Objective To explore the clinical significance of expressing multiple autoantibodies in patients with autoimmune encephalitis.Methods Cerebrospinal fluid and serum were tested in patients with undefined encephalitis admitted to Peking Union Medical College Hospital from May 2013 to December 2014.Indirect immunofluorescence test was firstly used to identify the antibodies to neuronal cell-surface or synaptic receptors (including N-methyl-D-aspartate receptor (NMDAR),contactin-associated protein-like 2 (CASPR2),α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR),leucine-rich glioma inactivated protein 1 (LGI1),and gamma-aminobutyric acid beta receptor (GABABR)).In those patients with positive antibodies,antibodies against intracellular neuronal antigens associated with paraneoplastic neurological symptoms were tested.Anti-aquaporin protein-4 (AQP4) antibody was tested depending on patients' clinical manifestations.Results Ten patients were detected combined with additional autoantibodies in 531 patients with positive antibodies related to autoimmune encephalitis.AntiHu antibody was positive in 5 patients with anti-GABABR encephalitis,in 1 of whom anti-NMDAR antibody was also identified;anti-AQP4 antibody was positive in 1 patient with relapsing anti-NMDAR encephalitis;anti-CASPR2 and anti-Yo antibodies were respectively positive in 2 patients with anti-LGI1 encephalitis;anti-CV2 and anti-Hu antibodies were respectively positive in 2 patients with anti-AMPAR encephalitis.Clinical presentation of all cases was consistent with typical encephalitis or limbic encephalitis.Brain stem was involved in 3 patients.Peripheral sensory neuropathy was present in 1 patient,while myalgia and fasciculation were present in 1 patient.Seven patients responded well to the immunotherapy.Tumors were pathologically or radiologically confirmed in 7 cases,including lung cancer in 5 cases,suspected thymoma in 1 case and highly suspected mediastinal tumor without pathological identification in 1 case.Conclusions Due to the pathological mechanism,co-existence of multiple autoantibodies affects clinical manifestations of patients and results in variation and overlap of them.The additional positivity of onconeuronal antibodies directs the search for occult tumor.

Sj?gren′s syndrome is a chronic autoimmune inflammatory disease characterized by exocrine gland and extraglandular involvement. Cases of Sj?gren′s syndrome-associated aseptic meningitis (SS-AM) are relatively rare, and a case of recurrent aseptic meningitis with leukopenia and mild anemia associated with primary Sj?gren′s syndrome is reported, whose symptoms basically disappeared after treatment with prednison and hydroxychloroquine. The purpose of reporting this case is to raise awareness of SS-AM among fellow clinicians.

Objective:To report the clinical characteristics of a case of childhood amyotrophic lateral sclerosis (ALS) caused by SPTLC2 c.778G>A (p.Glu260Lys) mutation. Methods:Whole exon sequencing or whole genome sequencing data from 1 936 patients in the ALS cohort of Peking Union Medical College Hospital were screened for SPTLC2 gene mutations. Clinical data, laboratory examination, neurophysiological examination and genetic test results of the proband were collected. Results:Only one 9-year-old male child with SPLTC2 gene mutation was found. He was admitted to the Department of Neurology, Peking Union Medical College Hospital in December 2022 due to"progressive limb weakness for more than 4 years". Physical examination revealed atrophy and fasciculations of the tongue. Weakness of 4 limbs, muscle atrophy, as well as bilateral hyperreflexia, clonus, and Babinski sign were present. Whole genome sequencing indicated that SPTLC2 gene had c.778G>A (p.Glu260Lys) missense mutation, and no other pathogenic mutations of ALS related genes were detected. Sanger sequencing and family verification showed that neither father nor mother carried the mutation, suggesting that it was a de novo mutation. Nerve conduction velocity test showed no abnormalities, and electromyography suggested neurogenic lesions. Neurofilament light chain in cerebrospinal fluid and serum were increased significantly. The patient′s symptoms continued worsening even after oral administration of L-serine. Conclusion:SPTLC2 gene mutation can cause childhood ALS, and further study of its potential pathogenesis is helpful to uncover another potential pathway of ALS and a novel therapeutic target.

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

Objective To establish a test of autoantibody-panel for the diagnosis of autoimmune cerebellitis (AC) and determine the prevalence of AC in patients with cerebellar ataxia of unknown etiology.Methods Autoantibody screening tests with indirect immunofluorescence were performed in serum and cerebrospinal fluid (CSF) samples of 400 previously'idiopathic'Chinese patients with cerebral ataxia (inpatients and outpatients in Peking Union Medical College Hospital or referred from hospitals of Beijing Encephalitis Group from 2016 to 2018).Immunotherapy was given to autoantibody positive patients and the effectiveness of immunotherapy was assessed.Detailed AC autoantibodies panel included anti-glutamate decarboxylase 65 (GAD65) antibody,anti-Tr (delta notch-like epidermal growth factor-related receptor (DNER)) antibody,anti-zinc finger protein 4 (ZIC4) antibody,anti-inositol 1,4,5-trisphosphate receptor 1 (ITPR1) antibody,anti-homer protein homolog 3 (Homer 3) antibody,anti-neurochondrin (NCDN) antibody,anti-carbonic anhydrase-related protein (CARP) antibody and anti-Purkinje cell antibody 2 (PCA2) antibody.Results Eight out of 400 (2％) ataxia patients were positive for this AC panel tests,of whom two were positive for anti-GAD65 antibody,two for anti-Tr antibody,one for anti-PCA2 antibody,one for anti-Homer 3 antibody and two were positive for serum anti-NCDN antibody.Autoantibodies against ZIC4,ITPR1 and CARP were not detected in this cohort.Two of the eight ataxia patients also presented with limbic encephalitis,and only one anti-GAD antibody patient was screened with underlying small cell lung carcinoma (SCLC).All the eight patients received immunotherapy and four experienced partial response.Conclusions Autoimmune cerebellitis is the cause of acquired cerebellar ataxia.Tests of autoantibodies associated with AC have diagnostic value for paraneoplastic and non-paraneoplastic cerebellar ataxia.Immunotherapy may yield partial response in patients with AC.

Objective:To investigate the clinical and electrophysiological characteristics of facial onset sensory motor neuronopathy (FOSMN) syndrome.Methods:Ten patients diagnosed with FOSMN syndrome in Peking Union Medical College Hospital from January 2012 to December 2022 were included. The clinical and electrophysiological characteristics of patients were analyzed and summarized, and the genetic testing was also performed in these patients.Results:The age of onset was (56.6±6.5) years, and the longest survival duration of disease was 10 years. All patients had numbness around the face and mouth as the first symptom and abnormal blink reflex. A total of 52 sensory nerve conduction nerves were detected, among which 2 median nerves and 2 μlnar nerves showed decreased amplitude of sensory nerve action potential. Needle electromyography showed neurogenic lesions, with both progressive and chronic denervation. Whole exome sequencing identified the heterozygous variant c.272A>C in the exon 4 of the SOD1 gene resulting in the amino acid change p.Asp90Ala in 1 patient. In all patients, the disease progressed relentlessly and eventually led to involvement of respiratory muscle. Conclusion:FOSMN syndrome is characterized by abnormal blink reflex and sometimes abnormal sensory nerve conduction may be shown on electrophysiologic testing.