Incidence and predictors of futile recanalisation after endovascular therapy in acute vertebrobasilar artery occlusion patients: insight from the ANGEL-ACT registry.

OBJECTIVES: To identify the occurrence rate and predictors of futile recanalisation after endovascular therapy (EVT) for acute vertebrobasilar artery occlusion (VBAO). METHODS: Participants of the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischaemic Stroke (ANGEL-ACT) registry were selected for the analysis. Futile recanalisation was defined as patients did not achieve a 90-day good outcome (modified Rankin Scale ≤3) despite successful recanalisation (modified Treatment in Cerebral Ischaemia Scale ≥2b) after the procedure. Multivariable logistic regression analysis was conducted to find independent predictors of futile recanalisation in VBAO patients undergoing EVT. RESULTS: Three hundred and fifteen patients with VBAO who achieved successful recanalisation after EVT were included in current analysis, of whom, 155 (49.2%) suffered futile recanalisation, and 160 achieved effective recanalisation. After the multivariable analysis, we found admission National Institutes of Health Stroke Scale (NIHSS) ≥19 (OR 4.81, 95% CI 2.76 to 8.39, p<0.001), platelet-lymphocyte ratio (PLR) ≥162.2 (OR 1.93, 95% CI 1.14 to 3.27, p=0.001), onset-to-puncture time (OTP) ≥334 min (OR 2.15, 95% CI 1.25 to 3.68, p=0.005) and use of general anesthesia (GA) (OR 1.87, 95% CI 1.09 to 3.22, p=0.024) were associated with futile recanalisation. CONCLUSIONS: Futile recanalisation after EVT occurred 49.2% of VBAO patients in the ANGEL-ACT registry. NIHSS≥19, PLR≥162.2, OTP≥334 min and use of GA were independent predictors of futile recanalisation.

Efficacy of transcutaneous auricular vagus nerve stimulation on radiotherapy-related neuropathic pain in patients with head and neck cancers (RELAX): protocol for a multicentre, randomised, double-blind, sham-controlled trial.

INTRODUCTION: Radiotherapy-related neuropathic pain (RRNP) is one of the most distressing complications after radiotherapy for head and neck cancers. Drug therapy is not sufficiently effective and has limitations in terms of dose titration period and side effects. Transcutaneous auricular vagus nerve stimulation (taVNS), which stimulates the auricular branches of the vagus nerve through electrical impulses, has been proven to have analgesic effects in certain diseases. However, it is unknown whether taVNS can relieve RRNP. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blind, parallel, sham-controlled trial. We will include adult patients newly diagnosed with neuropathic pain after radiotherapy for head and neck cancers. One hundred and sixteen individuals will be recruited and randomly assigned in a 1:1 ratio to receive taVNS or sham stimulation. The interventions will last for 7 days, twice daily for 30 min each. The primary efficacy outcome is pain reduction on day 7. The secondary outcomes are changes in functional interference, psychological distress, fatigue, quality of life and serum inflammatory factors. The study may provide a new early intervention strategy for RRNP among patients with head and neck cancers. ETHICS AND DISSEMINATION: This study has been approved by the Medical Research Ethics Committee of Sun Yat-sen University (SYSKY-2022-109-01) and will be conducted in strict accordance with the Declaration of Helsinki. Ethical approvals will be obtained separately for all centres involved in the study. Study results will be published in peer-reviewed academic journals. The database of the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: NCT05543239.

Brain radial enhancement pattern in patients with negative glial fibrillary acidic protein-IgG: A cases series study.

