Frontiers in Neurology最新文献

Objective: To investigate the changes in circulating biomarkers of patients with acute anterior circulation large vessel occlusive cerebral infarction (ACLVO) following endovascular therapy (EVT), and to explore their potential utility as early predictors for the development of stroke-associated pneumonia (SAP).

Methods: Peripheral blood samples were collected from ACLVO patients on days 1, 3, and 7 following EVT. Samples were analyzed to detect monocyte human leukocyte antigen-DR (mHLA-DR) expression level, along with plasma levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT).

Results: Multivariate binary logistic regression analysis adjusted for clinical confounders identified decreased mHLA DR expression at day 1 and dysphagia as independent SAP predictors (P < 0.001). Compared to the non-SAP group, the SAP group showed significantly lower expression of mHLA-DR on days 1, 3, and 7 (P < 0.001), plasma IL-6 and CRP levels were significantly higher on days 3 and 7 (P < 0.05), as was the plasma PCT level on day 7 (P < 0.05). Infarct volume was significantly larger in the SAP group (P < 0.001). In predictive modeling, expression of mHLA-DR on days 1 alone yielded an AUC of 0.914 (optimal cutoff: 55.75%). Decision curve analysis showed that expression of mHLA-DR on days 1 offered greater net benefit than other clinical scores, and that combining it with the A2DS2 score provided a superior, stable net benefit for SAP prediction.

Conclusion: In this exploratory study, our findings suggest that mHLA-DR expression levels may indicate some predictive value for SAP development after EVT in ACLVO patients, with the predictive performance appearing enhanced when combined with the A2DS2 score. Dysphagia and a large infarct volume emerged as potential risk factors for SAP. Conversely, within the context of our cohort, plasma levels of IL-6, CRP, and PCT did not demonstrate clear utility for the early prediction of SAP.

Alzheimer's disease (AD) is a gradual and irreversible decline in the brain's ability to function which is not only signified by amyloid-beta plaques and neurofibrillary tangles but also by and metabolic and mitochondrial changes that have a negative impact on the classical neuropathological hallmarks. It is becoming increasingly clear that the central roles in the process of synaptic dysfunction, neuronal death and cognitive decline are played by the brain's impaired glucose utilization, insulin resistance, lipid metabolism alterations, and energy homeostasis disruption. Mitochondrial dysfunctions in AD comprising of oxidative phosphorylation defects, ATP production decrease, reactive oxygen species generation over and above the normal level, poor mitochondrial dynamics, and vacuolar-type H+-ATPase-mediated cell death are the factors that further worsen the situation and hence speed up the process of neuronal death and eventually, disease progression. The metabolic and mitochondrial disturbances have a two-way relationship with amyloid-beta and tau pathology, neuroinflammation, and oxidative stress, thus creating a self-sustaining cycle of neurodegeneration. Besides, clinical and neuroimaging studies, fluorodeoxyglucose positron emission tomography, cerebrospinal fluid biomarkers, and peripheral metabolic profiling all support the notion that metabolic impairment is an early and clinically relevant feature of AD very convincingly. Thus, the attention of the scientific community has turned more and more toward the approaches that use the metabolic and mitochondrial pathways as their target. The new treatments are coming, including insulin sensitizers, ketogenic and Mediterranean diets, mitochondrial-targeted antioxidants, exercise, metabolic modulators, and new drugs, all aimed at bringing back equilibrium to bioenergetics and letting neurons live longer. In this review, we have considered the current mechanistic insights, clinical evidence, and therapeutic advances related to metabolic dysfunction and mitochondrial failure in AD together and their potential as early biomarkers and modifiable targets for disease prevention and treatment that are highlighted.

