Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To investigate the treatment regimens, therapeutic effects, and adverse events of immune checkpoint inhibitors (ICI) in the treatment of progressive multifocal leukoencephalopathy (PML).Methods:A retrospective analysis was performed on patients with PML who received ICI treatment at the Department of Neurology of Peking Union Medical College Hospital from October 2020 to September 2024. The patients′ demographic characteristics, baseline immune status, clinical manifestations, laboratory tests, treatment regimens, and clinical outcomes were analyzed.Results:A total of 2 male patients with PML, aged 40 and 59 years, received ICI treatment. One patient had underlying combined immunodeficiency, while the other had acute myeloid leukemia subtype M2 and had previously undergone umbilical cord blood stem cell transplantation. Both patients were treated with pembrolizumab (dosage range: 2-3 mg/kg, administered every 3-4 weeks), receiving a total of 2-4 courses of treatment. In terms of therapeutic effects, both patients showed significant improvement. Regarding adverse events, 1 patient experienced immune-related adverse event (irAE) of immune-related pneumonia combined with immune-related hypophysitis.Conclusions:ICI may be an effective treatment option for PML. However, the use of ICI may be accompanied by the occurrence of irAE, necessitating close monitoring during treatment.

Objective:To explore the relationship between the dynamic alterations of immune cell subsets in a patient with autoimmune encephalitis and the clinical relapses.Methods:For a patient with multiple relapses of anti-N-methyl-D-aspartate receptor encephalitis superimposed with myelin oligodendrocyte glycoprotein antibody-associated disease who visited Peking Union Medical College Hospital on July 18, 2018, the lymphocyte subsets were monitored dynamically over a long period and the relationship between lymphocyte subsets and the relapses was summarized.Results:The 38-year old male patient experienced a total of 5 episodes (including 4 relapses) during the six-year immunotherapy and follow-up process, and responded well to first-line and maintenance immunotherapy. His relapses occurred during drug reduction. Finally, the neurological symptoms resolved after rituximab treatment. A total of 39 tests of peripheral blood lymphocyte subsets were conducted during the follow-up, and 5 peaks of elevated CD19 positive B cells, 9 peaks of elevated CD3 positive T cells and 11 peaks of elevated natural killer cells were observed. The peak period of peripheral blood CD19 positive B cells exactly coincided with clinical relapses. While the consistency rates of clinical relapse and the peaks of peripheral blood CD3 positive T cells and natural killer cells were 5/9 and 2/11, respectively.Conclusions:The dynamic alterations of CD19 positive B cells in peripheral blood are correlated with the clinical relapse of autoimmune encephalitis and can predict clinical relapse.

The genetic susceptibility to autoimmune encephalitis (AE) is associated with the polymorphisms of human leukocyte antigen ( HLA) genes. This article summarizes the genetic characteristics and clinical associations of HLA genes in 4 AE subtypes: anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis, anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) antibody-associated encephalopathy, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, and anti-glutamic acid decarboxylase (GAD) antibody-associated neuroimmune syndrome. Significant associations have been identified between anti-LGI1 encephalitis and DRB1 *07∶01, and between anti-IgLON5 antibody-associated encephalopathy and DQB1 *05∶01. Furthermore, anti-NMDAR encephalitis is associated with DRB1 *16∶02 and DQB1 *05∶02, while anti-GAD antibody-associated neuroimmune syndrome is linked to HLA-DQB1 *02∶01. The HLA genes associated with different AE subtypes exhibit notable heterogeneity, suggesting that HLA polymorphisms may serve as potential molecular markers for the diagnosis, clinical phenotyping, and prognosis of AE.

