Neutrophil to lymphocyte ratio may be a useful marker in distinguishing MOGAD and MS and platelet to lymphocyte ratio associated with MOGAD activity.

BACKGROUND AND OBJECTIVE: Clinical overlap is observed between multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein immunoglobulin-G (MOG-IgG) associated disease (MOGAD) and the difficulty in distinguishing between the two diseases. Here, we measured and compared the readily available neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) to determine whether these three biomarkers can help to distinguish MOGAD and MS at disease onset. The impact of these three biomarkers on MOGAD and MS relapse also needs to be explored. METHODS: In this retrospective analysis, we obtained clinical and paraclinical data from the first attacks of MOGAD (N = 31) and MS (N = 50). Electronic medical records were used to collect demographic data (gender, age at onset), clinical symptoms, EDSS at onset, and medical treatments. The primary outcome was relapse within one year of onset. Four hematological parameters were recorded, including neutrophil count, platelet count, lymphocyte count, and monocyte count. NLR, PLR, and MLR were calculated and compared between MOGAD, MS, and HC. Receiver operator curve (ROC) analysis was performed to assess the ability of NLR, PLR, and MLR to distinguish between MOGAD and MS, MOGAD and HC, respectively. A logistic regression analysis was performed to determine the impact of NLR/PLR/MLR on MOGAD/MS relapse within one year of onset. RESULTS: Compared to HC, NLR is significantly higher in MOGAD and MS (p<0.001, p = 0.04, respectively). The PLR and MLR are elevated in MOGAD compared to HC (p<0.001, p<0.001, respectively), and MLR in MS are also statistically higher than in HC (p = 0.023). It is worth noting that NLR and PLR were much higher in MOGAD compared to MS (p<0.001, p = 0.001, respectively), but a significant difference regarding MLR has not been found between MOGAD and MS. Based on ROC curve analyses, we found that using NLR, PLR, and MLR to discriminate between MOGAD and MS yielded a ROC-plot area under the curve (AUC) value of 0.794, 0.727, and 0.681, respectively. Meanwhile, the AUC of NLR, PLR, and MLR to discriminate between MOGAD and HC were 0.926, 0.772, and 0.786. Furthermore, the logistics analysis revealed a significant positive association between PLR and MOGAD relapse. CONCLUSION: NLR helps differentiate MOGAD and MS in disease onset, and higher PLR was related to MOGAD relapse.

Plasma Complement 3 and Complement 4 Are Promising Biomarkers for Distinguishing NMOSD From MOGAD and Are Associated With the Blood-Brain-Barrier Disruption in NMOSD.

Background and Objective: Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) are autoimmune inflammatory demyelinating diseases of the central nervous system (CNS). As the clinical features of NMOSD are similar to MOGAD, diagnostic confusion exists between the two diseases. To better discriminate NMOSD from MOGAD, we investigated whether the plasma levels of complement 3 (C3) and complement 4 (C4) are different in NMOSD and MOGAD during the acute attacks of the diseases. We sought to determine whether C3 or C4 has an influence on the features of NMOSD. Methods: In this observational study, data from 73 aquaporin-4 antibodies (AQP4-IgG) positive NMOSD patients and 22 MOG-IgG positive MOGAD patients were collected retrospectively. Demographics, clinical characteristics, plasma parameters, and cerebrospinal fluid (CSF) findings will be analyzed for comparability between the two groups. Immunoglobulin-G (IgG) and albumin were measured in both plasma and CSF. Plasma levels of C3 and C4 were measured and compared between the NMOSD, MOGAD, and 42 healthy controls (HC). The correlations between plasma C3, C4, and NMOSD clinical parameters were analyzed. Results: The ages of onset were later in the AQP4-IgG positive NMOSD group and females predominated, which differed from the MOGAD group, whose ages were younger and with a slight male preponderance. The AQP4-IgG positive NMOSD patients presented with the clinical symptoms of optic neuritis (ON) and transverse myelitis (TM), whereas encephalitis symptoms were more prevalent in MOGAD patients. CSF analysis shows that slight but not significantly higher white cell count (WCC) and protein were observed in the MOGAD group than in the AQP4-IgG positive NMOSD group. The plasma levels of IgG in MOGAD patients are significantly lower (p = 0.027) than in NMOSD patients. On the contrary, the plasma levels of albumin in MOGAD were higher than in NMOSD, which reached statistical significance (p = 0.039). Both the plasma C3 and C4 levels in the NMOSD group were significantly lower than in MOGAD and HC. The receiver operating characteristic (ROC) curve of the prediction model comprises C3 and C4 to distinguish NMOSD from MOGAD [area under the curve (AUC): 0.731, 0.645], which are considered to have discriminatory values. The results of Spearman's analysis revealed that there was a significant positive correlation between the plasma C3 and the CSF WCC (r = 0.383, p = 0.040). There was an inverse correlation between plasma C4 and plasma IgG (r = -0.244, p = 0.038). Plasma C3 or C4 was significantly positively correlated with CSF albumin and Q-Alb, which is considered a measure of blood-brain barrier (BBB) disruption. Conclusion: During the acute phase of NMOSD and MOGAD, plasma C3 and C4 may become potential biomarkers for distinguishing the two diseases and reflecting the NMOSD BBB damage.

