Cerebrovascular Hemodynamic Responses to Breath-Holding in Migraine: A Longitudinal Functional Near-Infrared Spectroscopy Study Comparing a Calcitonin Gene-Related Peptide Monoclonal Antibody and Oral Preventive Treatment

Purpose: Altered cerebrovascular reactivity has been reported in migraine; however, longitudinal changes during preventive treatment remain unclear. This observational study aimed to describe and compare longitudinal cerebrovascular responses derived from functional near-infrared spectroscopy (fNIRS) during a breath-holding test between patients treated with a calcitonin gene-related peptide (CGRP) monoclonal antibody and those receiving oral preventive medications.Methods: Twenty-four patients with migraine were enrolled (CGRP group, n=12; oral group, n=12). fNIRS over the prefrontal cortex was performed at baseline and after 3 months during a standardized breath-holding protocol. Oxygenated (HbO), deoxygenated, and total hemoglobin signals were used to derive breath-holding and recovery indices. Clinical outcomes included monthly headache days, acute medication days, disability, mood scales, and Patient Global Impression of Change.Results: Monthly headache days decreased in both groups (CGRP: Δ=–2.00, p=0.26; oral: Δ=–1.50, p=0.48), with no between- group difference (p=0.85). Acute medication days were significantly reduced only in the CGRP group (Δ=–7.00, p=0.03). Migraine Disability Assessment (MIDAS) scores improved significantly in the CGRP group (Δ=–21.25, p=0.02), with no significant between-group differences. During breath-holding, HbO increased across channels in both groups and was followed by a gradual decline during the recovery phase. Longitudinal analyses demonstrated group-dependent differences in temporal change patterns, with a treatment×time interaction reaching significance at the uncorrected level in a representative channel (Channel 6: F(1,16)=8.448, p=0.010), but not after multiple-comparison correction (p=0.155).Conclusion: fNIRS with a breath-holding challenge enables longitudinal assessment of cerebrovascular responses during migraine preventive treatment. The observed differences should be interpreted descriptively in terms of temporal change patterns. Larger studies are needed to clarify clinical significance.