Cephalalgia最新文献

Background: Migraine is a common disorder, particularly affecting women during their reproductive years. This female preponderance has been linked to exposure to female sex hormones.

Methods: We used self-reported data from women born in 1943-1965 enrolled in the Norwegian Women and Cancer Study to examine the differences between women with migraine and women without migraine in a prospective design with respect to both endogenous and exogenous female sex hormone exposure.

Results: In total, 62,959 women were included in the study, of whom 24.8% reported previous migraine (n = 15,635). Using a Cox proportional hazards model, we found that higher age at menarche reduced the risk of migraine (hazards ratio (HR) = 0.96, 95% confidence interval (CI) = 0.95-0.98) and that oral contraceptive use and parity increased the risk of migraine (HR = 1.12, 95% CI = 1.06-1.18 and HR = 1.37, 95% CI = 1.29-1.46, respectively).

Conclusions: Older age at menarche appears to reduce migraine risk, whereas oral contraceptive use and having children appear to increase the risk. Further research is required to investigate the causality of these associations.

Objective: Preclinical and clinical studies implicate the vascular ATP-sensitive potassium (K_ATP) channel in the signaling cascades underlying headache and migraine. However, attempts to demonstrate that the K_ATP channel inhibitor glibenclamide would attenuate triggered headache in healthy volunteers have proven unsuccessful. It is questionable, however, whether target engagement was achieved in these clinical studies.

Methods: Literature data for human glibenclamide pharmacokinetics, plasma protein binding and functional IC₅₀ values were used to predict the K_ATP receptor occupancy (RO) levels obtained after glibenclamide dosing in the published exploratory clinical headache provocation studies. RO vs. time profiles of glibenclamide were simulated for the pancreatic K_ATP channel subtype Kir6.2/SUR1 and the vascular subtype Kir6.1/SUR2B.

Results: At the clinical dose of 10 mg of glibenclamide used in the headache provocation studies, predicted maximal occupancy levels of up to 90% and up to 26% were found for Kir6.2/SUR1 and Kir6.1/SUR2B, respectively.

Conclusions: The findings of the present study indicate that effective Kir6.1/SUR2B target engagement was not achieved in the clinical headache provocation studies using glibenclamide. Therefore, development of novel selective Kir6.1/SUR2B inhibitors, with good bioavailability and low plasma protein binding, is required to reveal the potential of K_ATP channel inhibition in the treatment of migraine.

Targeting CGRP-pathways has substantially expanded our options for treating individuals with migraine. Although the efficacy of these drugs on migraine aura is yet to be fully revealed, it seems from existing studies that CGRP antagonism reduces the number of migraine auras. The present perspective summarizes the evidence linking CGRP to the migraine aura and proposes a model by which targeting the CGRP-pathways and, thus, inhibition the interaction between C- and Aδ-trigeminal fibers might reverse a possible high cortical glutamate level leading to a reduced number of migraine auras.

Purpose: Treatments in medicine impact individuals beyond their intended effects, due to phenomena such as the placebo and nocebo effects. The placebo effect arises from the positive expectation of a treatment being beneficial, while the nocebo effect stems from the negative expectation of a treatment causing harm. Both in real-world practice and clinical trials, treatments can lead to outcomes unrelated to their intended mechanism of action, which we categorize as placebo and nocebo responses. These responses, combined with the inherent fluctuation in a condition's natural progression, regression to the mean, and random comorbidities, make up a significant part of the therapeutic experience. Particularly in pain management, placebo and nocebo effects play a substantial role. By addressing modifiable contextual factors such as patient expectations, lifestyle choices, and the therapeutic relationship, healthcare providers can enhance the effectiveness of migraine treatments, paving the way for a more comprehensive, individualized approach to patient care. We must also consider non-modifiable factors like personal experiences, beliefs, and information from social media and the internet.

Conclusion: This review offers a summary of our current understanding of the placebo and nocebo effects in migraine management.

Background: The distinction between a pre-existing primary headache and a secondary headache at the onset of a disorder is important and has not been taken into account in the International Classification of Headache Disorders-3. This study aimed to improve the general diagnostic criteria for secondary headaches using results of our previous studies.

Materials and methods: We analyzed characteristics of headaches including their changes in intensity, duration, frequency, localization and side, development of new accompanying symptoms, and therapeutic response at the onset of transient ischemic attacks (TIA) (n = 120, mean age 56.1, 55% females) and ischemic stroke (n = 550, mean age 63.1, 56% females) compared to the control group (n = 192, mean age 58.7, 64% females).

Results: Headache of a new type occurred in 8.4% of ischemic stroke patients and 5% of TIA patients on the day of admission but did not occur at all in the control group. Pre-existing headache with a change of at least one characteristic occurred significantly more often in stroke (5.4%) and TIA (7.5%) than in the control group (1%) (p = 0.01 and p = 0.003 respectively).

Conclusion: The presence of a new type of headache and a pre-existing headache with altered characteristics in close temporal relation to a disorder indicates causality. Based on these data we propose revised general diagnostic criteria for secondary headaches.

Introduction: Migraine's astonishing prevalence and preserved genetic background contrast with the definition of a disease and the biological meaning of experiencing recurrent, severe headache attacks is still puzzling.

Methods: To provide a comprehensive explanation of the migraine evolutionary meaning, we review (i) the putative role of the autonomic nervous system in migraine attacks, (ii) the inter-ictal autonomic, functional, and metabolic signature of migraine patients, (iii) the bio-behavioral perspective of pain, and (iv) the allostatic perception of migraine chronification.

Results: Migraineurs have inter-ictal cortical hyperexcitability and metabolic dysfunction that predisposes to brain energetic imbalance. Multiple precipitating factors may lead to brain energy consumption over the migraine attack generation threshold. In response, the brain engenders adaptive, evolutionary conserved, autonomic-behavior responses through the antidromic activation of the trigeminovascular system. The sickness behavior and severe pain experienced during migraine attacks result in avoiding mental and physical activity, allowing brain energy restoration. Chronic exposure to stressors may result in an allostatic overload, leading to maladaptive chronic activation of these responses. In this bio-behavioral perspective, the chronification of migraine should be envisioned as a pathological process, whereas the migraine itself should not.

Conclusion: Migraine has an evolutionary (Darwinian) meaning.

Background: Hypnic headache is a neurological disorder characterized by recurrent headache attacks that occur exclusively during sleep, leading to awakening. Synthesizing the available epidemiological data might inform clinical decision-making.

Methods: We searched PubMed and Embase for observational studies on hypnic headache published between 1 May 2004, and 22 December 2022. Two investigators independently screened titles, abstracts, and full-text articles. We performed a random-effects meta-analysis with meta-regression to estimate the prevalence of hypnic headache and its clinical features based on epidemiologic data from population-based and clinic-based studies.

Results: Fourteen studies, one population-based and 13 clinic-based, met our eligibility criteria. The population-based study did not identify any people with hypnic headache. From 11 clinic-based studies, the pooled relative frequency of hypnic headache was 0.21% (95%CI, 0.13 to 0.35%; I² = 87%) in adult patients evaluated for headache. The pooled mean age of onset was 60.5 years, with a slight female predisposition. Hypnic headache was typically bilateral (71%), pressing (73%), of moderate (38%) or severe (44%) pain intensity, and lasted about 115 minutes per attack.

Conclusions: Our data should be cautiously interpreted due to between-study heterogeneity. The identified clinical presentation of hypnic headache can guide clinical diagnosis, in addition to the International Classification of Headache Disorders.