With the increasing clinical use of anti-amyloid-β (Aβ) monoclonal antibodies in Alzheimer's disease (AD) in China, some patients have completed or are approaching the predefined treatment period, leading to emerging clinical questions regarding post-treatment maintenance, discontinuation, monitoring, and retreatment. However, no consensus has yet been established on long-term management or sequential-like treatment strategies after anti-Aβ monoclonal antibody therapy. Based on current clinical evidence and the practical experience of the Cognitive Center of Renji Hospital, Shanghai Jiao Tong University School of Medicine, this article proposes an experience-based protocol for sequential-like management of anti-Aβ monoclonal antibody therapy. The protocol uses amyloid PET-derived Centiloid values as the core objective reference and recommends stratified management according to clinical clearance status and prior amyloid clearance rate. After treatment discontinuation, dynamic monitoring with plasma p-tau217 protein and amyloid PET is recommended, and an increase in the Centiloid value to >24.1 CL may serve as an important reference for restarting anti-Aβ monoclonal antibody therapy. This protocol is intended to provide a clinical reference and requires further validation and optimization through real-world studies and long-term follow-up.
Objectives： Parkinson’s disease (PD) is a neurodegenerative disorder affecting multiple systems. Previous studies have indicated that autonomic dysfunction in PD patients may manifest in the early stages of the disease. This study aims to investigate the correlation between autonomic dysfunction and the progression of motor symptoms in PD patients.
Methods： A total of 738 PD patients participated in this research. The status of autonomic dysfunction was examined by Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT). And the motor progression was monitored by using Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Besides, neuropsychological status was recorded using Hamilton Depression Scale and Hamilton Anxiety Scale. The participants were followed up for 2 years (±3 months) and the MDS-UPDRS was reassessed to examine the progress in motor function.
Results： The SCOPA-AUT score was significantly correlated with the total MDS-UPDRS score (P＜0.001) as well as the changes in Part Ⅰ (P＝0.005), Part Ⅱ (P＜ 0.001), and Part Ⅲ (P＜0.001) scores (absolute difference between baseline and 2-year follow-up). Among the sub-items of SCOPA-AUT, the scores for autonomic dysfunction related to digestive system, urinary system, cardiovascular symptoms, skin symptoms, and drug use showed significant correlations with the total MDS-UPDRS score and certain sub-scores. However, sexual dysfunction and changes in motor scores did not show significant correlations with the total MDS-UPDRS score or changes in any sub-scores.
Conclusions： Autonomic dysfunction could be considered as a potential predictor of motor progression in PD.
Objective: To report the clinical features of a sporadic amyotrophic lateral sclerosis (ALS) patient carrying a HARS1 variant with mildly elevated cerebrospinal fluid (CSF) protein, and to discuss the clinical significance of CSF protein changes in ALS as well as the co-occurrence of the HARS1 variant and CSF protein elevation.
Methods: The patient's clinical symptoms, electrophysiology, imaging, cerebrospinal fluid, and genetic test results were documented, alongside a literature review and analysis.
Results: The patient, a middle-aged female, presented with a progressively worsening disease course. The primary clinical manifestations included increasing limb weakness, dysarthria, atrophy of the tongue muscles, hyperactive tendon reflexes, and positive pathological signs. Cerebrospinal fluid analysis revealed elevated protein levels. Electromyography demonstrated extensive neurogenic damage, while imaging studies indicated involvement of the corticospinal tract. Genetic testing identified a heterozygous variant of HARS1 c.210G>A (p.Met70Ile).Based on these findings, a clinical diagnosis of ALS was established. Following treatment with riluzole, coenzyme Q10, and short-term corticosteroid therapy, the patient's condition stabilized.
Conclusion: This ALS patient with a rare HARS1 variant suggests a broader clinical spectrum for this gene than previously known. The slight increase in CSF protein indicates blood-brain barrier dysfunction rather than an immune response. The pathogenicity of the HARS1 variant needs further study and additional cases for confirmation. As mild CSF protein elevation is not uncommon in ALS, it should not be interpreted as specifically attributable to the HARS1 variant; the two findings may be independent or indirectly linked by shared neurodegenerative pathology.
Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly population. Currently, the global number of AD patients has reached nearly 55 million, and there is still no cure for the disease to date. Traditional diagnostic methods rely heavily on clinical scales and subjective judgment, resulting in an early diagnostic sensitivity of less than 70%. However, in recent years, the rapid development of deep learning and large language models has provided brand-new technical approaches for AD’s early screening, accurate diagnosis, disease progression monitoring, drug development, and personalized intervention. This article systematically sorts out the main hypotheses regarding the pathogenesis of AD, and in-depth analyzes the application achievements of general large models (such as GPT-4, Llama 3, Gemma, etc.) and multimodal models (Flamingo, CLIP, ImageBind) in various aspects of AD management. On this basis, it proposes a domain-specific large model framework specifically designed for the full-course management of AD — AD Research Generative Pre-trained Transformer (ADR-GPT). By integrating knowledge, multi-task pre-training, deep learning, and interpretability modules, this framework is committed to achieving more accurate early prediction and personalized intervention under the premise of controllable data privacy. It provides a currently implementable technical solution to achieve the goal of “early diagnosis and treatment, precise intervention” for AD.
Alzheimer’s disease (AD) is a common progressive neurodegenerative disease characterized prominently by recent memory impairment, often accompanied by psychiatric and behavioral symptoms as well as varying degrees of functional impairment in daily living abilities. The insidious onset and gradual progression of AD pose substantial challenges to early clinical diagnosis. Under the amyloid β -tau-neurodegeneration (ATN) diagnostic framework proposed by the National Institute on Aging and Alzheimer’s Association (NIAAA) in 2024, the biological diagnosis of AD mainly relies on cerebrospinal fluid examination and positron emission tomography (PET), but the former is invasive and the latter is expensive and equipment dependent, severely limiting their clinical popularity. Therefore, exploring a non-invasive, economical, and dynamic functional biomarker that can reflect neurodegeneration (i. e., “N”) has become an urgent problem in this field. Electroencephalogram (EEG) has shown unique advantages in the study of cognitive impairment due to its low cost, non-invasive nature, high temporal resolution, and good reproducibility. Its signals are highly sensitive to synaptic dysfunction and abnormal network oscillations, and can capture real-time brain network dysfunction and directly map the electrophysiological basis of neurodegeneration. In recent years, the combined application of EEG with multimodal neuroimaging techniques, such as transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), and functional nearinfrared spectroscopy (fNIRS), has developed rapidly, providing rich functional information for early identification of AD from multiple dimensions, including cortical excitability, causal network connectivity, oscillation blood flow coupling, and neurovascular coupling. This article systematically reviews the application progress of resting-state EEG spectrum and microstate analysis, TMS-EEG, EEG-fMRI, and EEG-fNIRS in AD and mild cognitive impairment (MCI), focusing on how these non-invasive techniques complement and integrate with existing ATN diagnostic frameworks. At the same time, it analyzes the limitations faced by current research in sample size, standardization, and clinical translation, and looks forward to future technological optimization, multi-center validation, and potential pathway for intergrating the ATN diagnostic network.
Objective: To investigate the mechanism of Gandou Fumu Decoction in the treatment of hepatolenticular degeneration (HLD, also known as Wilson’s disease) using network pharmacology and molecular docking techniques.
Methods: The chemical constituents of Gandou Fumu Decoction and their corresponding targets were retrieved and screened using databases including TCMSP and UniProt. The intersection between the drug-related targets and disease targets was identified using R (v4.4.0) to determine the potential targets through which Gandou Fumu Decoction may exert therapeutic effects on Wilson’s disease, and the VennDiagram package was employed to visualize the overlapping targets via a Venn diagram. All node information from the network was imported into Cytoscape (v3.9.1) to construct a “traditional Chinese medicine-compound-target-disease” network. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the “clusterProfiler” and “org. Hs. eg. db” packages. Molecular docking simulations were then conducted between the core compounds and key targets to provide preliminary verification of the network pharmacology findings.
Results: Gandou Fumu Decoction may exert its therapeutic effects on Wilson’s disesase through active constituents such as quercetin, β -sitosterol, kaempferol, stigmasterol, and naringin, acting on key targets including B-cell lymphoma 2 (BCL2), RELA proto-oncogene NF- κB subunit (RELA), protein kinase C alpha (PRKCA), and prostaglandin-endoperoxide synthase 2 (PTGS2). The major enriched pathways include lipid metabolism and atherosclerosis, the tumor necrosis factor (TNF) signaling pathway, the PI3K-Akt signaling pathway, hepatitis B, hepatitis C, the interleukin (IL) -17 signaling pathway, the hypoxiainducible factor (HIF)-1 signaling pathway, alcoholic fatty liver disease, and hepatocellular carcinoma. Molecular docking analysis indicates strong binding affinities between the key components and their corresponding targets.
