Restoring neurological function: putting the neurosciences to work in neurorehabilitation

1. Restoring neurological function: putting the neurosciences to work in neurorehabilitation Action in Neurorehabilitation: Newbury Thursday 21st April 2005 Raymond C Tallis F Med Sci Newbury, 21 April 2005

3. Background • Prevalence of neurodisability • State of the science (craft, art) • Promise of neuroscience Newbury, 21 April 2005

4. Current prevalence (estimated UK total) Newbury, 21 April 2005

5. Future prevalence • Many causes of neurodisability strongly age-related • Population is ageing • Prevalence may therefore rise • Biggest challenge for health services in developed countries Newbury, 21 April 2005

6. Background • Prevalence of neurodisability • State of the science (craft, art) • Promise of neuroscience Newbury, 21 April 2005

7. Neurorehabilitation Aim to maximise independence in people with neurological impairments Triple strategy: • Prevent complications • Adaptation to impairments (physical, psychological, environmental, social) • Reversal of impairments Newbury, 21 April 2005

8. Rehabilitation Strategies Aids, Appliances, Adaptations Benefits Education ‘Higher level’ Interventions: Adaptation to impairment Support for carers Counselling Prevention of secondary complications Retraining ‘Lower level’, ‘hands-on’ interventions: Reducing impairment Sensory stimulation Perceptual cueing Antispastic manoeuvres Intensive repetitive activity Newbury, 21 April 2005 Progressive resistive exercises

9. Neurorehabilitation: state of the art Much progress (for example, stroke) in: • Preventing complications • Adaptation to impairments Less progress in reversing impairments Newbury, 21 April 2005

10. Crossing the Ecological Gap Abilities of client Aids, Appliances, Adaptations Support Services Demands of the world Newbury, 21 April 2005

11. Stroke Rehabilitation: The good news • Organised stroke care saves lives and reduces disability • Langhorne et al 1993, Stroke Trialists 1997 • These benefits are seen 5 and 10 years after the stroke • Indredavik, 1997, Indredavik, 2000, Lincoln, 2000 • Some of these benefits are due to rehabilitation • Stroke Trialists 1997, Kwakkel et al, 1998 Newbury, 21 April 2005

12. Stroke Rehabilitation: The less good news • We have little idea which components of the rehabilitation package are effective • There is some evidence that higher-level interventions (e.g. occupational therapy visits) are effective • Walker et al, 1999 • There is little evidence that specific ‘hands-on’ techniques have major or lasting effects on impairments • Lincoln et al, 1999, Pomeroy and Tallis, 2000 Newbury, 21 April 2005

13. Physical therapies to improve movement performance and functional ability post-stroke • A few techniques work • In many the evidence is equivocal • No technique has major sustained effects on impairments • This does not rule out major beneficial impact Pomeroy et al 2000 Newbury, 21 April 2005

14. Intensity: effect of augmented exercise therapy time after stroke: a meta-analysis Kwakkel et al Stroke 2004 31 papers, 2686 patients Small but favourable effect on ADL, IADL and walking speed but not for dexterity Newbury, 21 April 2005

15. Intensity meta-analysis: caveats • Methodological quality of papers ranged from 2-10 out of 14 • In most papers intensity not the primary variable investigated Newbury, 21 April 2005

16. Long term disability after first ever stroke and related prognostic factors in the Perth Community Stroke Study 1989-1990Hankey et al. Stroke 2002; 33:1034-1040 • Population of 138,700 sampled for first ever stroke over 18 months and followed up prospectively for 5 years • 370 cases of first ever stroke and 277 patients survived for 30 days • Of 30 day survivors of first ever stroke, approximately half survive 5 years • One third remain disabled • One in seven are in permanent institutional care Newbury, 21 April 2005

17. Current imperatives • Universalisation of best practice (less than half patients are admitted to stroke units at any time during hospital stay (Sentinel Audit, 2004) • More effective approaches to reversing impairments Newbury, 21 April 2005

18. Background • Prevalence of neurodisability • State of the science (craft, art) • Promise of neuroscience Newbury, 21 April 2005

19. The revolution in neuroscience • Understanding brain damage and recovery • New treatment modalities • Advances in current therapeutic approaches • New research methodologies Newbury, 21 April 2005

20. Understanding brain damage and recovery • Developmental neuroscience • Advances in cognitive neuroscience • Neuroimaging • PET, MRI, MEG, TMS Newbury, 21 April 2005

21. The revolution in neuroscience As it was Stable structure Function As it is Labile organisation Function Information (afferent input) Newbury, 21 April 2005

22. Reorganisation Microscopic – synaptic Macroscopic - maps Newbury, 21 April 2005

23. A 1 mm 1 cm B Somatosensory Cortex (black) before (A) and after (B) controlled tactile stimulation W.M.Jenkins et al J Neurophsiol. 1990;68:82-104 Newbury, 21 April 2005

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25. New technologies • To promote understanding of recovery • e.g. functional neuroimaging • To promote recovery • e.g. neural transplantation, drugs, electro-therapy Newbury, 21 April 2005

26. New treatment modalities • Electrical stimulation • Deep brain stimulation • Functional electrical stimulation • Neural transplantation • Drugs to promote neuroprotection and neuroplasticity Newbury, 21 April 2005

27. Advances in current therapeutic approaches • Maximising participation through rehabilitation • Physical therapies to restore movement • Rehabilitation engineering • Cybernetic technologies? • Robotics • Neuroimplantation devices Newbury, 21 April 2005

28. New research methodologies • Clinical trial designs: from single case studies to mega-trials • Outcome measures • Research synthesis Newbury, 21 April 2005

