Trigeminal neuralgia (TN) is one of the most excruciating pain syndromes known to man. While classical TN is usually responsive to medication and can be surgically cured by microvascular decompression, multiple sclerosis-associated trigeminal neuralgia (MS-TN) is a different story. These patients are younger and are often more severely impaired, and our treatments are generally less effective.^{Reference O’Connor, Schwid, Herrmann, Markman and Dworkin1,Reference Mohammad-Mohammadi, Recinos, Lee, Elson and Barnett2}

In this paper, Guillemette et al. report a series of 50 patients treated by CyberKnife radiosurgery for MS-TN. They demonstrate that the approach is safe, with a rate of bothersome facial numbness of 6%. Initial pain relief was achieved in 86% of patients, although it was only sustained for a median of 12.7 months, and 68% of patients experienced a recurrence during follow-up.

As one of the first reports on the use of CyberKnife for MS-TN, it provides a few interesting insights. First, with pain relief achieved after a median of 2 weeks, it contrasts sharply with the Gamma Knife series where a latency of 17 weeks is typically reported.^{Reference Leduc, Mathieu, Adam, Ferreira and Iorio-Morin3} The authors suggest this might be due to the nonisocentric delivery paradigm used by the CyberKnife. Presumably, this generates a more ovoid irradiation plan that might increase the integral dose received by the nerve. The dose rate also appears higher than in comparable Gamma Knife plans, which might increase the biologically effective dose – a parameter found by some to be predictive of response.^{Reference Tuleasca, Paddick and Hopewell4} Surprisingly, the treatments also appear less durable than contemporary reports using Gamma Knife in the same population (12.7 vs 29 months).^{Reference Leduc, Mathieu, Adam, Ferreira and Iorio-Morin3} Whether this is a real property of the different treatment modalities or a bias introduced by the retrospective nature of both cohorts is unclear. What is clear, however, is that these treatments are not durable enough.

As opposed to classical TN, MS-TN is associated with visible lesions in the brainstem, typically in the vicinity of the trigeminal tract. It is tempting to assume that pain is therefore generated within the brainstem, proximal to the sites where all surgical and radiosurgical interventions are performed. Procedures might work in this setting by impeding peripheral afferents from triggering a TN attack, but they are unlikely to prevent TN attacks from being perceived. We believe successful treatment of this challenging population will require entirely new strategies able to act proximal to the MS lesions. Potential candidates include deep brain stimulation (as currently trialed in Sherbrooke in NCT05451251) or gene therapy approaches.