuki WA. The effects of acute exercise on mood, cognition, neurophysiology, and neurochemical pathways: A review. Brain Plasticity 2016: 127-152. • Chin LM, Keyse RE, Duurney J, et al. Improved cognitive performance following aerobic exercise training in people with traumatic brain injury. Arch Phys Med Rehab 2015: 96; 954-959. • Devine JM, Wong B, Gervino E, et al. Independent, community-based aerobic exercise training for people with moderate-to-severe traumatic brain injury. Arch Phys Med Rehab 2016: 97; 1392-1397. • Devine JM, Zafonte RD. Physical exercise and cognitive recovery in acquired brain injury: A review of the literature. PM&R 2009:1(6); 560-575.  • Fogelman D, Zafonte R. Exercise to enhance neurocognitive function after traumatic brain injury. PM&R 2012: 4: 908-913. • Hoffman JM, Bell KR, Powell JM, et al. A randomized controlled trial of exercise to improve mood after traumatic brain injury. PM&R 2010: 2; 9-919. Kolakowsky-Hayner SA, Bellon K, Toda K, et al. A randomized control trial of walking to ameliorate brain injury fatigue: A NIDRR TBI model system centre-based study. Neuropsych Rehab 2017: 27(7); 1002-1018. • Kreber LA, Griesbach GS. The interplay between neuropathology and activity based rehabilitation after traumatic brain injury. Brain Research 2016: 152-163. • Lequerica AH, Boticello AL, Lengenfelder J, et al. Factors associated with remission of post-traumatic brain injury in the years following traumatic brain injury (TBI): A TBI model systems module study. Neuropsychological Rehabilitation 2017: 27(7); 1019-1030. • McDonnell MN, Smith AE, Mackintosh SF. Aerobic exercise to improve cognitive function in adults with neurological disorders: A systematic review. Arch Phys Med Rehabil 2011: 92; 1045-1052. • Mossberg KA, Amonette WE, Masel BE. Endurance training and cardiorespiratory conditioning after traumatic brain injury. J Head Trauma Rehabil 2010: 25(3); 173-183. Weinstein AA, Chin LK, Collins J, et al. Effect of aerobic exercise training on mood in people with traumatic brain injury: A pilot study. J Head Trauma Rehabil 2017: 32(3); E 49-E56. • Wise EK, Hoffman JM, Powell JM, et al. Benefits of exercise maintenance after traumatic brain injury. Arch Phys Med Rehabil 2012 :93; 1319-1323.

  29. Objective 2 Describe at least two ways to assess and address vestibular dysfunction, weakness, cognitive impairment and other common barriers to exercise after brain injury.

  30. Breaking Down Barriers • Barriers come in many forms: • Exercise Recommendations • Safety during exercise • Symptoms • Access to gyms

  31. Exercise Recommendations (1,2) • Myth: “People with TBI shouldn’t exercise because that will worsen their TBI” • FALSE: ACSM and research recommends exercise for people with TBI: • Mild to Moderate Symptoms: • 150 min of preferably moderate-intensity physical activity • OR 150 min of light-intensity if unable to sustain moderate intensity • At least 2 days per week of flexibility and muscle strengthening activities • Severe Symptoms: • 3-5 times a week, light-moderate activity for 20-60 mins at a time • Exercise is not recommended for those who are: • Unable to complete normal activities of daily living due to symptoms • Ex: Vestibular symptoms preventing ambulation • High Risk of cardiopulmonary decompensation during low-intensity exercise • Ex: unable to complete conventional PT session

  32. Engaging in Physical Activity (2) For Severe Symptoms: • Start Conservatively • Low-intensity interval training • Increase Slowly • Advance duration by 5 min every 2 weeks • Goal of 30 min low-intensity >3 days of week • Be Patient • Plan on taking 3-6 months to reaching time goals

  33. Safety and Exercise (1,3) • Myth: “People with severe TBI shouldn’t exercise because it isn’t safe” • FALSE: Cochrane Review showed exercise is safe • Recent Study showed that Chronic Moderate to Severe Brain Injury patients were able to complete Moderate to Intensive Physical activity 60-90 min sessions for 3 days a week for 6 weeks • No reports of harm during the interventions • Safety Considerations: • Exercise must be tailored to the individual • Use seated equipment when dealing with patients with high falls risk • Assistants are a necessity • Recommended to have 1-2 assistants (people who are familiar with brain injury sequlae and the equipment)

  34. Symptoms as Barrier (3) • Recent study interviewed participants to identify barriers to participation in exercise • Reported symptom barriers include: • Physical (vision, balance, incontinence) • Cognitive (memory, executive function, lack of self-awareness) • Emotional (anxiety)

  35. Vestibular Dysfunction in TBI (4) • Dizziness affects 23-81% of patients after TBI • Etiologies • Peripheral • Central • Vestibular Rehab Treatments • BPPV treatments • Gaze stability exercises • Balancing exercises https://www.swbh.nhs.uk/wp-content/uploads/2012/07/Brandt-Daroff-Exercises-ML3094.pdf https://excelptjackson.com/vestibular-rehab/

  36. Vestibular Rehabilitation (4,5) • 2018 RCT • Showed immediate improvement after VR intervention • Control matched intervention group after 2 months

  37. Novel Treatment Strategies • rTMS • Paxman, Stilling, Mercier, Debert, 2018 • Chronic Post-Concussive symptoms improved after 10 sessions

  38. Barriers to Access to Exercise (3, 7) • Transportation • Most cited reason for participants in a recent study • Public Transportation can be variable • Disability friendly exercise facilities • Lack of facilities that are capable of working with people with disabilities • Format Options • Group Sessions may not be accessible due to personal barriers (aphasia)

