Prumary trigeminal neuralgia (PTN) is supposedly caused by an ectatic blood vessel affecting the trigeminal nerve at the root entry zone of the brain stem, i.e. a neurovascular conflict (NVC). Recent evidence suggests an additional central component within trigeminal pain-processing in the pathophysiology of PTN. Consistently with this hypothesis structural grey and white matter alterations and functional cerebral changes in PTN patients have been described. In this study, we aim at investigating the link between NVC, trigeminal nerves and brain changes in PTN patients (TRI) compared to healthy controls (HC). Moreover, we will explore the association with clinical variables. Fifty patients with PTN will be enrolled in this study. Fifty matched HC will be also included. All subjects will undergo a complete neuropsychological assessment and MRI scan with a 3T system (Verio, Siemens). The MRI exam will include conventional sequences to identify neurovascular conflict, 3D-T2-weighted CISS sequences to obtain a quantitative evaluation of nerve volume, T1-FSPGR sequences to perform calculation of grey matter volumes using, BOLD fMRI sequences to evaluate functional brain connectivity. Data analysis will consist in evaluation of severity of neurovascular conflict (NVC: grade 0 no contact between nerve and vessel, grade 1 contact, grade 2 distortion or dislocation of nerve) quantitative evaluation of nerve volume and nerve volume asymmetry using MIPAV, quantification of grey matter volumes using voxel-based morphometry (VBM), surface based morphometry (SBM) and regional based morphometry (RBM) (CAT, SPM12), analysis of functional connectivity using both seed analysis and independent component analysis (CONN, SPM12). Statistical analysis will be conducted to investigate the relationship between clinical variables (age, duration of disease, pain intensity, duration and frequency of attacks) and MR imaging data (SPSS 25).
No studies have been published in literature that have performed in a single project and in a large cohort of subjects, a comprehensive evaluation of the nerve and of the brain in patients with primary trigeminal neuralgia.
Our group has been investigating trigeminal neuralgia for several years and has acquired a broad experience on the clinical and imaging characteristics of this disease, that is proven by the papers published on the topic. Furthermore, the Clinic of Neuropathic Pain at our institution is a well-known and highly considered referral center for patient with PTN, due to the expertise of Prof. Cruccu, Prof. Truini and their group as world renowned experts in the field. Therefore, we have access to a large cohort of patients, that can be adequately selected and informed to obtain their consent and willingness to participate to the study.
Furthermore the expertise of our group and of the international collaborators on advanced functional and structural techniques to study both nerve and brain will help better elucidate the characteristics of PTN.
Classical trigeminal neuralgia has been the subject of interest of several papers in the past decade, due to the difficulty in adequately diagnose and treat the disease. The advent of high field magnets has shed some light in the characteristics of the neuro-vascular conflict and nerve damage, still a definite consensus on the impact of NVC on PTN has not been fully elucidated. The recurrence of pain after decompressive surgery and the existence of a percentage of patients that has neuralgia in the absence of any vascular contact, as well as the knowledge of subject with NVC without pain, prompt the investigation of a) an accurate characterization of the NVC on a large cohort pf patients b) in-depth analysis of subjects without NVC and pain c) the investigation of cerebral morphological and functional modifications that may be contributing to the outcome and persistence of pain.