EFFECT OF INTERNET-ENABLED INTENSE EXERCISE THERAPY ON MOTOR STATUS AFTER SPINAY

互联网支持的剧烈运动疗法对 SPINAY 术后运动状态的影响

• 批准号: 7606648
• 负责人: STEVEN Michael CRAMER
• 金额: $ 2.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606648
• 关键词: Ablation; Advertisements; Affect; Age; Area; Asia; Behavioral; Body part; Brain; Caliber; Cerebral cortex; Clinical Trials; Clinical assessments; Computer Retrieval of Information on Scientific Projects Database; Corticospinal Tracts; Diagnosis; Disease; Electromyography; End Point; Enrollment; Evaluation; Event; Exercise; Fiber; Functional Magnetic Resonance Imaging; Funding; Grant; Hand; Home environment; Injury; Institution; Internet; Intervention; Lateral; Lesion; Localized; Magnetic Resonance Imaging; Maps; Measures; Medical; Methods; Minority; Motor; Motor Cortex; Motor Evoked Potentials; Movement; Muscle; Muscle Contraction; Neurons; Numbers; Outcome Assessment; Paralysed; Patient Participation; Patients; Persons; Physical therapy; Physical therapy exercises; Physiologic pulse; Physiological; Prevalence; Protocols documentation; Pulse taking; Quadriplegia; Randomized; Recovery; Reflex action; Reporting; Research; Research Personnel; Residual state; Resources; Scalp structure; Sensory; Signal Transduction; Source; Spinal; Spinal Cord; Spinal cord injury; Spinal cord injury patients; Stroke; Surface; System; Testing; Time; Transcranial magnetic stimulation; United States National Institutes of Health; Vertebral column; Walking; base; constraint induced therapy; cost; gray matter; improved; life time cost; magnetic field; mind control; neurophysiology; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Spinal cord injury (SCI) remains a major medical problem in the U.S. Over 11,000 new patients suffer and survive a new SCI each year(1), with U.S. prevalence of nearly a quarter million persons. SCI is compounded by numerous secondary medical problems. The lifetime cost in dollars varies with the age at SCI but exceeds 1-2 million dollars for most quadriplegics. In approximately half of all patients with SCI, the injury is said to be complete, meaning that none of the motor or sensory function below the level of SCI is controlled by the brain, instead arising solely from reflex or localized spinal cord events. In the other half of patients, injury is incomplete, meaning a fraction of the normal brain control of sub-lesional spinal cord events remains. Several lines of evidence suggest that, after SCI, behavioral deficits are often more severe than would be predicted from measures of anatomical injury. If true, this suggests the potential to improve motor status in the setting of a fixed lesion, even when deficits are severe. Evidence includes (1) Anatomical evidence: In most patients diagnosed with complete SCI, neuropathological observations suggest surviving anatomical connections between brain and spinal cord motor areas (2). Such patients have been termed discomplete (3). The minimum number of fibers in the lateral corticospinal tract of SCI patients with preserved voluntary motor function was 3,173 (normal 41,472); the mean number of fibers in this tract among complete SCI patients was not zero, but instead averaged 2,113. (2) Physiological evidence: Neurophysiological studies can demonstrate residual corticospinal tract function in some, alebit a minority, of patients with complete SCI. Transcranial magnetic stimulation (TMS) of motor cortex in these patients shows that electrical signals can be transmitted to spinal cord areas below the injury(4-6). (3) Analogous findings in patients with cortical stroke: We recently demonstrated that, among patients with stroke affecting the hand's primary motor cortex area, voluntary hand motor function was abolished when approximately 37%--and not 100%--of the normal hand motor cortex map was destroyed by the disease (7). (4) Reports of motor gains with extreme physiotherapy: After SCI (eg C. Reeve) (8) or stroke (reports of constraint induced therapy, eg a study from my lab by Schaechter et al (9)), motor status can be improved in patients with a fixed lesion and little or no movement. No recovery would be likely if initial plegia were due to ablation of all key motor substrates. The overall rationale of the proposed study is to evaluate the effect of intensive physical therapy