BACKGROUND AND OBJECTIVES: Brain radial enhancement pattern on magnetic resonance imaging (MRI) has been identified as typical lesions in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, the authors encountered several patients without GFAP-IgG showing that such specific imaging. In the present study, we reported the clinical pictures of 5 GFAP-IgG-negative patients with GFAP-A specific imaging pattern. METHODS: Data was retrospectively obtained from June 2013 through April 2023, and five GFAP-IgG-negative patients with valid data were recruited. Clinical information was either obtained by the investigators or retrieved from the referring clinicians and included prodromal symptoms, neurologic manifestations, comorbidities, results of ancillary studies. RESULTS: Altogether five GFAP-IgG-negative patients with "meningoencephalitis/encephalitis" manifestations and brain radial perivascular enhancement were confirmed. One patient had peripheral lymphoma. Four patients had other autoimmune antibody in serum and/or cerebrospinal fluid, of which one patient had positive aquaporin IgG. Clinical features of the five patients included headache, fever, epilepsy and abnormal behavioral symptoms. MRI of patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP-A. CONCLUSION: GFAP-A-like disorders with radial perivascular enhancement could be found in GFAP-IgG-negative patients with or without neoplasm, which could provide new insight into the differential diagnosis of GFAP-A.

MASTRO I: Meta-Analysis and Systematic Review of thrombectomy stent retriever outcomes: comparing functional, safety and recanalization outcomes between EmboTrap, Solitaire and Trevo in acute ischemic stroke.

Aim: Stent-retriever (SR) thrombectomy has demonstrated superior outcomes in patients with acute ischemic stroke compared with medical management alone, but differences among SRs remain unexplored. We conducted a Systematic Review/Meta-Analysis to compare outcomes between three SRs: EmboTrap®, Solitaire™, and Trevo®. Methods: We conducted a PRISMA-compliant Systematic Review among English-language studies published after 2014 in PubMed/MEDLINE that reported SRs in ≥25 patients. Functional and safety outcomes included 90-day modified Rankin scale (mRS 0-2), mortality, symptomatic intracranial hemorrhage (sICH), and embolization to new territory (ENT). Recanalization outcomes included modified thrombolysis in cerebral infarction (mTICI) and first-pass recanalization (FPR). We used a random effects Meta-Analysis to compare outcomes; subgroup and outlier-influencer analysis were performed to explore heterogeneity. Results: Fifty-one articles comprising 9,804 patients were included. EmboTrap had statistically significantly higher rates of mRS 0-2 (57.4%) compared with Trevo (50.0%, p = 0.013) and Solitaire (45.3%, p < 0.001). Compared with Solitaire (20.4%), EmboTrap (11.2%, p < 0.001) and Trevo (14.5%, p = 0.018) had statistically significantly lower mortality. Compared with Solitaire (7.7%), EmboTrap (3.9%, p = 0.028) and Trevo (4.6%, p = 0.049) had statistically significantly lower rates of sICH. There were no significant differences in ENT rates across all three devices (6.0% for EmboTrap, 5.3% for Trevo, and 7.7% for Solitaire, p = 0.518). EmboTrap had numerically higher rates of recanalization; however, no statistically significant differences were found. Conclusion: The results of our Systematic Review/Meta-Analysis suggest that EmboTrap may be associated with significantly improved functional outcomes compared with Solitaire and Trevo. EmboTrap and Trevo may be associated with significantly lower rates of sICH and mortality compared with Solitaire. No significant differences in recanalization and ENT rates were found. These conclusions are tempered by limitations of the analysis including variations in thrombectomy techniques in the field, highlighting the need for multi-arm RCT studies comparing different SR devices to confirm our findings.

Futile reperfusion of endovascular treatment for acute anterior circulation large vessel occlusion in the ANGEL-ACT registry.

