Therapeutic Benefits from Aggressive, Recovery Focused, Physical Therapy Program

1. Therapeutic Benefits from Aggressive, Recovery Focused, Physical Therapy Program Bill Thornton MPT Clinical Director Level Eleven Physical Therapy

2. Objectives • Review General TBI Statistics • Review TBI-Related Disabilities • Explain/Define Neuralplasticity • Explain/Define Aggressive Recovery Focused Therapy • Explain/Define Secondary Benefits of Aggressive Therapy

3. TBI Statistics • Leading cause of death among children and young adults (highest frequency = 15-25 y/0) • 5.3 million individuals with TBI-related disability in US • Two thirds of individuals with TBI are below the age of 36 • 78% of the above are male • Yearly incidence is 1/2000 Morris et al 2006 Hoofien et al 2001

4. TBI Statistics • 1.5 – 2 million TBI per year in US • 70,000 – 90,000 of these individuals incur a TBI that results in long-term loss of physical and mental function • Average life expectancy of an individual with a TBI is 50 years • There are very few studies that have looked at the long-term sequelae associated with TBI Hoofien et al 2001

5. TBI Related Disabilities • Impaired use of extremities • Impaired speech • Impaired cognition • Impaired vocational capabilities

6. Costs Comparisons Condition         Incidence        Deaths          Cost Brain injury       2 million         100,000        $25 billion Stroke            2.6 million       145,000        $25 billion SCI  10,000      unknown       $8 billion Cancer           1.1 million       510,000     $104 billion AIDS                 50,000          26,000     $15 billion http://www.headinjury.com/coststbi.htm

7. Intensive Recovery Focused Rehabilitation Philosophy • Anticipate/promote recovery and prevent learned non-use/substituted patterns • Bombard the CNS with sensory (afferent) information (when appropriate) • Couple the entire body when ever possible

8. Intensive Recovery Focused Rehabilitation Philosophy • Continually seek novel application of both new and current rehabilitation paradigms to stimulate, irritate, reactivate impaired CNS • Provide the most valid, reliable, and current education/rehabilitation concerning neuralplasticiy

9. Potential Physiological Effects/Changes Resulting from Intensive Rehabilitation • Increased O2 , hemoglobin, and EMG activity in the paralyzed limb (Kaashima etal 2005) • Possible gene expression and synaptic re-organization following FES (Donaldson etal 2000, Dobkins 2003, Keyvani etal 2004) • Improved leg function and over ground ambulation with FES, and BWSTT combined with FES (Donaldson etal 2000, Mirbagheri etal 2002, Postans etal 2004) • Increased production/secretion of brain derived neurotrophic growth factor (BDNF) (Gomez-Pinilla etal 2002, Kleim etal 2003) • Rehabilitation may need to first focus on influencing the older motor systems of the CNS (Wakabayashi et al 2001, Kakebeeke etal 2005)

10. ProposedIntensive Rehabilitation Parameters • 1-3 hours of therapy 3 to 5 days per week • Couple the entire body when ever possible • Implement closed chain exercise whenever possible • Implement exercises that take clients through numerous levels of developmental sequences in addition to pre-gait/gait training • Provide an enriched environment for all therapy procedures • The activity should be novel, complex, and involve in-depth cognitive processing

11. Relevance to Rehabilitation • In order to develop appropriate and efficient therapy programs for clients with TBI, several rehabilitative neuro-plastic paradigms must be considered. • The appropriate timing of physical rehabilitation • The appropriate type of physical rehabilitation • The appropriate intensity of physical rehabilitation • The appropriate environment for physical rehabilitation.

12. When should rehabilitation begin? • Education should begin from day one • Initiation of Intensive Physical Rehabilitation is dependent on: • Date of Injury • Nature/Type/Location of Injury • Comorbidities • There maybe an initial period in which rest is the most beneficial treatment for optimal recovery

13. What is Intensive Rehabilitation ? • There is currently no literature that accurately defines intensive rehabilitation • There is limited literature investigating the most efficient therapeutic exercise, treatment duration, and treatment intensity (Harkema, Field-Foote) • Outcome measures are currently being designed and investigated for accuracy (validity & reliability) • There maybe benefit to focus physical rehabilitation on coordination/activation of older motor systems (Kakebeeke etal 2005)

14. Neuralplasticity Defined • Neuralplasticity is the ability of neurons to alter their structure or function in the presence of an adequate stimulus or following perturbation. Examples include: • Axonal Regeneration • Long-Term Potentiation • Denervation Supersensitivity • Collateral Sprouting • Dendritic Pruning • Cortical Reorganization

