Disruption of blood-brain barrier integrity associated with brain lesions in Chinese neuromyelitis optica spectrum disorder patients

You, Xiao-fan; Yan, Lirong; Li, Xin; Pang, Ying; Guo, Xiaolei; Ye, Jing; Hu, Hongtao

doi:10.1016/j.msard.2018.10.114

Cited by 11 publications

(7 citation statements)

References 42 publications

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“…It was reported that patients with optic neuritis as the rst attack showed signi cantly higher serum titer than patients with acute myelitis or area postrema syndrome [19]. Another study showed that Qalb was signi cantly higher in patients with brain lesion [21]. However, in our study, we did not nd a correlation between lesion distribution and CSF AQP4-IgG titer.…”

Section: Discussioncontrasting

confidence: 93%

Factors influencing the cerebrospinal fluid antibodies to aquaporin-4: a study of 87 patients with neuromyelitis optica spectrum disorder

Xie

Peng

et al. 2023

Preprint

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Background: Serum AQP4 antibody (AQP4-IgG) is the causative antibody of neuromyelitis optica spectrum disorder (NMOSD). AQP4-IgG in cerebrospinal fluid (CSF) of NMOSD patients were seldom studied. In this study, we measured antibody titers in time-matched paired CSF and serum samples and explored the relation between CSF AQP4-IgG and patient’s clinical features. Methods: A total of 137 NMOSD patients admitted in the department of Neurology of Renji Hospital from January 2016 to July 2022 were retrospectively reviewed. 87 patients with complete results of paired serum and CSF AQP4-IgG assay were included. Their demographic, clinical, laboratory data and MRI images were collected and analyzed. Result: In this study, 77 patients were seropositive for AQP4-IgG and 10 patients were seronegative. Among the 77 patients seropositive for AQP4-IgG, 47 were CSF-positive and 30 were CSF-negative, while no patients were CSF-positive in the 10 seronegative patients. Between the CSF-positive and CSF-negative groups, there were significant difference in expanded disability status scale (EDSS) scores, relapse proportion, CSF IgG, and CSF IgM, and these indicators were higher in CSF-positive group. We also found a positive correlation between the serum and CSF titer (rs: 0.629, p<0.001). Further logistic multi-factor regression analysis of CSF AQP4-IgG titer revealed that only serum AQP4-IgG titer was ultimately included in the regression model (OR 1.004, 95% CI: 1.001-1.007, p<0.01). Conclusion: AQP4-IgG titer in CSF is mainly affected by serum AQP4-IgG titer. Higher EDSS and a higher presence of relapse status are more common in patients with positive CSF AQP4-IgG.

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Section: Discussioncontrasting

confidence: 93%

Factors influencing the cerebrospinal fluid antibodies to aquaporin-4: a study of 87 patients with neuromyelitis optica spectrum disorder

Xie

Peng

et al. 2023

Preprint

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“…The relatively high GFAP concentration in chronic HF suggests ongoing glial damage, which might be triggered by interleukin 6‐induced neuroinflammation 19 and/or neuronal and glial cell destruction upon hypoperfusion and hypoxia 20 . Future studies are needed to advance these hypotheses and to disclose how GFAP gets access to the systemic circulation in the absence of an overt blood–brain barrier disruption as it is found in neuromyelitis optica 21 . Because astrocyte feet are an integral component of the blood brain barrier, it is conceivable that astrocytic damage in HF patients concomitantly induces subtle leakage of the blood–brain barrier not strong enough to cause extravasation of the MRI contrast agent gadolinium‐diethylenetriaminepentacetate for detection but sufficient for release of GFAP.…”

Section: Discussionmentioning

confidence: 99%

Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure

et al. 2022

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Aims Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF. Methods and resultsUsing bead-based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters-HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty-six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = À4.7; P < 0.001), alanine aminotransferase (T = À2.1; P = 0.036), and the left atrial end-systolic volume index (T = 3.4; P = 0.004). NT-proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = À3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025). Conclusions Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.

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“…Currently, the onset time and degree of MRI enhancement can reflect disease activity to some extent (21)(22)(23). The destruction of the blood-brain barrier (BBB) is an important pathological process in the acute phase of NMOSD, and the degree of MRI enhancement can reflect the degree of BBB damage in NMOSD patients (35,36). We have revealed that RGMa expression consistent with the onset time according to the acute phase group had significantly higher serum RGMa expression level than that in the remission group.…”

Section: Discussionmentioning

confidence: 99%

Expression and Clinical Correlation Analysis Between Repulsive Guidance Molecule a and Neuromyelitis Optica Spectrum Disorders

et al. 2022

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ObjectivesThis study sought to explore the expression patterns of repulsive guidance molecules a (RGMa) in neuromyelitis optica spectrum disorders (NMOSD) and to explore the correlation between RGMa and the clinical features of NMOSD.MethodsA total of 83 NMOSD patients and 22 age-matched healthy controls (HCs) were enrolled in the study from October 2017 to November 2021. Clinical parameters, including Expanded Disability Status Scale (EDSS) score, degree of MRI enhancement, and AQP4 titer were collected. The expression of serum RGMa was measured by enzyme-linked immunosorbent assay (ELISA) and compared across the four patient groups. The correlation between serum RGMa levels and different clinical parameters was also assessed.ResultsThe average serum expression of RGMa in the NMOSD group was significantly higher than that in the HC group (p < 0.001). Among the patient groups, the acute phase group exhibited significantly higher serum RGMa levels than did the remission group (p < 0.001). A multivariate analysis revealed a significant positive correlation between RGMa expression and EDSS score at admission, degree of MRI enhancement, and segmental length of spinal cord lesions. There was a significant negative correlation between the expression of RGMa in NMOSD and the time from attack to sampling or delta EDSS.ConclusionsThe current study suggests that RGMa may be considered a potential biomarker predicting the severity, disability, and clinical features of NMOSD.

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Disruption of blood-brain barrier integrity associated with brain lesions in Chinese neuromyelitis optica spectrum disorder patients

Cited by 11 publications

References 42 publications

Factors influencing the cerebrospinal fluid antibodies to aquaporin-4: a study of 87 patients with neuromyelitis optica spectrum disorder

Factors influencing the cerebrospinal fluid antibodies to aquaporin-4: a study of 87 patients with neuromyelitis optica spectrum disorder

Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure

Expression and Clinical Correlation Analysis Between Repulsive Guidance Molecule a and Neuromyelitis Optica Spectrum Disorders

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