Agreed definitions and a shared vision for new standards in stroke recovery research: The Stroke Recovery and Rehabilitation Roundtable taskforce:
Julie Bernhardt1, Kathryn S Hayward2, Kathryn S Hayward1, Gert Kwakkel3, Gert Kwakkel4, Nick S. Ward5, Steven L. Wolf6, Karen Borschmann1, John W. Krakauer7, Lara A. Boyd2, S. Thomas Carmichael8, Dale Corbett9, Dale Corbett10, Steven C. Cramer11 •
Florey Institute of Neuroscience and Mental Health1, University of British Columbia2, Northwestern University3, VU University Amsterdam4, UCL Institute of Neurology5, Emory University6, Johns Hopkins University7, University of California, Los Angeles8, Heart and Stroke Foundation of Canada9, University of Ottawa10, University of California, Irvine11
TL;DR: This paper outlines the working definitions established by the Stroke Recovery and Rehabilitation Roundtable group and an agreed vision for accelerating progress in stroke recovery research.
Abstract: The first Stroke Recovery and Rehabilitation Roundtable established a game changing set of new standards for stroke recovery research. Common language and definitions were required to develop an agreed framework spanning the four working groups: translation of basic science, biomarkers of stroke recovery, measurement in clinical trials and intervention development and reporting. This paper outlines the working definitions established by our group and an agreed vision for accelerating progress in stroke recovery research.
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TL;DR: The results of a consensus meeting about measurement standards and patient characteristics that should be collected in all future stroke recovery trials are presented and a strong case is made for addition of kinematic and kinetic movement quantification.
Abstract: Finding, testing and demonstrating efficacy of new treatments for stroke recovery is a multifaceted challenge. We believe that to advance the field, neurorehabilitation trials need a conceptually rigorous starting framework. An essential first step is to agree on definitions of sensorimotor recovery and on measures consistent with these definitions. Such standardization would allow pooling of participant data across studies and institutions aiding meta-analyses of completed trials, more detailed exploration of recovery profiles of our patients and the generation of new hypotheses. Here, we present the results of a consensus meeting about measurement standards and patient characteristics that we suggest should be collected in all future stroke recovery trials. Recommendations are made considering time post stroke and are aligned with the international classification of functioning and disability. A strong case is made for addition of kinematic and kinetic movement quantification. Further work is being undertaken by our group to form consensus on clinical predictors and pre-stroke clinical data that should be collected, as well as recommendations for additional outcome measurement tools. To improve stroke recovery trials, we urge the research community to consider adopting our recommendations in their trial design.
355 citations
Cites background from "Agreed definitions and a shared vis..."
...The SRRR definitions paper contains rationale for time points and description of terms.(10)...
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TL;DR: Several large intervention trials targeting motor recovery report that participants' motor performance improved, but to a similar extent for both the intervention and control groups in most trials.
Abstract: Stroke remains a leading cause of adult disability and the demand for stroke rehabilitation services is growing. Substantial advances are yet to be made in stroke rehabilitation practice to meet this demand and improve patient outcomes relative to current care. Several large intervention trials targeting motor recovery report that participants' motor performance improved, but to a similar extent for both the intervention and control groups in most trials. These neutral results might reflect an absence of additional benefit from the tested interventions or the many challenges of designing and doing large stroke rehabilitation trials. Strategies for improving trial quality include new approaches to the selection of patients, control interventions, and endpoint measures. Although stroke rehabilitation research strives for better trials, interventions, and outcomes, rehabilitation practices continue to help patients regain independence after stroke.
338 citations
Lara A. Boyd1, Kathryn S Hayward2, Nick S. Ward3, Cathy M. Stinear4, Charlotte Rosso5, Rebecca J Fisher6, Alexandre R. Carter7, Alexander P. Leff8, David A. Copland9, Leeanne M. Carey2, Leonardo G. Cohen, D. Michele Basso10, Jane Maguire11, Steven C. Cramer12 •
University of British Columbia1, Florey Institute of Neuroscience and Mental Health2, UCL Institute of Neurology3, University of Auckland4, University of Paris5, University of Nottingham6, Washington University in St. Louis7, University College London8, University of Queensland9, Ohio State University10, University of Technology, Sydney11, University of California, Irvine12
TL;DR: A way forward for when and where biomarkers can be included in clinical trials is proposed to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke.
