Thesis defense

Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex is recommended as a third-line treatment for drug-resistant neuropathic pain. The objectives of this thesis are to assess the long-term benefit of rTMS in clinical practice, to optimize its efficacy by identifying predictive factors of response, and by combining this technique with mirror therapy, as well as to explore its underlying mechanisms of action.

Two real-world studies were conducted with over 200 neuropathic pain patients. The first study confirmed, over the very long term, the analgesic effectiveness, safety, and clinical applicability of rTMS in a large, complex patient population. Adopting a more holistic perspective, the second study reports motor benefits alongside pain relief and improvements in comorbidities such as fatigue and sleep disturbances. In addition, lesion type and fatigue level have been identified as potential predictors of treatment effectiveness. This work also suggests improvements to therapeutic strategies, such as increasing the number of sessions before evaluating effectiveness and supports the reintegration of epidural stimulation as a long-term solution.

A randomized controlled trial to further optimize rTMS efficacy by combining it with virtual reality-based mirror therapy is currently ongoing, with the premise that it could further engage the primary motor cortex. Two-fifths of the patients have already been recruited, and the preliminary results confirm the feasibility of this combined therapy, which is encouraging for further recruitment. This study also includes a previously unexplored neuroimaging component, using functional imaging to better understand the mechanisms of rTMS and to search for neurophysiological biomarkers that could provide valuable insights into predicting therapeutic success.

In conclusion, rTMS over the primary motor cortex is a safe and effective therapeutic option for patients with drug-resistant neuropathic pain. Its implementation in routine practice appears feasible and promising over the long term. The optimization of its efficacy could be achieved through the combination with other approaches, such as mirror therapy.