Association of subcortical structural shapes with fatigue in neuromyelitis optica spectrum disorder.
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ABSTRACT:
SUBMITTER: Seok JM
PROVIDER: S-EPMC8799731 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AIMS:Among patients with neuromyelitis optica spectrum disorder (NMOSD), fatigue is commonly complained about and is one of the most debilitating symptoms. This study aimed to investigate the incidence of fatigue and explore impacting factors attributed to fatigue in NMOSD. METHODS:Thirty-three patients with NMOSD and twenty matched healthy controls were enrolled. A battery of self-reported questionnaires was conducted to assess quality of sleep, daytime sleepiness, fatigue, depression, and level of activity of daily life. The structure of sleep was assessed by polysomnography with blood oxygen saturation monitored by noninvasive pulse oximeter. Brain and spinal cord lesions were evaluated by MRIs. RESULTS:Fatigue was more severe and more prevalent among the patients with NMOSD compared with controls (fatigue score which ranges from 0 to 11 with higher scores indicating more severe fatigue: 6.4 ± 0.6 vs. 3.8 ± 0.4, P = 0.002; incidence, 64% vs. 35%, P = 0.043), and it was negatively associated with daily activity level (r = 0.455, P = 0.008). The patients with fatigue had higher Pittsburgh Sleep Quality Index score, higher Epworth Sleepiness Scale score, lower blood oxygen state, and higher depression score than patients without fatigue; blood oxygen was especially negatively correlated with fatigue (nadir SpO2 , r = -0.558, P = 0.001; mean SpO2 , r = -0.457, P = 0.007); depression was also positively correlated with fatigue (r = 0.599, P < 0.001). CONCLUSION:Patients with NMOSD experienced significant fatigue, which had an obvious impact on their daily activity. Fatigue in these patients was related to hypoxemia, sleep disturbances, and depression.
| S-EPMC4478121 | biostudies-literature
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:ObjectivesWe investigated the sleep structure of patients with neuromyelitis optica spectrum disorder (NMOSD) and the association of abnormalities with brain lesions.MethodsThis was a prospective cross-sectional study. Thirty-three patients with NMOSD and 20 matched healthy individuals were enrolled. Demographic and clinical characteristics of patients were collected. Questionnaires were used to assess quality of sleep, daytime sleepiness, fatigue, and depression. Nocturnal polysomnography was performed.ResultsCompared with healthy controls, patients with NMOSD had decreases in sleep efficiency (7%; p = 0.0341), non-REM sleep N3 (12%; p < 0.0001), and arousal index (6; p = 0.0138). REM sleep increased by 4% (p = 0.0423). There were correlations between arousal index and REM% or Epworth Sleepiness Scale (r = -0.0145; p = 0.0386, respectively). Six patients with NMOSD (18%, 5 without infratentorial lesions and 1 with infratentorial lesions) had a hypopnea index >5, and all of those with sleep apnea had predominantly the peripheral type. The periodic leg movement (PLM) index was higher in patients with NMOSD than in healthy controls (20 vs 2, p = 0.0457). Surprisingly, 77% of the patients with PLM manifested infratentorial lesions.ConclusionsSleep architecture was markedly disrupted in patients with NMOSD. Surveillance of nocturnal symptoms and adequate symptomatic control are expected to improve the quality of life of patients with NMOSD.
| S-EPMC4405292 | biostudies-literature
Project description:Fatigue is a prevalent symptom and major burden in neuroimmunological diseases. In neuromyelitis optica spectrum disorder (NMOSD), a severe autoimmune central nervous system (CNS) inflammatory disease with autoantibodies reactive to aquaporin-4, there are few reports about fatigue and quality of life (QOL). We aimed to evaluate the severity of fatigue and its relationship with QOL in patients with NMOSD. We prospectively studied patients with NMOSD who were in remission and seropositive for anti-aquaporin-4 antibody, and they were divided into 2 groups based on the presence of fatigue assessed using the Functional Assessment of Chronic Illness Therapy-fatigue score. Sleep quality, depression, pain, and QOL were also evaluated. A total of 35 patients were enrolled (mean age, 46.5 ± 14.1 years; female: male = 29:6), and the median Expanded Disability Status Scale (EDSS) score was 2.0 (range, 0 to 8.0). The patients with fatigue (N = 25, 71.4%) had poorer sleep quality and more severe depression than those without fatigue (p = 0.009 and p = 0.001). Both the physical and mental QOL scores were lower in patients with fatigue than in those without fatigue (p = 0.033 and p = 0.004). Multiple linear regression analyses showed that the degree of fatigue with EDSS score and pain were independent predictors of physical aspects of QOL (B = 0.382, p = 0.001), whereas depression was the only predictor of the mental components of QOL (B = -0.845, p = <0.001). Fatigue is a common symptom and an important predictor of QOL in patients with NMOSD.
