scholarly journals Investigating the Presence of Interattack Astrocyte Damage in Neuromyelitis Optica Spectrum Disorder

2021 ◽  
Vol 8 (3) ◽  
pp. e965 ◽  
Author(s):  
Jae-Won Hyun ◽  
Yeseul Kim ◽  
So Yeon Kim ◽  
Min Young Lee ◽  
Su-Hyun Kim ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Single Molecule ◽  
Spectrum Disorder ◽  
Cancer Center ◽  
Multiple Time ◽  
Healthy Controls ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Cutoff Value

ObjectivesInformation on subclinical astrocyte damage can provide further insight into neuromyelitis optica spectrum disorder (NMOSD) pathophysiology and disease-monitoring strategies. To investigate whether astrocyte and neuroaxonal damage occurs during interattack periods in individuals with NMOSD through longitudinal measurement of serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) at multiple time points.MethodssGFAP and sNfL levels were measured in 187 serum samples from 20 participants with NMOSD treated with rituximab (median follow-up: 24 months) and 19 age-/sex-matched healthy controls using a highly sensitive single-molecule array assay. From the NMOSD cohort of National Cancer Center, Korea, 14 clinically stable participants were randomly selected for focused investigation of interattack periods, and 6 participants with clinical attacks despite treatment were enrolled for attack-related measurements.ResultsSignificant elevations of sGFAP levels were observed in all clinical attacks, and 95% (19/20) of patients showed reduction of sGFAP levels below the cutoff value (3 SDs above mean levels in age-/sex-matched healthy controls) within 3 months of their clinical attacks. The sGFAP levels were consistently low during interattack periods in 90% (17/19) of patients whose sGFAP levels returned to below the cutoff value. Changes in sNfL levels were similar to but slower than those in sGFAP levels.ConclusionsSubclinical astrocyte damage represented by increasing sGFAP levels rarely occurred during interattack periods in individuals with NMOSD; however, a certain degree of astrocyte damage did occur at the time of clinical attacks without exception, but it was not evident within 3 months of the attack.

scholarly journals Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder

2017 ◽  
Vol 3 (4) ◽  
pp. 205521731774242 ◽  
Author(s):  
Giannina Arru ◽  
Elia Sechi ◽  
Sara Mariotto ◽  
Alessia Farinazzo ◽  
Chiara Mancinelli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Neuromyelitis Optica ◽  
Humoral Immune Response ◽  
Serum Levels ◽  
Spectrum Disorder ◽  
Antigenic Peptides ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Serum Samples ◽  
Humoral Immune

Background A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD). Objective The objective of this paper is to investigate whether antibody (Ab) response against HERV-W env-su antigenic peptides differs between NMOSD and MS. Methods Serum samples were collected from 36 patients with NMOSD, 36 patients with MS and 36 healthy control individuals (HCs). An indirect ELISA was set up to detect specific Abs against HERV-W env-su peptides. Results Our data showed that two antigenic peptides, particularly HERV-Wenv93–108 and HERV-Wenv248–262, were statistically significantly present only in serum of MS compared to NMOSD and HCs. Thus, the specific humoral immune response against HERV-W env-su glycoprotein antigens found in MS is widely missing in NMOSD. Conclusion Increased circulating serum levels of these HERV-W Abs may be suitable as additional biomarkers to better differentiate MS from NMOSD.

scholarly journals Higher Disease and Pain Severity and Fatigue and Lower Balance Skills Are Associated with Higher Prevalence of Falling among Individuals with the Inflammatory Disease of Neuromyelitis Optica Spectrum Disorder (NMOSD)

2020 ◽  
Vol 9 (11) ◽  
pp. 3604
Author(s):  
Mahdi Barzegar ◽  
Dena Sadeghi Bahmani ◽  
Omid Mirmosayyeb ◽  
Reyhaneh Azarbayejani ◽  
Alireza Afshari-Safavi ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Fear Of Falling ◽  
Spectrum Disorder ◽  
Lower Limbs ◽  
Sensory Loss ◽  
Healthy Controls ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Balance Performance ◽  
Risk Of Falling ◽  
Related Factors

