Vitamin D status and neuromyelitis optica spectrum disease: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: There's an increasing body of evidence on vitamin D deficiency and the risk of neuromyelitis optica spectrum disorder (NMOSD). The aim of this meta-analysis was to assess serum vitamin D levels in patients with NMOSD versus healthy controls. METHODS: We searched PubMed, EMBASE, Cochrane Library, Web of Science and CNKI for publications up to November 2022 and explored the relationship between NMOSD and serum vitamin D levels. The standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated using a random-effects model. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Begg's test, Egger's test, and Egger's funnel plot were adopted to evaluate publication bias. RESULTS: 6 studies (including 319 patients and 595 healthy controls) met the inclusion criteria and all compared vitamin D levels in patients with NMOSD versus healthy controls. Levels of serum vitamin D detected in NMOSD patients were significantly lower than those in healthy controls (SMD=-1.57, 95% CI=-2.27 ∼ -0.87, P<0.001, I2 = 94.6%). The results of the different sensitivity analysis remained statistically significant, which demonstrated the robustness of the meta-analysis. There was no significant publication bias in our meta-analysis (P>0.05). CONCLUSION: Patients with NMOSD showed significantly reduced vitamin D levels compared with healthy controls. Our findings highlighted the importance of measuring vitamin D levels in patients with NMOSD. Multi-center randomized controlled trials with large samples will further confirm whether the association is casual and modifiable.

Asymptomatic spinal lesions in patients with AQP4-IgG-positive NMOSD: A real-world cohort study.

OBJECTIVE: This study aims to explore the frequency and influencing factors of asymptomatic spinal lesions (ASLs) and their impact on subsequent relapses in patients with AQP4-IgG-positive NMOSD (AQP4-NMOSD) in a real-world setting. METHODS: We retrospectively reviewed clinical information and spinal MRI data from AQP4-NMOSD patients who had at least one spinal cord MRI during their follow-ups. Kaplan-Meier curves and Cox proportional hazards models were employed to ascertain potential predictors of remission ASLs and to investigate factors associated with subsequent relapses. RESULTS: In this study, we included 129 patients with AQP4-NMOSD and reviewed 173 spinal MRIs during attacks and 89 spinal MRIs during remission. Among these, 6 ASLs (3.5%) were identified during acute attacks, while 8 ASLs (9%) were found during remission. Remission ASLs were linked to the use of immunosuppressive agents, particularly conventional ones, whereas no patients using rituximab developed ASLs (p = 0.005). Kaplan-Meier curve analysis indicated that patients with ASLs had a significantly higher relapse risk (HR = 4.658, 95% CI: 1.519-14.285, p = 0.007) compared to those without. Additionally, the use of mycophenolate mofetil (HR = 0.027, 95% CI: 0.003-0.260, p = 0.002) and rituximab (HR = 0.035, 95% CI: 0.006-0.203, p < 0.001) significantly reduced the relapse risk. However, after accounting for other factors, the presence of ASLs did not exhibit a significant impact on subsequent relapses (HR = 2.297, 95% CI: 0.652-8.085, p = 0.195). INTERPRETATION: ASLs may be observed in patients with AQP4-NMOSD. The presence of ASLs may signify an underlying inflammatory activity due to insufficient immunotherapy. The administration of immunosuppressive agents plays a key role in the presence of remission ASLs and the likelihood of subsequent relapses.