on motor status in patients with SCI. Outcome assessments will be measured in the lab, in the home, and at a center for therapy in Carlsbad ("Project Walk"). In addition to carefully evaluating the effects of extreme exercise therapy on SCI, the proposed study also represents a first step towards home-based patient assessments. SPECIFIC AIMS Definition of TMS-transcranial magnetic stimulation. A TMS coil gently set atop the scalp safely produces a magnetic field that activates an approximately 1 cm2 area of underlying cerebral cortex. TMS above motor cortex produces an electrical volley down the corticospinal tract. A typical response with current methods is a brief twitch in one muscle or muscle group. The current study will only use single pulse TMS, which is completely safe as applied in the current protocol. Definition of MEP-Motor evoked potential. The signal from TMS application to motor cortex goes down the spine and activates spinal gray matter neurons, after which muscles in the respective body part subsequently change their potential-this is the MEP. Sometimes this is a visible muscle twitch but sometimes this is a subvisible muscle contraction that can be measured with common surface electromyography (EMG) methods. In the proposed study, all subjects will be patients with SCI. All will undergo clinical assessment, TMS evaluation, and MRI exam including functional MRI (fMRI) twice: once at baseline and once 6 months later. In some patients, the intervening 6 months will be filled with participation at Project Walk. In other patients with SCI, who will serve as controls, the time will be spent in usual activities that will not include the extreme exercise intervention of Project Walk. Patients with SCI will not be randomly assigned to the two groups, as participation in Project Walk is expensive and current funding can not cover such costs. Instead, patient with SCI who enroll in Project Walk will be offered study participation; and patients with SCI who are identified from advertisements will be also offered participation as control subjects. THE SPECIFIC AIM OF THE PROPOSED STUDY is to test the hypothesis that intense exercise will improve motor system assessments more than the control (ie no exercise) intervention, an elementary yet little studied question in the field of SCI. The primary endpoint will be ASIA motor scale, the endpoint most often used in clinical trials of SCI. Secondary endpoints will include other measures of motor system function, internet-enabled assessments of motor function, TMS measures of neurophysiology, fMRI measures of motor system activation, and anatomical measures of spinal cord diameter.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在美国，脊髓损伤（SCI）仍然是一个主要的医疗问题，超过11,000名新患者每年遭受新的SCI（1），美国的患病率近25万。 SCI被许多二级医学问题所加重。 美元的寿命成本随SCI的年龄而异，但对于大多数四肢瘫痪，超过1-200万美元。 在大约一半的SCI患者中，据说损伤是完整的，这意味着低于SCI水平的电动机或感觉功能都由大脑控制，而是仅由反射或局部脊髓事件引起。 在另一半患者中，损伤是不完整的，这意味着仍然存在亚度脊髓事件的正常脑控制。 几条证据表明，在SCI之后，行为缺陷通常比解剖学损伤措施所预测的要严重。 如果是真的，这表明即使缺陷很严重，也有可能在固定病变的情况下提高运动状态。 证据包括 （1）解剖学证据：在大多数被诊断出患有完全SCI的患者中，神经病理学观察结果表明脑与脊髓运动区域之间的解剖学联系（2）。 这样的患者已被称为完整（3）。 保留的自愿运动功能的SCI患者的侧向脊髓脊髓中的最小纤维数量为3,173（正常41,472）；完整的SCI患者中该区域中纤维的平均数量不是零，而是平均2,113。 （2）生理证据：神经生理学研究可以证明某些人（Alebit a a a Alebit A）的残留皮质脊髓束功能，其中少数患有完全SCI的患者。 这些患者的运动皮层的经颅磁刺激（TMS）表明，电信号可以传播到损伤以下的脊髓区域（4-6）。 （3）皮质中风患者的类似发现：我们最近证明，在影响手运动皮层的中风患者中，当大约37％（而不是100％）的正常手运动皮层图被疾病破坏时，自愿手机功能被废除了（7）。 （4）对具有极端物理疗法的运动增长的报告：SCI（例如C. Reeve）（8）或中风（例如，约束诱导治疗的报道，例如Schaechter等人（9）的实验室研究），可以改善固定病灶或不运动的患者的运动状态。 如果由于所有关键运动底物的消融造成的初始性质，可能不会恢复。 拟议的研究的总体原理是评估强化物理疗法对SCI患者运动状况的影响。 结果评估将在实验室，家庭和卡尔斯巴德的治疗中心（“项目步行”）中进行测量。 除了仔细评估极端运动疗法对SCI的影响外，拟议的研究还代表了迈向家庭患者评估的第一步。 具体目标 TMS-传输磁刺激的定义。 TMS线圈在头皮上轻轻地放在头皮上，可安全地产生一个磁场，该磁场激活了大约1 CM2的大脑皮层区域。 运动皮层上方的TMS在皮质脊髓段下方产生电彩力。 当前方法的典型响应是一个肌肉或肌肉组的短暂抽搐。 当前的研究将仅使用单个脉冲TM，这是当前协议中所应用的完全安全的。 MEP运动的定义引起了潜力。 从TMS应用到运动皮层的信号沿着脊柱降低并激活脊柱灰质神经元，此后各个身体部位的肌肉随后改变了潜力 - 这是MEP。 有时，这是一种可见的肌肉抽搐，但有时这是一种可亚参见的肌肉收缩，可以通过公共表面肌电图（EMG）方法来测量。 在拟议的研究中，所有受试者均为SCI患者。 所有人将接受临床评估，TMS评估和MRI检查，包括功能性MRI（fMRI）两次：在基线时一次，一次在6个月后。 在某些患者中，六个月的中间将在项目步行中的参与。 在其他将充当控制的SCI患者中，将花在通常的活动中，这将不包括项目步行的极端运动干预。 SCI患者不会随机分配给两组，因为参与项目步行很昂贵，目前的资金无法支付此类费用。 取而代之的是，参加项目步行的SCI患者将获得研究参与；从广告中识别出的SCI的患者也将作为控制对象参与。 拟议的研究的具体目的是检验以下假设：激烈的运动将改善运动系统评估，而不是对照（即无运动）干预，这是SCI领域中的基础尚未研究的问题。 主要终点是亚洲运动量表，这是SCI临床试验中最常使用的终点。 次要终点将包括运动系统功能的其他措施，支持运动功能的评估，TMS神经生理学的TMS度量，fMRI的运动系统激活测量以及脊髓直径的解剖学测量。