What proportion of people with migraine report postdromal symptoms? A systematic review and meta-analysis of observational studies.

BACKGROUND: Postdromal symptoms, following headache resolution, are said to constitute a distinct phase of the migraine attack. We question the evidence for this, with regard both to the nature of such symptoms and to how often they are reported to occur. METHODS: We searched the Pubmed and Embase databases for relevant articles from their inception until 25 May 2023. We included observational studies recording the proportions of participants with migraine reporting one or more postdromal symptoms or specific individual symptoms. Two reviewers independently screened studies for relevance (agreeing on those to be included), extracted data and assessed risk of bias. Data were analyzed using random-effects meta-analysis to establish the proportions of those with migraine reporting one or more postdromal symptoms, whether among the general population or patients in clinic-based samples. RESULTS: Large majorities of participants in either case reported postdromal symptoms: 97% in the only population-based study, and a mean of 86% (95% CI: 71-94%) in four clinic-based studies. The most commonly reported specific symptoms were fatigue (52%; 95% CI: 44-60%), concentration difficulties (35%; 95% CI: 14-65%) and mood changes (29%; 95% CI: 9-64%), none of these being clearly described. These estimates could not be considered reliable: they were subject to substantial study heterogeneity, none of the studies applied International Classification of Headache Disorders definitions of postdromal symptoms, and all had high risk of bias. CONCLUSION: Postdromal symptoms in migraine appear to be very commonly reported, but the data are unreliable with regard both to their nature and to how often they occur. Further studies are needed to conclude that they constitute a distinct phase of migraine.

White matter hyperintensities and cerebral microbleeds in persistent post-traumatic headache attributed to mild traumatic brain injury: a magnetic resonance imaging study.

OBJECTIVE: To examine whether white matter hyperintensities (WMHs) and cerebral microbleeds (CMBs) are more prevalent in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI), compared with healthy controls. METHODS: A magnetic resonance imaging (MRI) study of adults with persistent post-traumatic headache attributed to mild TBI and age- and gender-matched healthy controls. A semi-structured interview and validated self-report instruments were used to record data on demographics, clinical characteristics, and comorbidities. Imaging data were obtained on a 3T MRI Scanner using a 32-channel head coil. Participants and controls underwent a single MRI session, in which fluid-attenuated inversion recovery was used to visualize WMHs, and susceptibility-weighted imaging was used to detect CMBs. The primary outcomes were (I) the difference in the mean number of WMHs between participants with persistent post-traumatic headache and healthy controls and (II) the difference in the mean number of CMBs between participants with persistent post-traumatic headache and healthy controls. All images were examined by a certified neuroradiologist who was blinded to the group status of the participants and controls. RESULTS: A total of 97 participants with persistent post-traumatic headache and 96 age- and gender-matched healthy controls provided imaging data eligible for analyses. Among 97 participants with persistent post-traumatic headache, 43 (44.3%) participants presented with ≥ 1 WMH, and 3 (3.1%) participants presented with ≥ 1 CMB. Compared with controls, no differences were found in the mean number of WMHs (2.7 vs. 2.1, P = 0.58) and the mean number of CMBs (0.03 vs. 0.04, P = 0.98). CONCLUSIONS: WMHs and CMBs were not more prevalent in people with persistent post-traumatic headache than observed in healthy controls. Future studies should focus on other MRI techniques to identify radiologic biomarkers of post-traumatic headache.

Premonitory symptoms in migraine: a systematic review and meta-analysis of observational studies reporting prevalence or relative frequency.

BACKGROUND: Observational studies on the prevalence of premonitory symptoms in people with migraine, preceding the headache pain (or aura) phase, have shown conflicting results. We conducted a systematic review and meta-analysis to estimate the prevalence, and relative frequency among clinic populations, of premonitory symptoms in people with migraine, overall and of the multifarious individual symptoms, and to review the methodologies used to assess them. METHODS: We searched PubMed and Embase for studies published from database inception until 31st of May 2022. Two investigators independently screened titles, abstracts, and full texts. We retrieved observational studies that reported the prevalence/relative frequency of one or more premonitory symptoms in people with migraine. Two investigators independently extracted data and assessed risk of bias. Results were pooled using random-effects meta-analysis. Our main outcomes were the percentage of people with migraine who experienced at least one premonitory symptom and the percentages who experienced different individual premonitory symptoms. To describe our outcomes, we used the terms prevalence for data from population-based samples and relative frequency for data from clinic-based samples. We also descriptively and critically assessed the methodologies used to assess these symptoms. RESULTS: The pooled estimated prevalence in population-based studies of at least one premonitory symptom was 29% (95% CI: 8-63; I2 99%) and the corresponding pooled estimated relative frequency in clinic-based studies was 66% (95% CI: 45-82; I2 99%). The data from clinic-based studies only supported meta-analysis of 11 of 96 individual symptoms, with relative frequency estimates ranging from 11 to 49%. Risk of bias was determined as high in 20 studies, moderate in seven, and low in two. CONCLUSIONS: The substantial between-study heterogeneity demands cautious interpretation of our estimates. Studies showed wide methodological variations, and many lacked rigor. Overall, the evidence was insufficient to support reliable prevalence estimation or characterization of premonitory symptoms. More data are needed, of better quality, to confirm the existence of a distinctive premonitory phase of migraine, and its features. Methodological guidelines based on expert consensus are a prerequisite.

CGRP-induced migraine-like headache in persistent post-traumatic headache attributed to mild traumatic brain injury.

