ARTICLE IN BRIEF
With continued epidural stimulation and task-specific sensory input, a patient who had had a spinal cord injury was able to begin stepping on a treadmill assisted by therapists; after seven months, he recovered supraspinal control of some leg movements.
Epidural stimulation of the spinal cord combined with intensive task-specific training enabled a 23-year-old patient with complete spinal cord injury (SCI) to stand — with assistance for balance — for over four minutes.
With continued epidural stimulation and task-specific sensory input the patient was able to begin stepping on a treadmill assisted by therapists. Additionally, seven months after implantation of the electrode rays, the patient recovered supraspinal control of some leg movements, but only during epidural stimulation.
The case report, which appeared May 20 in the online edition of The Lancet, has received widespread coverage in the lay press and attracted the attention of neurologists and patients worldwide. But in interviews with Neurology Today, the lead author of the case report and other SCI experts who reviewed it emphasized that the case represents a research advance, providing “proof of concept” that electrical stimulation can activate latent neural networks in the lumbosacral spinal cord without any input from the brain.
More refinement of the technique and replication will be required before it is clinically available, they said. Moreover, it is unknown how widely applicable the procedure in the case report — which involved a young man who had been a gifted athlete, who still retained partial preservation of sensation below the T1 cord segment, and who underwent extraordinary amounts of task-specific training — will be to the millions of individuals with paralysis due to SCI.
“This advance opens up a whole new avenue for recovery from paralysis, but it is not ready for clinical application yet,” lead author Susan Harkema, PhD, professor in the department of neurological surgery at the University of Louisville and director of the Christopher & Dana Reeve Foundation's NeuroRecovery Network, said. “We have to replicate it in similar patients, and there needs to be significant advancement in the technology, because right now the technology we used in this case study is not ready to be used in a clinical environment. Then we have to extend the technique to other patient groups.”
“Nevertheless, it is very exciting and we are in a good situation to know what the next steps are,” Dr. Harkema said. “So it is time and resources, not new discoveries, that will determine when this becomes clinically available.”
The study subject was completely paralyzed in his lower extremities following a hit-and-run accident in July 2006. Formerly an athlete in extraordinary physical condition, he suffered a complete motor injury at the C7/T1 level, which was classified as “ASIA B” on the American Spinal Injury Association's scale since he did retain some sensation in his legs.
Prior to implantation of the epidural stimulator, he underwent 170 locomotor training sessions with no stimulation over a period of 26 months in order to ensure that the training alone was not responsible for any subsequent improvements. The investigators observed no measurable effect from the locomotor training alone.
The researchers then used an epidural spinal cord stimulation unit to electrically stimulate the lumbosacral enlargement. A 16-electrode array was implanted under fluoroscopic control at T11–L1 over spinal cord segments L1–S1; the electrode lead was tunneled to a subcutaneous abdominal pouch where the pulse generator was implanted.
Varying combinations of stimulation were systematically assessed to obtain optimum efferent patterns for standing and stepping. Spinal cord stimulation was done during sessions that lasted up to 250 minutes, with stimulation duration ranging from 40 to 120 minutes.
TWO SURPRISING FINDINGS
Dr. Harkema told Neurology Today that the voluntary movement of toes, ankles, knees, and hips while being stimulated was a surprise. “It suggests that the way we have thought about control of motor behavior has to be re-examined,” she said. “We have known from animal research going back to the 1970s that the general motor behaviors of locomotion were mediated by a sophisticated circuitry in the spinal cord. This circuitry, like the brain, can learn, remember and forget. But the novel finding here was that voluntary movement — the conscious decision to move one's toes or ankles — is also mediated by the spinal cord, not by the brain.”
The second important finding from the case study is that control of motor behavior appears to be crucially influenced by sensory input from the environment. Dr. Harkema noted that the electrical stimulation incites the neural circuitry into a physiological state so that it can interpret sensory information; so when the patient leaned forward and put weight on his legs to stand, that movement provided a sensory cue to the neural circuitry that initiated the process of standing.
“The stimulation remains constant and doesn't change, but the combination of the two — stimulation and the sensory information derived from the movement of the patient leaning forward and placing weight on his legs to stand — were needed to produce assisted locomotion on the treadmill. This has important implications clinically for how we train the circuitry to produce the desired behavior.”
Neurologists who were not involved with the report hailed it as an important experimental advance but one that should not be oversold to a public eager for remedies for a devastating injury.
“This is a small advance, but one that could have life-changing implications for a small percentage of patients with complete spinal cord injury,” said John W. McDonald, MD, PhD, director of the International Center for Spinal Cord Injury at the Kennedy Krieger Institute. “We are already getting calls from people, and neurologists need to know that this is not going to be applicable to the majority of people who are paralyzed.”
Bruce H. Dobkin, MD, professor of neurology and director of the Neurologic Rehabilitation and Research Program at the University of California-Los Angeles Geffen School of Medicine, emphasized that the case study extends research on stimulation of spinal neural circuits going back several decades.
“Pulsed electrical stimulation in this case, presumably exciting the bilateral dorsal horns and neurons and interneurons of the ventral horns over several segments, was able to trigger limited output from the cord that was not present without stimulation,” Dr. Dobkin said. “The EMG increased a bit with further training to stand. Then, stance was accomplished with only support for balance for a few minutes. Low voltage EMG also appeared during fully assisted leg movements during treadmill training. This response from a combination of interventions is novel.”
But Dr. Dobkin said he doubted the strategy, as currently configured, would enable walking. “Most patients will probably not have enough motor units activated to manage gait, especially not energy efficient gait,” he said. “On the other hand, the study authors and others are devoted to this line of translational research, so maybe additional interventions, including neural repair strategies, will lead to stepping in the future.
“Other researchers will likely try to push this combinational strategy for patients who walk poorly from other causes of an incomplete myelopathy or perhaps hemiplegia,” he noted.
Dr. Dobkin added, however, that insurance coverage for the experimental strategy is likely to be problematic. “I cannot get insurance to cover a $5,000 functional electrical stimulator placed on an arm to enable grasping for a hemiplegic patient,” he said. “Who will pay for a surgically implanted $25K device and over 100 sessions of treadmill training?”