Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system that primarily affects the optic nerves and spinal cord. Most patients have positive serum antibody of aquaporin-4 (AQP4), which targets the AQP4 protein expressed on the end-feet of astrocytes. Although the prevalence of NMOSD is limited, the recurrence rate is high. Repeated and severe immune-mediated attacks can quickly lead to blindness and paralysis if undiagnosed and untreated. While high-dose methylprednisolone and plasma exchange are used in the acute phase, the treatment for recurrent prevention is limited. In recent years, researchers developed several kinds of monoclonal antibodies targeting different nodes of immune pathogenic process, including satralizumab (an interleukin-6 receptor inhibitor), inebilizumab (an antibody against CD19+ B cells), and eculizumab (an antibody blocking the C5 component of complement). In several randomized controlled clinical trials, these monoclonal antibodies decreased the relapse rate significantly in NMOSD. These emerging treatments have greatly changed the treatment of NMOSD.
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.
Objective To observe the clinical features and visual function of recurrent neuromyelitis optica (NMO). Methods Thirty-four patients with NMO were enrolled in this retrospective case series study. The patients included two males and 32 females. The average first onset age was (35.03plusmn;14.56) years old and the average recurrent rate were (4.24plusmn;2.45) times. The recurrent rate of optic neuritis (ON) ranged from two to 12 times. The recurrent rate of ON was two times in 15 eyes of 10 patients, ge;three times in 37 eyes of 24 patients. Vision acuity, direct ophthalmoscope, fundus pre-set lens examination, visual field and visual evoked potential (VEP) were evaluated. Clinical features were observed. The abnormal rate of optic nerve including optic edema and atrophy; abnormal rate of visual field including decreasing retinal sensitivity, central and paracentral scotoma, ring scotoma, half field defects, tunnel visual field, visual field centrality constriction; abnormal rate of VEP including Prolonged latent phase and/or decreasing amplitude of P100 wave from patients of first episode or recurrence was analyzed. Serum NMO-IgG was detected from 28 patients by indirect immunofluorescence technique to observe its positive rate. Results All patients were characterized by repeated episodes of ON and myelitis. The main clinical feature of ON was visual loss, and the main clinical features of myelitis included sensory disability, dyskinesia and vesicorectal disorder. Blindness rate was 41.67% after the first attack of ON, 33.33% after two relapses, and 64.86% after ge; three relapses. The difference of blindness rate between first attack and two episodes was not significant (chi;2=0.270,P=0.603). However, the blindness rate in patients having ge; three episodes was significantly higher than those having two episodes (chi;2=4.300,P=0.038). With recurrence rate increasing, the abnormal rate of the optic nerve (chi;2=6.750,P=0.034）and VEP（chi;2=6.990,P=0.030）increased. But the abnormal rate of visual field did not increase along with recurrent rate (chi;2=0.660,P=0.718). Seropositive rate of NMO-IgG did not differ significantly between patients with first attack ON and that with recurrent ON (chi;2=1.510,P=0.470). But the seropositive patients had significantly higher bilateral blindness rate than seronegative patients (chi;2=5.063,P=0.027). Conclusions NMO are characterized by recurrent ON and myelitis. Visual loss, sensory disability, dyskinesia and vesicorectal disorder are the main clinical features. With recurrence rate increasing, the blindness rate, abnormalities the optic nerve and the abnormity rate of VEP increase. Seropositive recurrent NMO patients have higher bilateral blindness rate than seronegative patients.
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.
