Role of serum complement C3 in blood–brain barrier injury and prognosis of anti-NMDAR encephalitis

Role of serum complement C3 in blood–brain barrier injury and prognosis of anti-NMDAR encephalitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Role of serum complement C3 in blood–brain barrier injury and prognosis of anti-NMDAR encephalitis Jinwei Zhang, Ling Ling, Lei Xiang, Wenxia Li, Liqin Yang, Zhiying Wang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7220180/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Feb, 2026 Read the published version in BMC Neurology → Version 1 posted 11 You are reading this latest preprint version Abstract Background Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune disease, with some patients experiencing poor clinical outcomes. Complement activation may contribute to disease progression, but its clinical significance remains unclear. This study investigated the correlation between serum complement C3 with blood–brain barrier (BBB) injury and prognosis in anti-NMDAR encephalitis. Methods This retrospective study enrolled 82 patients diagnosed with anti-NMDAR encephalitis at the Tianjin Huanhu Hospital. Spearman correlation analysis was used to assess the relationship between serum C3 level, disease severity, and BBB injury marker albumin quotient (Q-Alb). Binary logistic regression analysis and Cox proportional hazards models were used to investigate independent impact of serum C3 on disease prognosis and relapse. Sensitivity, interaction, and stratification analyses were performed to further verify the reliability of the results. Receiver operating characteristic curves were used to assess diagnostic value of serum C3 level for disease prognosis and relapse. Results The median follow-up time of this study was 37.70 (24.23–55.72) months. Serum C3 level significantly positively correlated with the initial modified Rankin scale (mRS) scores (r = 0.327, P = 0.003) and Q-Alb (r = 0.307, P = 0.005). Mediation analysis showed that BBB injury mediated the effect of serum C3 on disease severity ( P < 0.05). Multivariate logistic regression analysis showed that serum C3 was an independent risk factor for poor prognosis (odds ratio = 1.60, 95% confidence interval [CI] = 1.08–2.39, P = 0.020). Multivariate Cox analysis showed that serum C3 (hazard ratio [HR] = 1.32, 95% CI = 1.04–1.66, P = 0.023) and Q-Alb (HR = 1.14, 95% CI = 1.03–1.26, P = 0.009) were significant predictors of relapse. Conclusion BBB injury mediated the effect of serum C3 on disease severity in patients with anti-NMDAR encephalitis. Serum C3 was an independent risk factor for poor prognosis and disease relapse. anti-N-methyl-d-aspartate receptor encephalitis complement blood–brain barrier C3 prognosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Autoimmune encephalitis (AE) is a neuroinflammatory disorder mediated by antibodies targeting neuronal antigens [ 1 ]. Among its subtypes, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent, with an annual incidence of 5–10 cases per 100,000 individuals [ 2 , 3 ]. Clinical manifestations of anti-NMDAR encephalitis include psychiatric and neurological symptoms, such as abnormal mental behavior, cognitive dysfunction, speech disorders, memory loss, seizures, movement disorders, autonomic dysfunction, and decreased levels of consciousness [ 4 ]. However, the exact pathophysiological mechanisms underlying anti-NMDAR encephalitis remain unclear. Viruses and tumors that disrupt the blood–brain barrier (BBB) through immune and inflammatory responses are thought to be plausible triggers of anti-NMDAR encephalitis [ 5 ]. Anti-NMDAR antibodies in serum enter the CNS through the disrupted BBB and react with NMDARs, inducing their internalization and degradation, especially in hippocampal neurons. The resulting decrease the density of cell-surface and synaptic NMDARs leads to impaired neuronal function [ 6 ]. First-line treatment of anti-NMDAR encephalitis is usually immunotherapy, including intravenous immunoglobulin, steroids, or plasma exchange to remove autoantibodies that cause the disease, whereas the second-line treatment is monoclonal antibody rituximab to non-selectively remove CD20 + B cells [ 7 ]. However, the drugs currently used to treat anti-NMDAR encephalitis are insufficient for complete recovery, and some patients experience severe mental or cognitive impairment, memory deficit, refractory epilepsy, relapse, and even death [ 8 , 9 ]. Therefore, identifying biomarkers to predict the relapse risk of anti-NMDAR encephalitis is important to influence disease progression and improve the prognosis of patients through early intervention. The complement system, an important component of the innate immune response, can be activated via the classical, alternative, and lectin pathways [ 10 ]. Complement activation and cascade reactions are involved in inflammatory processes within the CNS, and their hypo- or hyperactivation may lead to neuronal cell damage, BBB destruction, and brain dysfunction [ 11 ]. Activation of the complement system plays a vital role in various autoimmune neurological disorders, such as multiple sclerosis (MS) [ 12 ], myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) [ 13 ], neuromyelitis optica spectrum disorder (NMOSD) [ 14 , 15 ],Guillain–Barré syndrome (GBS) [ 16 ], and myasthenia gravis (MG) [ 17 , 18 ]. Recent studies have shown that serum C3 levels are elevated during the acute phase and correlate with disease severity [ 19 , 20 ]. Thus, an elevated serum C3 level may reflect a systemic inflammatory response in anti-NMDAR encephalitis. However, the relationship between serum complement levels and anti-NMDAR encephalitis prognosis remains to be determined. In this study, we investigated the correlation between serum complement C3 level with BBB injury and poor disease outcomes in anti-NMDAR encephalitis. Methods Study subjects We conducted a retrospective analysis of 232 patients diagnosed with AE at the Tianjin Huanhu Hospital between September 2016 and June 2023. The enrolled patients met the following inclusion criteria: 1) patients first diagnosed with anti-NMDAR encephalitis according to the Graus and Dalmau criteria [ 21 ]; 2) manifestation of at least one of the six major symptoms, namely a) mental and behavioral abnormalities or cognitive disorders; b) speech disorders; c) seizures; d) dyskinesia/involuntary movements; e) decreased level of consciousness; and f) autonomic dysfunction or central hypoventilation; 3) cerebrospinal fluid (CSF) positivity for anti-NMDAR antibodies; and 4) exclusion of other etiologies. Exclusion criteria included: 1) immunotherapy, such as hormones, immunosuppressants, prophylaxis, and plasma exchange, prior to admission; 2) incomplete clinical information or loss to follow-up. A total of 82 patients met the criteria and were included in this study. The screening process is illustrated in Fig. 1 . Data collection Basic information, clinical data, and laboratory test results of the patients were collected using an electronic medical record system. Basic information included age at onset, gender, medical history, and personal history. Clinical data included clinical manifestations and treatment plans. Laboratory test results included serum anti-NMDAR antibody status, white cell count (WCC), monocytes, lymphocytes, neutrophils, C3, C4, serum immunoglobulin G (IgG), serum albumin, CSF pressure, CSF WCC, glucose, chloride, protein, CSF IgG, CSF albumin, Q-IgG, Q-Alb, and IgG indices. Q-IgG is the ratio of CSF IgG to serum IgG, and Q-Alb is the ratio of CSF albumin to serum albumin, which were used to assess BBB integrity. The ratio of Q-IgG to Q-Alb was calculated as the IgG index, which represented intrathecal synthesis. Peripheral venous blood samples were collected between 6:00 a.m. and 7:00 a.m. the next day after admission. CSF samples were collected before immunotherapy, and head magnetic resonance imaging (MRI) was performed. The detection data closest to admission were used. Baseline serum and CSF anti-NMDAR antibody levels were measured via the cell-based assay (CBA), following the manufacturer’s protocol. Head MRI was performed at the Magnetic Resonance Unit of the Tianjin Huanhu Hospital using a 3T MAGNETOM Skyra scanner (Siemens Healthcare, Erlangen, Germany). Lesion locations were recorded as lobes and sulci, deep cerebral white matter, paraventricular white matter, thalamus, basal ganglia region, hippocampus, insula, pituitary gland, brainstem, and cerebellum. Disease severity was evaluated on admission by at least two qualified neurologists using the modified Rankin Scale (mRS) as the primary metric [ 22 , 23 ]. The cohort was categorized into two groups, mRS < 4 and mRS ≥ 4, according to the severity of the clinical presentation. Follow‑up data The primary outcome was disease prognosis, defined as the mRS score at 12 months after onset. The final mRS score ≤ 2 was considered a good prognosis, and the final mRS score > 2 was considered a poor prognosis [ 24 ]. The secondary outcome was disease relapse, defined as worsening of previous symptoms or appearance of new symptoms after at least 2 months of improvement or stabilization [ 21 , 25 ]. Follow-up results were obtained through annual outpatient or telephone visits; the last follow-up was conducted on June 1st, 2025. Statistical analysis Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 8.0. Normality testing incorporated both calculating the Kolmogorov-Smirnov statistic and graphical methods (Q-Q plots and histograms). Normally distributed variables were expressed as the mean ± standard deviation. Comparisons between the two groups were made using the independent samples t-test. Variables that were not normally distributed are expressed as the median and interquartile range, and comparisons between two groups were done using the Mann–Whitney U test. Categorical information is expressed as percentage (%), and the two groups were compared using the chi-squared test or Fisher's exact test. Spearman correlation analysis was performed to assess the correlation between clinically relevant parameters and disease severity, as well as between serum complement levels and CSF relevant parameters. To investigate the mechanism of the effect of serum C3 on disease severity, Q-Alb was substituted into the structural equation model as the intermediary variable, and the process plug-in was used to test the mediation effect. The bootstrap method was used to verify the mediation effect of BBB injury between serum C3 and disease severity. Binary logistic regression model was used to assess the risk factors of poor prognosis. To eliminate the influence of confounding factors on the results, we screened variables with P < 0.05 in the univariate analysis as well as factors possibly associated with disease prognosis for inclusion in the multivariate models. Multivariate model I adjusted for age and gender, and model II adjusted for age, gender, C4, and Q-Alb. Cox analysis was performed to assess risk factors for disease relapse. Model I was adjusted for age and gender, whereas model II was adjusted for age, gender, C4, and initial mRS score. To verify the reliability of the results, we excluded patients with autoimmune diseases from the sensitivity analysis. Interaction and stratified analyses were used to examine the effect of different genders on the results. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of serum complement C3 for disease prognosis and relapse. Statistical significance threshold was set at P < 0.05. Results Demographic and clinical characteristics of patients with anti-NMDAR encephalitis Eighty-two patients with first-attack anti-NMDAR encephalitis were enrolled in this study. Their median age at onset was 33 (21–45) years, 39 patients were female (47.6%), and 67 patients were adults (81.7%). Thirteen patients had the final mRS score > 2 (15.9%) and 19 patients (23.2%) experienced relapse during follow-up, with a median follow-up time of 37.70 (24.23–55.72) months. The cohort was divided into two groups, mRS 0.05). Compared with characteristics of patients with mild severity at admission, patients with initial mRS scores > 4 had higher final mRS score ( P = 0.001) and a higher proportion of individuals with poor prognosis ( P = 0.008). Eight patients had previous hypertension (9.8%), three had diabetes (3.7%), and three had coronary artery disease (3.7%). Seven (8.5%) patients had autoimmune disorders, including nephritis and thyroid dysfunction. Five patients had comorbid neoplasms (6.1%), including teratomas (uterus, ovary, and anterior mediastinum), brain gliomas, and esophageal smooth muscle tumors. Some of the patients smoked (26.8%) or consumed alcohol (19.5%). No significant differences were found in the medical and personal histories between the two groups ( P > 0.05). A total of 33 patients presented with prodromal symptoms (40.2%), including fever, headache, and upper respiratory tract infection. Mental behavioral abnormalities (72.0%), speech disorders (52.4%), and cognitive dysfunction (51.2%) were the most common clinical manifestations. Depending on the clinical manifestations and economic conditions, patients received treatment regimens of hormones (89.0%), prophylaxis (65.9%), immunosuppressants (14.6%), rituximab (1.2%), and plasma exchange (17.1%). No significant differences ( P > 0.05) were found in the clinical presentation and treatment regimens between the two groups (Table 1 ). Table 1 Demographic and clinical characteristics categorized by initial mRS scores. Total (n = 82) mRS < 4 (n = 57) mRS ≥ 4 (n = 25) P Demographic characteristics Age at onset, years, median (IQR) 33 (21–45) 32 (18–47) 34 (27-43.5) 0.590 Adults, ≥ 18, n (%) 67 (81.7) 44 (77.2) 23 (92.0) 0.133 Gender, female, n (%) 39 (47.6) 30 (52.6) 9 (36.0) 0.165 Medical history , n (%) Hypertension 8 (9.8) 5 (8.8) 3 (12.0) 0.961 Diabetes 3 (3.7) 1 (1.8) 2 (8.0) 0.454 Autoimmune diseases 7 (8.5) 6 (10.5) 1 (4.0) 0.431 Cerebrovascular disease 3 (3.7) 2 (3.5) 1 (4.0) 1.000 Tumor 5 (6.1) 4 (7.0) 1 (4.0) 1.000 Personal history , n (%) Drinking 16 (19.5) 9 (15.8) 7 (28.0) 0.199 Smoking 22 (26.8) 15 (26.3) 7 (28.0) 0.874 Clinical manifestation , n (%) Prodrome 33 (40.2) 23 (40.4) 10 (40.0) 0.976 Consciousness disorders 30 (36.6) 19 (33.3) 11 (44.0) 0.356 Cognitive dysfunction 42 (51.2) 30 (52.6) 12 (48.0) 0.699 Mental and behavioral abnormalities 59 (72.0) 41 (71.9) 18 (72.0) 0.995 Seizures 30 (36.6) 20 (35.1) 10 (40.0) 0.671 Speech dysfunction 43 (52.4) 29 (50.9) 14 (56.0) 0.669 Movement disorders 12 (14.6) 10 (17.5) 2 (8.0) 0.328 Involuntary movements 18 (22.0) 11 (19.3) 7 (28.0) 0.381 Autonomic dysfunction 10 (12.2) 7 (12.3) 3 (12.0) 1.000 Sleep dysfunction 24 (29.3) 15 (26.3) 9 (36.0) 0.375 Therapy regimens, n (%) Corticosteroid 73 (89.0) 52 (91.2) 21 (84.0) 0.335 Immunosuppressant 12 (14.6) 11 (19.3) 1 (4.0) 0.094 Intravenous immunoglobulin 54 (65.9) 39 (68.4) 15 (60.0) 0.459 Rituximab 1 (1.2) 1 (1.8) 0 (0.0) 1.000 PE 14 (17.1) 7 (12.3) 7 (28.0) 0.082 Final mRS scores, median (IQR) 1 (1–2) 1 (0–2) 2 (1–3) 0.001* Poor prognosis, n (%) 13 (15.9) 5 (9.6) 8 (32.0) 0.008* Relapse, n (%) 19 (23.2) 13 (22.8) 6 (24.0) 0.906 Follow-up time, median (IQR) 37.70 (24.23–55.72) 37.77 (25.64–56.17) 35.63 (20.58–55.60) 0.650 Continuous variables were presented as mean ± SD or median (IQR = 25th − 75th percentile), and categorical variables were described as percentages (%) mRS, modified Rankin scale; PE,plasma exchange *Statistically significant difference Laboratory test and imaging results of patients with anti-NMDAR encephalitis All patients in this cohort tested positive for CSF anti-NMDAR antibodies, and 41 tested positive for serum antibodies (50.0%). Among the serum-related parameters, C3 ( P = 0.012) and C4 ( P = 0.032) levels were significantly higher in the mRS ≥ 4 group than in the mRS 0.05). Among the CSF parameters, CSF IgG ( P = 0.019), albumin ( P = 0.010), Q-IgG ( P = 0.027), and Q-Alb ( P = 0.020) levels were significantly higher in the mRS ≥ 4 group than in the mRS 0.05 for all parameters). Regarding the imaging presentations, 55 (67.1%) patients had abnormal head MRI findings. The lesions were most commonly located in the lobes and sulci (39/55, 70.9%), paraventricular white matter (18/55, 32.7%), and basal ganglia (12/55, 21.8%). In some patients, lesions were located in the thalamus (7/55, 12.7%), brainstem (6/55, 10.9%), cerebellum (5/55, 9.1%), hippocampus (4/55, 7.3%), insula (4/55, 7.3%), pituitary gland (2/55, 3.6%), and deep brain white matter (2/55, 3.6%). No significant difference ( P > 0.05) was observed in the location of the lesions on head MRI between the groups (Table 2 ). Table 2 Laboratory test and imaging results categorized by initial mRS scores. Total (n = 82) mRS < 4 (n = 57) mRS ≥ 4 (n = 25) P Laboratory test results Serum, median (IQR) WCC, *10 9 /L 8.59 (6.60-11.57) 8.48 (6.56–12.32) 8.90 (6.67–10.66) 0.825 Monocytes, ×10 9 /L 0.51 (0.37–0.71) 0.50 (0.34–0.68) 0.60 (0.46–0.75) 0.147 Lymphocytes, ×10 9 /L 1.54 (1.09–2.07) 1.51 (1.13–2.03) 1.56 (1.05–2.26) 0.751 Neutrophil, ×10 9 /L 5.93 (4.42–9.18) 5.94 (4.50-10.54) 5.89 (4.42–8.17) 0.513 C3, g/dL 10.85 (9.40–13.20) 10.10 (9.15–12.05) 12.30 (10.60-13.55) 0.012* C4, g/dL 2.43 (1.92–2.90) 2.40 (1.92–2.80) 2.90 (2.10–3.20) 0.032* IgG, mg/L 10.60 (8.72–13.53) 10.80 (8.92–13.93) 10.10 (8.31–13.27) 0.375 Albumin, g/L 40.83 (37.58–44.05) 40.75 (37.55–44.09) 41.20 (38.15–44.91) 0.650 Anti-NMDAR antibody (+) 41 (50.0) 32 (56.1) 9 (36.0) 0.093 CSF, median (IQR) Pressure, mmH 2 O 164.00 (133.75-228.75) 160.00 (137.50–230.00) 180.00 (130.00-235.00) 0.912 WCC, *10 6 /L 11.00 (4.00-56.50) 10.00 (4.00–38.00) 20.00 (4.00–84.00) 0.377 Protein, g/L 0.37 (0.26–0.56) 0.37 (0.26–0.57) 0.34 (0.28–0.57) 0.972 Glucose, mmol/L 3.43 (2.79–4.21) 3.42 (2.87–4.33) 3.49 (2.78–4.06) 0.429 Chloride, mmol/L 126.00 (124.00-128.03) 126.00 (123.50–128.00) 126.00 (124.65-128.55) 0.724 IgG, mg/L 41.65 (25.98–67.53) 38.00 (24.95–58.95) 64.70 (35.80-88.45) 0.019 * Albumin, g/L 194.30 (132.75–305.80) 161.70 (118.10-282.45) 271.00 (167.40-476.35) 0.010 * Q-IgG a 3.83 (2.09–6.79) 3.03 (1.90–5.05) 4.61 (2.93–8.85) 0.027 * Q-Alb b 4.69 (3.13–8.05) 4.26 (2.91–7.42) 6.16 (3.99–11.59) 0.020 * IgG index 0.72 (0.57–0.85) 0.73 (0.52–0.89) 0.70 (0.61–0.84) 0.813 Abnormal head-MRI, n (%) 55 (67.1) 37 (64.9) 18 (72.0) 0.530 Cerebral lobes and sulcus 39 (70.9) 25 (67.6) 14 (77.78) 0.536 Deep WM 2 (3.6) 2 (5.4) 0 (0.0) 1.000 Periventricular WM 18 (32.7) 14 (37.8) 4 (22.2) 0.361 Thalamus 7 (12.7) 4 (10.8) 3 (16.67) 0.671 Basal ganglia 12 (21.8) 8 (21.6) 4 (22.2) 1.000 Hippocampus 4 (7.3) 2 (5.4) 2 (11.1) 0.590 Insula 4 (7.3) 3 (8.1) 1 (5.5) 1.000 Pituitary 2 (3.6) 1 (2.7) 1 (5.5) 1.000 Cerebellum 5 (9.1) 4 (10.8) 1 (5.5) 1.000 Brainstem 6 (10.9) 5 (13.5) 1 (5.5) 0.651 Continuous variables were presented as mean ± SD or median (IQR = 25th − 75th percentile), and categorical variables were described as percentages (%) mRS, modified Rankin scale; WCC, white cell count; anti-NMDAR, anti-N-methyl-d-aspartate receptor; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; WM, white matter a Q-IgG is the ratio of CSF IgG to serum IgG; b Q-Alb is the ratio of CSF albumin to serum albumin *Statistically significant difference Correlation analysis of clinical parameters and disease severity Spearman analysis showed that serum C3 (r = 0.327, P = 0.003), CSF albumin (r = 0.378, P < 0.001), Q-IgG (r = 0.329, P = 0.003), and Q-Alb (r = 0.334, P = 0.002) significantly and positively correlated with mRS score at disease onset in patients with anti-NMDAR encephalitis. CSF IgG (r = 0.284, P = 0.010) and serum C4 (r = 0.276, P = 0.012) were significantly associated with disease severity; however, the correlation was weak. No correlation was found between serum IgG, serum albumin, CSF WCC, IgG index, and initial mRS scores ( P > 0.05) (Table 3 and Fig. 2 ). Table 3 Correlation analysis of clinical parameters and initial mRS scores. r P C3, g/L 0.327 0.003* C4, g/L 0.276 0.012* Serum IgG, mg/L −0.187 0.092 Serum albumin, g/L 0.092 0.412 CSF WCC, ×10 6 /L 0.117 0.297 CSF IgG, mg/L 0.284 0.010* CSF albumin, g/L 0.378 <0.001* Q-IgG a 0.329 0.003* Q-Alb b 0.334 0.002* IgG index 0.035 0.752 mRS, modified Rankin scale; WCC, white cell count; CSF, cerebrospinal fluid. a Q-IgG, ratio of CSF IgG to serum IgG b Q-Alb, ratio of CSF albumin to serum albumin *Statistically significant difference Correlation analysis of serum complement levels and CSF parameters Spearman analysis showed that serum C3 (r = 0.227, P = 0.041) significantly correlated with CSF IgG levels, but the correlation was weak. In addition, serum C3 significantly correlated with CSF albumin (r = 0.365, P = 0.001) and Q-Alb (r = 0.307, P = 0.005) but not with serum IgG, albumin, CSF WCC, or Q-IgG ( P > 0.05). Serum C4 (r = 0.218, P = 0.049) also positively but weakly correlated with CSF albumin (Table 4 and Fig. 3 ). Table 4 Correlation analysis of serum complement levels and CSF parameters. C3 C4 r P r P Serum IgG, mg/L -0.022 0.846 -0.045 0.689 Serum albumin, g/L 0.139 0.211 -0.012 0.852 CSF WCC, *10 6 /L 0.014 0.902 -0.077 0.492 CSF IgG, mg/L 0.227 0.041* 0.177 0.113 CSF albumin, g/L 0.365 0.001* 0.218 0.049* Q-IgG a 0.200 0.071 0.136 0.224 Q-Alb b 0.307 0.005* 0.188 0.091 IgG index -0.067 0.547 0.022 0.847 WCC, white cell