Decreased kynurenine in cerebrospinal fluid and potential role in neuromyelitis optica spectrum disorder.

Tryptophan (Trp) metabolism has been implicated in neuroinflammatory and neurodegenerative disorders, but its relationship with neuromyelitis optica spectrum disorder (NMOSD) is unclear. In this pilot study, cerebrospinal fluid (CSF) was prospectively collected from 26 NMOSD patients in relapse and 16 controls with noninflammatory diseases and 6 neurometabolites in the tryptophan metabolic pathway, including 5-hydroxytryptamine (5-HT), kynurenine (KYN), melatonin (MLT), 5-hydroxyindoleacetic acid (5HIAA), 3-hydroxy-o-aminobenzoic acid (3-HAA), and kynurenic acid (KYA), were measured by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The association of Trp metabolites with NMOSD and its clinical parameters was evaluated. The role of KYN, which is a Trp metabolite involved in the binding of NMOSD-IgG antibody to aquaporin 4 (AQP4), was also evaluated in vitro. CSF KYN was significantly decreased in patients with relapsing NMOSD compared to controls, and CSF KYN was associated with CSF white blood cells in NMOSD. In vitro experiments showed that NMOSD-IgG specifically recognized KYN, which reversed the NMOSD-IgG-induced downregulation of AQP4 expression. Our results show that abnormal Trp metabolism occurs in NMOSD and that KYN might be a potential target for the treatment of AQP4-IgG-positive NMOSD patients.

Cystatin C predicts the risk of incident cerebrovascular disease in the elderly: A meta-analysis on survival date studies.

BACKGROUND: Stroke is the third leading cause of global year of life lost in all-age and second-ranked cause of disability adjusted life years in middle-aged and elder population. Therefore, it is critical to study the relationship between vascular-related risk factors and cerebrovascular diseases. Several cross-sectional studies have shown that Cystatin C (Cys C) is an independent risk factor for cerebrovascular diseases and levels of Cys C are significantly higher in stroke patients than in healthy individuals. In this meta-analysis, we introduce a Cox proportional hazards model to evaluate the causality between Cys C and the risk of cerebrovascular accident in the elderly. METHODS: We searched PubMed, EMBASE, the Web of Science, and the Cochrane Library from 1985 to 2019 for studies on the relationship between serum Cys C and incidence stroke with Cox proportional hazards models. We conducted a subgroup analysis of the selected studies to determine a connection between atherosclerosis and stroke. Finally, 7 research studies, including 26,768 patients without a history of cerebrovascular, were studied. RESULTS: After comparing the maximum and minimum Cys C levels, the hazard ratio for all types of stroke, including ischemic and hemorrhagic stroke, was 1.18 (95% confidence interval 1.04-1.31) with moderate heterogeneity (I2 = 43.0%; P = .119) in a fixed-effect model after pooled adjustment for other potential risk factors. In the subgroup analysis, the hazard ratio and 95% confidence interval for Cys C stratified by atherosclerosis was 1.85 (0.97-2.72). As shown in Egger linear regression test, there was no distinct publication bias (P = .153). CONCLUSION: Increased serum Cys C is significantly associated with future stroke events in the elderly, especially in patients with carotid atherosclerosis. Thus, serum levels of Cys C could serve as a predicted biomarker for stroke attack.

Myelin oligodendrocyte glycoprotein antibody-associated disorders coexisting with ankylosing spondylitis: Potential association between demyelination and tumor necrosis factor inhibitors.

Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) is a newly described demyelinating disease. Ankylosing spondylitis (AS) is an inflammatory disease that predominantly affects the axial skeleton. Treatments for AS, such as tumor necrosis factor alpha (TNFα) inhibitors, may induce demyelination. We report the first case of MOGAD coexisting with AS and postulate a potential association with TNFα inhibitors. Further studies are needed to clarify the risk of demyelinating events following anti-TNFα therapy and to elucidate the relationship between MOGAD and AS.