Clinical characteristics of double negative atypical inflammatory demyelinating disease: A prospective study.

OBJECTIVE: This study aimed to investigate the clinical characteristics and predictors of relapse in double negative atypical inflammatory demyelinating disease (IDD) and to explore potential antigenic targets by tissue-based assays (TBA) using rat brain indirect immunofluorescence. METHODS: We compared the clinical, laboratory, and MRI data of double negative atypical IDD with other IDD patients. Serum samples were collected for TBA. The predictors of relapse were examined over a minimum of 24 months follow-up. RESULTS: In our cohort of 98 patients with double negative atypical IDD, there was no significant female predominance (58.2%, 57/98). The lesions primarily affected the spinal cord and brain stem, with fewer cases of involvement in the area postrema (5.1%, 5/98) and longitudinally extensive transverse myelitis (43.9%, 43/98). A total of 62.5% (50/80) patients tested positive for anti-astrocyte antibodies based on rat brain TBA. Over a median duration of 39.5 months, 80 patients completed the entire follow-up, and 47.5% (38/80) patients exhibited monophasic course. A total of 36% (18/50) patients positively for anti-astrocyte antibodies had a monophasic course, which is significantly lower than patients negatively for anti-astrocyte antibodies (66.7%, 20/30) (p = 0.008). The presence of anti-astrocyte antibodies (hazard ratio (HR), 2.243; 95% CI, 1.087-4.627; p = 0.029) and ≥4 cerebrum lesions at first attack (HR, 2.494; 95% CI, 1.224-5.078; p = 0.012) were risk factors for disease relapse, while maintenance immunotherapy during remission (HR, 0.361; 95% CI, 0.150-0.869; p = 0.023) was protective factor. INTERPRETATION: Double negative atypical IDD are unique demyelinating diseases with a high relapse rate. Maintenance immunotherapy is helpful to the prevention of relapse, particularly in patients with anti-astrocyte antibodies or ≥4 cerebrum lesions at first attack.

Lymphoplasmapheresis versus plasma exchange in severe myasthenia gravis: a retrospective cohort study.

Background: Lymphoplasmapheresis (LPE) is a new therapy developed on the basis of traditional plasma exchange (PE) in combination with leukapheresis. Currently, it remains unclear whether PE and LPE show differences in efficacy for severe MG. Methods: A retrospective analysis was conducted on 198 MG patients, 75 in the PE group and 123 in the LPE group, and the patients' Myasthenia Gravis Foundation of America (MGFA) Clinical Classification was Class IV. The treatment outcome was the change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to the end of treatment. Propensity score matching (PSM) was applied for the balance of confounders between the two groups. Results: In this study cohort, the safety profile of LPE and PE was good and no serious adverse events were observed. Based on PSM, 62 patients treated with LPE and 62 patients treated with PE were entered into a comparative efficacy analysis. In the PE group, patients underwent a total of 232 replacements, with a mean of 3.74. PE significantly improved the patients' QMGS performance, with the mean QMGS decreasing from 22.98 ± 4.03 points at baseline to 18.34 ± 5.03 points after treatment, a decrease of 4.68 ± 4.04 points (p < 0.001). A decrease of ≥3 points in QMGS was considered a significant improvement, with a treatment response rate of 67.7% in the PE group. In the LPE group, patients received a total of 117 replacements, with a mean of 1.89. The patients' mean QMGS was 23.19 ± 4.11 points at baseline and was 16.94 ± 5.78 points after treatment, a decrease of 6.26 ± 4.39 points (p < 0.001). The improvement in QMGS was more significant in patients treated with LPE compared to the PE group (p = 0.039). The treatment response rate in the LPE group was 79%, which was not significantly different compared to the PE group (p = 0.16). The LEP group had a shorter mean length of stay compared to the PE group (10.86 ± 3.96 vs. 12.14 ± 4.14 days), but the difference was not statistically significant (p = 0.13). During the 2-month follow-up period, LPE may be associated with better functional outcomes for patients, with lower QMG score and relapse rate. LPE and PE were both effective in reducing the levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and AChR-Ab. Compared to PE, LPE was superior in the reduction of AChR-Ab titer. Conclusion: In severe MG, LPE may be a more preferred treatment option than PE. It achieves treatment outcomes that are not inferior to or even better than PE with fewer replacements. This study provides further evidence to support the application of LPE as a new treatment option for MG.

