A University of Alberta clinical trial could offer new hope for people worldwide living with one of the most painful conditions there is.
Trigeminal neuralgia — once dubbed the “suicide disease” — leads to excruciating, stabbing facial pain set off by daily activities like eating, brushing the teeth or yawning. About 700 new cases are diagnosed in Alberta each year.
Patients are usually treated with nerve pain medications but, as repurposed anti-seizure medications, these have side-effects such as blurry vision, imbalance and allergies. And they eventually stop working for about half of those who take them.
Until now, non-invasive surgery using Gamma Knife radiation has been offered as a last resort after medications stop being effective.
“We treat trigeminal neuralgia by giving a pretty high dose of radiation to the trigeminal nerve on the affected side, but the longer you wait before you offer Gamma Knife, the less likely it is to lead to long-term remission of the disease,” explains Tejas Sankar, associate professor of surgery and neurosurgery research director in the Faculty of Medicine & Dentistry.
Now Sankar and his team are recruiting 80 patients from across the province to receive immediate Gamma Knife neurosurgery at the Scott and Brown Families Gamma Knife Centre at the University of Alberta Hospital, the only facility of its kind in the province.
Half of the patients will receive the usual medications; the other half will receive “ultra-early” Gamma Knife surgery. Patients in the control arm will have the option of receiving Gamma Knife treatment later if they choose.
Sankar explains that his team’s research using functional MRI indicates that living with trigeminal neuralgia actually changes the way the brain works. The trial aims to stop those changes before they become permanent.
“What we found was — and this shouldn’t come as too much of a surprise — the longer you have this facial pain condition, the more lasting changes occur in the brain both structurally and functionally,” Sankar says.
Sankar’s research shows that the limbic system, which is responsible for emotion, memory and behaviour, becomes hyperactive in people with chronic pain, while other parts of the brain that should dampen pain messages are unable to do so.
“The longer you have the disease, the more profound these changes are. So we have a scientific basis to argue in favour of earlier surgical intervention before these irreversible brain changes occur,” Sankar says.
“Gamma Knife is an approved treatment, so we’re not trying to reinvent the wheel here. If we find that those patients who undergo early Gamma Knife surgery are less likely to develop severe chronic pain in the future, then everybody would end up getting that as the first line of treatment,” Sankar adds.
“They wouldn’t have to go through all these medication side-effects and wait for the inevitable failure of the medication. It would change the way we treat this illness.”
Sankar’s team will follow patients for five years, evaluating their pain using the standard Barrow Neurological Institute Facial Pain Scale.
Sankar’s recent work also involved collaborations with colleagues at the Peter S. Allen MR Research Centre to develop new MRI scans to visualize the trigeminal nerve in more detail than was previously possible.
They are now using these scans to look for biomarkers to better predict which patients will respond to surgery, and they’re working to improve imaging and surgical techniques.
“Previously it was thought that if you did a successful operation, the nerve would just repair itself. But it turns out that you may actually have to intentionally disrupt the nerve a little bit. And right now there’s no way to know during surgery that you actually achieve the right degree of disruption,” he notes.
The goal is for the Gamma Knife surgery to damage the nerve enough to interrupt the pain signals and stop it from over-firing.
“If you think about a nerve, there’s a lot of cables within it, and some of them in the trigeminal nerve will carry information on feeling, some of them will carry information on chewing, but some of them will carry pain information,” he explains. “It might be that they’re talking to each other too much. Perhaps by inducing some subtle damage, you prevent that cross-talk.”
Sankar’s lab is also working on advances in Parkinson’s disease, including a recent paper on tools to perform deep brain stimulation more accurately.
Tejas Sankar’s work is funded by the Canadian Institutes of Health Research and the University Hospital Foundation. He is deputy director of clinical research with the Neuroscience and Mental Health Instituteand editor-in-chief of the Canadian Journal of Neurological Sciences.
