A patient with Parkinson’s disease (PD) can now walk with a normal gait without balance problems or fear of falling after implantation of a neuroprosthetic device.
The neuroprosthesis involves targeted epidural electrical stimulation of areas of the lumbosacral spinal cord that produce walking.
This new therapeutic tool offers hope to patients with PD and, combined with existing approaches, may alleviate a motor sign in PD for which there is currently “no real solution,” study investigator Eduardo Martin Moraud, PhD, who leads PD research at the Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland, told Medscape Medical News.
“This is exciting for the many patients that develop gait deficits and experience frequent falls, who can only rely on physical therapy to try and minimize the consequences,” he added.
The findings were published online November 6 in Nature Medicine.
About 90% of people with advanced PD experience gait and balance problems or freezing-of-gait episodes. These locomotor deficits typically don’t respond well to dopamine replacement therapy or deep brain stimulation (DBS) of the subthalamic nucleus, possibly because the neural origins of these motor problems involve brain circuits not related to dopamine, said Moraud.
Continuous electrical stimulation over the cervical or thoracic segments of the spinal cord reduces locomotor deficits in some people with PD, but the broader application of this strategy has led to variable and unsatisfying outcomes.
The new approach focuses on correcting abnormal activation of circuits in the lumbar spinal cord, a region that hosts all the neurons that control activation of the leg muscles used for walking.
The stimulating device is placed on the lumbar region of the spinal cord, which sends messages to leg muscles. It is wired to a small impulse generator implanted under the skin of the abdomen. Sensors placed in shoes align the stimulation to the patient’s movement.
The system can detect the beginning of a movement, immediately activate the appropriate electrode, and so facilitate the necessary movement, be that leg flexion, extension, or propulsion, said Moraud. “This allows for increased walking symmetry, reinforced balance, and increased length of steps.”
The concept of this neuroprosthesis is similar to that used to allow patients with a spinal cord injury (SCI) to walk. But unlike patients with SCI, those with PD can move their legs, indicating that there is a descending command from the brain that needs to interact with the stimulation of the spinal cord, and patients with PD can feel the stimulation.
“Both these elements imply that amplitudes of stimulation need to be much lower in PD than SCI, and that stimulation needs to be fully personalized in PD to synergistically interact with the descending commands from the brain.”
After fine-tuning this new neuroprosthesis in animal models, researchers implanted the device in a 62-year-old man with a 30-year history of PD who presented with severe gait impairments, including marked gait asymmetry, reduced stride length, and balance problems.
Gait Restored to Near Normal
The patient had frequent freezing-of-gait episodes when turning and passing through narrow paths, which led to multiple falls a day. This was despite being treated with DBS and dopaminergic replacement therapies.
But after getting used to the neuroprosthesis, the patient now walks with a gait akin to that of people without PD.
“Our experience in the preclinical animal models and this first patient is that gait can be restored to an almost healthy level, but this, of course, may vary across patients, depending on the severity of their disease progression, and their other motor deficits,” said Moraud.
When the neuroprosthesis is turned on, freezing of gait nearly vanishes, both with and without DBS.
In addition, the neuroprosthesis augmented the impact of the patient’s rehabilitation program, which involved a variety of regular exercises, including walking on basic and complex terrains, navigating outdoors in community settings, balance training, and basic physical therapy.
Frequent use of the neuroprosthesis during gait rehabilitation also translated into “highly improved” quality of life as reported by the patient (and his wife), said Moraud.
The patient has now been using the neuroprosthesis about 8 hours a day for nearly 2 years, only switching it off when sitting for long periods of time or while sleeping.
“He regained the capacity to walk in complex or crowded environments such as shops, airports, or his own home, without falling,” said Moraud. “He went from falling five to six times per day to one or two [falls] every couple of weeks. He’s also much more confident. He can walk for many miles, run, and go on holidays, without the constant fear of falling and having related injuries.”
Moraud stressed that the device does not replace DBS, which is a “key therapy” that addresses other deficits in PD, such as rigidity or slowness of movement. “What we propose here is a fully complementary approach for the gait problems that are not well addressed by DBS.”
One of the next steps will be to evaluate the efficacy of this approach across a wider spectrum of patient profiles to fully define the best responders, said Moraud.
A ‘Tour de Force’
Asked to comment, Michael S. Okun, MD, director of the Norman Fixel Institute for Neurological Diseases, University of Florida, and medical director of the Parkinson’s Foundation, noted that the researchers used “a smarter device” than past approaches that failed to adequately address progressive walking challenges of patients with PD.
Although it’s “tempting to get excited” about the findings, it’s important to consider that the study included only one human subject and did not target circuits for both walking and balance, said Okun. “It’s possible that even if future studies revealed a benefit for walking, the device may or may not address falling.”
In an accompanying editorial, Aviv Mizrahi-Kliger, Department of Neurology, University of California, San Francisco, and Karunesh Ganguly, Neurology and Rehabilitation Service, San Francisco VA Health Care System, called the study an “impressive tour de force,” with data from the nonhuman primate model and the individual with PD “jointly” indicating that epidural electrical stimulation (EES) “is a very promising treatment for several aspects of gait, posture and balance impairments in PD.”
But although the effect in the single patient “is quite impressive,” the “next crucial step” is to test this approach in a larger cohort of patients, they said.
They noted the nonhuman model does not exhibit freezing of gait, “which precluded the ability to corroborate or further study the role of EES in alleviating this symptom of PD in an animal model.”
In addition, stimulation parameters in the patient with PD “had to rely on estimated normal activity patterns, owing to the inability to measure pre-disease patterns at the individual level,” they write.
The study received funding from the Defitech Foundation, ONWARD Medical, CAMS Innovation Fund for Medical Sciences, National Natural Science Foundation of China, Parkinson Schweiz Foundation, European Community’s Seventh Framework Program (NeuWalk), European Research Council, Wyss Center for Bio and Neuroengineering, Bertarelli Foundation, and Swiss National Science Foundation.
Moraud and other study authors hold various patents or applications in relation to the present work; see paper for additional study author disclosures. Mizrahi-Kliger has no relevant conflicts of interest; Ganguly has a patent for modulation of sensory inputs to improve motor recovery from stroke and has been a consultant to Cala Health.
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Publish date : 2023-11-14 14:29:40
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