29. Where we are now • A better understanding of natural recovery of the damaged nervous system • A better understanding of the scope of such recovery • A better understanding of the ways in which such recovery may be promoted • A better understanding of the way new treatments should be evaluated • In short, promise of more effective ways of reversing impairments Newbury, 21 April 2005

30. Towards a science of neurorehabilitation • Characterising disorders • What are we trying to treat? • Characterising treatments • What are we treating with? • Measuring outcomes • Precisely what effect(s) do we expect? • Devising treatments • Biologically plausible strategies that will not interfere with good acute brain care Newbury, 21 April 2005

31. The challenge • Turning this new knowledge into benefits for patients • Crossing the gap between basic neuroscience and clinical care • Ensuring continuing (two-way) dialogue and collaboration between basic neuroscientists, clinical scientists and practitioners Newbury, 21 April 2005

32. Barriers • Physical and cultural distances between basic scientists and clinicians • Lack of knowledge and understanding of each other’s agenda and achievements • Limited career opportunities for working on the interface and in wider collaborations • Lack of infrastructure to support research strategies able to exploit the opportunities created by the neuroscience revolution Newbury, 21 April 2005

33. Physical Therapy (e.g. “branded” therapies for stroke) Rationale ill-defined, or intuitive and incorrect Content & dose vague Target Population poorly characterised Inappropriate outcome measures Pharmacotherapy (e.g. ACEIs for cardiac failure Clearly defined rationale (science-based) Content & dose specified Target population well characterised Appropriate outcome measures The adolescent clinical science of neuro-rehabilitation Newbury, 21 April 2005

34. Physiotherapy for patients with mobility problems more than 1 year after stroke: a randomised controlled trial • Modest, transient benefits • However, problems • Theoretical framework of treatment unclear • Content of treatment not specified • Deficits characterised only according to side • Outcome measures – Rivermead Index • Green et al, Lancet, 2002 Newbury, 21 April 2005

36. Mission of Academy The independent Academy of Medical Sciences promotes advances in medical science and campaigns to ensure these are translated as quickly as possible into benefits for patients. Newbury, 21 April 2005

37. What is it and what does it do? • Established in 1998 • Equivalent of Royal Society • Promote medical science across disciplinary boundaries • Fellowship of 700 leading medical scientists in the UK Newbury, 21 April 2005

38. Terms of reference of the report • To identify, characterise and document opportunities arising out of advances in neuroscience to improve the care of patients with neurodisability Newbury, 21 April 2005

39. Some possible misconceptions • Report implies there has been no progress in rehabilitation • Report has greater scope than it actually has • Report suggests that biological science can deliver alone • do it without psycho-social sciences • welfare of people with disability does not depend enormously on widest psycho-social context Newbury, 21 April 2005

40. Report highlights multifaceted rehabilitation “A fundamental insight of rehabilitation is that limitations imposed on an individual by a disabling disease are not simply proportional to the quantity of biological impairment but also reflect material and social circumstances that individuals contend with” Acad Med Scis 2004;p11 Newbury, 21 April 2005

41. Will the emergent science displace… • The art of rehabilitation? • Traditional therapies? Newbury, 21 April 2005

42. Environment matters Regeneration unorganised by appropriate information Neural hairballs Regeneration organised by appropriate information Neural circuitry Newbury, 21 April 2005

43. Nothing works without it Behavioural benefits of foetal neocortical cell transplants in lesioned cortex seen only if animal housed in an enriched environment Mattson et al, 1997 Inhibitors of plasticity may be as important as stimulation for successful outcome in ischaemic lesions Karj et al 1999, Wenk et al, 1999 Brain derived growth factor reduced in an environment enriched post-ischaemic animal Johansson et al,1999 Newbury, 21 April 2005

44. Attention in rehabilitation • We learn nothing we do not attend to • Rehabilitation is about learning • Patients need to attend to the treatment we give Robertson, 1999 • The patient is a person in a world not just a nervous system in a skull and vertebral column Newbury, 21 April 2005

45. Stimulation alters gene expression • Huntington’s mice with enriched environment have delayed onset of symptoms • Such stimulated mice have a larger peristraital cell volume by 13% Blakemore, Nature 2000 Newbury, 21 April 2005

46. Reversing Impairment Neural transplantation [Dis]Organisation [Loss of] Function Drugs Information ‘External’ Input Assisted activity/Constraint induced therapy Prosthetic information (eg electrotherapy) Newbury, 21 April 2005

47. Report highlights complexity of rehabilitation “A neuroscience-based approach to the reversal of impairment will not replace a multidisciplinary multi-agency approach. The complex mixture of cognitive, behavioural, psychosocial and environmental elements contribute to recovery of function. They form the clinical context within which the impact of neuroscience intervention must be evaluated” Summarised from:Acad Med Scis 2004;p11 Newbury, 21 April 2005

48. Recommendations • Regional Neurorehabilitation Research Centres • Highly skilled workforce • Research and infrastructure funding • Research culture development Newbury, 21 April 2005

49. Recommendation 1Regional Neurorehabilitation Research Centres “The NHS & academic community should collaborate to create a number of Regional Neurorehabilitation Research Centres (RNRCs) each closely associated with one or more universities” Neurobiologists Psychologists Rehabilitation engineers Nurses User groups, clinicians & researchers Sociologists Therapists Radiologists Clinical psychologists Movement scientists Doctors Newbury, 21 April 2005

50. Recommendation 2Highly skilled workforce “Recruitment, training and career structures should be improved as incentives for those undertaking or wishing to undertake research into neurorehabilitation” • Current initiatives for undergraduate and postgraduate training in neurorehabilitation research should be strengthened • New full-time academic posts needed • Appropriate contractual arrangements to facilitate research activity by nurses, PAMs and others • Staffing needs of service delivery nationally Newbury, 21 April 2005