15. Learned Non Use Model Unsuccessful Motor Attempts Failure Injury Behavior Suppression Masked Ability Learned Nonuse Compensatory Behavior + Reinforcement Reinforcement of less effective behavior Figure recreated from Taub et al. 1997

16. Long-Term Potentiation (LTP) • Long-Term Potentiation is a long-lasting increase in effectiveness of nerve conduction following high frequency stimulation of sensory (afferent) fibers • Simply put, when a nerve pathway is adequately stimulated, it becomes more responsive to subsequent stimulation

17. Denervation Supersensitivity • Neurons that lose a synaptic input become more sensitive to the application of the involved neurotransmitter. • One example is Parkinson's disease

18. Collateral Sprouting • When a nerve undergoes injury, sprouting of neurites from neighboring spared axons occurs. • When injury occurs in the CNS, the distance of growth is generally restricted to 250  m. • The functional significance of collateral sprouting is not known. • Collateral sprouting may be of benefit to subjects with spinal cord injuries due to the correlation between sprouting and hyperreflexia.

19. Example of Collateral Sprouting http://www.jccc.net/~aalarabi/axonreg.html

20. Dendritic Pruning • Loss or altered innervation may result in modified post-synaptic neuronal structure/morphology • Segregation of the altered inputs occurs in different regions of the dendritic tree • If this results in a reduction or loss of sensory pathways, there is a selective reduction in the size of the affected dendritic arbor

21. Example of Pruning http://www.jccc.net/~aalarabi/axonreg.html

22. What are Central Pattern Generators (CPG)? • “CPGs refer to functional networks that generate rhythm and shape the pattern of motorneurons” Zher etal 2004 • Examples are the rhythmic movements seen in crawling, walking, running, swimming…

23. What is the difference between volitional and autonomic movement? • “What is volitional in voluntary movement is its purpose” MacKay-Lyons 2002 • The same motor programs are involved for both volitional and autonomic movements • The environment or situation greatly influence the coordination between the cortex (your mind) and spinal cord (CPG)

24. Dendrites with loss of connections Numerous connections between uninjured neurons still exist, collateral sprouting or pruning may occur

25. Cortical Reorganization • Neuronal connections and cortical maps are continuously remodeled by our experiences or in response to CNS injury • This may be the result of neurogenesis, LTP, unmasking of preexisting connections or increased synthesis of neurotrophic factors • We must make sure that the reorganization and/or neuroplastic changes are positive/wanted

26. Cortical ReorganizationField-Fote 2004 • Artificial stimulation (electrical, vibrational) applied to sensory fibers can modify CNS circuitry • Electrical stimulation (ES) may be more effective with upper motor neuron injuries in reducing the stretch reflex along with other forms of inhibition • Effective prolonged stimulation of peripheral nerves has the potential to increase the excitability of the motor cortex • Additionally, sensory level ES combined with training may help prevent/reverse the maladaptive reorganization of the cortex and spinal cord Summary: Multiple studies have shown that sensory stimulation of an impaired limb (TBI, CVA,SCI) results in improved function of the limb. This indicates reorganization of the brain

27. Cortical ReorganizationKleim et al 2003 • This article reviewed current research looking at motor enrichment associated with exercise and the induction of plasticity before or after brain injury • Functional activity, treadmill training, and forced use have all demonstrated some form of improved “brain health” • This may be in the form of neurotrophic factors, neurogenisis, synaptogenesis, pre/post synaptic modulation • Exercise has shown a “prophylactic effects with TBI and CVA” In other words to help prevent more severe damage • It is possible that exercise has the potential to reactivate plastic mechanisms in chronic brain injury Summary: Combined use of multiple muscles during exercise/activities seems to have a beneficial effect on the CNS

28. Cortical ReorganizationThomas et al 2005 • Ten individuals (ASIA C & D, age 29-78) with Incomplete SCI under went body weight support treadmill training (BWSTT) for one hour 3-5 days/wk for 3-5 months • Subjects performed BWSTT on a motorized treadmill with manual assistance for leg movement • Cortical (Brain) Stimulation to certain muscles was provided via transcranial magnetic stimulation (TMS) • Intense BWSTT combined with TMS increased the connectivity of spared corticospinal pathways (Central Effect) • Further research is needed to clarify the correlation between motor improvement and locomotor function Summary: Stimulation of specific areas of the brain lead to strong contractions of leg muscles indicating that the change occurred in the spinal cord and not the muscle

