The Future of Restorative Neurosciences in Stroke: Driving the Translational Research Pipeline From Basic Science to Rehabilitation of People After Stroke

Background. Major advances during the past 50 years highlight the immense potential for restoration of function after neural injury, even in the damaged adult human brain. Yet, the translation of these advances into clinically useful treatments is painstakingly slow. Objective. Here, we consider why the traditional model of a “translational research pipeline” that transforms basic science into novel clinical practice has failed to improve rehabilitation practice for people after stroke. Results. We find that (1) most treatments trialed in vitro and in animal models have not yet resulted in obviously useful functional gains in patients; (2) most clinical trials of restorative treatments after stroke have been limited to small-scale studies; (3) patient recruitment for larger clinical trials is difficult; (4) the determinants of patient outcomes and what patients want remain complex and ill-defined, so that basic scientists have no clear view of the clinical importance of the problems that they are addressing; (5) research in academic neuroscience centers is poorly integrated with practice in front-line hospitals and the community, where the majority of patients are treated; and (6) partnership with both industry stakeholders and patient pressure groups is poorly developed, at least in the United Kingdom where research in the translational restorative neurosciences in stroke depends on public sector research funds and private charities. Conclusions. We argue that interaction between patients, front-line clinicians, and clinical and basic scientists is essential so that they can explore their different priorities, skills, and concerns. These interactions can be facilitated by funding research consortia that include basic and clinical scientists, clinicians and patient/carer representatives with funds targeted at those impairments that are major determinants of patient and carer outcomes. Consortia would be instrumental in developing a lexicon of common methods, standardized outcome measures, data sharing and long-term goals. Interactions of this sort would create a research-friendly, rather than only target-led, culture in front-line stroke rehabilitation services.

[1]  T. Jones,et al.  Motor Skill Training, but not Voluntary Exercise, Improves Skilled Reaching After Unilateral Ischemic Lesions of the Sensorimotor Cortex in Rats , 2008, Neurorehabilitation and neural repair.

[2]  S. Woolf The meaning of translational research and why it matters. , 2008, JAMA.

[3]  S. Dunnett,et al.  Stem cell transplantation for neurodegenerative diseases , 2007, Current opinion in neurology.

[4]  M. Chopp,et al.  Post‐ischemic treatment with erythropoietin or carbamylated erythropoietin reduces infarction and improves neurological outcome in a rat model of focal cerebral ischemia , 2007, British journal of pharmacology.

[5]  J. Démonet,et al.  Pharmacotherapy of aphasia: Myth or reality? , 2007, Brain and Language.

[6]  C. McKevitt,et al.  Clinical determinants of long-term quality of life after stroke. , 2007, Age and ageing.

[7]  D. Corbett,et al.  Enriched environment enhances transplanted subventricular zone stem cell migration and functional recovery after stroke , 2007, Neuroscience.

[8]  Jamie L Banks,et al.  Outcomes Validity and Reliability of the Modified Rankin Scale: Implications for Stroke Clinical Trials: A Literature Review and Synthesis , 2007, Stroke.

[9]  J. Westfall,et al.  Practice-based research--"Blue Highways" on the NIH roadmap. , 2007, JAMA.

[10]  W. Byblow,et al.  Functional potential in chronic stroke patients depends on corticospinal tract integrity. , 2006, Brain : a journal of neurology.

[11]  Ann M. Stowe,et al.  A Single Injection of d-Amphetamine Facilitates Improvements in Motor Training Following a Focal Cortical Infarct in Squirrel Monkeys , 2006, Neurorehabilitation and neural repair.

[12]  P. Fitzgerald,et al.  A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition , 2006, Clinical Neurophysiology.

[13]  CHAPTER 48 – REHABILITATION AFTER STROKE , 2006 .

[14]  J. Fawcett,et al.  Inosine promotes recovery of skilled motor function in a model of focal brain injury. , 2006, Brain : a journal of neurology.

