Successful treatment with traditional Japanese medicine (kampo medicine) Yokukansan as a migraine prophylactic drug: A case report.

RATIONALE: The use of anti-CGRP antibody drugs as migraine preventive drugs is increasing worldwide, but there are still a certain number of cases where antibody drugs are ineffective or cannot be used due to high prices. Conventional prophylactic drugs or traditional Japanese medicine (kampo medicine) are still often used in such cases. However, to date, only limited evidence supports the efficacy of kampo medicine for headaches because these treatments have been used primarily empirically and traditionally. However, in recent years studies have begun to be published that describe the efficacy of kampo medicine for various types of headache. Here, we report the case of a patient who achieved a marked reduction in migraine frequency and severity by prophylactic therapy with the kampo drug yokukansan (TSUMURA Yokukansan Extract Granules). PATIENT CONCERNS AND DIAGNOSES: The patient was a 50-year-old woman. She began to experience headaches around high school age and was diagnosed with migraine without aura at 42 years of age. INTERVENTIONS AND OUTCOMES: She started prophylactic therapy with amitriptyline and topiramate and this treatment reduced the frequency of migraines for several years. However, the frequency began to increase again around 47 years, which is when she presented at our hospital. We achieved a temporary reduction in migraine frequency by adjusting the dose of drugs in her prophylactic therapy regimen, but the frequency increased again around age 49. We then tried monotherapy with the kampo medicine yokukansan, and this markedly reduced migraine frequency and severity over the following year. This therapy has remained effective to date. LESSONS: We speculate that, in this case, migraine without aura was improved by prophylactic therapy with yokukansan due to its action on the glutamatergic system or serotonin system through suppression of orexin-A secretion or its anti-inflammatory effects as reported in previous animal studies. Yokukansan could be a usable kampo medicine for migraine prophylaxis in countries all over the world and should be investigated in a large clinical trial as soon as possible.

A importância da alimentação e nutrição para indivíduos com enxaqueca / La importancia de la alimentación y nutrición para personas con jaqueca / The importance of food and nutrition for people with chronic migraines

Introdução: As cefaleias são consideradas um importante problema de saúde pública e estima-se que são a segunda queixa mais comum de dor, sendo a enxaqueca uma das mais presentes. O tratamento da enxaqueca pode ser sintomático ou profilático, a fim de reduzir os sintomas em períodos de crise e evitar que novas crises se instalem, destacando a importância da adoção de hábitos saudáveis e uma alimentação equilibrada. Objetivo: O objetivo deste estudo foi realizar uma revisão integrativa da literatura, destacando os principais achados sobre a importância da alimentação e nutrição para indivíduos acometidos pela enxaqueca. Metodologia: foi realizado um levantamento de estudos nas bases de dados: Biblioteca Virtual em Saúde (BVS); Medline, LILACS, SciELO e Google Acadêmico, além de ter sido considerada a lista de referências dos trabalhos consultados, utilizando a estratégia PECO, onde P (population) indica a população, a letra E (exposure) exposição, C (comparison) comparação e a letra O (outcome) se refere aos desfechos esperados, assim gerou a pergunta norteadora do estudo: "Qual é a importância da alimentação e nutrição para indivíduos com enxaqueca?". Resultados: Foram selecionados 15 estudos para a produção do presente trabalho e foi realizada uma síntese descritiva dos resultados obtidos da relação e influência de hábitos alimentares com a enxaqueca. Conclusões: Conclui-se que os hábitos alimentares e a nutrição adequada têm grande influência e importância para indivíduos com enxaqueca, pois dessa forma, podem reduzir os sintomas apresentados e crises, já que as substâncias presentes nos alimentos estão relacionadas com o início e intensificação das crises (AU).

Introduction: Headaches are considered an important public health problem and are estimated to be the second most common pain complaint, with migraines being one of the most common. Migraine treatment is symptomatic and prophylactic to reduce symptoms when an attack starts and prevent new ones from forming, highlighting the importance of adopting healthy habits and a balanced diet. Objective: The purpose of this study was to carry out an integrative review of the literature in order to highlight the main findings on the influence of eating habits and the importance of nutrition for migraine patients. Methodology:A survey study was performed in the following databases: Virtual Health Library (VHL); Medline, LILACS, SciELO, and Google Scholar, in addition to considering the reference list of the consulted works. The PECO P (population) E (exposure) C (comparison) O (outcome) strategy was used, which generated the guiding question of the study: 'How important is food and nutrition for people with chronic migraines?'. Results:A total of 15 studies were selected to analyze in this work and a descriptive synthesis of the results was performed on the relationship and influence of eating habits of people with chronic migraines. Conclusions:It was concluded that eating habits and adequate nutrition have great influence and importance for migraine patients, as they are one of the main culprits of triggering and intensifying attacks (AU).