BACKGROUND: Some patients with large vessel occlusion (LVO) still cannot achieve functional independence despite successful reperfusion after endovascular treatment (EVT), named futile reperfusion. We aimed to explore the incidence and predictors of futile reperfusion of EVT for anterior circulation LVO in the Chinese population based on a nationwide prospective multicenter registry. METHODS: We selected patients from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) registry. Successful reperfusion was defined as modified Treatment In Cerebral Ischemia (mTICI) 2b-3 after EVT, and functional independence was defined as 90-day modified Rankin Scale (mRS) 0-2. A multivariable regression model was performed to identify the independent predictors of futile reperfusion in anterior circulation LVO patients. RESULTS: A total of 1158 anterior circulation LVO patients were included in our study. 600 of the 1158 patients (51.8%) suffered futile reperfusion. Age ≥69 (adjusted OR (aOR) 1.69, 95% CI 1.21 to 2.35, P=0.002), baseline National Institutes of Health Stroke Scale (NIHSS) ≥14 (aOR 2.36, 95% CI 1.71 to 3.27, P<0.001), baseline serum glucose ≥6.5 mmol/L (aOR 1.73, 95% CI 1.27 to 2.36, P=0.001), drip and ship (aOR 1.56, 95% CI 1.11 to 2.18, P=0.011), and general anesthesia (aOR 2.28, 95% CI 1.66 to 3.14, P<0.001) were associated with a high risk of futile reperfusion in the anterior LVO patients after EVT, whereas baseline Alberta Stroke Program Early CT Score (ASPECTS) ≥8 (aOR 0.65, 95% CI 0.47 to 0.91, P=0.011) and complete reperfusion (aOR 0.62, 95% CI 0.43 to 0.89, P=0.010) were associated with a low risk of futile reperfusion in the anterior LVO patients after EVT. CONCLUSIONS: In the ANGEL-ACT registry, 51.8% of anterior circulation LVO patients suffered futile reperfusion after EVT. Age ≥69 years, baseline NIHSS ≥14, baseline serum glucose ≥6.5 mmol/L, drip and ship, general anesthesia, baseline ASPECTS <8, and incomplete reperfusion were the independent predictors of futile reperfusion.

Malnutrition Defined by Geriatric Nutritional Risk Index Predicts Outcomes in Severe Stroke Patients: A Propensity Score-Matched Analysis.

Background: Malnutrition's prognostic impact in patients with severe stroke requiring ICU admission is not well known. This study aimed to assess the nutritional status of severe stroke patients using the geriatric nutritional risk index (GNRI) and examine the association of GNRI with mortality in that population. Methods: We identified 1145 severe stroke patients requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-III) database and divided them into low GNRI (≤98) or high GNRI (>98) groups. We used a propensity score matching (PSM) method to reduce confounding. Cox proportional hazards regression and restricted cubic splines were used to elucidate the association between GNRI and mortality. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results: A total of 397 (35%) patients were in the low GNRI group (at risk of malnutrition). After PSM, patients in the low GNRI group still suffered higher mortality compared with the high GNRI group at 28 days (27.9 vs. 20.8%), 90 days (35.5 vs. 25.7%), and 1 year (43.4 vs. 30.9%) (p < 0.05). A low GNRI was significantly associated with an increased mortality (HR: 1.38, 95% CI 1.03−1.86 in 28 days; HR: 1.45, 95% CI 1.11−1.89 in 90 days; HR: 1.51, 95% CI 1.19−1.92 in 1 year). Sensitivity analyses yielded consistent results. Restricted cubic splines showed a progressively decreasing risk of mortality with increasing GNRI scores up to 110, approximately. Conclusion: Severe stroke patients with malnutrition experienced an increased risk of death compared to those without malnutrition. GNRI, as a simple and practical nutritional screening tool, can be used as a routine approach to the nutritional status of stroke patients.

Comparison of predictors of failure of early neurological improvement after successful endovascular treatment for posterior and anterior circulation large vessel occlusion: Data from ANGEL-ACT registry.

