The field of autoimmune encephalitis (AE) has undergone a profound paradigm shift in diagnosis and treatment over the past decade. Previously considered a rare and difficult-to-recognize condition, AE is now established as a major category of inflammatory central nervous system diseases. This evolution has fundamentally changed how neurologists evaluate acute encephalitis, new-onset neuropsychiatric symptoms, and rapidly progressive cognitive dysfunction. The driving force behind this shift has been the ongoing discovery of specific neural autoantibodies, together with refined characterization of their associated clinical syndromes and underlying pathology mechanisms. Despite these advances, several challenges remain. Key issues include diagnosing seronegative AE, balancing standardized and individualized treatment strategies, and managing long-term cognitive and psychiatric sequelae. This article systematically reviews the major developments underlying this paradigm shift, analyzes the core challenges currently confronting the field, and outlines future directions for achieving more precise and comprehensive patients management.

PET imaging plays a crucial role in the diagnosis and management of autoimmune encephalitis (AE). By detecting the distribution of radiotracers, PET provides a direct visualization of cerebral metabolic activity, revealing distinct metabolic patterns associated with different types of AE. Furthermore, it allows for effective monitoring of disease progression and therapeutic response, offering robust support for clinical decision-making. This review aims to elucidate the cerebral ¹⁸F-FDG PET metabolic patterns in AE associated with various antibodies, and to discuss the applications of other emerging PET tracers, with the goal of advancing the precise diagnosis and treatment of this condition.

Central nervous system (CNS) autoimmune diseases are characterized by complex pathogenesis involving interactions among diverse immune cells originating from both the CNS and the peripheral immune system. Single-cell sequencing technology enables high-resolution expression profiling at the single-cell level, allowing precise characterization of cellular heterogeneity and functional phenotypic dynamic. In recent years, this technology has been increasingly applied to the study of CNS autoimmune diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), autoimmune encephalitis (AE), and myasthenia gravis (MG). Single-cell sequencing technology has shown unique advantage in elucidating the immunopathogenesis of disease, identifying pathogenic immune cell subsets, elucidating clonal evolution patterns, and facilitating the discovery of potential biomarkers and therapeutic targets. This review summarizes the development of single-cell sequencing technology and highlights the applications in CNS autoimmune diseases, with an emphasis on the implications for advancing the understanding of disease mechanisms and supporting precision diagnosis and targeted therapeutic strategies.

Objective To investigate the metabolic patterns of anti-glutamate decarboxylase 65 (GAD65) antibody-associated encephalitis using ¹⁸F-FDG PET, and to analyze the correlations between these patterns and clinical or neuroimaging features. Methods A total of 25 patients with anti-GAD65 antibody-associated encephalitis admitted to Beijing Tiantan Hospital, Capital Medical University, from January 2018 to July 2024 were enrolled. All patients underwent ¹⁸F-FDG PET imaging. The whole brain of each patient was segmented into 116 brain regions, and cerebellum-normalized standard uptake value ratio (SUVRc) was calculated for each region. Principal component analysis (PCA) was used to reduce the dimensionality of SUVRc, and k-means clustering algorithm was applied to divide the patients into 2 clusters. Pearson and partial correlation analyses were performed to explore the correlations between metabolic activity of key brain regions and clinical indicators or MRI volumes. Results PCA showed that the top 5 brain regions contributing most to Principal Component 1 were all located in the occipital lobe, in order of left cuneus, right cuneus, right lingual gyrus, left inferior occipital gyrus and right inferior occipital gyrus. The k-means clustering algorithm divided the patients into 2 clusters (14 cases in Cluster 1, 11 cases in Cluster 2). There were statistically significant differences in SUVRc of the left cuneus (F = 7.946, P = 0.000), right cuneus (F = 8.406, P = 0.000), right lingual gyrus (F = 9.447, P = 0.000), left inferior occipital gyrus (F = 17.036, P = 0.000), and right inferior occipital gyrus (F = 18.312, P = 0.000) between the 2 clusters and healthy controls. Further pairwise comparisons revealed that compared with the health controls, Cluster 2 had increased SUVRc in the left cuneus (t = 3.809, P = 0.000), right cuneus (t = 2.959, P = 0.000), right lingual gyrus (t = 3.726, P = 0.000), left inferior occipital gyrus (t = 3.948, P = 0.000), and right inferior occipital gyrus (t = 3.846, P = 0.000), so it was defined as the occipital lobe hypermetabolism cluster; Cluster 1 showed a decreasing trend in metabolic activity of these regions, thus defined as the non-occipital lobe hypermetabolism cluster. MRI volume analysis revealed that the brain regions with significant volume differences between the non-occipital lobe hypermetabolism cluster and occipital lobe hypermetabolism cluster were the cuneus (t = -2.214, P = 0.038), superior occipital gyrus (t = -2.213, P = 0.038), orbital gyrus (t = -2.829, P = 0.010), lateral part of the superior temporal gyrus (t = -2.246, P = 0.035), occipito-temporal medial sulcus (collateral sulcus), and lingual gyrus sulcus (t = -2.160, P = 0.042). Conclusions Different metabolic patterns of anti-GAD65 antibody-associated encephalitis were identified by ¹⁸F-FDG PET combined with cluster analysis, and their associations with clinical and neuroimaging features were revealed, which deepens the understanding of the pathophysiological mechanisms of this disease.

