重症筋無力症

Objective Although experimental studies suggest that diabetes mellitus (DM) exacerbates immune dysregulation in myasthenia gravis (MG), its precise impact on clinical outcomes remains unclear. Therefore, we investigated the influence of pre-existing glucose metabolism abnormalities in immunotherapy-naïve patients with MG.Methods Abnormal glucose metabolism was defined as receiving DM treatment or a glycated hemoglobin A1c level ≥ 6.0%. The prevalence of glucose metabolism abnormalities was compared with that of the general Japanese population, and MG outcomes were assessed between patients with and without these abnormalities.Patients or Materials We retrospectively studied 108 immunotherapy-naïve MG patients initially presenting to Chiba University Hospital between 2016 and 2020.Results Twenty-eight patients (25.9%) had abnormal glucose metabolism, similar to that of the general population. The prevalence in late-onset MG (LOMG) was 37.3%, which also showed no significant difference from the general population aged ≥ 50 years (34.2%). In LOMG, the abnormal glucose metabolism group had significantly higher MG Activities of Daily Living (MG-ADL) scores at 1-year follow-up (median [range]: 1 [0-5] vs. 0 [0-3], p = 0.017). In generalized LOMG, the abnormal glucose metabolism group showed significantly higher MG Foundation of America classes at peak severity within 1 year (3 [2-5] vs. 2 [2-4], p ＜0.001), higher MG-ADL scores at 1-year follow-up (1 [0-5] vs. 0 [0-2], p = 0.027), and required higher maximum daily prednisolone doses within 1 year (30.0 [0-50.0] vs. 10.0 [0-50.0] mg, p = 0.026) and at 1-year follow-up (9.0 [0-20.0] vs. 3.8 [0-10.0] mg, p = 0.029).Conclusion Abnormal glucose metabolism may negatively affect the clinical course of MG. In our evaluable LOMG cohort, this negative impact was most prominent in generalized cases, in which patients showed less satisfactory clinical improvement and required higher corticosteroid doses.

INTRODUCTION/AIMS: Early recognition and treatment are critical in juvenile myasthenia gravis (JMG), yet pediatric-specific evidence remains limited. We aimed to describe treatment patterns, remission rates, and predictors in a Canadian cohort. METHODS: We conducted a retrospective study of patients under 18 years diagnosed with JMG at The Hospital for Sick Children, Toronto, between 2015 and 2025. Clinical, treatment, and outcome data were collected. Diagnosis was confirmed by antibody positivity or electrophysiology, and outcomes were classified using the Myasthenia Gravis Foundation of America postintervention status (MGFA-PIS). Kaplan-Meier and Cox regression analyses were used to evaluate remission and its predictors. RESULTS: Thirty-six patients were included, 16 with generalized MG (GMG) and 20 with ocular MG (OMG). Mean age at diagnosis was 8.7 years; 50% were female. Acetylcholine receptor-positive, muscle-specific kinase-positive, and seronegative MG accounted for 55.6%, 5.6%, and 38.9% of the cohort, respectively. Repetitive nerve stimulation was abnormal in 82.6% tested. Most patients received pyridostigmine and corticosteroids initially, with additional immunosuppressants in selected cases. Seven received rituximab, and seven underwent thymectomy, with most achieving complete stable remission (CSR). The estimated 3-year remission rate was 36.1%, and 66.7% achieved CSR at last follow-up (median 45.5 months). Older age at onset and early immunosuppression predicted remission, while GMG had a higher rate than OMG (56.2% vs. 20.6%, p = 0.044). DISCUSSION: Earlier immunosuppression was associated with a higher remission rate, whereas treatment tended to be initiated later and remission was less frequent in OMG. These findings support a timely treatment approach in JMG.

The therapeutic significance of acetylcholinesterase (AChE) inhibition is most prominently observed in the management of various neurodegenerative and neuromuscular disorders, including Alzheimer's disease (AD), and myasthenia gravis (MG). The present review examines isatin-based compounds as a promising class of drugs for treating these conditions, focusing on their ability to inhibit AChE. While AD is characterized by a significant loss of cholinergic neurons leading to a deficiency in acetylcholine (ACh), MG is an autoimmune disease where the body produces antibodies that block or destroy ACh receptors at the neuromuscular junction. By inhibiting AChE, therapeutic agents increase the availability of ACh, thereby enhancing cholinergic neurotransmission and improving muscle strength or cognitive function. The underlying issue in MG is the reduced number of functional receptors rather than a primary decrease in AChE production. However, inhibition of the enzyme remains a vital strategy for symptom management. Accordingly, this review provides a systematic overview of the various synthetic strategies reported in the literature over the last decade for enhancing isatin-based AChE inhibitory activity. These strategies include modifications of the isatin nitrogen, such as N-alkylation, N-acylation, or N-arylation. Another strategy is aromatic ring substitution, where various substituents (e.g., halogens, nitro, amino, and alkyl groups) are introduced typically at the C5, C6, and/or C7 positions. C3-carbonyl functionalization is also reported, exemplified by the formation of Schiff bases, hydrazones, or spirocyclic derivatives. Our findings highlight the exceptional potential and adaptability of isatin derivatives in medicinal chemistry, highlighting the major advances within the last 10 years and the future directions.