PURPOSE: To identify and compare the predictors of failure of early neurological improvement (fENI)after successful EVT for anterior circulation large vessel occlusion (ACLVO) and posterior circulation LVO (PCLVO). METHODS: Subjects were selected from the ANGEL-ACT registry. fENI was defined as unchanged or worsened in National Institutes of Health Stroke Scale score (NIHSS) between admission and 24 h after EVT. Predictors of fENI after successful EVT (mTICI 2b-3) were determined via center-adjusted analyses. Univariable and multivariable comparisons between ACLVO and PCLVO were performed. RESULTS: A total of 1447 patients, 1128 were with ACLVO, and 319 were with PCLVO. Among the patients with ACLVO, there were 409 patients (36.3%) with fENI and 719 patients (63.7%) with ENI. We observed that pre-stroke mRS scale score of 2 (odd ratio[OR] 95% confidence interval[CI], 6.93[1.99-24.10], P = 0.002), initial NIHSS score (OR per point[95%CI], 0.97[0.95-0.99], P = 0.012), diabetes (OR[95%CI], 1.56[1.08-2.25], P = 0.017), previous ICH (OR[95%CI] 9.21[1.76-48.15], P = 0.008), local anesthesia (OR[95%CI] 1.63[1.10-2.42], P = 0.014), onset-to-puncture time (OR[95%CI], 1.001[1.000-1.001], P = 0.009), symptomatic ICH (OR[95%CI] 3.90[2.27-6.69], P < 0.001), and continued use of tirofiban within 2 h after EVT (OR[95%CI], 0.69[0.51-0.93], P = 0.014) were independent predictors of fENI of ACLVO after EVT. Among the patients with PCLVO, there were 112 patients (35.1%) with fENI and 207 patients (64.9%) with ENI. In contrast, admission SBP (OR[95%CI], 0.98[0.97-0.99], P = 0.012), and vascular dissection within 2 h after EVT (OR[95%CI], 7.23[1.33-39.13], P = 0.022) were independent predictors of fENI of PCLVO after EVT. CONCLUSION: In selected patients, successful EVT can lead to similar outcomes in PCLVO and ACLVO. Some predictors of fENI in both anterior circulation and posterior circulation were identified in our study, which should be highly considered in the clinical practice in LVO patients undergoing EVT.

Serological biomarkers in autoimmune GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.

Development of a Nomogram for Predicting Asymptomatic Coronary Artery Disease in Patients with Ischemic Stroke.

BACKGROUND: Coronary artery stenosis (CAS) ≥50% often coexists in patients with ischemic stroke, which leads to a significant increase in the occurrence of major vascular events after stroke. This study aimed to develop a nomogram for diagnosing the presence of ≥50% asymptomatic CAS in patients with ischemic stroke. METHODS: A primary cohort was established that included 275 non-cardioembolic ischemic stroke patients who were admitted from January 2011 to April 2013 to a teaching hospital in southern China. The preoperative data were used to construct two models by the best subset regression and the forward stepwise regression methods, and a nomogram between these models was established. The assessment of the nomogram was carried out by discrimination and calibration in an internal cohort. RESULTS: Out of the two models, model 1 contained eight clinical-related variables and exhibited the lowest Akaike Information Criterion value (322.26) and highest concordance index 0.716 (95% CI, 0.654-0.778). The nomogram showed good calibration and significant clinical benefit according to calibration curves and the decision curve analysis. CONCLUSION: The nomogram, composed of age, sex, NIHSS score on admission, hypertension history, fast glucose level, HDL cholesterol level, LDL cholesterol level, and presence of ≥50% cervicocephalic artery stenosis, can be used for prediction of ≥50% asymptomatic coronary artery disease (CAD). Further studies are needed to validate the effectiveness of this nomogram in other populations.

Estimation of critical closing pressure using intravascular blood pressure of the common carotid artery.

