Central effects of galcanezumab in migraine: a pilot study on Steady State Visual Evoked Potentials and occipital hemodynamic response in migraine patients

Abstract

Background The discovery of the prominent action of Calcitonin Gene Related Peptide –CGRP- on trigeminal afferents and meningeal vessels, opened a new era in migraine treatment. However, how the block of nociceptive afferents could act on central mechanisms of migraine is still not clear. In this pilot study we aimed to test the effect of 3 months Galcanezumab (CGA) therapy on occipital visual reactivity in migraine patients, using the Steady State Visual Evoked Potentials-SSVEPs and Functional Near Infrared Spectroscopy –fNIRS. Method Thirteen migraine patients underwent clinical and neurophysiological examination in basal condition (T0), 1 h after GCA injection (T1) and after 3 months of GCA treatment (T2). Ten healthy volunteers were also evaluated. Results At T2, there was a reduction of headache frequency and disability. At T2, the EEG power significantly diminished as compared to T0 and T1 at occipital sites, and the topographical analysis confirmed a restoration of SSVEPs within normal values. The Oxyhemoglobin levels in occipital cortex, which were basically increased during visual stimulation in migraine patients, reverted to normal values at T2. Conclusions The present pilot study indicates that Galcanezumab could act on cortical targets located beyond the pain network, restoring the abnormal occipital reactivity. This effect could indicate the possible disease modifying properties of CGRP related monoclonal antibodies.

Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: A real-world evidence study

“…There is accumulating evidence on how modulation the periphery in migraine can have an impact on central mechanisms. In fact, other studies have demonstrated changes in central neuroimaging (39,40), and neurophysiological parameters (41)(42)(43) or have even shown an impact on migraine aura (44,45), as in our case. Interestingly, a previous exploratory study found that treatment with anti-CGRP mAbs could prevent prodromal symptoms such as aura, stress or anxiety and could modulate sleep and weight (25).…”

Galcanezumab treatment changes visual related EEG connectivity patterns in migraine patients

“…We particularly aimed to investigate the changes of the EEG perturbation under visual stimuli, which could be less influenced by the generic beneficial effect of galcanezumab with respect to resting state EEG, and rather indicate a possible reset of abnormal sensory reactivity proper of migraine (4,8). The study is of paramount importance to confirm and better understand the results obtained with standard analysis in our previous work (15) that we now reproduce in the present work, including the new subjects enrolled, so that a direct comparison with the connectivity analysis was possible. In this regard, we used graph theory to perform an explorative and unsupervised analysis aiming to understand whether graph theory could find connectivity patterns related to some beneficial effect of the therapy without imposing any constraint such as specific frequencies, time segments or locations.…”

“…four frequency bands that we considered: delta (0.5-3.5 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”

“…As also specified in our pilot study (15), we did not have ethical permission for a placebo because of the severe form of migraine that affected patients. The test after 1 hour could detect the influence of suggestion on EEG features, and certainly not the clinical placebo effect, which could help to determine whether the subjective improvement could contribute at least in part to restoring the abnormal EEG patterns…”

Anticuerpos monoclonales anti-PRGC y modificación de la historia natural de la migraña

“…Ambos trabajos sugieren, por tanto, que el tratamiento induce modificaciones funcionales centrales del procesamiento nociceptivo. -A nivel de las aferencias visuales y el córtex occipital, en un estudio de 13 pacientes se demostró una normalización de los potenciales visuales evocados steady state y de los niveles de oxihemoglobina en el córtex occipital medidos por espectroscopia funcional con infrarrojos a los tres meses de tratamiento con galcanezumab, sugiriendo una acción a nivel cortical que restauraría la reactividad occipital anormal más allá de las redes del dolor 28 . Por otro lado, se han descrito también hallazgos de neuroimagen funcional que apoyarían efectos centrales de los anticuerpos anti-PRGC (Tabla 1):…”