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Importance: Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden., Objective: To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments., Design, Setting, and Participants: The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021. This pragmatic trial was conducted at 84 centers across 17 countries. Overall, participants 18 years or older with a 12-month or longer history of migraine, and 4 or more but fewer than 15 monthly migraine days (MMDs) were included., Interventions: Patients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent)., Main Outcomes and Measures: The primary end point was the proportion of patients completing 1 year of the initially assigned treatment and achieving a reduction of 50% or greater from baseline in MMDs at month 12. Secondary end points included the cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders according to the Patients' Global Impression of Change (PGIC) scale at month 12 for patients taking the initially assigned treatment., Results: A total of 866 patients were screened, of whom 245 failed the screening and 621 completed the screening and baseline period. Of the 621 randomized patients (mean [SD] age, 41.3 [11.2] years; 545 female [87.8%]; 413 [66.5%] in the erenumab group; 208 [33.5%] in the OMPM group), 523 (84.2%) completed the treatment phase, and 98 (15.8%) discontinued the study. At month 12, significantly more patients assigned to erenumab vs OMPM achieved the primary end point (232 of 413 [56.2%] vs 35 of 208 [16.8%]; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). Compared with OMPMs, treatment with erenumab showed higher responder rate (314 of 413 [76.0%] vs 39 of 208 [18.8%]; OR, 13.75; 95% CI, 9.08-20.83; P <.001) on the PGIC scale (≥5 at month 12). Significant reduction in cumulative average MMDs was reported with erenumab treatment vs OMPM treatment (-4.32 vs -2.65; treatment difference [SE]: -1.67 [0.35] days; P < .001). Substantially fewer patients in the erenumab arm compared with the OMPM arm switched medication (9 of 413 [2.2%] vs 72 of 208 [34.6%]) and discontinued treatment due to adverse events (12 of 408 [2.9%] vs 48 of 206 [23.3%]). No new safety signals were identified., Conclusions and Relevance: Results of this randomized clinical trial demonstrated that earlier use of erenumab in patients with EM who failed 1 or 2 previous preventive treatments provided greater and sustained efficacy, safety, and adherence than continuous OMPM., Trial Registration: ClinicalTrials.gov Identifier: NCT03927144.

Background: Erenumab, the first-in-class fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor, was shown to be efficacious and safe for the prophylactic treatment of migraine in adults in randomized clinical trials. Large-scale, real-world evidence in multi-centre settings is still needed to confirm these results. Erenumab patient profiles outside clinical trials and physicians' treatment patterns, as well as data from patients treated in Germany, a severely impacted population, are not published yet., Methods: TELESCOPE was a multi-centre survey gathering real-world data from 45 German headache centres between July 2019 and December 2019. The project consisted of two parts. In the first part, treating physicians shared their experiences on current erenumab treatment with regard to patient profiles, treatment patterns and treatment responses. In the second part, a retrospective chart review was conducted of 542 migraine patients treated with erenumab for at least three months. Treatment responses focused on various aspects of patients' quality of life., Results: The analysis of 542 patients' charts revealed that three-month treatment with erenumab significantly reduced monthly headaches, migraine and acute medication days. Furthermore, headache intensity and frequency were reduced in over 75 % and accompanying aura in 35 % of patients. The clinical global impression scale revealed a general improvement in 91 % of patients. According to the treating physicians' professional judgement, 83 % of patients responded to erenumab and 80 % were satisfied with the treatment. Physicians evaluated restricted quality of life, the number of monthly migraine days and previous, prophylactic treatments as the main components of the current patient profile for monoclonal antibody recipients. Based on the assessment of physicians, erenumab reduced migraine symptoms in 65 % and increased quality of life in more than 75 % of their patients., Conclusions: TELESCOPE confirms positive treatment responses with erenumab shown in clinical trials in a real-world multi-centre setting. The results show consistently positive experiences of physicians utilizing erenumab in clinical practice and underline that therapy with this monoclonal antibody is effective in migraine patients, particular in those, who have failed several prophylactic therapies., (© 2021. The Author(s).)