PURPOSE: Radial artery, femoral artery, and aortic arterial blood pressures (ABPs) can be used to estimate cerebral critical closing pressure (CrCP) and resistance-area product (RAP). However, the use of the common carotid artery (CCA) intravascular blood pressure to estimate CrCP is unclear. Thus, using continuous ABP monitoring, we compared the CrCP and RAP estimated from CCA measurements with the corresponding values acquired from the radial artery. METHODS: In this retrospective cross-sectional study, we analyzed CrCP and RAP estimations from 21 patients with normal cerebral blood vessels between July 23, 2010, and February 9, 2011, using linear regression of the cerebral blood flow velocity-ABP relationship. RESULTS: Bland-Altman analysis showed that the average differences (95% limits of agreement) between the radial artery and the left CCA were -6.3 (-53.1 - 40.6) mmHg and -0.08 (-0.41 - 0.25) mmHg s cm-1 for CrCP and RAP, respectively. CONCLUSIONS: The CrCP and RAP estimated from the CCA measurements are consistent with the corresponding values obtained from the radial artery.

Serum molecular biomarkers in neuromyelitis optica and multiple sclerosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory demyelinating disorder of the central nervous system (CNS), which mainly affects the optic nerves and spinal cord. The aims of this study were to determine whether the expression levels of serological cytokines could distinguish 1) NMOSD from healthy controls (HCs); and 2) NMOSD patients with and without the aquaporin-4 (AQP4) antibody biomarker from each other; and 3) NMOSD patients without the antibody to AQP4 from MS patients. METHODS: The expression levels of 200 proteins in serum from 41 NMOSD (32 with antibodies to AQP4, 9 without antibodies to AQP4), 12 MS patients, and 34 HCs were measured using glass-based antibody arrays. None of the patients received any immunosuppressive treatment. In parallel, the correlation between protein expression in NMOSD/MS patients and clinical traits was determined with Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Thirty-nine serological proteins were differentially expressed in NMOSD patients compared to HCs, with 29 of these proteins not observed in MS patients. In addition, the data reveal 15 differentially-expression proteins (DEPs) between AQP4-IgG seronegative and AQP4-IgG seropositive NMOSD patients, and 9 DEPs between NMOSD and MS patients who did not have AQP4-IgG. CONCLUSION: Serological IL-17B is significantly upregulated in both NMOSD and MS patients compared to HCs, and could be a key biomarker of NMOSD and MS. Serological VEGF, MPIF-1 and NrCAM were positively associated with AQP4-IgG titer. We also demonstrate that EGF may be involved in the breakdown of the BBB by downregulating Claudin-5.

[Characteristics of grassland degradation and its relationship with climate factors on Qinghai-Tibetan Plateau, China]. / é’è—é«˜åŽŸè‰åœ°é€€åŒ–ç‰¹å¾åŠå ¶ä¸Žæ°”å€™å› å­çš„å ³ç³».

Understanding the distribution, characteristics, and changing trend and persistence of grassland degradation and revealing its mechanism on the Qinghai-Tibetan Plateau can provide scientific basis for effective grassland management and conservation. We selected grassland coverage as the remote sensing monitoring index to establish the remote sensing monitoring and evaluation index system of grassland degradation and evaluate grassland degradation during 2016 to 2020 on the Qinghai-Tibet Plateau. The changing trend and persistence of grassland coverage were analyzed using linear regression and Hurst index analysis on a long time series scale (1982-2020). The partial correlation analysis was used to examine the influence of climate on grassland degradation. The results showed that grassland degradation reached 24.3% during 2016 to 2020, which was mainly light and moderate degradation, and largely distributed in low altitude and high fractional vegetation cover areas. From 1982 to 2020, grassland coverage tended to increase in the north, west and southwest, and decreased in the east and center of the Qinghai-Tibetan Plateau. The Hurst index of grassland coverage was less than 0.5 in 98.1% of the total grassland, indicating grassland coverage showed negatively persistent. The partial correlation coefficient between grassland coverage and precipitation (0.096) was higher than that of temperature (-0.033). About 16.0% area was dominated by temperature, which was mainly distributed in the central and southeast. About 12.2% area was dominated by precipitation, which was distributed in the northeast and west of the Qinghai-Tibetan Plateau.

