Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable

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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.

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Most cited references 5

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Longitudinal study of motor recovery after stroke: recruitment and focusing of brain activation.

A Feydy, R. Carlier, A Roby-Brami … (2002)

The goal of this study was to characterize cortical reorganization after stroke and its relation with the site of the stroke-induced lesion and degree of motor recovery using functional MRI (fMRI). Fourteen stroke patients with an affected upper limb were studied longitudinally. Three fMRI sessions were performed over a period of 1 to 6 months after stroke. Upper limb recovery, Wallerian degeneration of the pyramidal tract, and responses to transcranial magnetic stimulation were assessed. Two main patterns of cortical reorganization were found. Pattern 1 was focusing, in which, after initial recruitment of additional ipsilateral and contralateral areas, activation gradually developed toward a pattern of activation restricted to the contralateral sensorimotor cortex in 9 patients. Five patients were found to have pattern 2, persistent recruitment, in which there was an initial and sustained recruitment of ipsilateral activity. Occurrence of recruitment or focusing seemed to depend mainly on whether the primary motor cortex (M1) was lesioned; persistent recruitment was observed in 3 of 4 patients with M1 injury, and focusing was seen in 8 of 10 patients with spared M1. These patterns had no relation to the degree of recovery; in particular, focusing did not imply recovery. However, there was a clear relation between the degree of recovery and the degree of Wallerian degeneration. These results suggest that ipsilateral recruitment after stroke corresponds to a compensatory corticocortical process related to the lesion of the contralateral M1 and that the process of compensatory recruitment will persist if M1 is lesioned; otherwise, it will be transient.

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Predicting speech fluency and naming abilities in aphasic patients

Jasmine Wang, Sarah Marchina, Andrea C. Norton … (2013)

There is a need to identify biomarkers that predict degree of chronic speech fluency/language impairment and potential for improvement after stroke. We previously showed that the Arcuate Fasciculus lesion load (AF-LL), a combined variable of lesion site and size, predicted speech fluency in patients with chronic aphasia. In the current study, we compared lesion loads of such a structural map (i.e., AF-LL) with those of a functional map [i.e., the functional gray matter lesion load (fGM-LL)] in their ability to predict speech fluency and naming performance in a large group of patients. The fGM map was constructed from functional brain images acquired during an overt speaking task in a group of healthy elderly controls. The AF map was reconstructed from high-resolution diffusion tensor images also from a group of healthy elderly controls. In addition to these two canonical maps, a combined AF-fGM map was derived from summing fGM and AF maps. Each canonical map was overlaid with individual lesion masks of 50 chronic aphasic patients with varying degrees of impairment in speech production and fluency to calculate a functional and structural lesion load value for each patient, and to regress these values with measures of speech fluency and naming. We found that both AF-LL and fGM-LL independently predicted speech fluency and naming ability; however, AF lesion load explained most of the variance for both measures. The combined AF-fGM lesion load did not have a higher predictability than either AF-LL or fGM-LL alone. Clustering and classification methods confirmed that AF lesion load was best at stratifying patients into severe and non-severe outcome groups with 96% accuracy for speech fluency and 90% accuracy for naming. An AF-LL of greater than 4 cc was the critical threshold that determined poor fluency and naming outcomes, and constitutes the severe outcome group. Thus, surrogate markers of impairments have the potential to predict outcomes and can be used as a stratifier in experimental studies.

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Fiber-tracking method reveals sensorimotor pathway involvement in stroke patients.

Osamu Kizu, Osamu Tanaka, K Yoshikawa, … (2003)

We tested the feasibility of a new MRI technique that provides visualization of the sensorimotor tracts in vivo in a group of stroke victims. Fourteen patients with small infarctions involving the white matter of the supratentorial brain were evaluated. Sensorimotor tracts on the lesional and contralesional sides were successfully depicted in all cases. The position of the sensorimotor tracts relative to the infarct was in good agreement with clinical symptoms. The overall sensitivity and specificity for sensorimotor tract involvement were 100% and 77%, respectively. Our proposed fiber-tracking method was shown to be a clinically feasible technique that correlates well with clinical symptoms.

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Author and article information

Journal

Title: International Journal of Stroke

Abbreviated Title: International Journal of Stroke

Publisher: SAGE Publications

ISSN (Print): 1747-4930

ISSN (Electronic): 1747-4949

Publication date Created: July 2017

Publication date (Electronic): July 12 2017

Publication date (Print): July 2017

Volume: 12

Issue: 5

Pages: 480-493

Affiliations

[1 ]Department of Physical Therapy & the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada

[2 ]Department of Physical Therapy, University of British Columbia, Vancouver, Canada; Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia

[3 ]Sobell Department of Motor Neuroscience, UCL Institute of Neurology, Queen Square, London, UK

[4 ]Department of Medicine and Centre for Brain Research, University of Auckland, Auckland, New Zealand

[5 ]Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France

[6 ]AP-HP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France

[7 ]Division of Rehabilitation & Ageing, University of Nottingham, Nottingham, UK

[8 ]Department of Neurology, Washington University in Saint Louis, St Louis, MO, USA

[9 ]Department of Brain Repair and Rehabilitation, Institute of Neurology & Institute of Cognitive Neuroscience, University College London, Queens Square, London, UK

[10 ]School of Health & Rehabilitation Sciences, University of Queensland, Brisbane, Australia; and University of Queensland Centre for Clinical Research, Brisbane, Australia

[11 ]School of Allied Health, College of Science, Health and Engineering, La Trobe, University, Bundoora, Australia; and Neurorehabilitation and Recovery, Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia

[12 ]Human Cortical Physiology and Neurorehabilitation Section, NINDS, NIH, Bethesda, MD, USA

[13 ]School of Health and Rehabilitation Sciences, The Ohio State University, Columbus, OH, USA

[14 ]Faculty of Health, University of Technology, Ultimo, Sydney, Australia

[15 ]University of California, Irvine, CA, USA; Depts. Neurology, Anatomy & Neurobiology, and Physical Medicine & Rehabilitation, Irvine, CA, USA

Article

DOI: 10.1177/1747493017714176

PMC ID: 6791523

PubMed ID: 28697711

SO-VID: 331f98a7-1638-4542-a143-a545f8426ba9

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Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable

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Most cited references 5

Longitudinal study of motor recovery after stroke: recruitment and focusing of brain activation.

Predicting speech fluency and naming abilities in aphasic patients

Fiber-tracking method reveals sensorimotor pathway involvement in stroke patients.

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Cited by 131