Objective To explore the cerebrospinal fluid (CSF) results of anti-aquaporin-4 (AQP4) IgG positive neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) and compare their similarities and differences to provide a reference for its diagnosis and differential diagnosis. Methods and Results From April 2019 to August 2023, 38 patients with serum AQP4 -IgG-positive for NMOSDs, 14 patients with MOGAD and 27 patients with GFAP-A who were hospitalised in General Hospital of Ningxia Medical University were selected. The clinical data and CSF pressure, cytology, biochemistry and IgG of the 3 groups were collected after admission. Compared with the NMOSDs group, the MOGAD group and the GFAP -A group, the CSF pressure (F = 10.530, P = 0.000), white blood cell (WBC) count (χ² = 11.892, P = 0.003), proportion of patients with WBC count ≥ 50 × 10⁶/L (χ² = 22.503, P = 0.000), proportion of eosinophils (χ² = 13.551, P = 0.001), protein quatification (χ² = 20.391, P = 0.000), glucose level (χ² = 8.653, P = 0.013), proportion of patients with glucose < 2.20 mmol/L (Fisher′s exact probability: P = 0.010), and IgG (χ² = 13.899, P = 0.001) were statistically significant. Further pairwise comparisons revealed that, compared with the NMOSDs group and the MOGAD group, the GFAP-A group had a higher CSF pressure (t = -80.012, P = 0.000; t = -61.222, P = 0.002), a higher WBC count (Z = -3.178, P = 0.001; Z = -2.618, P = 0.009), a higher proportion of cases with WBC count ≥ 50 × 10⁶/L (Z = -4.163, P = 0.000; Z = -3.173, P = 0.002), higher level of protein quantification (Z = -4.193, P = 0.000; Z = -3.373, P = 0.001) and IgG (Z = -2.925, P = 0.003; Z = -3.375, P = 0.001), and a lower glucose level (Z = 2.433, P = 0.015; Z = 2.561, P = 0.010). Compared with the NMOSDs group, the GFAP-A group had a higher proportion of cases with eosinophils (Z = 3.643, P = 0.000) and a lower proportion of glucose < 2.20 mmol/L (Z = 2.795, P = 0.005). Conclusions The CSF of NMOSDs and MOGAD patients is similar in terms of pressure, cytology and biochemistry. Compared with NMOSDs and MOGAD, the CSF pressure and WBC count of GFAP-A patients are higher, eosinophil infiltration is more common, protein quatification and IgG levels are significantly increased, and glucose levels are generally reduced. These features may aid in the diagnosis and differential diagnosis of GFAP-A.