Background: Chronic migraine (CM) is a primary headache type associated with a severe reduction in the quality of life. The association of sensorimotor dysfunction in the neck, measured with the joint position error test (JPE), and CM is largely unknown, even though up to 60% of migraine patients report neck pain accompanying the migraine., Methods: This manuscript reports a systematic review of the literature on JPE in patients with headache as well as data on an observational study. To determine the JPE of migraine patients, 37 subjects with CM were tested and compared with a control group (CG; n = 22). In an additional analysis, CM patients were divided into two subgroups based on the medical treatment approach. The measurements were taken in the three movement dimensions with five repetitions in each direction using a laser pointer fixed to the head., Results: The mean JPE in the sagittal plane was 3.7° (SD ± 1.4°) and 3.1° (SD ± 1.1°) for CM (n = 37) and CG, respectively. In the transverse plane it was measured as 3.7° (SD ± 1.5°) for CM and 3.2° (SD ± 1°) for the CG, while it was 3.6° (SD ± 1.2°; CM) and 3.3° (SD ± 1.1°; CG) in the frontal plane. The between group difference was not significant for all movement planes. When groups according to the treatment regimen, both groups showed similar migraine and neck pain features but the JPE was significantly larger in the CM + BTh group compared to the CM without BTh group and the CG. In the sagittal plane, the JPE was 4.21° (SD ± 1.8°) for the CM + BTh compared to 2.99° (SD ± 1.2°) in CM without BTh and 3.21° (SD ± 1.2°) in the CG (p = 0.0053). The difference between CM + BTh and CM without BTh was 1.52° (p = 0.016) after propensity score matching in the sagittal plane., Conclusions: Only patients in the CM + BTh group showed a statistically increased JPE. The influence of neck pain does not explain the between group difference. A possible factor is the degree of chronification. This study indicates that the JPE might discriminate a subgroup of migraine patients.

Background: Increased cortical excitability has been hypothesized to play a critical role in various neurological disorders, such as restless legs syndrome, epilepsy and migraine. Particularly for migraine, local hyperexcitability has been reported. Levels of regional excitatory and inhibitory neurotransmitters are related to cortical excitability and hence may play a role in the origin of the disease. Consequently, a mismatch of the excitatory-inhibitory neurotransmitter network might contribute to local hyperexcitability and the onset of migraine attacks. In this study we sought to assess local levels of glutamate / glutamine (GLX) and gamma-aminobutyric acid (GABA) in the occipital cortex and right thalamus of migraineurs and healthy subjects., Methods: We measured interictally local biochemical concentrations in the occipital lobe and the right thalamus in patients with migraine (without aura) and healthy controls (HCs) using proton magnetic resonance spectroscopy at 3 T. GLX levels were acquired using PRESS and GABA levels using the GABA-sensitive editing sequence MEGA-PRESS. Regional GLX and GABA levels were compared between groups., Results: Statistical analyses revealed significantly increased GLX levels in both the primary occipital cortex and thalamus. However, we found no group differences in GABA levels for these two regions. Correlation analyses within the migraine group revealed no significant correlations between pain intensity and levels of GLX or GABA in either of the two brain regions., Conclusions: Further research is needed to investigate the role of GABA/GLX ratios in greater depth and to measure changes in neurotransmitter levels over time, i.e. during migraine attacks and interictally.

