Two Spinal Cord Injured People Walk Again After Activating a Non-Walking Area of ​​the Brain | Science

It weighs just five grams and makes up 0.3% of the volume of the entire brain, but hidden deep in the brain, the hypothalamus is huge: it synthesizes several hormones and activates or controls basic functions such as body temperature, heart rate, thirst, hunger and satiety center , sexual desire, motivation… Now a group of Swiss researchers talk in detail in a scientific journal Natural medicine who have discovered an unexpected role, but which will give hope to people with spinal cord injuries. They confirmed that by activating the lateral hypothalamus with electrodes, two accident victims with partially severed spinal cords were able to walk again.

EPFL neuroscientist Grégoire Courtin has spent many years researching the connection between the brain and the spinal cord and the damage associated with the loss of this connection. Ten years ago he managed to make a rat with a broken spine walk again. During that time, his team has made progress on several fronts, such as allowing three paraplegics to walk independently using walkers or, most recently, allowing dozens of paraplegics to improve their dexterity using their arms. Last year, a team led by Spaniard Eduardo Martin Morauda, ​​also from Curtin’s group, made great progress in a parallel line of research: a man who had suffered from Parkinson’s disease for 25 years could walk again. Now the Swiss scientist, together with his long-term partner, neurosurgeon Jocelyne Bloch, have made a discovery that could have great significance – the role of neurons in the lateral hypothalamus, which previously had nothing to do with the musculoskeletal system.

In an effort to create an atlas of the brain after spinal cord injury, Bloch, Curtin and their team took MRI images of the brains of rats with partial spinal cord injury at the level of the back. In these situations, the brain reorganizes and tries in any way to force the body to respond to its nerve stimuli again. If the partition is complete there isn’t much to do, but if some residual connection still exists, that could be the basis for recovery. The MRI gave them a surprise: when they regained some control of their hind legs, the rodents showed more activity in the hypothalamus, especially in a set of neurons that activate or inhibit the neurotransmitter glutamate.

“This seminal study, which created detailed maps of the whole brain, allowed us to identify the lateral hypothalamus in gait recovery,” says Jordan Squire, study co-author and student, in an EPFL de Courtin and scientist note. at .Neurorestore, a company created as a result of this research. “Without this fundamental work, we would not have discovered the unexpected role this region plays in restoring mobility,” he adds. The next step was logical to increase the role of hypothalamic neurons projecting to the spinal cord. To do this, they placed electrodes in this part of the brain of injured mice and rats. The technique is not new: so-called deep brain stimulation (DBS) has been used for many years to control tremors in people with Parkinson’s disease. Once it was confirmed that rodents recover walking using electrical stimuli, it was time to test it in humans.

Bloch explains what happened when they started the test: “As soon as the electrodes were installed and the stimulation was done, the first patient immediately said, ‘I can feel my legs.’ As we increased the stimulation, he said, “I feel the need to go for a walk!” This real-time feedback confirmed that we were targeting the right area, even though this area has never been linked to leg control in humans. The neurosurgeon, co-director of .NeuroRestore, adds that it was then that she learned that they had witnessed “an important discovery of the anatomical organization of brain function.”

54-year-old Austrian Wolfgang Jaeger is the second of the patients. He has been in a wheelchair since a bad skiing accident in 2006 damaged his spine and damaged almost his entire spinal cord. After Bloch’s team implanted the electrodes at the University Hospital of Lausanne, Switzerland, Jäger took part in a six-month rehabilitation program. He explains the results himself in the video: “Now when I see a staircase with just a few steps, I know I can handle it.” His gait is still fragile (see video), but, as he says, “it’s a wonderful feeling not to have to depend on others all the time.”

According to the head of the neurology department of the National Hospital for Paraplegia in Toledo, Antonio Oliviero, the work is “very good and of high quality.” What caught his attention most was the discovery of a “modulatory role,” he says. the hypothalamus, although it remains questionable, “whether its intervention improves connections left behind (after injury) or is capable of regenerating them.” To this, Bloch explains in an email that “this treatment will not work for complete spinal cord injuries because lateral hypothalamic stimulation requires replacement connections from the brain to the spinal cord to work.” What Oliviero likes most about this work, however, is that “after the electrodes were turned off, the improvement persisted.” Indeed, two participants no longer needed deep brain stimulation to take walks, however short.

Several years ago, the biomedical neuroengineering group at the Bioengineering Institute of the Miguel Hernandez University discovered how changes occur in certain areas of the brain after spinal column injury. Alicante team director Eduardo Fernandez links this to ongoing work by the Swiss scientists: “Dr. Curtin’s group has now shown that these regions may be important and that there are some key regions whose electrical stimulation may promote spontaneous recovery of walking after partial spinal cord injury. However, Fernandez reminds that this is a pilot study with only two patients, “so more research is still needed to confirm the effectiveness of this therapeutic approach in more people and identify those patients who may benefit more from treatment.” from this type of therapeutic approach.”

Curtin and Bloch’s idea is to move on to study a larger group of patients in whom DBS electrodes can be implanted. The first thing they will explore in this new phase is the role and possible mid- and long-term effects of deep brain stimulation. They also want to combine them with spinal implants, which they have tried in the past. In the note, Curtin says, “Integrating our two approaches (brain and spinal cord stimulation) will offer a more comprehensive recovery strategy for patients with spinal cord injuries.”