Association between clinical factors and orofacial dyskinesias in anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND AND PURPOSE: We aimed to determine whether demographic information, clinical characteristics, laboratory tests, and imaging features are associated with orofacial dyskinesias (OFLD) in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: In this retrospective study, patients who were diagnosed with anti-NMDAR encephalitis were enrolled. All patients' factors, including demographic information, clinical characteristics, laboratory tests, and imaging features, were obtained at the time of hospitalization. The neurological function was assessed using the modified Rankin scale (mRS). Univariate and multivariate logistic regressions were used to examine the associations between clinical factors and OFLD. RESULTS: In total, 119 patients (median age: 28.0 [19.0-41.0] years; 67 females) were recruited. Of 119 patients, 44 (37.0%) had OFLD. OFLD was associated with increased mRS at admission, serum sodium, lumbar puncture pressure, female biologic sex, fever, psychiatric symptoms, seizures, impaired consciousness, autonomic dysfunction, and central hypoventilation in univariate logistic regression, respectively. Multivariate regression analysis revealed that female biologic sex (odds ratios [OR], 4.73; 95% confidence interval [CI], 1.27-17.64; p = .021), increased mRS at admission (OR, 2.09; 95% CI, 1.18-3.71; p = .011), psychiatric symptoms (OR, 7.27; 95% CI, 1.20-43.91; p = .031), and seizures (OR, 5.11; 95% CI, 1.22-21.43; p = .026) were associated with OFLD, after adjusting for confounding factors. CONCLUSIONS: Our analysis suggests that the following clinical factors are associated with OFLD: female biologic sex, increased mRS at admission, psychiatric symptoms, and seizures.

Carotid vulnerable plaque coexisting with cerebral small vessel disease and acute ischemic stroke: a Chinese Atherosclerosis Risk Evaluation study.

OBJECTIVES: We aimed to investigate the associations between carotid vulnerable plaque features coexisting with cerebral small vessel diseases (CSVDs) and acute ischemic stroke (AIS) and, furthermore, to determine whether coexisting diseases had a stronger association with AIS than a single disease. METHODS: Patients with cerebrovascular symptoms and carotid plaque were recruited from the cross-sectional, multicenter CARE-II study. The population was divided into two groups (AIS and transient ischemic stroke (TIA)). MRI features of carotid plaques (including luminal stenosis and plaque vulnerabilities) and CSVDs (such as white matter hyperintensities (WMHs) and lacunes) were evaluated. Coexisting diseases were defined as the presence of at least one carotid plaque features and one or more CSVDs feature. Multivariate logistic regression was performed to examine the associations between coexisting diseases and AIS. RESULTS: Of the recruited 634 patients (mean age: 59.1 ± 11.3 years; 429 males), 312 (49.2%) patients had AIS. These subjects had a higher prevalence of carotid vulnerable plaques, lacunes, and moderate-to-severe WMHs (a total Fazekas score of 3-6) than those with TIA (42.6% vs. 29.5%, 59.6% vs. 26.4%, 69.9% vs. 60.6%, respectively, all p < 0.05). Multivariate analysis revealed that carotid plaque features coexisting with lacunes or moderate-to-severe WMHs had a stronger association with AIS compared to carotid lesions alone (all p < 0.05) (i.e., vulnerable plaque coexisting with lacunes vs. vulnerable plaque alone, adjusted odds ratio: 3.67 vs. 1.62). CONCLUSIONS: Carotid vulnerable plaque features coexisting with CSVDs, particularly lacunes, had a stronger association with AIS compared to carotid lesions alone in a large, symptomatic, cohort. TRIAL REGISTRATION: Clinical trial registration URL: http://www. CLINICALTRIALS: gov , unique identifier: NCT02017756 KEY POINTS: • Carotid vulnerable plaque features coexisting with cerebral small vessel diseases, such as lacunes, had a stronger association with acute ischemic stroke compared to single diseases in symptomatic patients. • A comprehensive assessment of coexisting cerebrovascular diseases may help stratify the risk of acute ischemic stroke.

