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

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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.