A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke.

Objective: To explore the efficacy of ginkgo diterpene lactone (GDLM) on cognitive function in patients with acute ischemic stroke (AIS). Methods: A total of 126 patients with AIS in Shaanxi Provincial People's Hospital from July 2019 to December 2020 were collected and randomly divided into the control group and treatment group (n = 63). All patients received conventional treatment, on which 25 mg/day GDLM was administered in the treatment group. Coagulation and inflammation indexes, National Institutes of Health Stroke Scale (NIHSS) and activities of daily living scale (ADL) scores were measured before and 14 days after treatment. NIHSS and ADL scores were performed again after 3 months. Cognitive function was assessed by Montréal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, and potential P300. Results: After 14 days of treatment, all biochemical indices were lower than before treatment (P < 0.05). The NIHSS and ADL scores of the treatment group were significantly better than those of the control group after treatment (P < 0.05). The MoCA and MMSE scores of the treatment group improved more significantly compared with the control group (P < 0.05). After treatment, the P300 indexes of both groups were significantly better than before treatment (P < 0.05). Conclusion: Conventional treatment of AIS combined with GDLM can effectively improve the cognitive function of patients, which is worthy of clinical recommendation.

Safety of teriflunomide in Chinese adult patients with relapsing multiple sclerosis: A phase IV, 24-week multicenter study.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant (n = 42) and wild type groups (n = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] µg/mL; wild type, 49.1 [32.0] µg/mL) and area under plasma concentration-time curve over a dosing interval (AUCtau) (variant, 1731.3 [769.0] µg∙h/mL; wild type, 1564.5 [1053.0] µg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION: NCT04410965, https://clinicaltrials.gov.

Case report: Hyponatremia is an initial presentation of Neuromyelitis optica spectrum disorder.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) is often misdiagnosed or delayed because of the complex and diverse clinical manifestations, especially the atypical initial presentation. Hyponatremia can be an infrequently isolated initial presentation of NMOSD and is associated with hypothalamus involvement. Awareness of this mechanism will help clinicians to identify NMOSD early, treat it in time and improve the prognosis. METHODS: We describe a 36-year-old woman who developed repeated hyponatremia and then experienced diplopia. Serum AQP4, MOG, MBP and GFAP antibody were detected, and NMOSD was finally diagnosed. RESULTS: She responded well to high-dose glucocorticoids. Sequential treatment with mycophenolate mofetil (MMF) was prescribed. Two-month follow-up revealed full recovery. So far, after 10 months, the patient still has no recurrence. CONCLUSION: For young patients, repeated hyponatremia, with or without slight fever, and no evidence of obvious infection, brain magnetic resonance imaging (MRI) and serum AQP4/MOG antibody detection may be useful to determine whether there is a possibility of NMOSD.

Pain in neuromyelitis optic spectrum disorder.

BACKGROUND: Pain is a common symptom of neuromyelitis optica spectrum disorder (NMOSD), but there are relatively few studies on NMOSD pain. METHODS: We retrospectively reviewed the medical records of 145 patients with NMOSD admitted to our hospital between July 2016 and June 2019. RESULTS: The clinical characteristics of pain and factors related to NMOSD were analyzed, revealing that the incidence of pain in NMOSD is high and can be used for disease localization. CONCLUSION: Different types of pain occur at different stages of the disease, and serum aquaporin-4 antibody (AQP4-ab) positivity is an independent risk factor for NMOSD pain. Hormones and biological immune agents may also be effective in some cases.

The circadian rhythms regulated by Cx43-signaling in the pathogenesis of Neuromyelitis Optica.