Introducción: Las cefaleas son consideradas un importante problema de salud pública y se estima que son la segunda queja más común de dolor, siendo la jaqueca una de las más frecuentes. El tratamiento de la jaqueca puede ser sintomático o profiláctico, con el fin de reducir los síntomas en periodos de crisis y evitar que nuevas ocurran, destacando la importancia de una adopción de hábitos saludables y una alimentación equilibrada. Objetivo: El objetivo de este estudio fue realizar una revisión integrativa de la literatura, destacando los principales hallazgos sobre la importancia de la alimentación y nutrición en personas afectadas por la jaqueca. Metodología: Fue realizada una investigación de los estudios en las bases de dados: Biblioteca Virtual en Salud (BVS); Medline, LILACS, SciELO y Google Académico, además de considerar la lista de referencias de los trabajos consultados, utilizando la estrategia PECO, donde P (population) indica la población, la letra E (exposure) exposición, C (comparison) comparación y la letra O (outcome) se refiere a los resultados esperados, así fue generada la pregunta guía del estudio: "¿Cuál es la importancia de la alimentación y nutrición para las personas con jaqueca?" Resultados: Fueron seccionados 15 estudios para la producción del presente trabajo y fue realizada una síntesis descriptiva de los resultados obtenidos de la relación e influencia de los hábitos alimentarios con la jaqueca. Conclusiones: Se concluye que los hábitos alimentarios y la nutrición adecuada tienen gran influencia e importancia para las personas conjaqueca, pues de esta forma, pueden reducir los síntomas presentados y crisis, ya que las sustancias presentes en los alimentos están relacionadas con el inicio e intensificación de las crisis (AU).

Effect of Propranolol Prophylaxis on Headache Frequency in Children with Migraine Without Aura: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To compare the efficacy of propranolol prophylaxis with placebo on headache frequency in children with migraine over the 3-mo follow-up. METHODS: In this randomized, double-blind, placebo-controlled trial children aged 6-12 y with newly diagnosed migraine without aura as per the International Classification for Headache Disorders, 3rd edition (ICHD-3) criteria were enroled. They were randomized to the intervention group receiving oral propranolol (1-3 mg/kg/d, BID) and the control group receiving a similar looking, inert, oral placebo for migraine prophylaxis for 3 mo. The number of migraine attacks over the 3-mo follow-up (using a headache diary) was the primary outcome. Pediatric Migraine Disability Assessment Scale (PedMIDAS) was used for assessing disability and Visual analogue scale was used for assessing headache severity. Analysis was done on intention-to-treat basis. RESULTS: Twenty children (10 in each group) completed the study. The two groups were similar at baseline. Both the study drugs produced significant reduction of headache frequency after the study intervention (p = 0.002). However, there was no difference between the two groups with respect to either the median (IQR) number of headache attacks [22 (20, 25) vs. 14 (10, 20); p = 0.05], headache severity [1 (0, 1) vs. 0.5 (0, 1); p = 0.48] or migraine disability [39.5 (28, 44) vs. 35 (22, 38); p = 0.27]. Adverse effects were higher in the intervention group (p = 0.52). CONCLUSIONS: Propranolol was effective for migraine prophylaxis in children but the effect was not higher than placebo. Larger placebo-controlled trials of propranolol need to be conducted to decide its place in migraine prophylaxis in children. TRIAL REGISTRATION: Thailand Clinical Trials Registry; TCTR20200621001.

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial.

OBJECTIVE: To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. METHODS: A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study. RESULTS: Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo (p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) (p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo (p < 0.001).Conclusions and relevance: Early treatment with intravenously administered sumatriptan prevented PACAP38-induced migraine. Prevention of migraine attacks was associated with vasoconstriction by sumatriptan in the earliest phases of PACAP provocation. These results suggest that sumatriptan prevents PACAP38-induced migraine by modulation of nociceptive transmission within the trigeminovascular system.Trial Registration: ClinicalTrials.gov (NCT03881644).

