Comparing Perimenstrual and Nonperimenstrual Migraine Attacks Using an e-Diary

BackgroundEndogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to non-perimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms.ObjectivesTo compare perimenstrual and non-perimenstrual migraine attack characteristics and assess premenstrual syndrome (PMS) in women with migraine.MethodsWomen with migraine were invited to complete a headache E-diary. Characteristics of perimenstrual attacks and non-perimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in those without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and non-menstrually related migraine (non-MRM), and women with a natural menstrual cycle and women using hormonal contraceptives.ResultsA representative group of n=500 participants completed the E-diary for at least one month. Perimenstrual migraine attacks (n=998) compared with non-perimenstrual attacks (n=4097) were associated with longer duration (20.0 vs 16.1 hours, 95%CI [0.2-0.4]), higher recurrence risk (OR 2.4 [2.0-2.9]), increased triptan intake (OR 1.2 [1.1-1.4]), higher headache intensity (OR 1.4 [1.2-1.7]), less pain coping (mean difference -0.2 [-0.3- -0.1]), more pronounced photophobia (OR 1.3 [1.2-1.4]) and phonophobia (OR 1.2 [1.1-1.4]) and less aura (OR 0.8 [0.6-1.0]). In total 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs. 15%).DiscussionThe longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.

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Escape from X Chromosome Inactivation and the Female Predominance in Autoimmune Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22031114 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1114

Author(s):

Ali Youness ◽

Charles-Henry Miquel ◽

Jean-Charles Guéry

Keyword(s):

Autoimmune Diseases ◽

X Chromosome ◽

Gene Dosage ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

X Chromosomes ◽

Female Sex Hormones ◽

Inactive X Chromosome ◽

Immune Related Genes ◽

Female Specific

Women represent 80% of people affected by autoimmune diseases. Although, many studies have demonstrated a role for sex hormone receptor signaling, particularly estrogens, in the direct regulation of innate and adaptive components of the immune system, recent data suggest that female sex hormones are not the only cause of the female predisposition to autoimmunity. Besides sex steroid hormones, growing evidence points towards the role of X-linked genetic factors. In female mammals, one of the two X chromosomes is randomly inactivated during embryonic development, resulting in a cellular mosaicism, where about one-half of the cells in a given tissue express either the maternal X chromosome or the paternal one. X chromosome inactivation (XCI) is however not complete and 15 to 23% of genes from the inactive X chromosome (Xi) escape XCI, thereby contributing to the emergence of a female-specific heterogeneous population of cells with bi-allelic expression of some X-linked genes. Although the direct contribution of this genetic mechanism in the female susceptibility to autoimmunity still remains to be established, the cellular mosaicism resulting from XCI escape is likely to create a unique functional plasticity within female immune cells. Here, we review recent findings identifying key immune related genes that escape XCI and the relationship between gene dosage imbalance and functional responsiveness in female cells.

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Toward a pragmatic migraine model for drug testing: 1. Cilostazol in healthy volunteers

Cephalalgia ◽

10.1177/0333102415583986 ◽

2015 ◽

Vol 36 (2) ◽

pp. 172-178 ◽

Cited By ~ 12

Author(s):

Emma Katrine Hansen ◽

Song Guo ◽

Messoud Ashina ◽

Jes Olesen

Keyword(s):

