Provoked versus spontaneous migraine attacks: pathophysiological similarities and differences

Ashina, Håkan; Christensen, Rune Häckert; Ashina, Messoud

doi:10.1186/s10194-022-01464-2

Cited by 9 publications

(8 citation statements)

References 34 publications

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“…Human provocation studies that use trigger substances, such as CGRP, have provided important insights into the signaling pathways and drug targets that are relevant to migraine [ 61 ]. However, only one provocation study of 13 patients has investigated prediction of efficacy of mAbs against CGRP signaling [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

Karlsson¹,

Ashina²,

Cullum³

et al. 2023

J Headache Pain

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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).

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Section: Discussionmentioning

confidence: 99%

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

Karlsson¹,

Ashina²,

Cullum³

et al. 2023

J Headache Pain

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“…Finally, beyond the above mentioned limitation of animal models, caution is mandatory in the interpretation of data from human provocative studies, due to the fact that despite the similarities shared by provoked and spontaneous migraine attacks, substantial differences exist, mainly the source of migraine-inducing substances (exogenous vs. endogenous source) along with the absence of premonitory symptoms, underpinned by the different functional changes making the brain prone to an impending migraine attack [15,188]. In other terms, there is the high risk to focus, by inducing migraine-like attacks, on a snapshot of a very complex and multiphasic process.…”

Section: Evidence-related Issuesmentioning

confidence: 99%

Migraine Treatment: Towards New Pharmacological Targets

Silvestro,

Iannone,

Orologio

et al. 2023

IJMS

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Migraine is a debilitating neurological condition affecting millions of people worldwide. Until a few years ago, preventive migraine treatments were based on molecules with pleiotropic targets, developed for other indications, and discovered by serendipity to be effective in migraine prevention, although often burdened by tolerability issues leading to low adherence. However, the progresses in unravelling the migraine pathophysiology allowed identifying novel putative targets as calcitonin gene-related peptide (CGRP). Nevertheless, despite the revolution brought by CGRP monoclonal antibodies and gepants, a significant percentage of patients still remains burdened by an unsatisfactory response, suggesting that other pathways may play a critical role, with an extent of involvement varying among different migraine patients. Specifically, neuropeptides of the CGRP family, such as adrenomedullin and amylin; molecules of the secretin family, such as pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP); receptors, such as transient receptor potential (TRP) channels; intracellular downstream determinants, such as potassium channels, but also the opioid system and the purinergic pathway, have been suggested to be involved in migraine pathophysiology. The present review provides an overview of these pathways, highlighting, based on preclinical and clinical evidence, as well as provocative studies, their potential role as future targets for migraine preventive treatment.

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“…Episodic migraine may transform into chronic migraine in the process of chronification [ 23 ]. There are more classifications of migraine, including its categorization into migraine with or without aura - sensory disturbances, such as flashes of light, blind spots, and other vision changes or tingling in hand or face [ 24 ]. The clinical pictures of migraine with and without aura are so diverse that some researchers suggest considering them as two different entities [ 25 , 26 ].…”

Section: Migrainementioning

confidence: 99%

Different Aspects of Aging in Migraine

Fila¹,

Pawłowska²,

Szczepańska³

et al. 2023

Aging and disease

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Migraine is a common neurological disease displaying an unusual dependence on age. For most patients, the peak intensity of migraine headaches occurs in 20s and lasts until 40s, but then headache attacks become less intense, occur less frequently and the disease is more responsive to therapy. This relationship is valid in both females and males, although the prevalence of migraine in the former is 2-4 times greater than the latter. Recent concepts present migraine not only as a pathological event, but rather as a part of evolutionary adaptive response to protect organism against consequences of stress-induced brain energy deficit. However, these concepts do not fully explain that unusual dependence of migraine prevalence on age. Many aspects of aging, both molecular/cellular and social/cognitive, are interwound in migraine pathogenesis, but they neither explain why only some persons are affected by migraine, nor suggest any causal relationship. In this narrative/hypothesis review we present information on associations of migraine with chronological aging, brain aging, cellular senescence, stem cell exhaustion as well as social, cognitive, epigenetic, and metabolic aging. We also underline the role of oxidative stress in these associations. We hypothesize that migraine affects only individuals who have inborn, genetic/epigenetic, or acquired (traumas, shocks or complexes) migraine predispositions. These predispositions weakly depend on age and affected individuals are more prone to migraine triggers than others. Although the triggers can be related to many aspects of aging, social aging may play a particularly important role as the prevalence of its associated stress has a similar age-dependence as the prevalence of migraine. Moreover, social aging was shown to be associated with oxidative stress, important in many aspects of aging. In perspective, molecular mechanisms underlying social aging should be further explored and related to migraine with a closer association with migraine predisposition and difference in prevalence by sex.

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Provoked versus spontaneous migraine attacks: pathophysiological similarities and differences

Cited by 9 publications

References 34 publications

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

Migraine Treatment: Towards New Pharmacological Targets

Different Aspects of Aging in Migraine

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