summary: Nerve stimulation therapy has shown promising results in treating spinal cord injuries in animal models. The researchers hope that the treatment can be used in humans with SCI to help restore movement to the limbs.
Source: Columbia University
In 1999, when Jason Karmel, MD, was a sophomore at Columbia University Medical School, his twin brother suffered a spinal cord injury, paralyzing him from his chest down and limiting the use of his hands.
Jason Karmel’s life changed that day, too. His brother’s injury eventually led Carmel to become a neurologist and neuroscientist, with the goal of developing new therapies to restore movement for paralyzed people.
Now, a nerve stimulation therapy developed by Carmel at Columbia is showing promise in animal studies and may eventually allow people with spinal cord injuries to regain function in their arms.
“The stimulation technique targets the connections of the nervous system that survive the injury, enabling it to take over some of the lost functions,” says Karmel, MD, a neurologist at Columbia University and New York-Presbyterian.
In recent years, some notable studies on electrical stimulation of the spinal cord have allowed a small number of incompletely paralyzed people to begin standing and taking steps again.
Karmel’s approach differs because it targets the arm and hand and because it combines stimulation of the brain and spinal cord, with electrical stimulation of the brain followed by stimulation of the spinal cord.
“When the two signals converge at the level of the spinal cord, within about 10 milliseconds of each other, we get the stronger effect,” he says, and that combination seems to enable the remaining connections in the spinal cord to take over. “
In his latest study, Carmel tested his technique — called associative plasticity of the spinal cord (SCAP) — on mice with moderate spinal cord injuries. Ten days after infection, mice were randomized to receive 30 min of SCAP for 10 days or sham stimulation. At the end of the study period, the rats that received SCAP targeting their arms were significantly better at handling food, compared to those in the control group, and had near-normal reflexes.
“Improvements in both function and physiology continued throughout the period they were measured, up to 50 days,” Karmel says.
The results were recently published in the journal brain, it is suggested that SCAP causes synapses (the connections between neurons) or neurons themselves to undergo permanent change. “The dual cues essentially mimic the natural sensory-motor integration that must come together to perform a skilled movement,” Karmel says.
From mice to humans
If the same technique works in people with spinal cord injuries, patients could regain something else they lost in the injury: independence. Many studies of spinal cord stimulation focus on walking, but “if you ask people with a cervical spinal cord injury, which is the majority, what movement they’d like to regain, they’d say hand and arm function,” says Karmel.
“Hand and arm function allows people to be more independent, such as moving from a bed to a wheelchair or getting dressed and feeding themselves.”
Karmel is now testing SCAP on spinal cord injury patients at Columbia, Cornell and the VA Bronx Health Care System in a clinical trial sponsored by the National Institute of Neurological Disorders and Stroke.
Stimulation will be done either during clinically indicated surgery or non-invasively, using magnetic stimulation of the brain and skin stimulation in the front and back of the neck. Both methods are routinely performed in clinical settings and are known to be safe.
In the experiment, the researchers hope to learn more about how SCAP works and how the timing and strength of the signals affect motor responses in the fingers and hands. This would lay the groundwork for future trials to test the technique’s ability to meaningfully improve hand and arm function.
Looking further, the researchers believe this approach could be used to improve movement and sensation in patients with lower body paralysis.
Meanwhile, Jason Carmel’s twin is at work, married, and raising a twin of his own. “His life is complete, but I hope we can restore more functionality to him and others with similar injuries,” Karmel says.
About this research on spinal cord injury news
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“Associative plasticity of the spinal cord improves sensory function of the forelimbs after cervical injuryWritten by Ajay Pal et al. brain
Associative plasticity of the spinal cord improves sensory function of the forelimbs after cervical injury
Associative plasticity occurs when two stimuli converge on a common neuronal target. Previous efforts to enhance associative plasticity have targeted the cerebral cortex with modulatory and intermediate effects. In addition, target circuits are inferred rather than tested directly. In contrast, we sought to target the strong convergence between motor and sensory systems in the spinal cord.
We developed the associative plasticity of the spinal cord, precisely timed coupling of the motor cortex and stimulation of the dorsal spinal cord, to target this interaction. We tested the hypothesis that properly timed paired stimulation would strengthen sensorimotor connections in the spinal cord and improve recovery after spinal cord injury. We tested the physiological effects of dual stimulation, the pathways that mediate it, and its function in a preclinical experiment.
Subthreshold spinal cord stimulation that robustly increased the motor cortex elicited muscle potentials at the time of their coupling, but only when they synchronously reached the spinal cord. This paired stimulus effect is dependent on both the cortical motor and the proprioceptive spinal cord; Selective inactivation of any of these pathways completely abolished the effect of paired stimulation. Associative plasticity of the spinal cord, repeated pairing of these pathways for 5 or 30 minutes in awake rats increased spinal excitability for hours after the pairing ended.
To apply the associative plasticity of the spinal cord as a treatment, we optimized the parameters to enhance the robust and long-lasting effects. This effect was as strong in rats with cervical spinal cord injury as it was in uninjured rats, demonstrating that connections salvaged after moderate spinal cord injury were sufficient to support plasticity. In a blinded experiment, mice received a moderate C4 spinal cord injury. Ten days after injury, they were randomly assigned to 30 minutes of associative plasticity of the spinal cord each day for 10 days or placebo stimulation.
Rats with associative plasticity of the spinal cord had significantly improved function on the primary outcome measure, a test of dexterity while manipulating food, 50 days after the spinal cord injury. In addition, rats with associative plasticity of the spinal cord had consistently stronger responses to cortical and spinal stimulation than sham-stimulation rats, indicating a locus of plasticity in the spine.
After associative plasticity of the spinal cord, the rats had nearly normalized H-reflex modulation. The groups had no difference in the rat’s grimace scale, which is a measure of pain.
We conclude that the associative plasticity of the spinal cord strengthens sensory connections within the spinal cord, resulting in partial restoration of reflex modulation and forelimbs function after moderate spinal cord injury. Because both motor cortex and spinal cord stimulation are routinely performed in humans, this approach could be tried in people with spinal cord injury or other disorders that damage sensorimotor connections and impair dexterity.