Qinming Zhou

Background: Anti-IgLON5 disease, a rare autoimmune neurological disorder, remains understudied in Eastern populations. This study aimed to characterize the clinical characteristics, treatment responses, and long-term outcomes of Chinese patients with anti-IgLON5 disease in a multicenter Chinese cohort. Methods: This retrospective multicenter study enrolled 24 patients with anti-IgLON5 disease confirmed by serum and/or cerebrospinal fluid antibody testing from 17 centers in China. Human leukocyte antigen (HLA) typing was performed on patient blood samples. Clinical characteristics, mRS/ICS outcomes, treatment response, relapse, and long-term outcomes were analyzed. Short-term response was defined as improvement in mRS from admission to discharge, and relapse was defined as recurrence or worsening of symptoms after initial clinical improvement. Results: The mean age at onset was 59.6 years. Among 18 patients who received immunotherapy, 10/18 (55.6%) met the definition of achieving a short-term response. Responders included more women (6/10 vs. 2/8), fewer patients with bulbar symptoms (4/10 vs. 5/8), and more frequently had HLA-DRB1*10:01 or HLA-DQB1*05:01 (8/10 vs. 4/8) compared with non-responders. Men aged ≥ 65 years had poorer outcomes, whereas younger men and most women responded well. Long-term follow-up was performed on 16 patients (median 18 months, range 3–60 months), and eight withdrew from follow-up. Relapse occurred in 4/16 patients (25.0%). It typically occurred about 6–12 months after discharge, often following abrupt treatment withdrawal, and was effectively controlled with re-treatment. Kaplan–Meier analysis indicated that relapse risk was the highest within the first 6 months post-discharge. Early treatment (≤ 6 months) tended to be associated with more favorable outcomes. Overall, 10/14 immunotherapy-treated patients with long-term follow-up (71.4%) showed improvement, and 7/14 (50.0%) became asymptomatic. In this cohort, HLA-DQA1*01:05 and HLA-DRB1*10:01/HLA-DQB1*05:01 were over-represented among the typed patients, and the response rate to immunotherapy was numerically higher than that in the Western population (55.6% vs. 40%). The misdiagnosis rate was 33.3%. The median diagnostic delay was 2 months (IQR, 1–12 months; range, 2 days–6 years). Conclusions: As the largest cohort of anti-IgLON5 disease in China to date, this multicenter series demonstrated that Chinese and Western patients with anti-IgLON5 disease have both shared and distinct clinical characteristics. Chinese patients exhibited relatively favorable responses to early immunotherapy, relapse susceptibility requiring prolonged treatment, and potential HLA associations, offering new insight into disease management.

Background: Creutzfeldt–Jakob disease (CJD) is a fatal neurodegenerative disorder caused by prion proteins, with microglial activation being a key immunopathological feature. This case report demonstrates the application of ¹⁸ F-DPA-714 positron emission tomography (PET)/MRI, a second-generation translocator protein ligand, to visualise microglial activation in vivo in a patient with sporadic CJD (sCJD). Case presentation: A 57-year-old woman presented with progressive rapid cognitive decline and behavioural change. MRI revealed restricted diffusion within the patchy cortical ribbon of bilateral frontal, parietal, occipital lobes and right caput nuclei caudate. Lumbar puncture revealed positive 14-3-3 protein and robustly positive real-time quaking-induced conversion assay, fulfilling the diagnostic criteria for definite sCJD. ¹⁸ F-DPA-714 PET/MRI showed extensive tracer uptake in bilateral cortical regions, caudate nuclei and the thalamus, indicating widespread microglial activation. The extent of abnormality on PET exceeded that seen on initial MRI, suggesting higher sensitivity for early pathological changes. Conclusions: This is the first reported case of sCJD evaluated with ¹⁸ F-DPA-714 PET/MRI. The findings suggest that ¹⁸ F-DPA-714 PET/MRI may provide complementary sensitivity beyond structural MRI, potentially improving early diagnostic confidence in sCJD.