BACKGROUND: Myasthenia gravis (MG) exhibits clinical heterogeneity ranging from ocular to generalized forms. Although gut microbiota has been implicated in autoimmune diseases, its relationship with clinical subtype and antibody burden in MG remains unclear. METHODS: We conducted a cross-sectional study of fecal microbiota in 14 patients with MG (3 ocular and 11 generalized) and 10 healthy controls using 16S rRNA sequencing. Patients with MG were stratified according to acetylcholine receptor antibody (AChR-Ab) titers into low (n = 5), moderate (n = 5), and high (n = 4) groups. RESULTS: Alpha and beta diversity did not differ significantly between clinical subtypes or antibody-defined groups. Exploratory genus-level analyses identified nominal differences in the relative abundance of several bacterial genera across both clinical subtype and antibody-defined groups. SCFA-associated taxa, including Anaerostipes, Blautia, and Faecalibacterium, appeared relatively more abundant in ocular MG and lower antibody groups, whereas Streptococcus and Bacteroides appeared relatively more abundant in generalized MG and higher antibody groups. PICRUSt2-based analyses were used to explore variation in predicted metabolic pathways between groups; however, no pathway remained significant after correction for multiple testing. CONCLUSIONS: Descriptive genus-level microbiome patterns were observed across both clinical subtype and antibody-defined groups despite similar global diversity measures. These exploratory findings suggest that microbiome variation within MG may be associated with multiple aspects of disease heterogeneity. However, given the small sample size, particularly within the ocular MG subgroup, these observations should be considered hypothesis-generating and require validation in larger independent cohorts.

INTRODUCTION: Endoscopic enucleation of benign prostatic hyperplasia (BPH) is currently considered a treatment of choice for patients with BPH of any volume, including those in whom discontinuation of anticoagulant or antiplatelet therapy is not feasible. However, urinary incontinence remains one of the most common postoperative complications, significantly affecting patients quality of life. OBJECTIVE: to evaluate the incidence and patterns of urinary incontinence following endoscopic enucleation, as well as to compare preoperative and intraoperative characteristics among patients with different types of incontinence. MATERIALS AND METHODS: This single-center observational cohort study included patients with BPH who underwent endoscopic enucleation between March 2019 and December 2025. Data were collected prospectively and analyzed retrospectively. Urinary incontinence was defined as any involuntary leakage of urine. Statistical analysis was performed using the R programming language (RStudio version 2025.05.1+513). RESULTS: Among 1,094 patients, urinary incontinence (of any type) was observed in 13.7% of cases (150/1094). Of these, 48 patients (32.0%) had urge incontinence, 75 (50.0%) had stress incontinence, and 27 (18.0%) had mixed incontinence. In the majority of cases, incontinence was transient: 61 patients (40.7% of incontinent patients and 5.6% of the total cohort) experienced symptoms lasting up to 1 month, 80 patients (53.3% and 7.3%, respectively) between 1 and 3 months, and 9 patients (6.0% and 0.8%, respectively) for more than 3 months. Persistent incontinence beyond 12 months was observed in only one patient (0.091%) with myasthenia gravis. The time to continence recovery did not differ significantly between incontinence types (p = 0.95). Comparative analysis of preoperative, intraoperative, and postoperative parameters demonstrated that patients with stress urinary incontinence had a higher body mass index, less pronounced storage symptoms according to IPSS, less frequent use of antimuscarinics and beta-3-agonists prior to surgery, and a lower rate of early apical sphincter release during enucleation. Patients with mixed incontinence more commonly had cerebrovascular disease. CONCLUSION: Urinary incontinence following endoscopic prostate enucleation occurs in 13.7% of patients and is transient in the majority of cases, resolving within the first three postoperative months. The rate of continence recovery is comparable across different types of incontinence, indicating a favorable functional prognosis in this patient population.