Correlation of GABA+ levels in the medial prefrontal cortex and circulating follicular helper T cells in neuromyelitis optica spectrum disorder patients with cognitive impairment.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) associated with cognitive impairment (CI) is acknowledged. However, the underlying pathogenesis and involvement of the immune system remain unclear. OBJECTIVES: This study aimed to investigate the alterations in immune cells, cytokines, and GABA+ levels in NMOSD patients with cognitive deficits. METHODS: Thirty-eight NMOSD patients and 38 healthy controls (HCs) were included. NMOSD patients were stratified as NMOSD-CI and NMOSD-CP groups. The difference in cognitive functions, Tfh and cytokines, and GABA+ levels were assessed, and their correlations were calculated. RESULTS: NMOSD-CI patients showed worse performance on all cognitive tests, and the percentage of circulating follicular helper T cells (cTfh) was significantly elevated. The frequency of cTfh was positively and negatively correlated with Stroop-A and AVLT long-delayed scores, respectively. IL-21 was remarkably higher in NMOSD-CI and NMOSD-CP. The level of GABA+ in medial prefrontal cortex (mPFC) was significantly decreased in NMOSD-CI and was proved positively and negatively correlated with Symbol Digit Modalities Test and the frequency of circulating Tfh cells, respectively. CONCLUSION: In NMOSD-CI patients, all cognitive domains were impacted, , while GABA+ levels in mPFC were decreased. GABA+ levels in NMOSD-CI were negatively correlated with the frequency of cTfh, suggesting the underlying coupling mechanism between immune responses and neurotransmitter metabolism in CI in NMOSD patients.

Corrigendum: Plasma exchange for two patients with autoimmune GFAP astrocytopathy with rapid progression to respiratory failure: a case report.

[This corrects the article DOI: 10.3389/fimmu.2023.1265609.].

Plasma exchange for two patients with autoimmune GFAP astrocytopathy with rapid progression to respiratory failure: a case report.

Background: Patients with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy can present with early neurological deterioration, but rapidly progressive respiratory failure is rarely reported. We present the cases of two patients with autoimmune GFAP astrocytopathy who experienced rapid progression to respiratory failure and were effectively treated using plasma exchange therapy. Case report: Two patients were diagnosed with autoimmune GFAP astrocytopathy. Their initial symptoms were consistent with those of previously observed cases of autoimmune GFAP astrocytopathy. However, they experienced rapid progression to respiratory failure due to their lesion location. Specifically, case 1 had lesions in the medulla oblongata, and case 2 had lesions in the high cervical spinal cord, which are both common sites of lesions causing respiratory failure. The patients did not respond well to intravenous methylprednisolone and intravenous immunoglobulin initially and could not be withdrawn from ventilator support. Fortunately, subsequent plasma exchange therapy led to significant clinical improvements and successful withdrawal from ventilator support. Discussion: Patients with autoimmune GFAP astrocytopathy can present with rapidly progressive respiratory failure. Early treatment with plasma exchange can be beneficial in withdrawing patients from ventilator support.

Effect of Intravenous Thrombolytic Dose of Alteplase on Long-Term Prognosis in Patients with Acute Ischemic Stroke.

INTRODUCTION: This study aimed to investigate the long-term prognostic effects of different alteplase doses on patients with acute ischemic stroke (AIS). METHODS: In this cohort study, we enrolled 501 patients with AIS treated with intravenous thrombolysis with alteplase, with the primary endpoint event of recurrence of ischemic stroke and the secondary endpoint event of death. The effects of different doses of alteplase on recurrence of ischemic stroke and death were analyzed using a Cox proportional risk model. RESULTS: Among 501 patients with AIS treated with thrombolysis, 295 patients (58.9%) and 206 patients (41.1%) were treated with low-dose and standard-dose alteplase, respectively. During the study period, 61 patients (12.2%) had a confirmed recurrence of ischemic stroke. Multivariate Cox proportional risk analysis showed that standard-dose alteplase thrombolysis (HR 0.511, 95% CI 0.288-0.905, P = 0.021) was significantly associated with a reduced risk of long-term recurrence of AIS, whereas atrial fibrillation was associated with an increased risk of long-term recurrence of AIS. Thirty-nine (7.8%) patients died during the study period. Multivariate Cox proportional risk analysis showed that age, baseline National Institutes of Health Stroke Scale (NIHSS) score, and symptomatic steno-occlusion were associated with an increased long-term risk of death from AIS. The alteplase dose was not associated with the risk of death from AIS. CONCLUSIONS: Standard-dose alteplase treatment reduced the risk of long-term recurrence of AIS after hospital discharge and the alteplase dose was not associated with the long-term risk of death from AIS.

Case Report: Ofatumumab treatment in a patient with rituximab-intolerant refractory autoimmune GFAP astrocytopathy.