Introduction: Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). NMO manifests as selective and severe attacks on axons and myelin of the optic nerve and spinal cord, resulting in necrotic cavities. The circadian rhythms are well demonstrated to profoundly impact cellular function, behavior, and disease. This study is aimed to explore the role and molecular basis of circadian rhythms in NMO. Methods: We used an Aquaporin 4(AQP4) IgG-induced NMO cell model in isolated astrocytes. The expression of Cx43 and Bmal1 were detected by real-time PCR and Western Blot. TAT-Gap19 and DQP-1105 were used to inhibit Cx43 and glutamate receptor respectively. The knockdown of Bmal1 were performed with the shRNA containing adenovirus. The levels of glutamate, anterior visual pathway (AVP), and vasoactive intestinal peptide (VIP) were quantified by ELISA kits. Results: We found that Bmal1 and Clock, two essential components of the circadian clock, were significantly decreased in NMO astrocytes, which were reversed by Cx43 activation (linoleic acid) or glutamate. Moreover, the expression levels of Bmal1 and Clock were also decreased by Cx43 blockade (TAT-Gap19) or glutamate receptor inhibition (DQP-1105). Furthermore, adenovirus-mediated Bmal1 knockdown by shRNA (Ad-sh-Bmal1) dramatically decreased the levels of glutamate, AVP, and VIP from neurons, and significantly down-regulated the protein level of Cx43 in NMO astrocytes with Cx43 activation (linoleic acid) or glutamate treatment. However, Bmal1 knockdown did not alter these levels in normal astrocytes with Cx43 blockade (TAT-Gap19) or glutamate receptor inhibition (DQP-1105). Discussion: Collectively, these results suggest that Cx43-glutamate signaling would be a critical upstream regulator that contributes to the NMO-induced rhythmic damage in SCN astrocytes.

Factors Influencing the Degree of Disability in Patients With Multiple Sclerosis.

Objective: To explore the factors influencing the degree of disability in patients with multiple sclerosis (MS), and to provide evidence for its early diagnosis, prognostic evaluation and clinical intervention. Methods: This retrospective observational study included 72 patients with relapsing-remitting multiple sclerosis (RRMS) at the First Hospital of Shanxi Medical University. All patients completed craniocerebral and spinal cord MRI (with or without Gd enhancement) and were evaluated for Expanded Disability Status Score (EDSS) scores before receiving treatment. Results: Among 72 patients with RRMS, 45 (62.5%) had an EDSS score ≤3; A total of 27 patients (37.5%) had an EDSS score >3 points. Univariate analysis showed that age, annual recurrence rate (ARR), drug use, albumin (ALB), triglycerides (TG), and total number of lesions in groups with EDSS score ≤3 were significantly different from those with an EDSS score > 3 points (P < 0.05). Multivariate logistic regression analysis showed that ALB, total number of lesions, and drug use were independent influencing factors of the degree of disability in patients with MS, and the difference was statistically significant (P < 0.05). An ROC curve was constructed using ALB and the total number of lesions. The AUC of ALB was 0.681, P < 0.05, and the best cut-off value was 44.2 g/L. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 85.2%, while its specificity was 51.1%. The AUC of the total number of lesions was 0.665 (P < 0.05) and the best cut-off value was 5.5. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 70.4%, while its specificity was 64.4%. The AUC of the combined ALB, total number of lesions, and drug use was 0.795 (P < 0.05), sensitivity was 77.8, and specificity was 73.3%. The optimal diagnostic cut-off value of the regression equation for the EDSS score of patients with multiple sclerosis was 0.420. Conclusion: Serum ALB, total number of lesions, and drug use in patients with multiple sclerosis were independent factors influencing the degree of disability. These findings provide clinical evidence for the prognostic evaluation and early intervention of patients with multiple sclerosis.

A comparison of the effects of rituximab versus other immunotherapies for MOG-IgG-associated central nervous system demyelination: A meta-analysis.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is now recognised as a nosological entity with specific clinical and paraclinical features to aid early diagnosis. Rituximab (RTX) is a chimeric monoclonal antibody directed against CD20 epitope expressed on pre-B and mature B cells and is used to treat B-cell-derived lymphoid neoplasms and antibody-mediated autoimmune diseases. In this review, we performed a meta-analysis to evaluate RTX efficacy and assessed the treatment efficacies based on relapse rates. METHODS: This study was conducted according to the PRISMA (Preferred Reporting Items for Systemic review and Meta-Analysis) statement. We searched for publications on the PubMed, Embase, Cochrane Library, clinical trials up to December 2020. We compiled 5 studies, Meta-analysis forest plots was conducted for the ARR ratio change pre and post-treatment between rituximab and other disease modifying drugs. A sensitivity analysis was performed with mean difference (MD) of the efficacy of RTX versus other immunotherapies and subgroup analysis was also performed based on site of study. RESULTS: A meta-analysis of 5 studies with 239 participants was conducted. Patients have received rituximab were recorded in 82 of 239 (34.31%). The mean difference of ARR ratio of rituximab therapy versus other immunotherapies was 0.16 (95%CI, -0.15 to 0.47). No studies found to significantly affect heterogeneity. No major differences occurred in 9.2% of China patients (95% CI: -0.20-1.86; I2=0%) and 90.8% of non- China patients (95% CI: -0.24-0.42; I2=0%). Meanwhile there was no significant subgroup difference (p = 0.18) between them. CONCLUSION: RTX reduces the relapse frequency in most patients with MOG antibody disease, but there is no differences between rituximab and other immunotherapies in MOG antibody disease. Future a large multicenter randomized controlled clinical trial to thoroughly characterize the efficacy of rituximab for MOG antibody disease is necessary.

