Related Migraine Research Articles

Sleep-related and non-sleep-related migraine: interictal sleep quality, arousals and pain thresholds

BackgroundThe mechanisms associating sleep and migraine are unknown. No previous polysomnographic (PSG) or pain-threshold (PT) study has compared patients with sleep-related migraine attacks (SM), non-sleep related migraine attacks (NSM) and healthy controls.MethodsWe have performed a blinded, prospective exploratory study with case–control design. Thirty-four healthy controls, 15 patients with SM and 18 patients with NSM had interictal PSG heat-, cold- and pressure PT (HPT, CPT, PPT) recordings and completed diary- and questionnaire on sleep and headache related aspects.ResultsNSM patients had more slow-wave sleep (SWS) and more K-bursts than SM patients (K-bursts: p = 0.023 and SWS: p = 0.030) and controls (K-bursts: p = 0.009 and SWS: 0.041). NSM patients also had lower HPT and CPT than controls (p = 0.026 and p = 0.021). In addition, SM patients had more awakenings and less D-bursts than controls (p = 0.025 and p = 0.041).ConclusionSM- and NSM patients differed in objective-, but not subjective sleep quality. NSM patients had PSG findings indicating foregoing sleep deprivation. As foregoing sleep times were normal, a relative sleep deficit might explain reduced PT among NSM patients. The SM patients had signs of slightly disturbed sleep.

Frovatriptan plus dexketoprofen in the treatment of menstrually related migraine: an open study

At least 50 % of female migraineurs experience migraine associated with the perimenstrual period, even though they may also suffer from attacks at other times of the cycle (menstrually related migraine, MRM). MRM attacks tend to be longer and more intense than those arising in other phases of the menstrual cycle, and are often aggravated by more pronounced vegetative phenomena. In this open preliminary trial, we tested the efficacy of associating frovatriptan and dexketoprofen for the treatment of an acute attack of MRM, diagnosed according to the criteria of the International Headache Society, in 24 patients between 19 and 45 years of age (mean 31.33 ± 7.33). Twenty-one of them completed the study. Pain relief was achieved by 76 % of patients at 2 h and by 86 % at 4 h. A pain-free state was achieved by 48 % at 2 h and by 62 % at 4 h from taking the product. A pain-free state at 24 h was present in 76 % of MRM sufferers, 33 % of whom showed a sustained pain-free state at 24 h. A rescue medication was needed by eight patients. While decidedly encouraging, the data of this study obviously need confirmation with double blind studies involving a greater number of patients.

Effect of a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) in women with menstrually-related migraine (MRM)

BackgroundCombined hormonal contraception might worsen migraine in sensitive women, especially during the free-hormone interval, and raise concerns about the vascular risk. The characteristics of a contraceptive pill containing estradiol valerate/dienogest (E2V/DNG) might be of potential benefit in women with menstrually related migraine (MRM) who choose to use oral contraception for birth control. Study designThis was a prospective diary-based pilot study. Thirty-two women (age >35 years) [n=18 who had never used combined oral contraceptives (COCs) and n=14 who had previously used COCs] diagnosed with MRMs according to the International Headache Society criteria were included. During the observational period, women filled in a diary with the clinical characteristics of migraine attacks. After a three-cycle run-in period, each subject received a COC containing E2V/DNG (Qlaira®/Natazia®; Bayer HealthCare, Berlin, Germany) administered using an estrogen step-down and progestogen step-up approach. Follow-up evaluations were scheduled at the last cycle of run-in and at the third and sixth cycles of treatment. ResultsThe number of migraine attacks was significantly reduced at the third (p<.001) and sixth cycles (p<.001) in comparison with the run-in period. A similar result was evident for the duration (p<.001 at the third and p<.001 at the sixth cycle) as well as for the severity of head pain (p<.001 at the third and p<.001 at the sixth month). Indeed, a significantly lower number of analgesics were used at the third cycle (p<.001) in comparison with baseline, and a further decrease was evident at the sixth cycle (p<.001) in comparison with the third cycle of E2V/DNG use. Interestingly, duration and severity of head pain were significantly correlated with the number of days of dysmenorrhea at the third cycle (r=.89, p=.000 and r=.67, p=.02; respectively) and at the sixth cycle (r=.76, p=.000 and r=.62, p=.04; respectively) in women without complete remission of menstrual cramps during the study period. ConclusionsThe present diary-based pilot study indicates that the use of a pill containing EV2/DNG for six cycles has a positive effect in women with MRM and suggests an association between dysmenorrhea with COCs use as a potential feature of refractory head pain.