count; CSF, cerebrospinal fluid a Q-IgG is the ratio of CSF IgG to serum IgG; b Q-Alb is the ratio of CSF albumin to serum albumin *Statistically significant difference Mediating role of BBB injury between serum C3 and disease severity in anti-NMDAR encephalitis The results of mediation analysis are shown in Fig. 4 and Table 5 . Serum C3 had a significant effect on Q-Alb (a: β = 0.32, P = 0.003), and Q-Alb and had a significant effect on the initial mRS (b: β = 0.27, P = 0.017). Serum C3 had a significant effect on initial mRS (c ': β = 0.23, P = 0.038), and the direct effect was 0.124 (95% confidence interval [CI]: 0.069–0.241), accounting for 72.9% of the total effect. After adding the intermediary variable, the effect of serum C3 on the severity of disease mediated by BBB injury was still significant (c: β = 0.32, P = 0.004). The indirect effect was 0.046 (95% CI: 0.004–0.098), accounting for 27.1% of the total effect. BBB injury played a partial mediating role between serum C3 and disease severity. Table 5 The mediating role of BBB injury between serum C3 and disease severity in anti- Effect SE LLCI ULCI Total effect 0.170 0.057 0.056 0.284 Direct effect 0.124 0.059 0.069 0.241 Indirect effect 0.046 0.024 0.004 0.098 anti-NMDAR, anti-N-methyl-d-aspartate receptor; BBB, blood-brain barrier; SE, standard error; LLCI, lower level of confidence interval; ULCI, upper level of confidence interval. Analysis of risk factors for disease prognosis Univariate analysis showed that serum C3 (odds ratio [OR] = 1.53, 95% CI = 1.13–2.08, P = 0.007) and initial mRS (OR = 2.49, 95% CI = 1.33–4.66, P = 0.004) significantly positively correlated with the prognosis (Table 6 ). No correlation was found between age at onset, gender, past medical history, personal history, serum anti-NMDAR antibody status, serum leukocytes, monocytes, neutrophils, lymphocytes, C4, blood albumin, CSF pressure, WCC, glucose, chloride, IgG, Q-IgG, IgG index, Q-Alb, or abnormal head MRI findings, and disease prognosis ( P > 0.05 for all parameters). To eliminate the influence of confounding factors on the results, multivariate model I adjusted for age and gender. Model II adjusted for age, gender, C4, and Q-Alb. The results of both models showed that serum C3 level and initial mRS were independent risk factors for poor prognosis in patients with first-attack anti-NMDAR encephalitis ( P < 0.05) (Table 7 ). Table 6 Univariate binary logistic regression analysis of poor prognosis in patients with anti- NMDAR encephalitis. Factor Univariate analysis OR (95% CI) P Age at onset 0.99 (0.95–1.03) 0.493 Adults, ≥ 18 0.70 (0.17–2.94) 0.628 Gender, female 0.94 (0.29–3.07) 0.912 Hypertension 0.74 (0.08–6.56) 0.785 Diabetes 2.79 (0.23–33.26) 0.417 Autoimmune diseases 0.88 (0.10–7.94) 0.906 Tumor 1.35 (0.14–13.19) 0.794 Drinking 1.29 (0.31–5.37) 0.724 Smoking 0.79 (0.20–3.18) 0.740 Serum anti- NMDAR antibody (+) 0.57 (0.17–1.93) 0.368 Serum WCC 1.00 (0.86–1.15) 0.957 Monocytes 0.20 (0.02–2.77) 0.231 Lymphocytes 1.37 (0.67–2.82) 0.388 Neutrophil 0.97 (0.83–1.13) 0.710 C3 1.53 (1.13–2.08) 0.007* C4 1.52 (0.73–3.14) 0.263 Serum IgG 0.92 (0.81–1.06) 0.242 Serum albumin 1.01 (0.91–1.13) 0.799 CSF pressure 1.00 (1.00-1.01) 0.272 CSF WCC 1.01 (1.00-1.01) 0.279 CSF glucose 0.55 (0.25–1.19) 0.130 CSF chloride 1.03 (0.90–1.17) 0.688 CSF IgG 1.01 (1.00-1.02) 0.392 CSF albumin 1.00 (1.00-1.01) 0.266 Q-IgG a 1.05 (0.93–1.19) 0.457 Q-Alb b 1.08 (0.95–1.22) 0.255 IgG index 1.14 (0.47–2.80) 0.769 Abnormal head-MRI 1.13 (0.31–4.05) 0.857 Initial mRS 2.49 (1.33–4.66) 0.004* anti-NMDAR, anti-N-methyl-d-aspartate receptor; OR, odds ratio; CI, confidence interval; WCC, white cell count; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; mRS, modified Rankin scale. a Q-IgG is the ratio of CSF IgG to serum IgG; b Q-Alb is the ratio of CSF albumin to serum albumin *Statistically significant difference Table 7 Multivariate binary logistic regression analysis of poor prognosis in patients with anti-NMDAR encephalitis. Model I Model II OR (95% CI) P OR (95% CI) P Age at onset 0.97(0.91–1.03) 0.258 0.96(0.91–1.03) 0.232 Gender, female 1.34 (0.32–5.60) 0.687 1.30 (0.30–5.57) 0.724 C3 1.50 (1.05–2.14) 0.027* 1.60 (1.08–2.39) 0.020* Initial mRS 2.33 (1.16–4.68) 0.017* 2.49 (1.17–5.28) 0.018* C4 - - 0.69 (0.27–1.72) 0.420 Q-Alb a - - 0.99 (0.85–1.15) 0.855 anti-NMDAR, anti-N-methyl-d-aspartate receptor; mRS, modified Rankin scale. a Q-Alb is the ratio of CSF albumin to serum albumin *Statistically significant difference Analysis of risk factors for disease relapse Kaplan–Meier curves showed that elevated serum C3 level was a risk factor for relapse in patients with anti-NMDAR encephalitis (log-rank P = 0.011). The relapse rate in the high C3 group was higher than that in the low C3 group over the same period, with relapse rates at 12 and 24 months of 4.9% and 7.3% in the high C3 group and 12.2% and 24.4% in the low C3 group, respectively (Fig. 5 ). Univariate Cox analysis showed that serum C3 (hazard ratio [HR] = 1.34, 95% CI = 1.10–1.63, P = 0.004), CSF albumin (HR = 1.00, 95%CI = 1.00–1.01, P = 0.003), and Q-Alb (HR = 1.17, 95%CI = 1.07–1.27, P <0.001) each had an independent effect on the first relapse (Table 8 ). To eliminate the influence of confounding factors on the results, we screened the factors flagged by the univariate analysis ( P < 0.05) as well as factors possibly associated with disease prognosis for inclusion in the multivariate Cox models. Model I was adjusted for age and gender, whereas model II was adjusted for age, gender, C4, and initial mRS scores. CSF albumin was excluded because of its covariance with Q-Alb. The results of both models showed that serum C3 and Q-Alb levels were independent risk factors for relapse in patients with first-attack anti-NMDAR encephalitis ( P < 0.05) (Table 9 and Fig. 6 ). Table 8 Univariate Cox analysis of relapse in patients with anti-NMDAR encephalitis. Factor • Univariate analysis HR (95% CI) P Age at onset 1.01 (0.98–1.03) 0.690 Adults, ≥ 18 2.10 (0.49–9.11) 0.321 Gender, female 0.58 (0.23–1.48) 0.253 Hypertension 1.01 (0.23–4.37) 0.992 Diabetes 1.53 (0.20-11.59) 0.678 Autoimmune diseases 1.72 (0.39–7.52) 0.471 Tumor 0.70 (0.09–5.26) 0.729 Drinking 1.95 (0.74–5.14) 0.177 Smoking 1.51 (0.57–4.01) 0.405 Serum anti- NMDAR antibody (+) 0.62 (0.25–1.55) 0.305 Serum WCC 1.00 (0.89–1.12) 0.985 Monocytes 1.03 (0.20–5.41) 0.973 Lymphocytes 0.95 (0.52–1.76) 0.877 Neutrophil 1.00 (0.88–1.12) 0.930 C3 1.34 (1.10–1.63) 0.004* C4 1.35 (0.78–2.34) 0.279 Serum IgG 0.95 (0.86–1.04) 0.229 Serum albumin 0.96 (0.89–1.05) 0.361 CSF pressure 1.00 (0.99–1.01) 0.792 CSF WCC 1.00 (1.00-1.01) 0.255 CSF glucose 1.12 (0.71–1.77) 0.623 CSF chloride 1.05 (0.95–1.17) 0.353 CSF IgG 1.00 (0.99–1.02) 0.505 CSF albumin 1.00 (1.00-1.01) 0.003* Q-IgG a 1.04 (0.95–1.14) 0.347 Q-Alb b 1.17 (1.07–1.27) <0.001* IgG index 0.48 (0.15–1.57) 0.226 Abnormal head-MRI 1.49 (0.54–4.14) 0.446 Initial mRS 1.16 (0.81–1.66) 0.409 anti-NMDAR, anti-N-methyl-d-aspartate receptor; HR, hazard ratio; CI, confidence interval; WCC, white cell count; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; mRS, modified Rankin scale a Q-IgG is the ratio of CSF IgG to serum IgG; b Q-Alb is the ratio of CSF albumin to serum albumin *Statistically significant difference Table 9 Multivariate Cox analysis of relapse in patients with anti-NMDAR encephalitis. Model I Model II HR (95% CI) P HR (95% CI) P Age at onset 0.99 (0.96–1.03) 0.650 0.99 (0.95–1.03) 0.527 Gender, female 1.30 (0.47–3.59) 0.613 1.36 (0.48–3.85) 0.562 C3 1.28 (1.02–1.60) 0.032* 1.32 (1.04–1.66) 0.023* Q-Alb a 1.13 (1.03–1.24) 0.009* 1.14 (1.03–1.26) 0.009* C4 - - 0.82 (0.43–1.58) 0.551 Initial mRS - - 0.94 (0.64–1.37) 0.731 anti-NMDAR, anti-N-methyl-d-aspartate receptor; HR, hazard ratio; CI, confidence interval; mRS, modified Rankin scale a Q-Alb is the ratio of CSF albumin to serum albumin *Statistically significant difference Sensitivity analysis After we excluded patients with autoimmune diseases from the sensitivity analysis, complement C3 and initial mRS were still associated with poor prognosis in patients with anti-NMDAR encephalitis in both models ( P < 0.05) (Supplementary Table 1). This is consistent with the results in the overall population, confirming that complement C3 and initial mRS correlate with disease prognosis independently of autoimmune disease. Similar results were observed in the sensitivity analysis of the correlation of disease relapse. After excluding patients with autoimmune diseases, complement C3 and Q-Alb were still significantly associated with disease relapse ( P < 0.05) (Supplementary Table 2). To further analyze the effect of gender on the results, stratified and interaction analyses were performed. No interactions between gender and complement C3 or initial mRS were observed in the analysis of risk factors for poor prognosis ( P > 0.05). In the analysis of risk factors for disease relapse, gender did not interact with complement C3 or Q-Alb either ( P > 0.05) (Supplementary Table 3). Likewise, no statistically significant differences were found in the correlations between complement C3 and disease outcomes in patients of different genders. Diagnostic value of serum C3 in the prognosis of patients with anti-NMDAR encephalitis The diagnostic value of serum C3 level in the assessment of prognosis and relapse in patients with anti-NMDAR encephalitis was analyzed by ROC curves. For disease prognosis, the AUC was 0.748 (95% CI = 0.61–0.89, P = 0.005), with an optimal cut-off value for C3 of 13.25 g/dL, sensitivity of 0.615, and specificity of 0.841. When serum C3 was ≥ 13.25 g/dL, the risk of poor disease prognosis was high. For disease relapse, the AUC was 0.697, the best cutoff value was C3 = 11.4 g/dL, with sensitivity of 0.737 and specificity of 0.667 (95% CI = 0.56–0.84, P = 0.009). The risk of disease relapse was high when serum C3 level was > 11.4 g/dL. (Fig. 7 ). Discussion We retrospectively analyzed data from 82 patients with anti-NMDAR encephalitis, primarily from northern China, and established the following: 1) serum C3 and Q-Alb positively correlated with disease severity in patients with anti-NMDAR encephalitis, and serum C3 level significantly positively correlated with the extent of BBB injury, 2) BBB injury mediated the effect of serum C3 on disease severity, 3) serum C3 was an independent risk factor for poor prognosis and disease relapse. Patients in our cohort had a higher median onset age (33 [IQR 21–45] years) compared to the reported ages of onset in other Chinese anti-NMDAR encephalitis studies [ 24 ]. This may be related to the particular healthcare system in Tianjin, which is characterized by a large number of specialized hospitals. Our hospital specializes in brain functions and receives few infants and children. The proportion of adult patients in this cohort was 81.7%, which also affected the median age at onset. The proportion of females in this cohort was 47.6%, which may be related to the different sample sizes. The pathogenesis of AE may involve tumor-derived antigen-triggered autoimmunity [ 26 ], viral infection-induced antigen exposure [ 27 , 28 ], or defective immune tolerance mechanisms [ 25 ]. High complement levels are associated with infections and tumors [ 29 , 30 ]. The complement system is an important part of the innate immune response. Most complement proteins are produced in the liver and circulate in blood and lymph [ 31 ]. C3 and C4 are the core components of the complement system, and complement C3, at the intersection of the three complement activation pathways, is considered the central molecule that ultimately drives the complement cascade reaction [ 32 ]. Previous studies have reported increased complement protein expression and complement signaling activation in autopsy tissues from patients with NMO and in hsAQP4-IgG passive transfer mouse models [ 33 , 34 ]. Serum levels of complement C3 and C4 as well as CSF levels of C3 are elevated in patients with MS compared with their levels in healthy controls or in patients with non-inflammatory neurological diseases [ 35 ]. The intrathecal activation products of the classical and alternative pathways (C4a, C3a, and Ba) strongly correlate with MS severity [ 36 ]. Complement activation is significantly increased in children and adults with MOGAD. This suggests that activated complement proteins contribute to CNS tissue damage [ 13 ]. Recent studies have found that serum C3 and C4 levels are elevated during the acute phase response and correlate with disease severity [ 19 , 20 ], consistent with our findings. We found that serum C3 level positively correlated with the severity of the first-attack anti-NMDAR encephalitis. Patients with severe disability (mRS ≥ 4) demonstrated significantly elevated C3 and C4 levels compared to those in patients with milder symptoms (mRS < 4). Therefore, we hypothesized that elevated serum C3 and C4 levels reflect a systemic inflammatory response in the disease. We also investigated the correlation between serum complement C3 and prognosis of anti-NMDAR encephalitis, and found that baseline serum C3 level was an independent predictor for poor prognosis and relapse of the disease ( P < 0.05). When serum C3 ≥ 13.25 g/dL, the risk of poor disease prognosis is high, and when serum C3 ≥ 11.4g/dL, the risk of disease relapse is high. The sensitivity and stratified analysis confirmed the reliability of our results. Martinez-Hernandez et al. demonstrated that anti-NMDAR antibodies (immunoglobulin G (IgG) 1 and IgG3 isoforms) are produced within the sheaths of antibody-secreting cells infiltrating the CNS of patients with anti-NMDAR encephalitis, which may activate the complement system [ 37 ]. Anti-NMDAR antibodies synthesized in the CNS of patients may cross the intact BBB into the bloodstream through leaky areas, which activate the serum complement system, leading to elevated serum complement levels associated with intense inflammation and oxidative stress [ 38 , 39 ]. Thus, severely impaired patients may experience a stronger complement-mediated inflammatory response. Complement-mediated neuronal toxicity in anti-CASPR2 and anti-LGI1 encephalitis has been supported by autopsy findings [ 32 ]. Höoftberger et al. reported that in all MOGAD cases, some deposition of activated complement in lesions was observed [ 40 ]. Characteristic patterns of complement deposition activated at the edges of the vascular centers and rosettes were also found in patients with NMOSD [ 41 ]. However, antibodies against NMDAR encephalitis could bind to the complement in vitro, and no complement deposition was detected in the brains of these patients [ 37 , 42 ]. Therefore, we hypothesized that the effects of the complement system on disease progression in anti-NMDAR encephalitis do not rely on effector mechanisms associated with end-pathway activation and membrane attack complex formation but rather impair neuronal cell function through non-complement deposition. It has been suggested that synaptic abnormalities occurring in the gray matter of patients with progressive MS are related to the complement system activation [ 43 – 45 ]. Microglia play a crucial role in maintaining synaptic plasticity [ 46 ]. Michailidou et al. showed co-localization of the activated C1q-C3 axis with microglia and lysosomes in the hippocampus of patients with MS. Neurons in this region showed signs of damage, decreased density of presynaptic terminals, and increased immunoreactivity for mitochondrial stress protein mtHSP70 [ 47 ]. This suggests that in the hippocampus of patients with MS, complement labels synapses to be phagocytosed by microglia, which in turn affects neuronal function [ 48 ]. The primary molecular mechanism of anti-NMDAR encephalitis is autoantibody-mediated NMDAR hypofunction at neuronal synapses [ 49 ]. Whether the complement system affects synaptic function through microglial activation, which, in turn, affects disease progression and prognosis, requires further investigation. BBB destruction can occur early in anti-NMDAR encephalitis, leading to neuronal damage [ 5 ]. This is consistent with our results, in which CSF albumin, Q-IgG, and Q-Alb were positively associated with anti-NMDAR encephalitis disease severity ( P <0.05). In anti-NMDAR encephalitis observed in the humanized mouse model injected with human peripheral blood mononuclear cells, claudin-5, occludin, ZO-1, and other tight junction proteins were downregulated, whereas the expression of inflammatory factors such as IL-1β was upregulated, leading to the invasion of antibodies and inflammatory cells into the central nervous system and aggravation of neurological damage [ 50 ]. We also found that Q-Alb, a biomarker of BBB disruption, was associated with the disease relapse ( P < 0.05). The possible mechanism is that after BBB disruption, inflammatory factors are released continuously, forming a chronic neuroinflammatory environment and increasing the relapse risk. It may also be related to the instability of BBB function, as the residual antibody may still enter the brain and increase the risk of relapse. The specific mechanism of BBB disruption leading to the recurrence of anti NMDAR encephalitis needs further investigation. The BBB is particularly vulnerable to complement, as it is exposed to circulating and locally synthesized complement proteins. In our study, serum C3 level positively correlated with CSF albumin and Q-Alb. Our findings corroborate prior observations in patients with NMOSD [ 14 ]. The mediation analysis proved that BBB disruption mediated the effect of C3 on disease severity, which may reveal an important way for complement system to play an inflammatory role in anti-NMDAR encephalitis. BBB dysfunction may be associated with complement dysregulation, and when the complement system is overwhelmed, complement activation may impair BBB integrity [ 51 ]. Serum C3 may be a potential biomarker reflecting BBB damage in anti-NMDAR encephalitis. Most complement proteins do not cross the BBB. They are expressed by brain-resident cells and enter the brain when the BBB is compromised [ 52 ]. Microglia and astrocytes are thought to be the main producers of complement C3, with neurons, endothelial cells, and oligodendrocytes being additional producers [ 53 ]. Previous studies have shown that microglia C3-C3aR signaling plays a crucial role in the pathogenesis of demyelination and neurodegenerative diseases by regulating alternative complement pathways. Activated M1 microglia release pro-inflammatory cytokines [ 54 – 56 ]. Overexpression of complement C3 in A1 astrocytic glial cells of a mouse model of MS during the acute phase of the disease induced neuronal and oligodendrocyte death and impaired oligodendrocyte maturation [ 57 ]. In a mouse model of NMO, AQP4 autoantibody-stimulated astrocytes released complement C3. This complement binds to C3aR, which disrupts neuronal development by inhibiting β-catenin signaling [ 53 ]. Endothelial cells of cerebral microvessels produce complement regulatory proteins and components of classical and alternative pathways [ 58 ]. The complement activation products C3a and C5a induce brain endothelial cell activation and increase the infiltration of inflammatory cells into the brain by increasing the expression of P-selectin, E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 [ 58 ]. We hypothesized that antibodies would disrupt the BBB in anti-NMDAR encephalitis. This disruption allows serum complement to infiltrate the brain, potentially intensifying neuroinflammation associated with anti-NMDAR encephalitis. Additionally, complement activation in astrocytes, microglia, and vascular endothelial cells may aggravate BBB damage, leading to secondary neurological issues deficits. The pathological mechanism by which complement C3 aggravates the severity of anti-NMDAR encephalitis through BBB disruption and thereby leads to poor prognosis remains to be determined. The complement therapy drug eculizumab showed beneficial effects in paroxysmal nocturnal hemoglobinuria and MG [ 59 ]. Other complement inhibitors, such as ravulizumab, zilucoplan, and pozelimab, are under development [ 59 ]. In clinical practice, focusing on serum complement levels in the early stages of pathogenesis and using complement inhibitors/antagonists provides a new treatment possibility, which may be necessary for protecting the BBB, mitigating disease progression, and reducing the risk of relapse. Animal and clinical studies are warranted to confirm this. This study has some limitations. First, this was a single-center retrospective study, and a multicenter prospective study with a larger sample size and long-term follow-up is needed to confirm the findings presented herein. Second, some difficult to control confounding factors, such as living and dietary habits as well as intake of different medications, may have impacted the outcomes of this study. Third, our conclusions may be affected by selection bias, as some cases were excluded owing to incomplete clinical information and others because of incomplete clinical data and loss to follow up. Conclusion This is the first study in which serum complement C3 was found to correlate with BBB injury and prognosis in patients with anti-NMDAR encephalitis. We also demonstrated the mediating role of BBB disruption on the relationship between C3 and disease severity. Serum complement C3 level was an independent predictor for poor prognosis and relapse of anti-NMDAR encephalitis. Serum C3 may aggravate the severity of anti-NMDAR encephalitis through BBB disruption, thus leading to poor prognosis. This suggests that complement C3 level must be monitored at early stages of the disease to assess the risk of relapse and improve patient prognosis. Inhibitors targeting complement or complement receptors are potential therapeutic targets for anti-NMDAR encephalitis. However, the specific mechanism of the complement system involvement in BBB disruption and neurological dysfunction in anti-NMDAR encephalitis requires further studies. Abbreviations AE autoimmune encephalitis AUC area under the ROC curve BBB blood–brain barrier CI confidence interval CNS central nervous system CSF cerebrospinal fluid GBS Guillain–Barré syndrome HR hazard ratio IgG immunoglobulin G MG myasthenia gravis MOGAD myelin oligodendrocyte glycoprotein antibody–associated disease MRI magnetic resonance imaging mRS modified Rankin scale MS multiple sclerosis NMDAR N-methyl-D-aspartate receptor NMOSD neuromyelitis optica spectrum disorder OR odds ratio Q-Alb albumin quotient ROC receiver operating characteristic WCC white cell count Declarations Ethics approval and consent to participate The study followed the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Huanhu Hospital (202410281325000227905). