Ultrasound assessment of cerebrovascular risk via breath-holding index in migraine patients treated with anti-CGRP monoclonal antibodies: a pilot study

Aim: Migraine is the second most disabling condition worldwide. Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway represent an effective prophylactic treatment; however, their impact on cerebral hemodynamics remains unclear. The aim of this pilot study was to evaluate cerebrovascular risk in patients with migraine without aura treated with these therapies, by calculating the breath-holding index (BHI) of the anterior cerebral circulation using transcranial color-coded Doppler (TCCD) ultrasonography. Material and methods: Cerebral vasomotor reactivity to hypercapnia was assessed using the breath-holding test combined with TCCD ultrasonography in 40 patients with migraine without aura undergoing treatment with anti-CGRP monoclonal antibodies and 40 healthy subjects. BHI values and other key cerebrovascular parameters were compared between the groups. Results: The BHI values in patients with migraine without aura were not below the threshold predictive of increased cerebrovascular risk (less than 0.69% per second, as referenced in the general population). No significant differences were observed in major cerebrovascular parameters between cases and controls. Additionally, a subanalysis revealed no significant differences based on the specific monoclonal antibody (erenumab, fremanezumab, or galcanezumab) or clinical response status (responders versus non-responders). Conclusions: Our findings suggest that treatment with anti-CGRP monoclonal antibodies is not associated with a BHI indicative of increased cerebrovascular risk. Notably, this is the first study to include galcanezumab and fremanezumab in the evaluation of cerebrovascular risk using ultrasound, highlighting TCCD ultrasonography as a practical and non-invasive tool for the assessment of cerebrovascular reactivity in migraine.