Search

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 (&#95;s/&#95;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&#95;s (F global =5.86, p<0.001; block 1: R2a&#95;s: -28%, p<0.001) and R2a&#95;ns (F global =8.22, p<0.001, block 1: R2a&#95;ns: -22%, p=0.003) were significantly decreased, and R2h&#95;ns was significantly enhanced (F global =3.07, p<0.001; block 6: R2h&#95;ns: r=-1.36, p=0.007) from V0 to V3. The global test for changes of R2h&#95;s was non-significant (F global =1.46, p=0.095). Changes of R2h significantly correlated with improvement of headache frequency (R2h&#95;s, r=0.56, p=0.010; R2h&#95;ns: r=0.45, p=0.045). None of the nBR parameters assessed at baseline predicted treatment response., 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)., (© 2021. The Author(s).)

Background: Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAB) are the first specific migraine prophylactic medication. Erenumab is the only CGRP mAB targeting the CGRP receptor. Clinical data regarding efficacy and tolerability of erenumab in highly therapy-refractory patients are not available, yet, although many patients treated with CGRP mAB under real world conditions can be considered as highly therapy-refractory., Methods: Clinical routine data of highly therapy-refractory migraine patients treated with erenumab 70 mg for 3 months between November 2018 and December 2019 in the West German Headache Center, University Hospital Essen, Germany, were analysed. Monthly migraine days (MMD), monthly headache days (MHD) and days of acute medication intake (AMD) were assessed. Statistical analysis was performed using the Wilcoxon test. Descriptive statistics were performed to evaluate changes of vegetative symptoms, acute medication response, side effects, as well as treatment satisfaction., Results: Complete clinical data were available for 26 episodic (EM) and 74 chronic (CM) migraineurs. Sixty-six % (n = 49) of CM patients had an additional medication overuse headache (MOH). After 3 months 57.7% of EM patients and 41.9% of CM patients had a 50% or greater reduction of MMD. The mean number of MMD was reduced by 3.43 (SE 1.26) in EM, and by 4.72 (SE 0.87) in CM. Thirty-nine patients (52.7%) returned from chronic to episodic course of migraine. After 3 months, 23 patients (46.9%) were not suffering from a MOH anymore., Conclusions: Erenumab seems to be a promising therapeutic option in highly therapy-refractory migraine patients., Trial Registration: Retrospective registered.

Background: Neuroinflammation and maladaptive neuroplasticity play pivotal roles in migraine (MIG), trigeminal autonomic cephalalgias (TAC), and complex regional pain syndrome (CRPS). Notably, CRPS shares connections with calcitonin gene-related peptide (CGRP) in its pathophysiology. This study aims to assess if the documented links between CRPS and MIG/TAC in literature align with clinical phenotypes and disease progressions. This assessment may bolster the hypothesis of shared pathophysiological mechanisms. Methods: Patients with CRPS (n = 184) and an age-/gender-matched control group with trauma but without CRPS (n = 148) participated in this case–control study. Participant answered well-established questionnaires for the definition of CRPS symptoms, any headache complaints, headache entity, and clinical management. Results: Patients with CRPS were significantly more likely to suffer from migraine (OR: 3.23, 95% CI 1.82–5.85), TAC (OR: 8.07, 95% CI 1.33–154.79), or non-classified headaches (OR: 3.68, 95% CI 1.88–7.49) compared to the control group. Patients with MIG/TAC developed CRPS earlier in life (37.2 ± 11.1 vs 46.8 ± 13.5 years), had more often a central CRPS phenotype (60.6% vs. 37.0% overall) and were three times more likely to report allodynia compared to CRPS patients with other types of headaches. Additionally, these patients experienced higher pain levels and more severe CRPS, which intensified with an increasing number of headache days. Patients receiving monoclonal antibody treatment targeting the CGRP pathway for headaches reported positive effects on CRPS symptoms. Conclusion: This study identified clinically relevant associations of MIG/TAC and CRPS not explained by chance. Further longitudinal investigations exploring potentially mutual pathomechanisms may improve the clinical management of both CRPS and primary headache disorders. Trial registration: German Clinical Trials Register (DRKS00022961). [ABSTRACT FROM AUTHOR]

The article presents the case of a young female with mitochondrial encephalopathy, lactate acidosis, and stroke-like episodes (MELAS) syndrome with a stroke-like episode to discuss the efficacy of erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, as a treatment of migraine. Topics include the pathophysiology of mitochondrial vasculopathy and erenumab as treatment of highly refractory migrainous headache.