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article. Availability of data and materials The original contributions presented in the study are included in Supplementary Table 4; further inquiries can be directed to the corresponding author. Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding This work was supported by Tianjin Health Commission Science and Technology Projects (TJWJ2021QN061 and ZC20134) and Tianjin Key Medical Discipline (Specialty) Construction Project (No. TJYXZDXK-052B). Authors' contributions All authors made a significant contribution to the study. The authors’ responsibilities were as follows: ZJW conceived and designed the research.ZJW, YLQ, WZY and LYM organized the database.ZJW and LWX performed the statistical analysis. ZJW and WZY conducted regular follow-up of all cases. ZJW wrote the first draft of the manuscript. LL, XL and YW revised the manuscript critically. All authors approved the final version of the manuscript. They agreed on the journal to which the article has been submitted, and agreed to be accountable for all aspects of the work. Acknowledgements Not applicable. References Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10 1:63–74. 10.1016/s1474-4422(10)70253-2 . Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10 12:835–44. 10.1016/s1473-3099(10)70222-x . Jmor F, Emsley HC, Fischer M, Solomon T, Lewthwaite P. The incidence of acute encephalitis syndrome in Western industrialised and tropical countries. Virol J. 2008;5:134. 10.1186/1743-422x-5-134 . Josep D, Francesc G, Antibody-Mediated Encephalitis. N Engl J Med. 2018;378:9. 10.1056/NEJMra1708712 . Gong Z, Lao D, Wu Y, Li T, Lv S, Mo X, et al. Inhibiting PI3K/Akt-Signaling Pathway Improves Neurobehavior Changes in Anti-NMDAR Encephalitis Mice by Ameliorating Blood-Brain Barrier Disruption and Neuronal Damage. Cell Mol Neurobiol. 2023;43 7:3623–37. 10.1007/s10571-023-01371-3 . Jézéquel J, Johansson EM, Dupuis JP, Rogemond V, Gréa H, Kellermayer B, et al. Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients. Nat Commun. 2017;8(1:1791). 10.1038/s41467-017-01700-3 . Alexopoulos H, Dalakas MC. The immunobiology of autoimmune encephalitides. J Autoimmun. 2019;104:102339. 10.1016/j.jaut.2019.102339 . Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7 12:1091–8. 10.1016/s1474-4422(08)70224-2 . Jingxiao Z, Yatong L, Lei L, Feifei D, Yujing P, Qiuying M, et al. Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients. BMC Neurol. 2024;24(1). 10.1186/s12883-024-03724-x . Chen M, Edwards SR, Reutens DC. Complement in the Development of Post-Traumatic Epilepsy: Prospects for Drug Repurposing. J Neurotrauma. 2020;37 5:692–705. 10.1089/neu.2019.6942 . Ziabska K, Ziemka-Nalecz M, Pawelec P, Sypecka J, Zalewska T. Aberrant Complement System Activation in Neurological Disorders. Int J Mol Sci. 2021;22:9. 10.3390/ijms22094675 . Aeinehband S, Lindblom RP, Al Nimer F, Vijayaraghavan S, Sandholm K, Khademi M, et al. Complement component C3 and butyrylcholinesterase activity are associated with neurodegeneration and clinical disability in multiple sclerosis. PLoS ONE. 2015;10(4):e0122048. 10.1371/journal.pone.0122048 . Keller CW, Lopez JA, Wendel EM, Ramanathan S, Gross CC, Klotz L, et al. Complement Activation Is a Prominent Feature of MOGAD. Ann Neurol. 2021;90 6:976–82. 10.1002/ana.26226 . Lin L, Wu Y, Hang H, Lu J, Ding Y. 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. Front Immunol. 2022;13:853891. 10.3389/fimmu.2022.853891 . Stathopoulos P, Dalakas MC. The role of complement and complement therapeutics in neuromyelitis optica spectrum disorders. Expert Rev Clin Immunol. 2022;18 9:933–45. 10.1080/1744666x.2022.2105205 . Min YG, Ju W, Seo JW, Ha YE, Ban JJ, Kwon YN, et al. Serum C3 complement levels predict prognosis and monitor disease activity in Guillain-Barré syndrome. J Neurol Sci. 2023;444:120512. 10.1016/j.jns.2022.120512 . Dalakas MC. Role of complement, anti-complement therapeutics, and other targeted immunotherapies in myasthenia gravis. Expert Rev Clin Immunol. 2022;18 7:691–701. 10.1080/1744666x.2022.2082946 . Stascheit F, Chuquisana O, Keller CW, Ambrose PA, Hoffmann S, Gross CC, et al. Complement activation profiles in anti-acetylcholine receptor positive myasthenia gravis. Eur J Neurol. 2023;30 5:1409–16. 10.1111/ene.15730 . Shu Y, Chen C, Chen Y, Xu Y, Chang Y, Li R, et al. Serum complement levels in anti-N-methyl-d-aspartate receptor encephalitis. Eur J Neurol. 2018;25(1):178–84. 10.1111/ene.13495 . Liu X, Fan K, Lin Q, Tang M, Wang Q, Huang E, et al. Serum-Derived Exosomal miR-140-5p as a Promising Biomarker for Differential Diagnosis of Anti-NMDAR Encephalitis With Viral Encephalitis. Front Immunol. 2022;13:840003. 10.3389/fimmu.2022.840003 . Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15 4:391–404. 10.1016/s1474-4422(15)00401-9 . van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19 5:604–7. 10.1161/01.str.19.5.604 . Brenner J, Mariotto S, Bastiaansen AEM, Paunovic M, Ferrari S, Alberti D, et al. Predictive Value of Serum Neurofilament Light Chain Levels in Anti-NMDA Receptor Encephalitis. Neurology. 2023;100 21:e2204–13. 10.1212/wnl.0000000000207221 . Xu X, Lu Q, Huang Y, Fan S, Zhou L, Yuan J, et al. Anti-NMDAR encephalitis: A single-center, longitudinal study in China. Neurol Neuroimmunol Neuroinflamm. 2020;7(1). 10.1212/nxi.0000000000000633 . Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12 2:157–65. 10.1016/s1474-4422(12)70310-1 . Kreye J, Wenke NK, Chayka M, Leubner J, Murugan R, Maier N, et al. Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis. Brain. 2016;139:2641–52. 10.1093/brain/aww208 . Dubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166–77. 10.1002/ana.25131 . Armangue T, Spatola M, Vlagea A, Mattozzi S, Cárceles-Cordon M, Martinez-Heras E, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol. 2018;17 9:760–72. 10.1016/s1474-4422(18)30244-8 . Walport MJ, Complement. First of two parts. N Engl J Med. 2001;344 14:1058–66. 10.1056/nejm200104053441406 . Jiang F, Liu H, Liu Z, Song J, Li L, Ding K, et al. High serum levels of complements C3 and C4 as novel markers for myeloma bone disease. Ann Hematol. 2017;96 2:331–3. 10.1007/s00277-016-2863-z . Zarkadis IK, Mastellos D, Lambris JD. Phylogenetic aspects of the complement system. Dev Comp Immunol. 2001;25. 10.1016/s0145-305x(01)00034-9 . 8–9:745 – 62; doi:. Negro-Demontel L, Maleki AF, Reich DS, Kemper C. The complement system in neurodegenerative and inflammatory diseases of the central nervous system. Front Neurol. 2024;15:1396520. 10.3389/fneur.2024.1396520 . Asavapanumas N, Tradtrantip L, Verkman AS. Targeting the complement system in neuromyelitis optica spectrum disorder. Expert Opin Biol Ther. 2021;21 8:1073–86. 10.1080/14712598.2021.1884223 . Carpanini SM, Torvell M, Morgan BP. Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System. Front Immunol. 2019;10:362. 10.3389/fimmu.2019.00362 . Lunemann JD, Hegen H, Villar LM, Rejdak K, Sao-Aviles A, Carbonell-Mirabent P, et al. Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024;11 4:e200270. 10.1212/nxi.0000000000200270 . Oechtering J, Stein K, Schaedelin SA, Maceski AM, Orleth A, Meier S, et al. Complement Activation Is Associated With Disease Severity in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024;11 2:e200212. 10.1212/nxi.0000000000200212 . Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, Sangha N, Martinez-Lage M, Dalmau J. Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology. 2011;77 6:589–93. 10.1212/WNL.0b013e318228c136 . Doi H, Matsushita T, Isobe N, Matsuoka T, Minohara M, Ochi H, et al. Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody. Mult Scler. 2009;15 3:304–10. 10.1177/1352458508099139 . Liu Z, Tang Q, Wen J, Tang Y, Huang D, Huang Y, et al. Elevated serum complement factors 3 and 4 are strong inflammatory markers of the metabolic syndrome development: a longitudinal cohort study. Sci Rep. 2016;6:18713. 10.1038/srep18713 . Höftberger R, Guo Y, Flanagan EP, Lopez-Chiriboga AS, Endmayr V, Hochmeister S, et al. The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody. Acta Neuropathol. 2020;139 5:875–92. 10.1007/s00401-020-02132-y . Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 2002;125 Pt 7:1450–61; 10.1093/brain/awf151 Bien CG, Vincent A, Barnett MH, Becker AJ, Blümcke I, Graus F, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain. 2012;135:1622–38. 10.1093/brain/aws082 . Olivero G, Taddeucci A, Vallarino G, Trebesova H, Roggeri A, Gagliani MC, et al. Complement tunes glutamate release and supports synaptic impairments in an animal model of multiple sclerosis. Br J Pharmacol. 2024;181 12:1812–28. 10.1111/bph.16328 . Peterson JW, Bö L, Mörk S, Chang A, Trapp BD. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001;50 3:389–400. 10.1002/ana.1123 . Werneburg S, Jung J, Kunjamma RB, Ha SK, Luciano NJ, Willis CM, et al. Targeted Complement Inhibition at Synapses Prevents Microglial Synaptic Engulfment and Synapse Loss in Demyelinating Disease. Immunity. 2020;52. 10.1016/j.immuni.2019.12.004 . 1:167 – 82.e7. Wu Y, Dissing-Olesen L, MacVicar BA, Stevens B, Microglia. Dynamic Mediators of Synapse Development and Plasticity. Trends Immunol. 2015;36 10:605–13. 10.1016/j.it.2015.08.008 . Michailidou I, Willems JG, Kooi EJ, van Eden C, Gold SM, Geurts JJ, et al. Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus. Ann Neurol. 2015;77 6:1007–26. 10.1002/ana.24398 . Saez-Calveras N, Stuve O. The role of the complement system in Multiple Sclerosis: A review. Front Immunol. 2022;13:970486. 10.3389/fimmu.2022.970486 . Ingram G, Hakobyan S, Hirst CL, Harris CL, Pickersgill TP, Cossburn MD, et al. Complement regulator factor H as a serum biomarker of multiple sclerosis disease state. Brain. 2010;133:1602–11. 10.1093/brain/awq085 . Shu Y, Peng F, Zhao B, Liu C, Li Q, Li H, et al. Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model. J Neuroinflammation. 2023;20(1:164). 10.1186/s12974-023-02844-4 . Alexander JJ. Blood-brain barrier (BBB) and the complement landscape. Mol Immunol. 2018;102:26–31. 10.1016/j.molimm.2018.06.267 . Veerhuis R. Histological and direct evidence for the role of complement in the neuroinflammation of AD. Curr Alzheimer Res. 2011;8 1:34–58. 10.2174/156720511794604589 . Zhu F, He P, Jiang W, Afridi SK, Xu H, Alahmad M, et al. Astrocyte-secreted C3 signaling impairs neuronal development and cognition in autoimmune diseases. Prog Neurobiol. 2024;240:102654. 10.1016/j.pneurobio.2024.102654 . Xu L, Xu H, Chen S, Jiang W, Afridi SK, Wang Y, et al. Inhibition of complement C3 signaling ameliorates locomotor and visual dysfunction in autoimmune inflammatory diseases. Mol Ther. 2023;31 9:2715–33. 10.1016/j.ymthe.2023.07.017 . Chen T, Lennon VA, Liu YU, Bosco DB, Li Y, Yi MH, et al. Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion. J Clin Invest. 2020;130 8:4025–38. 10.1172/jci134816 . Dubbelaar ML, Kracht L, Eggen BJL, Boddeke E. The Kaleidoscope of Microglial Phenotypes. Front Immunol. 2018;9:1753. 10.3389/fimmu.2018.01753 . Takai Y, Misu T, Suzuki H, Takahashi T, Okada H, Tanaka S, et al. Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders. Brain. 2021;144 8:2401–15. 10.1093/brain/awab102 . Wu F, Zou Q, Ding X, Shi D, Zhu X, Hu W, et al. Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain. J Neuroinflammation. 2016;13:23. 10.1186/s12974-016-0485-y . Smets I, Titulaer MJ. Antibody Therapies in Autoimmune Encephalitis. Neurotherapeutics. 2022;19 3:823–31. 10.1007/s13311-021-01178-4 . Additional Declarations No competing interests reported. Supplementary Files SupplementaryTables.docx Supplementary Table 1 Sensitivity analysis of poor prognosis after exclusion of patients with autoimmune disease. Supplementary Table 2 Sensitivity analysis of relapse after exclusion of patients with autoimmune disease. Supplementary Table 3 Stratification analysis of prognosis in patients with anti-NMDAR encephalitis. Suplementarytable4.xlsx Cite Share Download PDF Status: Published Journal Publication published 16 Feb, 2026 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 24 Oct, 2025 Reviews received at journal 21 Oct, 2025 Reviewers agreed at journal 20 Oct, 2025 Reviews received at journal 25 Sep, 2025 Reviewers agreed at journal 22 Sep, 2025 Reviewers agreed at journal 27 Aug, 2025 Reviewers invited by journal 25 Aug, 2025 Editor assigned by journal 25 Aug, 2025 Editor invited by journal 04 Aug, 2025 Submission checks completed at journal 02 Aug, 2025 First submitted to journal 02 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7220180","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":507918630,"identity":"1c7b0af6-ca6a-487b-9dd9-89ab3cc3c04f","order_by":0,"name":"Jinwei Zhang","email":"","orcid":"","institution":"Huanhu Hospital Affiliated to Tianjin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jinwei","middleName":"","lastName":"Zhang","suffix":""},{"id":507918631,"identity":"5dd7f2d5-a37c-4010-ae91-31ad62993ccd","order_by":1,"name":"Ling Ling","email":"","orcid":"","institution":"Huanhu Hospital Affiliated to Tianjin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Ling","suffix":""},{"id":507918632,"identity":"5d68f0c4-d3dc-4c75-9b07-ee26636793ad","order_by":2,"name":"Lei Xiang","email":"","orcid":"","institution":"Huanhu Hospital Affiliated to Tianjin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Xiang","suffix":""},{"id":507918633,"identity":"840cf10b-e274-44e2-9145-9e6301eaee3f","order_by":3,"name":"Wenxia Li","email":"","orcid":"","institution":"Huanhu Hospital Affiliated to Tianjin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenxia","middleName":"","lastName":"Li","suffix":""},{"id":507918634,"identity":"4460188b-906f-4180-b979-32e881da76d1","order_by":4,"name":"Liqin Yang","email":"","orcid":"","institution":"Huanhu Hospital Affiliated to Tianjin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Liqin","middleName":"","lastName":"Yang","suffix":""},{"id":507918635,"identity":"f6676cb4-a29e-48fc-9bc4-fbd5c3497a64","order_by":5,"name":"Zhiying Wang","email":"","orcid":"","institution":"Huanhu Hospital Affiliated to Tianjin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhiying","middleName":"","lastName":"Wang","suffix":""},{"id":507918636,"identity":"bce6f69f-5c75-4dd4-8cd0-b84ad5c80ea5","order_by":6,"name":"Youming Li","email":"","orcid":"","institution":"Huanhu Hospital Affiliated to Tianjin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Youming","middleName":"","lastName":"Li","suffix":""},{"id":507918637,"identity":"77e783c0-94bc-4b95-990b-945990060b88","order_by":7,"name":"Wei Yue","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYBACAwkIzcPPzNj44IOBjR3xWiTbmw8bzihISyZaC4PBmWNp0jwfDjE2ENJiLt1jJvGxzUaG4UaOsbGNwQFmBvbDRzfg02I554yZ5My2NB7GGTmGj3MM7vAx8KSl3cDrsBs5ZtK82w7zMEsAbckxeMbMIMFjRljL323/edgkgAwLg8OMDURpYdx2gIeHB+h9BuK0pBVb9v5L5pFgBwZyj0FaMhthvyRvvPHjjJ29/WFgVP74Y2PHz374GF4tDAwcBqh8NvzKQYD9AWE1o2AUjIJRMLIBAL+bSljHxdqlAAAAAElFTkSuQmCC","orcid":"","institution":"Huanhu Hospital Affiliated to Tianjin Medical University","correspondingAuthor":true,"prefix":"","firstName":"Wei","middleName":"","lastName":"Yue","suffix":""}],"badges":[],"createdAt":"2025-07-26 09:38:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7220180/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7220180/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-026-04671-5","type":"published","date":"2026-02-16T15:58:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90470017,"identity":"18508b1c-5ac0-445c-bceb-54e758d49f54","added_by":"auto","created_at":"2025-09-03 06:12:48","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1331122,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study.\u003cstrong\u003e \u003c/strong\u003eAE, autoimmune encephalitis; anti-NMDAR, anti-N-methyl-d-aspartate receptor; CSF, cerebrospinal fluid\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/5f72e29f230d64e368778eff.jpg"},{"id":90471865,"identity":"f0208f04-e7ee-48b5-9b2f-f2ec7d9243e8","added_by":"auto","created_at":"2025-09-03 06:28:48","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":194232,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots of the correlations between C3 (a), C4 (b), CSF IgG (c), CSF albumin (d), Q-IgG (e), Q-Alb (f), and initial mRS score. CSF, cerebrospinal fluid; mRS, modified Rankin scale.\u003cem\u003e *P \u003c/em\u003e\u0026lt; 0.05\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/c3b881cba9081f178b2f837f.jpg"},{"id":90471101,"identity":"525fb868-ed16-46d1-96a8-14e8de5c15de","added_by":"auto","created_at":"2025-09-03 06:20:48","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":138966,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots of the correlations between CSF IgG (a), CSF albumin (b), Q-Alb (c) and C3, and between CSF albumin (d) and C4. CSF, cerebrospinal fluid\u003cem\u003e. *P \u003c/em\u003e\u0026lt; 0.05\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/188c5486d831fb70303a6c3c.jpg"},{"id":90470032,"identity":"e2a202b7-8143-4adb-9f26-3dc45a34407f","added_by":"auto","created_at":"2025-09-03 06:12:48","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":591126,"visible":true,"origin":"","legend":"\u003cp\u003eThe mediating role of BBB injury between serum C3 and disease severity in anti-NMDAR encephalitis. BBB, blood-brain barrier; anti-NMDAR, anti-N-methyl-d-aspartate receptor; mRS, modified Rankin scale.\u003cem\u003e *P \u003c/em\u003e\u0026lt; 0.05\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/3a49684ac14e8afd05510dd7.jpg"},{"id":90470038,"identity":"2fa449e7-06d5-4a68-aad7-a27de5cf0889","added_by":"auto","created_at":"2025-09-03 06:12:48","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":110400,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan−Meier curves categorized according to C3. \u003cem\u003e*P \u003c/em\u003e\u0026lt; 0.05\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/5d56ad3d3f0cca5456dfd298.jpg"},{"id":90471102,"identity":"802ff339-4bfd-4d38-9e82-b8860f1db9d2","added_by":"auto","created_at":"2025-09-03 06:20:48","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":105125,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of model I (a) and model II (b) for potential factors associated with relapse. mRS, modified Rankin scale.\u003cem\u003e *P \u003c/em\u003e\u0026lt; 0.05\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/75f6f819b11a07f92ed3dced.jpg"},{"id":90470043,"identity":"2ffa2658-49f0-402a-9c7c-f825408700e6","added_by":"auto","created_at":"2025-09-03 06:12:49","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":123817,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve analysis of the diagnostic value of serum complement C3 for disease prognosis (a) and relapse (b) in anti-NMDAR encephalitis. anti-NMDAR, anti-N-methyl-d-aspartate receptor; mRS, modified Rankin scale.\u003cem\u003e *P \u003c/em\u003e\u0026lt; 0.05\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"figure7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/788d24fed88768ff6370b909.jpg"},{"id":103251354,"identity":"703c227e-cded-40d5-86db-001331bd6e66","added_by":"auto","created_at":"2026-02-23 16:08:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4043166,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/f0e80157-833b-4075-8e04-dc067d912f06.pdf"},{"id":90470013,"identity":"0317935d-fffd-47d1-8c28-1e56187f9906","added_by":"auto","created_at":"2025-09-03 06:12:47","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16540,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Table 1 \u003c/strong\u003eSensitivity analysis of poor prognosis after exclusion of patients with autoimmune disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Table 2\u003c/strong\u003e Sensitivity analysis of relapse after exclusion of patients with autoimmune disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Table 3\u003c/strong\u003e Stratification analysis of prognosis in patients with anti-NMDAR encephalitis.