This study is a descriptive analysis that systematically delineates the perioperative outcome profiles of Kawase, endoscope-assisted retrosigmoid, and pterional approaches for resecting petrous apex lesions within the clinical decision-making framework of "anatomical location first." A retrospective series of 27 patients was included. Based on the core anatomical location of the lesion, surgery was performed via the Kawase approach (anteromedial region, n = 14), the endoscope-assisted retrosigmoid approach (posterior region, n = 7), or the pterional approach (superoanterior region, n = 6). The results demonstrate that surgical approaches corresponding to different anatomical subregions exhibited characteristic outcome profiles. For anteromedial petrous apex lesions, the Kawase approach achieved a high gross total resection rate (100%), but was associated with longer operative time and a higher risk of postoperative intracranial infection. For posterior lesions, the endoscope-assisted retrosigmoid approach provided excellent exposure with minimal tissue trauma and a relatively balanced complication spectrum. For superoanterior lesions, the pterional approach, while allowing direct access, was associated with higher rates of postoperative cranial nerve dysfunction (trigeminal nerve injury 50%, facial nerve palsy 67%) and speech impairment (50%). In a subgroup analysis focusing on the predominant pathology (meningioma, n = 20), these outcome differences linked to specific anatomical location-approach pairings persisted. The findings indicate that surgical outcomes for petrous apex lesions are closely associated with the approach dictated by their anatomical location, presenting a predictable characteristic profile. Therefore, clinical decision-making should prioritize the precise anatomical location of the lesion when selecting the surgical approach, and fully acknowledge the inherent perioperative risk profile specific to each "anatomical region-surgical approach" pairing. The integration of ancillary techniques such as neuroendoscopy with classic approaches holds promise for further optimizing outcomes in complex cases. This study is a single-center, retrospective, descriptive analysis with a limited sample size; its conclusions require validation by prospective, large-sample studies.

Background: Eye movements play an essential role in the assessment of the unconscious patient and offer a window to the function of the brain. We review the range of ocular motor and vestibular findings in patients with impaired consciousness and present a practical approach to these patients.

Methods: Based on a structured review of the literature (Pubmed, Embase) 54 suitable citations were identified amongst 4,241 total citations. A manual search of the reference list of selected papers added another 57 papers. Based on these publications the spectrum of eye movement abnormalities in the unconscious patient was characterized.

Results: The pattern of eye movement abnormalities seen in the unconscious patient depends on the underlying cause and the extent/location of brain damage. Conjugate eye deviations may be observed with either supratentorial or infratentorial lesions, while disconjugate deviations may indicate superimposed eye muscle palsies or decompensated strabismus. The presence of a full range of spontaneous horizontal, oscillatory eye movements (e.g., ping-pong gaze) in the comatose patient usually indicates bilateral cerebral hemisphere dysfunction. With vertical spontaneous eye movements, the identification of a slower and faster phase helps to distinguish between nystagmus and ocular bobbing and its variants. Combined with absent reflexively-induced eye movements, typical ocular bobbing strongly suggests a structural pontine lesion, whereas other vertical spontaneous eye movement patterns do not predict specific (focal) damage. The reflexive eye movements, i.e., the vestibulo-ocular reflex (VOR), can be assessed in comatose patients either by head rotations, caloric irrigation or galvanic stimulation. Intact slow-phase responses indicate relatively preserved brainstem function and inability to keep the eyes in an eccentric position suggest a deficient velocity-to-position integrator either from brainstem or cerebellar involvement.

Conclusion: Ocular motor and vestibular testing in unconscious patients offer a unique opportunity to assess both brainstem and cerebellar function and its interplay with higher cortical areas. It may also help predict outcome. Challenges to overcome include a lack of standardized diagnostic approaches to unconscious patients. Quantitative eye movement analysis, based on videooculography (VOG) and artificial intelligence using large multimodal data sets are promising new tools for diagnosis, longitudinal observational studies and prediction of outcome.

Background: The associations of modified triglyceride-glucose (TyG) indices with risks of dementia subtypes and brain structural changes remain unclear. This study prospectively examines whether modified TyG indices, including TyG with body mass index (TyG-BMI) and TyG with waist circumference (TyG-WC), are associated with the risks of Alzheimer's disease (AD) and vascular dementia (VaD) and with structural brain alterations.

Materials and methods: This study analyzed 356,454 dementia-free participants from the UK Biobank. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident AD and VaD. Restricted cubic spline (RCS) analyses assessed nonlinear relationships. Linear regression models evaluated associations between modified TyG indices and brain structures, including hippocampal volume and white matter hyperintensity (WMH) volume. Subgroup analyses and sensitivity analyses were performed to test robustness.