Physical Activity ◽

Healthy Volunteers ◽

Migraine Headache ◽

Drug Testing ◽

Rescue Medication ◽

No Reduction ◽

Healthy Individuals ◽

Double Blind ◽

Headache Intensity ◽

Accompanying Symptoms

Background A model for the testing of novel antimigraine drugs should ideally use healthy volunteers for ease of recruiting. Cilostazol provokes headache in healthy volunteers with some migraine features such as pulsating pain quality and aggravation by physical activity. Therefore, this headache might respond to sumatriptan, a requirement for validation. The hypothesis of the present study was that sumatriptan but not placebo is effective in cilostazol-induced headache in healthy individuals. Methods In a double-blind, randomized, cross-over design, 30 healthy volunteers of both sexes received cilostazol 200 mg on two separate days, each day followed by oral self-administered placebo or sumatriptan 50 mg. Headache response and accompanying symptoms were registered in a questionnaire by the participants themselves. Results Cilostazol induced a reproducible headache in 90% of the participants. The headache had several migraine-like features in most individuals. Median peak headache score was 2 on the sumatriptan day and 3 on the placebo day ( p = 0.17). There was no reduction in headache intensity two hours after sumatriptan ( p = 0.97) and difference in AUC 0 to four hours between two experimental days was not significant ( p = 0.18). On the placebo day eight participants took rescue medication compared to 3 on the sumatriptan day ( p = 0.13). Conclusion Despite similarities with migraine headache, cilostazol-induced headache in healthy volunteers does not respond to sumatriptan.

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Thrombin generation and venous thromboembolism

Hämostaseologie ◽

10.1055/s-0037-1616919 ◽

2008 ◽

Vol 28 (01/02) ◽

pp. 37-39 ◽

Cited By ~ 6

Author(s):

S. Eichinger

Keyword(s):

At Risk ◽

Venous Thromboembolism ◽

Thrombin Generation ◽

Recurrence Risk ◽

Hormonal Contraceptives ◽

Antithrombin Deficiency ◽

Unknown Risk ◽

Patients At Risk ◽

Recurrent Venous Thrombosis

SummaryVenous thromboembolism is a chronic and potential fatal disease. Determination of recurrence risk is time-consuming and costly, and sometimes not feasible: many patients carry more than one risk factor, the relevance of some factors with regard to risk of recurrence is unknown, and existence of thus far unknown risk factors must be considered. A laboratory assay that measures multifactorial thrombophilia would be useful to identify patients at risk of thrombosis. The process of thrombin generation is the central event of the hemostatic process. Thrombin generation is increased in patients at risk of thrombosis including those with antithrombin deficiency or those who are taking hormonal contraceptives. Risk of first and recurrent venous thrombosis is higher in patients with increased thrombin generation. Thus, by use of a simple global marker of coagulation stratification of patients according to their risk of thrombosis is possible. Future studies are needed to improve the management of patients with VTE and increased thrombin generation.

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Acute and Preventive Management of Migraine during Menstruation and Menopause

Journal of Clinical Medicine ◽

10.3390/jcm10112263 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2263

Author(s):

Raffaele Ornello ◽

Eleonora De Matteis ◽

Chiara Di Felice ◽

Valeria Caponnetto ◽

Francesca Pistoia ◽

...

Keyword(s):

Combined Treatment ◽

Hormonal Contraceptives ◽

Future Research ◽

Short Term ◽

Female Sex Hormones ◽

Calcitonin Gene ◽

Migraine Pathogenesis ◽

Long Acting ◽

Short Term Prophylaxis ◽

Increased Susceptibility

Migraine course is influenced by female reproductive milestones, including menstruation and perimenopause; menstrual migraine (MM) represents a distinct clinical entity. Increased susceptibility to migraine during menstruation and in perimenopause is probably due to fluctuations in estrogen levels. The present review provides suggestions for the treatment of MM and perimenopausal migraine. MM is characterized by long, severe, and poorly treatable headaches, for which the use of long-acting triptans and/or combined treatment with triptans and common analgesics is advisable. Short-term prophylaxis with triptans and/or estrogen treatment is another viable option in women with regular menstrual cycles or treated with combined hormonal contraceptives; conventional prevention may also be considered depending on the attack-related disability and the presence of attacks unrelated to menstruation. In women with perimenopausal migraine, hormonal treatments should aim at avoiding estrogen fluctuations. Future research on migraine treatments will benefit from the ascertainment of the interplay between female sex hormones and the mechanisms of migraine pathogenesis, including the calcitonin gene-related peptide pathway.

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Conversion From Chronic To Episodic Migraine In Patients Treated With Erenumab: Real-Life Data From An Italian Region

10.21203/rs.3.rs-45618/v2 ◽

2020 ◽

Author(s):

Raffaele Ornello ◽

Alfonsina Casalena ◽

Ilaria Frattale ◽

Valeria Caponnetto ◽

Amleto Gabriele ◽

...