\u003c/p\u003e","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/899ee0ce8e7c3ac367334e4c.docx"},{"id":90470014,"identity":"a8afc641-2080-4c7e-b41c-00947388d4c6","added_by":"auto","created_at":"2025-09-03 06:12:48","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":44120,"visible":true,"origin":"","legend":"","description":"","filename":"Suplementarytable4.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7220180/v1/bc70b889c60f3fa15438ca1d.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Role of serum complement C3 in blood–brain barrier injury and prognosis of anti-NMDAR encephalitis","fulltext":[{"header":"Background","content":"\u003cp\u003eAutoimmune encephalitis (AE) is a neuroinflammatory disorder mediated by antibodies targeting neuronal antigens [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Among its subtypes, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent, with an annual incidence of 5\u0026ndash;10 cases per 100,000 individuals [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Clinical manifestations of anti-NMDAR encephalitis include psychiatric and neurological symptoms, such as abnormal mental behavior, cognitive dysfunction, speech disorders, memory loss, seizures, movement disorders, autonomic dysfunction, and decreased levels of consciousness [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the exact pathophysiological mechanisms underlying anti-NMDAR encephalitis remain unclear. Viruses and tumors that disrupt the blood\u0026ndash;brain barrier (BBB) through immune and inflammatory responses are thought to be plausible triggers of anti-NMDAR encephalitis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Anti-NMDAR antibodies in serum enter the CNS through the disrupted BBB and react with NMDARs, inducing their internalization and degradation, especially in hippocampal neurons. The resulting decrease the density of cell-surface and synaptic NMDARs leads to impaired neuronal function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. First-line treatment of anti-NMDAR encephalitis is usually immunotherapy, including intravenous immunoglobulin, steroids, or plasma exchange to remove autoantibodies that cause the disease, whereas the second-line treatment is monoclonal antibody rituximab to non-selectively remove CD20\u003csup\u003e+\u003c/sup\u003e B cells [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, the drugs currently used to treat anti-NMDAR encephalitis are insufficient for complete recovery, and some patients experience severe mental or cognitive impairment, memory deficit, refractory epilepsy, relapse, and even death [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, identifying biomarkers to predict the relapse risk of anti-NMDAR encephalitis is important to influence disease progression and improve the prognosis of patients through early intervention.\u003c/p\u003e\u003cp\u003eThe complement system, an important component of the innate immune response, can be activated via the classical, alternative, and lectin pathways [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Complement activation and cascade reactions are involved in inflammatory processes within the CNS, and their hypo- or hyperactivation may lead to neuronal cell damage, BBB destruction, and brain dysfunction [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Activation of the complement system plays a vital role in various autoimmune neurological disorders, such as multiple sclerosis (MS) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], myelin oligodendrocyte glycoprotein antibody\u0026ndash;associated disease (MOGAD) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], neuromyelitis optica spectrum disorder (NMOSD) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e],Guillain\u0026ndash;Barr\u0026eacute; syndrome (GBS) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and myasthenia gravis (MG) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecent studies have shown that serum C3 levels are elevated during the acute phase and correlate with disease severity [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Thus, an elevated serum C3 level may reflect a systemic inflammatory response in anti-NMDAR encephalitis. However, the relationship between serum complement levels and anti-NMDAR encephalitis prognosis remains to be determined. In this study, we investigated the correlation between serum complement C3 level with BBB injury and poor disease outcomes in anti-NMDAR encephalitis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eStudy subjects\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a retrospective analysis of 232 patients diagnosed with AE at the Tianjin Huanhu Hospital between September 2016 and June 2023. The enrolled patients met the following inclusion criteria: 1) patients first diagnosed with anti-NMDAR encephalitis according to the Graus and Dalmau criteria [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]; 2) manifestation of at least one of the six major symptoms, namely a) mental and behavioral abnormalities or cognitive disorders; b) speech disorders; c) seizures; d) dyskinesia/involuntary movements; e) decreased level of consciousness; and f) autonomic dysfunction or central hypoventilation; 3) cerebrospinal fluid (CSF) positivity for anti-NMDAR antibodies; and 4) exclusion of other etiologies. Exclusion criteria included: 1) immunotherapy, such as hormones, immunosuppressants, prophylaxis, and plasma exchange, prior to admission; 2) incomplete clinical information or loss to follow-up. A total of 82 patients met the criteria and were included in this study. The screening process is illustrated in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBasic information, clinical data, and laboratory test results of the patients were collected using an electronic medical record system. Basic information included age at onset, gender, medical history, and personal history. Clinical data included clinical manifestations and treatment plans. Laboratory test results included serum anti-NMDAR antibody status, white cell count (WCC), monocytes, lymphocytes, neutrophils, C3, C4, serum immunoglobulin G (IgG), serum albumin, CSF pressure, CSF WCC, glucose, chloride, protein, CSF IgG, CSF albumin, Q-IgG, Q-Alb, and IgG indices. Q-IgG is the ratio of CSF IgG to serum IgG, and Q-Alb is the ratio of CSF albumin to serum albumin, which were used to assess BBB integrity. The ratio of Q-IgG to Q-Alb was calculated as the IgG index, which represented intrathecal synthesis. Peripheral venous blood samples were collected between 6:00 a.m. and 7:00 a.m. the next day after admission. CSF samples were collected before immunotherapy, and head magnetic resonance imaging (MRI) was performed. The detection data closest to admission were used. Baseline serum and CSF anti-NMDAR antibody levels were measured via the cell-based assay (CBA), following the manufacturer\u0026rsquo;s protocol. Head MRI was performed at the Magnetic Resonance Unit of the Tianjin Huanhu Hospital using a 3T MAGNETOM Skyra scanner (Siemens Healthcare, Erlangen, Germany). Lesion locations were recorded as lobes and sulci, deep cerebral white matter, paraventricular white matter, thalamus, basal ganglia region, hippocampus, insula, pituitary gland, brainstem, and cerebellum.\u003c/p\u003e\n\u003cp\u003eDisease severity was evaluated on admission by at least two qualified neurologists using the modified Rankin Scale (mRS) as the primary metric [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. The cohort was categorized into two groups, mRS\u0026thinsp;\u0026lt;\u0026thinsp;4 and mRS\u0026thinsp;\u0026ge;\u0026thinsp;4, according to the severity of the clinical presentation.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFollow‑up data\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was disease prognosis, defined as the mRS score at 12 months after onset. The final mRS score\u0026thinsp;\u0026le;\u0026thinsp;2 was considered a good prognosis, and the final mRS score\u0026thinsp;\u0026gt;\u0026thinsp;2 was considered a poor prognosis [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. The secondary outcome was disease relapse, defined as worsening of previous symptoms or appearance of new symptoms after at least 2 months of improvement or stabilization [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. Follow-up results were obtained through annual outpatient or telephone visits; the last follow-up was conducted on June 1st, 2025.\u003c/p\u003e\n\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003eStatistical analysis was performed using SPSS 26.0 and GraphPad Prism 8.0. Normality testing incorporated both calculating the Kolmogorov-Smirnov statistic and graphical methods (Q-Q plots and histograms). Normally distributed variables were expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Comparisons between the two groups were made using the independent samples t-test. Variables that were not normally distributed are expressed as the median and interquartile range, and comparisons between two groups were done using the Mann\u0026ndash;Whitney U test. Categorical information is expressed as percentage (%), and the two groups were compared using the chi-squared test or Fisher\u0026apos;s exact test. Spearman correlation analysis was performed to assess the correlation between clinically relevant parameters and disease severity, as well as between serum complement levels and CSF relevant parameters. To investigate the mechanism of the effect of serum C3 on disease severity, Q-Alb was substituted into the structural equation model as the intermediary variable, and the process plug-in was used to test the mediation effect. The bootstrap method was used to verify the mediation effect of BBB injury between serum C3 and disease severity. Binary logistic regression model was used to assess the risk factors of poor prognosis. To eliminate the influence of confounding factors on the results, we screened variables with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in the univariate analysis as well as factors possibly associated with disease prognosis for inclusion in the multivariate models. Multivariate model I adjusted for age and gender, and model II adjusted for age, gender, C4, and Q-Alb. Cox analysis was performed to assess risk factors for disease relapse. Model I was adjusted for age and gender, whereas model II was adjusted for age, gender, C4, and initial mRS score. To verify the reliability of the results, we excluded patients with autoimmune diseases from the sensitivity analysis. Interaction and stratified analyses were used to examine the effect of different genders on the results. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of serum complement C3 for disease prognosis and relapse. Statistical significance threshold was set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eDemographic and clinical characteristics of patients with anti-NMDAR encephalitis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eEighty-two patients with first-attack anti-NMDAR encephalitis were enrolled in this study. Their median age at onset was 33 (21\u0026ndash;45) years, 39 patients were female (47.6%), and 67 patients were adults (81.7%). Thirteen patients had the final mRS score\u0026thinsp;\u0026gt;\u0026thinsp;2 (15.9%) and 19 patients (23.2%) experienced relapse during follow-up, with a median follow-up time of 37.70 (24.23\u0026ndash;55.72) months. The cohort was divided into two groups, mRS\u0026thinsp;\u0026lt;\u0026thinsp;4 and mRS\u0026thinsp;\u0026ge;\u0026thinsp;4, based on the mRS score at admission. These groups did not significantly differ in the age at onset, proportion of adults, proportion of females, or relapse rate (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Compared with characteristics of patients with mild severity at admission, patients with initial mRS scores\u0026thinsp;\u0026gt;\u0026thinsp;4 had higher final mRS score (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and a higher proportion of individuals with poor prognosis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008).\u003c/p\u003e\u003cp\u003eEight patients had previous hypertension (9.8%), three had diabetes (3.7%), and three had coronary artery disease (3.7%). Seven (8.5%) patients had autoimmune disorders, including nephritis and thyroid dysfunction. Five patients had comorbid neoplasms (6.1%), including teratomas (uterus, ovary, and anterior mediastinum), brain gliomas, and esophageal smooth muscle tumors. Some of the patients smoked (26.8%) or consumed alcohol (19.5%). No significant differences were found in the medical and personal histories between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). A total of 33 patients presented with prodromal symptoms (40.2%), including fever, headache, and upper respiratory tract infection. Mental behavioral abnormalities (72.0%), speech disorders (52.4%), and cognitive dysfunction (51.2%) were the most common clinical manifestations. Depending on the clinical manifestations and economic conditions, patients received treatment regimens of hormones (89.0%), prophylaxis (65.9%), immunosuppressants (14.6%), rituximab (1.2%), and plasma exchange (17.1%). No significant differences (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) were found in the clinical presentation and treatment regimens between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic and clinical characteristics categorized by initial mRS scores.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003emRS\u0026thinsp;\u0026lt;\u0026thinsp;4\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003emRS\u0026thinsp;\u0026ge;\u0026thinsp;4\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDemographic characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at onset, years, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33 (21\u0026ndash;45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (18\u0026ndash;47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34 (27-43.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.590\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdults, \u0026ge;\u0026thinsp;18, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67 (81.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44 (77.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23 (92.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.133\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, female, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (47.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (52.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (36.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.165\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedical history\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (9.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (8.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.961\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (3.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (8.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.454\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutoimmune diseases\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (8.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.431\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebrovascular disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (3.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (6.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (7.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePersonal history\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDrinking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (19.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (15.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (28.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.199\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (26.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (26.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (28.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.874\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical manifestation\u003c/b\u003e, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProdrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33 (40.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (40.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.976\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConsciousness disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (36.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (44.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.356\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCognitive dysfunction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42 (51.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (52.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (48.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.699\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMental and behavioral abnormalities\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59 (72.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41 (71.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (72.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.995\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSeizures\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (36.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (35.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.671\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSpeech dysfunction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43 (52.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29 (50.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (56.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.669\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMovement disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (14.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (17.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (8.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.328\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInvoluntary movements\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (22.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (19.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (28.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.381\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutonomic dysfunction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (12.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (12.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (12.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleep dysfunction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (29.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (26.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (36.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.375\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTherapy regimens, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCorticosteroid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73 (89.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (91.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (84.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.335\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmunosuppressant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (14.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (19.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (4.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntravenous immunoglobulin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (65.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39 (68.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.459\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRituximab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (17.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (12.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (28.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.082\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFinal mRS scores, median (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0\u0026ndash;2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (1\u0026ndash;3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePoor prognosis, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (15.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (9.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (32.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.008*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRelapse, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (23.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (22.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (24.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.906\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFollow-up time, median (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37.70\u003c/p\u003e\u003cp\u003e(24.23\u0026ndash;55.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37.77\u003c/p\u003e\u003cp\u003e(25.64\u0026ndash;56.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35.63\u003c/p\u003e\u003cp\u003e(20.58\u0026ndash;55.