Objective To explore clinical characteristics of myelin oligodendrocyte glycoprotein (MOG) antibody-associated cortical encephalitis. Methods and Results Retrospective analysis was conducted on clinical data of 8 patients diagnosed with MOG antibody-associated cortical encephalitis in Tianjin Huanhu Hospital from January 2021 to January 2025. The male-to-female ratio was 1∶1, with a mean age of (32.13 ± 13.21) years old. The initial symptoms were primarily headache, fever and epileptic seizures. All patients tested positive for serum anti-MOG antibodies. Cerebrospinal fluid (CSF) analysis showed elevated pressure in 6 cases, and an increased white blood cell count in 6 cases. No definitive evidence of neoplasms was identified in all patient. MRI showed unilateral (5 cases) or bilateral (3 cases) diffuse cortical FLAIR hyperintensity in 8 patients. The lesions involved the frontal lobes in 6 cases, temporal lobes in 6 cases, parietal lobes in 7 cases, and occipital lobes in 2 cases. All patients improved after treatment with glucocorticoid or intravenous immunoglobulin (IVIg). During follow-up, the relapse occurred in 3 patients, who subsequently recovered well after retreatment with glucocorticoid or IVIg, and experienced no further recurrence. Conclusions The clinical manifestations of MOG antibody-associated cortical encephalitis are non-specific. Head MRI shows unilateral or bilateral cortical abnormal signals, which are often misdiagnosed as viral encephalitis. Glucocorticoid is effective in combination with immunotherapy. Although some patients may experience recurrence, the symptoms of recurrence are mild. For patients with cortical encephalitis who have poor response to anti-infection treatment, it is necessary to be vigilant about MOG antibody-associated cortical encephalitis, identify it early and provide combination hormone and immunotherapy in a timely manner.

Objective To explore the individual features of acute symptomatic seizures across various subtypes of antibody-mediated autoimmune encephalitis (AE), and to identify the influencing factors for the progression to chronic epilepsy. Methods A total of 84 patients diagnosed with antibody-mediated AE at The First Affiliated Hospital of Dalian Medical University from January 2016 to December 2024 were included. The data collected encompassed society demographic information, clinical manifestations, long-term video-electroencephalography (LT-VEEG), MRI, treatment and prognostic outcomes. Univariate and multivariate stepwise Logistic regression analyses were conducted to identify influencing factors for the progression from acute symptomatic seizures to chronic epilepsy. Furthermore, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to determine the predictive efficacy of the influencing factors Results 1) The incidence of acute symptomatic seizures in antibody-mediated AE by different antibody subtypes was 85.71% (72/84). The primary seizure types were generalized tonic-clonic seizures (GTCS; 72.22%, 52/72), focal impaired consciousness seizure (FIC; 51.39%, 37/72), focal preserved consciousness seizure (FPC; 41.67%, 30/72), and focal to bilateral tonic-clonic seizure (FBTCS; 43.06%, 31/72), with status epilepticus (SE; 29.17%, 21/72) and subclinical electrical seizures (8.33%，6/72) were also frequently observed. Among them, the acute symptomatic seizures in anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated encephalitis (n = 35) manifested as mesial temporal lobe epilepsy (mTLE)-like seizures, faciobrachial dystonic seizures (FBDS), or both. In anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (n = 16) and anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis (n = 5), acute symptomatic seizures were primarily GTCS, often accompanied by focal seizures of neocortical origin, and were prone to SE. In anti-γ-aminobutyric acid receptor type B (GABA_BR, n = 12) antibody-associated encephalitis and anti-glutamic acid decarboxylase 65 (GAD65) antibody-associated encephalitis (n = 10), acute symptomatic seizures often presented as mTLE-like seizures. 2) Of the 72 patients with acute symptomatic seizures, 23 (31.94%) developed chronic epilepsy; among them, anti-GAD65 and anti-GABA_BR antibody-associated encephalitis had the highest proportions (8/ 8 and 8/12, respectively). 3) Logistic regression analysis showed limbic system atrophy was identified as risk factor (OR = 24.985, 95%CI: 2.873-217.304; P = 0.004)，while a normal blood neutrophil count was protective factor (OR = 0.172, 95%CI: 0.038-0.786; P = 0.023) for the progression from acute symptomatic seizures to chronic epilepsy. ROC curve showed that the AUC of limbic system atrophy and normal blood neutrophil count were 0.654 and 0.638, respectively. The AUC of the combined indicator increased to 0.784, indicating improved predictive efficacy (Z = 2.310, P = 0.021; Z = 2.715, P = 0.007). Conclusions Acute symptomatic seizures in antibody-mediated AE by various subtypes of antibodies exhibit both shared and distinct characteristics. Among them, patients with anti-GAD65 and anti-GABA_BR antibody-associated encephalitis have the highest proportions of developing chronic epilepsy. Limbic system atrophy serves as an independent risk factor, whereas a normal blood neutrophil count acts as an independent protective factor against the progression of acute symptomatic seizures to chronic epilepsy. The combined index has better predictive efficacy.

