論文

Purpose: To evaluate the real-world effectiveness and safety of satralizumab over 2.5 years using medical data charts of satralizumab-treated Japanese patients with aquaporin-4 immunoglobulin-G seropositive neuromyelitis optica spectrum disorder (AQP4[+] NMOSD). Major findings: Overall, 124 patients were evaluated (mean ± standard deviation: age, 51.1 ± 14.0 years; disease duration, 7.0 [6.0] years). At baseline, 72.6%, 16.9%, and 35.5% of patients received oral glucocorticoids (GCs), azathioprine (AZA), and tacrolimus (TAC), respectively. The annualized relapse rate (ARR [95% confidence interval]) decreased from 0.45 (0.34–0.58) within 52 weeks before satralizumab initiation to 0.03 (0.02–0.07) after 130 weeks of satralizumab initiation; relapse-free rate was 91.8% at 130 weeks. Nine patients had nine relapses; seven were re-administered satralizumab after relapse. At 130 weeks, 48.8% of relapse-free patients were not receiving oral GCs (89.3% received ⩽5 mg/day); mean oral GC dose reduced from 10.3 to 2.5 mg/day. In patients receiving AZA and TAC at baseline, 80.0% and 47.1% were no longer receiving AZA and TAC at 130 weeks, respectively. Serious drug reactions occurred in 9.7% of patients (serious infections, 6.5%). Conclusion: The real-world relapse-free rate at 2.5 years was 91.8% (ARR = 0.03) in satralizumab-treated patients with AQP4[+] NMOSD, supporting the relapse-preventive effect of satralizumab without new safety concerns. Registration number: UMIN000050027

Introduction: The thyrotropin-releasing hormone (TRH) analog protirelin has short-term benefits for cerebellar ataxia (CA), but its long-term efficacy and the subtype-specific responsiveness of spinocerebellar degeneration (SCD) patients remain unclear. Methods: We retrospectively reviewed the records of 92 SCD patients (273 courses) treated with protirelin between July 2011 and October 2025, including patients with idiopathic CA (IDCA), multiple system atrophy with predominant CA (MSA-C) or parkinsonism (MSA-P), and genetic subtypes including spinocerebellar ataxia (SCA) type 6, SCA31 and dentatorubral-pallidoluysian atrophy (DRPLA). Responders were defined as showing ≥1-point improvement on the Scale for the Assessment and Rating of Ataxia (SARA). Results: Protirelin was effective in 64.1% of subjects, with significant improvement overall (p < 0.001) and significant SARA gains in MSA-C (p = 0.047), IDCA (p = 0.02), and SCA31 (p = 0.01). Change in SARA score (ΔSARA) correlated negatively with age and positively with total protirelin dose in IDCA, and negatively with age and disease duration and positively with baseline SARA score in SCA31. Several IDCA and DRPLA patients maintained clinical benefit for more than 10 years. All MSA-P discontinued protirelin within 2 years and all MSA-C within 5 years; some SCA6, and SCA31 patients continued for ≥5 years. Adverse effects were infrequent (2/92, 2.2%). Conclusion: Protirelin is efficacious in SCD patients and well-tolerated, particularly in slow-progressing phenotypes (IDCA and SCA31); its benefit in rapidly progressing ataxias (MSA-C) may be confined to early disease stages. Prospective studies with standardized dosing and long-term follow-up are warranted to establish evidence-based protocols for TRH-related therapy for CA.

We present the case of a patient who began experiencing cognitive decline in her 30 s and was diagnosed with duplication of the amyloid precursor protein (Dup-APP) associated early-onset Alzheimer's disease (EOAD). The diagnosis was supported by the presence of amyloid and tau biomarkers. The clinical course, neuroimaging findings, and genetic testing excluded other diseases known to cause early-onset cognitive impairment. Our case exhibited a markedly large duplication of 19 Mb and did not present with cerebral amyloid angiopathy. Our findings suggest a potential association between the size of the duplication and the clinical phenotype.