Status of Immunotherapy Acceptance in Chinese Patients With Multiple Sclerosis: Analysis of Multiple Sclerosis Patient Survival Report 2018.

Objective: The prevalence of multiple sclerosis (MS) in China is low, although it has been increasing recently. Owing to the paucity of data on immunotherapy acceptance in the Chinese population, we conducted this study to analyze factors affecting the acceptance of immunotherapy and selection of disease-modifying therapies (DMTs) based on personal and clinical data of patients with MS. Methods: In this study, data were obtained from the Multiple Sclerosis Patient Survival Report 2018, which was the first national survey of patients with MS in China. There were 1,212 patients with MS from 31 provinces who were treated at 49 Chinese hospitals over a 4-month period from May 2018 to August 2018, and the patients were asked to complete online questionnaires to assess their understanding of the disease. Results: In general, highly educated patients with frequent relapses were more willing to receive treatment regardless of DMTs or other immunotherapy, and patients with more understanding of the disease opted to be treated. Younger patient population, patients with severe disease course, and those with more symptoms were likely to choose the treatment. Moreover, a higher proportion of women chose to be treated with DMTs than with other immunotherapies. Conclusions: Education status and patient awareness of the disease impact the treatment acceptance in Chinese patients with MS. Therefore, we call for improving the awareness of MS disease and social security to help patients to improve their quality of life.

Low-dose rituximab treatment for new-onset generalized myasthenia gravis.

The aim of this retrospective case series study was to evaluate the response and durability of rituximab in patients with new-onset acetylcholine receptor positive (AChR +) generalized myasthenia gravis (MG). Patients were initiated with low-dose rituximab treatment within 3.5 months of onset without concomitant oral immunosuppressants. Seventeen patients (89%) remained relapse-free with a mean follow-up of 51.3 months. Clinical improvement was observed in parallel with the maintenance of low-dose corticosteroids or the complete discontinuation of corticosteroids. Long-term depletion of B cells with low-dose rituximab treatment has shown favorable efficacy and tolerance in reducing disease activity for AChR+ generalized MG.

Immunotherapy choice and maintenance for generalized myasthenia gravis in China.

AIMS: To compare long-term efficacy and safety of immunotherapeutic strategies as maintenance to prevent disease relapses of generalized myasthenia gravis (MG) in real-world settings. METHODS: This is a retrospective cohort study on generalized MG conducted in seven major neurological centers across China. Eligible participants were patients with generalized MG who were under minimal manifestation status or better. Main outcome measures were probability of patients free of relapses and causes of drug discontinuation. RESULTS: Among 1064 patients enrolled, the median (interquartile range) age was 50.3 (37.0-62.5) years and 641 (60.2%) were women. Disease relapse was significantly lower for rituximab (6.1%) compared with all the other monotherapies (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030). As combination therapies, tacrolimus in combination with corticosteroids reduced risk of disease relapses compared with azathioprine with corticosteroids (HR = 0.45, 95% CI 0.25 to 0.81, P = .0077) or mycophenolate mofetil with corticosteroids (HR = 0.32, 95% CI 0.15 to 0.67, P = .0020). Otherwise, lower-dose corticosteroids or azathioprine as monotherapy significantly increased risk of disease relapses (HR = 2.78, 95% CI 1.94 to 3.99, P < .0001; HR = 2.14, 95% CI 1.42 to 3.23, P = .0003, respectively). The proportion of discontinuation was lowest in patients with rituximab (20.4%) as monotherapy and tacrolimus with corticosteroids (23.6%). Overall, combination treatment of immunosuppressants with corticosteroids had a lower rate of discontinuation compared with corresponding monotherapy (HR = 0.51, 95% CI 0.36 to 0.71, P < .0001). CONCLUSIONS: Rituximab as monotherapy and tacrolimus with corticosteroids displayed better clinical efficacy as well as drug maintenance to prevent disease relapses in patients with generalized MG.

