Attacking key cells in the spinal cord made paralyzed patients walk again

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By Amy Norton

health day reporter

WEDNESDAY, November 9, 2022 (HealthDay News) — In an advance in the treatment of spinal cord injuries, researchers have pinpointed nerve cells that are key to allowing people with paralysis to walk again.

The findings come in part from nine patients involved in an ongoing Swiss study aimed at restoring movement to people with paralysis.

All nine quickly regained the ability to stand and walk using implants that electrically stimulate the spinal nerves that control movement of the lower body.

Now the researchers report that they have identified a specific group of cells in the lower spine that appear necessary for this movement recovery to occur.

The hope, experts say, is that the discovery will help refine electrical stimulation therapy — and eventually help develop even more sophisticated ways to give complex movement back to people with paralysis.

According to the American Association of Neurological Surgeons, up to 450,000 people are living with a spinal cord injury in the United States alone. Just over half of these injuries affect people under the age of 30, most of whom are male – often to blame for traffic accidents or violence.

Spinal cord injuries essentially cut off communication between the brain and the spinal nerves, which are located below the level of the injury.

But these nerve cells are not useless – just offline. And for years, researchers have been studying epidural electrical stimulation (EES) as a way to get those neurons firing and return some level of movement to people with paralysis.

EES involves implanting electrodes that deliver electrical currents to neurons in the spinal cord. The electrodes are connected to a pulse generator implanted in the abdomen.

EES has been used to treat pain for 50 years, said Eiman Azim, a researcher at the Salk Institute in La Jolla, California, who studies the mechanisms underlying human movement.

Along the way, the researchers realized that EES also affects movement. Over the past decade, various research teams have used EES along with intensive physical rehabilitation to help a small number of paralyzed patients regain the ability to stand and walk to some degree.

According to Azim, the Swiss team has made “big leaps” in the further development of the approach in recent years.

For example, they have developed electrodes that precisely target the “dorsal root” regions of the spinal cord that control leg and trunk movement. They’ve also incorporated sophisticated technology that stimulates nerves in a pattern that better mimics how the brain would do the work.

The team from the Swiss Federal Institute of Technology and the University of Lausanne reported on their three latest patients earlier this year. The patients, all males between the ages of 29 and 41, had suffered spinal cord injuries that left them with no sensation or movement in their legs.

All underwent surgery in 2020 to have the EES hardware implanted. The implants were paired with software that allows patients and physiotherapists to set up semi-automated stimulation programs that allow for a variety of movements. People can operate these programs themselves using a tablet and small remote controls that communicate wirelessly with the pulse generator.

These three patients were able to stand and walk with assistance immediately after recovery from surgery.

Along the way, the Swiss team discovered something particularly intriguing: Some of their nine patients were able to walk even with electrical stimulation turned off — suggesting, Azim said, that neurons involved in walking were “reorganized.”

To delve deeper, the researchers turned to laboratory mice to simulate many of the key features of EES in people with spinal cord injuries. They were able to focus on a group of neurons – called Vsx2 neurons – that appear ‘essential’ for restoring walking with EES.

“Silencing” the neurons prevented laboratory mice with EES from regaining their ability to walk; Activating the neurons restored their movement.

“This study asked what’s going on in the spinal cord during stimulation?” Azim said. “It’s a big black box.”

dr Greg Nemunaitis, director of spinal cord injury rehabilitation at the Cleveland Clinic in Ohio, called the regained function in these nine patients “amazing.”

He also said the discovery of “recovery-organizing neurons” in mice is “a first step toward understanding and improving function in humans until the ‘cure’ is found.”

Azim said the insights into these key neurons could help further refine EES in the short term.

Looking ahead, he said a better understanding of how EES promotes exercise recovery could help develop even more sophisticated treatments. Technologies are advancing to the point where it may eventually be possible to safely access the spinal cord and “rebuild” damaged circuitry, Azim noted.

“It’s not a pipe dream,” he said.

The results were published online on November 9 in the journal Nature.

More information

The US National Institute of Neurological Disorders and Stroke has an overview of spinal cord injuries.

SOURCES: Eiman Azim, PhD, Associate Professor, Salk Institute for Biological Studies, La Jolla, California; Greg Nemunaitis, MD, Director, Spinal Cord Injury Rehabilitation, Cleveland Clinic, and Professor, Case Western Reserve University School of Medicine, Cleveland, Ohio; Nature, 9 Nov 2022 online

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