Neuromyelitis optica spectrum disorder (NMOSD) is a kind of demyelinating disease of central nervous system which mainly affect optic nerve and spinal cord. Because of its serious blindness and disability, how to effectively prevent relapse has become the focus of ophthalmologists. With the deep understanding of the pathogenesis and the progress of scientific and technological means, more and more monoclonal antibodies(mAb) continue to enter clinical trials. B cell surface antigen CD20 blocker, rituximab, has become a first-line drug for the treatment of NMOSD. CD19 blocker, inebilizumab, can reduce the recurrence and disability of NMOSD patients. The addition of interleukin 6 receptor blocker, satralizumab, and complement C5 inhibitor, eculizumab, reduce the recurrence. Some mAbs such as natalizumab and alemtuzumab may not be effective for the treatment of NMOSD. The expansion of mAb treatment indications and the launch of new drugs still require more clinical trials which are large-scale and international cooperation. At the same time, its potential adverse events and cost issues cannot be ignored.
【摘要】 目的 在实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)模型中,比较常规T2加权成像(T2weighted imaging,T2WI)、钆二乙三胺五醋酸(gadoliniumdiethylenetriamine pentaacetic acid,GdDTPA)和超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)增强图像之间的差异,探讨巨噬细胞在多发性硬化(multiple sclerosis,MS)炎性活动病灶中的细胞学标志。方法 在EAE模型临床症状的亚临床期、初发期、高峰期,13只复发缓解(relapsingremitting,RR)EAE大鼠模型组和13只正常对照组大鼠在注入对比剂之前均行常规T2WI扫描,接着分别在其尾静脉注入GdDTPA后5 min行T1加权成像(T1weighted imaging,T1WI),再注入SPIO,24 h后行T2WI扫描。扫描完毕后立即处死大鼠取脑,行脑组织切片的ED1免疫组织化学染色和Prussian blue染色。结果 EAE模型组大鼠在第11天出现临床症状(初发期),第14天达到高峰期;MRI检查:SPIO增强图像对EAE病灶的显示较常规T2WI和GdDTPA增强图像好。病理学检查:ED1染色,在SPIO显示为低信号的区域内出现了炎症细胞(以巨噬细胞为主)浸润;Prussian blue染色示病灶内巨噬细胞胞质内出现了蓝染颗粒,沉积部位与T2WI上低信号区对应。对照组大鼠均无异常。结论 SPIO较GdDTPA更好地显示EAE模型中炎性活动性病灶内血管周围以巨噬细胞为主的浸润。
ObjectiveTo preliminary investigate the impact of the diagnosis-related groups (DRG) payment method reform on the diagnosis and treatment of inpatient medical insurance patients with neuromyelitis optica spectrum disorders (NMOSD), and to propose potential improvement strategies. MethodsA single-center, retrospective study. From October 1, 2020, to September 30, 2022, 44 hospitalized medical insurance patients with acute-phase NMOSD diagnosed and treated at the First Affiliated Hospital of Northwest University (Xi'an First Hospital) were included in the study. Among them, there were 11 males and 33 females, with an average age of (40.8±20.2) years. According to the implementation time of DRG payment, patients were divided into two groups: group A, which consists of cases one year before the implementation of DRG payment from October 1, 2020 to September 30, 2021, and group B, which consists of cases one year after the implementation of DRG payment from October 1, 2021 to September 30, 2022, with 20 and 24 cases, respectively. Detailed information such as hospitalization duration, treatment methods, and hospitalization costs of the two groups of patients was collected. Comparative analysis was conducted on hospitalization costs and treatment methods between the two groups. For intergroup comparison, t-test was used for normally distributed data, and Mann-Whitney U test was used for skewed distributed data. ResultsAmong the 44 patients, 5 cases (5/24, 20.8%) received plasma exchange (PE) treatment, all of whom were in group B. The numbers of patients who received and did not receive intravenous immunoglobulin (IVIG) treatment were 9 and 11 in group A, respectively, and 7 and 12 in group B (except for 5 cases who received PE treatment), respectively. Compared with group A, there was no significant decrease in hospitalization duration (t=0.004) and total hospitalization costs (Z=0.036), as well as costs for western medicine (Z=0.036), examinations (Z=0.011), laboratory tests (Z=0.040), treatments (Z=0.017), and nursing (Z=3.131) in group B, and the differences were not statistically significant (P＞0.05). For patients receiving PE treatment, except for the cost of western medicine (Z=0.062, P=0.804), the other costs (Z=8.288, 5.013, 11.400, 10.925, 9.126) were significantly higher than those of patients not receiving PE treatment, and the hospitalization duration (t=20.474) was significantly prolonged, with statistically significant differences (P＜0.05). The total hospitalization costs of patients receiving IVIG treatment were significantly higher than those not receiving IVIG treatment in both group A and group B, with statistically significant differences (Z=7.690, 10.314; P＜0.05). There was no statistically significant difference in the comparison of total hospitalization costs between patients receiving IVIG treatment in group A and group B (Z=0.137, P＞0.05). ConclusionsThere is no significant decrease in various hospitalization costs of NMOSD medical insurance patients in Xi'an after the implementation of DRG payment, especially for patients receiving PE treatment. It is suggested to optimize the rate stratification of NMOSD patients when implementing DRG payment methods.