Analysis of LAP+ and GARP+ Treg subsets in peripheral blood of patients with neuromyelitis optica spectrum disorders.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a group of antibody-mediated inflammatory demyelinating central nervous system diseases. T lymphocytes participate in NMOSD pathogenesis, with regulatory T cells (Treg) being the core in maintaining immune homeostasis. Studies have revealed that different Treg subsets play different roles in autoimmune diseases. The distribution of LAP+ or GARP+ Treg subsets in NMOSD may help us deeply understand their immune mechanism. METHODS: This study reviewed 22 NMOSD patients and 20 normal controls. Flow cytometric analysis was utilized to detect subsets of Treg cells expressing Foxp3, Helios, LAP, or GARP in peripheral blood. ELISA was used to detect plasma TGF-ß1 and IL-10. In addition, changes in the proportion of Treg cell subsets before and after glucocorticoid treatment in 10 patients were analyzed. RESULTS: Compared with healthy controls, LAP and GARP expressions were significantly downregulated in the peripheral blood of NMOSD patients. TGF-ß1 expression in NMOSD patients was lower and was positively correlated with the ratio of CD4+GARP+ Treg cells. After treatment with glucocorticoid, LAP and GARP expressions in the peripheral blood of NMOSD patients were upregulated. CONCLUSIONS: The proportion of Treg cells expressing LAP and GARP is downregulated, implying that Treg cells with the best inhibitory function are insufficient to maintain autoimmune homeostasis in NMOSD patients. Upregulation of Treg cells expressing LAP and GARP in NMOSD patients may be one of the mechanisms of glucocorticoid treatment.

Application of lymphoplasmapheresis in the treatment of severe myasthenia gravis.

Background: Lymphoplasmapheresis (LPE) is a treatment that combines traditional plasma exchange and lymphocyte removal technique. It has been applied to treat a variety of autoimmune diseases, but its application value in the treatment of severe myasthenia gravis (MG) is not yet clear. Therefore, the aim of this study was to investigate the efficacy and safety of LPE in severe MG. Methods: Clinical data of 123 severe patients with MG (Myasthenia Gravis Foundation of America Clinical Classification, Class IV) who received LPE treatment were included in a retrospective analysis. Efficacy was evaluated by the change of Quantitative Myasthenia Gravis score (QMGS) before and after treatment. Univariate and multivariate logistic regression analysis was used to explore clinical factors affecting efficacy. Results: A total of 220 replacements were performed in 123 patients, with an average of 1.79 replacements per patient. The overall safety of LPE was good, and no serious adverse reactions occurred. After treatment, the mean QMGS of patients decreased significantly, from 23.40 ± 4.25 points before treatment to 17.93 ± 5.61 points after treatment, a decrease of 5.47 ± 4.16 points. 75.6% of patients experienced remission of clinical symptoms. During a 2-month follow-up of 64 patients, a progressive improvement in QMGS was found. Each muscle group involved in MG responded well to LPE treatment. In addition, LPE significantly reduced the levels of AChR-Ab and inflammatory cytokines in patients. Age ≥ 50 years and co-infection were unfavorable factors affecting the efficacy. Conclusions: In this study cohort, LPE is safe for the treatment of severe MG and achieves good treatment outcome with fewer replacements. In patients with MG, the avoidance and timely control of infection are necessary. Our study provides a potential new treatment option for severe MG.

Vaccination in neuromyelitis optica spectrum disorders: Friend or enemy?

