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Pain freedom after 2 hours should be the primary outcome in controlled trials treating migraine attacks.

Pain freedom after 2 hours is the recommended primary endpoint by the International Headache Society in randomized trials investigating drug treatment of acute migraine attacks. In order to demonstrate an early effect of a drug, some drug companies, however, have promoted headache relief (improvement from severe or moderate pain to mild or no pain) at earlier time points than 2 hours as outcome parameter.

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Types of Triggers in Migraine – Factor Structure of the Headache Triggers Sensitivity and Avoidance Questionnaire and Development of a New Short Form (HTSAQ-SF).

To examine the factor structure of the Headache Triggers Sensitivity and Avoidance Questionnaire (HTSAQ) and its German version (HTSAQ-G), in order to identify potential different types of triggers. Furthermore, a short form of the questionnaire was developed.

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Moving the Needle, the Clinical Perspective.

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Is there a reliable brain morphological signature for migraine?

Voxel-based morphometry (VBM) is a popular non-invasive magnetic resonance imaging technique to investigate brain gray matter (GM) differences between groups. Recently, two VBM studies in migraine have been published in The Journal of Headache and Pain. Reviewing the two and those previous published VBM studies, we found considerable variations of the results. Spatially diverse brain regions with decreased and increased GM alterations and null findings have been reported. It is interesting to know whether there is a reliable brain morphological signature for migraine. Coordinate-based meta-analysis (CBMA) is increasingly used to quantitatively pool individual neuroimaging studies to identify consistent and reliable findings. Several CBMA have been conducted, however, their results were inconsistent. The algorithms for CBMA have evolved and more eligible VBM studies in migraine have been published. We therefore conducted an updated CBMA using the latest algorithms for CBMA, seed-based d mapping with permutation of subject images (SDM-PSI). The present CBMA of 32 VBM studies (41 datasets comprising 1252 patients and 1025 healthy controls) found no evidence of consistent GM alterations in migraine. Sensitivity analysis, subgroup meta-analyses, and meta-regression analyses revealed that the result was robust. This negative result indicates that there is no reliable brain morphological signature for migraine. VBM investigations in migraine remain a heterogeneous field. Many potential confounding factors, such as underpowered sample sizes, variations in demographic and clinical characteristics, and differences in MRI scanners, head coils, scanning parameters, preprocessing procedures, and statistical strategies may cause the inconsistences of the results. Future VBM studies are warranted to enroll well-characterized and homogeneous subtype samples with appropriate sample sizes, comprehensively assess comorbidities and medication status, and use well-validated and standardized imaging protocols and processing and analysis pipelines to produce robust and replicable results in migraine.

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Visual snow syndrome: is it normal or a disorder – and what to do with patients?

Recently in the journal, epidemiological data are presented on visual snow syndrome (VSS) using a crowdsourcing online platform [1]. The authors applied criteria for VSS to a sample of people matched for age, sex, and ethnicity to United Kingdom census data. Further, they assessed frequent headache lasting longer than 4 hours, which was interpreted as migraine, and neurological symptoms during headache, interpreted as aura.

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Cortical spreading depolarisation-induced facial hyperalgesia, photophobia and hypomotility are ameliorated by sumatriptan and olcegepant.

Cortical spreading depolarisation (CSD), the neural mechanism underlying migraine aura, may cause headache by sensitising the trigeminal system. Photophobia, the most bothersome accompanying symptom during migraine attacks, is more prevalent in migraine with aura than in migraine without aura. Whether CSD plays a role in developing photophobia remains unknown. Moreover, migraine-induced physical hypoactivity contributes to loss of productivity. We aimed to investigate the development of trigeminal sensitisation, photophobia and locomotive abnormality after KCl-induced CSD using 86 male C57BL/6 mice. Sham-operated mice were used as controls. We confirmed the presence of trigeminal sensitisation and photophobia at 24 h after CSD. CSD-subjected mice also exhibited significantly reduced locomotive activity in both light and dark zones. Hence, the CSD-induced hypomobility was likely to be independent of photophobia. The 5-HT agonist, sumatriptan, corrected all these CSD-induced abnormalities. Moreover, dose dependency was demonstrated in the ameliorating effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, olcegepant, on these abnormalities. Sumatriptan and olcegepant improved mouse locomotion with therapeutic lags ranging from 20 to 30 min. Collectively, CSD caused trigeminal sensitisation, photophobia and hypomobility that persisted for at least 24 h by a mechanism involving the 5-HT and CGRP activity.