Abstract: The most difficult clinical questions in stroke rehabilitation are “What is this patient’s potential for recovery?” and “What is the best rehabilitation strategy for this person, given her/his clinical profile?” Without answers to these questions, clinicians struggle to make decisions regarding the content and focus of therapy, and researchers design studies that inadvertently mix participants who have a high likelihood of responding with those who do not. Developing and implementing biomarkers that distinguish patient subgroups will help address these issues and unravel the factors important to the recovery process. The goal of the present paper is to provide a consensus statement regarding the current state of the evidence for stroke recovery biomarkers. Biomarkers of motor, somatosensory, cognitive and language domains across the recovery timeline post-stroke are considered; with focus on brain structure and function, and exclusion of blood markers and genetics. We provide evidence for biomarkers that are considered ready to be included in clinical trials, as well as others that are promising but not ready and so represent a developmental priority. We conclude with an example that illustrates the utility of biomarkers in recovery and rehabilitation research, demonstrating how the inclusion of a biomarker may enhance future clinical trials. In this way, we propose a way forward for when and where we can include biomarkers to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke.
223 citations
TL;DR: The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial.
Abstract: Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain’s dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful.
219 citations
Cites background from "Agreed definitions and a shared vis..."
...As other experts have observed, development of biomarkers and other tools to reliably stratify patients by recovery potential early in the course of stroke would be of enormous benefit to future trialists [89]....
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TL;DR: This review summarized the state of the art regarding kinematic upper limb assessments poststroke with respect to the assessment task, measurement system, and performance metrics with their clinimetric properties and provided evidence-based recommendations for future applications of upper limb kinematics in stroke recovery research.
Abstract: Background and Purpose- Assessing upper limb movements poststroke is crucial to monitor and understand sensorimotor recovery. Kinematic assessments are expected to enable a sensitive quantification of movement quality and distinguish between restitution and compensation. The nature and practice of these assessments are highly variable and used without knowledge of their clinimetric properties. This presents a challenge when interpreting and comparing results. The purpose of this review was to summarize the state of the art regarding kinematic upper limb assessments poststroke with respect to the assessment task, measurement system, and performance metrics with their clinimetric properties. Subsequently, we aimed to provide evidence-based recommendations for future applications of upper limb kinematics in stroke recovery research. Methods- A systematic search was conducted in PubMed, Embase, CINAHL, and IEEE Xplore. Studies investigating clinimetric properties of applied metrics were assessed for risk of bias using the Consensus-Based Standards for the Selection of Health Measurement Instruments checklist. The quality of evidence for metrics was determined according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Results- A total of 225 studies (N=6197) using 151 different kinematic metrics were identified and allocated to 5 task and 3 measurement system groups. Thirty studies investigated clinimetrics of 62 metrics: reliability (n=8), measurement error (n=5), convergent validity (n=22), and responsiveness (n=2). The metrics task/movement time, number of movement onsets, number of movement ends, path length ratio, peak velocity, number of velocity peaks, trunk displacement, and shoulder flexion/extension received a sufficient evaluation for one clinimetric property. Conclusions- Studies on kinematic assessments of upper limb sensorimotor function are poorly standardized and rarely investigate clinimetrics in an unbiased manner. Based on the available evidence, recommendations on the assessment task, measurement system, and performance metrics were made with the goal to increase standardization. Further high-quality studies evaluating clinimetric properties are needed to validate kinematic assessments, with the long-term goal to elucidate upper limb sensorimotor recovery poststroke. Clinical Trial Registration- URL: https://www.crd.york.ac.uk/prospero/ . Unique identifier: CRD42017064279.
160 citations
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TL;DR: The coagulation cascade, haemoglobin breakdown products, and inflammation all play a part in ICH-induced injury and could provide new therapeutic targets and new therapeutic interventions for this severe form of stroke.
Abstract: Summary The past decade has resulted in a rapid increase in knowledge of mechanisms underlying brain injury induced by intracerebral haemorrhage (ICH). Animal studies have suggested roles for clot-derived factors and the initial physical trauma and mass effect as a result of haemorrhage. The coagulation cascade (especially thrombin), haemoglobin breakdown products, and inflammation all play a part in ICH-induced injury and could provide new therapeutic targets. Human imaging has shown that many ICH continue to expand after the initial ictus. Rebleeding soon after the initial haemorrhage is common and forms the basis of a current clinical trial using factor VIIa to prevent rebleeding. However, questions about mechanisms of injuries remain. There are conflicting data on the role of ischaemia in ICH and there is uncertainty over the role of clot removal in ICH therapy. The next decade should bring further information about the underlying mechanisms of ICH-induced brain injury and new therapeutic interventions for this severe form of stroke. This review addresses our current understanding of the mechanisms underlying ICH-induced brain injury.