[15]  Susan Redmond,et al.  Lessons Learned in Participant Recruitment and Retention: The EXCITE Trial , 2006, Physical Therapy.

[16]  J. P. Miller,et al.  Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. , 2006, JAMA.

[17]  C. Mihalopoulos,et al.  Economic Evaluation of Australian Stroke Services: A Prospective, Multicenter Study Comparing Dedicated Stroke Units With Other Care Modalities , 2006, Stroke.

[18]  D. Piazzini,et al.  Long-term outcome after stroke: evaluating health-related quality of life using utility measurement. , 2006, Stroke.

[19]  Theresa A. Jones,et al.  Epidural cortical stimulation enhances motor function after sensorimotor cortical infarcts in rats , 2006, Experimental Neurology.

[20]  Cynthia K Thompson,et al.  Single subject controlled experiments in aphasia: the science and the state of the science. , 2006, Journal of communication disorders.

[21]  C. Weiller,et al.  Dynamics of language reorganization after stroke. , 2006, Brain : a journal of neurology.

[22]  B. Kolb,et al.  Chronic low-dose administration of nicotine facilitates recovery and synaptic change after focal ischemia in rats , 2006, Neuropharmacology.

[23]  C. McKevitt,et al.  Relationships between long-term stroke disability, handicap and health-related quality of life. , 2006, Age and ageing.

[24]  J. Cheatwood,et al.  Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-a neutralization. , 2006, Cerebral cortex.

[25]  C. Fraser,et al.  Evaluating Oral Stimulation as a Treatment for Dysphagia after Stroke , 2006, Dysphagia.

[26]  Steven C Cramer,et al.  Motor Cortex Stimulation for the Enhancement of Recovery from Stroke: A Prospective, Multicenter Safety Study , 2006, Neurosurgery.

[27]  M. Hallett,et al.  Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke. , 2006, Brain : a journal of neurology.

[28]  W. McIlroy,et al.  Physiotherapy Coupled With Dextroamphetamine for Rehabilitation After Hemiparetic Stroke: A Randomized, Double-Blind, Placebo-Controlled Trial , 2006, Stroke.

[29]  L. Ada,et al.  Relation between spasticity, weakness and contracture of the elbow flexors and upper limb activity after stroke: An observational study , 2006, Disability and rehabilitation.

[30]  T. Bakas,et al.  Outcomes Among Family Caregivers of Aphasic Versus Nonaphasic Stroke Survivors , 2006, Rehabilitation nursing : the official journal of the Association of Rehabilitation Nurses.

[31]  Uwe Siebert,et al.  Long-Term Outcome After Stroke: Evaluating Health-Related Quality of Life Using Utility Measurements , 2006, Stroke.

[32]  M. Husain,et al.  Noradrenergic modulation of space exploration in visual neglect , 2006, Annals of neurology.

[33]  Ann M. Stowe,et al.  Extensive Cortical Rewiring after Brain Injury , 2005, The Journal of Neuroscience.

[34]  A. Thrift,et al.  Long-Term Outcome in the North East Melbourne Stroke Incidence Study: Predictors of Quality of Life at 5 Years After Stroke , 2005, Stroke.

[35]  S. Knecht,et al.  Dopaminergic effects on encoding of a motor memory in chronic stroke , 2005, Neurology.

[36]  Cathy J Price,et al.  The latest on functional imaging studies of aphasic stroke , 2005, Current opinion in neurology.

[37]  L. Cohen,et al.  Mechanisms underlying recovery of motor function after stroke , 2005, Postgraduate Medical Journal.

[38]  Á. Pascual-Leone,et al.  Improved picture naming in chronic aphasia after TMS to part of right Broca’s area: An open-protocol study , 2005, Brain and Language.

[39]  Peter Langhorne,et al.  Early supported discharge services for stroke patients: a meta-analysis of individual patients' data , 2005, The Lancet.

