Introduction: Efgartigimod is effective and well-tolerated in patients with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG). However, the therapeutic potential and the safety profile of efgartigimod in myasthenic crisis (MC) remained largely unknown.Methods: This is an observational, prospective, multicenter, real-world study to follow 2 MC patients who initiated efgartigimod as a first-line rescue therapy and 8 cases who used it as an add-on therapy. Baseline demographic features and immunotherapies were collected, and the MG-activities of daily living (MG-ADL) scale was evaluated every week since efgartigimod treatment for 8 weeks. Additionally, serum IgG and anti-AChR antibody levels and the peripheral CD4⁺ T lymphocytes were measured before and after one cycle of treatment.Results: Ten patients with MC were enrolled in the study, including 9 anti-AChR antibody positive and 1 anti-muscle-specific kinase (MuSK) positive. All patients were successfully weaned from the ventilation after receiving efgartigimod treatment, with a length of 10.44 ± 4.30 days. After one cycle of infusions, the MG-ADL score reduced from 15.6 ± 4.4 at the baseline to 3.4 ± 2.2, while the corticosteroid dose was tapered from 55.0 ± 20.7 mg to 26.0 ± 14.1 mg. The proportions of regulatory T cells and naïve T cells (% in CD4⁺ T) significantly decreased post-efgartigimod treatment (5.48 ± 1.23 vs. 6.90 ± 1.80, P=0.0313, and 34.98 ± 6.47 vs. 43.68 ± 6.54, P=0.0313, respectively).Conclusion: These findings validated the rapid action of efgartigimod in facilitating the weaning process with a good safety profile in patients with MC.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neuropsychiatric disease. Brain access of anti-NMDAR autoantibody through the blood–brain barrier (BBB) is essential for pathogenesis. Most previous animal models limit the investigation of etiologies of BBB damage in patients. Methods: In this study, we established a novel humanized mouse model of anti-NMDAR encephalitis by intraperitoneal injection of patients’ peripheral blood mononuclear cells (PBMCs) into BALB/c Rag2^−/−Il2rg^−/−Sirpα^NODFlk2^−/− mice. Results: We found that engraftment of patients’ PBMCs not only produced potent anti-GluN1 autoantibodies, but also disrupted BBB integrity to allow brain access of autoantibodies, resulting in a hyperactive locomotor phenotype, anxiety- and depressive-like behaviors, cognitive deficits, as well as functional changes in corresponding brain regions. Transcriptome analysis suggested an exaggerated immune response and impaired neurotransmission in the mouse model and highlighted Il-1β as a hub gene implicated in pathological changes. We further demonstrated that Il-1β was produced by endothelial cells and disrupted BBB by repressing tight junction proteins. Treatment with Anakinra, an Il-1 receptor antagonist, ameliorated BBB damage and neuropsychiatric behaviors. Conclusions: Our study provided a novel and clinically more relevant humanized mouse model of anti-NMDAR encephalitis and revealed an intrinsic pathogenic property of the patient’s lymphocytes.

Whether metagenomic next-generation sequencing (mNGS) could benefit patients with suspected severe central nervous system (CNS) infection in terms of diagnosis and antibiotic treatment remains unknown. We retrospectively analyzed 79 patients with suspected CNS infection and undertook mNGS. The value of mNGS was investigated in terms of identification of pathogen and guidance for the adjustment of antibiotic treatment. The relationship between the time of initiating mNGS since onset and the Glasgow Outcome Scale (GOS) score after 90-day follow-up were analyzed. Fifty out of 79 cases with suspicious severe CNS infection were finally diagnosed. Despite previous routine laboratory tests, mNGS further promoted the accurate identification of pathogens in 23 cases (47.9%). The sensitivity, specificity, and accuracy of mNGS test in this study were 84.0, 79.3, and 82.3%, respectively. Furthermore, mNGS facilitated the adjustment of empirical antibiotic treatments in 38 cases (48.1%). The time of taking mNGS since onset had an insignificant weak positive correlation with GOS after 90-day follow-up (r = −0.73, P = 0.08). mNGS facilitated the accurate identification of pathogens in suspicious severe CNS infections and promoted the accurate antibiotic therapy even empirical antibiotics were administrated. It should be taken as early as possible to improve the clinical outcome of patients with suspicious severe CNS infection.