Autoimmune encephalitis (AE) comprises immune-mediated neuroinflammatory disorders presenting diverse neuropsychiatric symptoms and antibody-specific manifestations. Despite standard immunotherapy, residual disability, treatment intolerance, and relapse risks highlight unmet clinical needs. Telitacicept, a dual target fusion protein that inhibits B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), suppresses pathogenic B cell activation and autoantibody production, presenting a mechanism-driven therapeutic potential for AE management. Three AE cases with distinct therapeutic complexities are detailed in our study: (1) An anti-N-methyl-D-aspartate receptor (NMDAR) antibody-positive patient experienced recurrent relapses and was a comorbid individual with upper gastrointestinal bleeding. (2) An anti-leucine-rich glioma inactivated 1 (LGI1) antibody patient resisted corticosteroids, intravenous immunoglobulin, and ofatumumab treatment. (3) A newly diagnosed, anti-LGI1 antibody and anti-contactin-associated protein 2 (CASPR2) antibody dual-positive patient required sequential therapy to consolidate the remission and facilitate prednisone tapering. Telitacicept administration achieved symptom remission across all cases, accompanied by reduced antibody titers and stable outcomes over six months. Our case series evaluates the use of telitacicept in AE patients with varied antibody subtypes, particularly for patients with relapsed or refractory disease, intolerance to CD20-targeted agents, or steroid-related complications. Moreover, telitacicept may serve as an effective sequential therapy to sustain remission and reduce long-term steroid dependency.

Objective This study investigated the efficacy of ofatumumab (OFA) combined with corticosteroids in autoimmune encephalitis (AE) patients refractory to conventional treatment. Methods Eighteen AE patients admitted to Ruijin Hospital between June 2022 and September 2023 received four subcutaneous 20-mg OFA injections at 0, 1, 6, and 12 weeks combined with standard corticosteroid therapy. Results Clinical symptoms, modified Rankin scale (mRS) scores, Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores, serum immunoglobulin (Ig) levels (IgG and IgM), and peripheral blood CD20 + B cell levels were documented before OFA administration and at 1, 2, 6, 12, and 24 weeks post-treatment. OFA treatment significantly improved psychiatric symptoms (P = 0.025), cognitive dysfunction (P = 0.008), and seizure frequency (P = 0.014). The mRS and CASE scores improved after two injections in patients with anti-NMDAR encephalitis (P = 0.041), but not in patients with anti-LGI1 encephalitis (P > 0.05). The mRS scores significantly improved at 12 weeks post-treatment in antibody-negative encephalitis. Blood CD20 + B cell levels dropped to zero after an average of 2.5 injections. No significant changes could be observed in serum IgG and IgM levels (P > 0.05). Seven patients had mild fever or pulmonary infections post-treatment. Conclusion This study suggests that OFA is a safe and effective treatment for a subset of AE patients, particularly in cases of anti-NMDAR encephalitis, though further research is needed on long-term outcomes and recurrence.

Antibodies against N-methyl-d-aspartate receptors (NMDARs) are most frequently detected in persons with autoimmune encephalitis (AE) and used as diagnostic biomarkers. Elucidating the structural basis of monoclonal antibody (mAb) binding to NMDARs would facilitate the development of targeted therapy for AE. Here, we reconstructed nanodiscs containing green fluorescent protein-fused NMDARs to label and sort individual immune B cells from persons with AE and further cloned and identified mAbs against NMDARs. This allowed cryo-electron microscopy analysis of NMDAR–Fab complexes, revealing that autoantibodies bind to the R1 lobe of the N-terminal domain of the GluN1 subunit. Small-angle X-ray scattering studies demonstrated NMDAR–mAb stoichiometry of 2:1 or 1:2, structurally suitable for mAb-induced clustering and endocytosis of NMDARs. Importantly, these mAbs reduced the surface NMDARs and NMDAR-mediated currents, without tonically affecting NMDAR channel gating. These structural and functional findings imply that the design of neutralizing antibody binding to the R1 lobe of NMDARs represents a potential therapy for AE treatment.

Objective: Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease.Methods: We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes.Results: The average age at diagnosis was 45.93 ± 4.62 years (range: 11–72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on ¹⁸F-fluorodeoxyglucose positron-emission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up.Conclusion: The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis.

