Comprehensive, Programmatic Approach to Treatment Development at TIRR Memorial Hermann

For decades, TIRR Memorial Hermann researchers have taken a leadership role in the development of novel approaches for stroke rehabilitation, brain injury recovery and spasticity management. In spasticity management, for example, the treatments derived from this groundbreaking research range from now established approaches such as the use of botulinum toxin, first introduced in the United States in the late 1990s, as well as other toxins approved for spasticity by the U.S. Food and Drug Administration (FDA) in the years since. In addition, researchers at TIRR Memorial Hermann helped pioneer newer technologies, such as intrathecal baclofen.

Meanwhile, similar initiatives are exploring the use of vagus nerve stimulation for post-stroke rehabilitation and a brain-machine interface for controlling the movement of an upper-limb exoskeleton in patients following brain injury. Additionally, Sheng Li, MD, PhD, a renowned physical medicine and rehabilitation (PM&R) specialist at TIRR Memorial Hermann, was the first physician in the United States to use cryoneurolysis to provide patients with relief from spasticity. The noninvasive procedure, now available to patients at TIRR Memorial Hermann, involves inserting a needlelike probe containing highly pressurized nitrous oxide gas chilled into the skin and placing it on the nerve that is causing the condition.

“I’m in my 27th year—28th if you include an additional year of training—here at TIRR Memorial Hermann,” notes Gerard Francisco, MD, the health system’s chief medical officer. “It’s a phenomenon—the largest medical center in the world, and we’re advancing the field of rehabilitation and spasticity management.”

Botulinum toxin is an effective treatment for spasticity and lacks the sedating effect of oral medications. Phenol neurolysis, originally used for cancer pain, also blocks sensation in nerves and is sometimes used in lieu of or in conjunction with botulinum. Newer phenol-like medications are currently being researched by Dr. Francisco’s team. A more recent addition to the anti-spasticity arsenal is intrathecal baclofen, which is administered via a hockey puck-sized pump that is placed in the abdominal wall and then connected to the spine with a catheter. The pump is programmable to deliver as much or as little medication as needed, at whatever time of day.

“We have a comprehensive, programmatic approach to spasticity management,” Dr. Francisco notes. “However, I look at these medications and procedures as a way to allow the therapist to work with patients. Stretching is still the best treatment for muscle tightness, but if the spasticity is very severe, the therapist will not be able to get the work done, no matter how strong and talented the therapist is.”

Dr. Francisco is leading the TIRR Memorial Hermann team and its involvement in the development of other new approaches as well. Together with an international team from 19 stroke rehabilitation centers in both the United States and the United Kingdom, the group compared vagus nerve stimulation and a placebo stimulation procedure in patients with moderate-to-severe arm weakness for at least nine months following ischemic stroke. Patient groups were provided with an intensive physiotherapy routine of 90-minute sessions three times a week for six weeks, followed by a home exercise regimen.

“We only included patients in this study who had some movement of the wrist or fingers—as long as they can activate those muscles independently,” Dr. Francisco says. “Many of the participants had been told that their recovery had plateaued and essentially been written off—but it’s important to understand that when people plateau, it is not because they cannot recover anymore—it’s because we clinicians don’t have anything else to offer.”

The results showed that the upper limb function of study participants who received the actual vagus nerve stimulation plus physiotherapy regimen improved on Day 1 as well as Day 90. Clinical response on Day 1 was about twice that seen in those receiving the placebo stimulation plus physiotherapy, and nearly half of participants who got the active stimulation had “clinically meaningful improvements,” as per Fugl-Meyer motor assessment (FMA) test scores.¹

“There is an unwritten dictum in rehabilitation that says that the more substrate for recovery one has, the more likely it is that you will recover,” Dr. Francisco says. “This study indicates that those who had the most movement to begin with are the ones who recovered the most. This therapy won’t work for everybody, but I think this therapy should be offered to patients who have a particular set of characteristics.”

About eight years ago, armed with funding from the National Institutes of Health, Dr. Francisco and collaborators from the University of Houston and Rice University set up a feasibility study that explored whether it is possible to use an upper-limb robot, paired with brain signals from the patient, to enhance mobility and function following chronic stroke. Four chronic stroke patients, whose motor impairments were varied, participated in the study; all four were able to use the EEG-based brain-machine interface to control the exoskeleton.

The study found that “motor intent from brain activity” in patients with chronic stroke can be detected and used to steer the motion of an upper-body powered exoskeleton.²

“There are no implanted devices,” he explains. “Instead, the patient wears an EEG cap that has electrodes, much like an EEG cap for someone who has seizures. We are essentially training the person to use the robot—they wear the cap, and this signals the neurons in the brain to encourage the use of the robot. It looks like that this will work best for those with moderate impairments.”

References

¹ Lancet. 2021;397:1545-1553.
² Frontiers of Neuroscience. 2016;10:122