Objective:To observe the effects of testosterone on optic nerve an d retinal ganglion cells (RGC) in experimental autoimmune encephalomyelitis (EAE ). Methods:Fourty one female Wistar rats were randomly divide d into 3 groups: the normal group (10 rats), the untreated control group (15 rats) and the testos terone group (16 rats). The rats in the first two groups were fed with 1% ethano l every day, and the rats in the testosterone group were fed with methyltestoste rone (0.25 mg/kg) every day. On the 20th day, EAE model was induced in the untre ated control group and the testosterone group by injecting guinea pig spinal cor d homogenate in complete Freund's adjuvant and bordetella pertussis vaccine. RGC were labeled with flurogold (FG) by injecting it in superior colliculus and lat eral geniculate body 7 days before establishing EAE model. All rats were fed wit h drugs continuously, and after 1430 days, rats in normal group and rats in un t reated control and testosterone groups who had symptoms within 48～72 hours were observed by light microscopy and flash visual evoked potential (FVEP) to detect the functional and morphological changes of optic nerve. The number of RGC was counted by fluorescence microscopy，and apoptosis of RGC was observed by termina l deoxynucleotidyl transferasemediated biotinylated UTP nick end labeling (TUN E L) Results:EAE rats presented weakness or paralysis of tail a nd hind limbs 10 days after establishing EAE model. Compared with the rats in the untreated contr ol group, the rats in the testosterone group had longer disease delitescence and lower clinical score (P=0.042). Extensive demyelination of optic nerves wi th the circuitous configuration was found in the untreated control group; while mild demyelination of optic nerves with regular figure was found in the testosterone group. In the testosterone group, the latency of N1、P and N2 wave was shorter w hile the amplitude ofN1-P and P-N2was higher than that in the untreated cont rol group (Plt;0.05). The number of RGC was (2284plusmn;132), (934plusmn;78, and (1725 plusmn;95)cells/mm2 in the normal, untreated control and testosterone groups, respectively; w hich was higher in testosterone group than that in untreated control group (P=0.028). The number of TUNEL positive cells was (4.02plusmn;0.16), (24.44plusmn;2.22), and (9.84plusmn;2.36) cells per high power field (times;400) in the 3 grou ps, respectively; wh ich was less in testosterone group than that in untreated control group (P＝0.025). Conclusions:Testosterone may reduce the incidence and clinical score of EAE, inhibit the apoptosis of RGC, alleviate the demyelinatio n of optic nerves, and improved the conduction function of optic nerves.
【摘要】 目的 分析急性播散性脑脊髓炎的临床特点，提高诊疗。 方法 收集1999年1月-2010年1月住院的急性播散性脑脊髓炎患者42例，对其临床症状体征、实验室检查、影像学改变及治疗进行全面回顾性分析。 结果 42例患者中5～14岁者11例（26.19%）；15～40岁者20例（47.62%），感染后引起的23例（54.76%），无明显诱因占15例（35.71%）；脑脊液23例（23/34，67.65%）异常；脑电图异常者27例（27/32，84.38%）；CT检查阳性率26例（26/40，65.00%），MRI阳性率25例（25/28，89.29%）；糖皮质素、丙种球蛋白治疗有效。 结论 急性播散性脑脊髓炎是一组临床表现多样的免疫介导的炎性疾病，脑脊液、MRI和脑电图有重要诊断价值。急性期大剂量皮质素、静脉丙种球蛋白治疗均有较好疗效。【Abstract】 Objective To analysis the clinical features of acute disseminated encephalomyelitis so as to improve medical treatment. Methods From January, 1999 to January, 2010, 42 inpatients with acute disseminated encephalomyelitis were collected and their clinical data were analyzed retrospectively. Results Out of these 42 patients, 11 (26.19% ) were within 5 to 14 years, 20 (47.62%) ithin 15 to 40 years; 23 (54.76%) had definite infection, and 15 (35. 71%)had no any causes; 23 (23/34, 67.65%) had abnormal cerebrospinal fluid; 27 (27/32, 84.38%) had abnormal electro-encephalograph; 26 (26/40, 65.00%) were CT positive, 25 (25/28, 89.29%) MRI positive; corticosteroids and gamma globulin were effective in the treatment of disseminated encephalomyelitis. Conclusion Acute disseminated encephalomyelitis is a kind of inflammatory disease with various clinical manifestation and mediated by immune. Cerebrospinal fluid, MRI, and electro-encephalograph have important roles in its diagnosis. Large dose of corticosteroids and gamma globulin are effective in the treatment of acute disseminated encephalomyelitis.