29. Cortical ReorganizationField-Fote 2004 • Review article exploring how electrical stimulation (ES) modifies spinal and cortical neural circuitry • Sensory information is essential for refined coordinated motor tasks • This information regulates spinal reflexes • This sensory information becomes disorganized or non existent with neurological injuries (TBI, CVA, SCI) • Long-term reflex plasticity can be operantly conditioned (simple stated, a given stimulus can help relearn a movement when the movement is properly reinforced in the correct environment)

30. Cortical ReorganizationField-Fote 2004 • Artificial stimulation (electrical, vibrational) applied to sensory fibers can modify CNS circuitry • Electrical stimulation (ES) may be more effective with upper motor neuron injuries in reducing the stretch reflex along with other forms of inhibition • Effective prolonged stimulation of peripheral nerves has the potential to increase the excitability of the motor cortex • Additionally, sensory level ES combined with training may help prevent/reverse the maladaptive reorganization of the cortex and spinal cord Summary: Multiple studies have shown that sensory stimulation of an impaired limb (TBI, CVA,SCI) results in improved function of the limb. This indicates reorganization of the brain

31. Cortical ReorganizationTaub et al 2003 • Review article exploring constraint induced movement therapy and the need to bridge the gap from primate laboratory to human CVA rehabilitation • Constraint induced movement therapy has the potential to significantly reduce motor deficient with individuals suffering form chronic CVA’s • The cortical re-organization is use dependent • Two modifications have been made to existing constraint induced theory • More intense use of the affected arm • Less restraint of the less-affected arm • “It is not the constraint in CI therapy that is important, it is the intensive practice of correct use with the affected limb” Summary: Research indicates that more intense use of the impaired limb results in improved function indicating reorganization of the brain

32. Potential Physiological Effects/Changes Resulting from Intensive Rehabilitation • Increased O2 , hemoglobin, and EMG activity in the paralyzed limb (Kaashima etal 2005) • Possible gene expression and synaptic re-organization following FES (Donaldson etal 2000, Dobkins 2003, Keyvani etal 2004) • Improved leg function and over ground ambulation with FES, and BWSTT combined with FES (Donaldson etal 2000, Mirbagheri etal 2002, Postans etal 2004) • Increased production/secretion of brain derived neurotrophic growth factor (BDNF) (Gomez-Pinilla etal 2002, Kleim etal 2003) • Rehabilitation may need to first focus on influencing the older motor systems of the CNS (Wakabayashi et al 2001, Kakebeeke etal 2005)

33. Neuralplastic Rehabilitation Paradigms • Forced-Use or Constraint-Induced Model • Traditional Model • PNF • NDT • Intensive Coordinated Rehabilitation • Environmental Enrichment Model

34. Forced-Use/Constraint-Induced Model • Constraint-Induced (CI) movement therapies evolved from animal deafferentation research that strongly suggested the lack of involved extremity use may be result of learned non-use (Taub,1997, 2003). • CI therapies focus on restricting the use of the unaffected extremity by different means (casting, sling, padded mitten) thereby forcing the use of the affected limb. • Research, involving CI therapies on both animal and human models, has demonstrated significant improvements of motor function in the involved extremity (Dromeric, 2000; Liepert, 2000; Schallert, 2000; Taub, 1997, 2003; Whitall, 2000)

35. Small Well Large Well Forced-Use or Constraint-Induced Model Large and Small Well experimental setup (Nudo et al, 1997)

36. Nudo etal (1997) Forced-Use or Constraint-Induced Model These results indicate that cortical reorganization is effected by learning new motor skills, not repetitive motor use (Nudo et al, 1997).

37. Traditional Models • Proprioceptive Neuromuscular Facilitation (PNF) • Neurodevelopmental Treatment (NDT)

38. Proprioceptive Neuromuscular Facilitation (PNF) • Proprioceptive neuromuscular facilitation is a philosophy and treatment method developed by Dr. Herman Kabat with later help from Margaret Knott and Dorothy Voss (Adler, 2000). • PNF is a common physical therapy treatment employed to help restore motor function in patients who have sustained various CNS insults (Adler, 2000). • Basic procedures of PNF include the combination of manual contact, resistance, stretch, timing, traction/approximation, stimulus irradiation and verbal guidance to produce synergistic mass movements or movement components necessary for normal motion (Adler, 2000).

