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Objective: Our study aimed to investigate the utility of 18 F-FDG PET imaging in diagnosing and monitoring patients with anti-leucine-rich glioma-inactivated 1 antibody autoimmune encephalitis (anti-LGI1 AE). We also sought to understand the mechanisms of faciobrachial dystonic seizures (FBDSs)., Patients and Methods: We analyzed 18 F-FDG PET scans from 50 patients with anti-LGI1 AE, using visual and semiquantitative methods, and compared these with 24 healthy controls. All patients tested positive for anti-LGI1 antibodies in serum or cerebrospinal fluid before PET imaging. The patients were divided into FBDS and non-FBDS groups to compare metabolic differences using voxel-based semiquantitative analysis. Finally, we separately analyzed PET images of patients with symptom recurrence., Results: The sensitivity of 18 F-FDG PET was superior to MRI (97.9% vs 63.8%, respectively; P < 0.001). Semiquantitative analysis revealed hypermetabolism in the basal ganglia, medial temporal lobe, and brainstem, and hypometabolism in most neocortical regions compared with healthy controls. The FBDS group exhibited hypometabolism in the frontal and temporal lobes compared with the non-FBDS group. Among 7 recurrent patients, 3 were confirmed as recurrence and 3 as sequelae by PET. One patient relapsed shortly after discontinuing corticosteroids when PET indicated active lesions., Conclusions: 18 F-FDG PET scans were more sensitive than MRI in detecting anti-LGI1 AE, which displayed a pattern of hypermetabolism in the basal ganglia and medial temporal lobe, as well as neocortex hypometabolism. Hypometabolism in the frontal and temporal lobes was associated with FBDS. Furthermore, 18 F-FDG PET scans can differentiate recurrence from sequelae and guide the timing of immunotherapy cessation., Competing Interests: Conflicts of interest and sources of funding: This work was financially supported by a grant (2022-PUMCH-B-070) from the National High Level Hospital Clinical Research Funding. All authors involved in this work have declared no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients., Methods: The patients admitted to our hospital with the diagnosis of RM in the past 8 years were retrospectively analyzed., Results: Six patients with RM were identified among 933 patients admitted with rheumatoid arthritis (RA). The symptoms of meningitis occurred after onset of arthritis in five patients and before onset in one. Headache (n=6), hyperacute focal neurological deficits (n=4) and seizures (n=3) were the most prevalent symptoms. The nadir modified Rankin Scale score was ≥3 in five patients. Rheumatoid factor was elevated in all patients, and interleukin-6 levels in cerebrospinal fluid were dramatically elevated in three of four tested patients. Magnetic resonance imaging of the brain revealed that the meninges were affected in all patients and the cerebral parenchyma was affected in one patient. The lesions were generally located in the frontoparietal region and showed restricted diffusion along the adjacent subarachnoid space. RM occurred during disease-modifying therapy in four patients. In the acute episode, three patients improved on tocilizumab and the other three improved on pulse corticosteroids. For maintenance therapy, two patients received combined therapy of tocilizumab and other immunosuppressive agents, one received adalimumab and methotrexate, and two received low-dose oral corticosteroids with an immunosuppressive agent. Five patients had a good outcome, and one died of Pneumocystis jirovecii pneumonia after stabilization of his neurologic conditions. No relapse of RM occurred on immunotherapy during follow-up., Conclusions: Chinese patients with RM share some remarkable clinical and neuroimaging features and respond well to appropriate immunotherapy. Tocilizumab could be a treatment option for this severe complication of RA., 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., (Copyright © 2023 Fan, Zhao, Hou, Liu, Niu, Zhou, Mao, Ren, Feng, Li, Zeng, Zhu and Guan.)

