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Purpose: In two 24‐week migraine prevention studies in Japan, erenumab was associated with significantly greater reductions in migraine frequency versus placebo over Weeks 13–24 (primary endpoint). This post hoc analysis evaluated the onset of efficacy within the first 4 weeks after the initiation of erenumab from the 24‐week double‐blind periods of these studies. Methods: Placebo‐adjusted differences in least squares mean (LSM) change from baseline in weekly migraine days (WMD) were assessed weekly in each study and by migraine type (episodic (EM]/chronic [CM]) (Study 20170609). Results: A total of 407 patients from Study 20120309 (70 mg: N = 135; 140 mg: N = 136; placebo: N = 136) and 261 patients from Study 20170609 ([EM] 70 mg: N = 78; placebo: N = 81; [CM] 70 mg: N = 52; placebo: N = 50) were included. For Study 20120309, onset of efficacy was observed as early as Week 1 in favor of erenumab versus placebo. Placebo‐adjusted differences in LSM (95% confidence interval [CI]) change from baseline in WMD at Week 1 were −0.38 (−0.71 to −0.05; p =.022) and −0.49 (−0.82 to −0.16; p =.004) in favor of erenumab 70 and 140 mg, respectively. For Study 20170609, significant placebo‐adjusted differences were observed with erenumab 70 mg at Week 1 in patients with EM (LSM [95% CI]: −0.55 [−0.97 to −0.12; p =.012]), and at Week 2 in patients with CM (LSM [95% CI]: −0.81 [−1.53 to −0.09; p =.028]) and for the overall population (LSM [95% CI]: −0.71 [−1.09 to −0.33; p <.001]). Conclusions: Erenumab treatment significantly reduced WMD compared with placebo. Onset of erenumab efficacy occurred as early as Week 1 in patients with migraine. [ABSTRACT FROM AUTHOR]

Introduction: The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) assessed the impact and burden of migraine in Japan. Methods: OVERCOME (Japan) was a cross-sectional, observational, population-based web survey of Japanese people with migraine conducted between July and September 2020. The burden and impact of migraine were assessed using the Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), and Work Productivity and Activity Impairment-Migraine scale. Results were stratified by average number of monthly headache days (0–3, 4–7, 8–14, ≥ 15). Results: In total, 17,071 Japanese people with migraine completed the survey. Of these, 14,033 (82.2%) met International Classification of Headache Disorders, 3rd edition criteria for migraine and 9667 (56.6%) reported a physician diagnosis of migraine. Overall, 20.7% of respondents experienced moderate-to-severe disability (MIDAS). Moderate-to-severe interictal burden (MIBS-4) was experienced by 41.5% of respondents. MSQ scores in all domains were lowest in respondents with the most frequent headaches (≥ 15 monthly headache days) and highest in those with the lowest frequency headaches (≤ 3 monthly headache days), indicating poorer quality of life in those with more frequent headaches. Work time missed due to migraine (absenteeism) increased with increasing headache frequency, from 3.8 to 6.2%; presenteeism affected 29.8–49.9% of work time. Although migraine burden was greatest in people with the most frequent headaches, those with the lowest headache frequency still experienced substantial disability, interictal burden, and impacts on productivity and quality of life. There was also substantial unmet need for migraine care: 36.5% of respondents had ever hesitated to seek medical care for their headaches, and 89.8% had never used preventive medication. Conclusion: In Japan, the burden of migraine and barriers to migraine care are substantial. Improving patient awareness and healthcare provider vigilance may help improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Primary brain calcification (PBC) is a rare neurodegenerative disorder characterized by bilateral calcification in the brain. No nationwide survey on headache has been performed in Japan. Aim: A questionnaire survey was performed to clarify the situation of headache in PBC patients. Methods: The first questionnaire survey was conducted on 173 patients diagnosed as having PBC in Japan. Subsequently, the second survey was performed using two types of questionnaire: Headache Impact Test (HIT‐6) and Migraine Disability Assessment (MIDAS). Results: In the first survey, 27 of 82 patients had headaches. Only one patient was able to be classified in accordance with the criteria as having migraine without aura. In the second survey, 10 of 17 patients showed a significant score of 50 and higher in HIT‐6, and five of 17 patients showed a significant score of 6 and higher in MIDAS. No significant correlation was found between total calcification score and HIT‐6 score or MIDAS score in the second survey. All patients carrying the PDGFB variant and two of three patients carrying the SLC20A2 variant showed some effects of headache on their daily life as judged from their MIDAS scores or HIT‐6 score. Conclusions: The headaches in PBC patients could not be classified as the primary headache. Those headaches in PBC patients may be of the secondary headache caused by the dysfunction of the blood‐brain barrier. This first report on headaches of Japanese patients with PBC will contribute to the understanding of PBC patients' difficulties in their daily lives. [ABSTRACT FROM AUTHOR]

Objective: Restless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.Methods: We combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.Results: The post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m2) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.Conclusions: Our results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment. [ABSTRACT FROM AUTHOR]

