Objective To evaluate the efficacy and safety of repeated treatments with low-dose rituximab for relapsing neuromyelitis optica spectrum disorder (NMOSD). Methods A perspective study. 21 patients who were diagnosed with NMOSD one year ago were recruited for rituximab treatment. Of 21 patients, one was male, 20 were females. Onset age was 10 - 51 years, the mean onset age was (26.2±12.0) years. Duration of disease was 2.3 - 25.8 years, the mean duration was (9.2±5.9) years. Best corrected vision activity (BCVA), expanded disability status scale (EDSS), annualized relapsing rate (ARR) were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. The BCVA was examined using Snellen chart, and converted to logMAR. The mean BCVA was 1.13±1.09, the mean BCVA in better eyes was 0.4±0.68, the mean BCVA in latter eyes was 1.87±0.90. The mean EDSS was 3.09±0.70. The mean ARR was 1.04±0.65. All patients underwent two cycles of RTX treatment. The annually induction treatment was RTX 100 mg per week for 4 weeks. Of 21 patients, 12 patients had treatment within one month after attack. The mean follow-up period was (28.4±4.9) months. The side effects were recorded, BCVA, EDSS, ARR were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. Paired t test, independent sample t test and Chi-squared test were used. Results The mean BCVA at last follow-up was 0.62±0.91, the mean BCVA in better eye was 0.62±0.91, the BCVA in latter eye was 1.0±1.01. The mean EDSS was 2.26±1.07. The mean ARR was 0.21 ± 0.3. After the treatment, patient had significant improvement on BCVA in worst eye (t=4.256), ARR (t=2.900), EDSS (t=4.620) with the significant differences (P＜0.05).Thirteen relapses in 9 patients were observed. B lymph cells were more than 0.01% in all relapses. There was no significant difference on the BCVA in better eye (t=1.840, P＞0.05). There were 9 patients had relapse, 13 times in total. Of 13 relapses, B lymph cell count was performed in 12 relapses, and the counts were 0.01% - 0.14%. There were no significant difference between relapsed patients and non-relapsed patients on onset age (t=0.67, P=0.51), whether underwent plasma exchange treatment (χ2=1.61, P＞0.05), with/without auto-immune antibody ratio (χ2=1.61, P＞0.05). Of 21 patients, 8 patients had side effects, including 5 patients with infection, 4 patients with chest congestion, 3 patients with hair losing, 2 patients with skin rashes, headache and short of breath, 1 patient with tinnitus, palpitation and fatigue. Four patients had more than one symptom. Of all patients who had side effects, slowing down the infusion speed of RTX or infusing 5 mg of dexamethasone could relieve the discomfort. Conclusion Lose-dose rituximab reduces the frequency of NMOSD relapses and is well tolerated.
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 分析合并免疫指标异常的视神经脊髓炎临床特点。 方法 回顾性分析2009年5月-2010年11月收治的62例视神经脊髓炎患者中24例合并免疫指标异常患者的临床资料。24例均为女性，发病年龄14~53岁。对其临床表现、视觉诱发电位、影像学检查结果、免疫检查结果进行分析。 结果 所有患者均有脊髓和视神经同时或先后受累的表现。24例视觉诱发电位检查23例异常。脊髓MRI显示病变集中于颈段、上胸段脊髓。颈段和胸段脊髓同时受累17例，单纯颈段脊髓受损6例，单纯胸段脊髓受损1例。所有患者抗核抗体滴度均≥1∶100，合并抗SSA抗体阳性14例（55.5％），同时合并抗SSB抗体阳性11例（45.8％），合并抗Rib抗体阳性1例，合并抗SCL-70抗体阳性1例，合并抗dsDNA抗体1例。 结论 视神经脊髓炎合并免疫指标异常的患者以女性较为多见，易复发，青壮年患者发病率最高。脊髓MRI示病变集中于颈段、上胸段脊髓，表现为长节段脊髓损害。视神经脊髓炎患者合并结缔组织病的病例较多。【Abstract】 Objective To analyze the clinical features of neuromyelitis optica (NMO) combined with abnormal immune parameters. Methods We retrospectively reviewed the clinical data of 24 patients with NMO and abnormal immune parameters among the 62 NMO patients who were admitted into our department between May 2009 and November 2010. All patients were female, aged from 14 to 53 years. We analyzed their clinical manifestations, visual evoked potentials, imaging results, and immunological examinations. Results All patients had simultaneous or successive spinal cord and optic nerve involvement. Twenty-three patients had abnormal visual evoked potential. MRI showed that the lesions focused on the cervical and upper thoracic spinal cord. Both cervical and thoracic spinal cord were involved in 17 cases; there were 6 cases of simple cervical spinal cord injury and 1 case of simple thoracic spinal cord damage. Antinuclear antibody titer of all the patients was ≥1∶100. Combined positive anti-SSA antibody occurred in 14 patients (55.5%); Concomitant positive anti-SSB antibodies occurred in 11 patients (45.8%); Combined positive anti-Rib antibodies occurred in 1 patient; Combined positive anti-SCL-70 antibody occurred in 1 patient; and combined positive anti-dsDNA antibodies occurred in 1 patient. Conclusions NMO combined with abnormal immune parameters mainly occurs in female patients, especially in young people. Recurrence rate is high. MRI shows that the lesions focus mainly on the cervical and upper thoracic spinal cord, manifesting the characteristic of long segment damage. And NMO is frequently combined with connective tissue disease.