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.650\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eContinuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (IQR\u0026thinsp;=\u0026thinsp;25th\u0026thinsp;\u0026minus;\u0026thinsp;75th percentile), and categorical variables were described as percentages (%)\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003emRS, modified Rankin scale; PE,plasma exchange\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Statistically significant difference\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eLaboratory test and imaging results of patients with anti-NMDAR encephalitis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAll patients in this cohort tested positive for CSF anti-NMDAR antibodies, and 41 tested positive for serum antibodies (50.0%). Among the serum-related parameters, C3 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) and C4 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.032) levels were significantly higher in the mRS\u0026thinsp;\u0026ge;\u0026thinsp;4 group than in the mRS\u0026thinsp;\u0026lt;\u0026thinsp;4 group. No significant differences in serum leukocyte, monocyte, lymphocyte, and neutrophil counts, or in IgG and albumin levels were found between the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Among the CSF parameters, CSF IgG (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.019), albumin (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010), Q-IgG (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027), and Q-Alb (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020) levels were significantly higher in the mRS\u0026thinsp;\u0026ge;\u0026thinsp;4 group than in the mRS\u0026thinsp;\u0026lt;\u0026thinsp;4 group. There were no significant differences in CSF pressure, WCC, protein quantification, glucose, chloride, or IgG index between the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05 for all parameters).\u003c/p\u003e\u003cp\u003eRegarding the imaging presentations, 55 (67.1%) patients had abnormal head MRI findings. The lesions were most commonly located in the lobes and sulci (39/55, 70.9%), paraventricular white matter (18/55, 32.7%), and basal ganglia (12/55, 21.8%). In some patients, lesions were located in the thalamus (7/55, 12.7%), brainstem (6/55, 10.9%), cerebellum (5/55, 9.1%), hippocampus (4/55, 7.3%), insula (4/55, 7.3%), pituitary gland (2/55, 3.6%), and deep brain white matter (2/55, 3.6%). No significant difference (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) was observed in the location of the lesions on head MRI between the groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLaboratory test and imaging results categorized by initial mRS scores.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003emRS\u0026thinsp;\u0026lt;\u0026thinsp;4\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003emRS\u0026thinsp;\u0026ge;\u0026thinsp;4\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLaboratory test results\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum, median (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWCC, *10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.59 (6.60-11.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8.48 (6.56\u0026ndash;12.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.90 (6.67\u0026ndash;10.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.825\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocytes, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.51 (0.37\u0026ndash;0.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.50 (0.34\u0026ndash;0.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.60 (0.46\u0026ndash;0.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.147\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.54 (1.09\u0026ndash;2.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.51 (1.13\u0026ndash;2.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.56 (1.05\u0026ndash;2.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.751\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.93 (4.42\u0026ndash;9.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5.94 (4.50-10.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.89 (4.42\u0026ndash;8.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.513\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3, g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.85 (9.40\u0026ndash;13.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.10 (9.15\u0026ndash;12.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12.30 (10.60-13.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.012*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4, g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.43 (1.92\u0026ndash;2.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.40 (1.92\u0026ndash;2.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.90 (2.10\u0026ndash;3.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.032*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgG, mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.60 (8.72\u0026ndash;13.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.80 (8.92\u0026ndash;13.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.10 (8.31\u0026ndash;13.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.375\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40.83\u003c/p\u003e\u003cp\u003e(37.58\u0026ndash;44.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e40.75\u003c/p\u003e\u003cp\u003e(37.55\u0026ndash;44.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e41.20\u003c/p\u003e\u003cp\u003e(38.15\u0026ndash;44.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.650\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnti-NMDAR antibody (+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32 (56.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9 (36.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.093\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCSF, median (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePressure, mmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e164.00\u003c/p\u003e\u003cp\u003e(133.75-228.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e160.00\u003c/p\u003e\u003cp\u003e(137.50\u0026ndash;230.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e180.00\u003c/p\u003e\u003cp\u003e(130.00-235.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.912\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWCC, *10\u003csup\u003e6\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.00 (4.00-56.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10.00 (4.00\u0026ndash;38.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20.00 (4.00\u0026ndash;84.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.377\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProtein, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.37 (0.26\u0026ndash;0.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.37 (0.26\u0026ndash;0.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.34 (0.28\u0026ndash;0.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.972\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlucose, mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.43 (2.79\u0026ndash;4.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.42 (2.87\u0026ndash;4.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.49 (2.78\u0026ndash;4.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.429\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChloride, mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e126.00\u003c/p\u003e\u003cp\u003e(124.00-128.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e126.00\u003c/p\u003e\u003cp\u003e(123.50\u0026ndash;128.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e126.00\u003c/p\u003e\u003cp\u003e(124.65-128.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.724\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgG, mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41.65\u003c/p\u003e\u003cp\u003e(25.98\u0026ndash;67.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38.00\u003c/p\u003e\u003cp\u003e(24.95\u0026ndash;58.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e64.70\u003c/p\u003e\u003cp\u003e(35.80-88.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.019\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e194.30\u003c/p\u003e\u003cp\u003e(132.75\u0026ndash;305.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e161.70\u003c/p\u003e\u003cp\u003e(118.10-282.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e271.00\u003c/p\u003e\u003cp\u003e(167.40-476.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.010\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eQ-IgG\u003c/b\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.83 (2.09\u0026ndash;6.79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.03 (1.90\u0026ndash;5.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.61 (2.93\u0026ndash;8.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.027\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eQ-Alb\u003c/b\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.69 (3.13\u0026ndash;8.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.26 (2.91\u0026ndash;7.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6.16 (3.99\u0026ndash;11.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.020\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIgG index\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.72 (0.57\u0026ndash;0.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.73 (0.52\u0026ndash;0.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.70 (0.61\u0026ndash;0.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.813\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAbnormal head-MRI, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (67.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37 (64.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e18 (72.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.530\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebral lobes and sulcus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (70.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25 (67.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14 (77.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.536\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeep WM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (5.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePeriventricular WM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (32.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (37.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (22.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.361\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThalamus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (12.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (16.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.671\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBasal ganglia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (21.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8 (21.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4 (22.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHippocampus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (7.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (5.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.590\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInsula\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (7.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3 (8.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePituitary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebellum\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBrainstem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (10.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.651\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eContinuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (IQR\u0026thinsp;=\u0026thinsp;25th\u0026thinsp;\u0026minus;\u0026thinsp;75th percentile), and categorical variables were described as percentages (%)\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003emRS, modified Rankin scale; WCC, white cell count; anti-NMDAR, anti-N-methyl-d-aspartate receptor; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; WM, white matter\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Q-IgG is the ratio of CSF IgG to serum IgG; \u003csup\u003eb\u003c/sup\u003e Q-Alb is the ratio of CSF albumin to serum albumin\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Statistically significant difference\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eCorrelation analysis of clinical parameters and disease severity\u003c/em\u003e\u003c/p\u003e\u003cp\u003eSpearman analysis showed that serum C3 (r\u0026thinsp;=\u0026thinsp;0.327, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), CSF albumin (r\u0026thinsp;=\u0026thinsp;0.378, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), Q-IgG (r\u0026thinsp;=\u0026thinsp;0.329, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), and Q-Alb (r\u0026thinsp;=\u0026thinsp;0.334, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) significantly and positively correlated with mRS score at disease onset in patients with anti-NMDAR encephalitis. CSF IgG (r\u0026thinsp;=\u0026thinsp;0.284, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010) and serum C4 (r\u0026thinsp;=\u0026thinsp;0.276, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) were significantly associated with disease severity; however, the correlation was weak. No correlation was found between serum IgG, serum albumin, CSF WCC, IgG index, and initial mRS scores (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelation analysis of clinical parameters and initial mRS scores.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.327\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.003*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.276\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.012*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum IgG, mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;0.187\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.092\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum albumin, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.092\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.412\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF WCC, \u0026times;10\u003csup\u003e6\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.117\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.297\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF IgG, mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.284\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.010*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF albumin, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.378\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-IgG\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.329\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.003*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-Alb\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.334\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.002*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgG index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.035\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.752\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003emRS, modified Rankin scale; WCC, white cell count; CSF, cerebrospinal fluid.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003ea\u003c/sup\u003eQ-IgG, ratio of CSF IgG to serum IgG\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003eb\u003c/sup\u003eQ-Alb, ratio of CSF albumin to serum albumin\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Statistically significant difference\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eCorrelation analysis of serum complement levels and CSF parameters\u003c/em\u003e\u003c/p\u003e\u003cp\u003eSpearman analysis showed that serum C3 (r\u0026thinsp;=\u0026thinsp;0.227, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041) significantly correlated with CSF IgG levels, but the correlation was weak. In addition, serum C3 significantly correlated with CSF albumin (r\u0026thinsp;=\u0026thinsp;0.365, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and Q-Alb (r\u0026thinsp;=\u0026thinsp;0.307, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) but not with serum IgG, albumin, CSF WCC, or Q-IgG (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Serum C4 (r\u0026thinsp;=\u0026thinsp;0.218, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049) also positively but weakly correlated with CSF albumin (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelation analysis of serum complement levels and CSF parameters.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum IgG, mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.846\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.045\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.689\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum albumin, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.211\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.852\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF WCC, *10\u003csup\u003e6\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.902\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.077\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.492\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF IgG, mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.227\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.041*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.177\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.113\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF albumin, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.365\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.218\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.049*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-IgG\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.071\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.136\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.224\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-Alb\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.307\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.005*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.188\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.091\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgG index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.067\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.547\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.847\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eWCC, white cell count; CSF, cerebrospinal fluid\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Q-IgG is the ratio of CSF IgG to serum IgG; \u003csup\u003eb\u003c/sup\u003e Q-Alb is the ratio of CSF albumin to serum albumin\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Statistically significant difference\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eMediating role of BBB injury between serum C3 and disease severity in anti-NMDAR encephalitis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe results of mediation analysis are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Serum C3 had a significant effect on Q-Alb (a: β\u0026thinsp;=\u0026thinsp;0.32, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), and Q-Alb and had a significant effect on the initial mRS (b: β\u0026thinsp;=\u0026thinsp;0.27, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017). Serum C3 had a significant effect on initial mRS (c ': β\u0026thinsp;=\u0026thinsp;0.23, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038), and the direct effect was 0.124 (95% confidence interval [CI]: 0.069\u0026ndash;0.241), accounting for 72.9% of the total effect. After adding the intermediary variable, the effect of serum C3 on the severity of disease mediated by BBB injury was still significant (c: β\u0026thinsp;=\u0026thinsp;0.32, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). The indirect effect was 0.046 (95% CI: 0.004\u0026ndash;0.098), accounting for 27.1% of the total effect. BBB injury played a partial mediating role between serum C3 and disease severity.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eThe mediating role of BBB injury between serum C3 and disease severity in anti-\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEffect\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLLCI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eULCI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal effect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.170\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.057\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.056\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.284\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDirect effect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.124\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.059\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.069\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.241\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndirect effect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.046\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.098\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eanti-NMDAR, anti-N-methyl-d-aspartate receptor; BBB, blood-brain barrier; SE, standard error; LLCI, lower level of confidence interval; ULCI, upper level of confidence interval.