Vestibular migraine (VM) is a common episodic vestibular disorder characterized by a high misdiagnosis rate. It substantially impairs patients’ health-related quality of life and imposes considerable medical and socioeconomic burdens. In recent years, significant advances have been achieved globally and in China in the diagnosis and management of VM, laying a solid foundation for promoting standardized outpatient care and establishing a medical quality control evaluation system. Against this background, the Chinese Expert Collaboration Group for Medical Quality Control of Vestibular Migraine fully drew on international and domestic research evidence, closely integrated the current situation and clinical practice of dizziness and headache management in China, and strictly followed the Delphi procedure. The initial draft was formulated through systematic literature retrieval, and multiple rounds of anonymous questionnaires were conducted to extensively solicit opinions from national and regional experts, with continuous revisions until consensus was reached. The expert panel comprehensively reviewed relevant literature and guidelines worldwide, combined with expert interviews and multiple group discussions. After repeated demonstration and refinement, the panel finally established a complete set of 13 outpatient medical quality control indicators covering the whole clinical pathway of VM, including initial consultation, diagnosis, comorbidity evaluation, treatment and follow-up, among which 8 are assessment indicators and 5 are reference indicators. The present expert consensus embraces these indicators as a standardized tool to systematically promote the standardization and quality improvement of clinical practice for vestibular migraine.

OBJECTIVE:The objectives of this study were to observe the differences between the left and right eyes in healthy individuals during binocular video head impulse testing (vHIT) and to identify the optimal eye for a more precise evaluation of the vestibulo-ocular reflex (VOR) gain. MATERIALS AND METHODS:This is a prospective two-center study involving 41 healthy individuals. All participants included in the study underwent binocular vHIT, which was performed by experienced technicians. RESULTS:Significant differences in VOR gain were observed between the left and right eyes across all six semicircular canals when binocular vHIT was used (t 1 = 3.621, P 1 = 0.001; t 2 = 13.929, P 2 < 0.001; t 3 = -3.598, P 3 = 0.001; t 4 = -3.929, P 4 < 0.001; t 5 = -14.380, P 5 < 0.001; t 6 = 5.507, P 6 < 0.001). The gains were higher in the adduction eye than in the abduction eye (t 1 = 13.929, P 1 < 0.001; t 2 = -14.38, P 2 < 0.001). The gains were lower in the left eye than in the right eye when the left posterior-right anterior (LPRA) plane was tested (t 1 = 5.507, P 1 < 0.001; t 2 = 3.621, P 2 = 0.001) and the gains were lower in the right eye than in the left eye when the right posterior-left anterior (RPLA) plane was tested (t 1 = -3.598, P 1 = 0.001; t 2 = -3.929, P 2 < 0.001). CONCLUSIONS:The binocular vHIT can be used as an optimization of monocular vHIT, assisting in selecting the ideal test eye in clinical protocols, aiming for a VOR gain closer to 1. We suggest using the anterior eye as the reference eye during testing of the vertical semicircular canal (SCC) plane and selecting the abducting eye as the reference when testing the horizontal SCC plane. LEVELS OF EVIDENCE:3.

Alzheimer's disease is a debilitating, progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins, including amyloid plaques and intracellular tau tangles, primarily within the brain. Lysosomes, crucial intracellular organelles responsible for protein degradation, play a key role in maintaining cellular homeostasis. Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases, including Alzheimer's disease. Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer's disease. Currently, the efficacy of drugs in treating Alzheimer's disease is limited, with major challenges in drug delivery efficiency and targeting. Recently, nanomaterials have gained widespread use in Alzheimer's disease drug research owing to their favorable physical and chemical properties. This review aims to provide a comprehensive overview of recent advances in using nanomaterials (polymeric nanomaterials, nanoemulsions, and carbon-based nanomaterials) to enhance lysosomal function in treating Alzheimer's disease. This review also explores new concepts and potential therapeutic strategies for Alzheimer's disease through the integration of nanomaterials and modulation of lysosomal function. In conclusion, this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer's disease. The application of nanotechnology to the development of Alzheimer's disease drugs brings new ideas and approaches for future treatment of this disease.

