鵜沢 顕之

OBJECTIVES: Minimal symptom expression (MSE), defined as myasthenia gravis (MG) activities of daily living profile (MGADL) score 0 or 1, has been recently used as an indicator of treatment goal in MG. However, no study has determined when MSE is achieved. The current study aimed to investigate the timing and incidence of MSE achievement in generalized MG patients. METHODS: Eighty-five patients with acetylcholine receptor antibody-positive generalized MG were included. They were followed-up maximum 3 years after starting immunotherapy, and we reviewed the MGADL score, prednisolone dose, and achievement of MSE and minimal manifestations (MM) or better status. RESULTS: MSE was achieved in 37.6, 45.2, 55.8, 60.3, and 57.1% of the patients at 3, 6, 12, 24, and 36 months after treatment, respectively. Most patients who achieved MSE showed MM or better status at any phase. In addition, more than 2 years after the starting treatment, about 80% of patients who achieved MSE showed MM or better status with an oral prednisolone dose of 5 mg/day or less (MM-5 mg). Noteworthy, during the early stage of treatment, the proportion of patients who achieved MSE was higher than that who achieved MM-5 mg. CONCLUSION: From the early phases of immunotherapy, MSE is a good marker of therapeutic goal in patients with generalized MG.

This study examined the role of Tfh and Treg associated molecules also known as checkpoint molecules, their ligands, and IL-21 in myasthenia gravis (MG) pathogenesis. Serum levels of sPD-1, sPD-L1, sICOS, sICOSLG, sCTLA4, and IL-21 were measured in 39 patients with acetylcholine receptor (AChR) antibody-positive generalized MG and 27 controls. sPD-1 and IL-21 levels were higher in MG patients than in controls. Additionally, sPD-1 levels correlated positively with the levels of IL-21, sICOSLG, sCTLA4, and AChR antibody titers. sICOS are correlated with MGADL and AChR antibody titers. These Tfh associated molecules could be used as biomarkers of MG disease activity.

INTRODUCTION: The management of myasthenia gravis (MG) has been improved due to immunotherapy advances, but 20% of individuals with MG are refractory to the conventional therapy, and the need for novel biological drugs remains. AREA COVERED: The Japanese clinical guidelines for MG published in May 2022 include the concept that treatment is often lifelong and should aim to maintain a sufficient quality of life and mental health. We provide an overview of the therapeutic strategy for generalized MG in Japan, in comparison with the international consensus. We summarize the clinical efficacy, safety, and tolerability of efgartigimod, the first approved anti-neonatal Fc receptor inhibitor for MG. A phase III study showed that efgartigimod was well-tolerated and efficacious in patients with generalized MG. EXPERT OPINION: Efgartigimod is a promising biological drug for patients with moderate to severe generalized MG with or without anti-acetylcholine receptor antibodies in Japan.

We describe a 46-year-old woman who developed multiple cerebral infarctions in the left middle cerebral artery territory and deep vein thrombosis, presumably related to uterine adenomyosis. Uterine adenomyosis can cause coagulation abnormalities, as observed in Trousseau's syndrome. Along with previous reports, our case experienced a stroke during menstruation and presented with increased cancer antigen 125 (CA125) levels. A hysterectomy was performed to prevent the recurrence of cerebral infarction. Our case also had complicated deep vein thrombosis, which is also known as a complication of uterine adenomyosis. We consider cerebral infarction and deep vein thrombosis with uterine adenomyosis might be caused by a common mechanism, hypercoagulation. Hysterectomy requires careful discussion before undergoing it because of fertility problems, but it might be the most effective approach for preventing the recurrence of brain infarction derived from adenomyosis and may be effective for both cerebral infarction and deep vein thrombosis.

Objective: We aimed to investigate the hypothesis that amplitudes of compound muscle action potential (CMAP) elicited by single stimulation decrease by baseline neuromuscular blocking in myasthenia gravis (MG), and to examine correlation of CMAP amplitudes with baseline muscle weakness.Methods: One hundred ninety-four consecutive patients who underwent repetitive 3 Hz nerve stimulation tests (RNST) at our laboratory were included in the study. Of these, 109 patients were diagnosed as suffering from MG, and the remaining 85 with other disease served as the non--MG controls. RNST was performed on the nasalis, trapezius, and abductor digiti minimi (ADM) muscles. CMAP amplitudes elicited by the first stimulation were compared between the two groups. In MG patients, we studied the correlation of CMAP amplitudes with MG Foundation of America (MGFA) class, total scores of manual muscle testing (MMT), and 4th decrement (%) of RNST.Results: Compound muscle action potential amplitudes in MG were significantly lower than in controls ( p < 0.05 in all muscles tested). Decreases in CMAP amplitudes were more prominent in generalized than in ocular MG (p < 0.05), and in patients with MGFA III-V classes than in those with 0-II (p < 0.01 in the trapezius and ADM). CMAP amplitudes partially correlated with total MMT scores and MG-ADL scale scores. Additionally, CMAP amplitudes elicited by the first stimulation correlated with the 4th decrement of RNST (p < 0.01 in all muscles tested). Conclusion: Compound muscle action potential amplitudes are reduced in MG, presumably by baseline neuromuscular transmission block, and could reflect persistent muscle weakness, rather than fatigue, in MG patients.