Analysis of subjects with menstrually related migraine vs. Non-menstrually related migraine treated with MAP0004

Menstrually related migraine (MRM) is defined as occurring from days -2 to +3 of menstruation in at least 2 out of 3 menstrual cycles, and additionally at other times of the menstrual cycle. MRM is generally longer lasting, more severe, and more difficult to treat compared to non-MRM attacks. MAP0004 is an investigational orally inhaled dihydroergotamine (DHE) for the acute treatment of migraine. In a large Phase 3 study, MAP0004 was effective and well tolerated in treating an acute migraine attack compared to placebo. This post-hoc analysis compares the efficacy of MAP0004 in treating MRM versus non-MRM, including an analysis of recurrence rates using 4 different, previously published recurrence rate definitions. The efficacy of MAP0004, as measured by pain relief at 2 hours, pain free at 2 hours, sustained pain relief at 2-24 and 2-48 hours, and sustained pain free at 2-24 and 2-48 hours values, was not significantly different between subjects with MRM and non-MRM. Furthermore, the MRM recurrence rates after pain relief were not statistically higher than that of non-MRM treated with MAP0004. There were no significant differences in the frequency of adverse events for MRM vs. non-MRM subjects, and no drug-related serious adverse events were reported. In the study, MAP0004 was effective and well-tolerated for both MRM and non-MRM.

A Cyclic Pain

Catamenial migraine is a headache disorder occurring in reproductive-aged women relevant to menstrual cycles. Catamenial migraine is defined as attacks of migraine that occurs regularly in at least 2 of 3 consecutive menstrual cycles and occurs exclusively on day 1 to 2 of menstruation, but may range from 2 days before (defined as -2) to 3 days after (defined as +3 with the first day of menstruation as day +1). There are 2 subtypes: the pure menstrual migraine and menstrually related migraine. In pure menstrual migraine, there are no aura and no migraine occurring during any other time of the menstrual cycle. In contrast, menstrually related migraine also occurs in 2 of 3 consecutive menstrual cycles, mostly on days 1 and 2 of menstruation, but it may occur outside the menstrual cycle. Catamenial migraine significantly interferes with the quality of life and causes functional disability in most sufferers. The fluctuation of estrogen levels is believed to play a role in the pathogenesis of catamenial migraine. In this review, we discuss estrogen and its direct and indirect pathophysiologic roles in menstrual-related migraine headaches and the available treatment for women. Obstetricians and gynecologists, family physicians. After completing this CME activity, physicians should be better able to discuss the pathophysiology of catamenial migraine, identify the risk factors for catamenial migraine among women, and list the prophylactic and abortive treatments for migraines.

Analysis of subjects with menstrually related migraine vs. Non-menstrually related migraine treated with MAP0004

Analysis of subjects with menstrually related migraine vs. Non-menstrually related migraine treated with MAP0004

Migraine-related ischemic stroke?

Migraine, especially migraine with aura, has been described to be associated with an increased risk for ischemic stroke. An increased incidence of silent lesions in the posterior circulation has also been described. Six cases with migraine and stroke in close relation over time were retrospectively reviewed. All patients had previously known MA or MO and suffered from a stroke within the first 24-hour period after an acute migraine attack. None of the patients fulfilled the IHS criteria for migrainous infarction. Four out of these six patients had a patent foramen ovale (PFO) or an atrial septal defect (ASD). None of these cases can be categorized as migrainous infarctions according to IHS. However, the migraine attack might have been involved in the mechanisms for the development of the infarctions.