[40]  L. von Koch,et al.  A Randomized Controlled Trial of Early Supported Discharge and Continued Rehabilitation at Home After Stroke: Five-Year Follow-Up of Patient Outcome , 2005, Stroke.

[41]  J. Rothwell,et al.  Theta Burst Stimulation of the Human Motor Cortex , 2005, Neuron.

[42]  Geoffrey A. Donnan,et al.  Quality of Life After Stroke: The North East Melbourne Stroke Incidence Study (NEMESIS) , 2004, Stroke.

[43]  S. Frantz Therapeutic area influences drug development costs , 2004, Nature Reviews Drug Discovery.

[44]  Alan J Thompson,et al.  The influence of time after stroke on brain activations during a motor task , 2004, Annals of neurology.

[45]  L. Kalra,et al.  Training carers of stroke patients: randomised controlled trial , 2004, BMJ : British Medical Journal.

[46]  Shaheen Hamdy,et al.  Induction of long-term plasticity in human swallowing motor cortex following repetitive cortical stimulation , 2004, Clinical Neurophysiology.

[47]  Jacquie Kurland,et al.  Transcranial Magnetic Stimulation as a Complementary Treatment for Aphasia , 2004, Seminars in speech and language.

[48]  C. Sommer,et al.  Effect of Brain-Derived Neurotrophic Factor Treatment and Forced Arm Use on Functional Motor Recovery After Small Cortical Ischemia , 2004, Stroke.

[49]  A. Thrift,et al.  Determinants of Handicap After Stroke: The North East Melbourne Stroke Incidence Study (NEMESIS) , 2004, Stroke.

[50]  R. Popat,et al.  Stroke Impact Scale-16. A Brief Assessment of Physical Function , 2004 .

[51]  Andreas R. Luft,et al.  Lesion location alters brain activation in chronically impaired stroke survivors , 2004, NeuroImage.

[52]  D. Corbett,et al.  Efficacy of Rehabilitative Experience Declines with Time after Focal Ischemic Brain Injury , 2004, The Journal of Neuroscience.

[53]  P. Langhorne,et al.  Rehabilitation therapy services for stroke patients living at home: systematic review of randomised trials , 2004, The Lancet.

[54]  N. Hogan,et al.  Robot-aided sensorimotor arm training improves outcome in patients with chronic stroke , 2003, Neurology.

[55]  J. Kleim,et al.  Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult , 2003, Neurological research.

[56]  Ann M. Stowe,et al.  Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: A feasibility study in primates , 2003, Neurological research.

[57]  N. Young,et al.  Cortical stimulation improves skilled forelimb use following a focal ischemic infarct in the rat , 2003, Neurological research.

[58]  R. Teasell,et al.  Intensity of Aphasia Therapy, Impact on Recovery , 2003, Stroke.

[59]  Stephen B. Johnson,et al.  Central challenges facing the national clinical research enterprise. , 2003, JAMA.

[60]  Wilma M Hopman,et al.  Quality of Life During and After Inpatient Stroke Rehabilitation , 2003, Stroke.

[61]  L. Bouter,et al.  Occupational Therapy for Stroke Patients: A Systematic Review , 2003, Stroke.

[62]  V. Feigin,et al.  Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century , 2003, The Lancet Neurology.

[63]  Paul E. Kaplan,et al.  Rehabilitation of Stroke , 2002 .

[64]  D. Howard,et al.  Phonological therapy for word-finding difficulties: A re-evaluation , 2002 .

[65]  Lyndsey Nickels,et al.  Improving word finding: Practice makes (closer to) perfect? , 2002 .

[66]  S. Wood-Dauphinée,et al.  Activity, participation, and quality of life 6 months poststroke. , 2002, Archives of physical medicine and rehabilitation.

[67]  B. Kolb,et al.  Inosine induces axonal rewiring and improves behavioral outcome after stroke , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[68]  B. Bussel,et al.  Longitudinal Study of Motor Recovery After Stroke: Recruitment and Focusing of Brain Activation , 2002, Stroke.

