Critical Period After Stroke Study (CPASS): A phase II clinical trial testing an optimal time for motor recovery after stroke in humans.

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Citation: Proceedings of the National Academy of Sciences of the United States of America. 118(39), 2021 09 28.PMID: 34544853Institution: MedStar National Rehabilitation NetworkForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov'tSubject headings: *Motor Activity/ph [Physiology] | *Recovery of Function | *Stroke Rehabilitation/mt [Methods] | *Stroke/th [Therapy] | Aged | Case-Control Studies | Female | Follow-Up Studies | Humans | Male | Middle Aged | Prognosis | Prospective StudiesYear: 2021ISSN:
  • 0027-8424
Name of journal: Proceedings of the National Academy of Sciences of the United States of AmericaAbstract: Restoration of human brain function after injury is a signal challenge for translational neuroscience. Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained if task-specific motor training occurs during this sensitive window. We extended these findings to adult humans with stroke in a randomized controlled trial applying the essential elements of rodent motor training paradigms to humans. Stroke patients were adaptively randomized to begin 20 extra hours of self-selected, task-specific motor therapy at <=30 d (acute), 2 to 3 mo (subacute), or >=6 mo (chronic) after stroke, compared with controls receiving standard motor rehabilitation. Upper extremity (UE) impairment assessed by the Action Research Arm Test (ARAT) was measured at up to five time points. The primary outcome measure was ARAT recovery over 1 y after stroke. By 1 y we found significantly increased UE motor function in the subacute group compared with controls (ARAT difference = +6.87 +/- 2.63, P = 0.009). The acute group compared with controls showed smaller but significant improvement (ARAT difference = +5.25 +/- 2.59 points, P = 0.043). The chronic group showed no significant improvement compared with controls (ARAT = +2.41 +/- 2.25, P = 0.29). Thus task-specific motor intervention was most effective within the first 2 to 3 mo after stroke. The similarity to rodent model treatment outcomes suggests that other rodent findings may be translatable to human brain recovery. These results provide empirical evidence of a sensitive period for motor recovery in humans. Copyright (c) 2021 the Author(s). Published by PNAS.All authors: Barth J, Brady K, Dromerick AW, Edwards DF, Edwardson MA, Geed S, Giannetti ML, Mitchell A, Newport EL, Tan MT, Zhou YOriginally published: Proceedings of the National Academy of Sciences of the United States of America. 118(39), 2021 09 28.Fiscal year: FY2022Fiscal year of original publication: FY2022Digital Object Identifier: ORCID: Date added to catalog: 2021-11-01
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Journal Article MedStar Authors Catalog Article 34544853 Available 34544853

Restoration of human brain function after injury is a signal challenge for translational neuroscience. Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained if task-specific motor training occurs during this sensitive window. We extended these findings to adult humans with stroke in a randomized controlled trial applying the essential elements of rodent motor training paradigms to humans. Stroke patients were adaptively randomized to begin 20 extra hours of self-selected, task-specific motor therapy at <=30 d (acute), 2 to 3 mo (subacute), or >=6 mo (chronic) after stroke, compared with controls receiving standard motor rehabilitation. Upper extremity (UE) impairment assessed by the Action Research Arm Test (ARAT) was measured at up to five time points. The primary outcome measure was ARAT recovery over 1 y after stroke. By 1 y we found significantly increased UE motor function in the subacute group compared with controls (ARAT difference = +6.87 +/- 2.63, P = 0.009). The acute group compared with controls showed smaller but significant improvement (ARAT difference = +5.25 +/- 2.59 points, P = 0.043). The chronic group showed no significant improvement compared with controls (ARAT = +2.41 +/- 2.25, P = 0.29). Thus task-specific motor intervention was most effective within the first 2 to 3 mo after stroke. The similarity to rodent model treatment outcomes suggests that other rodent findings may be translatable to human brain recovery. These results provide empirical evidence of a sensitive period for motor recovery in humans. Copyright (c) 2021 the Author(s). Published by PNAS.

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