| S-EPMC5441592 | biostudies-literature
Project description:The terminal complement protein (C5) inhibitor eculizumab (Soliris®) is the first agent to be specifically approved in the EU, USA, Canada and Japan for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are aquaporin-4 water channel autoantibody (AQP4-IgG) seropositive and (in the EU only) for those with a relapsing course of disease. In the phase III PREVENT trial, eculizumab significantly reduced the risk of adjudicated relapse relative to placebo in patients with AQP4-IgG-seropositive NMOSD, approximately a quarter of whom did not receive concomitant immunosuppressive therapies. The beneficial effect of eculizumab was seen across all patient subgroups analysed and was accompanied by improvements in neurological and functional disability assessments, as well as generic health-related quality of life measures; it was sustained through 4 years of treatment, according to combined data from the PREVENT trial and an interim analysis of its ongoing open-label extension study. The safety profile of eculizumab in AQP4-IgG-seropositive NMOSD was consistent with that seen for the drug in other approved indications. Thus, eculizumab provides an effective, generally well tolerated and approved treatment option for this rare, disabling and potentially life-threatening condition.
| S-EPMC7183484 | biostudies-literature
Project description:BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system, characterized by optic neuritis and longitudinally extensive transverse myelitis. Magnetic resonance imaging abnormalities may be observed in various brain regions of NMOSD patients. Only a few studies have addressed the cognitive functions in NMOSD, but none among Egyptian patients.ObjectiveTo investigate cognitive performance in a cohort of 20 Egyptian patients with NMOSD.DesignObservational, prospective study.PatientsWe studied 20 Egyptian patients with NMOSD and compared them with 18 healthy Egyptian controls matched for age, sex, and educational level.Main outcome measureWe applied an Arabic translation of MOCA and BICAMS Tests for Multiple Sclerosis.ResultsCognitive performance was significantly worse in the NMOSD group than in healthy controls for CVLT (P = 0.0099), SDMT (P = 0.0112), BVSMT (P = 0.019) and BICAMS in total (P = 0.0014). Patients with a later disease onset performed worse in MOCA and BVSMT.ConclusionsThis study confirms the concept of cognitive involvement in NMOSD among Egyptian patients. Information processing speed was the function most commonly impaired.
| S-EPMC7002275 | biostudies-literature
Project description:Inebilizumab (Uplizna®) is a recently approved monoclonal antibody for use in adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody seropositive. Inebilizumab targets the B cell antigen CD19 and effectively depletes circulating B cells, thus suppressing inflammatory NMOSD attacks that are potentially disabling or life-threatening. It is approved as an intravenous infusion in several countries. In the pivotal phase 2/3 N-MOmentum trial, inebilizumab reduced the risk of NMOSD attacks compared with placebo, including in AQP4-antibody seropositive patients. Inebilizumab also significantly reduced the risk of disability score worsening, the number of NMOSD-related hospitalisations and MRI lesion count, but had no significant effect on low-contrast binocular vision. The treatment effect on relapse risk and disability scores was sustained in inebilizumab-treated patients for ≥ 4 years during the open-label extension. Inebilizumab was generally well tolerated, with the most common adverse events being urinary tract infection and arthralgia. Thus, inebilizumab is an effective treatment option for adults with AQP4-antibody seropositive NMOSD.
