Brain connectivity modifications induced by monoclonal antibodies targeting the CGRP pathway in migraine patients: a prospective HD-EEG, open-label, study

Abstract text (incl. figure legends and references)

Question: Monoclonal antibodies targeting the CGRP pathway (mAbs) proved effective and safe as migraine preventive treatment. Due to their molecular weight, mAbs act outside of the blood brain barrier, namely in the peripheral component of the trigeminovascular system. Nonetheless, a reduced sensitization of the first order neuron in the trigeminal ganglion may induce secondary effects at central level. Here we aim to study the changes induced by mAbs in cortical brain connectivity recorded by means of high-density electroencephalography (HD-EEG).

Methods: We plan to perform 5 resting state HD-EEG recordings, at baseline (before mAbs treatment), and then every 3 months for one year. Here we present data regarding 16 migraine patients (age 44.7±10.6, 14 females, 11 with CM) who completed the first three months of mAbs treatment (T3). We aim to study the connectivity changes in the nodes of the default mode network (DMN): the right and left angular gyrus (RANG and LANG), the medial pre-frontal cortex (MPC) and the posterior cingulate cortex (PCC).

Results: At T3, mAbs treatment induced an inter-nodal connectivity reduction between MPC-PCC (p=0.025), MPC-LANG (p=0.020), MPC-RANG (p=0.043), and PCC-LANG (p=0.005). By contrast, the connectivity was enhanced between PCC-RANG (p=0.005) and LANG-RANG (p=0.003). At T3, 7 patients qualified as "Responder" to mAbs (reduction in monthly migraine days of at least 50% when compared to baseline). Responders were characterized by a baseline enhanced connectivity between MPC-PCC (p=0.042) and MPC-RANG (p=0.032), and by a reduced connectivity between LANG-RANG (p=.016).

Conclusions: We described brain connectivity modifications in the DMN of migraine patients after three months of mAbs treatment. We hypothesize that a reduced sensitization of the peripheral component of the trigeminovascular system may account for the observed findings. In addition, Responder patients showed a specific baseline brain connectivity pattern.