Clinical significance of anti-SSA/Ro antibody in Neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS), also described as CNS autoimmune astrocytopathy, due to the production of pathogenic antibodies against aquaporin-4 (AQP4) expressed on the foot of astrocytes. NMOSD coexists with autoimmune diseases and related autoantibodies [anti-Sjogren's syndrome A (anti-SSA)/Ro antibody, anti-Sjogren's syndrome B (anti-SSB)/La antibody, anti-nuclear (anti-ANA) antibodies, anti-double-stranded DNA (anti-dsDNA) antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody]. OBJECTIVES: No precise conclusion has been drawn on the role of the anti-SSA/Ro antibody in NMOSD. Therefore, the aim of this work was to evaluate whether the anti-SSA/Ro antibody has an impact on the clinical manifestation or prognosis of NMOSD. METHODS: Data were retrospectively collected from 102 patients with NMOSD diagnosed by experienced neurologists. The study population was divided into two groups based on the serum anti-SSA/Ro antibody status: NMOSD with or without anti-SSA/Ro antibody. The clinical, neuroimaging and laboratory parameters were compared between the two groups, including the neurological symptoms, MRI results, frequency of systemic autoantibodies, Expanded Disability Status Scale (EDSS), and NMOSD relapse rate. The EDSS and relapse were applied as measures of the NMOSD patient prognostic value. Cox regression analysis was used to evaluate the prognostic impact of anti-SSA/Ro antibody on NMOSD. RESULTS: Among the 102 NMOSD patients, striking differences were observed in the positive rate of AQP4-IgG (89.2% vs. 72.3%, p = 0.046) between those patients with and without the anti-SSA/Ro antibody. In addition, NMOSD patients with anti-SSA/Ro antibody showed the presence of more frequent anti-ANA antibodies (p = 0.002), anti-SSB/La antibody (p < 0.001), anti-dsDNA antibody (p < 0.002), Sjogren's syndrome (SS, p < 0.001) and systemic lupus erythematosus (SLE, p = 0.045). Univariate and multivariate Cox regression analysis were performed to confirm that the anti-SSA/Ro antibody affected the EDSS score and the relapse of NMOSD patients. The analysis of the survival curve revealed that the EDSS score in the NMOSD patients positive for the anti-SSA/Ro antibody reached 4.0 (p = 0.035) and relapsed (p = 0.039) earlier than in the negative group. CONCLUSION: The anti-SSA/Ro antibody could be associated with disease activity and severe disability in NMOSD.

Clinical Characteristics of Cognitive Impairment and 1-Year Outcome in Patients With Anti-LGI1 Antibody Encephalitis.