Keyword(s):

Clinical Practice ◽

Rating Scale ◽

Numerical Rating Scale ◽

Central Italy ◽

Real Life ◽

Episodic Migraine ◽

Main Body ◽

Life Study ◽

Headache Intensity ◽

Acute Medication

Abstract Background. Most patients treated with erenumab in clinical practice have chronic migraine (CM). We assessed the rate and possible predictors of conversion from CM to episodic migraine (EM) in a real-life study.Main body. We performed a subgroup analysis of patients treated with erenumab from January 2019 to February 2020 in the Abruzzo region, central Italy. Treatment was provided according to current clinical practice. For the purpose of the present study, we included patients fulfilling the definition of CM for the three months preceding erenumab treatment and with at least 6 months of follow-up after treatment. We assessed the rate of conversion to EM from baseline to Months 4-6 of treatment and during each month of treatment. To test the clinical validity of conversion to EM, we also assessed the decrease in monthly headache days (MHDs), acute medication days, and median headache intensity on a Numerical Rating Scale (NRS). We included in our study 91 patients with CM. At Months 4-6, 62 patients (68.1%) converted from CM to EM; the proportion of converters increased from Month 1 to Month 5. In the overall group of patients, median MHDs decreased from 26.5 (IQR 20-30) to 7.5 (IQR 5-16; P<0.001) compared with baseline, while median acute medication days decreased from 21 (IQR 16-30) to 6 (IQR 3-10; P<0.001) and median NRS scores decreased from 8 (IQR 7-9) to 6 (IQR 4-7; P<0.001). Significant decreases were found both in converters and in non-converters. We found no significant predictors of conversion to EM among the patients’ baseline characteristics.Conclusions. In our study, two thirds of patients with CM converted to EM during 6 months of treatment with erenumab. MHDs, acute medication use, and headache intensity decreased regardless of conversion from CM to EM.

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Treatment Strategies for Menstrually Related Migraine

Women s Health ◽

10.2217/whe.12.37 ◽

2012 ◽

Vol 8 (5) ◽

pp. 529-541 ◽

Cited By ~ 4

Author(s):

Gianni Allais ◽

Ilaria Castagnoli Gabellari ◽

Ornella Mana ◽

Chiara Benedetto

Keyword(s):

Sex Hormones ◽

Gold Standard ◽

Prophylactic Treatment ◽

Treatment Strategies ◽

Menstrual Migraine ◽

Preventive Strategies ◽

Menstrually Related Migraine ◽

Menstrual Flow ◽

Female Sex Hormones ◽

Analgesic Agents

Approximately 50% of migrainous women suffer from menstrually related migraine (MRM), a type of migraine in which the attacks occur at the same time as or near the menstrual flow. Attacks of MRM tend to be longer, more intense and disabling and sometimes less responsive to treatment than non-menstrual migraines. Similar to the management of non-menstrual migraine, the use of triptans and NSAIDs is the gold standard for MRM treatment. In this paper, the most important studies in the literature that report the effectiveness of triptans, of certain associated drugs and other analgesic agents are summarized. Preventive strategies that can be used if a prophylactic treatment is needed is also analyzed, with particular attention paid to the use of perimenstrual prophylaxis with triptans and/or NSAIDs. Moreover, considering the peculiar interaction between menstrual migraine and female sex hormones, brief mention is made to possible hormonal manipulations.