Introduction: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are effective in clinical trials and real-world settings. However, data other than headache frequency remains limited in East Asia. Thus, we investigated long-term efficacy, tolerability, and patient-reported satisfaction of CGRP mAbs in clinical practice. Methods: This single-center observational study included patients with migraine who were administered one of three CGRP mAbs (erenumab, galcanezumab, and fremanezumab) between August 2021 and February 2023. Baseline demographic and headache characteristics were recorded, and treatment outcomes, adverse events, migraine-associated symptoms, and satisfaction levels were assessed over time. Results: We enrolled 150 patients with episodic (n = 81) or chronic migraine (n = 69), including 40 with migraine aura. At six and twelve months, 36/67 (54%) and 22/42 (52%) patients achieved at least 50% reduction in monthly migraine days. Multivariate logistic regression showed that among differences in demographic and headache characteristics between responders and non-responders, the response rate at 3 months was associated with the 6-month response. Migraine-associated symptoms and aura showed improving trends until 5 months after CGRP mAbs initiation. As for safety, injection site reaction was seen in 35/146 (24%), 14/57 (25%), and 4/37 (11%) at 1, 6, and 12 months, respectively. Regarding satisfaction, 74%, 92%, and 94% answered “very satisfied” or “somewhat satisfied” at 1, 6, and 12 months, respectively. Conclusion: This study highlighted the role of early response in predicting the long-term response to CGRP mAbs. We also emphasized the importance of documenting satisfaction, migraine aura frequency, in addition to migraine frequency, for deeper insights into migraine pathophysiology.

Background: Natalizumab (TYSABRIⓇ) is known to be an efficacious treatment at a standard-interval dosing (SID; 300 mg administered intravenously every 4 weeks) for patients with relapsing-remitting sclerosis (RRMS). However, the SID of natalizumab is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Lengthening the time between doses of natalizumab beyond 4 weeks, also known as extended-interval dosing (EID), is associated with lower risk of PML in patients with RRMS, and patients have been switched from SID to EID without meaningful loss of efficacy. In this multicenter, retrospective, observational study, REFIND, we examined real-world natalizumab dosing patterns and MS disease activity in patients with RRMS in Japan. Methods: REFIND retrospectively collected data from medical records of patients at 20 study centers in Japan. Patients with MS aged 20 years and older who received at least one dose of natalizumab after January 1, 2018, and had at least one clinical assessment were included. The primary endpoints were dosing patterns used in clinical practice and MS disease activity by dosing patterns. SID was defined as a mean natalizumab dosing interval ≤35 days, and EID was defined as a mean natalizumab dosing interval ≥36 to ≤84 days. Dosing pattern groups included SID-only, EID-only, or SID followed by EID (SID/EID). For each dosing pattern group, the annualized relapse rate (ARR) before and after administration of natalizumab was compared using a negative binomial regression model. Results: Of the 203 patients with MS eligible for inclusion in the REFIND study, 120 patients with RRMS were treated with natalizumab for ≥1 year, with a mean ± standard deviation (SD) age of 36.0 ± 9.4 years and a mean ± SD administration period of 32.8 ± 18.8 months. Among these patients, 13 had an SID-only natalizumab dosing pattern, 49 had EID-only, and 58 had SID/EID, with mean ± SD dosing intervals of 30.8 ± 1.6 days, 45.9 ± 3.4 days, and 38.7 ± 3.4 days, respectively. Overall ARR 1 year before vs 1 year after initiation of natalizumab was 1.03 vs 0.12 (P < 0.0001). ARR before vs after natalizumab in the SID-only group was 1.08 vs 0.62 (P = 0.378), in the EID-only group was 0.95 vs 0.02 (97.9% reduction, P = 0.0005), and in the SID/EID group was 1.08 vs 0.09 (91.7% reduction, P < 0.0001). Proportions of patients with new or enlarging T2 lesions in the SID-only, and the EID-only, and SID/EID groups were reduced by 89.1%, 83.5%, and 95.7%, respectively, after natalizumab initiation compared with the year before natalizumab. Conclusions: The significant reduction in ARR observed with EID or SID/EID suggests that there is little difference between these dosing regimens in this retrospective dataset in Japan. The effectiveness of natalizumab in reducing the number of new or enlarging T2 lesions was similar across all dosing groups and consistent with known high efficacy of natalizumab in controlling disease activity. These real-world data on natalizumab EID in Japan may help inform treatment choices for Asian populations.