A review of the use of frovatriptan in the treatment of menstrually related migraine

Menstrual migraine (MM) is a highly prevalent condition associated with considerable disability. Migraine attacks occur exclusively around the menstrual period in approximately 10% of women with migraine, that is, pure menstrual migraine, while at least 50% of them also experience migraine at other times of the month, that is, menstrually related migraine (MRM). The therapeutic approach to patients with MRM is based on treatment of the attack, or prophylactic strategies. Triptans are recommended as first-line treatments for moderate to severe migraine attacks, including MM. Frovatriptan is one of the newest triptans. Its high affinity for 5-HT1B/1D receptors and long half-life contribute to its distinctive clinical effect, characterized by a more sustained and prolonged effect than other triptans. Indeed, frovatriptan proved to be effective in treating the acute attack, but was particularly effective in the short-term preventive therapy of MM. In addition, frovatriptan is one of the safest triptans, with the lowest risk of treatment-emergent adverse events. Following extensive evidence from randomized pharmacological trials, frovatriptan has now gained a grade A recommendation from the guidelines for short-term prophylaxis of MM. Recent post-hoc analyses of direct comparative trials also suggest that frovatriptan might have an important role in the acute treatment of MRM. In these studies, frovatriptan showed pain relief and pain-free rates similar to those of zolmitriptan, rizatriptan, and almotriptan, but with significantly lower recurrence rates. More well-designed, randomized, prospective studies, specifically enrolling women with MM, will be needed in the near future to confirm the efficacy of frovatriptan in this migraine subtype.

Cutaneous allodynia in patients with episodic migraine

Cutaneous allodynia may be observed in patients with migraine and this reflects the central sensitization of the trigeminal neurons. We aimed to investigate the frequency of cutaneous allodynia in patients with episodic migraine and to compare clinical characteristics of migraine patients with and without allodynia. One hundred and eighty-six consecutive patients with episodic migraine attacks were prospectively included in the study. The cutaneous allodynia symptoms that occurred during headache attacks were documented using a questionnaire for assessing cephalic and extracephalic cutaneous allodynia. One hundred and fourteen patients (61.3 %) were observed to develop allodynia during migraine attacks and the ratio of the female gender was found higher among the patients with allodynia (p < 0.001). Migraine disease duration was longer (p = 0.004) and accompanying nausea and phonophobia were more common (p = 0.003 and p = 0.005, respectively) in the patients with allodynia. Menstrually related migraine was found to be associated with both allodynia (p = 0.049) and its severity (p = 0.003). The results of present study revealed that cutaneous allodynia was rather frequent in episodic migraine, particularly in patients having longer disease duration. Higher frequency of allodynia in women and its association with menstrually related migraine may be related to the effects of hormonal factors on cutaneous pain thresholds and central sensitization. Association of nausea and phonophobia with allodynia may be interpreted as the common pathways are shared in the development of these symptoms.

Unilateral cranial autonomic symptoms in patients with migraine

The aim of this study is to investigate the frequency of unilateral cranial autonomic symptoms during migraine attacks, and to compare the clinical characteristics of migraine patients with and without unilateral cranial autonomic symptoms. One hundred and eighty-six consecutive patients with episodic migraine attacks were prospectively included. Cranial autonomic symptoms of the patients occurred during headache, frequency, duration, severity and character of headache, disease duration, presence of aura, laterality of headache, accompanying symptoms, relation of migraine attacks with menstruation, lesions detected on magnetic resonance images, and family history of migraine were recorded. The patients with and without unilateral cranial autonomic symptoms during headache were compared in terms of above-mentioned parameters. Seventy-seven (41.4 %) patients were observed to develop unilateral cranial autonomic symptoms during migraine attack. Disease duration was longer in the patients with unilateral cranial autonomic symptoms than in those without (p = 0.045). Headache was unilateral in 83.1 % of the patients with unilateral cranial autonomic symptoms (p = 0.001). Pure menstrual or menstrually related migraine attacks were more common in the patients with unilateral cranial autonomic symptoms (p = 0.043) and is thought that menstruation-related hormonal factors might have a triggering role on the trigeminal-autonomic reflex pathway. The longer disease duration in patients with unilateral cranial autonomic symptoms might be associated with the activation of pathophysiological mechanisms that cause cranial autonomic symptoms in time. Frequent unilateral pain in migraine patients with unilateral cranial autonomic symptoms is likely to indicate that the development of autonomic symptoms may share common mechanisms with the pathogenesis of trigeminal autonomic cephalalgias.