Background: Ofatumumab, a fully humanized anti-CD20 monoclonal antibody, has shown promising efficacy in limited cases of neuromyelitis optica spectrum disorder, but there is a lack of studies on its use in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. We present a case of refractory GFAP astrocytopathy with poor response to conventional immunosuppressants and rituximab who responded well to subcutaneous ofatumumab. Case report: The patient is a 36-year-old woman with a diagnosis of GFAP astrocytopathy and high disease activity. She experienced five relapses over three years despite immunosuppressive treatment with oral prednisone, azathioprine, mycophenolate mofetil, and intravenous rituximab. Additionally, her circulating B cells were not completely depleted during the second administration of rituximab and an allergic reaction occurred. Based on insufficient B cell depletion and allergic reaction to rituximab, subcutaneous ofatumumab was introduced. After twelve injections of ofatumumab without injection-related reactions, she had no further relapses and was sufficiently depleted of the circulating B cells. Discussion: This case illustrates the effective use and good tolerance of ofatumumab in GFAP astrocytopathy. Further studies are needed to investigate the efficacy and safety of ofatumumab in refractory GFAP astrocytopathy or those intolerant to rituximab.

Reflections from a NMOSD case with serum AQP4-Ab negativity but CSF positivity: narrative review of how to interpret AQP4-Ab test results.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system. The differential diagnosis of NMOSD in clinical practice is often challenging despite the phenotypical and serological characteristics of the disease. The discovery of anti-aquaporin-4 antibody (AQP4-Ab) enabled clinicians to diagnose NMOSD relatively earlier and more easily, as the AQP4-Ab can mediate the pathogenesis of NMOSD. Testing for AQP4-Ab in the serum of patients can play a crucial role in the diagnosis of NMOSD. Three-quarters of patients with NMOSD have serum immunoglobulin-G (IgG) autoantibodies to the AQP4 channel. Nevertheless, the test results for AQP4-Ab can be affected by several factors, such as assay methods, clinical stages, the types of treatment, sample status, and pre-test error, among others. In patients with seronegative NMOSD, it would be better to test serum and CSF AQP4-Ab together to improve the positive rate, especially when NMOSD is highly suspected. This article aims to update readers on the recent developments in AQP4-Ab testing and how to interpret the results of the AQP4-Ab test.

Prevalence and associated factors of basilar artery dolichosis in patients with acute cerebral infarction.

Introduction: Little attention has been given to the factors associated with basilar artery (BA) dolichosis. This study aims to elucidate the prevalence and associated factors of BA dolichosis in patients with acute cerebral infarction (ACI). Methods: We collected the clinical and laboratory data of 719 patients with ACI admitted to our department. Magnetic resonance angiography was used to evaluate the geometric parameters of the BA and intracranial vertebral arteries (VAs). A BA curve length > 29.5 mm or bending length (BL) > 10 mm was identified as BA dolichosis. Univariate and multivariate logistic regression were performed to determine the factors associated with BA dolichosis. Results: Among 719 patients with ACI, 238 (33.1%) demonstrated BA dolichosis, including 226 (31.4%) with simple BA dolichosis and 12 (1.7%) with basilar artery dolichoectasia (BADE). Pearson correlation analyses showed that BA curve length was positively correlated with BL (r = 0.605). Multivariate logistic regression analysis demonstrated that current smoking (OR = 1.50, 95% CI: 1.02-2.21, p = 0.039), diabetes mellitus (OR = 1.66, 95% CI: 1.14-2.41, p = 0.008), BA diameter (OR = 3.04, 95% CI: 2.23-4.13, p < 0.001), BA bending (OR = 4.24, 95% CI: 2.91-6.17, p < 0.001) and BL (OR = 1.45, 95% CI: 1.36-1.55, p < 0.001) were significantly associated with BA dolichosis. Conclusion: This study suggests that BA dolichosis was common in patients with ACI, and the morphological parameters of the vertebrobasilar artery and acquired risk factors (including smoking and diabetes) were risk factors for BA dolichosis.

B-cell proliferation characteristics and monitoring significance under the modified reduced-dose rituximab regimen for NMOSD: A real-world case series study.

