Background: The approval of monoclonal antibodies for prevention of migraine has revolutionized treatment for patients. Oral preventatives are still considered first line treatments as head-to-head trials comparing them with antibodies are lacking. Methods: The main purpose of this study was to provide a comparative overview of the efficacy of three commonly prescribed migraine preventative medication classes. For this systematic review and meta-analysis, we searched the databases CENTRAL, EMBASE, and MEDLINE until 20 March 2020. We included RCTs reporting the 50% response rates for topiramate, Botulinum Toxin Type A and monoclonal antibodies against CGRP(r). Studies were excluded if response rates were not reported, treatment allocation was unclear, or if study quality was insufficient. Primary outcome measure were the 50% response rates. The pooled odds ratios with 95% confidence intervals were calculated with the random effects model. The study was registered at PROSPERO (CRD42020222880). Findings: We identified 6552 reports. Thirty-two were eligible for our review. Studies assessing monoclonal antibodies included 13,302 patients and yielded pooled odds ratios for the 50% response rate of 2.30 (CI: 2.11–2.50). Topiramate had an overall effect estimate of 2.70 (CI: 1.97–3.69) with 1989 included patients and Botulinum Toxin Type A achieved 1.28 (CI: 0.98–1. 67) with 2472 patients included. Interpretation: Topiramate, botulinum toxin type A and monoclonal antibodies showed higher odds ratios in achieving a 50% response rate compared to placebo. Topiramate numerically demonstrated the greatest effect size but also the highest drop-out rate.

Background: Calcitonin gene-related peptide plasma levels have frequently been determined as a biomarker for primary headaches. However, published data is often inconsistent resulting from different methods that are not precisely described in most studies. Methods: We applied a well-proven enzyme-linked immunosorbent assay to measure calcitonin gene-related peptide concentrations in human blood plasma, we modified parameters of plasma preparation and protein purification and used calcitonin gene-related peptide-free plasma for standard solutions, which are described in detail. Results: Calcitonin gene-related peptide levels are stable in plasma with peptidase inhibitors and after deep-freezing. Calcitonin gene-related peptide standard solutions based on synthetic intercellular fluid or pooled plasma with pre-absorbed calcitonin gene-related peptide influenced the measurements but yielded both comprehensible results. In a sample of 56 healthy subjects the calcitonin gene-related peptide plasma levels varied considerably from low (500 pg/mL) values. After a 12-hour exposure of these subjects to normobaric hypoxia the individual calcitonin gene-related peptide levels remained stable. Conclusion: Buffering with peptidase inhibitors and immediate freezing or processing of plasma samples is essential to achieve reliable measurements. Individuals show considerable differences and partly high calcitonin gene-related peptide plasma levels without detectable pathological reason. Thus plasma measurements are suited particularly to follow calcitonin gene-related peptide levels in longitudinal studies. The use of data for this study was approved by the Ethics Committee of the Medical University of Innsbruck ( https://www.i-med.ac.at/ethikkommission/ ; EK Nr: 1242/2017).

Background: For future experimental studies or the development of targeted pharmaceutical agents, a deeper insight into the pathophysiology of migraine is of utmost interest. Reliable methods to trigger migraine attacks including aura are desirable to study this complex disease in vivo. Methods: To investigate hypoxia as a trigger for migraine and aura, we exposed volunteers diagnosed with migraine, with (n = 16) and without aura (n = 14), to hypoxia utilizing a hypoxic chamber adjusted to a FiO₂ of 12.6%. The occurrence of headache, migraine, aura, and accompanying symptoms were registered and vital signs were collected for 6 hours under hypoxia and 2 hours of follow-up. A binary logistic regression analysis examined the probability of triggering headaches, migraines, aura, photo- and phonophobia. Findings: Of 30 participants, 24 (80.0%) developed headaches and 19 (63.3%) migraine, five (16.7%) reported aura. Two patients that developed aura never experienced aura symptoms before in their life. The increase of mean heart frequency was higher in patients developing headaches or migraine. Mean SpO₂ during hypoxia was 83.39%. Conclusion: Hypoxia was able to trigger migraine attacks and aura independently of any pharmacological agent.