Neuromyelitis optica spectrum disorders (NMOSDs) are uncommon antibody-mediated autoimmune diseases of the central nervous system (CNS), mainly occurring in optic nerves and spinal cord, which can cause visual impairment, paralysis, and occasionally bulbar dysfunction. Such neurological deficits can adversely affect pulmonary functions and increase complicated infection risk. Besides, most NMOSD patients undergo immunosuppressive therapy. All these factors make NMOSD patients the potential high-risk group under the current pandemic of coronavirus disease 2019 (COVID-19). Meanwhile, COVID-19 infection has already been demonstrated as a risk factor for NMOSD relapses. This review discusses the basic immunology of vaccination and common problems, including immunogenicity, safety, and efficacy of vaccination on NMOSD patients. Additionally, we offered vaccination recommendations, health care and treatment advice for NMOSD patients under the background of COVID-19.

Serological markers exploration and real-world effectiveness and safety of teriflunomide in south Chinese patients with multiple sclerosis.

BACKGROUND: Since September 2012, when teriflunomide was approved as a disease-modifying treatment for relapsing multiple sclerosis, real-world observational studies on teriflunomide in Chinese patients are limited. METHODS: We collected demographic characteristics and peripheral blood samples at different time points. Clinical symptoms, magnetic resonance imaging data, and concentrations of neurofilament light chains and multiple cytokines at different time points were compared to assess the efficacy. Moreover, the safety was assessed by blood routine, liver and kidney function, and a questionnaire to report adverse reactions. RESULTS: Teriflunomide significantly reduced serum levels of neurofilament light chains and several inflammatory cytokines. After accepting teriflunomide treatment, many clinical symptoms improved, scores of the expanded disability status scale decreased from 2.0 to 1.75, and annualized relapse rates decreased from 1.45 to 0.31. 29 (80.56%) and 15 (78.95%) patients achieved the no evidence of disease activity-3 status after 6 months and 12 months treatment, respectively. Teriflunomide was associated with mild or moderate discomfort, and discontinuation rates due to adverse events were low. CONCLUSION: Serum neurofilament light chain protein is sensitive to teriflunomide treatment, suggesting that it has the potential to be used as an indicator to assess the efficacy of teriflunomide. Teriflunomide can significantly reduce the concentrations of inflammatory cytokines, indicating that teriflunomide may regulate neuroinflammation through the inhibitory effect on a variety of immune cells and their cytokines. Teriflunomide can improve clinical symptoms and disease severity in MS patients in southern China, and patients have good compliance.

Case Report: Antibodies to the N-Methyl-D-Aspartate Receptor in a Patient With Multiple Sclerosis.

The association between multiple sclerosis and anti-N-Methyl-D-Aspartate receptor encephalitis is limited to merely a few case reports, and the exploration of the pathogenic mechanisms underlying the overlap of these two disease entities is very limited. Therefore, case reports and literature review on N-Methyl-D-aspartate receptor antibody in patients with multiple sclerosis are unusual and noteworthy. A young female had the first episode of paresthesia and motor symptoms with positive anti-N-Methyl-D-Aspartate receptor antibody and recovered after immunotherapy, and at the first relapse, the patient developed disorders of consciousness with positive anti-N-Methyl-D-Aspartate receptor antibody, findings of magnetic resonance imaging showed features of autoimmune encephalitis, which was also controlled by immunotherapy. At the second relapse, anti-N-Methyl-D-Aspartate receptor antibody turned negative while oligoclonal bands presented positive, and findings of magnetic resonance imaging showed features of multiple sclerosis. Afterwards, we followed the patient after receiving disease modifying treatment to monitor the efficacy and safety of teriflunomide. Based on literature review, demyelinating diseases patients with anti-neuronal antibody have complex, diverse and atypical symptoms; therefore, high attention and increased alertness are necessary for neurologists. Conclusively, anti-neuronal antibody may present in many neuroinflammatory conditions, and diagnostic criteria should be used with caution if the clinical presentation is atypical, and neurologists should not rely excessively on laboratory tests to diagnose neurological diseases. Timely and comprehensive examination and consideration as well as early standardized treatment are the key factors to reduce patient recurrence and obtain a good prognosis.