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Effect of lockdown during COVID-19 on migraine: A longitudinal cohort study

Cephalalgia ◽

10.1177/0333102420981739 ◽

2021 ◽

pp. 033310242098173

Author(s):

Iris E Verhagen ◽

Daphne S van Casteren ◽

Simone de Vries Lentsch ◽

Gisela M Terwindt

Keyword(s):

Cohort Study ◽

The Netherlands ◽

Well Being ◽

Pain Coping ◽

Negative Effects ◽

Social Lives ◽

Acute Medication ◽

Scaling Down ◽

Headache Center ◽

Migrainous Headache

Background The objective of this study was to assess whether migraine-related outcomes changed during intelligent lockdown when compared with the prior period. Methods This was a cohort study evaluating the first month of intelligent lockdown in the Netherlands (12 March to 8 April 2020) compared with one baseline month (13 February to 11 March 2020). We identified 870 migraine patients treated at the Leiden Headache Center with headache e-diaries during the period of interest. Adherence to the e-diary had to be ≥80%, yielding 592 enrolled patients. Results Intelligent lockdown led to a decrease in monthly migraine days (−0.48; 95% CI: −0.78 to −0.18, p = 0.002) and acute medication days (−0.48; 95% CI: −0.76 to −0.20, p < 0.001), and an increase in general well-being (0.11; 95% CI: 0.06 to 0.17, p < 0.001). No differences in non-migrainous headache days and pain coping were observed. Consistent results were found in a subset that was followed for 4 months. Conclusions Our findings imply that intelligent lockdown measures can improve migraine disability despite of the potential negative effects of COVID-19 and lockdown. We hypothesise that this effect is a combined result of working from home, scaling down demanding social lives, and freedom to choose how to organise one’s time.

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Pooled retrospective analysis of 70 mg erenumab in episodic and chronic migraine: a two tertiary headache centers experience during clinical practice

Acta Neurologica Belgica ◽

10.1007/s13760-021-01770-7 ◽

2021 ◽

Author(s):

P. Storch ◽

P. Burow ◽

B. Möller ◽

T. Kraya ◽

S. Heintz ◽

...

Keyword(s):

Chronic Migraine ◽

Retrospective Analysis ◽

Medication Overuse ◽

Real Life ◽

Clinical Trial Data ◽

Headache Intensity ◽

Acute Medication ◽

Calcitonin Gene ◽

Before And After ◽

Male Patients

AbstractErenumab is a monoclonal antibody, targeted against the calcitonin gene-related peptide (CGRP) receptor. Clinical studies have demonstrated prophylactic efficacy in both episodic (EM) and chronic migraine (CM). The aim of the present study is to evaluate the efficacy of treatment in tertiary headache centers under real-life conditions. In a retrospective analysis, the period of 3 months before and after initiation of erenumab therapy was compared. Relevant parameters (headache days, headache intensity, headache duration, acute medication, previous prophylaxis treatments) were collected from medical charts of all migraine patients (N = 82) who started treatment with erenumab between November 1st 2018 and May 1st 2019 at two tertiary headache centers in Germany. The sample included 68 female (82.9%) and 14 male patients aged between 22 and 78 years (mean 51.1 years, SD 10.5 years). Of these patients, 57.3% met the criteria for CM and 56.9% overused acute medication. Under therapy with erenumab, a significant reduction of headache days was observed from the first month on. The effect was most pronounced in the third month with a decrease in monthly headache days from 16.6 to 11.6 days (p < 0.001). There was also a significant reduction in reported headache intensity (p = 0.004) and average duration of headache attacks (p = 0.016). The 50% responder rate in patients with CM was lower in the first month compared to EM but then increased similarly to EM. Patients with medication overuse (MO) also responded to the therapy. There was a reduction in medication overuse from 57% at baseline to 29% after therapy (p = 0.011). Overall, a positive result of treatment with erenumab can be shown in a highly selected sample with severely affected migraine patients and a refractory course prior to treatment. This re-confirms the clinical trial data also for this highly selected group.

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Conversion From Chronic to Episodic Migraine in Patients Treated With Erenumab: Real-life Data From an Italian Region

10.21203/rs.3.rs-45618/v1 ◽

2020 ◽

Author(s):

Raffaele Ornello ◽

Alfonsina Casalena ◽

Ilaria Frattale ◽

Valeria Caponnetto ◽

Amleto Gabriele ◽

...