[Responses of Different Degradation Stages of Alpine Wetland on Soil Microbial Community in the Yellow River Source Zone].

MiSeq sequencing technology was used to analyze the microbial community diversity of soil in alpine wetlands to understand the degradation processes and environmental factors in these areas. The results showed that the severity of soil degradation changed the species diversity of soil microorganisms at the level of OTUs, and grass patches contained more species than frozen-thawing patches. The soil fungi species of OTUs changed significantly. The diversity indexes of bacteria (between the frozen-thawing patches and the grass patches) were higher than that of fungi. The dominant microbial species were consistent among different degradation stages. The dominant species of bacteria and fungi were Proteobacteria and RB41, and Ascomycota and Mortierella, respectively. The abundance of dominant microorganisms was significantly between un-degraded and heavily degraded areas, except for RB41 (P<0.05). The dominant microorganisms in the grass patches were more sensitive than those in the frozen-thawing patches. It was found that the main factors affecting the microbial community structure of soil were water content, organic carbon, microbial biomass carbon, microbial biomass nitrogen, and sedge coverage. Microbial diversity may decrease in heavily degraded alpine wetlands. Thus, the frozen-thawing patches and sedge species should be first protected, and the supplements of soil water content, soil organic carbon, microbial biomass carbon, and nitrogen should be strengthened for alpine wetland restoration.

A novel technique for the surgical management of intraocular lens-capsular bag-capsular tension ring complex dislocation.

The present study describes a surgical technique for the management of complex dislocation and subluxation of the intraocular lens (IOL)-capsular bag (CB)-capsular tension ring (CTR) complex. During the procedure, one double-curved suture was inserted through the sclera into the posterior chamber, passing through the anterior capsules and then into the anterior chamber. The suture lines were pulled out from above and below the IOL-CB-CTR complex and a knot was tied 1 mm away from the corneoscleral incision. The IOL-CB-CTR complex was repositioned by adjusting the suture length. This novel method does not require explanting of the original IOL, allowing the IOL-CB-CTR complex to be immobilized in a simple and effective way.

Development of an Antibacterial Bone Graft by Immobilization of Levofloxacin Hydrochloride-Loaded Mesoporous Silica Microspheres on a Porous Scaffold Surface.

An effective local drug delivery system remains an urgently needed product for the treatment of chronic osteomyelitis in the clinic. In this study, we developed an antibacterial functionalization bone graft by immobilizing levofloxacin hydrochloride-loaded mesoporous silica microspheres (LFH @ MSNs) on the surface of a nanohydroxyapatite/polyurethane (n-HA/PU) bioactive composite scaffold. Through pretreatment of the n-HA/PU scaffold by chitosan solution and subsequent crosslinking by vanillin, LFH @ MSNs were uniformly and stably immobilized on the scaffold surface. The results of drug release experiments showed that the release of LFH from LFH @ MSN-modified n-HA/PU scaffolds (LFH @ MSN/n HA/PU) lasted up to 42d. The antibacterial assays indicated that LFH @ MSN/n-HA/PU offers satisfactory antibacterial activity against both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria. The biosafety assays demonstrated that the LFH @ MSN/n-HA/PU scaffold could satisfy the requirements of the biosafety standards. The constructed LFH @ MSN/n-HA/PU porous scaffolds with an antibacterial surface and favorable biosafety are deemed a promising candidate for infectious bone defect repair.

Astrocytic damage in glial fibrillary acidic protein astrocytopathy during initial attack.

