This study presents the first nationwide survey of migraine in Japan. A representative sample of 4029 subjects aged 15 years or older was selected from the Japanese population according to the quota method. A combination of telephone interview and mailed questionnaire methods was used. Diagnosis of migraine was based on the International Headache Society (IHS) Classification. The overall prevalence of migraine in the past year was 8.4%; 5.8% was migraine without aura and 2.6% was migraine with aura. Significant correlation was found between the prevalence of migraine and such variables as gender, age and district of residence. Doctor attendance rate was very low and 69.4% with migraine had never consulted a physician for headache. Yet, 74.2% complained that migraine headache impaired their daily activity significantly. Only 11.6% were aware that their headache was migraine and 56.9% were using only the over-the-counter drugs. The study revealed a comparably high prevalence of migraine in the general population of Japan compared with other countries. A genetic factor was speculated as the cause of regional difference in migraine prevalence.

Single-photon emission computed tomography (SPECT) was used for the measurement of regional cerebral blood volume (CBV) and hematocrit (Hct) in normal healthy human volunteers (mean age 30 +/- 8 years). Regional cerebral red blood cell (RBC) volume and plasma volume were determined separately and their responses to carbon dioxide were investigated. Ten right-handed healthy volunteers were the subjects studied. SPECT scans were performed following intravenous injection of the RBC tracer (99mTc-labeled RBC) and plasma tracer (99mTc-labeled human serum albumin) with an interval of 48 h. Regional cerebral Hct was calculated as the regional ratio between RBC and plasma volumes and then was used for calculating CBV. Mean regional CBV in the resting state was 4.81 +/- 0.37 ml/100 g brain, significantly greater in the left hemisphere compared with the right by 3.8% (p less than 0.01). Mean regional RBC volumes (1.50 +/- 0.09 ml/100 g brain) were less than mean regional plasma volumes (3.34 +/- 0.28 ml/100 g brain), and mean regional cerebral Hcts were 31.3 +/- 1.8%, which was 75.9 +/- 2.1% of the large-vessel Hct. During 5% CO2 inhalation, increases in plasma volume (2.48 +/- 0.82%/mmHg PaCO2) were significantly greater than for RBC volume (1.46 +/- 0.48%/mmHg PaCO2). Consequently, the cerebral-to-large-vessel Hct ratio was reduced to 72.4 +/- 2.2%. Results emphasize the importance of cerebral Hct for the measurement of CBV and indicate that regional cerebral Hcts are not constant when shifted from one physiological state to another.

Magnetic resonance imaging (MRI) was studied in 91 patients with migraine and in 98 controls. Risk factors known to cause MRI lesions were carefully examined. In 36 patients with migraine (39.6%), small foci of high intensity on T2-weighted and proton-density-weighted images were seen in the white matter. Of patients with migraine who were less than 40 years old and without any risk factor, 29.4% showed lesions on MRI; this was significantly higher than the 11.2% for the group of age-matched controls (n = 98). The lesions were distributed predominantly in the centrum semiovale and frontal white matter in young patients, but extended to the deeper white matter at the level of basal ganglia in the older age group. The side of the MRI lesions did not always correspond to the side of usual aura or headache. Migraine-related variables such as type of migraine, frequency, duration or intensity of headache or consumption of ergotamine showed no significant correlation with the incidence of MRI abnormalities. Our data indicated that migraine may be associated with early pathologic changes in the brain.

Objective To determine the efficacy and safety of fremanezumab administration in Japanese and Korean patients with chronic migraine (CM). Background Available preventive treatments for CM are limited by various efficacy and safety issues. Fremanezumab, a monoclonal antibody that targets the calcitonin gene‐related peptide pathway involved in migraine pathogenesis, has been shown to be effective and well tolerated in large‐scale, international Phase 3 trials. Methods Randomized, placebo‐controlled trial of patients with CM who received subcutaneous fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. Primary endpoint was the mean change from baseline in the monthly (28‐day) average number of headache days of at least moderate severity during the 12 weeks after the first dose. Results Among 571 patients randomized (safety set, n = 569; full analysis set, n = 566), the least‐squares mean (±standard error [SE]) reduction in the average number of headache days of at least moderate severity per month during 12 weeks was significantly greater with fremanezumab monthly (–4.1 ± 0.4) and fremanezumab quarterly (–4.1 ± 0.4) than with placebo (–2.4 ± 0.4). The difference from the placebo group in the mean change (95% confidence interval [CI]) was −1.7 days (−2.54, −0.80) for the fremanezumab monthly group and −1.7 days (−2.55, −0.82) for the fremanezumab quarterly group (p < 0.001 vs. placebo for both fremanezumab groups). The percentage of patients with a ≥50% reduction in the average number of headache days of at least moderate severity per month (response rate) was higher with fremanezumab monthly (29.0%) and fremanezumab quarterly (29.1%) than with placebo (13.2%) in addition to other improvements in secondary endpoints, including reduction of acute medication use (mean change from baseline during 12‐week period ± SE: fremanezumab monthly, –3.7 ± 0.4; fremanezumab quarterly, –3.9 ± 0.4; placebo, –2.4 ± 0.4) and improvements in disability scores (mean change from baseline in six‐item Headache Impact Test score at 4 weeks after third injection ± SE: fremanezumab monthly, –8.1 ± 0.7; fremanezumab quarterly, –8.0 ± 0.7; placebo, –6.5 ± 0.7). Fremanezumab was well tolerated with a similar incidence of adverse events including injection‐site reactions as placebo (patients with at least one treatment‐emergent adverse event: fremanezumab total, n = 232 [61.4%]; placebo, n = 118 [61.8%]). Conclusion Fremanezumab effectively prevents CM in Japanese and Korean patients and was well tolerated. No safety signal was detected.