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.
ObjectiveTo observe the ocular manifestations and the titer of aquaporin 4 antibody (AQP-4) in NMO patients, and to evaluate the BCVA prognosis in patients with different titers of AQP-4Ab.MethodsA retrospective case study. From September 2009 to March 2014, 132 NMO patients diagnosed in Department of Neurology and Ophthalmology in Huashan Hospital of Fudan University were included in the study. Among the patients, 74 patients (56.06%) were involved in optic nerve for the first time, among which 63 patients (47.72%) were involved in optic nerve alone, and 11 patients (8.33%) were involved in optic nerve and spinal cord at the same time. The recurrence rate was 62.88% (twice or more). All patients underwent BCVA, slit lamp microscope, fundus examination, thyroid function, sex hormones, and serum AQP-4Ab detection. BCVA was recorded at admission and before discharge from hospital, and worse BCVA was recorded in binocular patients. The BCVA of patients with different titers of AQP-4Ab were analyzed comparatively.ResultsAmong the 74 patients with optic nerve involved in the first onset, 50 patients with BCVA＜0.1 at the initial diagnosis (67.57%); AQP-4Ab positive was found in 56 patients, which including 13, 9 and 34 patients of AQP-4Ab titer 5 - 60, 61 - 100 and ＞100 RSRU/ml. After 2 weeks of treatment, BCVA improved in 40 patients (71.42%), including 11 (84.62%), 6 (66.67%) and 23 (67.64%) of AQP-4Ab titer 5 - 60, 61 - 100 and ＞ 100 RSRU/ml. Among 132 patients, 98 patients (74.24%) were AQP-4Ab positive. There were 73 patients (55.30%) with abnormal immune rheumatoid index.ConclusionsThe optic nerve is involved in 56.06% patients with NMO for the first time, and 67.57% of the patients had poor vision with BCVA＜0.1. BCVA prognosis is better in patients with serum AQP-4Ab titer of 5 - 60 RSRU/ml.
Neuromyelitis optica (NMO) is an autoimmune inflammatory diseases of the central nervous systems (CNS) mainly affecting the optic nerves and spinal cord. It has the characteristics of high recurrence rate and poor prognosis. NMO related optic neuritis is a common neuro-ophthalmic disease which often results in permanent visual loss or even blindness. Aquaporin 4 (AQP4) antibody is a specific and pathogenic autoantibody in NMO patients. Although AQP4 is expressed in multiple tissues, NMO pathology is remarkably limited to the CNS. Corticosteroids and other immunosuppressive drugs are the standard managements for NMO patients, in order to reduce the relapses and the severity of the acute attack. Multiple avenues of investigation in the laboratory have significantly advanced our understanding of NMO pathophysiology, which is helpful for our understanding of immunologic and nonimmunologic mechanisms. Many offer significant means for NMO therapy by selectively targeting pathways. In the future, moving these agents from the bench to the bedside offers the opportunity to identify safe and effective therapies that limit CNS injury and preserve visual function.
Neuromyelitis optica spectrum disorder (NMOSD) is a immune-mediated demyelinating disease of the central nervous system, characterized by high recurrence and disability rates. Preventing relapses is crucial in the treatment of this condition. Monoclonal antibodies have emerged as a novel and rapidly evolving clinical therapeutic strategy targeting NMOSD in recent years. An increasing number of studies and clinical trials have also confirmed the effectiveness and safety of monoclonal antibodies. Rituximab, a monoclonal antibody targeting the B-cell surface antigen CD20, has been widely used in the treatment of NMOSD. Currently, in China, the only approved monoclonal antibody for treating NMOSD is Inebilizumab, which targets the B-cell surface antigen CD19. Additionally, various monoclonal antibodies, such as interleukin-6 receptor inhibitors and complement C5 inhibitors, have been used in the treatment of NMOSD. With the deepening of the research on the pathogenesis of NMOSD, the molecular mechanism of disease-related immune network is further clarified, and multi-center clinical trials are widely carried out. More accurate monoclonal antibody treatment strategies for NMOSD will be applied to clinical practice, benefiting more patients.
