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Background: An accurate prediction for prognosis can help in guiding the therapeutic options and optimizing the trial design for generalized myasthenia gravis (gMG). We aimed to develop and validate a predictive nomogram to assess the short-term outcome in patients with the anti-acetylcholine receptor (AChR) subtype gMG.Methods: We retrospectively reviewed 165 patients with AChR subtype gMG who were immunotherapy naïve at the first visit from five tertiary centers in China. The short-term clinical outcome is defined as the achievement of minimal symptom expression (MSE) at 12 months. Of them, 120 gMG patients from Huashan Hospital were enrolled to form a derivation cohort (n = 96) and a temporal validation cohort (n = 24) for the nomogram. Then, this nomogram was externally validated using 45 immunotherapy naïve AChR subtype gMG from the other four hospitals. Multivariate logistic regression was used to screen independent factors and construct the nomogram.Results: MSE was achieved in 70 (72.9%), 20 (83.3%), and 33 (73.3%) patients in the training, temporal validation, and external validation cohort, respectively. The duration ≤ 12 months (p = 0.021), ocular score ≤ 2 (p = 0.006), QMG score > 13 (p = 0.008), and gross motor score ≤ 9 (p = 0.006) were statistically associated with MSE in AChR subtype gMG. The nomogram has good performance in predicting MSE as the concordance indexes are 0.81 (95% CI, 0.72-0.90) in the development cohort, 0.944 (95% CI, 0.83-1.00) in the temporal validation cohort, and 0.773 (95% CI, 0.63-0.92) in the external validation cohort.Conclusion: The nomogram achieved an optimal prediction of MSE in AChR subtype gMG patients using the baseline clinical characters. [ABSTRACT FROM AUTHOR]

Introduction/aims: The study aims to investigate the short-term efficacy of low-dose rituximab and its effect on immunological biomarker levels in myasthenia gravis (MG) patients with antibodies against muscle-specific tyrosine kinase (MuSK-MG).Methods: Twelve MuSK-MG patients were enrolled in this prospective, open-label, self-controlled pilot study. Clinical severity was evaluated at baseline and 6 mo after a single rituximab treatment (600 mg). B lymphocyte subtypes, MuSK antibody titers, together with levels of immunoglobulins, serum B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L, and four exosomal microRNAs were evaluated. A correlation matrix to reveal pairwise relationships among above variables was also generated.Results: The single rituximab treatment significantly lowered the clinical severity scores and reduced daily dosage of prednisone (P = .032) at 6 mo. MuSK antibody titers decreased (P = .035) without significant changes in immunoglobulin levels. Serum BAFF level increased (P = .010), which negatively correlated with the percentages of B cells in lymphocytes as well as clinical severity. Additionally, serum exosomal miR-151a-3p showed a reduction of 28.1% (P = .031).Discussion: We confirmed the clinical efficacy of low-dose rituximab in MuSK-MG, accompanied by a decrease in MuSK antibody titers and an increase in serum BAFF. Serum BAFF levels negatively correlated with B-cell counts as well as clinical severity. [ABSTRACT FROM AUTHOR]

Background: Patients in China with juvenile-onset myasthenia gravis present early, with a high prevalence of purely ocular symptoms, spontaneous remission rates, and low antibody seropositivity. Antibody detection using a cell-based assay has been reported to increase the diagnostic sensitivity in adult-onset myasthenia gravis. However, this method in patients with juvenile-onset myasthenia gravis has not been investigated.Methods: Patients with juvenile-onset myasthenia gravis who had not received prednisone or immunosuppressive therapy were recruited between June 2015 and April 2018 at the Huashan Hospital. Clinical information was collected. Serum anti-acetylcholine receptor antibodies were detected via cell-based assay with HEK293T cells expressing acetylcholine receptor subunits and rapsyn. Additionally, the IgG antibody subclass was identified.Results: Eighty-two patients with juvenile-onset myasthenia gravis were enrolled in the current study. Among them, 48 patients were anti-acetylcholine receptor positive (58.5%) and 34 were seronegative (41.5%), as assessed via enzyme-linked immunosorbent assay. Cell-based assay yielded 63 positive subjects (76.8%) and 19 seronegative subjects (23.2%). All the enzyme-linked immunosorbent assay-positive samples showed robust immunofluorescence in the cell-based assay, whereas 15 of 34 enzyme-linked immunosorbent assay-negative patients (44.1%) were found to have low-affinity acetylcholine receptor antibodies. Among all the cell-based assay-positive patients, 41 were positive for both adult and fetal acetylcholine receptor antibodies (50.0%), 18 were found positive for only adult acetylcholine receptor antibodies (21.9%), and four were found to possess only fetal acetylcholine receptor antibodies (4.9%). Fifteen antibody-positive samples underwent subclassification and were confirmed to be IgG1 subclass predominant (n = 15, including eight adult and fetal acetylcholine receptor antibody positive, five only adult acetylcholine receptor antibody positive, and two only fetal acetylcholine receptor antibody positive). There were no significant differences in clinical features among patients with different antibody profiles.Conclusions: The cell-based assay showed increased sensitivity in acetylcholine receptor antibody detection in Chinese patients with juvenile-onset myasthenia gravis, and most cases of Chinese juvenile-onset myasthenia gravis are still acetylcholine receptor autoantibody mediated. Furthermore, the antibodies detected are predominately of the IgG1 subclass. [ABSTRACT FROM AUTHOR]

Introduction: Limb-girdle muscular dystrophy type 2A (LGMD2A) is characterized by progressive wasting of muscles for which the disease-monitoring tools are still deficient.Methods: We performed muscle MRI of the lower limbs in 32 LGMD2A patients and 21 controls. The modified Mercuri scale was employed to evaluate the degree of fatty infiltration.Results: Severe fatty infiltration in the long head of biceps femoris (modified Mercuri scale 3.99) and sparing of extensor digitorum longus (modified Mercuri scale 0.17) were observed. The sensitivity and specificity of this pattern in diagnostic testing was 76.00% and 90.48%, respectively. A comprehensive clinical and MRI evaluation revealed that progressive fatty infiltration in the upper leg correlated well with disease progression, but neither calf involvement nor muscle strength deterioration showed a good correlation.Discussion: The selective involvement pattern is potentially useful for LGMD2A diagnosis. Upper leg muscle MRI is a sensitive evaluation method for monitoring disease progression. Muscle Nerve 58: 536-541, 2018. [ABSTRACT FROM AUTHOR]