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

Abstract

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.

Leveraging Factors of Self-Efficacy and Motivation to Optimize Stroke Recovery

“…Moreover, these biopsychological factors also influence long term behavior change ( 122 ) and return to work post-stroke ( 123 ). Lastly, there is growing evidence of time and dose-dependent effects of rehabilitation on functional improvement post-stroke ( 124 – 126 ). As discussed earlier, self-efficacy and motivation influence an individual's engagement in and adherence to rehabilitation, and these factors may therefore also impact the treatment dosage that an individual receives.…”

Bilateral Cerebellar Intermittent Theta Burst Stimulation Combined With Swallowing Speech Therapy for Dysphagia After Stroke: A Randomized, Double-Blind, Sham-Controlled, Clinical Trial

“…After 3 months the rate of recovery decreases, but partial recovery is still possible. 45 Subgroup analysis of stroke types showed that recovery of swallowing in ischemic appeared to be superior to hemorrhage. However, the differences were not significant difference.…”

Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia

“…A recent example of the timing of specific and intensive stroke rehabilitation directly translated from rodent experiments to human, showing rehabilitation early within 30 days and late beyond 6 months are not effective. The most effective period has been proven to be 60–90 days ( Dromerick et al, 2021 ). Our experimental work on HUCB and its MNCs treating HIE can be fast-tracked to clinical trials when its availability, dosage and timing are worked out.…”