LAUSR

Dear Editor, As widely known, classic trigeminal neuralgia (TN) represents one of the most common craniofacial pain syndromes [9, 15]. Medical therapy, as first-line treatment, is effective in controlling pain in a high percentage of cases at short-time period; however, this rate does significantly decrease over time [15]. Microvascular decompression (MVD) represents historically the reference technique [15]. Despite several other therapeutic options, almost half of the patients may experience pain recurrence, negatively affecting their quality of life (QoL) [2, 14, 15]. Stereotactic radiosurgery (SRS), such as Gamma Knife radiosurgery (GKRS), has increasingly become a popular treatment for TN, for the lack of treatment-related toxicity and mortality, less invasiveness, and good pain control rates [2, 14–16]. However, the right timing for GKRS or MVD is still a great matter of debate and data in literature are uneven [15]. Other SRS techniques, such as LINAC based SRS, namely, Cyberknife and Novalis, have been adopted for TN, with similar outcome of GKRS [15]. For those patients who are not operable and need a quick minimal invasive treatment, percutaneous techniques can be considered, such as glycerol or radiofrequency rhizotomy and balloon compression, with high rates of immediate pain relief that are, however, not maintained over time [15]. A long history of pain is usually related to a higher probability of pain recurrence after bothMVD andGKRS [4, 10, 16]. Mousavi reported a shorter interval to pain relief, a longer interval of pain relief off medication, and a longer duration of pain control in those patients undergoing GKRS for TNwithin 3 years of pain onset [10]. Conversely, Lee et al. recently found that, even if early performed (< 5 vs. > 5 years), GKRS was related to a better outcome and a shorter latency before pain relief; pain history > 5 years was not related to treatment failure [4]. These data suggest that GKRS seems to be more effective when performed at the early stage of TN. Affected trigeminal nerves usually appears flattened and atrophic especially with a longstanding history of TN [8]. Longer pain history is likewise associated with nervous microstructural changes on diffusion tensor imaging studies, such as demyelination and loss of axon, conditioning minor pain response to surgical therapy [5]. In TN, as for epilepsy and chronic pain, the kindling of secondorder sensory neurons into the brainstem, may negatively affect outcome after therapies targeting first-order sensory neurons, such as GKRS and MVD [4, 5, 10]. Accordingly, these two surgical modalities should be carried out early, to improve pain control on shortand long-term periods [4, 10, 16]. Based on these findings, another issue comes out in the selection of the best strategy: which one must be undertaken first? Clinical outcome after GKRS and MVD is frequently better in those patients without history of previous therapies; nevertheless, this relationship seems to affect GKRS more than MVD [1, 2, 7, 15, 16]. For classic TN, outcome after GKRS is worse in those patients who underwent MVD before GKRS, leading to a lower probability of initial pain cessation but similar probability of maintaining pain relief without medication at 10 years [16]. Six studies comparing MVD to GKRS outcomes have been published to date [3, 6, 11–13, 18]. In their prospective non-randomized trial, Linskey and coworkers reported significant better results in MVD patients in terms of pain control; hence, they suggested to perform MVD to younger and healthy patients, while GKRS to those older or when surgery is contraindicated [6]. * Alfio Spina [email protected]