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eAnalysis of risk factors for disease prognosis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eUnivariate analysis showed that serum C3 (odds ratio [OR]\u0026thinsp;=\u0026thinsp;1.53, 95% CI\u0026thinsp;=\u0026thinsp;1.13\u0026ndash;2.08, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007) and initial mRS (OR\u0026thinsp;=\u0026thinsp;2.49, 95% CI\u0026thinsp;=\u0026thinsp;1.33\u0026ndash;4.66, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) significantly positively correlated with the prognosis (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). No correlation was found between age at onset, gender, past medical history, personal history, serum anti-NMDAR antibody status, serum leukocytes, monocytes, neutrophils, lymphocytes, C4, blood albumin, CSF pressure, WCC, glucose, chloride, IgG, Q-IgG, IgG index, Q-Alb, or abnormal head MRI findings, and disease prognosis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05 for all parameters). To eliminate the influence of confounding factors on the results, multivariate model I adjusted for age and gender. Model II adjusted for age, gender, C4, and Q-Alb. The results of both models showed that serum C3 level and initial mRS were independent risk factors for poor prognosis in patients with first-attack anti-NMDAR encephalitis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate binary logistic regression analysis of poor prognosis in patients with anti- NMDAR encephalitis.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.95\u0026ndash;1.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.493\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdults, \u0026ge;\u0026thinsp;18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.70 (0.17\u0026ndash;2.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.628\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.94 (0.29\u0026ndash;3.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.912\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.74 (0.08\u0026ndash;6.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.785\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.79 (0.23\u0026ndash;33.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.417\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutoimmune diseases\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.88 (0.10\u0026ndash;7.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.906\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.35 (0.14\u0026ndash;13.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.794\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDrinking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.29 (0.31\u0026ndash;5.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.724\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.79 (0.20\u0026ndash;3.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.740\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum anti- NMDAR antibody (+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.57 (0.17\u0026ndash;1.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.368\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum WCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.00 (0.86\u0026ndash;1.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.957\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.20 (0.02\u0026ndash;2.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.231\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.37 (0.67\u0026ndash;2.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.388\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.97 (0.83\u0026ndash;1.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.710\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.53 (1.13\u0026ndash;2.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.007*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.52 (0.73\u0026ndash;3.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.263\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum IgG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.92 (0.81\u0026ndash;1.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.242\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.01 (0.91\u0026ndash;1.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.799\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF pressure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.00 (1.00-1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.272\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF WCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.01 (1.00-1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.279\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF glucose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.55 (0.25\u0026ndash;1.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.130\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF chloride\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.03 (0.90\u0026ndash;1.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.688\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF IgG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.01 (1.00-1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.392\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.00 (1.00-1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.266\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-IgG\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.05 (0.93\u0026ndash;1.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.457\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-Alb\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.08 (0.95\u0026ndash;1.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.255\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgG index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.14 (0.47\u0026ndash;2.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.769\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbnormal head-MRI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.13 (0.31\u0026ndash;4.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.857\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial mRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.49 (1.33\u0026ndash;4.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.004*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eanti-NMDAR, anti-N-methyl-d-aspartate receptor; OR, odds ratio; CI, confidence interval; WCC, white cell count; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; mRS, modified Rankin scale.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003ea\u003c/sup\u003e Q-IgG is the ratio of CSF IgG to serum IgG; \u003csup\u003eb\u003c/sup\u003e Q-Alb is the ratio of CSF albumin to serum albumin\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Statistically significant difference\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate binary logistic regression analysis of poor prognosis in patients with anti-NMDAR encephalitis.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eModel I\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eModel II\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.97(0.91\u0026ndash;1.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.258\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.96(0.91\u0026ndash;1.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.232\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.34 (0.32\u0026ndash;5.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.687\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.30 (0.30\u0026ndash;5.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.724\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.50 (1.05\u0026ndash;2.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.027*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.60 (1.08\u0026ndash;2.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.020*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial mRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.33 (1.16\u0026ndash;4.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.017*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.49 (1.17\u0026ndash;5.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.018*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.69 (0.27\u0026ndash;1.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.420\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-Alb\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.99 (0.85\u0026ndash;1.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.855\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eanti-NMDAR, anti-N-methyl-d-aspartate receptor; mRS, modified Rankin scale.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Q-Alb is the ratio of CSF albumin to serum albumin\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Statistically significant difference\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eAnalysis of risk factors for disease relapse\u003c/em\u003e\u003c/p\u003e\u003cp\u003eKaplan\u0026ndash;Meier curves showed that elevated serum C3 level was a risk factor for relapse in patients with anti-NMDAR encephalitis (log-rank \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011). The relapse rate in the high C3 group was higher than that in the low C3 group over the same period, with relapse rates at 12 and 24 months of 4.9% and 7.3% in the high C3 group and 12.2% and 24.4% in the low C3 group, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eUnivariate Cox analysis showed that serum C3 (hazard ratio [HR]\u0026thinsp;=\u0026thinsp;1.34, 95% CI\u0026thinsp;=\u0026thinsp;1.10\u0026ndash;1.63, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004), CSF albumin (HR\u0026thinsp;=\u0026thinsp;1.00, 95%CI\u0026thinsp;=\u0026thinsp;1.00\u0026ndash;1.01, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), and Q-Alb (HR\u0026thinsp;=\u0026thinsp;1.17, 95%CI\u0026thinsp;=\u0026thinsp;1.07\u0026ndash;1.27, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) each had an independent effect on the first relapse (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). To eliminate the influence of confounding factors on the results, we screened the factors flagged by the univariate analysis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) as well as factors possibly associated with disease prognosis for inclusion in the multivariate Cox models. Model I was adjusted for age and gender, whereas model II was adjusted for age, gender, C4, and initial mRS scores. CSF albumin was excluded because of its covariance with Q-Alb. The results of both models showed that serum C3 and Q-Alb levels were independent risk factors for relapse in patients with first-attack anti-NMDAR encephalitis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate Cox analysis of relapse in patients with anti-NMDAR encephalitis.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e\u0026bull; Univariate analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR (95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01 (0.98\u0026ndash;1.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.690\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdults, \u0026ge;\u0026thinsp;18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.10 (0.49\u0026ndash;9.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.321\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.58 (0.23\u0026ndash;1.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.253\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01 (0.23\u0026ndash;4.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.992\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.53 (0.20-11.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.678\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutoimmune diseases\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.72 (0.39\u0026ndash;7.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.471\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.70 (0.09\u0026ndash;5.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.729\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDrinking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.95 (0.74\u0026ndash;5.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.177\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.51 (0.57\u0026ndash;4.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.405\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum anti- NMDAR antibody (+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.62 (0.25\u0026ndash;1.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.305\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum WCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.00 (0.89\u0026ndash;1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.985\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.03 (0.20\u0026ndash;5.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.973\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.95 (0.52\u0026ndash;1.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.877\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.00 (0.88\u0026ndash;1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.930\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.34 (1.10\u0026ndash;1.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.004*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.35 (0.78\u0026ndash;2.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.279\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum IgG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.95 (0.86\u0026ndash;1.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.229\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.96 (0.89\u0026ndash;1.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.361\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF pressure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.00 (0.99\u0026ndash;1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.792\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF WCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.00 (1.00-1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.255\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF glucose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.12 (0.71\u0026ndash;1.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.623\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF chloride\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.05 (0.95\u0026ndash;1.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.353\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF IgG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.00 (0.99\u0026ndash;1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.505\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF albumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.00 (1.00-1.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.003*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-IgG\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.04 (0.95\u0026ndash;1.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.347\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-Alb\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.17 (1.07\u0026ndash;1.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgG index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.48 (0.15\u0026ndash;1.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.226\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbnormal head-MRI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.49 (0.54\u0026ndash;4.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.446\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial mRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.16 (0.81\u0026ndash;1.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.409\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eanti-NMDAR, anti-N-methyl-d-aspartate receptor; HR, hazard ratio; CI, confidence interval; WCC, white cell count; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; mRS, modified Rankin scale\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003ea\u003c/sup\u003e Q-IgG is the ratio of CSF IgG to serum IgG; \u003csup\u003eb\u003c/sup\u003e Q-Alb is the ratio of CSF albumin to serum albumin\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Statistically significant difference\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate Cox analysis of relapse in patients with anti-NMDAR encephalitis.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eModel I\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eModel II\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at onset\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.99 (0.96\u0026ndash;1.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.650\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.99 (0.95\u0026ndash;1.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.527\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.30 (0.47\u0026ndash;3.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.613\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.36 (0.48\u0026ndash;3.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.562\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.28 (1.02\u0026ndash;1.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.032*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.32 (1.04\u0026ndash;1.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.023*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQ-Alb\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.13 (1.03\u0026ndash;1.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.009*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.14 (1.03\u0026ndash;1.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.009*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.82 (0.43\u0026ndash;1.58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.551\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial mRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.94 (0.64\u0026ndash;1.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.731\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eanti-NMDAR, anti-N-methyl-d-aspartate receptor; HR, hazard ratio; CI, confidence interval; mRS, modified Rankin scale\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Q-Alb is the ratio of CSF albumin to serum albumin\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Statistically significant difference\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eSensitivity analysis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAfter we excluded patients with autoimmune diseases from the sensitivity analysis, complement C3 and initial mRS were still associated with poor prognosis in patients with anti-NMDAR encephalitis in both models (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Supplementary Table\u0026nbsp;1). This is consistent with the results in the overall population, confirming that complement C3 and initial mRS correlate with disease prognosis independently of autoimmune disease. Similar results were observed in the sensitivity analysis of the correlation of disease relapse. After excluding patients with autoimmune diseases, complement C3 and Q-Alb were still significantly associated with disease relapse (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Supplementary Table\u0026nbsp;2).\u003c/p\u003e\u003cp\u003eTo further analyze the effect of gender on the results, stratified and interaction analyses were performed. No interactions between gender and complement C3 or initial mRS were observed in the analysis of risk factors for poor prognosis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In the analysis of risk factors for disease relapse, gender did not interact with complement C3 or Q-Alb either (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Supplementary Table\u0026nbsp;3). Likewise, no statistically significant differences were found in the correlations between complement C3 and disease outcomes in patients of different genders.