Advances in cancer screening and treatment have improved survival, while neurological complications in patients with cancer are gaining clinical relevance. Many of these complications are not attributable to direct tumor invasion, compression, or metastasis, but rather reflect immune-mediated mechanisms, treatment exposure, systemic disturbances, or tumor-associated biological processes. They are commonly discussed under categories such as paraneoplastic neurological syndromes, treatment-related neurotoxicity, immune-related adverse events, or related disorders. However, these categories often overlap and require integrated assessment across oncology and neurology. In this Correspondence, we propose “onco-neurology” as a term to describe cancer-associated neurological complications that extend beyond direct nervous system involvement. This concept complements neuro-oncology and paraneoplastic neurological syndromes by emphasizing treatment-related, immune-mediated, systemic, and mixed neurological disorders. Recognition of this field may reduce diagnostic fragmentation, support multidisciplinary evaluation, and promote tumor–immune–neural research.

Current treatments for neuromyelitis optica spectrum disorder (NMOSD) highlight recurrence management, while little attention is paid to the relief of residual neurological dysfunction. Here we aimed to evaluate the safety and efficacy of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in reducing relapses and mitigating neurological impairments. This trial, hUC-MSC-NMOSD (ChiCTR-INR-16008037), a single-arm, dose-escalation, open-label study, included 31 NMOSD patients of three dose groups received four infusions every three months, with 15-month follow-up. Primary outcome was time to first recurrence; secondary outcomes focused on clinical scores, MRI lesions and exploratory findings. HUC-MSC infusion was well tolerated in all groups of patients. Adverse events were mostly mild, with urinary tract infections being the most common. Severe adverse events were rare and unrelated to the treatment. The median relapse-free interval increased significantly post-treatment from 305 (95%CI 226-382·5) to 760 (589-1016·5) (p < 0·001), especially in the medium- and high-dose groups. During the two years before and after therapy, the mean Annualized Relapse Rate (ARR) dropped considerably from 1 (0·75-1) to 0 (0-0·5) (p < 0·001). Clinical scores improved in the low and medium-dose groups. The total volume of high-signal white matter lesions in brain significantly decreased after therapy from 4144·5 (2857·2-5508·6) to 2914·4 (2453-3684·11) (p = 0·016). Exploratory single-cell RNA sequencing and metabolomics detection revealed a potential participation of thioredoxin and oxidative phosphorylation (OXPHOS)-mediated boosting of Treg differentiation and suppressive capacity. This trial indicates that intravenous hUC-MSC administration is safe and shows potential efficacy in treating NMOSD. Medium dose might be the best possible compromise between safety and effectiveness.

Objective The potential role of physicochemical environmental exposures in triggering neuromyelitis optica spectrum disorder (NMOSD) remains incompletely understood. This report describes two cases of aquaporin-4 (AQP4) antibody-positive NMOSD with onset potentially linked to specific physicochemical events. Case Presentation A 29-year-old male developed optic neuritis in his right eye immediately after occupational ocular exposure to organic solvents from paint remover. He subsequently experienced six relapses over five years. A 47-year-old female presented with cervical myelitis two days after sustaining minor mandibular trauma. In both cases, serological testing confirmed AQP4-immunoglobulin G antibodies. Notably, the initial neurological manifestations (optic neuritis, myelitis) corresponded anatomically to the sites of exposure (eye, face/jaw). Conclusion These observations highlight a temporal and anatomical association between specific physicochemical exposures (organic solvents, mechanical trauma) and the onset of NMOSD in these susceptible individuals. While causality cannot be proven, the findings suggest that such factors may contribute to disease initiation in some patients, warranting further systematic investigation into environmental triggers in NMOSD pathogenesis.