Erenumab Efficacy on Comorbid Cluster Headache in Patients With Migraine: A Real-World Case Series.

BACKGROUND: Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) or its receptor have emerged as effective and well-tolerated preventive medications for migraine. The key role played by CGRP has been recently demonstrated also in the pathophysiology of cluster headache (CH), paving the way for studies aimed to investigate the effectiveness of mABs targeting CGRP also in CH. However, no trials have been conducted so far to test the efficacy and tolerability of erenumab as CH preventive treatment. CASE SERIES: We describe the cases of 5 patients with both migraines and CH with previous failures of preventive treatments. All patients were treated with monthly erenumab (70 or 140 mg) showing good results not only on migraine but also on CH attacks frequency and intensity. Improvements of both intensity and frequency of CH attacks occurred only after at least 3 months of treatment, with monthly erenumab 140 mg, suggesting that longer treatment and higher doses are needed in CH in comparison to migraine. DISCUSSION AND CONCLUSION: Our findings support the efficacy and tolerability of monthly erenumab 140 mg as a preventive treatment in patients suffering from both migraines without aura and CH. We speculate that erenumab could represent a low-risk alternative for CH patients (with or without comorbid migraine) who did not tolerate common CH preventatives therapies or for whom the therapies were not successful. Certainly, randomized trials are needed to confirm these observations and we hope that our data, showing a delayed therapeutic effect only with the highest dose of erenumab (140 mg/month), can be taken into account in designing future trials.

Effect of desogestrel 75 µg on headache frequency and intensity in women with migraine: a prospective controlled trial.

Objective: In contrast with combined hormonal contraception, progestin-only contraception is not associated with an increase in venous thromboembolism or stroke. Women with migraine are at increased risk of ischaemic stroke. Several studies have reported a reduction in migraine frequency and intensity with desogestrel 75 µg, a progestin-only pill. At present the quality of data is limited by retrospective study designs, lack of control groups and small sample sizes. We present the first prospective nonrandomised controlled trial. Methods: A total of 150 women with migraine visiting our clinic for contraceptive counselling were screened. The intervention group comprised women who opted for contraception with desogestrel (n = 98); the control group comprised women who continued their usual contraceptive (n = 36). Participants completed daily diaries for 90 days before the intervention and 180 days after the intervention. Results: In the intervention group, we found improvements in migraine frequency (p < .001), migraine intensity (p < .001) and the number of triptans used (p < .001). These improvements were already significant after 90 days of desogestrel use (p < .001). Disability scores also decreased significantly. No improvement was seen in the nonintervention group. Conclusion: These data demonstrate for the first time in a prospective controlled setting that daily use of the progestin desogestrel is associated with a decrease in migraine frequency, migraine intensity and pain medication use in women with migraine, with and without aura, who had previously been experiencing at least three days of migraine per month. Trial registration: The study is registered in the University of Zürich database ( www.research-projects.uzh.ch/unizh.htm ).

Preventive Treatment with Lomerizine Increases Cerebral Blood Flows during the Interictal Phase of Migraine.

BACKGROUND: Changes in regional cerebral blood flow (rCBF) were reported in migraineurs. However, little is known how preventive medications of migraine can influence rCBF. Lomerizine, a calcium channel blocker, has been used for migraine prophylaxis in Japan. We examined rCBF after lomerizine treatment. SUBJECTS AND METHODS: Migraine was diagnosed according to the criteria of the International Classification of Headache Disorders, Third Edition beta. Migraine subtype was classified into migraine with aura (MA) and migraine without aura (MO). Lomerizine (10 mg/day, per oral) was administered for 3 months. Headache Impact Test-6 (HIT-6) and blood pressure (BP) were compared at baseline and end point. Brain single photon emission computed tomography using 99mTc-ethyl cysteinate dimer was performed at the interictal period. Brain SPECT data were analyzed according to revised version of 3-dimensional stereotaxic region of interest template. Clinic-radiological variables were analyzed by paired Student's t test. RESULTS: Ten migraineurs (4 men and 6 women) participated in the present study. Mean age was 54.1 (standard deviation [SD] 10.1) years. Mean duration of migraine was 25.3 (SD 9.8) years. Migraine subtype showed 4 MA and 6 MO patients. Mean score of HIT-6 was 66.3 (SD 11.7). Lomerizine treatment decreased HIT-6 scores significantly (P < .01). BP did not differ significantly after lomerizine treatment. Lomerizine treatment increased rCBF 20% approximately in the frontal, the parietal, the temporal, and the occipital region. CONCLUSIONS: The present study indicated a significant increase in interictal rCBF after lomerizine treatment in migraineurs. The upregulation of rCBF could contribute to the antimigraine mechanism of lomerizine.