Objective:To analyze the clinical characteristics and prognosis of primary autoimmune cerebellar ataxia (PACA) patients with autoantibodies.Methods:Patients from the Department of Neurology, Peking Union Medical College Hospital (from March 2013 to December 2023) who met the modified diagnostic criteria of PACA were collected. Cell based assay and tissue based assay were used to detect anti-cerebellar antibodies. The clinical features, results of neuroimaging, cerebrospinal fluid examinations and the prognosis of the patients were analyzed. Modified Rankin Scale (mRS) score≤2 at the last follow-up was defined as a favorable prognosis. Exacerbation of cerebellar ataxia after clinical improvement or stabilization for at least 2 months was defined as relapse.Results:A total of 20 patients were included, including 7 males. The onset age was 48.4 (22.8, 59.3) years. Gait ataxia was the most common cerebellar symptom. Extracerebellar neurological abnormalities included pyramidal sign, peripheral neuropathy/radiculopathy and diplopia. Elevated cerebrospinal fluid white blood cells and positive specific oligoclonal bands were observed in 4/16 and 7/15 of patients, respectively. The brain magnetic resonance imaging examination of the patients showed that 8 patients had no obvious abnormalities, 9 patients showed cerebellar atrophy, and 3 patients showed abnormal signals in the brain or cerebellum. A total of 9 different anti-cerebellar antibodies were detected in the patient′s serum and (or) cerebrospinal fluid, with the most common being anti-Homer-3 antibodies ( n=7). After immunotherapy, 13/17 of patients improved. After 37.5 (21.0, 93.0) months of follow-up, the median mRS score of the patients was 3, and 8 patients (8/20) achieved good prognosis and 6 patients experienced disease recurrence. Conclusions:The clinical manifestations of PACA patients have certain heterogeneity, and positive anti-neuroantibodies and meeting PACA diagnostic criteria are the main basis for diagnosing the disease. Immunotherapy is effective for most patients, but there is still a considerable proportion of patients who have not achieved a good long-term functional prognosis.

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To investigate the treatment regimens, therapeutic effects, and adverse events of immune checkpoint inhibitors (ICI) in the treatment of progressive multifocal leukoencephalopathy (PML).Methods:A retrospective analysis was performed on patients with PML who received ICI treatment at the Department of Neurology of Peking Union Medical College Hospital from October 2020 to September 2024. The patients′ demographic characteristics, baseline immune status, clinical manifestations, laboratory tests, treatment regimens, and clinical outcomes were analyzed.Results:A total of 2 male patients with PML, aged 40 and 59 years, received ICI treatment. One patient had underlying combined immunodeficiency, while the other had acute myeloid leukemia subtype M2 and had previously undergone umbilical cord blood stem cell transplantation. Both patients were treated with pembrolizumab (dosage range: 2-3 mg/kg, administered every 3-4 weeks), receiving a total of 2-4 courses of treatment. In terms of therapeutic effects, both patients showed significant improvement. Regarding adverse events, 1 patient experienced immune-related adverse event (irAE) of immune-related pneumonia combined with immune-related hypophysitis.Conclusions:ICI may be an effective treatment option for PML. However, the use of ICI may be accompanied by the occurrence of irAE, necessitating close monitoring during treatment.

Objective:To explore the relationship between the dynamic alterations of immune cell subsets in a patient with autoimmune encephalitis and the clinical relapses.Methods:For a patient with multiple relapses of anti-N-methyl-D-aspartate receptor encephalitis superimposed with myelin oligodendrocyte glycoprotein antibody-associated disease who visited Peking Union Medical College Hospital on July 18, 2018, the lymphocyte subsets were monitored dynamically over a long period and the relationship between lymphocyte subsets and the relapses was summarized.Results:The 38-year old male patient experienced a total of 5 episodes (including 4 relapses) during the six-year immunotherapy and follow-up process, and responded well to first-line and maintenance immunotherapy. His relapses occurred during drug reduction. Finally, the neurological symptoms resolved after rituximab treatment. A total of 39 tests of peripheral blood lymphocyte subsets were conducted during the follow-up, and 5 peaks of elevated CD19 positive B cells, 9 peaks of elevated CD3 positive T cells and 11 peaks of elevated natural killer cells were observed. The peak period of peripheral blood CD19 positive B cells exactly coincided with clinical relapses. While the consistency rates of clinical relapse and the peaks of peripheral blood CD3 positive T cells and natural killer cells were 5/9 and 2/11, respectively.Conclusions:The dynamic alterations of CD19 positive B cells in peripheral blood are correlated with the clinical relapse of autoimmune encephalitis and can predict clinical relapse.

The genetic susceptibility to autoimmune encephalitis (AE) is associated with the polymorphisms of human leukocyte antigen ( HLA) genes. This article summarizes the genetic characteristics and clinical associations of HLA genes in 4 AE subtypes: anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis, anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) antibody-associated encephalopathy, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, and anti-glutamic acid decarboxylase (GAD) antibody-associated neuroimmune syndrome. Significant associations have been identified between anti-LGI1 encephalitis and DRB1 *07∶01, and between anti-IgLON5 antibody-associated encephalopathy and DQB1 *05∶01. Furthermore, anti-NMDAR encephalitis is associated with DRB1 *16∶02 and DQB1 *05∶02, while anti-GAD antibody-associated neuroimmune syndrome is linked to HLA-DQB1 *02∶01. The HLA genes associated with different AE subtypes exhibit notable heterogeneity, suggesting that HLA polymorphisms may serve as potential molecular markers for the diagnosis, clinical phenotyping, and prognosis of AE.