Autoimmune cerebellar ataxia (ACA) is an important cause of sporadic cerebellar ataxia. Technological innovation promotes the rapid development of cerebellar autoimmunity researches in recent years. More and more new antibodies have been proposed to be associated with ACA. Several autoantibodies against Purkinje cells (PCs) have been identified, which constitute the main components. These autoantigens are mainly located in the cytoplasm and dendrites of PCs, and exhibit a specific morphology in immunohistochemistry (IHC). Although the clinical features are relatively homogeneous, there were still some differences among different antibodies. Due to the lack of understanding of the disease and the limited detection technology, it is really difficult to diagnose and manage at present. However, unlike the most of hereditary ataxias, ACA is treatable, and even the neurological dysfunction of some patients may be reversible. Therefore, promptly identification, diagnosis and treatment may benefit some patients. Thus, this article elaborates on the clinical manifestations and laboratory characteristics of anti-PCs-antibody-associated ACA in order to help neurologists to understand ACA more comprehensively. At the same time, combining our previous exploratory work as well as the technology available, we try to propose a diagnostic strategy for ACA the text and the relevant differential diagnosis was illustrated in detail., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-20-2187/coif). The series “Laboratory Investigations in Neuroimmunological Diseases and Their Clinical Significance” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Objective: To describe clinical phenotypes and prognosis of neurological autoimmunity related to glutamic acid decarboxylase 65 (GAD65) antibodies in China., Method: In this retrospective observational study from Peking Union Medical College Hospital, we identified patients with neurological disorders related to GAD65 antibodies (cell-based assay) from May 2015 to September 2021. Clinical manifestations, immunotherapy responsiveness, and outcomes were collected after obtaining informed consent from all patients., Results: Fifty-five patients were included: 40 (72.73%) were women and initial neurological symptoms developed at 42(34-55) years of age. The median time to the nadir of the disease was 5 months (range from 1 day to 48 months). The clinical syndromes included limbic encephalitis (LE) or epilepsy (Ep) ( n = 34, 61.82%), stiff-person syndromes (SPS) ( n = 18, 32.73%), autoimmune cerebellar ataxia (ACA) ( n = 11, 20%), and overlap syndrome in eight (14.55%) patients. Thirty-two (58.2%) patients had comorbidities of other autoimmune diseases, including Hashimoto thyroiditis ( n = 17, 53.13%), T1DM ( n = 11, 34.78%), vitiligo ( n = 6, 18.75%), and others (n=5, 15.63%). Two (3.64%) patients had tumors, including thymoma and small cell lung cancer. Fifty-one (92.7%) patients received first-line immunotherapy (glucocorticoids and/or IV immunoglobulin), and 4 (7.3%) received second-line immunotherapy (rituximab). Long-term immunotherapy (mycophenolate mofetil) was administered to 23 (41.8%) patients. At the median time of 15 months (IQR 6-33.75 month, range 3-96 month) of follow-up, the patients' median modified Rankin Score (mRS) had declined from 2 to 1. Thirty-eight (70.4%) patients experienced clinical improvement (mRS declined ≥1), 47 (87%) had favorable clinical outcomes (mRS ≤2), and nine were symptom-free (16.7%). The sustained response to immunotherapy ranged from 7/15 (63.63%) in ACA patients and 22/34 (64.7%) in LE/Ep patients to 14/17 (82.35%) in SPS patients., Conclusions: LE/Ep was the most common neurological phenotype of GAD65 antibody neurological autoimmunity in our cohort. Most patients had comorbidities of other autoimmune diseases, but underlying tumors were rare. Most patients responded to immunotherapy. However, the long-term prognosis varied among different clinical phenotypes., 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., (Copyright © 2022 Bai, Ren, Liang, Lu, Lin, Liu, Fan, Cui and Guan.)

Introduction: Human gut dysbiosis has been implicated with the onset of many neurodegenerative disorders. However, the current data focused on the gut microbiota of patients with Creutzfeldt-Jakob disease (CJD) are still lacking. In our study, we explored the gut microbiota alteration in patients with CJD., Method: We performed 16S ribosomal RNA MiSeq sequencing in stool samples of patients with CJD and controls. Functional analysis of the gut microbiota between these two groups was based on Kyoto Encyclopedia of Genes and Genomes and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. Clinical rating scales were used to evaluate the association between cognitive impairment and gut microbiota alteration., Result: We identified a significant alteration in both the structure and the richness of the CJD group. Function analysis revealed that the gut microbiota of patients with CJD enriched in immune signaling molecule interactions and xenobiotics biodegradation. MoCA and survival times were found to be associated with gut microbiota in patients with CJD., Conclusion: We demonstrated an altered gut microbiota in patients with CJD, which was associated with the cognitive impairment and the survival time of these patients., 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., (Copyright © 2022 Guo, Xu, Lin, Zhen, Yi, Guan, Shi, Sun, Yang, Dong and Wang.)

