Convergence spasm due to aquaporin-positive neuromyelitis optica spectrum disorder.
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ABSTRACT:
SUBMITTER: Ozcelik P
PROVIDER: S-EPMC5721560 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
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Convergence spasm due to aquaporin-positive neuromyelitis optica spectrum disorder.
Özçelik Pınar P Tanriverdizade Tural T Men Süleyman S Akdal Gülden G
eNeurologicalSci 20170306
A female 27 presented with nausea and diplopia for 1 week. On examination she had normal vertical gaze but would develop convergence with miosis whenever she made horizontal saccades. Pupils were 6 mm and unreactive to light. MRI showed extensive hyperintensity in the dorsal midbrain and thalamus. Spinal MRI and CSF were both normal. Serum aquaporin-4-antibody was positive. She was treated with steroids and plasmapheresis and after 3 months convergence spasm resolved but pupils remained unreacti ...[more]
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Project description:ObjectiveTo investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome.MethodsAn international cohort of women with aquaporin-4 antibody-positive NMOSD and ?1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was associated with an increased risk of miscarriage (cohort of 40 women) or preeclampsia (cohort of 57 women).ResultsMiscarriage rate was higher in pregnancies after NMOSD onset (42.9% [95% confidence interval 17.7%-71.1%] vs. 7.04% [2.33%-15.7%]). Pregnancies conceived after, or up to 3 years before, NMOSD onset had an increased odds ratio of miscarriage (7.28 [1.03-51.6] and 11.6 [1.05-128], respectively), independent of maternal age or history of miscarriage. Pregnancies after, or up to 1 year before, NMOSD onset ending in miscarriage were associated with increased disease activity from 9 months before conception to the end of pregnancy, compared to viable pregnancies (mean annualized relapse rate 0.707 vs. 0.100). The preeclampsia rate (11.5% [6.27%-18.9%]) was significantly higher than reported in population studies. The odds of preeclampsia were greater in women with multiple other autoimmune disorders or miscarriage in the most recent previous pregnancy, but NMOSD onset was not a risk factor.ConclusionsPregnancy after NMOSD onset is an independent risk factor for miscarriage, and pregnancies conceived at times of high disease activity may be at increased risk of miscarriage. Women who develop NMOSD and have multiple other autoimmune disorders have greater odds of preeclampsia, independent of NMOSD onset timing.
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Project description:Objective Neuromyelitis optica and its spectrum disorders (NMOSD) are inflammatory demyelinating diseases (IDD) with a specific biomarker, aquaporin-4-IgG. Prior NMO/NMOSD epidemiological studies are limited by lack of aquaporin-4-IgG seroprevalence assessment, absence of population-based USA studies and under-representation of blacks. To overcome these limitations, we sought to compare NMO/NMOSD seroepidemiology across two ethnically divergent populations. Methods We performed a population-based comparative study of the incidence (2003-2011) and prevalence (on December 31, 2011) of NMO/NMOSD and aquaporin-4-IgG seroincidence and seroprevalence (sera collected in 80-84% of IDD) among patients with IDD diagnosis in Olmsted County, USA (82% white [Caucasian]) and Martinique (90% black [Afro-Caribbean]). Aquaporin-4-IgG was measured by M1-isoform-fluorescent-activated-cell-sorting assays. Results The age and sex adjusted incidence (7.3 vs 0.7/1,000,000 person-years [p<0.01]) and prevalence (10 vs 3.9/100,000[p=0.01]) in Martinique exceeded that in Olmsted County. The AQP4-IgG age and sex-adjusted seroincidence (6.5 vs 0.7/1,000,000 person-years [p<0.01]) and seroprevalence (7.9 vs 3.3/100,000[p=0.04]) were also higher in Martinique than Olmsted County. The ethnicity-specific prevalence was similar in Martinique and Olmsted County: 11.5 and 13/100,000 in blacks, and 6.1 and 4.0/100,000 in whites, respectively. NMO/NMOSD represented a higher proportion of IDD in Martinique than Olmsted County (16% vs 1.4%; p<0.01). The onset age (median, 35-37 years) and female:male distribution (8-9:1) were similar across both populations; 60% of prevalent cases were either blind in one eye, dependent on a gait aid or both. Interpretation This study reports the highest prevalence of NMO/NMOSD in any population (10/100,000 in Martinique), estimates it affects 16,000-17,000 in the USA (higher than previous predictions) and demonstrates it disproportionately affects blacks. This article is protected by copyright. All rights reserved.