The aim of this study is to report a possible implication of augmented vasogenic leakage in the mechanism of prolonged aura in sporadic hemiplegic migraine. A 35-year-old woman with sporadic hemiplegic migraine presented with headache followed by right arm weakness, right visual field defect, aphasia and confusion that persisted for 1 week. During the acute stage, focal hyperaemia was seen in the left cerebral hemisphere corresponding to persistent aura symptoms. Augmented vasogenic leakage was demonstrated on delayed enhanced fluid-attenuated inversion recovery image. Magnetic resonance angiography showed dilation of the left middle cerebral artery. During the convalescent stage, such abnormal findings were not seen. Based on these results, we speculate that augmented vasogenic leakage from the leptomeningeal vessels, probably associated with activation of the trigeminovascular system, may delay the recovery of hemiplegic migraine aura.

A preliminary study was undertaken to provide clinical evidence to support the hypothesis that: "Migraine with aura, migraine without aura and aura alone are the same condition, which differ in degree rather than pathophysiology." At the City of London Migraine Clinic, 50 patients consecutively attending the clinic with a past or present history of migraine with aura were questioned. Of the 50 patients questioned 36 (70%) had a combination of migraine with aura, migraine without aura and/or aura alone; i.e. 70% had had more than one type of migraine attack. The duration, severity and frequency of attacks did not differ between migraine with and migraine without aura. Conclusion--the results support the hypothesis that migraine with and migraine without aura, and aura alone are not separate conditions, because: (1) most patients suffer from more than one type of migraine attack; (2) there are no significant differences in the characteristics of the migraine attacks in the different groups; (3) there are no significant differences in the characteristics of the subjects.

International Headache Society published the International Classification of Headache Disorders 2nd Edition (ICHD‐II) in 2004. In response to this development, the “Clinical Practice Guideline for Chronic Headache” was compiled in Japan by the Study Group for Chronic Headache Clinical Practice Guideline Development. In 2006, the book entitled “The Clinical Practice Guideline for Chronic Headache (edited by Japanese Headache Society)” was published as the first edition. As triptans have become widely used, clinical practice for chronic headache has also been changed in Japan and there was a need to revise the first edition. Essentially based on the first edition, the new guideline has added the latest information and presented the concept of international standards of chronic headache care. This guideline included eight chapters and appendix: I. headache: general considerations, II. migraine, III. tension‐type headache, IV. trigeminal autonomic cephalalgias, V. other primary headache disorders, VI. medication‐overuse headache, VII. headaches in children, and VIII. genetics. We have published the second version in Japanese in 2013, but 1 month after we published the original guideline, the International Classification of Headache Disorders 3rd Edition beta version (ICHD‐3beta) was published. We changed this guideline to the new version in English based on ICHD‐3beta. This guideline is the final product of the Committee's efforts in 2015, which was opened in the home page of the Japanese Headache Society. This manuscript was written to show the main part of this guideline as Recommendation of each CQ. Among 121 CQs, only five CQ was selected to present full sentences including not only Recommendation but also other parts.

Objectives To assess the impacts of social situation changes due to the coronavirus disease 2019 (COVID-19) pandemic on headache-related disability and other symptoms in patients with migraine in Japan. Methods We conducted a multicentre, cross-sectional study including 659 outpatients with migraine diagnosed by headache specialists. The participants were asked about the impacts of the first wave of the COVID-19 pandemic on headache-related disability, headache days, headache intensity, stress, physical activity, hospital access and their work and home lives. For headache-related disability, the total Migraine Disability Assessment (MIDAS) score and part A and B scores were analysed. Multivariate stepwise linear regression analysis was performed to identify the clinical predictors of changes in the total MIDAS score before and during the COVID-19 pandemic. Logistic regression analysis was performed to determine the factors related to new-onset headache during the COVID-19 pandemic. Results Finally, 606 migraine patients (73 M/533 F; age, 45.2 ± 12.0 years) were included in the study, excluding those with incomplete data. Increased stress, substantial concern about COVID-19 and negative impacts of the first wave of the COVID-19 pandemic on daily life were reported in 56.8 %, 55.1 and 45.0 % of the participants, respectively. The total MIDAS and A and B scores did not significantly change after the first wave of the COVID-19 pandemic. New-onset headache, which was observed in 95 patients (15.7 %), was associated with younger age and worsened mood and sleep in the logistic regression analysis. The multivariate stepwise linear regression analysis of changes in the total MIDAS score before and during the first wave of COVID-19 pandemic identified worsened sleep, increased acute medication use, increased stress, medication shortages, comorbidities, the absence of an aura and new-onset headache were determinants of an increased total MIDAS score during the first wave of the COVID-19 pandemic. Conclusions In this multicentre study, clinical factors relevant to headache-related disability, such as new-onset headache, stress and sleep disturbances, were identified, highlighting the importance of symptom management in migraine patients during the first wave of the COVID-19 pandemic.