Treatment Strategies for Menstrually Related Migraine

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.

Migraine in Women

This article discusses hormonal milestones and the influence that hormonal fluctuations make in the frequency and severity of migraine in women and includes information on acute, short-term, and preventive strategies for hormonally influenced migraine and the situations in which hormonal therapies may be offered. Genomic patterns in adolescent girls differentiate between menstrually related migraine and non-menstrually related migraine. The age at initiation of estrogen replacement therapy appears to be significant with respect to stroke. No increase in stroke occurred in women on low-dose (50 µg or less) transdermal estrogen replacement compared to women not using estrogen replacement. Childhood maltreatment is more common in women with migraine and depression than in women with migraine alone. Management of hormonally influenced migraine involves a clear identification of the relationship between migraine and hormone change. A thorough history and detailed diary are critical in identifying this relationship and in predicting response or following response to hormonal therapies. The evolution of migraine in an individual may be strongly driven by hormonal shifts. Although limited, clinical evidence suggests that oral contraceptive use in young women with episodic migraine may transform their pattern into chronic migraine. Thus, particular attention to changes in migraine patterns following either endogenous or exogenous hormonal changes is crucial. Providing reassurance and education that migraine is a biological disorder and providing an understanding of the role of estrogen in the frequency and severity of migraine can guide treatment choices. Pharmacologic treatments include acute therapy, with short-term and standard prevention offered where appropriate. Hormonal therapies are not first-line therapies but may be important choices for a woman with migraine whose estrogen fluctuation is continually exacerbating migraine attacks. Given the many hormonal stages during the life of a woman with migraine, therapies may vary according to hormonal stage and status. Overall wellness should also be emphasized; regular exercise, balanced diet, smoking cessation, weight control, and sleep hygiene are important in the management of migraine.

The Impact of Extended‐Cycle Vaginal Ring Contraception on Migraine Aura: A Retrospective Case Series

To determine whether extended-cycle dosing of an ultralow dose vaginal ring contraceptive decreases frequency of migraine aura and prevents menstrual related migraine (MRM). Many women are denied therapy with combined hormonal contraceptives due to published guidelines that recommend against their use in migraine with aura (MwA). The concern is that these products might further elevate the risk of ischemic stroke that accompanies aura. Stroke risk has been reported to vary directly with aura frequency, and aura frequency in turn has been shown to have a direct relationship to estrogen concentration. With the evolution of increasingly lower dosed combined hormonal contraceptives, we now have formulations that--provided that ovulation is inhibited--result in lower peak levels of estrogen than the concentrations attained during the native menstrual cycle. These formulations would thus be expected to result in a lower frequency of migraine aura. Furthermore, as extended-cycle therapy eliminates monthly estrogen withdrawals, this therapy would likewise be expected to prevent MRM. This pilot study is an institutional review board-approved retrospective database review. We queried our database of 830 women seen in a subspecialty menstrual migraine clinic to identify women who met all inclusion criteria: (1) current history of MwA; (2) confirmed diagnosis of MRM; and (3) treatment with extended-cycle dosing of a transvaginal ring contraceptive containing 0.120 mg etonogestrel/15 µg ethinyl estradiol. Standardized calendars that specifically document bleeding patterns, headache details, and occurrence of aura are required of all patients in this clinic. Twenty-eight women met study criteria, none of whom were smokers. Of these, 5 discontinued use of etonogestrel/ethinyl estradiol within the first month, leaving 23 evaluable subjects. At baseline, subjects averaged 3.23 migraine auras/month (range: 0.1-12). With extended dosing of the vaginal ring contraceptive, median frequency was reduced to 0.23 auras per month following treatment after a mean observation of 7.8 months (P < .0005). No subject reported an increase in aura frequency. On this regimen, MRM was eliminated in 91.3% of the evaluable subjects. In this sample of women with both MwA and MRM, use of an extended-cycle vaginal ring contraceptive was associated with a reduced frequency of migraine aura and with resolution of MRM. This cannot be extrapolated to suggest that stroke risk in MwA will be similarly reduced. Studies to evaluate this relationship are warranted.

