Exploring the Therapeutic Potential of Quadripulse rTMS over the Visual Cortex: A Proof-of-Concept Study in Healthy Volunteers and Chronic Migraine Patients with Medication Overuse Headache

Alessandro Viganò; Tullia Sasso D'Elia; Simona Liliana Sava; Alfredo Colosimo; Vittorio Di Piero; Delphine Magis; Jean Schoenen

doi:10.3390/biomedicines12020288

Exploring the Therapeutic Potential of Quadripulse rTMS over the Visual Cortex: A Proof-of-Concept Study in Healthy Volunteers and Chronic Migraine Patients with Medication Overuse Headache

Biomedicines. 2024 Jan 26;12(2):288. doi: 10.3390/biomedicines12020288.

Authors

Alessandro Viganò¹, Tullia Sasso D'Elia^{1

2}, Simona Liliana Sava^{1

3}, Alfredo Colosimo⁴, Vittorio Di Piero⁵, Delphine Magis^{1

6}, Jean Schoenen¹

Affiliations

¹ Headache Research Unit, Department of Neurology, University of Liège, Citadelle Hospital, 4000 Liège, Belgium.
² IRCCS San Raffaele Alla Pisana, 00163 Rome, Italy.
³ Headache Clinic of Valdor-ISOSL, 4020 Liège, Belgium.
⁴ Department of Anatomy, Histology, Forensic Medicine and Orthopedics Sapienza, Sapienza-University of Rome, 00185 Rome, Italy.
⁵ Subintensive Neurology & Headache Centre, Department of Human Neurosciences, Sapienza-University of Rome, 00185 Rome, Italy.
⁶ Neurology Department and Pain Clinic (CMTD), CHR East Belgium, 4800 Verviers, Belgium.

Abstract

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed.

Keywords: central sensitization; chronic migraine; medication overuse headache; neuromodulation; quadripulse rTMS; visual evoked potentials.

Grants and funding

Sources of financial support: This work was supported by the research convention 3.4.650.09 of the National Fund for Scientific Research-Belgium to J.S., by research convention 1117427 of the CWALity program of the Walloon Region, and by the European Union’s Seventh Framework programme under grant agreement no. 602633.