Three-Month Treatment with Monoclonal Antibodies Targeting the CGRP Pathway Is Associated with Multi-Domain Changes in Sensory Processing and Cortical Network Efficiency in Migraine: Results from a Prospective Case–Control Study

Background/Objectives: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway are effective drugs for migraine prevention. The worsening of symptoms after treatment discontinuation has raised the question of whether these agents are associated with sustained central neurophysiological adaptation. This study investigated treatment-associated changes in sensory processing and cortical network efficiency during preventive treatment with CGRP monoclonal antibodies (mAbs). Methods: Twenty-two patients with episodic migraine (21 female, 46.2 ± 13.8 years) and 22 age- and sex-matched healthy controls underwent visual and somatosensory evoked-potential (VEP, SSEP) assessments and quantitative electroencephalography (qEEG). Patients were investigated before treatment initiation (V0) and after 3 months of CGRP mAb treatment (V3). Healthy controls were assessed once. Results: The lack of habituation of VEPs at V0 shifted toward habituation at V3 following treatment with CGRP mAbs (Δslope: −0.37 ± 0.83, p = 0.03). VEP habituation at V3 no longer differed significantly from controls. SSEP amplitudes remained stable and did not differ significantly between groups across the study interval. Exploratory qEEG parameters indicated a less efficient cortical network organization at V0 that was no longer significantly different from controls at V3. Conclusions: Three months of CGRP mAb treatment was associated with a partial normalization of selected neurophysiological parameters, particularly VEP habituation and exploratory qEEG network measures. Given the study design and small sample size, these findings indicate adaptive changes in multi-domain processing, yet these should not be overinterpreted as proof of disease modification.