Treatment of Perimenstrual Migraine with Triptans: an Update

Pure menstrual migraine (PMM) and menstrually related migraine (MRM) are difficult challenges in migraine management. Triptans are a class of highly selective serotonin receptor agonists, which interfere with the pathogenesis of migraine and are effective in relieving the associated neurovegetative symptoms. In recent years triptans have been extensively proposed for the treatment of severe, disabling, and recurrent perimenstrual migraine attacks. This review summarizes the different levels of recommendations for the use of triptans in the treatment of perimenstrual migraine. This review is also intended to offer an updated reasonable guide to physicians treating perimenstrual migraine in daily practice.

Frovatriptan versus almotriptan for acute treatment of menstrual migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study

The objective of the study was to compare the efficacy and safety of frovatriptan and almotriptan in women with menstrually related migraine (IHS Classification of Headache disorders) enrolled in a multicenter, randomized, double-blind, cross-over study. Patients received frovatriptan 2.5 mg or almotriptan 12.5 mg in a randomized sequence: after treating 3 episodes of migraine in no more than 3 months with the first treatment, the patient was switched to the other treatment. 67 of the 96 female patients of the intention-to-treat population of the main study had regular menstrual cycles and were thus included in this subgroup analysis. 77 migraine attacks classified as related to menses were treated with frovatriptan and 78 with almotriptan. Rate of pain relief at 2 and 4 h was 36 and 53 % for frovatriptan and 41 and 50 % for almotriptan (p = NS between treatments). Rate of pain free at 2 and 4 h was 19 and 47 % with frovatriptan and 29 and 54 % for almotriptan (p = NS). At 24 h, 62 % of frovatriptan-treated and 67 % of almotriptan-treated patients had pain relief, while 60 versus 67 % were pain free (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with frovatriptan (8 vs. 21 % almotriptan). This was the case also at 48 h (9 vs. 24 %, p < 0.05). Frovatriptan was as effective as almotriptan in the immediate treatment of menstrually related migraine attacks. However, it showed a more favorable sustained effect, as shown by a lower rate of migraine recurrence.

Efficacy of frovatriptan versus other triptans in the acute treatment of menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies

The objective of this study was to review the efficacy and safety of frovatriptan (F) versus rizatriptan (R), zolmitriptan (Z) and almotriptan (A), in women with menstrually related migraine (IHS criteria) through a pooled analysis of three individual studies. Subjects with a history of migraine with or without aura were randomized to F 2.5 mg or R 10 mg (study 1), F or Z 2.5 mg (study 2), and F or A 12.5 mg (study 3). The studies had an identical multicenter, randomized, double-blind, crossover design. After treating three episodes of migraine in no more than 3 months with the first treatment, patients had to switch to the next treatment for other 3 months. 346 subjects formed intention-to-treat population of the main study; 280 of them were of a female gender, 256 had regular menses and 187 were included in the menstrual migraine subgroup analysis. Rate of pain free at 2, 4 and 24 h was 23, 52 and 67 % with F and 30, 61 and 66 % with comparators (P = NS). Pain relief episodes at 2, 4 and 24 h were 37, 60 and 66 % for F and 43, 55 and 61 % for comparators (P = NS). Rate of recurrence was significantly (P < 0.05) lower under F either at 24 h (11 vs. 24 % comparators) or at 48 h (15 vs. 26 % comparators). Number of menstrual migraine attacks associated with drug-related adverse events was equally low (P = NS) between F (5 %) and comparators (4 %).