Conclusion: The therapeutic mechanism of Gandou Fumu Decoction in treating Wilson’s disease is characterized by multiple active components, multiple targets, and multiple pathways.
Modified electroconvulsive therapy (MECT) and repetitive transcranial magnetic stimulation (rTMS) are effective physical interventions for major depressive disorder (MDD); however, they exert opposing effects on cognitive function. MECT acts rapidly but is frequently accompanied by impairments in memory and executive function, whereas rTMS not only alleviates mood symptoms but also preserves and even enhances cognition. This review systematically delineates and compares the core mechanisms of these two treatments across four dimensions: synaptic plasticity, brain-derived neurotrophic factor (BDNF) signaling, neuroinflammation, and neurogenesis. The cognitive costs of MECT arise from generalized seizure-induced overactivation of N-methyl-D-aspartate (NMDA) receptors, dysregulated BDNF release, and a downstream neuroinflammatory cascade. In contrast, the cognitive protective mechanism of rTMS is rooted in the physiological activation of BDNF-tropomyosin receptor kinase B (TrkB) signaling and the induction of orderly long-term potentiation (LTP)-like effects, thereby achieving precise and benign modulation of synaptic plasticity. This article further dissects the intersections and divergences of these two modalities at key molecular nodes, proposes a mechanistic framework that transitions from a “cognitive paradox” to a “synergistic dialogue,” and provides a theoretical basis and future research directions for optimizing clinical parameters, designing combination treatment regimens, and guiding individualized treatment decisions in MDD.
Post-stroke upper-limb motor recovery is often slow, substantially compromising patients' ability to perform activities of daily living and quality of life. As a novel closed-loop neuromodulation strategy, brain-computer interface (BCI) rehabilitation robots can decode neural activity signals in real time and convert them into control commands, enabling information interaction between the brain and the rehabilitation robot. Training with BCI rehabilitation robots can effectively improve upper-limb motor dysfunction in stroke patients. This article systematically reviews the key research progress, neural mechanisms, and existing challenges in the application of BCI rehabilitation robots for upper-limb motor recovery after stroke, aiming to provide references for researchers and clinicians in the fields of rehabilitation medicine, neural engineering, and robotics.
Under the backdrop of the comprehensive promotion of ideological and political education in higher education curricula, the construction of ideological and political education in the neurology master’s program is of critical importance. This study focuses on the construction and practice of a teaching case library, aiming to deeply integrate ideological and political elements into professional teaching. By forming a multidisciplinary team, it delves into the ideological and political materials in the clinical, research, and disciplinary history of neurology, meticulously constructing a case library covering multiple dimensions including diagnostic and treatment standards and professional ethics for neurological disorders, the spirit of scientific research innovation, and medical humanistic care. Through practical application in the master’s program and evaluation by means of questionnaires and assessment of students’ academic performance, the results showed that the case library effectively enhanced students’ ideological and political literacy, stimulated their enthusiasm for professional learning, improved their communication skills with patients, and promoted their awareness of social responsibility. This provided a solid support for the cultivation of neurology master’s students and offered a practical example for the construction of ideological and political education in similar medical professional courses.
Objective: To characterize the imaging features, pathological basis, and diagnostic approach to the spinal cord “snake-eyes sign”, with particular emphasis on its relevance to acute spinal cord ischemia.
Methods: The clinical presentation, neurological examination, imaging findings, and laboratory data of a woman with acute-onset myelopathy and the “snake-eyes sign” on cervical spinal cord MRI was retrospectively reviewed, and the imaging characteristics and differential diagnosis were discussed in conjunction with the literature.
Results: The patient developed sudden back pain followed within hours by quadriparesis and urinary retention. Cervical spinal cord MRI showed an intramedullary lesion at the C5-7 levels, with bilateral symmetric round hyperintensities in the anterior horns on axial images, consistent with the “snake-eyes sign”. Spinal angiography showed poor visualization of the anterior spinal artery. Cerebrospinal fluid routine and biochemical studies were unremarkable, and relevant immunological antibody tests were negative. Anterior spinal artery syndrome was considered the leading diagnosis. Follow-up MRI at 3 months showed a reduction in lesion extent.
Conclusion: The “snake-eyes sign” indicates selective involvement of the anterior horns but is not specific for spinal cord ischemia. In patients with acute, rapidly progressive motor, sensory, and autonomic dysfunction, anterior spinal artery territory ischemia should be strongly considered, while the clinical course, MRI, vascular imaging, cerebrospinal fluid findings, and immunological studies should be integrated to distinguish ischemic lesions from compressive, inflammatory, and other myelopathies.