Objective: To evaluate the satisfaction, effectiveness, and usability of a telerehabilitation programme for Parkinson’s disease (PD) patients. Design: Prospective cohort study. Subjects/Patients: PD patients based on the diagnostic criteria for clinically established or probable PD published by the International Parkinson and Movement Disorder Society. Methods: The telerehabilitation was conducted twice a week via a Zoom meeting platform, using prerecorded rehabilitation contents shared during the sessions. In this study we administered several questionnaires, i.e., a self-report questionnaire on the effectiveness of telerehabilitation, the Parkinson’s Disease Questionnaire-39 (PDQ-39), and the Tele-health Usability Questionnaire (TUQ), in order to evaluate the satisfaction, effectiveness, and usability of our telerehabilitation programme. Results: Fifty-six PD patients were included in the analysis. After 6 months, 91.1% expressed satisfaction with the telerehabilitation and 91.9% reported telerehabilitation had helped them develop an exercise routine, but the PDQ-39 showed no significant improvement in quality of life. The TUQ showed higher scores for Usefulness (76.1%), Ease of Use and Learnability (73.5%), Interface Quality (75.4%), and Satisfaction and Future Use (82.2%). Conclusion: Satisfaction with telerehabilitation was high, particularly with regard to positive effects on emotional well-being. Telerehabilitation usability was also found to be high.

Background: We report ofatumumab's longer-term safety and efficacy in recently diagnosed (≤3 years) treatment-naive (RDTN) people living with relapsing multiple sclerosis (plwRMS). Methods: Safety analyses included RDTN participants receiving at least 1 ofatumumab dose in ASCLEPIOS I/II or other ALITHIOS feeder studies (APLIOS and APOLITOS). Efficacy analyses included participants randomised to ofatumumab in ASCLEPIOS I/II and treated continuously for up to 6 years. Efficacy outcomes include annualised relapse rate (ARR), MRI lesions, no evidence of disease activity-3 (NEDA-3), cognitive processing speed, and work status. Results: The safety analysis included 409 RDTN plwRMS. Exposure-adjusted incidence rates of serious infections and malignancies did not increase to the cut-off date (25-Sep-2025) of 6 years. Over 6 years, mean IgG levels remained stable and IgG was above the lower limit of normal (LLN: 5.65 g/L) in 98.0% of participants at all assessments; mean IgM levels decreased but IgM remained above LLN (0.4 g/L) in 64.1% of participants at all assessments. Of 314 RDTN participants receiving ofatumumab in ASCLEPIOS I/II (efficacy analysis), 233 entered ALITHIOS, and at data cut-off 181 (77.7%, 181/233) were still receiving ofatumumab. ARR decreased from 0.112 (Year 1) to 0.030 (Year 6). An almost complete suppression of MRI lesions was observed up to Year 6. NEDA-3 at Year 6 was observed in 94.4% of participants. At 6 years, up to 70.6% of participants experienced clinically meaningful improvement in cognitive processing speed. Reduced work absenteeism versus baseline was observed. Conclusions: Findings support ofatumumab's highly favourable longer-term benefit-risk profile as first-line therapy for plwRMS.