Efficacy of frovatriptan in the acute treatment of menstrually related migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study versus rizatriptan

The objectives of this study are to assess the efficacy and safety of frovatriptan, and rizatriptan in the subgroup of women with menstrually related migraine of a multicenter, randomized, double blind, cross-over study. Each patient received frovatriptan 2.5 mg or rizatriptan 10 mg in a randomized sequence: after treating 3 episodes of migraine in not more than 3 months with the first treatment, the patient had to switch to the other treatment. Menstrually related migraine was defined according to the criteria listed in the Appendix of the last IHS Classification of Headache disorders. 99 out of the 125 patients included in the intention-to-treat analysis of the main study were of a female gender: 93 had regular menstrual cycles and were, thus, included in this analysis. A total of 49 attacks classified as menstrually related migraine were treated with frovatriptan and 59 with rizatriptan. Rate of pain relief at 2 h was 58% for frovatriptan and 64% for rizatriptan (p = NS), while rate of pain free at 2 h was 31 and 34% (p = NS), respectively. At 24 h, 67 and 81% of frovatriptan-treated, and 61 and 74% of rizatriptan-treated patients were pain free and had pain relief, respectively (p = NS). Recurrence at 24 h was significantly (p < 0.01) lower with frovatriptan (10 vs. 32% rizatriptan). Frovatriptan was as effective as rizatriptan in the immediate treatment of menstrually related migraine attacks while showing a favorable sustained effect with a lower rate of migraine recurrence. These results need to be confirmed by randomized, double-blind, prospective, large clinical trials.

Course of migraine during pregnancy among migraine sufferers before pregnancy

To describe the course of migraine without aura and migraine with aura during pregnancy and factors that could influence its course, among migraine sufferers before pregnancy. A cross sectional study undertaken at the IMIP, Brazil. Out of 686 consecutively assisted women, at the first postnatal week, 266 were identified as migraine sufferers before pregnancy. There was migraine remission in 35.4%, 76.8% and 79.3% among migraine without aura sufferers and 20.7%, 58.6% and 65.5% among those with migraine with aura, respectively in the first, second and third trimesters. Statistically significant difference was found when the first trimester was compared with the second and third trimesters. The factors associated with the presence of migraine during pregnancy were: multiparity, menstrually related migraine without aura prior to pregnancy and illness during pregnancy. The study contributed to elucidate the course of migraine during pregnancy in migraine sufferers prior to pregnancy.

Almotriptan for menstrually related migraine

Introduction: Approximately 50% of migrainous women associate their headache temporally to menses. Menstrually related migraine (MRM) is a disabling form of migraine characterized by attacks that are generally longer, more severe and less drug-responsive than nonmenstrual ones. Since MRM may be difficult to treat, it is important to find an appropriate treatment option for women suffering from this condition.Areas covered: This paper provides an overview of the clinical features of MRM, with special attention on the use of almotriptan for its treatment. Four studies on almotriptan in the treatment of MRM are present in the medical literature. Two report post hoc analyses of data derived from larger studies on the use of almotriptan for migraine treatment. One reports the results from a study specifically dedicated to MRM and one illustrates a subanalysis on the accompanying symptomatology.Expert opinion: Evidence demonstrates that almotriptan is a molecule with a high efficacy in the treatment of MRM and with an excellent tolerability profile when compared with other triptans. Moreover, it shows a proven ability to control migraine-associated symptoms. All these qualities play a decidedly positive role in making almotriptan a product of choice for the treatment of MRM.

Menstrual Migraine: Current Strategies for Diagnosis and Management

Migraine is a common health problem among women and can cause significant disability. Approximately 60% of women with migraine report a correlation between migraine and their menstrual cycle. Because of this prevalence, the International Headache Society outlined criteria for the diagnosis of pure menstrual migraine and menstrually related migraine. After practitioners accurately diagnose menstrual migraine based upon these criteria, they can then work with individual clients to determine the best treatment plan. This article focuses on the accurate diagnosis of menstrual migraine and several evidence-based treatment options available to women who suffer from this debilitating condition.