METHODS: We enrolled 22 patients suffering episodic migraine (21 female, 46.2 ± 13.8 years of age) and 22 age-/gender-matched controls. Patients received assessments of the nBR (R2 component, 10 trials, 6 stimuli/trial) before (V0) and three months (V3) after treatment with CGRP antibodies started, controls were assessed once. The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) of the stimulated/non-stimulated side (_s/_ns) following repeated supraorbital stimulation provide a direct readout of brainstem excitability and habituation as key mechanisms in migraine.
RESULTS: All patients showed a substantial reduction of headache days/month (V0: 12.4±3.3, V3: 6.6 ± 4.9). R2a_s (Fglobal=5.86, p<0.001; block 1: R2a_s: -28%, p<0.001) and R2a_ns (Fglobal=8.22, p<0.001, block 1: R2a_ns: -22%, p=0.003) were significantly decreased, and R2h_ns was significantly enhanced (Fglobal=3.07, p<0.001; block 6: R2h_ns: r=-1.36, p=0.007) from V0 to V3. The global test for changes of R2h_s was non-significant (Fglobal=1.46, p=0.095). Changes of R2h significantly correlated with improvement of headache frequency (R2h_s, r=0.56, p=0.010; R2h_ns: r=0.45, p=0.045). None of the nBR parameters assessed at baseline predicted treatment response.
CONCLUSIONS: We provide evidence that three months of treatment with CGRP antibodies restores brain stem responses to painful stimuli and thus might be considered disease modifying. The nociceptive blink reflex may provide a biomarker to monitor central disease activity. Future studies should evaluate the blink reflex as a clinical biomarker to predict treatment response at baseline and to establish the risk of relapse after treatment discontinuation.
BACKGROUND: This trial was prospectively registered at clinicaltrials.gov (ID: NCT04019496, date of registration: July 15, 2019).