Critical Period After Stroke Study (CPASS): A phase II clinical trial testing an optimal time for motor recovery after stroke in humans.
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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DOI：
10.1073/pnas.2026676118
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发表时间：
2021-09-28
影响因子：
11.1
通讯作者：
Edwards DF
中科院分区：
文献类型：
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作者：
Dromerick AW;Geed S;Barth J;Brady K;Giannetti ML;Mitchell A;Edwardson MA;Tan MT;Zhou Y;Newport EL;Edwards DF
损伤后脑功能的恢复是一个信号神经科学的挑战。中风恢复的动物模型证明了提高运动恢复的时间限制窗口，类似于发育神经可塑性。然而，在人类中还没有证明等效的窗口。我们报告了一项随机对照试验，将动物运动训练范式的基本要素应用于人类，以确定成人中类似敏感期的存在。我们发现在脑卒中后60 ~ 90 d也有类似的敏感期或最佳期，≤30 d影响较小，6个月或以后无影响。这些发现前瞻性地证明了成年人中存在敏感期。我们敦促在中风发作后60至90天内提供更密集的运动康复。损伤后人脑功能的恢复是转化神经科学的一个信号挑战。啮齿类动物中风恢复研究确定了中风后强化运动训练的最佳或敏感时期：如果在这个敏感窗口期间进行特定任务的运动训练，则可以获得接近完全的恢复。我们在一项随机对照试验中将这些发现扩展到患有中风的成年人，该试验将啮齿动物运动训练范例的基本要素应用于人类。与接受标准运动康复的对照组相比，卒中患者在卒中后≤30 d（急性）、2 - 3 mo（亚急性）或≥6 mo（慢性）时适应性随机分配至开始额外20小时的自选、任务特异性运动治疗。上肢（UE）功能障碍的行动研究手臂测试（ARAT）评估，在五个时间点进行了测量。主要结果指标为卒中后1年内ARAT恢复情况。1年时，我们发现亚急性组与对照组相比，UE运动功能显著增加（ARAT差异= +6.87 ± 2.63，P = 0.009）。急性组与对照组相比，ARAT差异为+5.25 ± 2.59分，P = 0.043，但改善幅度较小。慢性组与对照组相比无显著改善（ARAT = +2.41 ± 2.25，P = 0.29）。因此，任务特定的运动干预是最有效的中风后的第一个2至3个月。与啮齿类动物模型治疗结果的相似性表明，其他啮齿类动物的发现可能适用于人脑恢复。这些结果为人类运动恢复的敏感期提供了经验证据。
Restoration of postinjury brain function is a signal neuroscience challenge. Animal models of stroke recovery demonstrate time-limited windows of heightened motor recovery, similar to developmental neuroplasticity. However, no equivalent windows have been demonstrated in humans. We report a randomized controlled trial applying essential elements of animal motor training paradigms to humans, to determine the existence of an analogous sensitive period in adults. We found a similar sensitive or optimal period 60 to 90 d after stroke, with lesser effects ≤30 d and no effect 6 mo or later after stroke. These findings prospectively demonstrated the existence of a sensitive period in adult humans. We urge the provision of more intensive motor rehabilitation within 60 to 90 d after stroke onset. 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.