\u003c/p\u003e\u003cp\u003e\u003cem\u003eDiagnostic value of serum C3 in the prognosis of patients with anti-NMDAR encephalitis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe diagnostic value of serum C3 level in the assessment of prognosis and relapse in patients with anti-NMDAR encephalitis was analyzed by ROC curves. For disease prognosis, the AUC was 0.748 (95% CI\u0026thinsp;=\u0026thinsp;0.61\u0026ndash;0.89, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005), with an optimal cut-off value for C3 of 13.25 g/dL, sensitivity of 0.615, and specificity of 0.841. When serum C3 was \u0026ge;\u0026thinsp;13.25 g/dL, the risk of poor disease prognosis was high. For disease relapse, the AUC was 0.697, the best cutoff value was C3\u0026thinsp;=\u0026thinsp;11.4 g/dL, with sensitivity of 0.737 and specificity of 0.667 (95% CI\u0026thinsp;=\u0026thinsp;0.56\u0026ndash;0.84, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009). The risk of disease relapse was high when serum C3 level was \u0026gt;\u0026thinsp;11.4 g/dL. (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe retrospectively analyzed data from 82 patients with anti-NMDAR encephalitis, primarily from northern China, and established the following: 1) serum C3 and Q-Alb positively correlated with disease severity in patients with anti-NMDAR encephalitis, and serum C3 level significantly positively correlated with the extent of BBB injury, 2) BBB injury mediated the effect of serum C3 on disease severity, 3) serum C3 was an independent risk factor for poor prognosis and disease relapse.\u003c/p\u003e\u003cp\u003ePatients in our cohort had a higher median onset age (33 [IQR 21\u0026ndash;45] years) compared to the reported ages of onset in other Chinese anti-NMDAR encephalitis studies [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This may be related to the particular healthcare system in Tianjin, which is characterized by a large number of specialized hospitals. Our hospital specializes in brain functions and receives few infants and children. The proportion of adult patients in this cohort was 81.7%, which also affected the median age at onset. The proportion of females in this cohort was 47.6%, which may be related to the different sample sizes.\u003c/p\u003e\u003cp\u003eThe pathogenesis of AE may involve tumor-derived antigen-triggered autoimmunity [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], viral infection-induced antigen exposure [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], or defective immune tolerance mechanisms [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. High complement levels are associated with infections and tumors [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The complement system is an important part of the innate immune response. Most complement proteins are produced in the liver and circulate in blood and lymph [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. C3 and C4 are the core components of the complement system, and complement C3, at the intersection of the three complement activation pathways, is considered the central molecule that ultimately drives the complement cascade reaction [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePrevious studies have reported increased complement protein expression and complement signaling activation in autopsy tissues from patients with NMO and in hsAQP4-IgG passive transfer mouse models [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Serum levels of complement C3 and C4 as well as CSF levels of C3 are elevated in patients with MS compared with their levels in healthy controls or in patients with non-inflammatory neurological diseases [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The intrathecal activation products of the classical and alternative pathways (C4a, C3a, and Ba) strongly correlate with MS severity [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Complement activation is significantly increased in children and adults with MOGAD. This suggests that activated complement proteins contribute to CNS tissue damage [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Recent studies have found that serum C3 and C4 levels are elevated during the acute phase response and correlate with disease severity [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], consistent with our findings. We found that serum C3 level positively correlated with the severity of the first-attack anti-NMDAR encephalitis. Patients with severe disability (mRS\u0026thinsp;\u0026ge;\u0026thinsp;4) demonstrated significantly elevated C3 and C4 levels compared to those in patients with milder symptoms (mRS\u0026thinsp;\u0026lt;\u0026thinsp;4). Therefore, we hypothesized that elevated serum C3 and C4 levels reflect a systemic inflammatory response in the disease. We also investigated the correlation between serum complement C3 and prognosis of anti-NMDAR encephalitis, and found that baseline serum C3 level was an independent predictor for poor prognosis and relapse of the disease (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). When serum C3\u0026thinsp;\u0026ge;\u0026thinsp;13.25 g/dL, the risk of poor disease prognosis is high, and when serum C3\u0026thinsp;\u0026ge;\u0026thinsp;11.4g/dL, the risk of disease relapse is high. The sensitivity and stratified analysis confirmed the reliability of our results.\u003c/p\u003e\u003cp\u003eMartinez-Hernandez et al. demonstrated that anti-NMDAR antibodies (immunoglobulin G (IgG) 1 and IgG3 isoforms) are produced within the sheaths of antibody-secreting cells infiltrating the CNS of patients with anti-NMDAR encephalitis, which may activate the complement system [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Anti-NMDAR antibodies synthesized in the CNS of patients may cross the intact BBB into the bloodstream through leaky areas, which activate the serum complement system, leading to elevated serum complement levels associated with intense inflammation and oxidative stress [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Thus, severely impaired patients may experience a stronger complement-mediated inflammatory response. Complement-mediated neuronal toxicity in anti-CASPR2 and anti-LGI1 encephalitis has been supported by autopsy findings [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. H\u0026ouml;oftberger et al. reported that in all MOGAD cases, some deposition of activated complement in lesions was observed [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Characteristic patterns of complement deposition activated at the edges of the vascular centers and rosettes were also found in patients with NMOSD [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. However, antibodies against NMDAR encephalitis could bind to the complement in vitro, and no complement deposition was detected in the brains of these patients [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Therefore, we hypothesized that the effects of the complement system on disease progression in anti-NMDAR encephalitis do not rely on effector mechanisms associated with end-pathway activation and membrane attack complex formation but rather impair neuronal cell function through non-complement deposition. It has been suggested that synaptic abnormalities occurring in the gray matter of patients with progressive MS are related to the complement system activation [\u003cspan additionalcitationids=\"CR44\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Microglia play a crucial role in maintaining synaptic plasticity [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMichailidou et al. showed co-localization of the activated C1q-C3 axis with microglia and lysosomes in the hippocampus of patients with MS. Neurons in this region showed signs of damage, decreased density of presynaptic terminals, and increased immunoreactivity for mitochondrial stress protein mtHSP70 [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. This suggests that in the hippocampus of patients with MS, complement labels synapses to be phagocytosed by microglia, which in turn affects neuronal function [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. The primary molecular mechanism of anti-NMDAR encephalitis is autoantibody-mediated NMDAR hypofunction at neuronal synapses [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Whether the complement system affects synaptic function through microglial activation, which, in turn, affects disease progression and prognosis, requires further investigation.\u003c/p\u003e\u003cp\u003eBBB destruction can occur early in anti-NMDAR encephalitis, leading to neuronal damage [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This is consistent with our results, in which CSF albumin, Q-IgG, and Q-Alb were positively associated with anti-NMDAR encephalitis disease severity (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). In anti-NMDAR encephalitis observed in the humanized mouse model injected with human peripheral blood mononuclear cells, claudin-5, occludin, ZO-1, and other tight junction proteins were downregulated, whereas the expression of inflammatory factors such as IL-1β was upregulated, leading to the invasion of antibodies and inflammatory cells into the central nervous system and aggravation of neurological damage [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. We also found that Q-Alb, a biomarker of BBB disruption, was associated with the disease relapse (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The possible mechanism is that after BBB disruption, inflammatory factors are released continuously, forming a chronic neuroinflammatory environment and increasing the relapse risk. It may also be related to the instability of BBB function, as the residual antibody may still enter the brain and increase the risk of relapse. The specific mechanism of BBB disruption leading to the recurrence of anti NMDAR encephalitis needs further investigation.\u003c/p\u003e\u003cp\u003eThe BBB is particularly vulnerable to complement, as it is exposed to circulating and locally synthesized complement proteins. In our study, serum C3 level positively correlated with CSF albumin and Q-Alb. Our findings corroborate prior observations in patients with NMOSD [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The mediation analysis proved that BBB disruption mediated the effect of C3 on disease severity, which may reveal an important way for complement system to play an inflammatory role in anti-NMDAR encephalitis. BBB dysfunction may be associated with complement dysregulation, and when the complement system is overwhelmed, complement activation may impair BBB integrity [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Serum C3 may be a potential biomarker reflecting BBB damage in anti-NMDAR encephalitis.\u003c/p\u003e\u003cp\u003eMost complement proteins do not cross the BBB. They are expressed by brain-resident cells and enter the brain when the BBB is compromised [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Microglia and astrocytes are thought to be the main producers of complement C3, with neurons, endothelial cells, and oligodendrocytes being additional producers [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Previous studies have shown that microglia C3-C3aR signaling plays a crucial role in the pathogenesis of demyelination and neurodegenerative diseases by regulating alternative complement pathways. Activated M1 microglia release pro-inflammatory cytokines [\u003cspan additionalcitationids=\"CR55\" citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. Overexpression of complement C3 in A1 astrocytic glial cells of a mouse model of MS during the acute phase of the disease induced neuronal and oligodendrocyte death and impaired oligodendrocyte maturation [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. In a mouse model of NMO, AQP4 autoantibody-stimulated astrocytes released complement C3. This complement binds to C3aR, which disrupts neuronal development by inhibiting β-catenin signaling [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Endothelial cells of cerebral microvessels produce complement regulatory proteins and components of classical and alternative pathways [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. The complement activation products C3a and C5a induce brain endothelial cell activation and increase the infiltration of inflammatory cells into the brain by increasing the expression of P-selectin, E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. We hypothesized that antibodies would disrupt the BBB in anti-NMDAR encephalitis. This disruption allows serum complement to infiltrate the brain, potentially intensifying neuroinflammation associated with anti-NMDAR encephalitis. Additionally, complement activation in astrocytes, microglia, and vascular endothelial cells may aggravate BBB damage, leading to secondary neurological issues deficits. The pathological mechanism by which complement C3 aggravates the severity of anti-NMDAR encephalitis through BBB disruption and thereby leads to poor prognosis remains to be determined.\u003c/p\u003e\u003cp\u003eThe complement therapy drug eculizumab showed beneficial effects in paroxysmal nocturnal hemoglobinuria and MG [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Other complement inhibitors, such as ravulizumab, zilucoplan, and pozelimab, are under development [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. In clinical practice, focusing on serum complement levels in the early stages of pathogenesis and using complement inhibitors/antagonists provides a new treatment possibility, which may be necessary for protecting the BBB, mitigating disease progression, and reducing the risk of relapse. Animal and clinical studies are warranted to confirm this.\u003c/p\u003e\u003cp\u003eThis study has some limitations. First, this was a single-center retrospective study, and a multicenter prospective study with a larger sample size and long-term follow-up is needed to confirm the findings presented herein. Second, some difficult to control confounding factors, such as living and dietary habits as well as intake of different medications, may have impacted the outcomes of this study. Third, our conclusions may be affected by selection bias, as some cases were excluded owing to incomplete clinical information and others because of incomplete clinical data and loss to follow up.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis is the first study in which serum complement C3 was found to correlate with BBB injury and prognosis in patients with anti-NMDAR encephalitis. We also demonstrated the mediating role of BBB disruption on the relationship between C3 and disease severity. Serum complement C3 level was an independent predictor for poor prognosis and relapse of anti-NMDAR encephalitis. Serum C3 may aggravate the severity of anti-NMDAR encephalitis through BBB disruption, thus leading to poor prognosis. This suggests that complement C3 level must be monitored at early stages of the disease to assess the risk of relapse and improve patient prognosis. Inhibitors targeting complement or complement receptors are potential therapeutic targets for anti-NMDAR encephalitis. However, the specific mechanism of the complement system involvement in BBB disruption and neurological dysfunction in anti-NMDAR encephalitis requires further studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eautoimmune encephalitis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAUC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003earea under the ROC curve\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBBB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eblood\u0026ndash;brain barrier\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003econfidence interval\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecentral nervous system\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecerebrospinal fluid\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGBS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGuillain\u0026ndash;Barr\u0026eacute; syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehazard ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIgG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eimmunoglobulin G\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emyasthenia gravis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMOGAD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emyelin oligodendrocyte glycoprotein antibody\u0026ndash;associated disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emagnetic resonance imaging\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003emRS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emodified Rankin scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emultiple sclerosis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNMDAR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eN-methyl-D-aspartate receptor\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNMOSD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eneuromyelitis optica spectrum disorder\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eodds ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eQ-Alb\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ealbumin quotient\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eROC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ereceiver operating characteristic\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWCC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ewhite cell count\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study followed the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Huanhu Hospital (202410281325000227905). Written informed consent to participate in this study was provided by the participants\u0026rsquo;\u0026nbsp;legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)\u0026rsquo;\u0026nbsp;legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in Supplementary Table 4; further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Tianjin Health Commission Science and Technology Projects (TJWJ2021QN061 and ZC20134) and Tianjin Key Medical Discipline (Specialty) Construction Project (No. TJYXZDXK-052B).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors made a significant contribution to the study. The authors\u0026rsquo;\u0026nbsp;responsibilities were as follows: ZJW conceived and designed the research.ZJW, YLQ, WZY and LYM organized the database.ZJW and LWX performed the statistical analysis. ZJW and WZY conducted regular follow-up of all cases. ZJW wrote the first draft of the manuscript. LL, XL and YW revised the manuscript critically. All authors approved the final version of the manuscript. They agreed on the journal to which the article has been submitted, and agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10 1:63\u0026ndash;74. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1474-4422(10)70253-2\u003c/span\u003e\u003cspan address=\"10.1016/s1474-4422(10)70253-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGranerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10 12:835\u0026ndash;44. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1473-3099(10)70222-x\u003c/span\u003e\u003cspan address=\"10.1016/s1473-3099(10)70222-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJmor F, Emsley HC, Fischer M, Solomon T, Lewthwaite P. The incidence of acute encephalitis syndrome in Western industrialised and tropical countries. Virol J. 2008;5:134. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1743-422x-5-134\u003c/span\u003e\u003cspan address=\"10.1186/1743-422x-5-134\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJosep D, Francesc G, Antibody-Mediated Encephalitis. N Engl J Med. 2018;378:9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMra1708712\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra1708712\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGong Z, Lao D, Wu Y, Li T, Lv S, Mo X, et al. Inhibiting PI3K/Akt-Signaling Pathway Improves Neurobehavior Changes in Anti-NMDAR Encephalitis Mice by Ameliorating Blood-Brain Barrier Disruption and Neuronal Damage. Cell Mol Neurobiol. 2023;43 7:3623\u0026ndash;37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10571-023-01371-3\u003c/span\u003e\u003cspan address=\"10.1007/s10571-023-01371-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJ\u0026eacute;z\u0026eacute;quel J, Johansson EM, Dupuis JP, Rogemond V, Gr\u0026eacute;a H, Kellermayer B, et al. Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients. Nat Commun. 2017;8(1:1791). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41467-017-01700-3\u003c/span\u003e\u003cspan address=\"10.1038/s41467-017-01700-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlexopoulos H, Dalakas MC. The immunobiology of autoimmune encephalitides. J Autoimmun. 2019;104:102339. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jaut.2019.102339\u003c/span\u003e\u003cspan address=\"10.1016/j.jaut.2019.102339\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7 12:1091\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1474-4422(08)70224-2\u003c/span\u003e\u003cspan address=\"10.1016/s1474-4422(08)70224-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJingxiao Z, Yatong L, Lei L, Feifei D, Yujing P, Qiuying M, et al. Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients. BMC Neurol. 2024;24(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12883-024-03724-x\u003c/span\u003e\u003cspan address=\"10.1186/s12883-024-03724-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen M, Edwards SR, Reutens DC. Complement in the Development of Post-Traumatic Epilepsy: Prospects for Drug Repurposing. J Neurotrauma. 2020;37 5:692\u0026ndash;705. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/neu.2019.6942\u003c/span\u003e\u003cspan address=\"10.1089/neu.2019.6942\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZiabska K, Ziemka-Nalecz M, Pawelec P, Sypecka J, Zalewska T. Aberrant Complement System Activation in Neurological Disorders. Int J Mol Sci. 2021;22:9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijms22094675\u003c/span\u003e\u003cspan address=\"10.3390/ijms22094675\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAeinehband S, Lindblom RP, Al Nimer F, Vijayaraghavan S, Sandholm K, Khademi M, et al. Complement component C3 and butyrylcholinesterase activity are associated with neurodegeneration and clinical disability in multiple sclerosis. PLoS ONE. 2015;10(4):e0122048. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0122048\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0122048\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKeller CW, Lopez JA, Wendel EM, Ramanathan S, Gross CC, Klotz L, et al. Complement Activation Is a Prominent Feature of MOGAD. Ann Neurol. 2021;90 6:976\u0026ndash;82. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ana.26226\u003c/span\u003e\u003cspan address=\"10.1002/ana.26226\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLin L, Wu Y, Hang H, Lu J, Ding Y. 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. Front Immunol. 2022;13:853891. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2022.853891\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2022.853891\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStathopoulos P, Dalakas MC. The role of complement and complement therapeutics in neuromyelitis optica spectrum disorders. Expert Rev Clin Immunol. 2022;18 9:933\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/1744666x.2022.2105205\u003c/span\u003e\u003cspan address=\"10.1080/1744666x.2022.2105205\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMin YG, Ju W, Seo JW, Ha YE, Ban JJ, Kwon YN, et al. Serum C3 complement levels predict prognosis and monitor disease activity in Guillain-Barr\u0026eacute; syndrome. J Neurol Sci. 2023;444:120512. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jns.2022.120512\u003c/span\u003e\u003cspan address=\"10.1016/j.jns.2022.120512\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDalakas MC. Role of complement, anti-complement therapeutics, and other targeted immunotherapies in myasthenia gravis. Expert Rev Clin Immunol. 2022;18 7:691\u0026ndash;701. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/1744666x.2022.2082946\u003c/span\u003e\u003cspan address=\"10.1080/1744666x.2022.2082946\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStascheit F, Chuquisana O, Keller CW, Ambrose PA, Hoffmann S, Gross CC, et al. Complement activation profiles in anti-acetylcholine receptor positive myasthenia gravis. Eur J Neurol. 2023;30 5:1409\u0026ndash;16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ene.15730\u003c/span\u003e\u003cspan address=\"10.1111/ene.15730\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShu Y, Chen C, Chen Y, Xu Y, Chang Y, Li R, et al. Serum complement levels in anti-N-methyl-d-aspartate receptor encephalitis. Eur J Neurol. 2018;25(1):178\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ene.13495\u003c/span\u003e\u003cspan address=\"10.1111/ene.13495\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu X, Fan K, Lin Q, Tang M, Wang Q, Huang E, et al. Serum-Derived Exosomal miR-140-5p as a Promising Biomarker for Differential Diagnosis of Anti-NMDAR Encephalitis With Viral Encephalitis. Front Immunol. 2022;13:840003. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2022.840003\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2022.840003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGraus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15 4:391\u0026ndash;404. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1474-4422(15)00401-9\u003c/span\u003e\u003cspan address=\"10.1016/s1474-4422(15)00401-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19 5:604\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/01.str.19.5.604\u003c/span\u003e\u003cspan address=\"10.1161/01.str.19.5.604\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrenner J, Mariotto S, Bastiaansen AEM, Paunovic M, Ferrari S, Alberti D, et al. Predictive Value of Serum Neurofilament Light Chain Levels in Anti-NMDA Receptor Encephalitis. Neurology. 2023;100 21:e2204\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/wnl.0000000000207221\u003c/span\u003e\u003cspan address=\"10.1212/wnl.0000000000207221\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu X, Lu Q, Huang Y, Fan S, Zhou L, Yuan J, et al. Anti-NMDAR encephalitis: A single-center, longitudinal study in China. Neurol Neuroimmunol Neuroinflamm. 2020;7(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/nxi.0000000000000633\u003c/span\u003e\u003cspan address=\"10.1212/nxi.0000000000000633\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTitulaer MJ, McCracken L, Gabilondo I, Armangu\u0026eacute; T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12 2:157\u0026ndash;65. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1474-4422(12)70310-1\u003c/span\u003e\u003cspan address=\"10.1016/s1474-4422(12)70310-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKreye J, Wenke NK, Chayka M, Leubner J, Murugan R, Maier N, et al. Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis. Brain. 2016;139:2641\u0026ndash;52. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/aww208\u003c/span\u003e\u003cspan address=\"10.1093/brain/aww208\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166\u0026ndash;77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ana.25131\u003c/span\u003e\u003cspan address=\"10.1002/ana.25131\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArmangue T, Spatola M, Vlagea A, Mattozzi S, C\u0026aacute;rceles-Cordon M, Martinez-Heras E, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol. 2018;17 9:760\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1474-4422(18)30244-8\u003c/span\u003e\u003cspan address=\"10.1016/s1474-4422(18)30244-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWalport MJ, Complement. First of two parts. N Engl J Med. 2001;344 14:1058\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/nejm200104053441406\u003c/span\u003e\u003cspan address=\"10.1056/nejm200104053441406\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJiang F, Liu H, Liu Z, Song J, Li L, Ding K, et al. High serum levels of complements C3 and C4 as novel markers for myeloma bone disease. Ann Hematol. 2017;96 2:331\u0026ndash;3. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00277-016-2863-z\u003c/span\u003e\u003cspan address=\"10.1007/s00277-016-2863-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZarkadis IK, Mastellos D, Lambris JD. Phylogenetic aspects of the complement system. Dev Comp Immunol. 2001;25. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0145-305x(01)00034-9\u003c/span\u003e\u003cspan address=\"10.1016/s0145-305x(01)00034-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 8\u0026ndash;9:745\u0026thinsp;\u0026ndash;\u0026thinsp;62; doi:.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNegro-Demontel L, Maleki AF, Reich DS, Kemper C. The complement system in neurodegenerative and inflammatory diseases of the central nervous system. Front Neurol. 2024;15:1396520. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fneur.2024.1396520\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2024.1396520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAsavapanumas N, Tradtrantip L, Verkman AS. Targeting the complement system in neuromyelitis optica spectrum disorder. Expert Opin Biol Ther. 2021;21 8:1073\u0026ndash;86. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/14712598.2021.1884223\u003c/span\u003e\u003cspan address=\"10.1080/14712598.2021.1884223\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarpanini SM, Torvell M, Morgan BP. Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System. Front Immunol. 2019;10:362. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2019.00362\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2019.00362\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLunemann JD, Hegen H, Villar LM, Rejdak K, Sao-Aviles A, Carbonell-Mirabent P, et al. Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024;11 4:e200270. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/nxi.0000000000200270\u003c/span\u003e\u003cspan address=\"10.1212/nxi.0000000000200270\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOechtering J, Stein K, Schaedelin SA, Maceski AM, Orleth A, Meier S, et al. Complement Activation Is Associated With Disease Severity in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024;11 2:e200212. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/nxi.0000000000200212\u003c/span\u003e\u003cspan address=\"10.1212/nxi.0000000000200212\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMartinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, Sangha N, Martinez-Lage M, Dalmau J. Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology. 2011;77 6:589\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/WNL.0b013e318228c136\u003c/span\u003e\u003cspan address=\"10.1212/WNL.0b013e318228c136\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDoi H, Matsushita T, Isobe N, Matsuoka T, Minohara M, Ochi H, et al. Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody. Mult Scler. 2009;15 3:304\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/1352458508099139\u003c/span\u003e\u003cspan address=\"10.1177/1352458508099139\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu Z, Tang Q, Wen J, Tang Y, Huang D, Huang Y, et al. Elevated serum complement factors 3 and 4 are strong inflammatory markers of the metabolic syndrome development: a longitudinal cohort study. Sci Rep. 2016;6:18713. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/srep18713\u003c/span\u003e\u003cspan address=\"10.1038/srep18713\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eH\u0026ouml;ftberger R, Guo Y, Flanagan EP, Lopez-Chiriboga AS, Endmayr V, Hochmeister S, et al. The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody. Acta Neuropathol. 2020;139 5:875\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00401-020-02132-y\u003c/span\u003e\u003cspan address=\"10.1007/s00401-020-02132-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 2002;125 Pt 7:1450\u0026ndash;61; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/awf151\u003c/span\u003e\u003cspan address=\"10.1093/brain/awf151\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBien CG, Vincent A, Barnett MH, Becker AJ, Bl\u0026uuml;mcke I, Graus F, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain. 2012;135:1622\u0026ndash;38. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/aws082\u003c/span\u003e\u003cspan address=\"10.1093/brain/aws082\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOlivero G, Taddeucci A, Vallarino G, Trebesova H, Roggeri A, Gagliani MC, et al. Complement tunes glutamate release and supports synaptic impairments in an animal model of multiple sclerosis. Br J Pharmacol. 2024;181 12:1812\u0026ndash;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/bph.16328\u003c/span\u003e\u003cspan address=\"10.1111/bph.16328\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePeterson JW, B\u0026ouml; L, M\u0026ouml;rk S, Chang A, Trapp BD. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001;50 3:389\u0026ndash;400. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ana.1123\u003c/span\u003e\u003cspan address=\"10.1002/ana.1123\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWerneburg S, Jung J, Kunjamma RB, Ha SK, Luciano NJ, Willis CM, et al. Targeted Complement Inhibition at Synapses Prevents Microglial Synaptic Engulfment and Synapse Loss in Demyelinating Disease. Immunity. 2020;52. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.immuni.2019.12.004\u003c/span\u003e\u003cspan address=\"10.1016/j.immuni.2019.12.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 1:167\u0026thinsp;\u0026ndash;\u0026thinsp;82.e7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu Y, Dissing-Olesen L, MacVicar BA, Stevens B, Microglia. Dynamic Mediators of Synapse Development and Plasticity. Trends Immunol. 2015;36 10:605\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.it.2015.08.008\u003c/span\u003e\u003cspan address=\"10.1016/j.it.2015.08.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMichailidou I, Willems JG, Kooi EJ, van Eden C, Gold SM, Geurts JJ, et al. Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus. Ann Neurol. 2015;77 6:1007\u0026ndash;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ana.24398\u003c/span\u003e\u003cspan address=\"10.1002/ana.24398\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaez-Calveras N, Stuve O. The role of the complement system in Multiple Sclerosis: A review. Front Immunol. 2022;13:970486. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2022.970486\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2022.970486\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIngram G, Hakobyan S, Hirst CL, Harris CL, Pickersgill TP, Cossburn MD, et al. Complement regulator factor H as a serum biomarker of multiple sclerosis disease state. Brain. 2010;133:1602\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/awq085\u003c/span\u003e\u003cspan address=\"10.1093/brain/awq085\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShu Y, Peng F, Zhao B, Liu C, Li Q, Li H, et al. Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model. J Neuroinflammation. 2023;20(1:164). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12974-023-02844-4\u003c/span\u003e\u003cspan address=\"10.1186/s12974-023-02844-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlexander JJ. Blood-brain barrier (BBB) and the complement landscape. Mol Immunol. 2018;102:26\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.molimm.2018.06.267\u003c/span\u003e\u003cspan address=\"10.1016/j.molimm.2018.06.267\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVeerhuis R. Histological and direct evidence for the role of complement in the neuroinflammation of AD. Curr Alzheimer Res. 2011;8 1:34\u0026ndash;58. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2174/156720511794604589\u003c/span\u003e\u003cspan address=\"10.2174/156720511794604589\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhu F, He P, Jiang W, Afridi SK, Xu H, Alahmad M, et al. Astrocyte-secreted C3 signaling impairs neuronal development and cognition in autoimmune diseases. Prog Neurobiol. 2024;240:102654. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pneurobio.2024.102654\u003c/span\u003e\u003cspan address=\"10.1016/j.pneurobio.2024.102654\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu L, Xu H, Chen S, Jiang W, Afridi SK, Wang Y, et al. Inhibition of complement C3 signaling ameliorates locomotor and visual dysfunction in autoimmune inflammatory diseases. Mol Ther. 2023;31 9:2715\u0026ndash;33. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ymthe.2023.07.017\u003c/span\u003e\u003cspan address=\"10.1016/j.ymthe.2023.07.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen T, Lennon VA, Liu YU, Bosco DB, Li Y, Yi MH, et al. Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion. J Clin Invest. 2020;130 8:4025\u0026ndash;38. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1172/jci134816\u003c/span\u003e\u003cspan address=\"10.1172/jci134816\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDubbelaar ML, Kracht L, Eggen BJL, Boddeke E. The Kaleidoscope of Microglial Phenotypes. Front Immunol. 2018;9:1753. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2018.01753\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2018.01753\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTakai Y, Misu T, Suzuki H, Takahashi T, Okada H, Tanaka S, et al. Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders. Brain. 2021;144 8:2401\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/awab102\u003c/span\u003e\u003cspan address=\"10.1093/brain/awab102\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu F, Zou Q, Ding X, Shi D, Zhu X, Hu W, et al. Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain. J Neuroinflammation. 2016;13:23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12974-016-0485-y\u003c/span\u003e\u003cspan address=\"10.1186/s12974-016-0485-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmets I, Titulaer MJ. Antibody Therapies in Autoimmune Encephalitis. Neurotherapeutics. 2022;19 3:823\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s13311-021-01178-4\u003c/span\u003e\u003cspan address=\"10.1007/s13311-021-01178-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"anti-N-methyl-d-aspartate receptor encephalitis, complement, blood–brain barrier, C3, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-7220180/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7220180/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAnti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune disease, with some patients experiencing poor clinical outcomes. Complement activation may contribute to disease progression, but its clinical significance remains unclear. This study investigated the correlation between serum complement C3 with blood\u0026ndash;brain barrier (BBB) injury and prognosis in anti-NMDAR encephalitis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis retrospective study enrolled 82 patients diagnosed with anti-NMDAR encephalitis at the Tianjin Huanhu Hospital. Spearman correlation analysis was used to assess the relationship between serum C3 level, disease severity, and BBB injury marker albumin quotient (Q-Alb). Binary logistic regression analysis and Cox proportional hazards models were used to investigate independent impact of serum C3 on disease prognosis and relapse. Sensitivity, interaction, and stratification analyses were performed to further verify the reliability of the results. Receiver operating characteristic curves were used to assess diagnostic value of serum C3 level for disease prognosis and relapse.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe median follow-up time of this study was 37.70 (24.23\u0026ndash;55.72) months. Serum C3 level significantly positively correlated with the initial modified Rankin scale (mRS) scores (r\u0026thinsp;=\u0026thinsp;0.327, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) and Q-Alb (r\u0026thinsp;=\u0026thinsp;0.307, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005). Mediation analysis showed that BBB injury mediated the effect of serum C3 on disease severity (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Multivariate logistic regression analysis showed that serum C3 was an independent risk factor for poor prognosis (odds ratio\u0026thinsp;=\u0026thinsp;1.60, 95% confidence interval [CI]\u0026thinsp;=\u0026thinsp;1.08\u0026ndash;2.39, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020). Multivariate Cox analysis showed that serum C3 (hazard ratio [HR]\u0026thinsp;=\u0026thinsp;1.32, 95% CI\u0026thinsp;=\u0026thinsp;1.04\u0026ndash;1.66, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023) and Q-Alb (HR\u0026thinsp;=\u0026thinsp;1.14, 95% CI\u0026thinsp;=\u0026thinsp;1.03\u0026ndash;1.26, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009) were significant predictors of relapse.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eBBB injury mediated the effect of serum C3 on disease severity in patients with anti-NMDAR encephalitis. Serum C3 was an independent risk factor for poor prognosis and disease relapse.\u003c/p\u003e","manuscriptTitle":"Role of serum complement C3 in blood–brain barrier injury and prognosis of anti-NMDAR encephalitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-03 06:12:43","doi":"10.21203/rs.3.rs-7220180/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-24T10:00:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-21T12:10:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"194560737428142489218216878237094952164","date":"2025-10-20T12:05:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-26T03:03:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"210856767045682069846091471693547000946","date":"2025-09-22T09:15:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"24025340267788670297255951204845460576","date":"2025-08-27T12:54:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-25T12:13:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-25T10:15:09+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-04T23:46:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-02T08:54:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-08-02T08:40:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a9f2a901-8e0f-41e1-8224-aa9942c87a26","owner":[],"postedDate":"September 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T16:04:52+00:00","versionOfRecord":{"articleIdentity":"rs-7220180","link":"https://doi.org/10.1186/s12883-026-04671-5","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2026-02-16 15:58:10","publishedOnDateReadable":"February 16th, 2026"},"versionCreatedAt":"2025-09-03 06:12:43","video":"","vorDoi":"10.1186/s12883-026-04671-5","vorDoiUrl":"https://doi.org/10.1186/s12883-026-04671-5","workflowStages":[]},"version":"v1","identity":"rs-7220180","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7220180","identity":"rs-7220180","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}