OC-03 | Transcranial magnetic stimulation in patients with chronic migraine and medication overuse headache

Elisa Maria Piella,¹ Fabio Ferrandes,¹ Gianluca Isoardo,¹ Alberto Mario Chiarandon,¹ Fausto Roveta,¹ Alessia Agostinelli,¹ Elisa Rubino,^1,2 Innocenzo Rainero,^1,2 | ¹Department of Neuroscience “Rita Levi Montalcini”, University of Turin; ²Headache Center, Department of Neuroscience and Mental Health, AOU Città della Salute e della Scienza di Torino, Turin, Italy

Background: Medication Overuse Headache (MOH) is a challenging secondary headache disorder frequently arising in patients with Chronic Migraine (CM). Over the past decades, neurophysiological investigations have significantly advanced our understanding of migraine pathophysiology. However, despite the availability of robust methodologies for assessing cortical and subcortical excitability, studies specifically focused on CM-MOH remain scarce. This study aimed measured Resting and Active Motor Thresholds (RMT, AMT) with Transcranial Magnetic Stimulation (TMS) in a population with CM-MOH.

Methods: In this cross-sectional case-control study, patients and healthy controls (HC) were consecutively recruited in our Headache Clinic. Diagnoses of CM and MOH were made according to ICHD-3 criteria. All participants underwent a standardized TMS protocol with single and paired TMS pulses delivered to the left primary motor cortex, starting at low stimulation intensity and gradually increasing to determine the key parameters. Data of AMT and RMT were compared between group, using appropriate parametric and non-parametric tests. Correlation matrices and linear regressions explored relationships between neurophysiological measures and clinical characteristics.

Results: We enrolled 10 females patients affected by CM-MOH (mean age ± SD: 56.6 ± 9.7 years) and 12 healthy controls (mean age ± SD: 34.3 ± 13.7 years). All participants were right-handed. CM-MOH patients demonstrated significantly lower RMT (median: 30; range: 27 - 32) compared to HC (median: 33.5; range: 31 - 39) suggesting heightened corticospinal excitability (r= -0.586, p=0.004). AMT showed a trend toward reduction (r= -0.394, p=0.070) but did not reach conventional significance. Regression analyses confirmed lower RMT as predictor of CM-MOH status (β = −0.398, p = 0.038).

 Conclusion: Our findings show that MOH may amplify the corticospinal hyperexcitability commonly seen in CM, as evidenced by lower RMT values. RMT distinguished patients from HC, suggesting they could serve as a prototype biomarker of MOH-related excitability changes. Future studies using larger, multi-center cohorts and longitudinal designs - focusing on medication subclasses and additional TMS measures - could help clarify whether these excitability changes revert upon drug withdrawal or define long-term risk.