OBJECTIVE: Determination of glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and myelin oligodendrocyte glycoprotein (MOG) levels in cerebrospinal fluid (CSF), and astrocytic damage analysis in patients with GFAP astrocytopathy (GFAP-A) and other conditions. METHODS: GFAP, AQP4, and MOG levels in CSF were detected via enzyme-linked immunosorbent assays. Anti-GFAP, anti-AQP4, and anti-MOG IgGs were detected via indirect immunofluorescence assays. RESULTS: In 32 GFAP-Astrocytopathy patients, CSF GFAP was significantly higher during acute exacerbation than it was in patients with MOG encephalomyelitis, multiple sclerosis, autoimmune encephalitis, and an "other inflammatory neurological disorders" group (all p < 0.0001). CSF GFAP levels were slightly higher in the GFAP-A group than in an anti-AQP4 IgG-positive neuromyelitis optica spectrum disorder group (p = 0.012). There were no significant differences between the CSF MOG and AQP4 levels in the GFAP-A group and those of other groups. CSF GFAP levels were significantly reduced after steroid treatment (p = 0.011). CSF GFAP levels differed significantly in GFAP-Astrocytopathy patients with and without encephalitis (p = 0.016). In GFAP-Astrocytopathy patients, CSF GFAP was correlated with Expanded Disability Status Scale (EDSS) score during attack (r = 0.545, p = 0.001). In follow-up examinations however, in GFAP-Astrocytopathy patients CSF GFAP level was not correlated with EDSS score 6 months later. CONCLUSIONS: CSF GFAP level and pathological examination of GFAP-Astrocytopathy patients revealed astrocyte damage. CSF GFAP level was associated with steroid treatment at the acute stage, therefore CSF GFAP may be a sensitive biomarker with respect to the effects of therapy during the acute stage.

Screening for autoantibodies in inflammatory neurological syndrome using fluorescence pattern in a tissue-based assay: Cerebrospinal fluid findings from 793 patients.

BACKGROUND: To evaluate indirect immunofluorescence patterns of auto-antibodies and the targeting antigens to Immunoglobulin Gs (IgGs) in the cerebrospinal fluid (CSF) by a tissue-based assay(TBA). METHODS: CSF samples were collected from 793 patients. Auto-antibody levels were measured via an immunofluorescence assay. RESULTS: 110 (13.9%) CSF samples with a specific response were confirmed. Of these, 37 showed a neuronal pattern, 57 an astrocyte pattern, 7 a neuronal and astrocyte pattern, and 9 samples showed an oligodendrocyte pattern. In the neuronal antibody group, 16 patients had NMDAR-IgGs, 3 had LGi1-IgGs, 2 had AMPA2-IgGs, 2 had GAD65-IgGs, 1 patient had GABA-IgGs, and 1 patient had overlapping NMDAR-IgGs and AQP4-IgGs. Of the unidentified neuronal antibodies, two were cellular surface antibodies, three were cellular surface and cytoplasm antibodies, three were cytoplasm antibodies, and four were nuclear and cytoplasm antibodies. Among the 57 patients with the astrocyte pattern, 28 patients were positive for AQP4-IgGs, 21 were positive for GFAP-IgGs, 5 patients had overlapping AQP4 and GFAP-IgGs, and 3 patients had an unidentified antigen. Seven patients showed neuronal and astrocyte patterns simultaneously; four of them had unknown neuronal antibodies. In the patients with an oligodendrocyte pattern, one was positive for MOG-IgGs and four for MBP-IgGs. CONCLUSIONS: The TBA is helpful for diagnosing autoimmune neurological syndrome, especially in patients with unknown antibodies and antigens. Presence of unidentified antibodies against neuronal or glial cells could be an interesting finding, but should be investigated in future studies which incorporate parallel serum samples at an appropriate IgG dilution.

SIRT6 protects retinal ganglion cells against hydrogen peroxide-induced apoptosis and oxidative stress by promoting Nrf2/ARE signaling via inhibition of Bach1.