BACKGROUND:Guillain-Barré syndrome (GBS) is an acute immune-mediated peripheral neuropathy for which therapeutic apheresis is an established treatment option. Various treatment modalities, including double filtration plasmapheresis (DFPP), are widely used in clinical practice; however, real-world data on their clinical outcomes and adjunctive treatment strategies remain limited. METHODS:We retrospectively analyzed 43 patients with GBS treated at a single tertiary center between June 2018 and October 2024, including 36 patients who received DFPP-containing regimens and 7 who received IVIG alone. Short-term functional outcomes were assessed using the modified Rankin scale (mRS) and Hughes functional grading scale (HFGS) at hospital admission before treatment and after completion of inpatient treatment. Changes in immunoglobulin and complement levels were evaluated in patients receiving DFPP. Exploratory analyses compared functional score changes across different treatment regimens. RESULTS:At hospital discharge, mRS and HFGS scores were significantly lower than baseline in patients receiving DFPP alone, DFPP combined with intravenous methylprednisolone, or IVIG alone. No significant differences in changes in functional scores were observed between the DFPP-alone and IVIG-alone groups or between the DFPP-alone and DFPP-plus-corticosteroid groups. DFPP significantly reduced serum immunoglobulin and complement levels; however, the percentage reductions in IgG, IgA, and IgM were not significantly correlated with short-term changes in mRS or HFGS scores. CONCLUSION:In this real-world cohort, DFPP-containing treatment was associated with short-term improvement in functional scores from hospital admission to hospital discharge. No statistically significant difference in short-term functional improvement was detected between the DFPP-alone and DFPP-plus-IVMP groups. However, the small sample size, heterogeneous treatment regimens, and lack of long-term follow-up preclude conclusions regarding sustained or comparative efficacy.

Autoimmune encephalitis (AE) is a group of disorders characterized by antibodies targeting neuronal cell surface, intracellular structures and synapse antigens. Treatment for AE involves reducing antibody levels and suppressing immune-mediated inflammation using intravenous immunoglobulin, plasma exchange (PE), and immune-modulating agents. PE is commonly used in autoimmune neurological diseases, but the safety issues of PE are worth continuous attention. This case report describes a 28-year-old patient who was diagnosed with anti-GAD65 AE and underwent treatments including double filtration plasmapheresis (DFPP), steroids, and immunosuppressive agents. However, complications arose when the patient developed thrombosis and was diagnosed with type II heparin-induced thrombocytopenia (HIT). He was treated with an oral anticoagulant and eventually recovered. One month later, follow-up examinations showed no presence of emboli and his epilepsy remained well controlled. There is a risk of HIT, a potentially dangerous adverse reaction to heparin during treatment of PE. The current case highlights the importance of monitoring for HIT during PE and the need for alternative anticoagulants.

In recent years, immune checkpoint inhibitor (ICI) has achieved remarkable success in cancer therapy. However, the occurrence of immune-related adverse event (irAE) has increasingly attracted attention. Among them, neurologic immune-related adverse event (n-irAE) is relatively uncommon, but can cause severe outcomes. n-irAE can involve multiple regions of the nervous system, including the peripheral nerves, neuromuscular junction, and central nervous system (CNS), and lead to myositis, myasthenia gravis, encephalitis, myelitis, and other disorders. The diagnosis of n-irAE requires a combination of evaluating the time correlation between symptoms and ICI medication, neurological localization assessments (neuroimaging, cerebrospinal fluid analysis, and electrophysiological studies), and the exclusion of alternative etiologies such as metastatic disease or infection. n-irAE is graded and treated based on clinical severity, and the common therapeutic approaches include corticosteroids, intravenous immunoglobulin, and plasma exchange. Multidisciplinary collaboration and early intervention are crucial for improving patient outcomes. Future efforts should focus on optimizing risk prediction models to achieve individualized management of n-irAE.

Objective: Rare disease Background: Varicella-zoster virus (VZV) encephalitis is a commonly reported form of encephalitis that clinically manifests as skin lesions, fever, headache, and neuropsychiatric symptoms. We present a case of a patient with VZV encephalitis complicated by cerebral hemorrhagic transformation, characterized by high levels of inflammation and protein in the cerebrospinal fluid. The aim is to highlight the risk of hemorrhagic transformation associated with VZV encephalitis. Case Report: The patient exhibited scattered herpes lesions on the head, neck, and chest. Notably, the cerebrospinal fluid (CSF) protein concentration was markedly elevated at 9049.3 mg/L, with a CSF white blood cell count of 950x106/L, of which lymphocytes constituted 80%. MRI revealed abnormal signal foci in the bilateral temporal lobes and the right frontal lobe, consistent with findings associated with herpes encephalitis. Despite initial treatment with anti-inflammatory agents, acyclovir antiviral, and antiepileptic medications, the patient did not show improvement, prompting the addition of double filtration plasmapheresis. However, the patient experienced hemorrhagic transformation and succumbed to the illness. Conclusions: This case highlights the challenge of managing VZV encephalitis in the context of significant inflammation and protein elevation in the CSF, and underscores the need for further research into more effective therapeutic strategies for this rare but potentially devastating condition.