Introduction: Migraine attacks notably impact people's daily lives, health-related quality of life (HRQoL), and ability to work. Triptans are widely used as acute medication for a migraine attack but are ineffective, poorly tolerated, or contraindicated in some patients. HRQoL and work productivity are therefore likely to pose particular problems for patients whose migraine attacks do not respond sufficiently to triptan acute treatment. This real-world study aimed to determine whether migraine-related HRQoL, disability, and work productivity differed between triptan insufficient responders (TIRs) and sufficient responders (TSRs) receiving this acute treatment for migraine in Japan. Methods: This was a retrospective analysis of 2017 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting patients with migraine in Japan. Patients had to be receiving a triptan as their sole acute prescribed medication for migraine. TIRs were defined as patients who achieved headache pain freedom within 2 h of taking triptan acute treatment in no more than three of five migraine attacks. Differences in outcomes between TIRs and TSRs were examined in adjusted analyses using a multivariable general linear model. Results: Of 200 patients receiving a triptan as their sole prescribed acute treatment for migraine, 88 (44.0%) were classed as TIRs. Migraine-Specific Quality of Life Questionnaire scores were significantly lower—indicating poorer HRQoL—among TIRs than TSRs, as were mean EuroQol 5-dimension utility and visual analog scale scores (p < 0.05 for comparisons). TIRs also reported significantly (p ≤ 0.003) greater impairment than TSRs across all Work Productivity and Activity Impairment domains, with the exception of work time missed. Migraine disability was higher among TIRs than TSRs. Conclusion: Migraine attacks had a negative impact on the HRQoL, disability, and work productivity of people with migraine in Japan reporting insufficient efficacy with acute triptan treatment, highlighting the need for more effective acute treatment options. [ABSTRACT FROM AUTHOR]

Background: Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. Methods: In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. Results: The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Conclusions: Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients. [ABSTRACT FROM AUTHOR]

Aims: To assess the safety and efficacy of pramipexole in Japanese patients with restless legs syndrome (RLS) and to investigate factors predictive of early treatment response. Methods: Patients with primary RLS and the International Restless Legs Syndrome Study Group rating scale (IRLS) total score of >15 were randomized to receive pramipexole 0.25, 0.5 or 0.75 mg/day for 6 weeks. Results: A total of 154 patients were recruited. Following treatment, the mean adjusted change in IRLS score in the 0.25, 0.5 and 0.75 mg/day groups was -12.3, -12.5 and -11.8, respectively. The proportion of IRLS responders at week 2, when all patients were receiving pramipexole at a dose of 0.25 mg/day, was 34.0-37.7%. At 6 weeks, when the patients were on 0.25, 0.5 or 0.75 mg/day, IRLS responders defined as those having a ≥50% reduction in IRLS score accounted for 60.4, 58.5 and 49.1%, respectively. Older age above the median value (≥55 years) and low IRLS score at baseline (<21.5 points) were significantly associated with early response to low-dose pramipexole therapy. The type and frequency of adverse events were consistent with the known safety profile for dopamine agonists in RLS. Conclusions: Pramipexole at 0.25-0.75 mg/day is efficacious, safe and well tolerated in Japanese patients with primary RLS. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 × 10−12, odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 × 10−6, odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis. [ABSTRACT FROM AUTHOR]

Poststroke depression (PSD) has an important impact on the quality of life of patients with stroke. We studied 100 stroke patients (mean age ± SD: 64.6 ± 11.6, range: 32–85 years) in the subacute phase (2–5 weeks after onset) and investigated the prevalence and clinical correlates of PSD in the subacute phase. The prevalences of PSD and major depression in the subacute phase evaluated by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were 20.0 and 5.0%, respectively. These values were lower than those reported in Caucasian studies. The Zung Self-Rating Depression Scale (SDS) did not underestimate the presence of PSD and was thus considered valuable for the initial screening of PSD. However, SDS may overestimate PSD especially in patients with anxiety disorders or somatoform disorders and vice versa. Apathy was observed in 40.2% of patients; however, it was widely distributed and observed even in patients without serious depression. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objective: We aimed to ascertain the efficacy and safety of transdermal rotigotine (2 and 3mg/24h) in Japanese patients with restless legs syndrome (RLS). Methods: In our double-blind placebo-controlled study, 284 Japanese patients with idiopathic RLS were randomly assigned to receive rotigotine 2mg/24h or 3mg/24h, or placebo, for 13weeks. The primary endpoint was the change in International Restless Legs Syndrome Study Group rating scale (IRLS) total score. Results: The placebo-subtracted decreases in IRLS total score for rotigotine 2mg/24h and 3mg/24h were −2.8±1.3 and −3.1±1.3, respectively, which were significant (P <0.05). The interaction between baseline Pittsburgh Sleep Quality Index (PSQI) and treatment group for the change in IRLS total score was significant, indicating greater improvements in IRLS total score in patients with severe insomnia. Overall, 80.0%, 86.2%, and 51.6% of patients in the rotigotine 2mg/24h, 3mg/24h, and placebo groups, respectively, experienced adverse events (AEs) including application site reactions in 42.1%, 50.0%, and 7.4% of patients, respectively. None of the AEs were severe. Conclusions: Our results showed that rotigotine was effective without major safety concerns at doses of up to 3mg/24h in Japanese patients with RLS. [Copyright &y& Elsevier]