A novel Co(II)-based metal-organic framework (MOF) {[Co2(TCPP)(BPY)](DMF)3}n (1) with a pillared structure based on 2,3,5,6-tetrakis(4-carboxyphenyl)pyrazine (H4TCPP) and 4,4'-bipyridine (BPY) is designed and synthesized via the solvothermal reaction. Furthermore, a green-hand grinding technique is implemented to reduce the particle size of complex 1 to generate nanoscale 1 (denoted as nano-1 hereafter). After the construction of the acute cerebral infarction animal model, the infarct area of the brain is measured after 2 weeks of treatment with the compound. Then, ELISA is performed to detect the content of hs-CRP and IL-1b and TNF-a in the serum.

RATIONALE:Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis characterized by diverse neurological and psychiatric symptoms. It predominantly affects young women, particularly those with ovarian teratomas. However, cases without teratomas are also commonly reported, often exhibiting poorer treatment responses and higher relapse rates. Persistent fever and signs of meningitis are rare in such cases. Diagnosis is confirmed through the detection of anti-NMDAR antibodies. PATIENT CONCERNS:A 15-year-old female presented with episodic loss of consciousness, fever, nuchal rigidity, limb convulsions, and psychiatric symptoms following a stressful exam period. Initial symptomatic treatments were ineffective. DIAGNOSIS:The diagnosis of anti-NMDAR encephalitis was confirmed through lumbar puncture, brain imaging, and the detection of anti-NMDAR antibodies in cerebrospinal fluid and serum. INTERVENTIONS:The patient received tailored first-line therapy, including high-dose methylprednisolone and 3 courses of intravenous immunoglobulin (IVIG). OUTCOMES:The patient exhibited significant clinical improvement, with a reduction in seizure frequency and eventual complete seizure control. Body temperature normalized, and follow-up showed progressive recovery in cognitive and motor functions. LESSONS:This case highlights the importance of early diagnosis and individualized treatment in anti-NMDAR encephalitis. Repeated IVIG courses proved effective, underscoring the need for personalized treatment plans in managing this condition. Persistent fever and signs of meningitis were rare and contributed to the diagnostic challenge, highlighting the clinical complexity of this case.

Objective: This study aims to explore the mechanism underlying the induction of phlebitis by aescinate and create an early-warning model of phlebitis based on metabolomics. Methods: Patients with cerebral infarction enrolled had been treated with aescinate. Plasma samples were collected either before administration of aescinate, upon the occurrence of phlebitis, or at the end of treatment. Non-targeted metabolomics and targeted amino acid metabolomics were carried out to analyze metabolic profiles and quantify the metabolites. Results: Untargeted metabolomics revealed six differential metabolites in baseline samples versus post-treatment samples and four differential metabolites in baseline samples from patients with or without phlebitis. Pathways of these differential metabolites were mainly enriched in amino acid metabolism. Ten differential amino acids with a VIP value of >1 were identified in the baseline samples, enabling us to distinguish between patients with or without phlebitis. A logistic regression model Y = -0.001*sarcosine - 0.01*hippuric acid + 2.46 was constructed (AUC 0.825) for early warning of phlebitis of grade 2 or higher. Conclusion: The occurrence of aescinate-induced phlebitis, which can be predicted early during onset, may be associated with perturbations of the endogenous metabolic profile, especially the metabolism of amino acids.

