Recovery of Cortical Control Over Locomotion After Spinal Cord Injury

Tempel, Zachary; Monaco, Edward A. III; Friedlander, Robert M.

doi: 10.1227/01.neu.0000419712.10158.62
Science Times

Spinal cord injury (SCI) is an important dilemma that has presented significant challenges to the field of neurological surgery since its inception. While modern clinical and laboratory research has shed light on the mechanisms and pathways of neuronal damage, tremendous progress has been lacking in the treatment of spinal cord injury. As a consequence, clinical outcomes and recovery of neurologic function following incomplete and complete spinal cord injury remain relatively unchanged. Modern research in the field of spinal cord injury has focused predominantly on mechanisms of neuronal degeneration and the role of stem cells and neuromodulators in neuronal plasticity and, ultimately, the recovery of neurologic function.

In the modern clinical setting, an interdisciplinary, multi-faceted approach to management of the SCI patient is paramount to achieving optimal clinical outcomes. Such treatment incorporates advanced imaging techniques, neurosurgical intervention for spinal cord decompression and bony stabilization, and expertise from critical care physicians and specialized physical therapy regimens tailored to the SCI patient. However, these endeavors, by themselves, rarely facilitate immediate return to neurologic function. A recent paper by van den Brand et al (van den Brand R, Heutschi J, Barraud Q, et al. Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science. 2012;336(6085):1182-1185.) enforces this point by illustrating the importance of regaining cortical stimulation in recovery of neurologic function following SCI in rats.

First, the authors created spinal cord injuries at 2 levels with intact intervening neurologic tissue, thus simulating SCI in humans where there are often some preserved connections in the cord. Paralyzed rats were then trained either on a treadmill or overground with a novel robotic postural interface in combination with an electrochemical prosthesis that utilized epidural electrical stimulation of lumbar segments and systemically administered serotonin and dopamine receptor agonists. Treadmill-restricted training in SCI rats, which yields little cortical stimulation, failed to elicit neuronal plasticity or recovery of neurologic function. However, SCI rats in which the robotic postural interface was used achieved significant recovery of neurologic function. This corresponded with molecular and anatomical evidence of reconstitution of spinal cord fibers. A molecular marker of neuronal activity, c-fos, was increased in cord neurons of the preserved region following active training. Immunohistochemical evaluation found that overground-trained rats reconstituted nearly 50% of their prelesional spinal cord fiber density. Finally, cortical connections through the injured region were confirmed via electrical stimulation of the motor cortex. Actively trained rats regained responses below the cord lesion following cortical stimulation. Moreover, the firing rate of motor cortex neurons increased significantly prior to voluntary locomotor movement. None of these phenomena were observed with passive treadmill training. The hypothesis here is that active overground training using the robotic postural interface in the setting of electrochemically enabled motor states requires the subject to initiate movement, and involves cortical processing and integration of complex sensory inputs in order to produce a coordinated motor response. In contrast, treadmill-restricted training stimulates primarily spinal cord reflex-type movement involving only the lumbosacral elements.

These findings have meaningful implications in the management of SCI patients in the post-acute phase, specifically during rehabilitation. Therapy targeted at stimulating the entire neuraxis may facilitate a higher degree of neurologic recovery and ultimately, independent living. Devices for long-term intrathecal drug administration, such as baclofen and dilaudid pumps, as well as electrostimulation devices, such as deep brain stimulators, are commonly implanted by neurosurgeons to treat a number of conditions. It is not unrealistic to think that combining these types of tools with active training using appropriate sensory cues in order to utilize spared neuronal tissue could enhance neuroplasticity and neurologic recovery following SCI in humans.

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