Background: Myasthenia gravis (MG) is the most common paraneoplastic syndromes of thymoma and closely related to thymus abnormalities. Timely detecting of the risk of MG would benefit clinical management and treatment decision for patients with thymoma. Herein, we developed a 3D DenseNet deep learning (DL) model based on preoperative computed tomography (CT) as a non-invasive method to detect MG in thymoma patients. Methods: A large cohort of 230 thymoma patients in a hospital affiliated with a medical school were enrolled. 182 thymoma patients (81 with MG, 101 without MG) were used for training and model building. 48 cases from another hospital were used for external validation. A 3D-DenseNet-DL model and five radiomic models were performed to detect MG in thymoma patients. A comprehensive analysis by integrating machine learning and semantic CT image features, named 3D-DenseNet-DL-based multi-model, was also performed to establish a more effective prediction model. Findings: By elaborately comparing the prediction efficacy, the 3D-DenseNet-DL effectively identified MG patients and was superior to other five radiomic models, with a mean area under ROC curve (AUC), accuracy, sensitivity, and specificity of 0.734, 0.724, 0.787, and 0.672, respectively. The effectiveness of the 3D-DenseNet-DL-based multi-model was further improved as evidenced by the following metrics: AUC 0.766, accuracy 0.790, sensitivity 0.739, and specificity 0.801. External verification results confirmed the feasibility of this DL-based multi-model with metrics: AUC 0.730, accuracy 0.732, sensitivity 0.700, and specificity 0.690, respectively. Interpretation: Our 3D-DenseNet-DL model can effectively detect MG in patients with thymoma based on preoperative CT imaging. This model may serve as a supplement to the conventional diagnostic criteria for identifying thymoma associated MG.

Objectives: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics. Methods: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat‐sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022. Results: A total of 18 cases diagnosed with thymoma‐associated autoimmune encephalitis (TAAE) and thymoma‐associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat‐sen University and the other 15 were published case reports. 5/18 patients had alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor antibody (AMPAR‐Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti‐acetylcholine receptor antibody (AChR‐Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence. Conclusions: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2‐Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.

Background: The prevalence of patients positive for muscle-specific kinase antibody (hereafter, MuSK-Ab) accounts for 5–8% of all myasthenia gravis (MG) cases. Currently, efgartigimod has shown good therapeutic effects in MUSK-Ab-positive MG patients in a phase III clinical trial. However, phase III clinical trials tend to exclude MG patients in exacerbation, and there are only few real-world studies on the efficacy of efgartigimod in MuSK-Ab-positive myasthenic crisis (MC) patients. This retrospective, real-world study aimed to explore the efficacy of efgartigimod in MuSK-Ab-positive MG with exacerbation.Methods: We reviewed the clinical data of four MuSK-Ab-positive patients with exacerbation of MG who received efgartigimod at the First Affiliated Hospital of Sun Yat-sen University, including two patients with MC. All patients were admitted between September 2023 and May 2024. Most patients are simultaneously undergoing rituximab treatment.Results: Each patient completed one cycle of efgartigimod. After the first administration, four patients showed a clinically meaningful decrease in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score (a reduction of more than 4 points compared to baseline), and all patients showed a decrease in IgG levels after one cycle of efgartigimod. Regarding safety, none of the patients experienced any obvious adverse effects. At the final follow-up, all patients achieved the minimal symptom expression status (an MG-ADL score of 0 or 1) following the first administration of efgartigimod for 8.75 ± 5.56 weeks. This article presents a case involving a patient who exhibited prompt alleviation of symptoms following the administration of a high dose of efgartigimod (20 mg/kg, given on days 1 and 5), without the use of any other fast-acting treatment.Conclusion: This retrospective real-world study demonstrates the effectiveness and safety of efgartigimod in these four MuSK-Ab-positive, female Asian patients with exacerbation of MG, as well as in patients experiencing MC. It is important to note that efgartigimod should not be viewed as a substitute for foundational immunotherapy; rather, it is intended as a rescue treatment during exacerbations and as an adjunctive therapy in the context of long-term immunotherapy. This non-invasive approach has the potential to become another treatment option for MuSK-Ab-positive MG patients.