Abstract: A phase III, open-label, long-term clinical study was performed to evaluate the safety and efficacy of pramipexole in a cohort of 141 Japanese patients with primary restless legs syndrome (RLS). The patients were started on pramipexole 0.25mg/day and were subsequently maintained on that dose or switched to 0.125, 0.5, or 0.75mg/day to achieve optimal efficacy and tolerability. The International Restless Legs Syndrome Study Group Rating Scale for restless legs syndrome (IRLS) score improved from 22.3±4.7 at baseline to 11.1±7.7 at week 8 and 4.9±5.9 at week 52. IRLS responders, defined as patients whose IRLS total score decreased by ≥50% from baseline, accounted for 67.4% at week 12 and 86.6% at week 52. Over 90% of patients were Clinical Global Impression-global improvement (CGI-I) and Patient Global Impression (PGI) responders. The Pittsburgh Sleep Quality Index (PSQI) score decreased from 7.9±3.1 at baseline to 4.6±2.9 at week 52. Similarly, the Japanese version of the Epworth Sleepiness Scale score decreased from 9.3±5.2 to 4.9±3.8. Baseline IRLS score ≤20 was significantly associated with a complete IRLS response in this long-term study. Adverse events were typical of nonergot dopamine agonists, mild in intensity, and decreased in frequency as the study progressed. RLS augmentation was not observed. Pramipexole 0.25–0.75mg/day is efficacious, safe, and well tolerated in patients with RLS. Pramipexole showed good efficacy, particularly in patients with an IRLS total score <20. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study was to assess the validity and the reliability of the Japanese version of the Parkinson''s disease sleep scale (PDSS)-2 and to use this scale to identify nocturnal symptoms and their impact on patient''s quality of life. Methods: A cross-sectional, case-controlled study was conducted consisting of 93 patients with Parkinson''s disease (PD) and 93 age- and gender-matched control subjects. The Japanese version of the PDSS-2 was used for the evaluation of nocturnal disturbances. The patient''s quality of life was evaluated with the Parkinson''s Disease Quality of Life questionnaire (PDQ-39) and their depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II), respectively. In addition, the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Parkinson Fatigue Scale (PFS) were administered. Results: As assessed using the PDSS-2, PD patients had significantly impaired scores compared with control subjects (15.0±9.7 vs. 9.1±6.6, p <0.001). The ESS, BDI-II and PFS scores were significantly impaired in PD patients compared with controls. A satisfactory internal consistency and test–retest reliability score were obtained for the PDSS-2 total score (Cronbach''s alpha=0.86). The PDSS-2 was correlated with the PSQI, ESS, BDI-II, PFS, PDQ-39 summary index, all of the PDQ-39 domains and Unified Parkinson''s Disease Rating Scale part III. The frequency of restless legs syndrome (RLS) was not significantly different between PD patients and controls (5.5% vs. 2.2%), but nocturnal restlessness was significantly more frequent in PD patients than controls. Stepwise linear regression analyses revealed the PDQ-39 summary index and the PSQI global score as significant predictors for the PDSS-2 total score. Conclusions: Our study confirmed the usefulness of the Japanese version of the PDSS-2 that enables the comprehensive assessment of nocturnal disturbances in PD. The association between RLS and nocturnal restlessness in PD requires further study. [Copyright &y& Elsevier]

Abstract: Background: REM sleep behavior disorder (RBD) is a parasomnia characterized by intermittent loss of normal skeletal muscle atonia during REM sleep and elaborate motor activity associated with dream mentation. Idiopathic RBD (iRBD) has a known association with neurodegenerative diseases such as synucleinopathies. Recently, a specific screening scale for assessment of REM sleep behavior disorder (RBDSQ) was validated. Detection of RBD using a Japanese version of the RBDSQ would be useful in the stepwise diagnostic process. We investigated the validity and reliability of a Japanese version of this instrument, the RBDSQ-J. Methods: Subjects were 52 patients with iRBD diagnosed according to criteria in the International Classification of sleep disorders, second edition, 55 obstructive sleep apnea syndrome (OSAS) patients who responded well to CPAP therapy after a diagnosis of RBD was ruled out by history and polysomnography (PSG) and 65 healthy subjects. Results: An RBDSQ-J score cut-off of 5.0 was considered useful for differentiating the iRBD group from the healthy subjects or the OSAS group. Cronbach’s alpha for the entire RBDSQ-J was 0.866. Conclusion: The RBDSQ-J had high sensitivity, specificity, and reliability and would be applicable as a screening method for iRBD in the elderly Japanese population. [Copyright &y& Elsevier]