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Background: Migraine is a multiphasic neurovascular disorder, where headache can be succeeded by postdromal symptoms. However, there are limited research on postdromal symptoms. This study aimed to investigate the proportion of individuals with migraine from a tertiary care unit reporting postdromal symptoms in adherence with the ICHD-3 definition. We also aimed to examine how the means of enquiry might influence the estimated proportions. Additionally, we explored whether any clinical features might affect the likelihood of reporting postdromal symptoms. Finally, we assessed to what extend the postdromal symptoms might impact the disease burden. Methods: In a cross-sectional study, we enrolled adult participants diagnosed with migraine who were asked to report their postdromal symptoms (i.e., unprompted reporting). Subsequently, a 16-item list was used to further ascertain the occurrence of postdromal symptoms (i.e., prompted reporting). Clinical characteristics were obtained through a semi-structured interview. Moreover, electronic questionnaires were used to assess the disease burden, i.e., the Six-Item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and the World Health Organization Disability Assessment 2.0 (WHODAS 2.0). Results: Among 631 participants with migraine, a higher proportion experienced at least one postdromal symptom when prompted (n = 509 [80.7%]) compared with unprompted reporting (n = 421 [66.7%], P < 0.001). Furthermore, the total number of postdromal symptoms experienced was greater with prompted than unprompted reporting (medians 3 [IQR 1 – 6] versus 1 [IQR 0 – 2]; P < 0.001). Furthermore, the likelihood of reporting postdromal symptoms increased with the presence of premonitory symptoms and decreased with higher number of monthly migraine days. Weak correlations were identified between the number of postdromal symptoms reported and both HIT-6 (ρ = 0.14; P < 0.001) and WHODAS scores (ρ = 0.15; P < 0.001), whilst no correlation was observed with MIDAS score (ρ = 0.08; P = 0.054). Conclusions: Postdromal symptoms are prevalent in individuals with migraine from a tertiary care unit. However, reported estimates warrant cautious interpretation as they depend on the means of enquiry, presence of premonitory symptoms, and frequency of monthly migraine days. Moreover, a weak correlation was identified between the number of postdromal symptoms and both HIT-6 and WHODAS scores, indicating only a marginal influence on the disease burden. [ABSTRACT FROM AUTHOR]

Background: Erenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion of patients do not respond to it. The Registry for Migraine study (REFORM) was initiated to discover biomarkers that can predict response to erenumab in patients with migraine. The specific objective was to investigate differences in erenumab efficacy based on clinical information, blood-based biomarkers, structural and functional magnetic resonance imaging (MRI), and response to intravenous infusion of calcitonin gene-related peptide (CGRP). In this first report of the REFORM study, we provide a comprehensive description of the study methodology, and present the baseline characteristics of the study population. Methods: The REFORM study was a single-center, prospective, longitudinal cohort study in adults with migraine who were scheduled to receive preventive treatment with erenumab as part of a separate, open-label, single-arm phase IV trial. The study included four periods: a 2-week screening period (Weeks -6 to -5), 4-week baseline period (Week -4 to Day 1), 24-week treatment period (Day 1 to Week 24), and a 24-week follow-up period without treatment (Week 25 to Week 48). Demographic and clinical characteristics were recorded using a semi-structured interview, whilst outcome data were obtained using a headache diary, patient-reported outcomes, blood sampling, brain MRI, and responsiveness to intravenous infusion of CGRP. Results: The study enrolled 751 participants, with a mean age ± SD of 43.8 ± 12.2 years, of which 88.8% (n = 667) were female. At enrollment, 64.7% (n = 486) were diagnosed with chronic migraine, and 30.2% (n = 227) had history of aura. The mean monthly migraine days (MMDs) was 14.5 ± 7.0. Concomitant preventive medications were used by 48.5% (n = 364) of the participants, and 39.9% (n = 300) had failed ≥ 4 preventive medications. Conclusion: The REFORM study enrolled a population with a high migraine burden and frequent use of concomitant medications. The baseline characteristics were representative of patients with migraine in specialized headache clinics. Future publications will report the results of the investigations presented in this article. Trial registration: The study and sub-studies were registered on ClinicalTrials.gov (NCT04592952; NCT04603976; and NCT04674020). [ABSTRACT FROM AUTHOR]

