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-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 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 clinical, radiographic features and prognosis of aquaporin-4 antibody positive pediatric optic neuritis (AQP4-PON).MethodsA retrospective case series. Twenty-three eyes of 14 children with AQP4-PON who were clinically confirmed in the Department of Ophthalmology of the First Medical Center of the Chinese PLA General Hospital from January 2015 to December 2018 were included in the study. All patients underwent BCVA, fundus color photography, and magnetic resonance imaging (MRI). OCT was performed on 15 eyes of 10 patients, and the peripapillary retinal nerve fiber layers (pRNFL), macular ganglion cell-inner plexiform layers (mGCIPL) thickness of the affected eyes were measured. Cell-based indirect fluorescent immunoassay was used to detect serum AQP4 antibodies and myelin oligodendrocyte glycoprotein antibodies. The follow-up time ranged from 28 to 59 months. The clinical, neuroimaging characteristics and prognosis of the children were analyzed.ResultsAmong 14 children, 2 were male (14.3%) and 12 were female (85.7%). The mean age of onset was 13.3 ± 3.0 years. On the first visit, there were 10 unilateral patients and 4 bilateral patients. The first manifestations were 11 patients of optic neuritis (78.6%), 2 patients of posterior pole syndrome (14.3%), and 1 patient of myelitis (7.1%). There were 10 patients (71.4%) with eye pain, and 5 patients (35.7%) combined with autoantibodies positive. When the first onset time was less than 2 weeks, fundus examination revealed disc edema in 7 eyes (38.9%). After 3 months, the average pRNFL and mGCIPL thickness of 15 eyes underwent OCT examination were 62.33 ± 11.07 and 54.17 ± 5.42 μm, respectively. Orbital MRI showed that the optic nerve showed a long T2 signal in 14 patients (100.0%) and 11 patients (78.6%) with T1 intensive lesions. When the first onset was less than 2 weeks, 16 eyes (88.9%) had BCVA≤0.1, and 7 eyes (38.9%) had BCVA≤0.1 and 9 eyes (50.0%) with BCVA≥0.5 after glucocorticoid treatment. Recurrence occurred in 11 patients during follow-up and was treated with immunosuppressive agents. At the last visit, in 14 patients, 9 eyes (64.3%) were involved in both eyes, and 5 patients (35.7%) progressed to neuromyelitis optica; in 23 eyes, 8 eyes (34.8%) had BCVA≥0.5.ConclusionsAQP4-PON patients are more common in women, severely impaired visual function, easy to relapse, and some patients will progress to neuromyelitis optica.
ObjectiveTo observe the changes of serum cytokines in patients with neuromyelitis optic neuromyelitis optic spectrum disorder (NMOSD) associated optic neuritis (NMOSD-ON) before and after intravenous methylprednisolone pulse (IVMP) treatment. MethodsA prospective clinical study. From November 2020 to December 2021, 24 NMOSD-ON patients who visited the Neuro-Ophthalmology Clinic of Beijing Tongren Hospital Affiliated to Capital Medical University were included. Among them, 9 patients were male; 15 patients were female. According to the detection results of aquaporin 4 (AQP4) immunoglobulin G (IgG) antibody (AQP4-IgG) in peripheral blood, the patients were divided into AQP4-lgG positive group and AQP4-lgG negative group, which were 10 and 14 cases respectively. Twenty healthy volunteers were selected as control group. Age (F=0.639) and sex (χ2=2.373) composition ratio of the three groups were compared, the difference were not statistically significant (P=0.504, 0.333). All patients were treated with 500 mg/d or 1 000 mg/d IVMP. Peripheral venous blood of all subjects, and quantitatively analyze interferon-gamma (IFN-γ), interleukin (IL)- 4, IL-31, IL-33, IL-17A, IL-6, IL-21, IL-23, IL-10, tumor necrosis factor (TNF)-α level in serum with Luminex FLEX MAP 3D liquid-phase suspension chip detection system were collected. The differences among groups were analyzed by one-way ANOVA and Kruskal Wallis H test. ResultsBefore IVMP treatment, serum IL-17A concentrations in AQP4-lgG positive group, AQP4-lgG negative group and control group were 2.39, 2.17 and 1.97 pg/ml, respectively. TNF-α concentrations were 5.60, 4.17 and 5.89 pg/ml, respectively. Compared with control group, serum IL-17A concentration in AQP4-IgG positive group was increased, while TNF-α concentration in AQP4-IgG negative group was decreased, with statistical significance (H=12.720, 10.900; P=0.040, 0.039). The levels of IL-17A, IL-6 and other cytokines did not change significantly. After IVMP treatment, serum IL-6 in AQP4-lgG positive group and AQP4-lgG negative group were 0.72 pg/ml and 0.73 pg/ml, respectively. TNF-α concentrations were 4.17 pg/ml and 3.88 pg/ml, respectively. IFN-γ concentrations were 2.15 pg/ml and 2.55 pg/ml, respectively. Compared with before treatment, serum levels of IL-6, TNF-α and IFN-γ in AQP4-lgG positive patients were significantly decreased, with statistical significance (Z=－2.668, －2.547, －2.201; P=0.008, 0.011, 0.028). Serum levels of IL-6 and TNF-α were significantly decreased in AQP4-lgG negative patients, and the difference was statistically significant (Z=－2.501, －1.978; P=0.012, 0.048). ConclusionGlucocorticoid may play a therapeutic role by affecting the levels of serum IL-6, TNF-α, IFN-γ in patients with NMOSD-ON.
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.
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.
Neuromyelitis spectrum disease (NMOSD) is an immune-mediated inflammatory demyelinating disease of the central nervous system. The breakdown of the blood-brain barrier (BBB), as an important link in the pathogenesis of NMOSD, has an important impact on the occurrence, development and prognosis of the disease. It is generally believed that the aquaporin 4 antibody produced in the peripheral circulation crosses the BBB cause damage to the central nervous system, and there are components involved in the destruction of BBB in the occurrence and development of NMOSD disease. At present, little is known about the molecular mechanism of BBB destruction in NMOSD lesions and there is still a lack of systematic theory. Further research and exploration of the regulatory mechanism of BBB permeability and the manifestation of barrier destruction in NMOSD diseases are of great significance for understanding the pathogenesis of NMOSD, so as to achieve early diagnosis and discover new therapeutic and preventive targets.