Neuromyelitis optica-related optic neuritis (NMO-ON) is a kind of severe optic nerve disease, which always leads to replase, poor prognosis, and even blindness. Aquaporin 4 antibody (AQP4-IgG) is the main diagnostic biomarker for neuromyelitis optica with high specificity. Serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG) is helpful for the diagnosis of AQP4-IgG negative patients. The study of biomarkers is helpful to deeply understand the pathogenesis of NMO-ON, help the diagnosis of the disease, and finally make precise treatment. Orbital MRI can help to differentiate MOG-IgG positive from AQP4-IgG positive neuromyelitis optica and optic neuritis, which is very important for the diagnosis of NMO-ON. At present, the standardized treatment of NMO-ON can be divided into two clinical stages: acute stage and remission stage. Corticosteroids and plasma exchange are the main treatments in acute stage, aiming at alleviating acute inflammatory reaction and improving prognosis. Immunosuppressive agents and biological agents are the main treatments in remission stage, aiming at preventing or reducing recurrence. With the development of the diagnosis and treatment of NMO-ON, we find that it is more and more important to strengthen the construction of neuro-ophthalmology team in China, establish clinical epidemiological database of NMO-ON, and carry out multi-centre, large-sample, prospective clinical control studies in China to provide evidence-based medicine for Chinese people. In addition, we need to strengthen efforts to establish and improve the diagnostic criteria for NMO-ON and the promotion of diagnostic and therapeutic criteria, and strive to improve the clinical diagnosis and treatment level of NMO-ON in China.
Objective To observe the correlation of serum aquaporin 4 (AQP4) antibodies and condition and visual prognosis in patients with severe neuromyelitis optica spectral disorders (NMOSD). Methods Fifty NMOSD patients with visual acuity of 20/200 or worse in at least one eye were enrolled in this retrospective analysis. There were 12 males and 38 females. The age ranged from 17 to 65 years, with the mean of (39.86±2.02) years. The patients were divided into two groups according to the serum AQP4-IgG status. The ophthalmologic examination, serum anti-nuclear antibodies (ANA), myelin oligodendrocyte glycoprotein (MOG) antibody detection and vision prognosis were compared and analyzed. Glucocorticoid therapy was delivered to 46 patients who were within 1 month of onset. The visual acuity of the patients after treatment was divided into complete recovery, partial recovery, stabilization and reduction, and the visual acuity of the two groups were analyzed. Results Among 50 patients, there were 30 (60%) seropositive patients (positive group), 20 (40%) seronegative patients (negative group). The positive group had significantly higher ratio of female to male (P=0.004), and more binocular optic neuritis (ON) (P=0.010) compared with the negative group. More recurrence ON were also found in the positive group, but without statistic difference between two groups (P=0.167). There was no difference of age, course, and vision damage degrees and abnormal orbital MRI scanning between two groups (P＞0.05). Among 24 patients who underwent serum ANA detection in the positive group, 8 patients were positive. All of 18 patients who underwent serum ANA detection in the negative group were negative. The difference of the ratio of serum ANA positive patients between two groups was significant (P=0.030). Serum MOG antibody detection in the positive group was negative (0/10). Sixteen patients who underwent MOG antibody detection in negative group, 4 patients were positive. After treatment, there were 23.3%, 23.3%, 53.3% patients with vision of complete recovery, partial recovery and reduction in the positive group; 25.0%, 30.0%, 25.0% patients with vision of complete recovery, partial recovery and reduction in the negative group, respectively. There was no difference in proportion of vision with complete recovery and partial recovery between two groups (P=0.163, 0.607), but significant difference was observed in proportion of vision with stabilization and reduction between two groups (P=0.021, 0.048). Conclusions The positive serum AQP4 antibody is common in patients with severe NMOSD. The patients with AQP4 antibody in the serum are more likely combined with immunological serological markers and poor vision prognosis.
Plasma exchange (PE) is a therapeutic blood component replacement method. The blood of patients is first separated into plasma and blood cell components using a blood cell separator in vitro, the plasma containing harmful pathogenic substances is then discarded and replaced with the same volume of exchange solution. Finally the separated blood cells together with the exchange solution are returned back to the blood circulation of patients. By reducing the circulating antibodies, abnormal plasma proteins or cytokines and other pathogenic molecules, PE can block the disease process. PE has a good therapeutic effect on neuromyelitis optica-related optic neuritis (NMO-ON), which shows resistant to glucocorticoid therapy for the first onset. The American Society for Apheresis guideline evaluates PE for acute optic neuritis as a recommended grade 1B, type II indication. In the implementation of PE treatment for NMO-ON and other diseases, indications and contraindications should be strictly adhered to the guideline, treatment procedures and protocols should be optimized, common adverse events and its prevention and management should be known and alerted. It is important to conduct multi-center clinical cooperation and a high standard clinical randomized controlled study, to find out the optimal time window, the best protocol, and the associated factors for the efficacy and prognosis of PE in NMO-ON.