Abstract: Migraine is a common disabling disease with a complex pathophysiology. Headache is a frequent side effect after intravenous adenosine administration, although adenosine receptor antagonist, caffeine, relieves migraine headache. These observations suggest a possible involvement of adenosine signaling in headache and migraine pathophysiology. In a randomized, double-blinded, placebo-controlled, crossover study, 18 participants diagnosed with migraine without aura received 120 µg/kg per minute adenosine or placebo over 20 minutes. Headache intensity, migraine-associated symptoms, vital signs, the diameter of the superficial temporal artery (STA), blood flow velocity in the middle cerebral artery (V MCA ), and facial skin blood flow were measured at baseline and every 10 minutes until 2 hours after infusion start. The primary end point was the difference in the incidence of migraine attacks after adenosine infusion compared with placebo. Eighteen participants completed the study. We found no difference in the incidence of migraine after adenosine infusion (7 of 18, 39%) compared with placebo (3 of 18, 17%) ( P = 0.29). Fourteen participants reported headache after adenosine infusion (14 of 18, 78%) compared with placebo (6 of 18, 33%) ( P < 0.01). Adenosine increased heart rate ( P < 0.001), facial skin blood flow ( P < 0.05), and STA diameter (AUC T0-20min , P = 0.01) and decreased V MCA (AUC T0-20min , P < 0.001) compared with placebo. Adenosine induced headache accompanied by a short-lasting (<30 minutes) dilation of intracerebral and extracerebral arteries. The nonsignificant migraine induction might be because of the presence of several adenosine receptors with counteracting signaling, highlighting the need of more selective modulators to dissect the implication of adenosine in migraine. [ABSTRACT FROM AUTHOR]

Background: Cytokines are important endogenous substances that are involved in immune and inflammatory responses. Neurogenic inflammation has been proposed to play a role in migraine involving altered cytokine levels. Therefore, we aimed to provide a systematic review on the current knowledge on cytokine levels in migraine patients during and outside attacks.Methods: Databases of PubMed and Embase were systematically searched for studies investigating cytokine levels in migraine patients during and outside attacks.Results: Screening yielded identification of 45 articles investigating 18 cytokines in total. We found that the interictal level of the anti-inflammatory cytokine, interleukin 10, was decreased, while the level of transforming growth factor beta 1 was increased in migraine patients compared to controls. Levels of pro-inflammatory cytokines, tumor necrosis factor α and interleukin 6, were increased outside attacks compared to controls. Ictal levels of cytokines were unchanged or varying compared to the interictal state in migraine patients. Three studies reported dynamic cytokines levels during the course of an attack.Conclusion: The findings of the current review underline a possible involvement of cytokines in the proposed inflammatory mechanisms of migraine. However, future studies are needed to expand our knowledge of the exact role of cytokines in the migraine pathophysiology with focus on cytokines TNF-α, IL-1ß, IL-6 and IL-10 while applying refined methodology. [ABSTRACT FROM AUTHOR]

Objective: To systematically review clinical studies investigating the involvement of adenosine and its receptors in migraine pathophysiology. Background: Adenosine is a purinergic signaling molecule, clinically used in cardiac imaging during stress tests. Headache is a frequent adverse event after intravenous adenosine administration. Migraine headache relief is reported after intake of adenosine receptor antagonist, caffeine. These findings suggest a possible involvement of adenosine signaling in migraine pathophysiology and its potential as a drug target. Methods: A search through PubMed and EMBASE was undertaken for clinical studies investigating the role of adenosine and its receptors in migraine, published until September 2021. Results: A total of 2510 studies were screened by title and abstract. Of these, seven clinical studies were included. The main findings were that adenosine infusion induced headache, and plasma adenosine levels were elevated during ictal compared to interictal periods in migraine patients. Conclusion: The present systematic review emphasizes a potentially important role of adenosine signaling in migraine pathogenesis. Further randomized and placebo-controlled clinical investigations applying adenosine receptors modulators in migraine patients are needed to further understand the adenosine involvement in migraine. [ABSTRACT FROM AUTHOR]

Background: Adenosine is a purinergic signaling molecule with a wide range of physiological functions including anti- and pronociceptive properties. Adenosine receptors are expressed in the trigeminovascular system, and adenosine receptor antagonist, caffeine, relieves migraine headache. We performed a systematic review of the literature of preclinical data addressing the role of adenosine in migraine pathophysiology. Methods: PubMed and EMBASE were searched for pre-clinical studies on the role of adenosine in migraine pathophysiology on September 5th, 2021. Results: A total of 2510 studies were screened by title and abstract. Of these, thirteen pre-clinical studies evaluating adenosine, adenosine A1, A2A and A3 receptors were included. These studies showed that adenosine signaling pathway is involved in controlling vascular tone. Furthermore, electrical stimulation of the trigeminal ganglion modulates the expression of adenosine A1 and A2A receptors in the trigeminal ganglion and trigeminal nucleus caudalis implicating adenosine signaling pathway in pain transmission. Conclusion: Preclinical studies showed that adenosine has a dual effect on vasodilation and trigeminal pain pathway due to different receptor activation, suggesting a possible role of adenosine in migraine pathophysiology. Studies investigating pharmacological characteristics of subtypes of adenosine receptors are needed to further elucidate their role as a potential target for migraine treatment. [ABSTRACT FROM AUTHOR]