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Triggers of Primary Headaches: Issues and Pathways Forward.

The triggers of primary headaches have considerable significance for our understanding and management of headache and migraine. Triggers explain the variance in headaches – why they occur when they do. Trigger management is generally viewed as an important component of a comprehensive treatment approach for headaches. Historically, however, triggers have not had a prominent place in the headache literature. This situation began to change 20 to 30 years ago, and the pace of change has increased exponentially in recent times. Nevertheless, the field is beset with issues that have held it back from achieving more. This review will focus on elaborating those issues with the goal of suggesting ways forward. The first issue considered will be the definition of a trigger, and how specific triggers are labeled. Consideration will then be given to a classification system for triggers. The review will discuss next the evidence relating to whether self-reported triggers can, indeed, precipitate headaches, and how the capacity to elicit headaches may be acquired or extinguished. Attention will be given to the very important clinical issue of trigger management. Finally, the pathways forward will be proposed. Perhaps the most useful thing to accomplish at this point in time would be agreement on a definition of headache triggers, a list of triggers, and a classification system for triggers. This would greatly assist in comparing research on triggers from different research groups as well as eliminating some of the issues identified in this review. An authoritative body such as the American Headache Society or the International Headache Society, could establish a multidisciplinary committee that would complete these tasks. Consideration should also be given to incorporating triggers into the International Classification of Headache Disorders as an axis or via the use of codes, as this would raise the profile of triggers in assessment and management.

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Triptan efficacy does not predict onabotulinumtoxinA efficacy but improves with onabotulinumtoxinA response in chronic migraine patients.

Chronic migraine (CM) is a highly disabling primary headache. Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with ~ 50% of patients responding after 24 weeks. A response predictor would prevent unnecessary treatments. Inhibiting calcitonin gene related peptide (CGRP) release from trigeminal nociceptive fibres is one of the modes of acting discussed for onabotulinumtoxinA in CM. Therefore, we hypothesized that the response to triptans might predict response to onabotulinumtoxinA. Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy. 49 CM patients scheduled for their first onabotulinumtoxinA treatment were included. Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients rated triptan efficacy and indicated number of headache days/month. At T1, patients additionally rated onabotulinumtoxinA efficacy. Headache days/month were on average reduced by 7.1 ± 7.0 days from T0 to T1 (p < 0.001). Triptan efficacy ratings at T0 did not predict onabotulinumtoxinA efficacy ratings at T1 (p = 0.19) or reduction of headache days (p = 0.37). However, triptan efficacy significantly improved from T0 to T1 in onabotulinumtoxinA responders (p < 0.001) but not in non-responders (p = 1.00). Triptan efficacy did not predict response to onabotulinumtoxinA in CM. However, triptan efficacy increased after successful onabotulinumtoxinA treatment. This supports the hypothesis that efficacy of acute migraine treatment with triptans improves with effective migraine prophylaxis.

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Identifying oxidized lipid mediators as prognostic biomarkers of chronic post-traumatic headache.

Chronic Post Traumatic Headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic non-traumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. Pain reduction was associated with alterations in oxylipins derived from n-3 and n-6 fatty acids, suggesting that oxylipins could potentially mediate clinical pain reduction. The objective of the present study was to investigate whether circulating oxylipins measured in the acute setting following TBI, could serve as prognostic biomarkers for developing chronic PTH. Participants enrolled in the Traumatic Head Injury Neuroimaging Classification Protocol provided serum within 3 days of TBI and were followed up at 90 days post-injury with a neurobehavioral symptom inventory (NSI) and satisfaction with-life-survey (SWLS). Liquid chromatography tandem mass spectrometry methods profiled 39 oxylipins derived from n-3 docosaheaxaenoic acid (DHA), and n-6 arachidonic acid (AA) and linoleic acid (LA).Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or SWLS scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (an LA derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.

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Remote Electrical Neuromodulation for the Acute Treatment of Migraine in Patients with Chronic Migraine: An Open-Label Pilot Study.

Remote electrical neuromodulation (REN) is a novel acute treatment of migraine. Upper arm peripheral nerves are stimulated to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. The REN device (Nerivio, Theranica Bio-Electronics LTD., Israel) is FDA-authorized for acute treatment of migraine in adults who do not have chronic migraine. The current study assessed the consistency of response over multiple migraine attacks in people with chronic migraine who are typically characterized with severe pain intensity, high disability, and less robust response to triptans.

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