Preventive treatment with CGRP monoclonal antibodies restores brain stem habituation deficits and excitability to painful stimuli in migraine: results from a prospective case-control study

Background & objectives!#!Calcitonin gene-related peptide ligand/receptor (CGRP) antibodies effectively reduce headache frequency in migraine. It is understood that they act peripherally, which raises the question whether treatment merely interferes with the last stage of headache generation or, alternatively, causes secondary adaptations in the central nervous system and might thus possess disease modifying potential. This study addresses this question by investigating the nociceptive blink reflex (nBR), which is closely tied to central disease activity, before and after treatment with CGRP antibodies.!##!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 (F!##!Discussion!#!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.!##!Trial registration!#!This trial was prospectively registered at clinicaltrials.gov (ID: NCT04019496, date of registration: July 15, 2019)

Treatment Realities of Headache Disorders in Rural Germany by the Example of the Region of Western Pomerania

(1) Background: Headache disorders are among the most disabling medical conditions but the supply with experienced providers is outpaced by the demand for service. It is unclear to what extent particularly patients in rural regions are affected by limited access to comprehensive care. Furthermore, it is unknown what role general practitioners (GPs) play in headache care. (2) Methods: First-time consultations to a specialised headache clinic at a tertiary care centre were asked to participate. Their socio-demographic background, general and headache-specific medical history, disability and quality of life (QoL) were assessed. Additionally, 176 GPs in neighbouring districts were contacted regarding headache management. (3) Results: We assessed 162 patients with first-time consultations (age 46.1 ± 17.0 years, 78.1% female), who suffered from migraine (72%), tension type, cluster and secondary headaches (each 5–10%). About 50% of patients received a new headache-diagnosis and 60% had treatment inconsistent with national guidelines. QoL was significantly worse in all domains compared to the general population. About 75% of GPs see headache patients at least several times per week, and mostly treat them by themself. (4) Conclusions: More than every second headache patient was neither correctly diagnosed nor received guideline adherent treatment. Headache-related disability is inferior to what is expected from previous studies. Access to specialised health care is more limited in rural than in urban regions in Germany and GPs request more training