1,195 citations
TL;DR: A valid prognosis of UE function can be made within 3 and 6 weeks in patients with mild and severe UE paresis, respectively, and a valid prediction should not be expected after 6 and 11 weeks respectively, in these groups of patients.
889 citations
TL;DR: There was a remarkable uniformity in the sequences of recovery of all patients, regardless of whether sensory disturbances were present and whether the dominant or nondominant hemisphere was involved; the patients progressed from one recovery phase to the next in an orderly fashion without any of the phases being omitted.
Abstract: The sequence of motor recovery of 121 patients with hemiplegia was Investigated at Boston City Hospital. These patients, with the exception of three, were diagnosed as cerebral vascular accidents caused by thrombosis or embolus of one of the cerebral vessels. At the time the report was written, no autopsy results were available, hence the exact location of the lesion could not be determined. Each patient was examined at regular intervals, and electromyographic records were obtained from some of the patients. The motor recovery of both upper and lower limbs were observed, but attention was focused on the upper limb, in particular on the course of restoration of the grasping function of the hand. Slight sensory defects were found present in 87 of the 121 patients. An analysis of the data collected in this study indicated that the recovery process followed a general pattern. There was a remarkable uniformity in the sequences of recovery of all patients. This was true regardless of whether sensory disturbances were present and whether the dominant or nondominant hemisphere was involved. The patients progressed from one recovery phase to the next in an orderly fashion without any of the phases being omitted. The same sequence was followed by patients who recovered completely as well as by those patients whose recovery was arrested at any one of the stages. Immediately following the cerebral vascular accident, the condition was essentially flaccid, with loss or hypoactivity of the tendon reflexes, Thereafter, the following recovery phases were observed:
828 citations
TL;DR: Sex, handedness, and side of stroke lesion were not independent outcome predictors, and the influence of age was minimal, but a valid prognosis of aphasia could be made within 1 to 4 weeks after the stroke depending on the initial severity.
Abstract: Knowledge of the frequency and remission of aphasia is essential for the rehabilitation of stroke patients and provides insight into the brain organization of language. We studied prospectively and consecutively an unselected and community-based sample of 881 patients with acute stroke. Assessment of aphasia was done at admission, weekly during the hospital stay, and at a 6-month follow-up using the aphasia score of the Scandinavian Stroke Scale. Thirty-eight percent had aphasia at the time of admission; at discharge 18% had aphasia. Sex was not a determinant of aphasia in stroke, and no sex difference in the anterior-posterior distribution of lesions was found. The remission curve was steep: Stationary language function in 95% was reached within 2 weeks in those with initial mild aphasia, within 6 weeks in those with moderate, and within 10 weeks in those with severe aphasia. A valid prognosis of aphasia could be made within 1 to 4 weeks after the stroke depending on the initial severity of aphasia. Initial severity of aphasia was the only clinically relevant predictor of aphasia outcome. Sex, handedness, and side of stroke lesion were not independent outcome predictors, and the influence of age was minimal.
748 citations
TL;DR: This Point of View describes the problem and offers a solution in the form of definitions of compensation and recovery at the neuronal, motor performance, and functional levels within the framework of the International Classification of Functioning model.
Abstract: There is a lack of consistency among researchers and clinicians in the use of terminology that describes changes in motor ability following neurological injury Specifically, the terms and definitions of motor compensation and motor recovery have been used in different ways, which is a potential barrier to interdisciplinary communication This Point of View describes the problem and offers a solution in the form of definitions of compensation and recovery at the neuronal, motor performance, and functional levels within the framework of the International Classification of Functioning model
739 citations
"Agreed definitions and a shared vis..." refers background in this paper
...In the motor domain, compensation strategies employ the use of intact muscles, joints and effectors in the affected limb, to accomplish the desired task or goal.(10,11) In the language system, compensation may refer to the use of an augmentative and alternative communication device, including a communication board....
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