Keyword(s):

Clinical Practice ◽

Rating Scale ◽

Numerical Rating Scale ◽

Central Italy ◽

Real Life ◽

Episodic Migraine ◽

Headache Intensity ◽

Acute Medication ◽

Numerical Rating ◽

Definition Of

Abstract BackgroundMost patients treated with erenumab in clinical practice have chronic migraine (CM). We assessed the rate and possible predictors of conversion from CM to episodic migraine (EM) in a real-life study.Main bodyWe performed a subgroup analysis of patients treated with erenumab from January 2019 to February 2020 in the Abruzzo region, central Italy. Treatment was provided according to current clinical practice. For the purpose of the present study, we included patients fulfilling the definition of CM for the three months preceding erenumab treatment and with at least 6 months of follow-up after treatment. We assessed the rate of conversion to EM from baseline to Months 4–6 of treatment and during each month of treatment. To test the clinical validity of conversion to EM, we also assessed the decrease in monthly headache days (MHDs), acute medication days, and median headache intensity on a Numerical Rating Scale (NRS). We included in our study 91 patients with CM. At Months 4–6, 62 patients (68.1%) converted from CM to EM; the proportion of converters increased from Month 1 to Month 5. In the overall group of patients, median MHDs decreased from 26.5 (IQR 20–30) to 7.5 (IQR 5–16; P < 0.001) compared with baseline, while median acute medication days decreased from 21 (IQR 16–30) to 6 (IQR 3–10; P < 0.001) and median NRS scores decreased from 8 (IQR 7–9) to 6 (IQR 4–7; P < 0.001). Significant decreases were found both in converters and in non-converters. We found no significant predictors of conversion to EM among the patients’ baseline characteristics.ConclusionsIn our study, two thirds of patients with CM converted to EM during 6 months of treatment with erenumab. MHDs, acute medication use, and headache intensity decreased regardless of conversion from CM to EM.

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Canadian Headache Society Guideline: Acute Drug Therapy for Migraine Headache

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100118943 ◽

2013 ◽

Vol 40 (S3) ◽

pp. S1-S3 ◽

Cited By ~ 54

Author(s):

Irene Worthington ◽

Tamara Pringsheim ◽

Marek J. Gawel ◽

Jonathan Gladstone ◽

Paul Cooper ◽

...

Keyword(s):

Migraine Headache ◽

Expert Consensus ◽

Current Evidence ◽

Migraine Treatment ◽

Controlled Trials ◽

Acute Migraine ◽

Acute Therapy ◽

Migraine Therapy ◽

Acute Medication ◽

Combination Analgesics

ABSTRACT:Objectives:The primary objective of this guideline is to assist the practitioner in choosing an appropriate acute medication for an individual with migraine, based on current evidence in the medical literature and expert consensus. It is focused on patients with episodic migraine (headache on < 14 days a month).Methods:A detailed search strategy was used to find relevant meta-analyses, systematic reviews and randomized double-blind controlled trials. Recommendations were graded with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group. In addition, a general literature review and expert consensus were used for aspects of acute therapy for which randomized controlled trials are not available.Results:Twelve acute medications received a strong recommendation for use in acute migraine therapy (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and acetaminophen). Four received a weak recommendation for use (dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol-containing combination analgesics). Three of these were NOT recommended for routine use (ergotamine, and codeine- and tramadol-containing medications). Strong recommendations were made to avoid use of butorphanol and butalbital-containing medications. Metoclopramide and domperidone were strongly recommended for use where necessary. Our analysis also resulted in the formulation of eight general acute migraine treatment strategies. These were grouped into: 1) two mild-moderate attack strategies, 2) two moderate-severe attack or NSAID failure strategies, 3) three refractory migraine strategies, and 4) a vasoconstrictor unresponsive-contraindicated strategy. Additional strategies were developed for menstrual migraine, migraine during pregnancy, and migraine during lactation.Conclusion:This guideline provides evidence-based advice on acute pharmacological migraine therapy, and should be helpful to both health professionals and patients. The available medications have been organized into a series of strategies based on patient clinical features. These strategies may help practitioners make appropriate acute medication choices for patients with migraine.

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