Migraine and percutaneous patent foramen ovale closure: a systematic review and meta-analysis.

BACKGROUND: The association between patent foramen ovale (PFO) and migraine with aura (MA) is well established. However, the benefits of PFO closure are less certain in patients with migraine without aura (MwoA). METHODS: We systematically searched Pubmed for pertinent clinical studies published from January 2000 to July 2015. The primary end-point was the elimination or significant improvement of migraine symptoms after PFO closure. RESULTS: Upon screening an initial list of 315 publications, we identified eight studies that included 546 patients. Overall, our analysis indicated a significant improvement of migraine in 81% of MA cases compared to only 63% of MwoA cases. The summary odds ratio was 2.5 (95% confidence interval 1.09-5.73), and the benefits of PFO closure were significantly greater for patients with MA compared to patients with MwoA (P = 0.03). CONCLUSIONS: The presence of aura provides a reference standard for the clinical selection of patients with migraine for PFO closure intervention.

Acupuncture for the prevention of episodic migraine.

BACKGROUND: Acupuncture is often used for migraine prevention but its effectiveness is still controversial. We present an update of our Cochrane review from 2009. OBJECTIVES: To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than sham (placebo) acupuncture; and c) as effective as prophylactic treatment with drugs in reducing headache frequency in adults with episodic migraine. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL: 2016, issue 1); MEDLINE (via Ovid, 2008 to January 2016); Ovid EMBASE (2008 to January 2016); and Ovid AMED (1985 to January 2016). We checked PubMed for recent publications to April 2016. We searched the World Health Organization (WHO) Clinical Trials Registry Platform to February 2016 for ongoing and unpublished trials. SELECTION CRITERIA: We included randomized trials at least eight weeks in duration that compared an acupuncture intervention with a no-acupuncture control (no prophylactic treatment or routine care only), a sham-acupuncture intervention, or prophylactic drug in participants with episodic migraine. DATA COLLECTION AND ANALYSIS: Two reviewers checked eligibility; extracted information on participants, interventions, methods and results, and assessed risk of bias and quality of the acupuncture intervention. The primary outcome was migraine frequency (preferably migraine days, attacks or headache days if migraine days not measured/reported) after treatment and at follow-up. The secondary outcome was response (at least 50% frequency reduction). Safety outcomes were number of participants dropping out due to adverse effects and number of participants reporting at least one adverse effect. We calculated pooled effect size estimates using a fixed-effect model. We assessed the evidence using GRADE and created 'Summary of findings' tables. MAIN RESULTS: Twenty-two trials including 4985 participants in total (median 71, range 30 to 1715) met our updated selection criteria. We excluded five previously included trials from this update because they included people who had had migraine for less than 12 months, and included five new trials. Five trials had a no-acupuncture control group (either treatment of attacks only or non-regulated routine care), 15 a sham-acupuncture control group, and five a comparator group receiving prophylactic drug treatment. In comparisons with no-acupuncture control groups and groups receiving prophylactic drug treatment, there was risk of performance and detection bias as blinding was not possible. Overall the quality of the evidence was moderate. Comparison with no acupunctureAcupuncture was associated with a moderate reduction of headache frequency over no acupuncture after treatment (four trials, 2199 participants; standardised mean difference (SMD) -0.56; 95% CI -0.65 to -0.48); findings were statistically heterogeneous (I² = 57%; moderate quality evidence). After treatment headache frequency at least halved in 41% of participants receiving acupuncture and 17% receiving no acupuncture (pooled risk ratio (RR) 2.40; 95% CI 2.08 to 2.76; 4 studies, 2519 participants) with a corresponding number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 6); there was no indication of statistical heterogeneity (I² = 7%; moderate quality evidence). The only trial with post-treatment follow-up found a small but significant benefit 12 months after randomisation (RR 2.16; 95% CI 1.35 to 3.45; NNT 7; 95% 4 to 25; 377 participants, low quality evidence). Comparison with sham acupunctureBoth after treatment (12 trials, 1646 participants) and at follow-up (10 trials, 1534 participants), acupuncture was associated with a small but statistically significant frequency reduction over sham (moderate quality