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory and autoimmune disorder that is associated with impaired vision, sensory loss, pain, fatigue, and spasms in the upper and lower limbs. Typically, persons with this disorder are also at higher risks of falls. Given this, the aims of the study were to compare the prevalence rates of falling for NMOSD cases and healthy controls (HCs), and to predict falling in the former group based on sociodemographic, psychological, and illness-related factors. Method: A total of 95 adults with NMOSD (Mean age = 34.89 years; 70.5% females) and 100 matched HCs took part in the study. All participants completed a series of questionnaires covering sociodemographic information and falling rates. The NMOSD individuals also reported on disease duration, pain, fatigue, and fear of falling, while their balance performance was objectively assessed. Results: Compared to healthy controls, the NMOSD cases had a 2.5-fold higher risk of falling. In this latter group, higher scores for pain, fatigue, fear of falling, and higher EDSS scores were distinguished between fallers and non-fallers, and objective balance skills had no predictive value. Conclusions: Compared to healthy controls, NMOSD sufferers had a 2.5-fold higher risk of experiencing falls. In this group, disease impairments (EDSS, fatigue, pain) predicted falling. Specific interventions such as regular resistance training might reduce the risk of falling.

scholarly journals Anti-Mycobacterial Antibodies in Paired Cerebrospinal Fluid and Serum Samples from Japanese Patients with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder

2018 ◽  
Vol 7 (12) ◽  
pp. 522 ◽  
Author(s):  
Kazumasa Yokoyama ◽  
Davide Cossu ◽  
Yasunobu Hoshino ◽  
Yuji Tomizawa ◽  
Eiichi Momotani ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neuromyelitis Optica ◽  
Japanese Patients ◽  
Spectrum Disorder ◽  
Oligoclonal Bands ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Serum Samples ◽  
Local Synthesis ◽  
Significant Difference

Local synthesis of antibodies and presence of oligoclonal bands in the cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS). We investigated the frequency of antibodies against mycobacterial and relevant human epitopes in the CSF of patients with MS or neuromyelitis optica spectrum disorder (NMOSD) and whether these antibodies differed from those present in the serum. Matched serum and CSF samples from 46 patients with MS, 42 patients with NMOSD, and 29 age-matched and sex-matched control subjects were screened retrospectively for the presence of antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) pentapeptide (MAP_5p), MAP_2694295–303, and myelin basic protein (MBP)85–98 peptides by using indirect ELISA. Serum levels of anti-MAP_5p and anti-MAP_2694295–303 antibodies were highly prevalent in patients with MS when compared to patients with NMOSD and controls. Several patients with MS had detectable anti-MAP_5p and anti-MAP_2694295–303 antibodies in the CSF. Furthermore, a group of patients with MS showed intrathecally restricted production of antibodies against these peptides. Women appeared to mount a stronger humoral response to mycobacterial peptides than men. No significant difference in the frequency of anti-MBP85–98 antibodies was found between patients with MS and those with NMOSD. These data highlight the zoonotic potential of MAP, which suggests its involvement in MS etiopathogenesis.

scholarly journals Comparison of macular structural and vascular changes in neuromyelitis optica spectrum disorder and primary open angle glaucoma: a cross-sectional study

2020 ◽  
pp. bjophthalmol-2020-315842
Author(s):  
Xiayin Zhang ◽  
Hui Xiao ◽  
Chunxin Liu ◽  
Lanqin Zhao ◽  
Jinghui Wang ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Structural Parameters ◽  
Spectrum Disorder ◽  
Inner Plexiform Layer ◽  
Healthy Controls ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Open Angle ◽  
Vascular Changes

AimsTo compare macular structure and vasculature between neuromyelitis optica spectrum disorder (NMOSD) and primary open angle glaucoma (POAG) using optical coherence tomography angiography.MethodsNMOSD patients (n=124) with/without a history of optic neuritis (ON) (NMO+ON: 113 eyes; NMO-ON: 95 eyes), glaucomatous patients (n=102) with early/advanced glaucoma (G-E: 74 eyes; G-A: 50 eyes) and healthy controls (n=62; 90 eyes) were imaged. The main outcome measures were macular ganglion cell-inner plexiform layer (GC-IPL) thickness, vessel density (VD) and perfusion density (PD) in the superficial capillary plexus, and diagnostic capabilities of the parameters as calculated by area under the curve (AUC).ResultsSignificant losses in GC-IPL, VD and PD were detected in both patients with NMOSD and POAG. With matched losses in the peripapillary retinal nerve fibre layer, NMOSD group showed significant thinning of GC-IPL in the nasal-superior quadrant, whereas in POAG group, significant thinning was observed in the inferior and temporal-inferior quadrants. GC-IPL thinning was more prominent in the superior, nasal-superior and nasal-inferior quadrants in NMO+ON eyes. In G-A eyes, significant GC-IPL thinning was seen in the temporal-inferior quadrant. The specific structural parameters combining VD and foveal avascular zone (FAZ) indices showed the best diagnostic accuracies. The FAZ area in eyes with NMOSD was significantly smaller than the eyes of healthy controls and POAG.ConclusionNMOSD and POAG have specific patterns of macular structural and vascular changes associated with pathophysiology. Our results indicate that FAZ could be a sensitive biomarker of macular changes in NMOSD.