[69]  J. Rothwell,et al.  Driving Plasticity in Human Adult Motor Cortex Is Associated with Improved Motor Function after Brain Injury , 2002, Neuron.

[70]  Philippa Clarke,et al.  Well-Being After Stroke in Canadian Seniors: Findings From the Canadian Study of Health and Aging , 2002, Stroke.

[71]  J. Kleim,et al.  Motor Learning-Dependent Synaptogenesis Is Localized to Functionally Reorganized Motor Cortex , 2002, Neurobiology of Learning and Memory.

[72]  Lalit Kalra,et al.  Can differences in management processes explain different outcomes between stroke unit and stroke-team care? , 2001, The Lancet.

[73]  John Todman,et al.  Single-case and Small-n Experimental Designs : A Practical Guide To Randomization Tests , 2001 .

[74]  J. Fridriksson,et al.  Aphasia Management During the Early Phases of Recovery Following Stroke , 2001 .

[75]  S. Studenski,et al.  The relation between impairments and functional outcomes poststroke. , 2000, Archives of physical medicine and rehabilitation.

[76]  R. Nudo,et al.  Effects of Postlesion Experience on Behavioral Recovery and Neurophysiologic Reorganization after Cortical Injury in Primates , 2000, Neurorehabilitation and neural repair.

[77]  S. Slørdahl,et al.  Stroke unit treatment. 10-year follow-up. , 1999, Stroke.

[78]  D. Clark,et al.  Development of a stroke-specific quality of life scale. , 1999, Stroke.

[79]  C Ballinger,et al.  Unpacking the black box of therapy – a pilot study to describe occupational therapy and physiotherapy interventions for people with stroke , 1999, Clinical rehabilitation.

[80]  M. Just,et al.  Plasticity of language-related brain function during recovery from stroke. , 1999, Stroke.

[81]  John C. Rothwell,et al.  Long-term reorganization of human motor cortex driven by short-term sensory stimulation , 1998, Nature Neuroscience.

[82]  N. Hogan,et al.  The effect of robot-assisted therapy and rehabilitative training on motor recovery following stroke. , 1997, Archives of neurology.

[83]  C. Hoffman,et al.  Persons with chronic conditions. Their prevalence and costs. , 1996, JAMA.

[84]  M. Fuhrer SUBJECTIVE WELL-BEING: IMPLICATIONS FOR MEDICAL REHABILITATION OUTCOMES AND MODELS OF DISABLEMENT , 1994, American journal of physical medicine & rehabilitation.

[85]  R. Robinson,et al.  The relationship between the perception of social support and post-stroke depression in hospitalized patients. , 1991, Psychiatry.

[86]  N. Schneiderman,et al.  Amphetamine promotes recovery from sensory-motor integration deficit after thrombotic infarction of the primary somatosensory rat cortex. , 1991, Stroke.

[87]  D. Hovda,et al.  Amphetamine with experience promotes recovery of locomotor function after unilateral frontal cortex injury in the cat , 1984, Brain Research.

[88]  H. Reisner [REHABILITATION IN STROKE]. , 1963, Wiener Zeitschrift fur Nervenheilkunde und deren Grenzgebiete.

[89]  G. Hankey,et al.  Organised inpatient (stroke unit) care for stroke , 2007 .

[90]  J. Blass Quality of Life After Stroke: The North East Melbourne Stroke Incidence Study (NEMESIS) , 2006 .

[91]  N. Ward Neural plasticity and recovery of function. , 2005, Progress in brain research.

[92]  T. Platz,et al.  Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial. , 2005, Restorative neurology and neuroscience.

[93]  M Husain,et al.  Hemispatial neglect. , 2004, Journal of neurology, neurosurgery, and psychiatry.

[94]  C. Wolfe,et al.  The impact of stroke. , 2000, British medical bulletin.

[95]  J. Davis,et al.  Post-lesion practice and amphetamine-facilitated recovery of beam-walking in the rat. , 1990, Restorative neurology and neuroscience.