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Bilateral focused ultrasound central lateral thalamotomy (CLT) for refractory trigeminal neuralgia (TN) was well tolerated and improved outcomes on several multidimensional pain instruments in a phase 1 pilot trial.

Preliminary results showed significant decreases in pain scores 6 months after treatment for TN, suggesting the phasic pain phenomenon may respond to CLT.

"Our conclusions are that bilateral central lateral thalamotomy for refractory TN is well tolerated," investigator Abdul-Kareem Ahmed, MD, a resident at the University of Maryland School of Medicine, Baltimore. "We did find this treatment has the potential to alleviate pain in these patients who have failed other classical treatments."

The findings were presented on May 4, 2024 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting, where Ahmed was the recipient of the William H. Sweet Young Investigator Award.

Expanding Existing Research

The current trial represents a follow-up and advance on the researchers' recent phase 1 trial of bilateral magnetic resonance-guided focused ultrasound (MRgFUS) posterior CLT to treat refractory neuropathic pain.

In that trial, ablation was successful in nine of the 10 patients, with no serious adverse events. One-year follow-up revealed decreases of 46.3% in the Brief Pain Inventory, 39.3% in the Pain Disability Index, and 42.8% in the Numeric Rating Scale, Ahmed said.

"We weren't powered for this — it was only nine patients — but we found that patients who had intermittent, phasic pain or allodynia were responding two to three times better than patients without, which is very interesting and actually encouraged us to try refractory trigeminal neuralgia," he added.

The present pilot study will eventually enroll 10 patients with refractory TN who failed or are ineligible for intervention or surgery, had also failed medications of two different classes, and have no other neurological diseases.

Seven patients (age, 36-67 years) have been treated thus far. The TN etiology was vascular in four and nonvascular in three.

Bilateral MRgFUS posterior CLT took about 2 hours and was well tolerated, with no serious adverse events, Ahmed said. Head tenderness and headache were common and mild. One patient had moderate peripheral cerebellar edema that resolved and was thought to be unrelated to treatment as the patient had severe COVID.

Promising Outcomes

At 6-month follow-up, the Brief Pain Inventory facial score decreased by 75% (P = .003) from 112.6 to 28.3; and scores on the Patient Global Impression of Change went from an average of 1.0 at screening to 5.7 (P = .001), with a score of 0 indicating no change and 7 indicating a considerable improvement in their painful condition, Ahmed reported.

There was a 36.6% change in Barrow Neurological Institute pain intensity scores, from 4.1 at screening to 2.6 at 6 months (P = .025), "which is important because 3-4 on this scale is where medication helps or not. So functionally that's also a very important direction there," he said.

There were too few patients to determine the effect of having vascular etiology on outcomes, he noted.

"Refractory trigeminal neuralgia is a source of tremendous suffering and can make it impossible for patients to lead anything approaching a normal life," Mary Heinricher, PhD, professor and vice chair for research, Department of Neurological Surgery, Oregon Health and Science University School of Medicine, Portland, Oregon, told Medscape Medical News.

She noted that although the mechanisms underlying how thalamocortical circuits change in challenging neuropathic pain states are still under study, dysregulation in these circuits must play an important role.

"Evidence that focused ultrasound targeting central lateral nucleus has the potential to provide relief is both a source of hope for these patients and likely tells us something about how this circuit has gone wrong," Heinricher added. "That information could put us on a path to better mechanistic understanding, which in turn, could lead to improved treatment."

Study funding was not disclosed. Ahmed and Heinricher had no financial relationships to disclose.

Patrice Wendling is a medical journalist based in Chicago.