| S-EPMC9550749 | biostudies-literature
Project description:Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system affecting primarily the spinal cord and optic nerves. Most NMOSD patients are seropositive for immunoglobulin G autoantibodies against astrocyte water channel aquaporin-4, called AQP4-IgG, which cause astrocyte injury leading to demyelination and neurological impairment. Current therapy for AQP4-IgG seropositive NMOSD includes immunosuppression, B cell depletion, and plasma exchange. Newer therapies target complement, CD19 and IL-6 receptors.Areas covered: This review covers early-stage pre-clinical therapeutic approaches for seropositive NMOSD. Targets include pathogenic AQP4-IgG autoantibodies and their binding to AQP4, complement-dependent and cell-mediated cytotoxicity, blood-brain barrier, remyelination and immune effector and regulatory cells, with treatment modalities including small molecules, biologics, and cells.Expert opinion: Though newer NMOSD therapies appear to have increased efficacy in reducing relapse rate and neurological deficit, increasingly targeted therapies could benefit NMOSD patients with ongoing relapses and could potentially be superior in efficacy and safety. Of the various early-stage therapeutic approaches, IgG inactivating enzymes, aquaporumab blocking antibodies, drugs targeting early components of the classical complement system, complement regulator-targeted drugs, and Fc-based multimers are of interest. Curative strategies, perhaps involving AQP4 tolerization, remain intriguing future possibilities.
| S-EPMC7941255 | biostudies-literature
Project description:Optic neuritis, an optic nerve inflammatory disease presenting with acute unilateral or bilateral visual loss, is one of the core symptoms of neuromyelitis optica spectrum disorder (NMOSD). The diagnosis of NMOSD-related optic neuritis is challenging, and it is mainly based on clinical presentation, optical coherence tomography, magnetic resonance imaging scans, and the status of serum aquaporin-4 antibodies. In the pathogenesis, aquaporin-4 antibodies target astrocytes in the optic nerves, spinal cord and some specific regions of the brain eliciting a devastating autoimmune response. Current pharmacological interventions are directed against various steps within the immunological response, notably the terminal complement system, B-cells, and the pro-inflammatory cytokine Interleukin 6 (IL6). Conventional maintenance therapies were off-label uses of the unspecific immunosuppressants azathioprine and mycophenolate mofetil as well as the CD20 specific antibody rituximab and the IL6 receptor specific antibody tocilizumab. Recently, four phase III clinical trials demonstrated the safety and efficacy of the three novel biologics eculizumab, inebilizumab, and satralizumab. These monoclonal antibodies are directed against the complement system, CD19 B-cells and the IL6 receptor, respectively. All three have been approved for NMOSD in the US and several other countries worldwide and thus provide convincing treatment options.
| S-EPMC9558477 | biostudies-literature
Project description:BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system. Although complement-dependent astrocyte damage mediated by anti-aquaporin 4 autoantibody (AQP4-Ab) is well acknowledged to be the core of NMOSD pathogenesis, additional inflammatory cascades may contribute to the establishment of lesion formation. Thus, in this study, we investigated the possible pathogenic role of immune-reactive mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) of NMOSD patients.MethodsUsing quantitative polymerase chain reaction, we measured extracellular mtDNA levels in CSF of NMOSD patients positive for AQP4-Ab. Patients with multiple sclerosis or other neurological diseases were examined as controls. Pre- and post-treatment extracellular mtDNA levels were also compared in the NMOSD group. Extracellular mtDNA release from human astrocytes was analyzed in vitro utilizing NMOSD sera, and interleukin (IL)-1? production was measured in supernatants of mixed glial cells stimulated with DNA fraction of CSF derived from NMOSD patients. Furthermore, specific innate immune pathways mediating the IL-1? production by mtDNA were investigated in peripheral blood mononuclear cells with selective inhibitors of Toll-like receptor 9 (TLR9) and NOD-like receptor protein 3 (NLRP3) inflammasomes.ResultsExtracellular mtDNA level was specifically elevated in acute phase of NMOSD CSF. In vitro studies provided the evidence that mtDNA is released from human astrocytes by NMOSD sera. In addition, DNA fraction isolated from NMOSD CSF promoted secretion of IL-1? from mixed glial cells. Selective inhibition of TLR9 and NLRP3 inflammasomes revealed that mtDNA-mediated IL-1? production depends on specific innate immune pathways.ConclusionExtracellular mtDNA is specifically elevated in the CSF of patients with acute phase NMOSD, and mtDNA released by AQP4-Ab-mediated cellular damage elicits the innate immune cascades via TLR9 and NLRP3 inflammasomes pathways. Our study highlights mtDNA-mediated innate immune pathways as a novel therapeutic target for future treatment of NMOSD patients.
| S-EPMC5924507 | biostudies-literature