目的：探讨复发型视神经脊髓炎(relapsing neuromyelitis optica，R-NMO)与复发型多发性硬化(relapsingremitting multiple sclerosis，RRMS)患者视神经的MRI影像表现。方法：对临床满足R-NMO最新Wingerchuk等制定的诊断标准及满足最新McDonald诊断标准的RRMS患者，进行脑部、脊髓及视神经的扫描，并将两组复发型患者视神经MRI表现特点，与32位健康自愿者进行对照研究。同时回顾性分析患者的VEP检查结果。结果：41例R-NMO患者MRI检查显示患者均有单侧或双侧视神经鞘膜腔信号明显增高，呈“轨道样”改变，22例患者(53.7%)伴有视神经增粗，或(和)扭曲，17例(41.5%)可看视神经内点状高信号表现。随着病程的延长，15例(36.6%)MRI上可见单侧或双侧视神经萎缩、变细，甚至扭曲。最终35例(80.5%)视神经内见到点状高信号表现。121例RRMS患者中，共81名(66.9%)患者在MRI上见到了视神经的异常表现，主要表现为单侧或双侧视神经鞘膜腔部分节段或全段呈“轨道样”高信号改变，其中23例(28.4%)表现为视神经球球后起始段局限性信号增高，视神经15例(12.4%)伴有视神经的肿胀，但视神经萎缩不及R-NMO患者明显。随着时间延长，12例(9.9%)可见视神经内点状高信号脱髓鞘改变。两组患者P100峰值延迟时间差异具有统计学意义(Plt;0.05)。结论：MRI可以成为视神经炎的首选影像学检查方法。两组患者MRI与VEP检查结果存在一定的差异性，可以成为鉴别诊断的依据。
ObjectiveTo investigate the alteration of retinal perfusion in aquaporin-4 antibody (AQP4-ab) positive neuromyelitis optica spectrum disorders (NMOSD) patients by optical coherence tomography angiography (OCTA).MethodsA case-control study. Forty-eight AQP4-ab positive NMOSD patients (96 eyes) and 20 age and gender matched healthy controls (40 eyes) were recruited from September 2015 to August 2017 at the Eye & ENT Hospital of Fudan University. Patients of both eyes were included in the groups. The patients were further divided into 4 subgroups (0 ON, 1 ON, 2 ON, 3+ ON group) according to the number of episodes of ON (0, 1, 2, or 3+) with respect to 30、22、31、13 eyes. 0 ON group had no history of ON episodes; 1 ON group, 2 ON group, and 3+ ON group had ON episodes 1, 2, ≥3 times, respectively. All patients underwent complete ophthalmological examinations including BCVA, visual field and OCTA examination. The BCVA was recorded for each eye using metric notation from the Snellen chart, and then converted to the logarithm of the minimum angle of resolution. The central visual field was assessed using a Humphrey Field Analyzer 750 and the mean deviation (MD) was determined. OCTA scans of the optic disc (4.5 mm × 4.5 mm) and macula (6 mm × 6 mm) were acquired. Radial peripapillary capillary (RPC) vessel density, superficial capillary plexus vessel density (SVD), the thickness of ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were determined. The generalized estimating equations was performed to compare the difference of BCVA, MD, pRNFL thickness, GCIPL thickness, RPC vessel density and SVD among the groups and the correlations between retinal perfusion and retinal structure, visual function were analyzed. ResultsThe RPC vessel density and SVD were significant lower in the 0 ON group compared with healthy group (Wald χ2=7.190, 10.134; P＜0.01), however, the BCVA, pRNFL and GCIPL thickness were not significant difference between the two groups (Wald χ2=2.308, 1.020, 2.558; P＞0.05). The BCVA, visual field MD, RPC vessel density, SVD, pRNFL and GCIPL were significant lower in 1 ON, 2 ON and 3+ ON groups compared with healthy group and 0 ON group (Wald χ2=12.390, 11.346, 38.860, 18.040, 45.418, 26.608; P＜0.001 ), but the parameters had no significant difference among the three groups (P＞0.05). The RPC vessel density was significantly correlated with pRNFL thickness (β=0.372, standard error=0.018, P＜0.001), and the SVD was significantly correlated with GCIPL thickness (β=0.115, standard error=0.204, P＜0.001). The MD and BCVA was significantly correlated with peripapillary vessel density after adjustment for other variables (BCVA: β=0.025, standard error=0.005, P=0.000; visual field MD: β=0.737, standard error=0.185, P=0.000).ConclusionsSubclinical primary retinal vasculopathy may occur in NMOSD prior to ON attack, the ON attack may further impair visual function, retinal structure and perfusion, however, the extent of injure is not relevant with the increase of ON attack. The peripapillary vessel density might be a sensitive predictor of visual outcomes in NMOSD patients.