Objective To report and analyze clinical features of anti-seizure related 6 homolog like 2 (SEZ6L2) antibody-associated encephalitis, and review relevant literatures. Methods and Results Two patients were all diagnosed and treated by Ruijin Hospital, Shanghai Jiaotong University School of Medicine from January 2022 to July 2024. The clinical manifestations were mainly with ataxia, gait abnormalities, cognitive dysfunction and bradykinesia. One case exhibited dysautonomia. Cerebrospinal fluid (CSF) white cell counts were elevated, and both serum and CSF antibodies related to autoimmune encephalitis were negative. Further testing for anti-SEZ6L2 antibody revealed that CSF and (or) serum were positive. MRI showed cerebellar atrophy, while ¹⁸F-DPA714 PET/MRI indicated abnormal increased uptake in the cerebellum. ¹⁸F-FDG PET did not reveal any malignant tumors, however, one case showed decreased metabolism in the cerebellum, frontal lobe and temporal lobe. The clinical diagnosis was anti-SEZ6L2 antibody-associated encephalitis, and after immunotherapy, the symptoms improved. Conclusions Anti-SEZ6L2 antibody-associated encephalitis is rare, and it has complicated clinical manifestations. There are difficulties in the early diagnosis and differential diagnosis, but early immunomodulatory treatment leads to a good prognosis in some patients.

Objective Autoimmune cerebellar ataxia associated with anti-seizure related 6 homolog like 2 (SEZ6L2) antibody was reported, with the literature review and summary clinical features and treatment. Methods and Results The patient was a 59-year-old female hospitaled in The First Affiliated Hospital of Zhengzhou University in July 2025, with progressive unsteady gait as the main clinical manifestation with dysarthria and mild cognitive dysfunction. Cell based assay (CBA) showed the titer of anti-SEZ6L2 antibody in serum was 1∶320, and cerebrospinal fluid was 1∶10. MRI showed cerebellar hemisphere and vermis mildly atrophy. The therapeutic effect of hormonotherapy was not good. After adding Efgartigimod α to eliminate pathogenic antibodies, the patient received sequential low-dose methylprednisolone therapy combined with mycophenolate mofetil for 3 months. The symptom was improved and could walk with unilateral assistance. Conclusions Cerebellar ataxia was one of the clinical features of anti-SEZ6L2 antibody-associated disease, is associated with a poor prognosis. Efgartigimod α can be used as a treatment option to improve the prognosis of patients.

Objective Two cases of IgG4 -related hypertrophic spinal pachymeningitis (IgG4 -RSP) were reported, and literatures were reviewed, in order to summarize the clinical characteristics of IgG4-RSP. Methods and Results The 2 female patients were diagnosed and treated at Xuanwu Hospital, Capital Medical University in 2023, aged 55 and 63 years old, respectively. The primary manifestations was spinal cord compression. Spinal cord MRI showed spinal dura mater thickening with enhancement. Serum IgG4 levels are within the normal range, while cerebrospinal fluid analysis showed an increased white blood cell count and elevated protein levels. Dural biopsy findings indicate extensive lymphocytes and plasma cells infiltration, spinal dura mater fibrosis, and a significant increase in IgG4⁺ cell counts. Based on these findings, the final diagnosis was IgG4-RSP. Following surgical decompression, along with glucocorticoid and immunosuppressive therapy, there was a marked improvement in symptoms. Conclusions IgG4-RSP is more common in middle-aged patients, with no gender difference. It mainly affects the cervical and thoracic spinal cord. The initial symptoms are often pain and numbness and weakness in the limbs due to spinal cord compression. Nearly 40% of patients have normal serum IgG4 levels. Therefore, the definite diagnosis mainly relies on the biopsy of the spinal dura mater. Surgical decompression, glucocorticoids and immunosuppressants are effective treatments.