Risk of COVID-19 infection in MS and neuromyelitis optica spectrum disorders.

OBJECTIVE: Disease-modifying drugs (DMDs) may alter the immune status and thus increase the susceptibility to coronavirus disease 2019 (COVID-19) in patients with MS or neuromyelitis optica spectrum disorders (NMOSD). However, evidence supporting this notion is currently lacking. In this study, we conducted a survey on the risk of COVID-19 in patients with MS and NMOSD. METHODS: The survey was conducted through the Chinese Medical Network for Neuroinflammation. Patients in 10 MS centers from 8 cities including Wuhan were included. Information about MS and NMOSD disease duration and the usage of DMDs were collected. Data of suspected cases of COVID-19 were obtained from hospital visits, questionnaires, and patient self-reporting. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was confirmed through clinical evaluation by a panel of experts in conjunction with chest CT and viral RNA detection. RESULTS: Eight hundred eighty-two of 1,804 (48.89%) patients with MS and 2,129 of 3,060 (69.58%) patients with NMOSD were receiving DMDs. There were no alterations in the patients' DMD regimen during January 15, 2020, to March 15, 2020, the 3-month period. None of the patients with MS treated with DMDs had COVID-19. However, 2 patients with relapsing NMOSD were diagnosed with COVID-19-related pneumonia. After treatment, both patients recovered from pneumonia and neither patient experienced new attacks due to predisposing SARS-CoV-2 infection in the following 2 months. CONCLUSIONS: No increased risk of COVID-19 infection was observed in patients with MS or NMOSD, irrespective of whether these patients received DMDs. A battery of stringent preventive measures adopted by neurologists to reduce COVID-19 infection in these patients may have contributed to low risk of COVID-19 infection.

Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Azathioprine is used as a first-line treatment to prevent relapses of neuromyelitis optica spectrum disorder (NMOSD). Tocilizumab has been reported to reduce NMOSD disease activity in retrospective case reports. We aimed to compare the safety and efficacy of tocilizumab and azathioprine in patients with highly relapsing NMOSD. METHODS: We did an open-label, multicentre, randomised, phase 2 trial at six hospitals in China. We recruited adult patients (aged ≥18 years) with highly relapsing NMOSD diagnosed according to 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, who had an Expanded Disability Status Scale (EDSS) score of 7·5 or lower, and had a history of at least two clinical relapses during the previous 12 months or three relapses during the previous 24 months with at least one relapse within the previous 12 months. Patients were randomly assigned (1:1) to intravenous tocilizumab (8 mg/kg every 4 weeks) or oral azathioprine (2-3 mg/kg per day) by an independent statistician using computer-generated randomisation software with permuted blocks of four. The central review committee, EDSS raters, laboratory personnel, and radiologists were masked to the treatment assignment, but investigators and patients were aware of treatment allocation. The minimum planned duration of treatment was 60 weeks following randomisation. The primary outcome was time to first relapse in the full analysis set, which included all randomly assigned patients who received at least one dose of study drug, and the per-protocol population, which included all patients who used azathioprine or tocilizumab as monotherapy. For the analyses of the primary outcome, the patients were prespecified into two subgroups according to concomitant autoimmune disease status. Safety was assessed in the full analysis set. This study is registered with ClinicalTrials.gov, NCT03350633. FINDINGS: Between Nov 1, 2017, and Aug 3, 2018, we enrolled 118 patients, of whom 59 were randomly assigned to tocilizumab and 59 were randomly assigned to azathioprine. All 118 patients received one dose of study drug and were included in the full analysis set. 108 participants were included in the per-protocol analysis (56 in the tocilizumab group and 52 in the azathioprine group). In the full analysis set, median time to the first relapse was longer in the tocilizumab group than the azathioprine group (78·9 weeks [IQR 58·3-90·6] vs 56·7 [32·9-81·7] weeks; p=0·0026). Eight (14%) of 59 patients in the tocilizumab group and 28 (47%) of 59 patients in the azathioprine group had a relapse at the end of the study (hazard ratio [HR] 0·236 [95% CI 0·107-0·518]; p<0·0001). In the per-protocol analysis, 50 (89%) of 56 patients in the tocilizumab group were relapse-free compared with 29 (56%) of 52 patients in the azathioprine group at the end of the study (HR 0·188 [95% CI 0·076-0·463]; p<0·0001); the median time to first relapse was also longer in the tocilizumab group than the azathioprine group (67·2 weeks [IQR 47·9-77·9] vs 38·0 [23·6-64·9]; p<0·0001). In the prespecified subgroup analysis of the full analysis set stratified by concomitant autoimmune diseases, among patients without concomitant autoimmune diseases, three (9%) of 34 patients in the tocilizumab group and 13 (35%) of 37 patients in the azathioprine group had relapsed by the end of the study. Among patients with concomitant autoimmune diseases, a lower proportion of patients in the tocilizumab group had a relapse than in the azathioprine group (five [20%] of 25 patients vs 15 [68%] of 22 patients; HR 0·192 [95% CI 0·070-0·531]; p=0·0004). 57 (97%) of 59 patients in the tocilizumab group and 56 (95%) of 59 patients in the azathioprine group had adverse events. Treatment-associated adverse events occurred in 36 (61%) of 59 tocilizumab-treated patients and 49 (83%) of 59 azathioprine-treated patients. One death (2%) occurred in the tocilizumab group and one (2%) in the azathioprine group, but neither of the deaths were treatment-related. INTERPRETATION: Tocilizumab significantly reduced the risk of a subsequent NMOSD relapse compared with azathioprine. Tocilizumab might therefore be another safe and effective treatment to prevent relapses in patients with NMOSD. FUNDING: Tianjin Medical University, Advanced Innovation Center for Human Brain Protection, National Key Research and Development Program of China, National Science Foundation of China.

Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study.

BACKGROUND: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. METHODS: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). RESULTS: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. CONCLUSIONS: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.

Alteration of Circadian Rhythms in 2D2 Transgenic Mice.

BACKGROUND Several immunological functions are dependent on circadian rhythms. However, there are still relatively few studies about circadian rhythms in neuromyelitis optica spectrum disorders (NMOSD) and 2D2 transgenic mice. We explore whether 2D2 mice have abnormalities in circadian rhythms and the potential underlying molecular mechanism. MATERIAL AND METHODS We first observed the wheel-running motion of the control and 2D2 mice using wheel-running measurements. The cytokine levels were also analyzed using enzyme-linked immunosorbent assay (ELISA), and the results of clock gene expressions in the suprachiasmatic nucleus (SCN) were investigated using real-time polymerase chain reaction (real-time PCR). RESULTS The wheel-running rhythm in 2D2 mice differed from that of the controls. The TNF-α and IL-10 rhythms were disrupted in 2D2 mice. Additionally, the rhythm of the clock genes, Per1 and Per2, and expression in the SCN of 2D2 mice were also changed. CONCLUSIONS The results presented here indicate that alteration of circadian rhythms in 2D2 mice affects behavior and immune function, and the potential molecular mechanism might be the Per1 and Per2 expression disorders in the SCN. 2D2 mice might be a suitable model for studying circadian disruption in NMOSD.

Effectiveness of low dose of rituximab compared with azathioprine in Chinese patients with neuromyelitis optica: an over 2-year follow-up study.

Neuromyelitis optical (NMO) and neuromyelitis optical spectrum disorder (NMOSD) are inflammatory autoimmune demyelination diseases affecting the central nervous system. We investigated the efficiency of low-dose rituximab treatment in 31 Chinese patients with NMO/NMOSD across a median period of 2.29 ± 0.97 years and azathioprine combined with corticosteroid treatment in 34 Chinese patients with NMO/NMOSD across a median period of 2.61 ± 0.94 years. Among the rituximab-treated patients, the mean Expanded Disability Status Scale (EDSS) was 5.62 ± 1.35 before treatment and 4.48 ± 0.78 at last follow-up, and the mean annualized relapse rate (ARR) was 1.39 ± 0.42 before treatment and 0.03 ± 0.13 at last follow-up. Among the azathioprine-treated patients, the mean EDSS was 5.63 ± 1.29 before treatment and 5.05 ± 1.00 at last follow-up, and the mean ARR was 1.28 ± 0.34 before treatment and 0.49 ± 0.21 at last follow-up. In this study, we showed that using low-dosage rituximab could benefit Chinese patients with NMO by reducing the new occurrence of relapses dramatically. Compared with the azathioprine-treated patients, we concluded that rituximab is more effective in preventing NMO relapse and could improve the symptoms.