  39. How to Break Down Barriers • Clinicians: • Be familiar with guidelines and encourage exercise • Work through safety plans with family/friends/staff who can assist • Family and Friends: • Encourage exercise and participate (it’s healthy for you too)! • Advocate for on-site appropriate equipment or transportation to appropriate exercise facilities • Staff: • Work in exercise times to patient’s schedules • Work on setting up a safe variety of exercise options (on site or off-site) • Educate fellow staff on exercising with patients

  40. References • Hassett, L, Moseley, A.M., Harmer, A.R. (2017). Fitness training for cardiorespiratory conditioning after traumatic brain injury. Cochrane Database of Systematic Reviews 12 • Moore, G.E., Durstine, J.L. Painter, P.L. (2016). Ch. 25. Stroke, Brain Trauma, and Spinal Cord Injuries. ACSM’s Exercise Management for Persons With Chronic Diseases and Disabilities, 4th Ed. Human Kinetics, Champaign, IL. • Lorenz, L.S. et al. (2018). Healthy body, healthy mind: A mixed methods study of outcomes, barriers and supports for exercise by people who have chronic moderate-to-severe acquired brain injury. Disability and Health Journal, 11 (2018) 70-78. • Kleffelgaard, I. et al. (2018). The effects of vestibular rehabilitation on dizziness and balance problems in patients after traumatic brain injury: a randomized controlled trial. Clinical Rehabilitation, 20:1115-1127. • Kleffelgaard, I. et al. (2016). Vestibular Rehabilitation after Traumatic Brain Injury: Case series. Physical Therapy: Journal of the American Physical Therapy Association, 96(6): 839-849 • Paxman, E., Stilling, J., Mercier, L., Debert, C.T. (2018). Repetitive transcranial magnetic stimulation (rTMS) as a treatment for chronic dizziness following mild traumatic brain injury. British Medical Journal Case Reports, Jan. https://casereports-bmj-com.ezp3.lib.umn.edu/content/2018/bcr-2018-226698.citation-tools • Calder, A.C., Sole, G., Mulligan, H. (2018). The accessibility of fitness centers for people with disabilities: A systematic review. Disability and Health Journal, 11 (2018) 525-536

  41. Objective 3 State at least three recommendations for developing and implementing exercise programs after brain injury.

  42. Getting Started • Educate, educate, educate • Importance, benefits, outcomes • Expectations • Marathon not a sprint • Encourage goal setting • What do they want to achieve/improve • The “why” behind it all • Promote self-efficacy • Make a plan • Address barriers  problem solve

  43. Aerobic Exercise • Focus of majority of the research • Especially important in this population due to: • Decreased peak aerobic capacity • Decreased VO2 max • Decreased anaerobic threshold • Impaired physiologic response to exercise • Decreased movement efficiency

  44. Aerobic Exercise • Frequency: ≥ 3x/week • Duration: ≥ 30 min/session • Intensity: moderate to high intensity • 60-80% age-adjusted HR Max • RPE 6-8/10 • Safe and feasible • Considerations: • BP restrictions, ICP • Options: • Walking/running – overground, treadmill • Elliptical • Stationary bike • Arm bike • May need to be creative

  45. Resistance Training • Frequency: 2x/week • Duration: 2-3 sets, 10-15 reps • Intensity: • 50-60% of 1 rep maximum • RPE 6-8/10 • Considerations: • Lifting restrictions, ICP • Focus on functional exercises: • Sit <> stand, squats, lunges, set-ups, heel raises • Push-ups, planks • May include: • Balance and flexibility

  46. Other Modes • Yoga, Tai Chi • Group fitness classes • Swimming • Walking program – pedometer • Consider dose response

  47. Bottom Line • How much? • 90-150 min/week of moderate to high intensity exercise • Best type? • Aerobic is key • Motivating and salient to the patient • It starts with education

  48. References • Analytis P, et al. Physical activity: perceptions of people with severe traumatic brain injury living in the community. Brain Injury. 2018;32(2):209-217. • Bateman A, et al. The Effect of Aerobic Training on Rehabilitation Outcomes After Recent Severe Brain Injury: A Randomized Controlled Evaluation. Arch Phys Med Rehabil. 2001;82:174-182. • Bellon K et al. A home-based walking study to ameliorate perceived stress and depressive symptoms in people with traumatic brain injury. Brain Injury. 2015;29(3):313-319. • Bhambhani Y, et al. Effects of Circuit Training on Body Composition and Peak Cardiorespiratory Responses in Patients With Moderate to Severe Traumatic Brain Injury. Arch Phys Med Rehabil. 2005;86:268-276. • Chin L, et al. Improved Cardiorespiratory Fitness With Aerobic Exercise Training in Individuals With Traumatic Brain Injury. J Head Trauma Rehabil. 2015;30(6):382-390. • Dawes H, et al. Exertional symptoms and exercise capacity in individuals with brain injury. Disability and Rehabilitation. 2006;28(20):1243-1250. • Driver S, et al. Creating an effective physical activity-based health promotion programme for adults with a brain injury. Brain Injury. 2012;26(12):1482-1492. • Ede A, et al. Circuit Training Recommendations for Individuals With a Traumatic Brain Injury. Strength and Conditioning Journal. 2011;33(4):48-51. • Mossberg K, et al. Endurance Training and Cardiorespiratory Conditioning after Traumatic Brain Injury. J Head Trauma Rehabil. 2010;25(3):173-183. • Weinstein A, et al. Effect of Aerobic Exercise Training on Mood in People With Traumatic Brain Injury: A Pilot Study. J Head Trauma Rehabil. 2017;32(3):49-56.

  49. Thank You!

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