evidence). The SMD was -0.18 (95% CI -0.28 to -0.08; I² = 47%) after treatment and -0.19 (95% CI -0.30 to -0.09; I² = 59%) at follow-up. After treatment headache frequency at least halved in 50% of participants receiving true acupuncture and 41% receiving sham acupuncture (pooled RR 1.23, 95% CI 1.11 to 1.36; I² = 48%; 14 trials, 1825 participants) and at follow-up in 53% and 42%, respectively (pooled RR 1.25, 95% CI 1.13 to 1.39; I² = 61%; 11 trials, 1683 participants; moderate quality evidence). The corresponding NNTBs are 11 (95% CI 7.00 to 20.00) and 10 (95% CI 6.00 to 18.00), respectively. The number of participants dropping out due to adverse effects (odds ratio (OR) 2.84; 95% CI 0.43 to 18.71; 7 trials, 931 participants; low quality evidence) and the number of participants reporting adverse effects (OR 1.15; 95% CI 0.85 to 1.56; 4 trials, 1414 participants; moderate quality evidence) did not differ significantly between acupuncture and sham groups. Comparison with prophylactic drug treatmentAcupuncture reduced migraine frequency significantly more than drug prophylaxis after treatment ( SMD -0.25; 95% CI -0.39 to -0.10; 3 trials, 739 participants), but the significance was not maintained at follow-up (SMD -0.13; 95% CI -0.28 to 0.01; 3 trials, 744 participants; moderate quality evidence). After three months headache frequency at least halved in 57% of participants receiving acupuncture and 46% receiving prophylactic drugs (pooled RR 1.24; 95% CI 1.08 to 1.44) and after six months in 59% and 54%, respectively (pooled RR 1.11; 95% CI 0.97 to 1.26; moderate quality evidence). Findings were consistent among trials with I² being 0% in all analyses. Trial participants receiving acupuncture were less likely to drop out due to adverse effects (OR 0.27; 95% CI 0.08 to 0.86; 4 trials, 451 participants) and to report adverse effects (OR 0.25; 95% CI 0.10 to 0.62; 5 trials 931 participants) than participants receiving prophylactic drugs (moderate quality evidence). AUTHORS' CONCLUSIONS: The available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches. Contrary to the previous findings, the updated evidence also suggests that there is an effect over sham, but this effect is small. The available trials also suggest that acupuncture may be at least similarly effective as treatment with prophylactic drugs. Acupuncture can be considered a treatment option for patients willing to undergo this treatment. As for other migraine treatments, long-term studies, more than one year in duration, are lacking.

Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study.

BACKGROUND: Uncontrolled studies in human have suggested that memantine might be a suitable option for migraine prophylaxis. OBJECTIVE: To assess the efficacy and tolerability of memantine for migraine prophylaxis. METHODS: This was a 12-week randomized double-blind placebo-controlled parallel-group study. Sixty patients with migraine without aura were randomized using a computer-generated list to receive memantine (10 mg/day) or placebo for 12 weeks. The primary outcome was the difference in change from baseline in the monthly attack frequency at week 12 between the two groups (using migraine diary). Secondary efficacy measures were assessed using several clinical, functional, and psychological instruments. We performed both complete case (CC) and intention-to-treat analyses (ITT). RESULTS: Twenty-five patients in the memantine group and 27 patients in the placebo group completed the study. Patients in the memantine group showed significantly greater reduction (mean change; 3.4; 95%CI, 2.3-4.4) in the monthly attack frequency than the placebo group (mean change, 1.0; 95%CI, 0.3-1.7) (mean difference [MD], 2.3; 95%CI, 1.1-3.5, P < .001). Both CC (MD, 4.9; 95%CI, 2.6-7.2 days), and ITT analyses (MD, 5.2; 95%CI, 2.0-8.5) showed significantly higher reduction in the mean number of migraine days in the memantine group than the placebo group (P < .01). Patients in the memantine group experienced greater reduction in the number of work absence days, severity, and disability score than the patients in the placebo group in both ITT and CC analyses. Changes in quality of life, sleep, depression, and anxiety did not differ between the two groups. Three patients in the memantine group complained of sedation, mild vertigo and nausea, and drowsiness. In the placebo group, one patient complained of nausea and another patient discontinued treatment after 2 weeks due to vertigo. CONCLUSION: Memantine might be a tolerable and efficacious option for prophylaxis in patients with migraine without aura. Tolerability, short duration required for titration, and safety profile in pregnancy might give memantine an advantage over other antimigraine medications. The study was registered in the Iranian Registry of Clinical Trials (Registration number: IRCT2013120115616N1).