Background and Objective: To present 6 new cases with Homer-3 antibodies that expand their clinical spectra and to evaluate the effect of immunotherapy., Methods: Patients with suspected autoimmune cerebellar disorder were tested for rare autoimmune cerebellar ataxia (ACA) antibodies (anti-Tr(DNER)/Zic4/ITPR1/Homer-3/NCDN/PKCγ/PCA-2/AP3B2/mGluR1/ATP1A3 antibodies) using both cell-based and tissue-based assays. Patients with positive serum or CSF results who were diagnosed with ACA were registered and followed up. This study reports and analyzes cases with Homer-3 antibodies., Results: Of the serum and CSF samples of 750 patients tested, 6 were positive for Homer-3 antibodies. All manifested subacute or insidious-onset cerebellar ataxia. Furthermore, 2 patients each exhibited encephalopathy, myeloradiculopathy, REM sleep behavior disorder, and autonomic dysfunction. Brain magnetic resonance images were normal (n = 1) or revealed cerebellar atrophy (n = 1), cerebellum and pons atrophy with the hot cross bun sign (n = 2), and bilateral cerebral abnormalities (n = 2). Definite leukocytosis was identified in the CSF of 2 patients, protein concentration elevation was observed in the CSF of 1 patient, and oligoclonal bands were present in 2 patients. All patients received immunotherapy, including corticosteroid, IV immunoglobulin, plasma exchange, and mycophenolate mofetil, after which the residual disability was still severe (modified Rankin Scale score ≥3 at the last follow-up in 4 patients and final Scale for the Assessment and Rating of Ataxia scores of 12-29), although 4 patients partially improved and 1 patient stabilized. The remaining 1 patient continued to deteriorate after repeated immunotherapy. Two patients relapsed., Discussion: Disorders associated with Homer-3 antibody can mimic multiple system atrophy with cerebellar features in both clinical and radiologic aspects. Accurate identification of autoimmune-mediated cases is critical. Timely, comprehensive immunotherapy is warranted, given the possibility of long-term clinical benefit., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To describe the clinical features and prognosis of pediatric anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis from a single center in northern China., Methods: The clinical and laboratory characteristics of hospitalized patients with anti-NMDAR encephalitis, stratified by age, were retrospectively studied. Risk factors including relapse and long-term (follow-up ≥1 year) outcomes were analyzed., Results: A total of 273 patients were included between November 2011 and December 2019, and the average age of onset was 7.5 ± 4.0 years (0.5-15.8 years). Of them, 159（58.2%） were female, and the proportion of females increased with age. Seizures were the most common initial symptom. Movement disorders（86.1%） and psychiatric（82.4%） symptoms were most frequent in the acute phase. In the acute stage, the incidence of movement disorders decreased with age (χ 2  = 10.676, p = 0.011), while the proportion of psychiatric symptoms increased with age (χ 2  = 21.85, p < 0.001) The recurrence rate was 9.6% (24/250). Demyelination was an independent risk factor for relapse (p = 0.006, OR = 5.877, 95% CI: 1.658-20.835). Among the 210 patients who were followed up for more than one year, 28 patients had a poor prognosis (mRS ≥3). Onset age (p = 0.038，OR = 0.844, 95% CI: 0.720-0.991), precursor of viral encephalitis (p = 0.007，OR = 9.876, 95% CI: 1.878-51.940), and ICU admission (p = 0.023，OR = 5.924, 95% CI: 1.280-27.064) significantly affected the prognosis. The mortality rate was 2.9%., Conclusions: The characteristics of anti-NMDAR encephalitis in children are age-dependent. Early-onset, the precursor of viral encephalitis, and ICU admission may indicate poor prognosis. Demyelination may be a risk factor for recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Anti-protein kinase Cgamma (anti-PKCγ) antibodies are rare onconeural antibodies associated with paraneoplastic cerebellar degeneration (PCD). To date, only two patients with PCD and anti-PKCγ antibodies have been reported. Here, we report a Chinese patient with PCD and anti-PKCγ antibodies. Screening for tumor revealed lymphoepithelial carcinoma in tonsil. The patient's symptoms improved gradually after radiotherapy for the lymphoepithelial carcinoma and intravenous immunoglobulin immunotherapy., Competing Interests: Declaration of Competing Interest All authors declare no competing interest., (Copyright © 2020. Published by Elsevier B.V.)