OBJECTIVE: To explore the B-cell proliferation characteristics and monitoring significance under the modified reduced-dose rituximab (mRTX) regimen for neuromyelitis optica spectrum disorder (NMOSD). METHODS: NMOSD patients treated with mRTX were recruited, and the percentages of total CD19+ B cells and CD27+ memory B cells were dynamically detected by flow cytometry. The annualized relapse rate (ARR) and expanded disability status scale (EDSS) scores were compared before and after mRTX treatment, and the differences in B-cell values were compared between groups. RESULTS: A total of 34 patients with NMOSD were ultimately enrolled. The EDSS score decreased from 2.5 (1.5, 3.0) to 1.3 (1.0, 2.0), and the ARR decreased from 1.0 (0, 2.0) to 0 (0, 0) (p < 0.001). Relapses occurred in 6 patients, with total CD19+ B-cell percentages of 3.25% (2.7%, 3.7%) and CD27+ memory B-cell percentages of 0.3% (0.2%, 0.3%) at initial relapse. Twenty-eight patients (82.4%) remained relapse-free with 84 doses of mRTX. Before 56 repeated doses, the total CD19+ B cells and CD27+ memory B cells were 4.00% (3.14%, 5.32%) and 0.26% (0.17%, 0.40%), respectively. The mean dosing interval was 9.2 months. Both total CD19+ B cells and CD27+ memory B cells proliferated over time after mRTX use, with significantly faster proliferation rates in the later stages. In 28 relapse-free patients, the mean time to reach 1% for total CD19+ B cells was 210 days, and the mean time to reach 3% was 240 days, with the mean interval from 1% to 3% of 65 days. Twenty-five relapse-free patients had no significant differences in maximum, minimum, and mean B-cell values compared to those of 6 patients with relapse. CONCLUSION: The high rate of B-cell proliferation under the mRTX regimen indicates that closer dynamic B-cell monitoring is required to guide repeated mRTX dosing. Sustained depletion of total CD19+ B cells targeting < 3% of lymphocytes may be feasible, enabling extended dosing intervals.

Basilar artery curvature increases the risk of posterior circulation infarction occurrence in patients without vertebrobasilar stenosis.

INTRODUCTION: Limited cross-sectional or case-control studies have identified the relationship between basilar artery (BA) curvature and posterior circulation infarction (PCI). This study aimed to identify the influence of BA curvature severity on the risk of PCI occurrence in patients without vertebrobasilar stenosis through a prospective cohort study. METHODS: In this study, we enrolled 171 patients with BA dolichosis but without vertebrobasilar stenosis. The BA geometric parameters were evaluated on MRA. The primary outcome was the occurrence of PCI, mainly referring to cerebellar and/or brainstem infarction. Cox proportional hazard models were used to detect possible predictors of PCI. RESULTS: Among them, 134 (78.4%) patients were diagnosed with BA curvature, including 124 with moderate curvature and 10 with prominent curvature. The defined PCI occurrence was observed in 32 (18.7%) patients with a median follow-up time of 45.6 months. Cox proportional hazard analysis showed that BA prominent curvature (HR = 6.09; 95% CI: 1.36-27.28; P = 0.018) significantly increased the risk of PCI occurrence, and bending length (BL) was also significantly associated with PCI occurrence, with the adjusted HR per 1-mm increase of BL of 1.09 (95% CI: 1.01-1.18; P = 0.040). In the subgroup analysis stratified by age, BA prominent curvature was highly associated with PCI occurrence in patients aged > 61 years (HR = 11.76; 95% CI: 1.21-113.90; P = 0.033). Additionally, good antiplatelet therapy adherence could significantly reduce the risk of PCI occurrence. CONCLUSION: BA curvature may increase the risk of PCI occurrence, especially in elderly patients with prominent curvature. Improving adherence to antiplatelet therapy can help reduce the risk of PCI occurrence.

Association between myasthenia gravis and cognitive disorders: a PRISMA-compliant meta-analysis.

