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      A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable

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          Abstract

          Rationale:

          Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities.

          Methods:

          We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed.

          Results:

          We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool.

          Conclusions:

          By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

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          Most cited references61

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          Plasticity during stroke recovery: from synapse to behaviour.

          Reductions in blood flow to the brain of sufficient duration and extent lead to stroke, which results in damage to neuronal networks and the impairment of sensation, movement or cognition. Evidence from animal models suggests that a time-limited window of neuroplasticity opens following a stroke, during which the greatest gains in recovery occur. Plasticity mechanisms include activity-dependent rewiring and synapse strengthening. The challenge for improving stroke recovery is to understand how to optimally engage and modify surviving neuronal networks, to provide new response strategies that compensate for tissue lost to injury.
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            Psychometric properties of the Fatigue Severity Scale and the Modified Fatigue Impact Scale.

            Fatigue is one of the most common, debilitating and life altering symptoms experienced by those with multiple sclerosis (MS) and has become the focus of therapeutic interventions and clinical rehabilitation. There is limited evidence regarding the psychometric properties and clinical relevance of fatigue outcomes for interpreting the effectiveness of intervention and rehabilitation strategies. This study determined the reliability, precision and clinically important change of the uni-dimensional Fatigue Severity Scale (FSS) and the multi-dimensional Modified Fatigue Impact Scale (MFIS). The FSS and MFIS along with physical, psychological and cognitive clinical outcomes were administered to a sample of 82 persons with MS in a clinical research setting on two time points, separated by six months. Intraclass correlation coefficient (ICC) analyses established reliability; standard error of measurement (SEM) and coefficient of variation (CV) determined precision; minimal detectable change (MDC) defined clinically important change. Participants varied in type of MS and disability status, with 77% of participants classified as having substantial fatigue, based on the criteria of a mean FSS score ≥4. The MFIS (ICC=0.863) and the FSS (ICC=0.751) had acceptable reliability over six months. Precision was reasonable for both scales (based on SEM and CV estimates) but better for the FSS. MDC estimates were established and were lower for the FSS. Reliability of the FSS and MFIS falls within acceptable ranges, and precision and clinically important change estimates provide guidelines for interpreting change in scores from these outcomes in clinical research of intervention and rehabilitation approaches for managing fatigue. Copyright © 2013 Elsevier B.V. All rights reserved.
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              The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders

              Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research.
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                Author and article information

                Journal
                Int J Stroke
                Int J Stroke
                WSO
                spwso
                International Journal of Stroke
                SAGE Publications (Sage UK: London, England )
                1747-4930
                1747-4949
                12 October 2023
                February 2024
                : 19
                : 2
                : 133-144
                Affiliations
                [1 ]School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
                [2 ]Heart and Stroke Program, Hunter Medical Research Institute, Newcastle, NSW, Australia
                [3 ]Department of Neurology, University of Kansas Medical Centre, University of Kansas Alzheimer’s Disease Research Centre, Kansas City, KS, USA
                [4 ]Department of Medicine (RMH), University of Melbourne, Heidelberg, VIC, Australia
                [5 ]School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
                [6 ]School of Health Sciences, University of Nottingham, Nottingham, UK
                [7 ]Queen Square Institute of Neurology, University College London, London, UK
                [8 ]Department of Neurology, Bashkir State Medical University, Ufa, Russia
                [9 ]Department of Interdisciplinary Health Sciences, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
                [10 ]Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway
                [11 ]Faculty of Health, Health and Education, Manchester Metropolitan University, Manchester, UK
                [12 ]IIMPACT in Health, University of South Australia, Adelaide, SA, Australia
                [13 ]Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
                [14 ]Department of Communication Sciences and Disorders, Syracuse University, Syracuse, NY, USA
                [15 ]Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia
                [16 ]Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
                [17 ]Department of Cellular and Molecular Medicine, University of Ottawa Roger Guindon Hall, Ottawa, ON, Canada
                [18 ]Ageing and Health, Usher Institute, University of Edinburgh, Edinburgh, UK
                Author notes
                [*]Coralie English, School of Health Sciences, College of Health, Medicine and Wellbeing, University of Newcastle, University Drive, Callaghan, NSW 2083, Australia. Email: Coralie.English@ 123456newcastle.edu.au
                [*]

                Co-senior authors.

                This contribution, first published in International Journal of Stroke, is being co-published in the following journals: Neurorehabilitation and Neural Repair.

                Author information
                https://orcid.org/0000-0001-5910-7927
                https://orcid.org/0000-0002-9386-4830
                https://orcid.org/0000-0002-1618-7207
                https://orcid.org/0000-0002-4288-0814
                https://orcid.org/0000-0003-1001-2024
                https://orcid.org/0000-0002-7144-5096
                https://orcid.org/0000-0003-0652-3104
                https://orcid.org/0000-0002-0791-0950
                https://orcid.org/0000-0002-9020-1847
                https://orcid.org/0000-0001-7494-2023
                Article
                10.1177_17474930231189135
                10.1177/17474930231189135
                10811972
                37424273
                a367110f-8895-4bef-a6e5-e398c8f9d63b
                © 2023 World Stroke Organization

                This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 16 May 2023
                : 27 June 2023
                Funding
                Funded by: unrestricted educational grants provided by Ipsen Pharma and Moleac, ;
                Funded by: NHMRC Centre of Research Excellence to Accelerate Stroke Trial Innovation and Translation, ;
                Award ID: GNT2015705
                Funded by: Canadian Partnership for Stroke Recovery, ;
                Categories
                Guidelines
                Custom metadata
                ts1

                Cardiovascular Medicine
                stroke,rehabilitation,recovery,consensus,fatigue,measurement,mechanisms
                Cardiovascular Medicine
                stroke, rehabilitation, recovery, consensus, fatigue, measurement, mechanisms

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