Introduction: A large-scale post-marketing surveillance (PMS) study is ongoing to evaluate the safety and effectiveness of satralizumab over 6 years in Japanese patients with neuromyelitis optica spectrum disorder (NMOSD) in real-world settings. We present the results of a 30-month interim analysis of the study. Methods: This PMS is being conducted across 234 sites in Japan. In this 30-month interim analysis, the end of the observation period was defined as either the date of data lock for the 30-month case report form for all patients or the last observation date for patients with satralizumab discontinuation. Primary outcomes include proportion of patients experiencing adverse drug reactions (ADRs), event rate, and oral glucocorticoid use. Secondary outcomes include time to relapse and relapse rate. Results: Of 571 patients included (mean age: 52.4 years), 91.76% were female. At baseline, 85.98% of patients received oral glucocorticoids. ADRs were reported in 28.72% of patients (event rate: 27.69 events/100 person-years), with infections being most common (11.73%; 8.97 events/100 person-years). Univariate analysis showed that at 30 months, serious infections occurred in 6.83% of patients (5.00 events/100 person-years vs 8.13 events/100 person-years during 0–6 months) and were more frequent in patients aged ≥ 75 years, with diagnosis-to-treatment initiation duration ≥ 10 years, ≥ 3 relapses within 2 years, and Expanded Disability Status Scale score ≥ 6. Mean glucocorticoid dose decreased from 12.27 mg/day (baseline) to 3.48 mg/day (30 months). Kaplan-Meier cumulative relapse-free rate was 85.86% at 30 months. The annualized relapse rate was 0.08/person-year. Overall, 9.63% and 3.50% of patients discontinued treatment because of adverse events and relapses, respectively. Conclusion: Serious infections were more common during the satralizumab treatment period, occurring most frequently within the first 6 months, highlighting the need for continuous monitoring of infections throughout satralizumab treatment. Satralizumab was found to be safe, without new safety concerns over 30 months. A reduction in concomitant immunosuppressive therapy usage was observed. The study demonstrated the effectiveness of satralizumab in preventing relapses in Japanese patients with NMOSD. Trial Registration: UMIN Clinical Trials Registry, UMIN000041047.

Electroconvulsive therapy (ECT), an established treatment for psychiatric disorders, shows promise in alleviating both motor and non-motor symptoms in patients with Parkinson’s disease (PD). We herein report a case of PRKN-associated PD presenting with characteristic psychosis and dystonic voice, which was effectively managed with maintenance ECT. A genetic analysis initially identified a single heterozygous PRKN deletion using multiple ligation-probe amplification. Subsequent Oxford Nanopore technology long-read sequencing revealed a second pathogenic variant, confirming a compound heterozygous PRKN mutation. This case highlights the utility of long-read sequencing in resolving genetic diagnoses and the potential of maintenance ECT for managing complex PD phenotypes.

Introduction: Ofatumumab demonstrated superior efficacy and similar safety versus teriflunomide in ASCLEPIOS I/II in people with relapsing multiple sclerosis; no new safety concerns and sustained efficacy were observed up to 4 years in the open-label extension study ALITHIOS. Here, we further characterise the safety and efficacy of ofatumumab up to 5 years by discussing infection outcomes in the COVID-19 era and providing a comprehensive overview of participant disability outcomes. Methods: Safety (N = 1969; participants who received ≥ 1 dose of ofatumumab in ASCLEPIOS I/II, APLIOS, APOLITOS, or ALITHIOS) and efficacy sets (N = 1882; participants randomised to ofatumumab [OMB-OMB] or teriflunomide [TER-OMB] in ASCLEPIOS I/II, regardless of whether they entered ALITHIOS) were analysed. Data cutoff: 25 September 2022. Results: The exposure-adjusted incidence rates (per 100 patient-years) of adverse events (AEs, 124.65), serious AEs (4.68), serious infections (1.63), and malignancies (0.32) remained consistent with previous findings up to 5 years of follow-up, with no new safety signals identified. With ofatumumab treatment up to 5 years, > 80% of patients remained free of 6-month confirmed disability worsening (6mCDW). Annualised relapse rates (ARR) remained low, and magnetic resonance imaging (MRI) activity was almost completely suppressed with OMB-OMB through years 1–5; after switching from teriflunomide (years 2–3), pronounced reductions in ARR/MRI activity were observed with low rates sustained through years 3–5. During year 5, 9 of 10 participants in both groups were free of disease activity (NEDA-3). Conclusion: Ofatumumab has a favourable benefit-risk profile that is sustained up to 5 years. Trial registration: ALITHIOS (NCT03650114): https://clinicaltrials.gov/ct2/show/NCT03650114

