NEW ORLEANS — Two women with severe thoracic paraplegia achieved some degree of voluntary movement, bladder and bowel control, and — for one of them — orgasmic functionafter epidural spinal cord stimulation years after spinal cord injury (SCI), University of Minnesota researchers report.
“To our knowledge, these are some of the first women with spinal cord injury who have been implanted,” said David Darrow, MD, a fifth-year resident in neurosurgery at the University of Minnesota in Minneapolis. “They are the oldest overall (both in their 40s), are the furthest out from their injury, and have severe MRI findings.”
While the restored function may, in some ways, seem minor, the magnitude of changes that matter to patients is not outwardly obvious: greater body support, which makes wheelchair operation easier and facilitates transfers. “These are big benefits to patients,” he said.
Senior investigator Uzma Samadani, MD, PhD, Rockswold Kaplan Endowed Chair for Traumatic Brain Injury Research at the University of Minnesota, further commented in an interview with Medscape Medical News, “Spinal cord injury has, until recently, been associated with a grim prognosis for recovery of function.”
“I believe our work provides hope for people who cannot do the things that most of us take for granted — not just standing and walking, but having unchanged blood pressure when we go upright, bowel, bladder, and sexual function,” Samadani said. “We are optimistic that we are making progress that will make a dramatic difference in people’s quality of life.”
The findings are first results of the Epidural Stimulation After Neurologic Damage (E-STAND) study, which were presented here at the American Association of Neurological Surgeons (AANS) 2018 Annual Meeting.
The study was designed to assess the effect of epidural spinal cord stimulation directly on movement and cardiovascular function of paraplegic patients.
“It’s been about 10 years since the serendipitous discovery that if you apply spinal cord stimulation below their lesion, patients with thoracic paraplegia can regain some ability to control their legs, despite not having moved them in up to 4 years,” Darrow said. “This changed the paradigm of how we think about complete spinal cord injury…and opened up the opportunity to look at the narrative of spinal cord injury from the perspective of neuromodulation.”
Mechanism Behind the Findings
Electrical stimulation is not directed to the actual site of the lesion but is delivered within a segment of the cord, irrespective of the SCI site. For example, a patient with a T4 lesion may have the electrodes implanted at T11, Darrow explained.
According to Darrow, it is known that there are “intact super spinal connections that pass through the spinal cord lesion,” but it has not been known whether these can be functionally restored, and, if so, how.
“There are still fibers that are surviving through that lesion. There’s no other way to explain it,” he said in an interview with Medscape Medical News. “We just flood the sensory system. It essentially removes the synaptic plasticity in those inner neurons and then all of a sudden those few fibers that are making it can actually do something.”
Senior investigator Ann Parr, MD, PhD, assistant professor of neurosurgery at the University of Minnesota, pointed out, “It’s not direct neural stimulation. It’s thought to act through the sensory system, so the spinal cord is basically sensing a signal and lowering the threshold for firing.”
The two patients were part of an ongoing study that enrolls adults with thoracic SCI between C6 and T10. All patients are American Spinal Injury Association Impairment Scale A or B with full arm strength, intact segmental reflexes below the lesion of injury, and no lower motor neuron injury. Patients had to be at least 1 year post-SCI. Patients were categorized according to whether they had or did not have significant cardiovascular dysautonomia; those with dysautonomia undergo periodic autonomic tests.
“We used broad inclusion criteria, as previous patients [in other studies] have all been young, healthy men, implanted soon after SCI, who underwent a significant amount of rehabilitation before and after being implanted,” he said.
“Ours, on the other hand, is a very broad, generalizable patient population. Our study involved no rehabilitation, and we made it easy on our patients by having them come in only for monthly visits,” he said.
Approximately 5 and 11 years after SCI, the two patients were implanted with a spinal cord stimulator individually optimized for the desired functions. “There are an infinite number of settings. We worked to determine the best settings for each outcome,” Parr explained.
During the implantation, the surgeons mapped for stimulator-evoked responses, setting the stimulator at low frequency and high amplitude and assuring coverage across the desired nerve roots. “We evoked motor responses, but with specific spatial patterns,” Darrow explained.
Functional Activity Observed
Darrow reported outcomes at 5 months for the first two patients, who were women with severe myelomalacia and syringomyelia with T8 and T4 lesions, 11 and 5 years out from SCI.
“At first, we didn’t think this would work. They had severe myelomalacia and almost transected cords, but it did work. We saw, in our first few patients, that spinal cord stimulation seems to have restored volitional movement in variable ways…and we hope this will continue to improve,” he said in an interview.
Lower-extremity volitional movement was demonstrated by both patients during functional lower-leg exercises assessed by surface electromyography (EMG) in stimulated and nonstimulated modes. Statistically significant changes were observed in overall surface EMG power for both patients, and significant changes were observed across all the muscle groups.
A video of one of the patients offered proof of the effect, as the patient raised her leg up to knee-level upon command.
Significant changes were also observed in bladder, bowel, and sexual function. Patients had a return of “synergy” (urination preceding defecation); patient 1 experienced a reduction in urinary incontinence, while patient 2 achieved volitional urination and was able to empty her bladder up to 100 mL on command. In both patients, bowel time was reduced from about 90 minutes to 30 minutes.
“But the most significant finding,” he reported, was restoration of orgasm with sexual intercourse in patient 2, who consistently reported this on her monthly visits.
Preoperative tilt-table assessment revealed significant hypotension in patient 2; within 2 days, autonomic neuromodulation via spinal cord stimulation reversed the orthostatic hypotension during tilt testing and did not cause hypertension.
“In both patients, immediately postop, we saw that spinal cord stimulation with our method appears to restore cardiovascular autonomic function if you target the right centers and does not alter normal cardiovascular function in patients with dysautonomia,” he explained.
“The important thing is that our study was in severe patients, it’s in female patients, and it’s in patients the furthest out from their injury,” Darrow said. “It shows that age, or time since injury, should not preclude this therapy.”
The E-STAND investigators hope to narrow the parameters for optimal patient selection and to develop a clinical decision support tool for clinicians. They have treated two more patients and are enrolling one new patient per month.
“Exciting Potential”
AANS session moderator Julie G. Pilitsis, MD, PhD, professor of neurosurgery at Albany Medical College in New York, said this research “shows exciting potential in restoring function after spinal cord injury for a diverse group of patients with the severest of injuries.”
“In addition to the remarkable motor movement the patients regain, a meaningful improvement in bowel and bladder function was observed, which can have a dramatic increase in quality of life,” Pilitsis said in an interview.
Among the attendees peppering the researchers with questions was Ajay Ananda, MD, a neurosurgeon at Kaiser Permanente in Los Angeles, California. “There seems to be a pretty significant effect,” he told Medscape Medical News. “While it’s obviously a very small number and only the beginning, the results are very encouraging.”
The outcomes, he offered, were “absolutely surprising… not only from what I saw from their MRIs but from what we know of neuroanatomy. It defies those things,” he said. “I do lots of neuromodulation surgery [deep-brain stimulation], and I find this to be an example of the nexus between neuroanatomy and technology.”
“These patients are such a helpless and almost hopeless subset of patients that we treat…. Any novel therapy that gives them hope — that has value, in itself,” he said.
Darrow, Parr, Samandani, and Ananda have disclosed no relevant financial relationships. Pilitisis consults and has received grant support from Abbott, which donated the equipment for this study; she has not, however, worked with the company in this area of research.
American Association of Neurological Surgeons (AANS) 2018 Annual Meeting. Abstract 536. Presented April 30, 2018.
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