OBJECTIVE: Myasthenia gravis (MG) is an antibody-mediated inflammatory disease affecting post-synaptic membranes of neuromuscular junctions, and objective biomarkers of MG disease activity are lacking. Pentraxin 3 (PTX3) is an acute-phase inflammatory glycoprotein in the same family as C-reactive protein that is associated with disease activity in several autoimmune disorders. Thus, we investigated whether circulating PTX3 is a useful biomarker of MG activity. METHODS: Serum PTX3 was measured in 40 patients with MG who were positive for anti-acetylcholine receptor antibody, and in 30 healthy and disease controls, using a commercial enzyme-linked immunosorbent assay kit. In patients with MG, the correlation of serum PTX3 levels with disease severity scales at serum sampling, including MG Foundation of America (MGFA) classification, MG activity of daily living (MG-ADL) score, and quantitative MG (QMG) score, were investigated. RESULTS: Although there was no significant difference in serum PTX3 between the MG and control groups (mean, 3346 pg/mL in MG group vs. 2870 pg/mL in control group, P = 0.56), serum PTX3 moderately correlated with all disease severity scores (MGFA classification: Spearman's ρ = 0.53, P = 0.0004; MG-ADL score: Spearman's ρ = 0.45, P = 0.004; QMG score: Spearman's ρ = 0.50, P = 0.004). CONCLUSION: Our results suggest that circulating PTX3 may reflect the extent of neuromuscular junction damage and might be involved in the pathogenesis of MG.

Recent studies have reported that autoantibodies against glial fibrillary acidic protein (GFAP), a major cytoskeletal protein expressed in astrocytes, can lead to GFAP astrocytopathy, an autoimmune central nervous system inflammatory disease. We herein report the unique case of a 59-year-old Japanese woman with GFAP astrocytopathy who presented with characteristic symptoms, including signs of meningeal irritation, cerebellar ataxia, and bladder/rectal dysfunction, in the absence of specific findings on initial brain magnetic resonance imaging (MRI). The patient exhibited new abnormal changes mainly in the brainstem on follow-up MRI, illustrating the need to recognize that MRI abnormalities may appear later in GFAP astrocytopathy.

Immune-mediated necrotizing myopathy (IMNM) is a pathologically defined diagnosis of idiopathic inflammatory myopathies. Adequate studies on cytokines of IMNM is lacking. We measured serum levels of 27 cytokines/chemokines in 22 IMNM patients, 10 sporadic inclusion body myositis (IBM) patients, and 23 other neurological disorders (ONDs) patients. In IMNM patients, the correlations between clinical features and cytokine/chemokine levels, and changes in cytokine/chemokine levels after immunosuppressive therapy were examined. Compared with ONDs patients, IMNM patients had significantly increased serum levels of several cytokines. In particular, IP-10 and MIP-1α levels were prominently increased, decreased after immunosuppressive-therapy, and correlated with serum creatine kinase levels. IP-10 and MIP-1α could play important roles in the IMNM pathogenesis.

OBJECTIVE: To investigate the difference in clinical course after the first optic neuritis (ON) between aquaporin-4 IgG-associated disorder (AQPAD) and myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) METHODS: In this study, 31 eyes in 24 patients with AQPAD and 26 eyes in 18 patients with MOGAD were included. The clinical course for the first 6 months after the first ON was monitored by a retrospective cohort study. Best-corrected visual acuity (BCVA) was observed before the onset and at nadir, 2 weeks (2 W), 1 month (1 M), 2 months (2 M), 3 months (3 M) and 6 months (6 M). The decimal BCVA was converted to the logarithm of the minimal angle of resolution (logMAR) for statistical analyses. RESULTS: MOGAD eyes showed longer median number of days from ON onset to nadir (6.0 vs. 11.5, P = 0.012) and to treatment (7.0 vs. 11.0, P = 0.020) than AQPAD eyes. The median logMAR was higher in AQPAD eyes than in MOGAD eyes at nadir (2.00 vs. 1.77, P = 0.050), 2 W (1.85 vs. 0.40, P = 0.001), 2 M (0.023 vs. - 0.079, P = 0.032) and 3 M (0.046 vs. - 0.079, P = 0.002). The median time to recovery of BCVA to 0.7 was longer in AQPAD eyes than in MOGAD eyes (44.0 vs. 21.0 days, P = 0.024), but that to BCVA 1.0 was not different between the two disorders (168.0 vs. 40.0 days, respectively, P = 0.056). CONCLUSION: Compared with MOGAD eyes, AQPAD eyes tended to show worse visual outcome even during the first ON episode.