Introduction: Anti-leucine-rich glioma-inactivated 1 antibody (anti-LGI1) encephalitis is one of the most common autoimmune encephalitis. Anti-LGI1 encephalitis presented with subacute or acute onset of cognitive impairment, psychiatric disturbances, faciobrachial dystonic seizures (FBDSs), convulsions, and hyponatremia. The common sequela of anti-LGI1 encephalitis is cognitive disorder, but there are few studies on the recovery of cognitive function after immunotherapy. This study aimed to explore clinical characteristics of cognitive impairment and 1-year outcome in patients with anti-LGI1 encephalitis. Methods: The clinical data and characteristics of cognitive impairment of 21 patients with anti-LGI1 encephalitis from 2016 to 2019 in Nanjing Brain Hospital were analyzed retrospectively. At the time of onset of hospitalization and 1 year after discharge, the cognitive functions in these patients were assessed using two cognitive screening scales-Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MoCA-B). Results: Among the 21 patients, 13 were male and 8 were female, aged 51.10 ± 14.69 (age range 20-72) years. Nineteen patients, comprising 90.48%, had recent memory deterioration. Routine electroencephalography (EEG) results of 13 cases were abnormal. EEG results were epileptic or slow-wave activity involving the temporal lobes. Eleven cases of brain MRI were abnormal, and the focus involved the hippocampus and mediotemporal lobe. The decrease of short-term memory [recall scores: 0.57 ± 0.81 (MMSE), 0.76 ± 1.34 (MoCA-B)] is the most obvious at the time of admission. After intravenous (IV) injection of methylprednisolone and/or immunoglobulin, the clinical symptoms of the patients improved obviously. Total MMSE and MoCA-B scores of patients were significant increased after 1 year (21.19 ± 3.54 vs. 26.10 ± 3.02, P < 0.001; and 19.00 ± 4.38 vs. 25.19 ± 4.25, P < 0.001, respectively). Recall scores and orientation scores of MoCA-B were significantly improved after 1 year (0.76 ± 1.34 vs. 3.24 ± 1.48, P < 0.001; and 3.10 ± 1.26 vs. 5.00 ± 1.22, P < 0.001, respectively). However, 3/21 (14.29%) patients still have obvious short-term memory impairment (recall scores ≤ 1). Conclusion: Cognitive impairment is one of the most common manifestations of anti-LGI1 encephalitis, with the main prominent being acute or subacute short-term memory loss. Although most patients with anti-LGI1 encephalitis respond well to immunotherapy, a small number of patients still have cognitive disorders, mainly recent memory impairment, after 1 year.

Irregularity of Carotid Plaque Surface Predicts Subsequent Vascular Event: A MRI Study.

BACKGROUND: The relationship between plaque compositions and irregular plaque surface and its predictive value for vascular events (VEs) are unknown. PURPOSE: To investigate the relationship between irregular carotid plaque surface and plaque compositional features and its predictive values for future VEs utilizing magnetic resonance (MR) vessel wall imaging. STUDY TYPE: Prospective study. POPULATION: In total, 140 patients with cerebrovascular symptoms were recruited. FIELD STRENGTH/SEQUENCE: 3T, black blood T1 -weighted, black blood T2 -weighted, 3D time-of-flight, magnetization-prepared rapid acquisition gradient echo (MP-RAGE), and 3D motion sensitized driven equilibrium rapid gradient echo (MERGE). ASSESSMENT: The carotid artery stenosis and maximum wall thickness (Max WT) were measured. The presence/absence of irregular carotid plaque surface, calcification, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrous cap rupture was determined. After baseline examination, all patients were followed-up for at least 1 year to record the VEs. STATISTICAL TESTS: Independent t-test, Mann-Whitney U-test, Chi-square, logistic regression, and Cox regression were used. RESULTS: In total, 82 (58.6%) had irregular plaque surfaces. The carotid Max WT, stenosis, and the presence of surface calcification, LRNC and IPH were significantly associated with irregular plaque surface (all P < 0.05). After adjusted for baseline confounding factors, these associations remained statistically significant (all P < 0.05). During the median follow-up time of 12.1 months, 37 (26.4%) patients had VEs. Univariable Cox regression analysis showed that the irregular carotid plaque surface was significantly associated with subsequent VEs (hazard ratio [HR], 11.02; 95% confidence interval [CI], 2.65-45.85; P = 0.001). After adjusted for baseline and follow-up confounding factors, this association remained statistically significant (HR, 13.03; 95% CI, 1.71-99.42, P = 0.013). After further adjusted for intracranial stenosis, this association also remained statistically significant (HR, 12.57; 95% CI, 1.63-96.83, P = 0.015). DATA CONCLUSION: The morphology of carotid atherosclerotic plaque surface determined by MR vessel wall imaging, particularly irregular plaque surface, is an independent predictor for subsequent vascular events. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;52:185-194.