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder of the central nervous system that predominantly affects the spinal cord and optic nerves. Aquaporin-4 antibodies have been identified as a distinguishing biomarker of NMOSD, allowing for differentiation from multiple sclerosis and other mimicking neurological conditions. Targeted monoclonal antibody treatments are evolving based on an improved understanding of the pathophysiology underlying NMOSD. Of particular influence is the idea that NMOSD is an autoantibody-mediated disease involving B cells. The hope is that targeted treatments will improve not only outcomes but also the impact and burden of the disease on patients. This review summarizes the latest evidence for B cell pathophysiology in NMOSD and highlights the cellular and molecular mechanisms of B cell-driven disease. Finally, we focus on the mechanisms of action of B cell-targeted therapies as they relate to the mechanisms of disease.

Objective To describe 5 confirmed cases of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) in Japan. Methods The Nationwide PML Surveillance Committee requires mandatory registration of all natalizumab cases and reporting by affiliated facilities conducting JC DNA testing. Suspected PML cases were reviewed by the committee and classified as definite, probable, possible, or non-PML based on established diagnostic criteria. Results From 2016 to 2024, the nationwide PML surveillance committee identified 8 NTZ-PML cases, of which 5 (all women and relapsing-remitting types) were registered as clinically definite PML cases. Four cases involved a switch from other disease-modifying drugs, while one involved natalizumab as the first-line treatment for multiple sclerosis (MS). In all cases, extended interval dosing therapy (EID) every 6–8 weeks was administered for at least 1 year before PML onset, and 3 cases had received EID from the outset. At PML onset, the viral DNA levels in the CSF were ≤100 copies/mL in 3 cases. Discussion Given the high prevalence of JC virus antibody positivity in Japan, additional risk factors may contribute to NTZ-PML susceptibility. Although EID of natalizumab is expected to reduce PML risk, its effectiveness may be limited, particularly in Japanese individuals with high JC virus antibody titers. Introduction Natalizumab is highly effective in preventing relapses in multiple sclerosis (MS)1; however, natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) is a concern.2 Recently, an extended interval dosing (EID) regimen, involving natalizumab administration every 6–8 weeks, has been introduced to reduce the risk of NTZ-PML without compromising therapeutic efficacy.2,3

Background: The effects of intravenous alteplase in patients with prior antiplatelet therapy (APT) remain controversial. We aimed to assess the efficacy and safety of imaging-based intravenous alteplase in patients with unknown onset stroke with prior APT. Methods: Data from randomized controlled trials comparing alteplase with placebo/standard care in patients with unknown onset acute ischemic stroke from the Evaluation of Unknown Onset Stroke Thrombolysis (EOS) individual patient data meta-analysis collaboration were analyzed. Favorable outcome was defined as a modified Rankin Scale score of 0–1 at 90 days post-stroke. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22–36 h and 90-day mortality. Results: Overall, 780 patients had available baseline data on prior APT. Compared with the no prior APT group (n = 523), the prior APT group (n = 257) was older (72 vs. 66 years) and had a higher prevalence of vascular risk factors. There was no interaction between prior APT and treatment effects of alteplase (p for interaction = 0.23). In the prior APT patients, 55/125 (45%) patients in the alteplase group and 39/132 (30%) patients in the control group had a favorable outcome (adjusted odds ratio [aOR], 2.07 [95% confidence interval, 1.18–3.64]). The rates of sICH and mortality in the alteplase and control groups were 5.6% and 0.8% (aOR, 7.78 [0.94–63.37]) and 6.5% and 6.1% (aOR, 1.12 [0.38–3.36]), respectively. In the no prior APT patients, 136 patients (50%) in the alteplase group and 112 patients (45%) in the control group had a favorable outcome (aOR, 1.39 [0.94–2.05]). Safety outcomes were not significantly different between the groups (sICH: 3 [1.1%] vs. 1 [0.4%]; mortality: 13 [4.9%] vs. 3 [1.2%]). Conclusions: Alteplase has consistent efficacy regardless of prior APT in patients with unknown onset stroke. In addition, prior APT does not significantly increase the risk of sICH or mortality.