The objective of this study is to assess effects of beta-blocker migraine prophylaxis on cortical excitability determined by transcranial magnetic stimulation (TMS). Phosphene and motor thresholds (PT, MT) were investigated in 29 patients with migraine, in 15 of them prior to and following preventive medication with metoprolol and in 14 patients without prophylaxis. Following prophylaxis headache frequency significantly decreased (p = 0.005) and mean PT were significantly increased (51.5 ± 7.5 vs. 63.6 ± 8.4%) compared to patients without preventive treatment (53.7 ± 5.3 vs. 52.3 ± 6.3%; p = 0.040). Mean MT did not significantly differ either between groups or due to treatment. In the group of all patients, a significant inverse correlation between headache frequency and the level of PT was found (R = -0.629; p < 0.01). There was, however, no significant correlation in the subgroups of patients. We conclude that (a) clinical efficacy of beta-blocker treatment in migraine could be (at least partly) linked to its ability to modulate the excitability of the visual cortex and (b) the PT determined by TMS appears suitable to assess the effects of prophylaxis on cortical excitability in the individual patient. This may be useful in clinical trials investigating migraine preventive drugs.

Objective: To determine the excitability of the visual cortex by phosphene thresholds (PT) in patients with migraine using transcranial magnetic stimulation (TMS) with single- and paired-pulses., Methods: Nineteen patients with migraine with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control subjects were included. Patients were free from preventive anti-migraine treatment and were investigated within 3 days before or after an acute migraine attack. In each subject, PT were assessed by single-pulse and paired-pulse TMS with an interstimulus interval of 50 ms., Results: The main effect of diagnosis indicated that mean PT were significantly lower in migraine patients than in control subjects (P = .001). Using single-pulse TMS, mean PT tended to be lower in MWoA-patients (57.7 +/- 11.8%) compared with control subjects (64.4 +/- 10.5%) (P = .064). In MWA-patients, mean PT (53.1 +/- 5.7%) were significantly lower compared with controls (P < .001). Using TMS with paired pulses, mean PT were significantly reduced in MWoA-patients (40.3 +/- 4.9%, P = .017) as well as in MWA-patients (39.6 +/- 4.2%, P = .005) compared with controls (44.6 +/- 6.0%). The main effect of stimulation type indicated that mean PT were lower determined with paired-pulse stimulation than with single pulses (P < .001)., Conclusions: PT are reduced in patients with migraine in the interictal state suggesting an increased excitability of visual cortical areas. Compared with single-pulse TMS, paired-pulse magnetic stimulation is more efficient to elicit phosphenes. This technique provides the opportunity to evaluate visual cortex excitability with lower stimulus intensities and less discomfort.

Objective: The study compared efficacy and tolerability of intravenous valproate (iVPA) with intravenous lysine-acetylsalicylic acid (iLAS) in acute migraine attacks. Background.-iLAS has been proven to be a highly effective treatment in acute migraine attacks, but it is not available in many countries and contraindicated in patients with asthma or peptic ulcers. Current data suggest that iVPA may be effective in the treatment of acute migraine attacks., Design/methods: In this randomized, double-blind, parallel-group phase-II study, 40 patients with acute migraine attacks (onset <5 hours, severe or moderate headache on a four-point IHS scale) alternately received iVPA 800 mg or iLAS 1000 mg. Primary outcome criteria were the percentage of patients reporting pain relief after 1 hour and patients who remained sustained pain free for 24 hours following drug administration. Secondary outcome criteria were relief of pain and associated migrainous symptoms (nausea, photophobia, and phonophobia) at 1, 2, 24, and 48 hours following drug administration., Results: There were no significant differences in demographic and clinical features between both treatment groups. Percentage of pain relief after 1 hour in the iVPA and iLAS groups were 25% and 30%, respectively, and of sustained pain free for 24 hours were 20% and 30%, respectively, without significant differences (P = 1 and P= .72, respectively). Both drugs improved associated migrainous symptoms without significant differences at the different time points, but again with a trend in favor of iLAS. No adverse events were observed., Conclusion: Both drugs were effective in acute migraine attacks with a trend in favor of iLAS. As both drugs were well tolerated, further studies with higher doses of iVPA for the treatment of acute migraine attacks are recommended.