ObjectiveThis study aims to investigate the impact of clinical characteristics, antibody types, timing of treatment, and tumor comorbidities on the efficacy and prognosis of patients with autoimmune encephalitis (AE), aiming to provide a reference for clinical management. MethodsA retrospective analysis was conducted on the medical records of 203 AE patients admitted to the Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from January 2020 to June 2025. Statistical analysis was performed on patients’ gender, age, disease course, antibody types, and tumor screening results to evaluate their impact on treatment efficacy. Additionally, the clinical assessment scale for autoimmune encephalitis (CASE) scoring system was used to assess treatment outcomes. ResultsA total of 203 AE patients were included in the study, in which 56.2% cases were male, a median age was 50 years, and most of the disease course was subacute (64.0%). The antibody profiles showed high heterogeneity, with N-methyl-D-aspartate receptor (NMDAR) antibodies being the most common (24.1%). Treatment outcomes revealed that an overall improvement rate is 79.8%, but the significant improvement rate was only 11.3%. The tumor comorbidity rate was 15.3%, and the efficacy of treatment in patients with tumors was slightly lower than that of the non-tumor group. ConclusionsThe efficacy of AE treatment is influenced by multiple factors, including antibody characteristics, timing of treatment, disease severity, and tumor comorbidities. Timely immunotherapy significantly impacts prognosis, and early diagnosis and treatment can improve clinical outcomes. Precise antibody testing and systematic tumor screening are crucial strategies for promoting the prognosis of AE patients. Future clinical management should strengthen comprehensive assessment of the above factors to achieve optimal treatment outcomes and enhance long-term prognosis.

The retinal astrocyte death induced by complement-dependent cytotoxicity (CDC) is the major etiology of retinal injury in patients with neuromyelitis optica spectrum disorders (NMOSD). Human umbilical cord-derived mesenchymal stromal cells (hUCMSCs) and their derived extracellular vesicles (EVs) have emerged as a potential therapeutic option due to their immunomodulatory capabilities. This study is aimed at establishing a serum-free culture system for hUCMSCs (SF-UCMSCs) and investigating the inhibiting effect of EVs derived from SF-UCMSCs on CDC-induced retinal astrocyte death. The results showed that SF-UCMSCs retained canonical mesenchymal stromal cells’ characteristics under serum-free culture conditions. Pharmacokinetic analysis showed that intravenously administered SF-UCMSCs predominantly accumulated in the lungs, liver, spleen, and kidneys, with no detectable localization in the retina. Notably, EVs derived from SF-UCMSCs exerted a protective effect against CDC-mediated damage to murine retinal astrocytes, as evidenced by reduced formation of C5b-9 + membrane attack complexes and diminished astrocyte death. Mechanistically, this protective effect was associated with the transfer of CD59 from EVs to astrocytes. In summary, the establishment of this serum-free culture system facilitates the development of hUCMSC-derived EVs as therapeutic agents, circumventing the risks of immune rejection and potential tumorigenicity associated with cellular transplantation. This study also provides a mechanistic basis and therapeutic strategy for managing autoimmune diseases characterized by CDC-mediated pathogenesis.

INTRODUCTION:Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system.METHODS:We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy.RESULTS:Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids.CONCLUSION:DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.

Objective: This study aims to evaluate the effectiveness of double-filtration plasmapheresis (DFPP) in reducing immunoglobulins and culprit antibodies in neuroimmune disorders. Methods: A retrospective analysis was conducted on 51 patients with neuroimmune diseases treated with DFPP, immunotherapy, and symptomatic treatment. Immunoglobulin and antibody levels were measured pre- and post-treatment, along with neurological function assessments using scales like the modified Rankin Scale (mRS), Expanded Disability Status Scale (EDSS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), and Myasthenia Gravis-specific scales. Results: The cohort included patients with neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AIE), myasthenia gravis (MG), anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD), and paraneoplastic neurological syndromes (PNS). DFPP significantly reduced immunoglobulin levels (IgG, IgA, IgM) by similar to 70 %. Most patients showed decreased antibody titers and significant neurological improvement. The median mRS score improved from 2 (IQR 2-3) to 1 (IQR 1-2) post-treatment, with further improvement at 90 days. Notable improvements were observed across various scales specific to NMOSD, MOGAD, AIE, and MG. Minor adverse events were reported, with no serious adverse events. Conclusions: DFPP is effective in reducing immunoglobulin and antibody levels, leading to improved neurological function in neuroimmune disorders. Further large-scale studies are warranted to confirm these findings.