Background: Antiseizure medications are often used as preventive treatment of migraine in appropriate cases; however, the efficacy of lacosamide (LCM), a sodium channel blocker, in preventing migraine attacks remains unclear. Cortical spreading depolarization (CSD) refers to a wave of slowly propagating depolarization across the cerebral cortex. CSD animal models have been extensively used to investigate migraine attacks and evaluate the effects of migraine medication. Herein, we examined the effects of single dose LCM (40 mg/kg) on CSD sensitivity in a mouse model. Findings: Thirty-two C57BL/6 mice (male, n = 16; female, n = 16) were intraperitoneally injected with either LCM (40 mg/kg) or saline before CSD sensitivity testing. Potassium chloride (KCl) was administered to induce CSD, and the CSD threshold, frequency, and propagation velocity were determined. The average CSD frequency induced by 1 M KCl was significantly lower (p = 0.030) and the CSD propagation velocity tended to be lower in the female LCM group than in the saline group. However, no significant differences were observed in any of the three CSD parameters in male mice. Conclusions: In female mice, single dose LCM treatment significantly reduced CSD frequency induced by KCl. Further investigations are warranted to assess the clinical potential of LCM in preventing migraine.

Objective Switching from one anti-calcitonin gene-related peptide monoclonal antibody (CGRP mAb) to another can be beneficial for treating patients with migraine who do not respond well to the first CGRP mAb. However, detailed and long-term follow-up reports of both efficacy and safety remain insufficient. We conducted a case-series analysis of patients with migraine who switched from galcanezumab to erenumab, both belonging to the class of CGRP mAbs. Methods We conducted a single-center retrospective real-world study. Patients with migraine who first received galcanezumab for !3 months and then switched to erenumab at Keio University Hospital were enrolled to investigate changes in monthly migraine days (MMD), response rate, and adverse effects (e.g., injection-site reactions). Additionally, we performed a narrative review of the literature on switching CGRP mAbs. Results Among the nine patients enrolled, the 50% response rate for MMD was 33% at 3 months after switching. Two patients (22%) initially responded at the 3-month assessment, but later reverted to baseline MMD levels. Switching from galcanezumab to erenumab increased the frequency of constipation, which was typically managed using laxatives. Participants who experienced injection-site reactions tended to exhibit similar reactions regardless of the type of CGRP mAb used. Five patients (56%) demonstrated an improvement in satisfaction after erenumab initiation at least once. A literature review revealed that the characteristics of the cohorts varied among studies. Conclusion Switching from galcanezumab to erenumab was effective in some patients, while it was associated with some tolerable side effects, and it improved patient satisfaction in approximately half of the patients, despite interindividual diversity in responses and fluctuating responses after switching, which warrants further investigation.

Mitochondrial diseases (MDs) are inherited metabolic disorders that affect multiple organ systems, including the kidneys. Variability in disease onset and phenotypic expression, combined with the absence of specific kidney pathological findings, pose significant challenges in diagnosing MD. Consequently, many undiagnosed cases of MD may exist among patients undergoing dialysis. No effective treatment for mitochondrial nephropathy has been established. We report the case of a 27-year-old female patient who presented with leg edema, nephrotic range proteinuria attributed to focal segmental glomerulosclerosis, and bilateral sensorineural hearing loss. Immunosuppressive therapy failed to achieve remission, resulting in progressive kidney function decline and eventual end-stage kidney disease. At hemodialysis initiation, worsening atypical cardiac function and hypertrophy prompted genetic testing, which identified an MT-TL1 m.3243 A > G mutation and confirmed the diagnosis of MD. After hemodialysis initiation, the patient experienced persistent fatigue and decreased physical activity levels despite dry weight management. Suspected stroke-like symptoms prompted the initiation of taurine supplementation, which significantly improved headache severity, cardiac function, and physical activity levels. This case highlights the therapeutic potential of taurine supplementation in patients with MD undergoing dialysis and the importance of maintaining clinical vigilance for MD across all stages of chronic kidney disease, even without characteristic renal pathological findings of mitochondrial nephropathy.