The objective of this study is to examine the efficacy of magnetic resonance imaging (MRI) features and peripheral blood biomarkers in assessing cognitive function in patients with cerebral small vessel disease (CSVD). A total of 58 CSVD patients were recruited. Six features of white matter hyperintensities (WMHs) were derived from MRI scans. Additionally, five neurodegenerative biomarkers (Aβ40, Aβ42, t-tau, p-tau181, NfL) and 13 serum inflammatory cytokines (VILIP-1, CCL2, IL-6, IL-18, TNF-α, CX3CL, sTREM-1/2, VEGF, s-RAGE, BNDF, TGF-β1, β-NGF) were quantified. Cognitive assessments were conducted using standardized neuropsychological scales. Spearman analysis revealed that the volumetric characteristics (absolute area, upper area, bottom area, absolute area percentage, upper percentage, and bottom percentage) of WMHs were negatively correlated with performance on all cognitive scale measures except the verbal fluency test (VFT) (r < -0.3, p > 0.05), while they were positively correlated with plasma neurofilament light (NFL) levels (r > 0.4, p < 0.05). Additionally, serum tumor necrosis factor-α (TNF-α) and soluble receptor for advanced glycation end-products (s-RAGE) showed significant correlations with scales of speech function. An integrated model incorporating WMHs features, neurodegenerative biomarkers, and neuroinflammatory markers was developed, demonstrating high predictive accuracy for cognitive impairment with an area under the curve (AUC) of 0.95 (accuracy 0.88, sensitivity 0.87, specificity 0.89). Another integrated model that includes features of WMHs and inflammatory cytokines for predicting cerebral microbleeds (CMBs) achieved an AUC of 0.95 (accuracy 0.88, sensitivity 0.82, specificity 0.92). Our findings suggest that these markers have the potential to be used for the early detection of cognitive decline and CMBs in patients with CSVD.

Alzheimer's disease (AD) poses a significant burden on the economy and healthcare systems worldwide. Although the pathophysiology of AD remains debatable, its progression is strongly correlated with the accumulation of tau aggregates. Therefore, tau clearance from brain lesions can be a promising strategy for AD therapy. To achieve this, the present study combined proteolysis-targeting chimera (PROTAC), a novel protein-degradation technique that mediates degradation of target proteins via the ubiquitin-proteasome system, and a neurotransmitter-derived lipidoid (NT-lipidoid) nanoparticle delivery system with high blood-brain barrier-penetration activity, to generate a novel nanomedicine named NPD. Peptide 1, a cationic tau-targeting PROTAC is loaded onto the positively charged nanoparticles using DNA-intercalation technology. The resulting nanomedicine displayed good encapsulation efficiency, serum stability, drug release profile, and blood-brain barrier-penetration capability. Furthermore, NPD potently induced tau clearance in both cultured neuronal cells and the brains of AD mice. Moreover, intravenous injection of NPD led to a significant improvement in the cognitive function of the AD mice, without any remarkable abnormalities, thereby supporting its clinical development. Collectively, the novel nanomedicine developed in this study may serve as an innovative strategy for AD therapy, since it effectively and specifically induces tau protein clearance in brain lesions, which in turn enhances cognition.

Age is a significant contributor to the onset of AD. Senolysis has been recently demonstrated to ameliorate aging-associated diseases that showing a great potential in AD therapy. However, due to the presence of BBB, the anti-AD activity of senolytics are significantly diminished. SSK1 is a prodrug that can be activated by beta-gal, a lysosomal enzyme commonly upregulated in senescent cells, and thus selectively eliminates senescent cells. Furthermore, the level of beta-gal is significantly correlated with conventional AD genes from clinical sequencing data. SSK1-loaded neurotransmitter -derived lipid nanoparticles are herein developed (SSK1-NPs) that revealing good BBB penetration and bioavailability of in the body. At the brain lesion, SSK1-NP treatment significantly reduces the expression of genes associated with senescence, induced senescent cells elimination, decreased amyloid-beta accumulation, and eventually improve cognitive function of aged AD mice. SSK1-NPs, a novel nanomedicine displaying potent anti-AD activity and excellent safety profile, provides a promising strategy for AD therapy. In this study, a novel nanomedicine is generated, SSK1-NPs, that efficiently delivers SSK1 into the brain, at where SSK1 is then specifically cleaved by lysosomal beta-gal that is expressed at higher levels in aged cells, followed by the release of its active form, gemcitabine, which in turn induces the apoptosis of senescent cells leading to the reduction of amyloid-beta accumulation and improvement of cognitive function in aged AD mice. image