Pseudorabies virus (PRV) is known to cause severe encephalitis in juvenile pigs and various non-native hosts; recent evidences suggest that PRV might cause encephalitis in humans. In a multicenter cohort study in China, next-generation sequencing of cerebrospinal fluid (CSF) was performed to detect pathogens in all patients with clinically suspected central nervous system infections. This study involved all the patients whose CSF samples were positive for PRV-DNA; their clinical features were evaluated, and species-specific PCR and serological tests were sequentially applied for validation. Among the 472 patients tested from June 1, 2016, to December 1, 2018, six were positive for PRV-DNA, which were partially validated by PCR and serological tests. Additionally, we retrospectively examined another case with similar clinical and neuroimaging appearance and detected the presence of PRV-DNA. These patients had similar clinical manifestations, including a rapid progression of panencephalitis, and similar neuroimaging features of symmetric lesions in the basal ganglia and bilateral hemispheres. Six of the patients were engaged in occupations connected with swine production. PRV infection should be suspected in patients with rapidly progressive panencephalitis and characteristic neuroimaging features, especially with exposure to swine.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a paraneoplastic limbic encephalitis, recently identified.To summarize our experience in the nursing care of patients with anti-NMDAR encephalitis managed with surgery and pharmacotherapy.This study included 45 patients treated between July 2015 and November 2016. Laparoscopic oophorocystectomy was performed in 11 female patients with teratomas. Eleven patients required tracheal intubation or tracheotomy and ventilation.The patients were hospitalized for an average of 25.2 days. The mental and neurological symptoms were significantly relieved 23.6 ± 4.8 days after surgery or immunotherapy. Near-normal function was restored in 11 patients, while 34 patients had varying degrees of dysfunction at discharge. After follow-up of 1 to 18 months, 24 patients were found to have permanent impairments.Appropriate symptomatic nursing care is required to ensure the safety of patients with anti-NMDAR encephalitis.

Objective: To describe the detailed clinical characteristics, immunotherapy, and long-term outcomes of patients with anti-NMDA receptor (NMDAR) encephalitis in China., Methods: A single-center, prospective study. Patients who met the diagnostic criteria were enrolled from 2011 to 2017 and followed up. The clinical features, treatment, and long-term outcomes were collected prospectively. Factors affecting the long-term prognosis were analyzed., Results: The study included 220 patients. The most common clinical presentations were psychosis (82.7%) and seizures (80.9%). Of the patients, 19.5% had an underlying neoplasm; of which ovarian teratoma was 100% of tumors in females and only one male had lung cancer. Most patients (99.5%) received first-line therapy (glucocorticoids, IV immunoglobulin, or plasmapheresis alone or combined), and only 7.3% received second-line immunotherapy (rituximab, cyclophosphamide alone, or combined). Long-term immunotherapy (mycophenolate mofetil or azathioprine >1 year) was administered to 53.2% of patients. During the first 12 months, 207 (94.1%) patients experienced improvement, and 5 (2.3%) died, whereas 38 (17.3%) experienced relapses. At 12-month follow-up, 92.7% had favorable clinical outcomes (modified Rankin Scale score ≤2)., Conclusions: Patients in China present with psychosis and seizure frequently but have a low percentage of underlying neoplasms. Re-enforced first-line immunotherapy is effective in managing anti-NMDAR encephalitis in the acute phase. Although relapse is relatively common, with combined first-line and long-term immunotherapy, most patients reached favorable outcomes., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Pseudorabies virus (PRV) has been thought to cause diseases only in animals. However, recent studies have shown that PRV can also cause illnesses in humans., Methods: This was a case series study. The cases of five patients with clinical symptoms of acute encephalitis, which were confirmed to be caused by PRV infections, were reviewed., Case Presentation: The five patients all had jobs involving the handling of pigs. They had acute onset and rapid progression of clinical presentations, which were consistent with central nervous system infections. Four of them had respiratory failure, which required ventilator support. Brain magnetic resonance imaging showed abnormal signals in the bilateral temporal lobes and insular cortex in all five patients, bilateral frontal lobes in one patient, and caudate nucleus in one patient. Cerebrospinal fluid analysis results were consistent with a viral infection. Next-generation sequencing of the cerebrospinal fluid confirmed the presence of