39. Neurodevelopmental Treatment (NDT) • The NDT concept was developed by Karel and Berta Bobath in 1943 with the intention of this treatment to be delivered by three disciplines, physical therapy, occupational therapy, and speech-language therapy (DeGangi, 1994). • Their treatment concept was originally designed in an effort to improve the function of individuals who had experienced a CVA and was later applied to individuals with cerebral palsy (DeGangi, 1994).

40. Neurodevelopmental Treatment (NDT) • NDT approach addresses three main areas of function, postural control, transitional movement, and functional activities within a given posture. • There is little scientific evidence concerning assumptions on the neurophysiology, and efficacy of the NDT approach (Fetters, 1996; Lennon, 2000). • Even though the NDT approach is widely applied in various clinical practices, controversy still exists as to what exactly constitutes: NDT, the appropriate environment for the delivery, and the appropriate treatment duration.

41. Neurodevelopmental Treatment (NDT) Lennon (2000) suggested that future researching concerning the efficacy of NDT should consider defining the following: • A theoretical rationale for the delivery of treatment • Parameters of approach • Validity and reliability of neuroplastic changes associated with the manipulation of sensory inputs through specific handling techniques

42. Environmental Enrichment Model (EE) • The first reports of environmental influence on problem solving skills was reported in 1949 (Schallert, 2000). • In this study, pet rats demonstrated improved problem- solving skills when compared to experimental rats caged in standard housing (Schallert, 2000). • This discovery led to the hypothesis that an enriched environment allowed for the use of new experiences(Schallert, 2000, Biernaskie et al 2001) • EE rehabilitation may act to modify and strengthen connections that are inherently formed after brain injury resulting in improved functional outcomes (Biernaskie et al 2001)

43. Recovery vs Adaptation • What is the difference? • Does it really matter or is it semantics? • Do certain therapeutic exercises or pieces of therapeutic equipment promote recovery?

44. Therapeutic Exercise and Equipment What is the most beneficial? • Full body ergometer • Total Gym (couple the entire body) • PNF, NDT, manual therapy • Dynamic standing frame (or dynamic upper extremity activity in static frame) • FES bike • Whole Body Vibration (WBV) • Body weight support treadmill training (BWSTT) • Second Step Gait System and over-ground training

45. Body Wgt Support Treadmill or Overground Training? Conventional over-ground gait training is more effective in improving gait symmetry n individuals with chronic TBI (Brown et al 2005) The physical therapy strategies of body weight support on a treadmill and defined overground mobility therapy did not produce different outcomes (Dobkins etal 2006). BWSTT is being used throughout the world…after SCI. This therapy, however, is very labor-intensive, and recent evidence suggests that it may not be superior to other more conventional forms of rehabilitation ( Hicks etal 2008).

46. Lower Extremity Bracing • Why brace? • Safety • Independence • What are the choices or alternatives • Adjustability • Electrical bracing • Common mistakes • Learned non-use • No follow up for progression or modification

47. Potential Health Benefits • Cardiovascular • Immunological • Musculoskeletal

48. Cardiorespiratory Conditioning After TBIHassettet al 2008 • Primary objective was to evaluate whether fitness training improves cardiorespiratory fitness in people with TBI • 10 electronic data bases were searched • Results demonstrated clinical diversity with regard to the interventions, time post-injury and the outcome measures used (could not pool data) • Cardiorespiratory conditioning was improved in one study (6 studies, 300 total subjects) • Insufficient evidence to draw conclusion about fitness training and cardiorespiratory benefits

49. Serum-mediated osteogenic effect in traumatic brain-injured patients • Gautschi et al 20009 • Aim of this study was to investigate whether serum from TBI patients is osteoinductive • Results demonstrated a higher mean proliferation rate of primary human osteoblasts at all time points of sampling • Conclusion, there is humoral mechanism • Question: How do we maximize humoral mechanisms after TBI’s?

50. Exercise normalizes levels of growth inhibitors after brain trauma. • Animal study by Chytrova et al 2009 that looked at the effect the effects of the on protein levels of two myelin-associated molecules (MAG and Nogo) • One week of voluntary running wheel exercise overcame the injury-related increase in MAG and Nogo-A • This was apparently the result of increased activation of BDNF (brain derived neurotrophic factor) • These results indicate that exercise promotes a permissive cellular environment for repair after TBI, in a process in which BDNF plays a central role.