Objective To observe the ocular manifestations and therapeutic effect of multiple sclerosis (MS) and neuromyelitis optica (NMO) with ocular symptoms.Methods The clinical data of 107 patients who was diagnosed with MS and NMO with ocular symptoms in our hospital were retrospectively analyzed, including 81 MS patients and 26 NMO patients.The counting of erythocytes and leukocyte，protein content and oligoclonal bands were detected by MRI and cerebrospinal fluid (CSF) in order to ensure the clinical diagnosis with MS and NMO. All the patients had undergone regular ophthalmologic examination of visual acuity，slit lamp microscope and fundus examination.In addition，visual field and visual evoked potential (VEP) examination were performed to analyze the clinical characteristics of ocular manifestations.The patients were received therapy with large dose methylprednisolone or activating blood and dissolving stasis and trophic nerve by chinese medicine. The effects of three methods on ocular manifestations were analyzed. All the patients were followed up for one month to five years. Results Among 81 MS patients，retrobulbar neuritis occurred in 24 patients (29.6%), the other common symptoms included paralytic strabismus and diplopia（30.3%）. Among 26 NMO patients，acute papillitis occurred in 12（46.2%），while retrobulbar neuritis occurred in 14 (53.8%). The most common symptom of both MS and NMO was impaired vision and high abnormal rate. The results of MRI showed that demyelinating lesions beside ventricle was the most performance in MS patients，while abnormalities in spinal cord were found in NMO patients.The results of CSF showed that the positive oligoclonal bands was 75.3% and 19.2% in MS and NMO patients respectively. The potential time delay and (or) amplitude declination were observed by VEP. Large dose methylprednisolone can improve vision and diplopia in a short period.Conclusion The abnormal ocular manifestations of MS and NMO patients are common and complicated. Ocular symptoms has important reference value in the early diagnosis of MS and NMO.
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-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.
ObjectiveTo study the relationship between brain white matter fiber occult lesions and P100 wave latency of visual evoked potential (VEP) in neuromyelitis optica (NMO) patients by diffusion tensor imaging (DTI). MethodsTwenty patients with NMO who were treated between July 2008 and April 2009 were selected as the trial group. According to the VEP test, the latency of P100 wave was prolonged, the NMO patients were divided into VEP abnormal group (trial group 1) and VEP normal group (trial group 2). Twenty healthy adult volunteers served as the control group. The DTI examination in brain was done to measure the fractional anisotropy (FA) value of optic nerve (FAn), optic tract (FAt), and optic radiation (FAr);and the mean diffusivity (MD) value of optic nerve (MDn), optic tract (MDt), and optic radiation (MDr). The FA, MD, and P100 wave latency were compared between groups, and the correlation between MD, FA, and P100 wave latency of NMO were analyzed. ResultsIn the 20 NMO patients, 13 patients with VEP had prolonged bilateral P100 wave latency prolongation or no wave (trial group 1), and 7 patients had normal bilateral P100 wave latency (trial group 2). Compared with the trial group 2 and the control group, the FA values were significantly decreased, and the MD values were significantly increased in the trial group 1 (P<0.05). There was no significant difference in the FA and MD values between the trial group 2 and the control group (P>0.05). All FA (FAn, FAt, and FAr) values of each part of NMO patients were negatively correlated with the latency of P100 wave (P<0.05), all MD (MDn, MDt, and MDr) values were positively correlated with the latency of P100 wave (P<0.05). ConclusionDTI could show small pathylogical changes in the white matter fibers of visual pathway, and there is a correlation between DTI and VEP in NMO, suggesting that a more comprehensive assessment to the condition and prognosis can be made through the VEP in the clinical indicators.
Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes, which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury. Vasculocentric deposition of activated complement is a prominent feature of NMO pathology. In recent years, a number of groups have found complements play an important role in the pathogenesis of NMO, and basic researches in NMO therapy due to its specificity and uniformity. Its inhibition would protect against proteins in the classical complement pathway so that cure the disease. This review will expound the the role of complement signaling pathway in the pathogenesis of NMO, and provide reference for a more in-depth understanding and clinical treatments of NMO.
Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory disorders of the central nervous system characterized by episodes of immune-mediated demyelination and axonal damage mainly involving optic nerves and spinal cord. Neuromyelitis optica related optic neuritis (NMO-ON) is a common neuro-ophthalmic disease which often results in permanent blindness. The discovery of aquaporin 4 antibodies confirms that neuromyelitis optica is a distinct disease entity different from multiple sclerosis. In patients with NMO-ON, the correct therapeutic approach has to recognize two distinct clinical situations: treatment of the acute attacks and prevention of the relapses. With the in-depth study of the pathogenesis of NMOSD, new treatments are emerging in different targets of the disease. This review gives an update of latest treatment of NMO-ON, emphasizing both current situation and future immunotherapy strategies.
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.
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.
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 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.