PRV. All patients received human immunoglobulin, glucocorticoids, antiviral agents, and symptomatic supportive treatments. All patients survived until discharge, but suffered from various sequelae. Pneumonia was the most common complication during the disease course., Conclusions: PRV encephalitis should be included in the differential diagnosis of patients with a clinical presentation of central nervous system infection, especially for those who have had recent contact with pigs., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the correlation between afterdischarges in motor nerve conduction studies and clinical motor hyperexcitability in patients with voltage-gated potassium channels (VGKC) antibodies., Methods: Six patients with positive serum antibodies to contactin-associated protein-like 2 (CASPR2) or/and leucine-rich glioma-inactivated protein 1 (LGI1) were recruited, including 5 with autoimmune encephalitis, and 1 with cramp-fasciculation syndrome. Electromyography (EMG), nerve conduction studies (NCS) and F waves were performed, and afterdischarges were assessed. One patient was followed up., Results: Five patients had clinical evidence of peripheral motor nerve hyperexcitability (myokymia or cramp), and four of them had abnormal spontaneous firing in concentric needle electromyography (EMG). Prolonged afterdischarges following normal M waves were present in all six patients, including the two patients who had no EMG evidence of peripheral nerve hyperexcitability (PNH). Afterdischarges disappeared after treatment with intravenous immunoglobulin (IVIG)., Conclusion: The afterdischarges in motor nerve conduction study might be a sensitive indicator of peripheral motor nerve hyperexcitability in patients with VGKC antibodies., Significance: Afterdischarges in motor nerve conduction study might be more sensitive than needle electromyography for detecting peripheral motor nerve hyperexcitability, and could disappear gradually in accordance with clinical improvement and reduction of antibodies.

Background and Purpose: Encephalitis caused by Listeria monocytogenes (L. monocytogenes) is rare but sometimes fatal. Early diagnosis is difficult using routine cerebrospinal fluid (CSF) tests, while next-generation sequencing (NGS) is increasingly being used for the detection and characterization of pathogens., Methods: This study set up and applied unbiased NGS to detect L. monocytogenes in CSF collected from three cases of clinically suspected listeria meningoencephalitis., Results: Three cases of patients with acute/subacute meningoencephalitis are reported. Magnetic resonance imaging and blood cultures led to a suspected diagnosis of L. monocytogenes, while the CSF cultures were negative. Unbiased NGS of CSF identified and sequenced reads corresponding to L. monocytogenes in all three cases., Conclusions: This is the first report highlighting the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) L. monocytogenes infection. Routine application of this technology in clinical microbiology will significantly improve diagnostic methods for CNS infectious diseases., Competing Interests: The authors have no financial conflicts of interest.

Objective: The aim of this study is to explore the clinical characteristics, treatment and prognosis of pareneoplastic neurological syndrome (PNS) associated with small cell lung cancer (SCLC) in a single-center cohort., Methods: We retrospectively and consecutively reviewed 34 patients (22 male and 12 female, mean age 55.4 years old) diagnosed as PNS associated with SCLC in our hospital from 2001 to 2014 and investigated the clinical features, related antibodies, treatment and prognosis in this cohort., Results: In a total of 34 patients, 31 (91.4%) presented with neurological symptoms prior to the diagnosis of cancer. Lambert-Eaton syndrome (13/34, 38.2%) was the most common subtype, followed by paraneoplastic sensory neuronopathy (10/34, 29.4%), paraneoplastic cerebellar degeneration (7/34, 20.6%), limbic encephalitis (6/34, 17.6%) and brainstem encephalitis (1/34, 3%). Anti-neuronal antibodies were positive in 9 out of a total of 24 patients (37.5%) who performed the tests. There were 28 (82.4%) patients who received the treatment for the primary tumor. Of them, operation of removing the tumor was performed in 4 patients. 5 patients received treatment of suppression of the immune response to PNS. Significant neurological improvement was found in a patient who received operation combined with immunotherapy after a 3-year follow-up., Conclusions: The majority of patients with PNS are unknown to have cancer at the time of diagnosis. Early recognition of PNS is helpful to the treatment of the tumor. PNS has diverse presentations, affecting both the central and peripheral nervous system, which makes the diagnosis hard. Operation of removing the tumor and immune suppression may slow the immune response, creating the greatest chance for neurologic improvement or symptom stabilization.