Predictors of Pain Relief after Index Gamma Knife Radiosurgery for Trigeminal Neuralgia: Retrospective Analysis of a 25-Year Series

Abstract – Introduction: Gamma Knife radiosurgery (GKRS) is an established treatment for trigeminal neuralgia; however, predictors of pain relief following treatment remain unclear. We aimed to identify the factors associated with pain relief after the index GKRS session for trigeminal neuralgia. Methods: We retrospectively analyzed a series of 204 patients with trigeminal neuralgia treated with GKRS between 1998 and 2023 (mean age 65.2 years, 68.5% female). Patient variables (pretreatment Roswell Park and Barrow Neurological Institute [BNI] pain scores, symptom duration, prior therapies, multiple sclerosis (MS) status), MRI metrics (neurovascular contact and trigeminal nerve dimensions), and radiosurgery parameters (isocenter location and radiation dose, including biologically effective dose [BED]) were assessed. Responders were defined as BNI <IIIb or RPS <3. Results: At last follow-up (median 20 months, range 6 months to 26 years), 57.3% of patients achieved pain relief. At ≥3-year follow-up, 74.1% of patients maintained adequate pain relief. MS and prior interventions were associated with lower response rates: MS patients had 27.7% response vs. 57.7% without MS (p = 0.008), and prior microvascular decompression (MVD) had 34.4% vs. 62.7% without prior MVD (p = 0.005). GKRS as first-line therapy yielded better outcomes than when used after other treatments (63.9% vs. 38.9%, p = 0.045). Responders had a smaller trigeminal nerve (mean diameter 3.04 vs. 3.42 mm, p = 0.007) and a greater isocenter-to-brainstem orthogonal distance (4.2 vs. 3.5 mm, p = 0.02). A BED ≥2000 Gy was associated with higher response rate (75.8% vs. 48.8%, p = 0.006). In multivariate analysis, absence of MS, no prior MVD, smaller nerve diameter, and BED ≥2000 Gy independently predicted pain relief. Conclusion: Non-modifiable factors that affected response included absence of MS and smaller trigeminal nerve size. Modifiable factors that were associated with higher response rates included no prior MVD, placing the isocenter farther from the brainstem surface, and BED ≥2000 Gy. These findings support individualized treatment sequencing and GKRS planning to optimize outcomes of GKRS for trigeminal neuralgia.