Safety and efficacy of melatonin in pediatric migraine prophylaxis.

OBJECTIVE: Preventive therapy in migraine must be started with frequent or disabling headaches in children, while, no drugs have been approved for migraine preventive therapy of them up to now. The aim of the present research was to investigate safety and efficacy of melatonin in pediatric migraine prophylaxis. METHODS: In a quasi- experimental study, monthly frequency, severity and duration of headache, migraine disability and clinical side effects in sixty migraineur referred children to Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd, Iran from January to June 2013 whom were treated with single dose of 0.3 mg/kg melatonin for three months, were evaluated. RESULTS: Thirty two (53.3%) girls and 28(46.7%) boys with mean age of 10.31 ± 2.39 years were evaluated, 38 of whom (63.3%) had migraine without aura. Clinical adverse events were seen in 23.3% (N=14) of children including sleepiness in seven, vomiting in four, mild hypotension in two and constipation in one child. Excessive daytime sleepiness as a serious side effect was seen in three children which caused the drug use to be stopped. Monthly frequency, severity and duration of headache reduced from 15.63 ± 7.64 to 7.07 ± 4.42 attacks, from 6.20 ± 1.67 to 3.55 ± 2.11 scores, and from 2.26 ± 1.34 to 1.11 ± 0.55 hours, respectively. Pediatric Migraine Disability Assessment score decreased from 31.72 ± 8.82 to 17.78 ± 10.64. (All p < 0.05). CONCLUSION: Melatonin might be considered as an effective and without life-threatening side effects drug in prophylaxis of migraine in children.

Prostaglandins and prostaglandin receptor antagonism in migraine.

Human models of headache may contribute to understanding of prostaglandins' role in migraine pathogenesis. The current thesis investigated the migraine triggering effect of prostaglandin E2 (PGE2) in migraine patients without aura, the efficacy of a novel EP4 receptor antagonist, BGC20-1531, in prevention of PGE2-induced headache and the ability of prostaglandin F2α (PGF2α) to trigger headache without any vasodilatation in healthy volunteers. All studies were designed as double-blind, placebo-controlled, cross-over experiments, where PGE2/PGF2α or saline were infused over 20-25 min. In the study with EP4 receptor antagonist healthy volunteers were pre-treated with two different doses of BGC20-1531 or placebo followed by PGE2 infusion over 25 min. The headache data were collected during the whole study day, whereas the possible vascular changes were measured during the in-hospital phase of 1.5 h. The infusion of PGE2 caused the immediate migraine-like attacks and vasodilatation of the middle cerebral artery in migraine patients without aura. The highly specific and potent EP4 receptor antagonist, BGC20-1531, was not able to attenuate PGE2-induced headache and vasodilatation of both intra- and extra-cerebral arteries. The intravenous infusion of PGF2α did not induce headache or statistically significant vasoconstriction of cerebral arteries in healthy volunteers. Novel data on PGE2-provoked immediate migraine-like attacks suggest that PGE2 may be one of the important final products in the pathogenesis of migraine. The lack of efficacy of EP4 receptor antagonist suggests that a single receptor blockade is not sufficient to block PGE2 responses, hence EP2 receptor should be investigated as a potential drug target for the treatment of migraine. The absence of headache during the PGF2α infusion demonstrates that vasodilating properties are necessary for the induction of headache and migraine.

Acupuncture versus valproic acid in the prophylaxis of migraine without aura: a prospective controlled study.