Objective To investigate the predictive value of quantitative parameters from high-resolution magnetic resonance vessel wall imaging (HR-VWI) for acute ischemic stroke (AIS). Methods The 120 patients with intracranial atherosclerosis who underwent both cranial CT and HR-VWI examinations at Second Affiliated Hospital of Nanjing Medical University from June 2021 to October 2024 and completed at least 6 months follow-up. These patients were divided into the training set (n = 84) and the testing set (n = 36) at a ratio of 7 ∶ 3. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO), and the final predictive model was constructed with the XGBoost model. Model predictive performance was assessed using receiver operating characteristic (ROC) curves and area under the curve (AUC), and generalization ability was further evaluated through learning curves. Shapley additive explanation (SHAP) was used to calculate the global contribution of each feature variable to the model′s prediction. Results Among the 120 patients, 27 cases (22.50%) experienced AIS within the 6 -month follow-up period. Specifically, there were 19 cases (22.62%) in the training set and 8 cases (22.22%) in the testing set. Multivariate Logistic regression identified calcified plaque volume ratio (OR = 0.123, 95%CI: 0.039-0.393; P = 0.000), plaque enhancement ratio (OR = 1.130, 95%CI: 1.046-1.221; P = 0.002), plaque hemorrhage (OR = 9.519, 95%CI: 2.453-36.968; P = 0.008), and luminal stenosis ratio (OR = 1.106, 95%CI: 1.032-1.185; P = 0.004) as predictors of AIS. ROC curves showed the AUC of Logistic regression model was 0.950 and 0.812 in the training set and the testing set, with sensitivity of 0.947 and 0.750 and specificity of 0.800 and 0.857, respectively. Similarly, the XGBoost model achieved an AUC of 0.986 in the training set and 0.844 in the testing set, with a sensitivity of 0.947 and 0.875, and a specificity of 0.923 and 0.857, respectiveiy. Learning curves analysis further confirmed that both models exhibited good stability and generalization ability as the training sample size increased, with XGBoost showing slightly better overall predictive performance. SHAP analysis indicated that the calcified plaque volume ratio contributed the most to model prediction. Conclusions Machine learning models that integrate calcified plaque volume ratio, plaque enhancement ratio, plaque hemorrhage and lumen stenosis ratio can significantly improve the predictive performance for AIS, exhibit good generalization ability, and provide a potential reference tool for clinical risk assessment.

Objective To explore the influencing factors of overal white matter hyperintensity (WMH) load and WMH load in different brain regions [periventricular white matter hyperintensity (PWMH) and deep white matter hyperintensity (DWMH)] load in patients with acute ischemic stroke (AIS). Methods A total of 1161 patients hospitalized in The First Affiliated Hospital of Zhengzhou University between July and December 2023 for acute ischemic stroke were included. The load of PWMH and DWMH were graded according to the Fazekas visual grading scale separately. The overal load of WMH (referred to as total WMH) was assessed according to the sum of PWMH and DWMH scores. The influencing factors of total high WMH load, PWMH load and DWMH load were investigated by univariate and multivariate Logistic regression analyses. Results According to Fazekas score, the 1161 patients were divided into low WMH load group (0-2 points, n = 493) and high WMH load group (3-6 points, n = 668), low PWMH load group (0-1 points, n = 560) and high PWMH load group (2-3 points, n = 601), low DWMH load group (0-1 points, n = 670) and high DWMH load group (2-3 points, n = 491). In multivariate Logitic analysis, based on the multiple imputation dataset, age (OR = 1.060, 95%CI: 1.046-1.075, P = 0.000; OR = 1.060, 95%CI: 1.046-1.075, P = 0.000; OR = 1.047, 95%CI: 1.033-1.060, P = 0.000) and a history of ischemic stroke (OR = 1.881, 95%CI: 1.389-2.546, P = 0.000; OR = 1.508, 95%CI: 1.132-2.010, P = 0.005; OR = 1.833, 95%CI: 1.380-2.434, P = 0.000) were the common risk factors of high load of WMH, PWMH and DWMH, while an increase in estimated glomerular filtration rate (eGFR) served as a common protective factor (b = -0.012, OR = 0.988, 95%CI: 0.979-0.996, P = 0.004; b = -0.012, OR = 0.988, 95%CI: 0.980-0.996, P = 0.004; b = -0.008, OR = 0.992, 95%CI: 0.983-1.000, P = 0.048). In addition, obesity were the risk factors of high WMH (OR = 1.620, 95%CI: 1.100-2.385; P = 0.014) and PWMH (OR = 1.712, 95%CI: 1.176-2.494; P = 0.005) load, while female (OR = 1.521, 95%CI: 1.118-2.068; P = 0.008) and hypertention (OR = 1.892, 95%CI: 1.391-2.573; P = 0.000) were the risk factors of high DWMH load. Conclusions Aging, obesity, a history of ischemic stroke, hypertension and a decline in eGFR are independent risk factors of high WMH load in patients with acute ischemic stroke. The risk factors of high PWMH and DWMH load are different. Attention should be paid to explore more risk factors of WMH and controlling them to improve the prognosis of acute ischemic stroke.