OBJECTIVE: This meta-analysis assessed the association between myasthenia gravis (MG) and cognitive disorders. METHODS: The PubMed, Web of Science, OVID, EMBASE, CNKI and Wanfang electronic databases were comprehensively searched from inception to October 2020 for relevant studies. The primary outcomes were scores of the cognitive function battery. A random effects model was used to evaluate the cognitive function of patients with MG. RESULTS: Eight cross-sectional studies containing 381 patients and 220 healthy controls were included in this meta-analysis. In relation to global cognitive function, patients with MG performed significantly worse than healthy individuals (SMD = -0.4, 95% CI = -0.63 to -0.16, p < 0.001, I2 = 10%). Specifically, the impaired cognitive domains included language, visuospatial function, information processing, verbal immediate and delayed recall memory, visual immediate recall memory, and response fluency, while attention, executive function, and visual delayed recall memory were unimpaired. The patients with early-onset (SMD= -0.527, 95% CI = -0.855 to -0.199, p = 0.002) and generalized MG (SMD= -0.577, 95% CI = -1.047 to -0.107, p = 0.016) had poorer global cognitive performance than the healthy population. CONCLUSIONS: Patients with MG may have cognitive disorders, including those associated with the domains of language, visuospatial function, information processing, verbal immediate and delayed recall memory, visual immediate recall memory and response fluency. Furthermore, the age of onset and disease severity may be associated with cognitive disorders in patients with MG.

Increased neutrophil-to-lymphocyte ratio is associated with unfavorable functional outcomes in acute pontine infarction.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is positively associated with unfavorable outcomes in patients with cerebral infarction. This study aimed to investigate the relationship between the NLR and the short-term clinical outcome of acute pontine infarction. METHODS: Patients with acute pontine infarction were consecutively included. Clinical and laboratory data were collected. All patients were followed up at 3 months using modified Rankin Scale (mRS) scores. An unfavorable outcome was defined as an mRS score ≥ 3. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cutoff values for patients with acute pontine infarction. risk factors can be predictive factors for an unfavorable outcome after acute pontine infarction. RESULTS: Two hundred fifty-six patients with acute pontine infarction were included in this study. The NLR was significantly higher in the unfavorable outcome group than in the favorable outcome group (P < 0.05). Additionally, the infarct size was significantly higher in the high NLR tertile group than in the low NLR tertile group (P < 0.05). Multivariate logistic regression analysis revealed that the baseline National Institutes of Health Stroke Scale (NIHSS) score, NLR, platelet count, and fasting blood glucose (FBG) level were significantly associated with unfavorable outcomes 3 months after acute pontine infarction. The optimal cutoff value of the NLR for predicting the 3-month outcome of acute pontine infarction was 3.055. The negative and positive predictive values of NLR were 85.7% and 61.3%, respectively, and the sensitivity and specificity of NLR were 69.2% and 80.9%. CONCLUSIONS: We found that the NLR may be an independent predictive factor for the outcome of acute pontine infarction.

The Relationship Between the Fibrinogen to Albumin Ratio and Early Outcomes in Patients with Acute Pontine Infarction.

BACKGROUND AND PURPOSE: Previous studies have indicated that fibrinogen and low serum albumin levels are associated with poor outcomes of acute ischemic stroke. The role of the fibrinogen-to-albumin ratio (FAR) as a novel inflammatory and thrombotic biomarker in acute ischemic stroke is unclear. This study aims to investigate the relationship between the FAR and 3-month outcomes of acute pontine infarction. Methods: Patients with acute pontine infarction were consecutively included. All patients were followed up at 3 months after onset, and the 3-month outcome was evaluated using modified Rankin Scale (mRS) scores. A score of 0 to 2 was defined as a good outcome, and a score ≥ 3 was defined as a poor outcome. Receiver operating curve (ROC) analysis was used to calculate the optimal cutoff values for patients with acute pontine infarction. Then, a binary logistic regression model was used to evaluate the risk factors for a poor outcome after acute pontine infarction. Results: A total of 264 patients with acute pontine infarction were included. Eighty (30.3%) patients were included in the poor outcome group. The optimal cutoff value of the FAR for predicting the 3-month outcome of acute pontine infarction was 8.199. The FAR was independently associated with a poor outcome at 3 months in patients with acute pontine infarction (odds ratio [OR] = 1.293, 95% confidence interval [CI]: 1.150-1.453). Conclusions: We found that a high FAR predicted poor 3-month outcomes in patients with acute pontine infarction.