BACKGROUND: The pharmacologic treatment of migraine still remains below the expectations. The aim of this study is to compare the effectiveness of traditional acupuncture and valproic acid in migraine prophylaxis. METHODS: A prospective, controlled study was performed in 100 patients affected by migraine without aura lasting for over one year. The patients were stratified for sex and randomly divided into two groups of 50 patients each. Patients belonging to Group A (acupuncture) were submitted to 20 sessions of acupuncture, while patients belonging to Group V valproate) were administered Valproic acid (Depakin Chrono®) at a dose of 600 mg/day; 10 mg Rizatriptan wafers were allowed as needed to treat the attacks. The Midas Index (MI) and pain intensity (PI, by VAS) were recorded before treatment (T0), at three (T1) and six (T2) months; a six-point scale Pain Relief score (PRS), the Rizatriptan intake and adverse events were recorded at T1 and T2. RESULTS: Eighty-two out of 100 patients completed the study (9 dropouts in each group). In both groups the MI improved at T1 and T2 (P<0.0001). Pain intensity was better at T1 in group V (P<0.0001), but PI and PRS (P=0.02) as well as rizatriptan intake (P=0.001) were better in group A at T2. The rate of adverse events was 47.8% in group V and 0% in group A. CONCLUSION: Our data show a lower pain intensity and lower Rizatriptan intake at six-months follow-up with no adverse events in acupuncture patients compared to those treated with valproic acid.

[Modern methods of neurovisualization and preventive treatment of migraine].

Forty-eight patients have been examined in the Centre of Headache Treatment. MRI of the brain revealed the changes in the white matter in 69% of patients, 39% had multiple foci (more than 3). The largest number of foci was seen in patients with frequent and chronic migraine without aura, but not in those with migraine with aura. The foci were located more often in frontal areas and less often in parietal and temporal areas. Twenty-three patients with frequent and chronic migraine received the preventive treatment with the anticonvulsant topiramate (topamax, capsules 25 and 50 mg). The duration of treatment was from 4 to 12 months depending on the disease severity. The decrease in frequency of migraine attacks was seen after 1 month of the treatment. After 6 months, mean score on the MIDAS decreased from 26.5 that indicated the severity of migraine and significant decrease in working capacity to 5.7 that corresponded to the mild form of migraine.

"Alice in Wonderland syndrome" associated with topiramate for migraine prevention.

Various visual and sensory phenomena have been described in migraine with aura. Among those, the 'Alice in Wonderland' syndrome is defined as a distortion of the body image with the patient being aware of its unreal nature. Here, the case of a 17-year-old girl with migraine without aura who developed an 'Alice in Wonderland' syndrome repeatedly on topiramate treatment was presented and potential pathophysiological concepts were discussed.

Perimenstrual migraines and their response to preventive therapy with topiramate.

INTRODUCTION: Preventive treatment with topiramate is effective for overall reduction of migraine frequency, but there are few data regarding its efficacy on perimenstrual migraines. To determine whether topiramate can prevent perimenstrual migraines, we analyzed data from premenopausal women as a subgroup of the Prolonged Migraine Prevention with Topiramate (PROMPT) study. METHODS: In total, 198 women from the PROMPT study with menstrually related migraine (MRM) were evaluated. After a one-to-two-month prospective baseline period, patients received open-label topiramate (50-200 mg/day) for six months. RESULTS: During topiramate treatment, mean monthly migraine frequency was reduced from 7.03 at baseline to 4.36 (mean change: -2.66; p < .001, endpoint analysis). Mean percentage reductions were similar for migraines during and outside the perimenstrual period (-45.9% and -46.1%, respectively). In patients with aura, reductions in migraine days with (-48.3%) or without (-43.4%) aura were similar to those in patients without aura (-45.4%). Reductions were also similar whether women were taking combined oral contraceptives (-47.0%) or were not (-46.6%). CONCLUSIONS: Topiramate reduces the frequency, but not severity or duration, of perimenstrual migraines in women with MRM, including migraines with and without aura, and regardless of combined oral contraceptive use.

On the methodology of drug trials in migraine with aura.

INTRODUCTION: Specific problems occur in clinical treatment trials for migraine with aura that differ from those encountered in treatment trials for migraine without aura. DISCUSSION: Based on our experience with four such trials, we point to a number of possible solutions and outline areas for future inquiry. We make recommendations about subject selection; the choice, definition and assessment of outcome measures; optimal treatments in relation to aura and headache; and we provide samples of study report forms used to record occurrence of aura and headache in this population.