Brain diseases, encompassing neurodegenerative disorders, strokes, and brain tumors, represent significant medical conditions with profound implications for human health. The blood-brain barrier (BBB) and the blood-cerebral-spinal cord barrier (BCSFB) limited drug penetration, poor drug targeting, and limited proliferation and easy death of mature neuronal cells greatly impair regeneration of the central nervous system after the injury, and thus call for more advanced therapeutic strategies in the clinic. Biomedical hydrogel research presents a potentially novel therapeutic approach for the management of brain disorders. Hydrogels are extremely biocompatible scaffolding materials that can be loaded with a variety of drugs for achieving effective treatments for brain disorders and can be customized with different mechanical properties to match the target organ or modulate its environment. This article offers an overview of recent research progress, challenges, and prospective developments in the utilization of hydrogels for treating brain disorders, with the objective of accentuating their potential as an early intervention in the preclinical phase. The unique mechanisms of drug release in hydrogels are examined in detail: extended-release medications, environmental release of drugs, and the material's own activity. An understanding of these mechanisms helps to make more effective drug delivery systems to the brain possible.

Background Epidemiological studies suggest a link between gastroesophageal reflux disease (GERD) and migraine, but the causal relationship remains unclear. This study aimed to clarify this relationship using two-sample Mendelian Randomization (MR). Methods Data on GERD and migraine, including subtypes with aura (MA) and without aura (MO), were collected from genome-wide association studies (GWAS). SNPs were selected as instrumental variables (IVs) by accounting for linkage disequilibrium and removing unbalanced connections. The primary analysis used the inverse variance-weighted (IVW) method with supplementary analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept, and MR-PRESSO. Finally, reverse causality was explored. Results The IVW method indicated a causal link between GERD and increased risk of migraine (OR = 1.381, 95% CI: 1.190–1.602, p = 2.04E-05), particularly the MO subtype (OR = 1.600, 95% CI: 1.311–1.953, p = 3.67E-06). No significant association was found for MA (OR = 1.193, 95% CI: 0.983–1.449, p = 0.074). Reverse MR analysis showed no causal relationship between migraine and GERD. Conclusion GERD is causally linked to an increased risk of migraine, especially the MO subtype. No reverse causal relationship was found, highlighting the importance of considering migraine subtypes in understanding their association with GERD.

Alzheimer's Disease Therapy SSK1-NPs efficiently delivered SSK1 into the brain, at where SSK1 is specifically cleaved by β-galactosidase, which in turn induces the apoptosis of senescent cells. Treatment of SSK1-NP induced apoptosis of senescence cells in the brain and improved cognitive function and memory in aged Alzheimer's disease mice. More in article number 2308574, Jian Zhang, Yi Luo, Yan Liu, Jie Gao, You Yin, and co-workers.

The current therapeutic drugs for Alzheimer's disease only improve symptoms, they do not delay disease progression. Therefore, there is an urgent need for new effective drugs. The underlying pathogenic factors of Alzheimer's disease are not clear, but neuroinflammation can link various hypotheses of Alzheimer's disease; hence, targeting neuroinflammation may be a new hope for Alzheimer's disease treatment. Inhibiting inflammation can restore neuronal function, promote neuroregeneration, reduce the pathological burden of Alzheimer's disease, and improve or even reverse symptoms of Alzheimer's disease. This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease; reports the mechanisms and characteristics of small-molecule drugs (e.g., nonsteroidal anti-inflammatory drugs, neurosteroids, and plant extracts); macromolecule drugs (e.g., peptides, proteins, and gene therapeutics); and nanocarriers (e.g., lipid-based nanoparticles, polymeric nanoparticles, nanoemulsions, and inorganic nanoparticles) in the treatment of Alzheimer's disease. The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