Background: Plasma biomarkers offer a promising alternative to amyloid beta (Aβ) positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers for diagnosing Alzheimer’s disease (AD). This cross-sectional study assessed the utility of multiple plasma biomarkers for diagnosing and staging AD in a Japanese cohort. Methods: The assessed plasma biomarkers included Aβ42/40, phosphorylated tau (p-tau181 and p-tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), individually and in combination. Aβ42/40 was measured using the HISCL® platform, while all other biomarkers were measured using the Simoa® platform. Participants were classified based on Aβ PET imaging and neuropsychological testing into healthy controls (HC), AD continuum (preclinical AD, mild cognitive impairment [AD-MCI], and mild dementia [AD-D]), and non-AD cognitive impairment (CI) groups. Receiver operating characteristic analyses were performed to predict the Aβ PET status, correlation with Centiloid (CL) values and cognitive scores, and biomarker comparisons across AD stages. Results: Sixty-nine HC, 13 preclinical AD, 38 AD-MCI, 44 AD-D, and 79 non-AD CI participants were included. The area under the curves (AUCs) for predicting Aβ PET status were 0.937 (Aβ42/40), 0.926 (p-tau217), and 0.946 (p-tau217/Aβ42); results of pair-wise DeLong tests revealed no significant differences among these three metrics (all p > 0.05). In the cognitively normal group, the AUCs were 0.968 (Aβ42/40), 0.958 (p-tau217), and 0.979 (p-tau217/Aβ42), while in the cognitively impaired group, they were 0.919 (Aβ42/40), 0.893 (p-tau217), and 0.923 (p-tau217/Aβ42). Among HC and AD continuum participants, CL correlations were − 0.74 (Aβ42/40), 0.81 (p-tau217), and 0.83 (p-tau217/Aβ42). In the HC and AD continuum, Aβ42/40 levels showed a bimodal distribution (cutoff = 0.096), with a shift from high to low occurring at 19.3 CL, compared to the PET positivity threshold of 32.9 CL. P-tau217 exhibited a linear increase with disease progression. All biomarkers correlated strongly with logical memory scores. Conclusions: Plasma biomarkers, Aβ42/40 and p-tau217, and particularly their ratio (p-tau217/Aβ42), show strong potential as Aβ PET alternatives for AD diagnosis. HISCL-based plasma Aβ42/40 detects Aβ accumulation earlier than Aβ PET visual reading threshold, underscoring its utility as an early diagnostic marker.

Myasthenia gravis (MG) is the most common autoimmune neuromuscular disorder, and is more common in women than in men. Anemia is also more common in women. The purpose of this study was to investigate factors associated with anemia and the negative impact of anemia in female MG patients. We investigated factors related to MG and anemia in 215 female patients with MG, who were attending the MG clinic of Keio Hospital between January and December 2021. We statistically evaluated clinical factors related to anemia in patients with and without anemia. Eighty-five patients (40%) had anemia in the past, and 130 patients did not have anemia in the past. There were no significant differences in age at study, age at MG onset, body mass index, or frequency of autoantibodies between the anemia and non-anemia groups. MG severity evaluated by the MG Foundation of America classification was greater in the anemia group than in the non-anemia group. History of anemia was associated with immunosuppressive treatment, such as prednisolone and calcineurin inhibitor treatment. There was a correlation between hemoglobin levels and the MG-quality of life score. Long term immunosuppressive therapy can cause anemia in female MG patients. Anemia may negatively affect the quality of life of female MG patients.