Treating headache recurrence after emergency department discharge: a randomized controlled trial of naproxen versus sumatriptan.

STUDY OBJECTIVE: Multiple parenteral medications are used to treat migraine and other acute primary headaches in the emergency department (ED). Regardless of specific headache diagnosis, no medication eliminates the frequent recurrence of primary headache after ED discharge. It is uncertain which medication primary headache patients should be given on discharge from an ED. The aim of this study is to compare the efficacy of oral sumatriptan with naproxen for treatment of post-ED recurrent primary headache. METHODS: This was a randomized, double-blind efficacy trial. We randomized patients to either naproxen 500 mg or sumatriptan 100 mg for headache recurrence after ED discharge. Patients were eligible if they received parenteral therapy for an acute exacerbation of a primary headache in the ED. Patients who met established criteria for migraine without aura were designated a priori as a homogenous subgroup of interest. We followed all patients by telephone 48 hours after ED discharge. The primary endpoint was the between-group difference in change in pain intensity during the 2-hour period after ingestion of either 500 mg naproxen or 100 mg sumatriptan. This difference was measured on a validated 11-point (0 to 10) verbal numeric rating scale (NRS). Satisfaction with the medication and adverse effects were also assessed. Patients who met criteria for migraine without aura were analyzed twice according to a priori design: once as a homogenous subgroup and then again combined with all other primary headaches. RESULTS: Of 410 patients randomized, 383 (93%) had outcome data available for analysis. Two hundred eighty (73%; 95% confidence interval [CI] 68% to 77%) reported headache post-ED discharge and 196 (51%; 95% CI 44% to 58%), including 88 with migraine, took the investigational medication provided to them. The naproxen group improved by a mean of 4.3 NRS points, whereas the sumatriptan group improved by 4.1 points (95% CI for difference of 0.2 points: -0.7 to 1.1 points). Findings were virtually identical among the migraine subset (4.3 versus 4.2 NRS points; 95% CI for difference of 0.1 points: -1.3 to 1.5 points). Seventy-one percent (95% CI 62% to 80%) of naproxen patients and 75% (95% CI 66% to 84%) of sumatriptan patients would want to take the same medication the next time. Adverse effect profiles were also comparable. CONCLUSION: In this trial, nearly three quarters of patients reported headache recurrence within 48 hours of ED discharge. Naproxen 500 mg and sumatriptan 100 mg taken orally relieve post-ED recurrent primary headache and migraine comparably. Clinicians should be guided by medication costs, contraindications, and a patient's previous experience with the medication.

Primary transcatheter patent foramen ovale closure is effective in improving migraine in patients with high-risk anatomic and functional characteristics for paradoxical embolism.

OBJECTIVES: In the present study, we sought to assess the effectiveness of migraine treatment by means of primary patent foramen ovale (PFO) transcatheter closure in patients with anatomical and functional characteristics predisposing to paradoxical embolism without previous cerebral ischemia. BACKGROUND: The exact role for transcatheter closure of PFO in migraine therapy has yet to be elucidated. METHODS: We enrolled 86 patients (68 female, mean age 40.0 +/- 3.7 years) referred to our center over a 48-month period for a prospective study to evaluate severe, disabling, medication-refractory migraine and documented PFO. The Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine. Criteria for intervention included all of the following: basal shunt and shower/curtain shunt pattern on transcranial Doppler and echocardiography, presence of interatrial septal aneurysm and Eustachian valve, 3 to 4 class MIDAS score, coagulation abnormalities, and medication-refractory migraine with or without aura. RESULTS: On the basis of our inclusion criteria, we enrolled 40 patients (34 females, mean age 35.0 +/- 6.7 years, mean MIDAS 35.8 +/- 4.7) for transcatheter PFO closure; the remainder continued on previous medical therapy. Percutaneous closure was successful in all cases, with no peri-procedural or in-hospital complications. After a mean follow-up of 29.2 +/- 14.8 months (range 6 to 48 months), PFO closure was complete in 95%; all patients (100%) reported improved migraine symptomatology (mean MIDAS score 8.3 +/- 7.8, p < 0.03). Specifically, auras were eliminated in 100% of patients after closure. CONCLUSIONS: Primary transcatheter PFO closure resulted in a very significant reduction in migraine in patients satisfying our criteria.