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Project description:BACKGROUND:In a minority of patients with neuromyelitis optica spectrum disorder (NMOSD) and aquaporin-4 antibodies (AQP4-IgG), the disease has a paraneoplastic origin. It is unknown whether these patients have distinctive clinical features. OBJECTIVE:To report the clinical features of a series of patients with paraneoplastic NMOSD and AQP4-IgG and to review previously reported cases. METHODS:Retrospective analysis of clinical records of 156 patients with NMOSD and AQP4-IgG and review of previously reported patients with paraneoplastic NMOSD and AQP4-IgG. Paraneoplastic patients were defined as those with cancer identified within 2 years of the diagnosis of NMOSD. RESULTS:Five (3.2%) of 156 patients had paraneoplastic NMOSD, and 12 previously reported patients were identified. The most common tumors were adenocarcinoma of the lung (five patients) and breast (five). Compared with the 151 non-paraneoplastic NMOSD patients, the 17 (5 current cases and 12 previously reported) were older at symptom onset (median age = 55 (range: 17-87) vs 40 (range: 10-77) years; p = 0.006), more frequently male (29.4% vs 6.6%; p = 0.009), and presented with severe nausea and vomiting (41.2% vs 6.6%; p < 0.001). The frequency of longitudinal extensive transverse myelitis (LETM) as heralding symptom was similar in both groups, but patients with paraneoplastic NMOSD were older than those with non-paraneoplastic NMOSD (median age: 63 (range: 48-73) vs 43 (range: 14-74) years; p = 0.001). CONCLUSION:Patients, predominantly male, with NMOSD and AQP4-IgG should be investigated for an underlying cancer if they present with nausea and vomiting, or LETM after 45 years of age.
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Project description:Intractable neuropathic pain is recognized as a common symptom of neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism of NMOSD pain remains to be elucidated. Here, we established NMOSD pain model by injecting anti-AQP4 recombinant autoantibodies (AQP4-Ab) generated from NMOSD patient’s plasmablasts into rat spinal cords and confirmed the development of mechanical allodynia. AQP4-Ab mediated extracellular ATP release from astrocytes and pharmacological inhibition of ATP receptor reversed mechanical allodynia in NMOSD pain model. Furthermore, transcriptome analysis revealed microglia activation and IL-1β elevation in NMOSD spinal cord. Inhibition of microglia activation and neutralization of IL-1β also attenuated neuropathic pain in NMOSD rat model. In addition, the human CSF ATP concentration was significantly higher in the acute and remission phase of NMOSD than in multiple sclerosis and other neurological disorder patients. These findings indicate ATP, microglial activation and IL-1β secretion orchestrates the pathogenesis of NMOSD neuropathic pain.
2021-08-24 | GSE150598 | GEO
Project description:Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system inflammatory disorders causing significant morbidities and mortality. The majority of NMOSD patients have autoimmunity against aquaporin-4 (AQP4), evidenced by seropositivity for autoantibodies against aquaporin-4 (AQP4-IgG). AQP4-IgG is pathogenic with neuroinflammation initiated upon binding of AQP4-IgG to astrocytic AQP4. Complement activation contributes to astrocytic cytotoxicity, neuroinflammation, and tissue necrosis in NMOSD, but the role of complement-independent mechanisms is uncertain. We studied the complement-independent pathogenic effects of AQP4-IgG by passive transfer of IgG from NMOSD patients to mice with breached blood-brain barrier (BBB). Mice, pretreated with bacterial proteins, received daily intraperitoneal injections of IgG purified from AQP4-IgG-seropositive NMOSD patients [IgG(AQP4+)], or IgG from AQP4-IgG-seronegative patients [IgG(AQP4-)] or healthy subjects [IgG(Healthy)] for 8?days. Motor function was tested by walking across narrow beams, and spinal cords were collected for immunofluorescent analysis. We found that human IgG infiltrated into cord parenchyma of mice with breached BBB without deposition of complement activation products. Spinal cord of mice that received IgG(AQP4+) demonstrated loss of AQP4 and glial fibrillary acidic protein (suggestive of astrocyte loss), decrease in excitatory amino acid transporter 2, microglial/macrophage activation, neutrophil infiltration, patchy demyelination, and loss in axonal integrity. Mice that received IgG(AQP4+) required longer time with more paw slips to walk across narrow beams indicative of motor slowing and incoordination. Our findings suggest that AQP4-IgG induces complement-independent cord pathologies, including astrocytopathy, neuroinflammation, demyelination, and axonal injuries/loss, which are associated with subtle motor impairments. These complement-independent pathophysiologies likely contribute to early NMOSD lesion development.
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