OBJECTIVE: To ascertain whether intravenous infusion of calcitonin gene-related peptide (CGRP) can induce migraine-like headache in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI) and no pre-existing migraine. METHODS: A non-randomized, single-arm, open-label study at a single site in Denmark. Eligible participants were aged 18 to 65 years and had a known history of persistent post-traumatic headache attributed to mild TBI for ≥ 12 months. All participants received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min. A headache diary was used to collect outcome data until 12 h after the start of CGRP infusion. The primary end point was the incidence of migraine-like headache during 12-hour observational period. RESULTS: A total of 60 participants completed the study protocol and provided data for the analysis of the primary end point. The median age was 32.5 (IQR, 25.5-43.0) years; 43 participants (72%) were female. Following CGRP infusion, 43 (72%) of 60 participants developed migraine-like headache during the 12-hour observational period. The median time to peak headache intensity was 40 min (IQR, 20-60), and the median peak headache intensity was 6 (IQR, 5-8) on the 11-point numeric rating scale. CONCLUSION: Intravenous infusion of CGRP is a potent inducer of migraine-like headache in people with persistent post-traumatic headache attributed to mild TBI. This observation underscores the importance of CGRP in the genesis of migraine-like headache that is often experienced by individuals who are afflicted by persistent post-traumatic headache. Further research is warranted to ascertain whether other signaling molecules also contribute to the disease mechanisms underlying post-traumatic headache.

Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms.

Intracranial aneurysms are pouch-like extrusions from the vessels at the base of the brain which can rupture and cause a subarachnoid hemorrhage. The pathophysiological mechanism of aneurysm formation is thought to be a consequence of blood flow (hemodynamic) induced changes on the endothelium. In this study, the results of a personalized aneurysm-on-a-chip model using patient-specific flow parameters and patient-specific cells are presented. CT imaging was used to calculate CFD parameters using an immersed boundary method. A microfluidic device either cultured with human umbilical vein endothelial cells (HUVECs) or human induced pluripotent stem cell-derived endothelial cells (hiPSC-EC) was used. Both types of endothelial cells were exposed for 24 h to either 0.03 Pa or 1.5 Pa shear stress, corresponding to regions of low shear and high shear in the computational aneurysm model, respectively. As a control, both cell types were also cultured under static conditions for 24 h as a control. Both HUVEC and hiPSC-EC cultures presented as confluent monolayers with no particular cell alignment in static or low shear conditions. Under high shear conditions HUVEC elongated and aligned in the direction of the flow. HiPSC-EC exhibited reduced cell numbers, monolayer gap formation and cells with aberrant, spread-out morphology. Future research should focus on hiPSC-EC stabilization to allow personalized intracranial aneurysm models.

Diagnosis and management of migraine in ten steps.

Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up.

Post-traumatic headache attributed to traumatic brain injury: classification, clinical characteristics, and treatment.

Post-traumatic headache is a common sequela of traumatic brain injury and is classified as a secondary headache disorder. In the past 10 years, considerable progress has been made to better understand the clinical features of this disorder, generating momentum to identify effective therapies. Post-traumatic headache is increasingly being recognised as a heterogeneous headache disorder, with patients often classified into subphenotypes that might be more responsive to specific therapies. Such considerations are not accounted for in three iterations of diagnostic criteria published by the International Headache Society. The scarcity of evidence-based approaches has left clinicians to choose therapies on the basis of the primary headache phenotype (eg, migraine and tension-type headache) and that are most compatible with the clinical picture. A concerted effort is needed to address these shortcomings and should include large prospective cohort studies as well as randomised controlled trials. This approach, in turn, will result in better disease characterisation and availability of evidence-based treatment options.

Efficacy, tolerability, and safety of erenumab for the preventive treatment of persistent post-traumatic headache attributed to mild traumatic brain injury: an open-label study.

BACKGROUND: Calcitonin gene-related peptide (CGRP) has recently been implicated in the pathogenesis of post-traumatic headache (PTH), which raises the prospect for therapeutic use of monoclonal antibodies targeting CGRP or its receptor. Therefore, we decided to assess the efficacy, tolerability, and safety of erenumab for prevention of persistent PTH attributed to mild traumatic brain injury. METHODS: A single-center, non-randomized, single-arm, open-label study of erenumab for adults aged 18-65 years with persistent PTH. Patients were assigned to receive 140-mg erenumab monthly by two subcutaneous 1-mL injections, given every 4 weeks for 12 weeks. The primary outcome measure was the mean change in number of monthly headache days of moderate to severe intensity from baseline (4-week pretreatment period) to week 9 through 12. Tolerability and safety endpoints were adverse events (i.e. number and type). RESULTS: Eighty-nine of 100 patients completed the open-label trial. At baseline, the mean monthly number of headache days of moderate to severe intensity was 15.7. By week 9 through 12, the number was reduced by 2.8 days. The most common adverse events were constipation (n = 30) and injection-site reactions (n = 15). Of 100 patients who received at least one dose of erenumab, two patients discontinued the treatment regimen due to adverse events. CONCLUSIONS: Among patients with persistent PTH, erenumab resulted in a lower frequency of moderate to severe headache days in this 12-week open-label trial. In addition, erenumab was well-tolerated as discontinuations due to adverse events were low. Placebo-controlled randomized clinical trials are needed to adequately evaluate the efficacy and safety of erenumab in patients with persistent PTH. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT03974360. Registered on April 17, 2019 - Retrospectively registered.