Rationale: Bilateral vestibulopathy is an important cause of imbalance. There are multiple etiologies of bilateral vestibulopathy (BVP), but reports of BVP due to otosyphilis are rare. Patient concerns: A 39-year-old male was referred to our medical center due to vertigo, persistent dizziness and gait disturbance for 2 months. Diagnoses: Bilateral vestibulopathy due to otosyphilis was considered in this case, as confirmed through analyses of vestibular function, laboratory tests, and penicillin treatment. Interventions: The patient was was treated with a high dose of penicillin G (24 × 106 IU/d) for 14 days. Outcomes: The patient’s symptoms had improved greatly following treatment, with dizziness and gait disturbance having completely resolved at 3 months following hospital discharge. Lessons: Bilateral vestibulopathy should be considered when evaluating patients with acute or subacute persistent dizziness. Clinicians should also be aware of the potential for otosyphilis among patients who report BVP.

Objective To investigate the diagnostic value of lean test in Benign paroxysmal positional vertigo of posterior semicircular canal(PC-BPPV).Methods We retrospectively included the clinical data of 220 patients with unilateral PC-BPPV who were admitted to the Department of Neurology,Jiaxing Second Hospital.All patients underwent lean test first,and then Dix-Hallpike test was performed to study the clinical characteristics of patients with vertigo induced by lean test.Results 133(60.5%)patients induced PC-BPPV typical upbeat torsional nystagmus during the lean test.During the Dix-Hallpike test,the maximum slow phase angular velocity(SPV)of the induced upbeat nystagmus was higher than the SPV value induced by the lean test,and the latency and duration of the induced nystagmus were significantly dif-ferent from the lean test(P<0.001).Conclusion The lean test has a certain reference value for the diagnosis of PC-BPPV.It is effective for the diagnosis of PC-BPPV.The lean test induces a small nystagmus and mild autonomic symp-toms compare to suspension position.In view of its simplicity,the lean test can be performed before the Dix-Hallpike op-eration.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is not just confined to the older population. Although developments have been made in AD treatment, various limitations remain to be addressed. These are partly contributed by biological hurdles, such as the blood–brain barrier and peripheral side effects, as well as by lack of carriers that can efficiently deliver the therapeutics to the brain while preserving their therapeutic efficacy. The increasing AD prevalence and the unavailability of effective treatments have encouraged researchers to develop improved, convenient, and affordable therapies. Functional materials based on primitive cells and nanotechnology are emerging as attractive therapeutics in AD treatment. Cell primitives possess distinct biological functions, including long-term circulation, lesion site targeting, and immune suppression. This review summarizes the challenges in the delivery of AD drugs and recent advances in cell primitive–based materials for AD treatment. Various cell primitives, such as cells, extracellular vesicles, and cell membranes, are presented together with their distinctive biological functions and construction strategies. Moreover, future research directions are discussed on the basis of foreseeable challenges and perspectives.

阿尔茨海默病(AD)是一种常见的中枢神经系统退行性疾病,其典型临床表现主要有认知功能进行性减退、记忆障碍、人格和行为改变、失语、失用、失认等,病理改变包括β淀粉样蛋白沉积形成的老年斑、Tau蛋白形成的神经纤维缠结、神经元及其突触的变性、胶质细胞激活增生等.该病是我国乃至全世界目前面临的巨大挑战.近年来随着全球人口老龄化,AD患者的数量也不断增加,对个人、家庭和社会都造成了极大的负担和损失.因此,对AD患者进行早期精准诊断从而尽早干预至关重要,研发用于缓解症状、延缓病情的药物也刻不容缓.本文综述了与AD精准诊断相关的诊断框架的发展历程、影像和体液生物标志物,以及目前AD治疗药物的研发进展.