Background Translocator protein (TSPO) PET has been used to visualize microglial activation in neuroinflammation and is a potential imaging tool for detecting autoimmune encephalitis (AIE). Purpose To compare the detection rate between TSPO radioligand fluorine 18 (¹⁸F) DPA-714 PET and conventional MRI and assess the relationship between ¹⁸F-DPA-714 uptake and clinical features in participants with AIE. Materials and Methods Healthy volunteers and patients with AIE were enrolled in this prospective study between December 2021 and April 2023. All participants underwent hybrid brain ¹⁸F-DPA-714 PET/MRI and antibody testing. Modified Rankin scale scoring and AIE-related symptoms were assessed in participants with AIE. Positive findings were defined as intensity of ¹⁸F-DPA-714 uptake above a threshold of the mean standardized uptake value ratio (SUVR) plus 2 SD inside the corresponding brain regions of healthy controls. The McNemar test was used to compare the positive detection rate between the two imaging modalities; the independent samples t test was used to compare continuous variables; and correlation with Bonferroni correction was used to assess the relationship between ¹⁸F-DPA-714 uptake and clinical features. Results A total of 25 participants with AIE (mean age, 39.24 years ± 19.03 [SD]) and 10 healthy controls (mean age, 28.70 years ± 5.14) were included. The positive detection rate of AIE was 72% (18 of 25) using ¹⁸F-DPA-714 PET compared to 44% (11 of 25) using conventional MRI, but the difference was not statistically significant (P = .065). Participants experiencing seizures exhibited significantly higher mean SUVR in the entire cortical region than those without seizures (1.23 ± 0.21 vs 1.15 ± 0.18; P = .003). Of the 13 participants with AIE who underwent follow-up PET/MRI, 11 (85%) demonstrated reduced uptake of ¹⁸F-DPA-714 accompanied by relief of symptoms after immunosuppressive treatment. Conclusion ¹⁸F-DPA-714 PET has potential value in supplementing MRI for AIE detection. Clinical trial registration no. NCT05293405 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Zaharchuk in this issue.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that is associated with selective and progressive loss of motor neurons. As a consequence, the symptoms of ALS are muscle cramps and weakness, and it eventually leads to death. The general markers for early diagnosis can assist ALS patients in receiving early intervention and prolonging their survival. Recently, some novel approaches or previously suggested methods have validated the potential for early diagnosis of ALS. The purpose of this review is to summarize the status of current general markers discovery and development for early diagnosis of ALS, including genes, proteins neuroimaging, neurophysiology, neuroultrasound, and machine learning models. The main genetic markers evaluated are superoxide dismutase 1 (SOD1), chromosome 9 open reading frame 72 (C9orf72), transactivation-responsive DNA binding protein 43 (TARDBP), and fused in sarcoma (FUS) genes. Among proteins, neurofilament light chain is still the most established disease-specific adaptive change in ALS. The expression of chitinases, glial fibrillary acidic protein (GFAP), and inflammatory factors are changed in the early stage of ALS. Besides, more patient-friendly and accessible feature assays are explored by the development of neuroimaging, neurophysiology, and neuroultrasound techniques. The novel disease-specific changes exhibited the promising potential for early diagnosis of ALS. All of these general markers still have limitations in the early diagnosis, therefore there is an urgent need for the validation and development of new disease-specific features for ALS.

JOURNAL/nrgr/04.03/01300535-202408000-00039/figure1/v/2026-05-08T111955Z/r/image-tiff Biomarkers are required for the early detection, prognosis prediction, and monitoring of amyotrophic lateral sclerosis, a progressive disease. Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarkers. In this study, we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral sclerosis compared with five healthy controls. Substantial upregulation of serum proteins related to multiple functional clusters was observed in patients with sporadic amyotrophic lateral sclerosis. Potential biomarkers were selected based on functionality and expression specificity. To validate the proteomics profiles, blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay. Eight substantially upregulated serum proteins in patients with sporadic amyotrophic lateral sclerosis were selected, of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls (area under the curve [AUC] = 0.713, P < 0.0001). To further enhance diagnostic accuracy, a multi-protein combined discriminant algorithm was developed incorporating five proteins (hemoglobin beta, cathelicidin-related antimicrobial peptide, talin-1, zyxin, and translationally-controlled tumor protein). The algorithm achieved an AUC of 0.811 and a P -value of < 0.0001, resulting in 79% sensitivity and 71% specificity for the diagnosis of sporadic amyotrophic lateral sclerosis. Subsequently, the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls, as well as patients with different disease severities, was examined. A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls (AUC = 0.766, P < 0.0001). Moreover, the expression of three proteins (FK506 binding protein 1A, cathelicidin-related antimicrobial peptide, and hemoglobin beta-1) was found to increase with disease progression. The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in combination with current clinical-based parameters.