Objective To study the updated prevalence and clinical features of myasthenia gravis (MG) in Japan during 2017. Methods We sent survey sheets to the randomly selected medical departments (number = 7,545). First, we asked the number of MG patients who visited medical departments from January 1, 2017, to December 31, 2017. Then, we sent the second survey sheet to the medical departments that answered the first survey to obtain the clinical information of patients who received MG diagnosis between January 1, 2015, and December 31, 2017. Results The received answer to the first survey were 2,708 (recovery rate: 35.9%). After all, the prevalence of the 100,000 population was estimated as 23.1 (95%CI: 20.5-25.6). As a result of the second survey, we obtained 1,464 case records. After checking the duplications and lacking data, we utilized 1,195 data for further analysis. The median [interquartile range (IQR)] from the onset age of total patients was 59 (43-70) years old. The male-female ratio was 1: 1.15. The onset age [median (IQR)] for female patients was 58 (40-72) years old, and that for male patients was 60 (49-69) years old (Wilcoxon-Mann-Whitney test, p = 0.0299). We divided patients into four categories: 1) anti-acetylcholine receptor antibody (AChRAb) (+) thymoma (Tm) (-), 2) AChRAb(+)Tm(+), 3) anti-muscle-specific kinase antibody (MuSKAb) (+), and AChRAb(-)MuSKAb(-) (double negative; DN). The onset age [median (IQR)] of AChRAb(+)Tm(-) was 64 (48-73) years old, and AChRb(+)Tm(+) was 55 (45-66), MuSKAb(+) was 49 (36-64), DN was 47 (35-60) year old. The multivariate logistic regression analysis using sex, initial symptoms, repetitive nerve stimulation test (RNST), and edrophonium test revealed that sex, ocular symptoms, bulbar symptoms, and RNST were factors to distinguish each category. The myasthenia gravis activities of daily living profile at the severest state were significantly higher in MuSKAb(+). MuSKAb(+) frequently received prednisolone, tacrolimus plasmapheresis, and intravenous immunoglobulin; however, they received less acetylcholine esterase inhibitor. 99.2% of AChRAb(+)Tm(+) and 15.4% of AChRAb(+)Tm(-) received thymectomy. MuSKAb(+) did not receive thymectomy, and only 5.7% of DN received thymectomy. The prognosis was favorable in all categories. Conclusion Our result revealed that the prevalence of Japanese MG doubled from the previous study using the same survey method in 2006. We also found that the onset age shifted to the elderly, and the male-female ratio reached almost even. Classification in four categories; AChRAb(+)Tm(-), AChRAb(+)Tm(+), MuSKAb(+), and DN, well describe the specific clinical features of each category and differences in therapeutic approaches.

Background: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are a favourable option for patients with migraine who experience distressful headache disability and fail to respond to traditional preventive treatment options. However, since CGRPmAb has been available for only 2 years in Japan, the difference between good and poor responders remains unknown. We aimed to investigate the clinical characteristics of patients with migraine in Japan who responded well to CGRPmAb based on real-world data. Methods: We analysed patients who visited Keio University Hospital, Tokyo, Japan, between the 12th of August 2021 and 31st of August 2022, and were prescribed one of three CGRPmAbs (erenumab, galcanezumab, and fremanezumab) for more than 3 months. We recorded the patients’ basic migraine characteristics, such as pain quality, monthly migraine days (MMD)/monthly headache days (MHD), and the number of prior treatment failures. We defined good responders as patients whose MMDs decreased by more than 50% after 3 months of treatment and other patients as poor responders. We compared the baseline migraine characteristics between the two groups and performed logistic regression analysis based on the items that showed statistically significant differences. Results: In total, 101 patients were considered eligible for the responder analysis (galcanezumab: 57 (56%), fremanezumab: 31 (31%), and erenumab: 13 (13%)). After 3 months of treatment, 55 (54%) patients achieved ≥ 50% reduction in MMDs. Comparisons between ≥ 50% responders and non-responders revealed that age was significantly higher (p = 0.003), and MHD and total prior treatment failures were significantly lower (p = 0.027, 0.040, respectively), in responders than in non-responders. Age was a positive predictive factor, and the total number of prior treatment failures and past medical history of immuno-rheumatologic diseases were negative predictive factors of CGRPmAb responsiveness in Japanese patients with migraine. Conclusions: Patients with migraine who are older, with fewer prior treatment failures and no past history of immuno-rheumatologic disease, may respond well to CGRPmAbs.