Results: During follow-up, 2,594 AD and 1,386 VaD cases were identified. In fully adjusted Cox models, both TyG-BMI and TyG-WC showed clear dose-response patterns with dementia risk. Using Q5 as the reference, participants in the lowest sextile (Q1) had a 47% higher risk of AD for TyG-BMI (HR = 1.47, FDR-adjusted p < 0.001) and a 23% higher risk for TyG-WC (HR = 1.23, FDR-adjusted p = 0.019), while those in the highest sextile (Q6) also tended to have increased AD risk. By contrast, VaD risk increased with higher modified TyG levels, and participants in the highest sextile had 32 and 45% higher VaD risk for TyG-BMI and TyG-WC, respectively (TyG-BMI: HR = 1.32, FDR-adjusted p = 0.029; TyG-WC: HR = 1.45, FDR-adjusted p = 0.011). Multivariable-adjusted restricted cubic spline analyses confirmed significant nonlinear relationships, showing a broad U-shaped association of modified TyG indices with AD and a J-shaped association with VaD. Higher modified TyG indices were additionally linked to larger hippocampal volume but greater WMH burden. The associations remained robust in multiple sensitivity analyses.

Conclusion: Modified TyG indices show nonlinear, differential associations with AD and VaD risks, and are linked to structural brain alterations. These findings highlight the importance of metabolic health in dementia prevention and brain aging.

Background: Pulmonary embolism (PE) and cerebrovascular disease are major global causes of mortality and may share common risk factors. This study analyzed U.S. all-cause mortality trends where PE and cerebrovascular diseases were recorded on the death certificate from 1999 to 2023.

Methods: Using national all-cause mortality data for adults aged over 25 years whose death certificates recorded both PE (ICD-10 I26) and cerebrovascular diseases (ICD-10 I60-I69), we calculated age-adjusted mortality rates (AAMRs), standardized to the 2000 U.S. population. Joinpoint regression was applied to identify significant trends and compute annual and average annual percent changes (APC and AAPC). Subgroup analyses were performed by sex, age, race, region, and urbanization level.

Results: Between 1999 and 2023, 59,075 U.S. deaths involved both pulmonary embolism and cerebrovascular disease, with 4,274 recorded in 2023. Age-adjusted mortality increased from 1.00 to 1.55 per 100,000 (AAPC: 1.93%), accelerating sharply during 2018-2021. Higher AAMR was observed in males, adults over 85 years, Non-Hispanic Black individuals, residents of the South, and non-metropolitan areas. Substantial geographic heterogeneity existed, with states such as Minnesota, Washington, Massachusetts, and Florida showing significant long-term upward trends.

Conclusion: The accelerating mortality and pronounced disparities across demographic and geographic groups highlight the need for more precise public health strategies. Mitigating this burden requires targeted interventions for high-risk populations, equity-focused policies, improved healthcare access, geriatric-sensitive care, and strengthened infrastructure in vulnerable regions.

Accurate and reliable segmentation of multiple sclerosis (MS) lesions from magnetic resonance imaging (MRI) is essential for diagnosis and monitoring disease progression. Therefore, a robust and efficient automated approach can rapidly provide information about the patient. Here, a convolutional neural network-based method is proposed to segment lesions from FLAIR images. The DenseLessystem includes two stages: pre-processing of image data (brain extraction, standardization), then segmentation of MS lesions using an end-to-end slice-wise dense network. We also identified the segmented lesions in specific locations [periventricular, (juxta)cortical, infratentorial, and spinal]. DenseLesis evaluated and compared to other methods on our assembled data and the public MSSEG 2016 MS challenge dataset. Our model demonstrates a significant improvement in segmentation quality over previous approaches, achieving an average Dice score of 0.80% on the Szeged MS dataset. On the MSSEG 2016 dataset, our method achieved Dice scores ranging from 0.32% to 0.73%, comparable to those of human raters.

