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.