Calcitonin gene-related peptide (CGRP)-targeted therapies, including monoclonal antibodies (mAbs) and gepants, represent a major advancement in migraine prevention, offering greater efficacy and improved tolerability compared with traditional treatments. These agents selectively inhibit the CGRP pathway, a key mediator in migraine pathophysiology, and are increasingly used even as first-line options in selected patients. While clinical trials and real-world data suggest a favorable cardiovascular (CV) safety profile, particularly in patients without major risk factors, evidence remains limited for those with established vascular disease or recent vascular events. Concerns persist regarding long-term effects and the safety of CGRP blockade in high-risk populations. This narrative review focuses on the CV and cerebrovascular safety of CGRP-targeted migraine treatments-an area of growing clinical relevance. We compare these newer agents with traditional migraine preventives and highlight the paucity of data in patients with previous stroke, subarachnoid hemorrhage, myocardial infarction, or significant CV comorbidities. In addition, we discuss the emerging topic of dual CGRP pathway blockade (mAbs plus gepants), which has not previously been reviewed in the context of vascular risk. Based on currently available scientific evidence, we offer structured clinical considerations to guide the use of CGRP-targeted therapies in patients with vascular risk or cerebrovascular disease. Our aim is to support informed decision making in a population that has often been excluded from clinical trials but is becoming increasingly important in clinical practice.

Objective: Head/neck pain is one of the primary symptoms associated with spontaneous cervical artery dissection. Still, data on pain quality, intensity, and long-term dynamics are scarce. Methods: Spontaneous cervical artery dissection subjects were included if mural hematoma was visualised through T1 fat-saturated MRI at baseline. All available medical records were evaluated and patients were invited to standardised clinical follow-up visits at least 1 year after the index event. Results: In total, 279 subjects were included in the ReSect-study with head/neck pain being the most frequent symptom of spontaneous cervical artery dissection (220 of 273, 80.6%). Pain was of pulling nature in 107 of 218 (49.1%), and extended to the neck area in 145 of 218 (66.5%). In those with prior headache history, pain was novel in quality in 75.4% (42 of 55). Median patient-reported pain intensity was 5 out of 10 with thunderclap-type headache being uncommon (12 of 218, 5.5%). Prior to hospital admission, head/neck pain rarely responded to self-medication (32 of 218, 14.7%). Characteristics did not differ between subjects with and without cerebral ischemia. Pain resolved completely in all subjects within a median of 13.5 days (IQR 12). Upon follow-up in 42 of 164 (25.6%) novel recurring headache occurred, heterogeneous in quality, localisation and intensity. Conclusion: We present an in-depth analysis of spontaneous cervical artery dissection-related head/neck pain characteristics and its long-term dynamics.

To demonstrate the importance of calibration measurements in 3 Tesla proton magnetic resonance (MR) spectroscopy (¹H-MRS) thermometry for human brain temperature estimation for routine clinical applications. In vitro proton MR spectroscopy to obtain calibration constants of the water–chemical shift was conducted at 3 Tesla with a temperature-controlled phantom, containing a pH-buffered aqueous solution of N-acetyl aspartate (NAA), creatine (Cr), methylene protons of Cr (Cr2), dimethyl silapentane sulfonic acid (DSS), and sodium formate (NaFor). Estimations of absolute human brain temperature were performed utilizing the correlation of temperature to the water–chemical shift for the resonances of NAA, Cr, and Cr2. Data for calibration of the metabolites' chemical shift differences and in vivo temperature estimations were acquired with single-voxel point-resolved spectroscopy (PRESS) sequences (repetition time/echo time = 2000/30 ms; voxel size 2 × 2 × 2 cm³). Spectroscopy data were quantified in the time-domain, and a Pearson correlation analysis was performed to estimate the correlation between the chemical shift of metabolites and measured temperatures. The correlation coefficients (r) of our calibration measurements were NAA 0.9975 (±0.0609), Cr −0.9979 (±0.0621), Cr2 − 0.9973 (±0.0577), DSS −0.9976 (±0.0615), and NaFor −0.8132 (±2.348). The mean calculated brain temperature was 37.78 ± 1.447°C, and the mean tympanic temperature was 36.83 ± 0.2456°C. Calculated temperatures derived from Cr and Cr2 provided significant (p = 0.0241 and p = 0.0210, respectively) correlations with measured temperatures (r = 0.4108 and r = −0.4194, respectively). Calibration measurements are vital for ¹H-MRS thermometry. Small numeric differences in measured signal and data preprocessing without any calibration measurements reduce accuracy of temperature calculations, which indicates that calculated temperatures should be interpreted with caution. Application of this method for clinical purposes warrants further investigation and a more practical approach.