Oxidative stress-induced damage of retinal ganglion cells (RGCs) is a major contributor to retinal degenerative diseases, such as glaucoma. Sirtuin 6 (SIRT6) has emerged as a cytoprotective protein against various insults. However, whether SIRT6 exerts a protective effect against oxidative stress-damaged RGCs remains unknown. In this study, we aimed to investigate the potential role and regulatory mechanism of SIRT6 in hydrogen peroxide (H2O2)-induced oxidative damage of RGCs in vitro. We found that SIRT6 expression was significantly downregulated in RGCs with H2O2 treatment. Functional experiments showed that overexpression of SIRT6 improved survival and reduced apoptosis and the production of reactive oxygen species (ROS) in H2O2-treated RGCs. In contrast, SIRT6 knockdown had the opposite effect. Moreover, we found that SIRT6 overexpression promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the activity of antioxidant response element (ARE). In addition, we found that the promotional effect of SIRT6 on Nrf2/ARE signaling was associated with inhibition of BTB and CNC homology 1 (Bach1), an inhibitor of Nrf2. However, overexpression of Bach1 or inhibition of Nrf2/ARE signaling partially reversed the SIRT6-mediated protective effect. Taken together, these results demonstrate that SIRT6 protects RGCs from oxidative stress-induced damage by promoting the activation of Nrf2/ARE signaling via inhibition of Bach1, suggesting a potential role of SIRT6 in retinal degenerative diseases.

Diagnostic ability of ganglion cell complex thickness to detect glaucoma in high myopia eyes by Fourier domain optical coherence tomography.

AIM: To evaluate the ability of macular ganglion cell complex (GCC) thickness using Fourier domain optical coherence tomography (FD-OCT) to detect glaucoma in highly myopic eyes. METHODS: Cross-sectional study. A total of 114 participants, consecutively were enrolled. Macular GCC thickness and peripapillary retinal nerve fiber layer (RNFL) thickness were obtained with RTVue FD-OCT. Receiver operating characteristics curves were constructed for each measurement parameter, and areas under the curves (AUCs) were compared. RESULTS: Both the average GCC and average RNFL thickness showed negative correlations with axial length (rGCC=-0.404, P=0.001; rRNFL=-0.561, P<0.001). The largest AUCs from GCC, and RNFL parameters were 0.968 [global loss volume (GLV)], and 0.855 (average RNFL), respectively. GLV was significantly better for detecting high myopic glaucoma than average RNFL (P<0.001). CONCLUSION: Macular GCC thickness has higher diagnostic power than peripapillary RNFL thickness to discriminate glaucoma patients from non-glaucoma subjects in high myopia.

Overlapping Autoimmune Syndromes in Patients With Glial Fibrillary Acidic Protein Antibodies.

BACKGROUND: Glial fibrillary acidic protein (GFAP) astrocytopathy, an autoimmune central nervous system disorder with a specific GFAP-IgG, often coexists with other antibodies. OBJECTIVE: The aim of this article was to study overlapping syndromes in autoimmune GFAP astrocytopathy. METHODS: Antibody was detected by indirect immunofluorescence assay. Patient data were analyzed retrospectively. RESULTS: Thirty patients with positive GFAP-IgG were included, of whom 10 were defined as overlapping syndrome. Four patients with positive aquaporin-4 (AQP4)-IgG, two with N-methyl-d-aspartate receptor-IgG, three with unknown neuronal antibodies, and one with double AQP4 and myelin oligodendrocyte glycoprotein-IgG were identified. GFAP-IgG and other specific antibodies occurred simultaneously at the initial attack in eight patients. The main symptoms included fever, headache, ataxia, psychosis, hypersomnia, dyskinesia, dementia, seizure, myelitis, and optical symptoms. Brain magnetic resonance imaging in four patients revealed characteristic radial enhancing patterns in the white matter. Cortical abnormalities were found in four patients. Other brain abnormalities occurred in the hypothalamus, midbrain, pons, medulla, cerebellum, and meninges. Six patients exhibited lesions in the spinal cord. In a subgroup study, patients with overlapping syndrome were younger at onset than those with non-overlapping syndrome. CONCLUSION: Overlapping antibodies are common in GFAP astrocytopathy.