Patients with both myasthenia gravis (MG) and SARS-CoV-2 infection face treatment challenges due to potential drug interactions. One common immunosuppressant for MG, Tacrolimus, is primarily metabolized by the cytochrome P450. However, Paxlovid, an antiviral medication, inhibits cytochrome P450 activity, which can lead to increased Tacrolimus levels and potential toxicity when the two drugs are combined. In this case report, we present the case of a 39-year-old woman with early-onset MG who was initially treated with Tacrolimus. Later, she received Paxlovid for SARS-CoV-2 infection, which resulted in a sudden spike in Tacrolimus levels due to the drug interaction. This case emphasizes the importance of personalized treatment plans and close monitoring of drug interactions in patients with multiple health conditions. Clinicians should exercise vigilance regarding potential Tacrolimus interactions and regularly monitor blood levels to prevent adverse effects. Caution and close monitoring of Tacrolimus levels are essential when administering Paxlovid to patients on Tacrolimus therapy.

Background Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC–MSCs) in treating NMOSD. Methods The trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC—MSCs. Patients will be treated with three different doses of hUC–MSCs: 1, 2, or 5 × 10 6 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years. Discussion Although hUC–MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC–MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC–MSC in treating NMOSD and might be able to determine the optimal dose of hUC–MSC for NMOSD patients. Trial registration The study was registered with the Chinese Clinical Trial Registry ( CHICTR.org.cn ) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.

目的:首次报道1例伴顽固性低钠血症的抗γ-氨基丁酸B受体(gamma-aminobutyric acid B receptor,GABABR)抗体相关脑炎合并小细胞肺癌患者,旨在进一步认识其临床特征、可能的发生机制、诊治方法以及预后.方法:报道1例伴顽固性低钠血症的抗GABABR抗体相关脑炎合并小细胞肺癌患者的临床表现、辅助检查结果、诊疗经过以及预后,并结合相关文献复习,分析可能的发生机制.结果:患者为老年女性,因"发作性意识不清伴四肢抽搐"就诊,并且很快进展为癫痫持续状态,伴有精神异常和认知障碍.血和脑脊液抗GABABR抗体阳性,合并顽固性低钠血症.头颅MRI检查未见明显异常.PET-CT检查显示,左侧肺门及左肺下叶结节及团块影,伴18F-氟代脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)代谢异常增高,考虑恶性病变可能.经皮肺穿刺活检诊断为左肺小细胞癌伴纵膈淋巴结转移.给予糖皮质激素冲击治疗、静脉滴注丙种球蛋白、小细胞肺癌化疗和放疗以及针对癫痫发作、精神症状和低钠血症的对症治疗后,患者的癫痫发作、精神症状和认知障碍均有所缓解,但低钠血症仍无法纠正,同时肺部肿瘤病灶逐渐增大.后续随访发现患者可能发生小细胞肺癌脑转移.结论:抗GABABR抗体相关脑炎伴顽固性低钠血症可能与自身免疫或小细胞肺癌所致的抗利尿激素异常分泌相关,但对其发生机制尚待进一步阐明.

目的 观察硫胺素缺乏对小鼠脑内Tau蛋白的影响.方法 小鼠随机分为硫胺素缺乏组和正常对照组,予以造模处理后,提取小鼠皮层及海马脑组织,HPLC测定硫胺素代谢产物含量,蛋白印迹分析总Tau蛋白及其磷酸化水平.结果 与正常对照组比较,硫胺素缺乏组脑内硫胺素代谢物含量显著降低(P<0.01),脑内过度磷酸化Tau蛋白含量显著增加(P<0.01),且Tau蛋白空间构建改变并提示蛋白聚集和难溶性Tau蛋白组分增加(P<0.01).结论 硫胺素缺乏引起Tau蛋白过度磷酸化及难溶性Tau蛋白水平增加,引起Tau蛋白过度聚集.