Background: Dizziness in anterior circulation stroke (ACS) has not been well characterized. We aimed to examine the frequency of dizziness and its associated factors in ACS, and to compare these findings with posterior circulation stroke (PCS).

Methods: We prospectively enrolled consecutive patients with acute ischemic stroke from July 2021 to July 2022, categorized into ACS and PCS groups. The presence of new-onset dizziness was assessed within 7 days of stroke onset in clinically stable patients, excluding those with severe deficits that precluded survey completion. Clinical variables, depressive symptoms (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), and neuroimaging findings were collected. Multivariable logistic regression analyses were performed to identify factors independently associated with dizziness.

Results: Among 169 patients (98 ACS, 71 PCS), dizziness was reported in 45.9% of patients with ACS and 60.6% of those with PCS. In the ACS group, the presence of cerebral microbleeds [adjusted odds ratio (aOR) = 3.19, 95% confidence interval (CI) 1.09-9.32, p = 0.034] or a higher number of microbleeds (aOR = 2.38, 95% CI 1.10-5.15, p = 0.026) were independently associated with dizziness. In the PCS group, dizziness was independently associated with medullary or cerebellar lesions (aOR = 3.13, 95% CI 1.01-9.74, p = 0.048).

Conclusion: Dizziness was common in patients with ACS, with a frequency comparable to that in PCS. The absence of an association with depressive or anxiety symptoms, together with the link to cerebral microbleeds, suggests that dizziness in ACS may reflect underlying structural or vascular mechanisms, warranting greater clinical attention.

Introduction: Alzheimer's disease (AD), the most common neurodegenerative disorder, poses significant challenges for early screening due to the clinical and environmental constraints of traditional neuropsychological assessments.

Methods: This study developed a mobile terminal-based cognitive assessment system (mCAS) and prospectively validated its screening efficacy through a diagnostic trial. We recruited 63 memory clinic patients (aged 20-75 years), all of whom independently completed mCAS testing after undergoing standardized MMSE and MoCA evaluations. Through a systematic review of 10 existing mild cognitive impairment (MCI) screening tools, we extracted 25 test items to construct the assessment framework.

Results: Our results demonstrated that, under the optimal Gradient Boosting model, mCAS achieved an area under the curve (AUC) of 0.884 for discriminating MCI while maintaining diagnostic equivalence in sensitivity compared to conventional instruments (p > 0.05 in all pairwise comparisons). Specificity was significantly lower than MoCA only for MCI identification (p = 0.027).

Discussion: The system's core innovations include: (1) A multimodal digital assessment framework that overcomes the environmental limitations of conventional scales; (2) Self-administration capability in non-medical settings; and (3) A dynamic cognitive baseline model to facilitate longitudinal monitoring. mCAS provides a convenient screening solution for early AD detection, with significant potential particularly in resource-limited regions. Future multicenter validation and biomarker integration studies are warranted.

Introduction: Leptomeningeal disease (LMD) of the brain and spinal cord can present with visual loss or diplopia. Although LMD can occur in many forms of neoplasia, thymoma-related LMD is exceedingly rare.

Patient presentation: A 53-year-old Hispanic male with a history of chest pain, weight loss, and night sweats was diagnosed with stage 4 thymoma with lung and pleural metastasis. He received chemotherapy for metastatic thymoma. Few months later, patient presented with severe right-sided facial pain and lip numbness, ptosis and double vision.

Primary diagnosis: The patient was diagnosed with multiple cranial and spinal nerve involvement due to thymomatous LMD, confirmed on magnetic resonance imaging and lumbar puncture.

Conclusion and importance: LMD is a rare presentation of a malignant thymoma. Current guidelines for thymoma management emphasize the importance of staging imaging to rule out distant metastasis. Our case highlights the importance of a head-to-mid-thigh positron emission tomography (PET) scan in patients with known metastatic thymomas, with multiple PET scans, if possible, at regular intervals, owing to the aggressive nature of metastatic thymomas. Clinicians should be aware of the neoplastic (e.g., metastatic disease and LMD) and paraneoplastic (e.g., thymoma-related myasthenia gravis) neuro-ophthalmic presentations of thymoma.