scholarly journals Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Patrick Schindler ◽  
Ulrike Grittner ◽  
Johanna Oechtering ◽  
David Leppert ◽  
Nadja Siebert ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neuromyelitis Optica ◽  
Single Molecule ◽  
Effect Size ◽  
Clinical Remission ◽  
Spectrum Disorder ◽  
Aquaporin 4 ◽  
Prognostic Biomarkers ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Neurofilament Light

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is a frequently disabling neuroinflammatory syndrome with a relapsing course. Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity and prognostic biomarkers in patients with aquaporin-4 immunoglobulin (Ig)G positive (AQP4-IgG+) NMOSD. Methods sGFAP and sNfL were determined by single-molecule array technology in a prospective cohort of 33 AQP4-IgG+ patients with NMOSD, 32 of which were in clinical remission at study baseline. Sixteen myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) patients and 38 healthy persons were included as controls. Attacks were recorded in all AQP4-IgG+ patients over a median observation period of 4.25 years. Results In patients with AQP4-IgG+ NMOSD, median sGFAP (109.2 pg/ml) was non-significantly higher than in MOG-IgG+ patients (81.1 pg/ml; p = 0.83) and healthy controls (67.7 pg/ml; p = 0.07); sNfL did not substantially differ between groups. Yet, in AQP4-IgG+, but not MOG-IgG+ patients, higher sGFAP was associated with worse clinical disability scores, including the Expanded Disability Status Scale (EDSS, standardized effect size = 1.30, p = 0.007) and Multiple Sclerosis Functional Composite (MSFC, standardized effect size = − 1.28, p = 0.01). While in AQP4-IgG+, but not MOG-IgG+ patients, baseline sGFAP and sNfL were positively associated (standardized effect size = 2.24, p = 0.001), higher sNfL was only non-significantly associated with worse EDSS (standardized effect size = 1.09, p = 0.15) and MSFC (standardized effect size = − 1.75, p = 0.06) in patients with AQP4-IgG+ NMOSD. Patients with AQP4-IgG+ NMOSD with sGFAP > 90 pg/ml at baseline had a shorter time to a future attack than those with sGFAP ≤ 90 pg/ml (adjusted hazard ratio [95% confidence interval] = 11.6 [1.3–105.6], p = 0.03). In contrast, baseline sNfL levels above the 75th age adjusted percentile were not associated with a shorter time to a future attack in patients with AQP4-IgG+ NMOSD. Conclusion These findings suggest a potential role for sGFAP as biomarker for disease severity and future disease activity in patients with AQP4-IgG+ NMOSD in phases of clinical remission.

Brain abnormalities as an initial manifestation of neuromyelitis optica spectrum disorder

2011 ◽  
Vol 17 (9) ◽  
pp. 1107-1112 ◽  
Author(s):  
Woojun Kim ◽  
Su-Hyun Kim ◽  
Sang Hyun Lee ◽  
Xue Feng Li ◽  
Ho Jin Kim
Keyword(s):  
Neuromyelitis Optica ◽  
Inflammatory Diseases ◽  
Age At Onset ◽  
Spectrum Disorder ◽  
Cancer Center ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Brain Abnormalities ◽  
Initial Manifestation ◽  
Imaging Characteristics

Background: Although brain abnormalities are being recognized more frequently in patients with neuromyelitis optica spectrum disorder (NMOSD), most brain lesions in previous reports have accompanied pre-existing NMOSD. Here, we describe clinical and imaging characteristics of patients with NMOSD who presented with brain symptoms as their first manifestation of the condition. Methods: Anti-aquaporin-4 antibody was measured using cell-based assays and/or enzyme-linked immunosorbent assay in the sera of 257 patients with inflammatory diseases of the central nervous system who attended the multiple sclerosis clinic of the National Cancer Center, Korea, between May 2005 and December 2009. Eighty-three were seropositive, and 15 of these who presented with brain symptoms were included in this study. We retrospectively reviewed these individuals’ clinical and radiological findings. Results: Patients with NMOSD were followed for a mean of 90 months. Median age at onset was 24 years (6–54 years) and there was a female preponderance (94%). The initial manifestation was classified into two groups according to clinical characteristics: encephalopathy mimicking acute disseminated encephalomyelitis or posterior reversible encephalopathy syndrome and characteristic brainstem symptoms such as intractable hiccup and vomiting. The majority of brain symptoms and lesions resolved. Intriguingly, eight patients (53%) experienced brain relapses that followed a similar pattern during the course of their disease. Conclusion: It is important to recognize that NMO or NMOSD can initially present with brain symptoms.

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