OBJECTIVES:Cognitive impairment caused by cerebrovascular disease accounts for more than half of vascular dementia. However, neuropsychological tests are limited by their subjectivity. Additional effective approaches to evaluate cognitive impairment in patients with cerebrovascular disease are necessary.METHOD:One hundred and thirty-two patients with cerebrovascular disease were recruited. One hundred participants met the criteria and completed neuropsychological scales. Sixty-nine participants proceeded with polysomnography, and 63 of them had their peripheral blood biomarkers measured. According to Mini-Mental State Examination scores, patients were divided into cognitively impaired and cognitively normal groups. The differences in biomarkers and sleep parameters between the groups were compared, and decision tree models were constructed to evaluate the evaluation ability of these indicators on cognitive decline.RESULTS:The integrated decision tree model of sleep parameters yielded an area under curve (AUC) of 0.952 (95% confidence interval [CI]: 0.911-0.993), while that of plasma biomarkers yielded an AUC of 0.872 (95% CI: 0.810-0.935) in the assessment of cognition status. Then the participants were automatically clustered into mild and severe cognitive impairment groups by multiple neuropsychological test results. The integrated plasma biomarker model showed an AUC of 0.928 (95% CI: 0.88-0.977), and the integrated sleep parameter model showed an AUC of 0.851 (95% CI: 0.783-0.919) in the assessment of mild/severe cognitive impairment.DISCUSSION:Integrated models which consist of sleep parameters and plasma biomarkers can accurately evaluate dementia status and cognitive impairment in patients with cerebral small vessel disease. This innovative study may facilitate drug development, early screening, clinical diagnosis, and prognosis evaluation of the disease.

Objective To explore the research hotspots and development trend on vascular dizziness/vertigo based on visual analysis.Methods The Web of Science Core Collection Database was searched for papers on vascular dizziness/vertigo from January 2008 to March 2023.The CiteSpace 6.2.R2 software was used for visual analysis of the literature.Results There were a total of 1298 papers,with an increasing number of published papers from January 2008 to March 2023.A total of 424 institutions from 83 countries/regions had published relevant papers.The United States ranked first in terms of the number of published papers(331 papers)and betweenness centrality(0.25).Johns Hopkins University was the number one institution in terms of the number of published papers(56 papers),Newman-toker and David E were the most prolific authors.The most common keyword was ischemic stroke.According to keyword clustering,research in this field focused on early diagnosis of vascular dizziness/vertigo from risk factors and bedside examinations and infarction of the anterior inferior cerebellar artery supply area.In recent years,researchers had more interests in case reports,video electronystagmograms,and pathophysiological mechanisms in this field.Conclusion There are growing international studies on vascular dizziness/vertigo.Early diagnosis of vascular dizziness/vertigo through risk factors and bedside examinations in the emergency room is a research hotspot in this field.Researchers should focus on these topics in future studies.

Objective To explore the effects of valproate on vestibular migraine(VM)symptom improvement and vestibular function.Methods The patients with VM treated in the Dizziness Diagnosis and Treatment Center of The Sec-ond Affiliated Hospital of Naval Medical University from September 1,2019 to May 1,2021 were randomly divided into Valproate group and Flunarizine group.The patients were treated with valproate or flunarizine for three months.Before and after the treatment,the frequency of VM as well as the scores of Visual Analogue Scale(VAS)and Dizziness Handi-cap Inventory(DHI)items were recorded.Vestibular function was compared in the Valproate group before and after treat-ment.Results The VM frequency,the total scores of VAS and DHI,and the scores of VAS and DHI items in both groups were significantly reduced after the treatment.The changes in VM frequency,VAS score,DHI-F score,DHI-P score,and total DHI score before and after treatment were significantly greater in the Valproate group than in the Flunari-zine group.There was no significant difference in the variation of DHI-E score before and after treatment between the two groups.Abnormal eye movement,gaze,and spontaneous nystagmus decreased significantly in the Valproate group after treatment.There were no significant differences in abnormal caloric test,c-VEMP,o-VEMP,saccade test,smooth pursuit test,and direction-changing positional nystagmus.Conclusion Valproate can significantly improve the symptoms of VM and reduce its frequency.Valproate is more efficient than flunarizine.