BACKGROUND AND AIMS:Elevated urinary albumin-creatinine ratio (ACR) is an established risk factor for lower extremity peripheral arterial disease (PAD) in non-diabetes individual. This study aimed to determine the relationship between urinary ACR level and PAD in diabetes population. METHODS AND RESULTS:A cross-section study with 1396 hospitalized diabetes participants from department of endocrinology and neurology were performed and the propensity score matching method was applied to reduce the effects of confounding factors between the matched PAD and Non-PAD groups. The relationship between urinary ACR and ankle-brachial index (ABI) was analyzed by linear curve fitting analyses and multiple logistic regression models. Our study showed that the prevalence of PAD (low ABI, ABI<0.9) was 7.09% in our diabetes patients. The ABI level was significantly lower in high ACR group compared with those in normal urinary ACR group (1.11 ± 0.17 vs 1.13 ± 0.15, p = 0.010). The prevalence of PAD was increased with the increased tertile's of log2-transformed ACR in total patients before and after propensity score matching (p < 0.001 and p = 0.007, respectively). The OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.70 (1.08-2.69, p = 0.022) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. After propensity score matching, the OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.85 (1.05-3.23, p = 0.031) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. CONCLUSION:The elevated urinary ACR level was associated with PAD in Chinese diabetes patients.

Imaging techniques including transcranial Doppler (TCD), magnetic resonance imaging (MRI), computed tomography (CT), and cerebral angiography are available for cerebrovascular disease diagnosis. TCD is a less expensive, non-invasive, and practically simpler approach to diagnosing cerebrovascular disorders than the others. TCD is a commonly available and inexpensive diagnostic tool. However, owing to its large operator dependency, it has a narrow application area. Cerebrovascular disease indicates a group of disorders that alter the flow of blood in the brain. The brain's functions can be temporarily or permanently impaired as a result of this change in blood flow. Timely diagnosis and treatment can restore the brain-impaired functions, resulting in a much-improved prognosis for the patients. This review summarizes the basic principles underlying the TCD imaging technique and its utility as a diagnostic tool for cerebrovascular disease.

Cell-based assays (CBAs) and radioimmunoprecipitation assay (RIPA) are the most sensitive methods for identifying anti-acetylcholine receptor (AChR) antibody in myasthenia gravis (MG). But CBAs are limited in clinical practice by transient transfection. We established a stable cell line (KL525) expressing clustered AChR by infecting HEK 293T cells with dual lentiviral vectors expressing the genes encoding the human AChR α1, β1, δ, ϵ and the clustering protein rapsyn. We verified the stable expression of human clustered AChR by immunofluorescence, immunoblotting, and real-time PCR. Fluorescence-activated cell sorting (FACS) was used to detect anti-AChR antibodies in 103 MG patients and 58 healthy individuals. The positive results of MG patients reported by the KL525 was 80.6% (83/103), 29.1% higher than the 51.4% (53/103) of RIPA. 58 healthy individuals tested by both the KL525 CBA and RIPA were all negative. In summary, the stable expression of clustered AChR in our cell line makes it highly sensitive and advantageous for broad clinical application in CBAs.

Cell trapping is a very useful technique in a variety of cell-based assays and cellular research fields. It requires a high-throughput, high-efficiency operation to isolate cells of interest and immobilize the captured cells at specific positions. In this study, a dentate spiral microfluidic structure is proposed for cell trapping. The structure consists of a main spiral channel connecting an inlet and an out and a large number of dentate traps on the side of the channel. The density of the traps is high. When a cell comes across an empty trap, the cell suddenly makes a turn and enters the trap. Once the trap captures enough cells, the trap becomes closed and the following cells pass by the trap. The microfluidic structure is optimized based on the investigation of the influence over the flow. In the demonstration, 4T1 mouse breast cancer cells injected into the chip can be efficiently captured and isolated in the different traps. The cell trapping operates at a very high flow rate (40 μL/s) and a high trapping efficiency (>90%) can be achieved. The proposed high-throughput cell-trapping technique can be adopted in the many applications, including rapid microfluidic cell-based assays and isolation of rare circulating tumor cells from a large volume of blood sample.