Frontiers in Neurology最新文献

Background: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) with rt-PA can precipitate rapid neurological deterioration, poor prognosis, and even death. The HALP score (hemoglobin, albumin, lymphocyte, and platelet) is a novel indicator developed to reflect both systemic inflammation and the nutritional status of patients. The goal of this study was to reveal the relationship between the HALP score and the risk of HT after IVT in people with acute ischemic stroke (AIS).

Methods: A total of 753 patients with AIS were included in this study. Patients were divided into quartiles according to baseline HALP score. The HALP score was calculated as follows: hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). Binary logistic regression was used to reveal the connection between HALP score and HT.

Results: The baseline HALP score were significantly lower in the HT than non-HT patients (p < 0.001). The HALP score were divided into four quartiles: Q1 (<27.4), Q2 (27.4-37.6), Q3 (37.7-49.6), Q4 (>49.6), respectively. Moreover, the severity of HT increased with decreasing HALP level (p < 0.001). In multivariable logistic regression, taking the Q4 as the reference, the association between Q1 and HT remained, after adjusting for confounding variables [odds ratio (OR) = 3.197, 95% confidence interval (CI) = 1.634-6.635, p = 0.003].

Conclusion: The HALP value can predict the HT risk after IVT in patients with AIS. A lower HALP level was associated with an increased severity of HT post-IVT.

Background: Migraine is a widespread, recurrent primary headache disorder primarily characterized by severe pulsatile headache, typically on one or both sides. It is often accompanied by nausea, vomiting, and hypersensitivity to sound and light. Despite the availability of multiple drugs for migraine management, the condition often becomes chronic due to untimely or irrational drug use, significantly distressing patients and increasing the burden on families and society. Over the past two decades, numerous clinical studies on migraine have been published. This study aimed to provide a comprehensive summary of the current status and trends of migraine clinical trials through bibliometric analysis.

Methods: We used visual network tools such as CiteSpace and VOSviewer to perform a knowledge graph analysis of publications related to migraine clinical trials extracted from the WoSCC.

Results: This study analyzed 1,129 articles published in 389 journals from 61 countries. The number of publications on migraine clinical trials has steadily increased from 2004 to 2023. The United States and Albert Einstein College of Medicine are the leading countries and institutions in this field, respectively. Richard B. Lipton is the most prolific author, making significant contributions to the research. The journal Headache has the highest number of publications and citations in this area. Keywords such as "efficacy," "RCT," "CGRP," "prophylaxis," "disability," "depression," "questionnaire," and "real-world effectiveness" received significant attention.

Conclusion: This study identified reliable research hotspots and provided directions for clinicians. The treatment of migraine continues to be challenging. Future trends may include continued growth in migraine classification, risk factor analysis, and comorbidity studies. Research on CGRP and epigenetics will advance the progress of precision medicine in the migraine field.

Background: Frailty, defined as multidimensional prognostic index (MPI), has been recently identified as strong predictor of disability and mortality in the elderly with acute ischemic stroke (AIS). The stress hyperglycemia ratio (SHR) is a recently introduced biomarker significantly associated with poor outcome in AIS.

Objectives: This study aimed to investigate in what extent frailty, measured by MPI, and SHR affects the 3-months outcome of patients > 65 years-old with AIS.

Methods: Consecutive patients with AIS >65 years-old who underwent intravenous thrombolysis (IVT) from 2015 to 2019 were enrolled in a German and an Italian Stroke Unit. The SHR was calculated by dividing the fasting plasma glucose at admission with glycated hemoglobin. Demographics and clinical premorbid data, stroke-related variables, including baseline and post-treatment NIHSS score were included in a logistic regression model. The 3-months functional outcome was evaluated by using modified Rankin scale (mRS); good outcome was defined as mRS 0-2, poor as mRS ≥ 3.

Results: One hundred and fifty-five AIS patients were enrolled in the study. Median MPI was 0.19 [0.13-0.31]; 118 (76.1%) patients were classified as "robust" and 37 (23.9%) as "frail." In regression analysis, age, NIHSS, and MPI demonstrated as the most significant predictor of 3-months good outcome in the whole cohort. In robust patients, SHR values were significantly associated with the outcome.

Conclusions: MPI is associated with the 3-months outcome in our cohort, in particular with good outcome. Conversely, SHR seems to be associated with a 3-months poor outcome in "robust" patients but not in frail patients.

Introduction: Dementia comprise a broad spectrum of cognitive declines affecting 47 million people worldwide, with numbers projected to reach 131 million by 2050. Predominantly associated with older adults, dementia can also impact younger individuals, having a significant impact on daily functioning of the affected patients, relatives, caregivers and the socioeconomic system. Recent research underscores the utility of social media, particularly X (previously designed as Twitter), in understanding public perceptions and sentiments related to neurological disorders. Despite some initial studies have explored social perceptions of dementia in X, broader and deeper analysis of this condition is still warranted.

Materials and methods: In this retrospective study, we collected and examined all tweets posted in English or Spanish from 2007 to 2023 that mentioned dementia and compare the information with other highly representative neurological disorders like migraines, epilepsy, multiple sclerosis, spinal cord injury, or Parkinson's disease. We developed a codebook to analyze tweets, classifying them by themes such as trivialization, treatment perceptions, and etiopathogenesis. Manually categorized tweets trained machine learning models, BERTWEET for English and BETO for Spanish, which then classified larger datasets with high accuracy. Statistical analysis, including ANOVA, Kruskal-Wallis, and chi-square tests, was conducted to explore linguistic and cultural differences in perceptions of neurological disorders, with results visualized.

Results: Our study reveals that dementia is by far the most frequently discussed neurological disorder on X. Likewise, this condition appears to be the most trivialized neurological disorder in Spanish tweets and the second most trivialized in English tweets, with notable differences in geolocation data. Additionally, we found significant differences in perceptions of dementia treatment and associated sentiments between Spanish and English tweets. Furthermore, our study identified varying perceptions of medical content (etiology) and non-medical content (positive/negative experiences and aid requests) related to dementia and other neurological disorders, unveiling a complex landscape of these topics on X.

Conclusions: This study explores the importance of X as a social platform for addressing various critical issues related to dementia, comparing it with other neurological disorders in English and Spanish tweets. Future research could further investigate the valuable role of social media in understanding public perceptions and needs regarding dementia and neurological disorders among X users.

Background: Mechanical thrombectomy (MT) is a well-established treatment for acute basilar artery occlusion (BAO)-induced posterior circulation ischemic stroke.

Objective: The objective of the study was to compare the outcomes of endovascular therapy (EVT) with and without bridging intravenous thrombolysis (IVT) in patients with acute BAO, using an updated meta-analysis.

Methods: A systematic literature search was conducted to identify studies that compared the efficacy and safety of EVT with and without IVT in the treatment of acute BAO ischemic stroke. The extracted data included sample size, patient age, National Institutes of Health Stroke Scale (NIHSS) scores, 90-day modified Rankin Scale (mRS) scores of 0-2 and 0-3, mortality rates, symptomatic intracranial hemorrhage (sICH), and occurrence of subarachnoid hemorrhage (SAH).

Results: Five studies that included a total of 1,578 patients (594 IVT + EVT vs. 984 EVT), met the inclusion criteria and were analyzed. The meta-analysis demonstrated that bridging IVT was associated with a higher likelihood of achieving a 90-day mRS score of 0-2 (41% vs. 34%; OR = 1.35, 95% CI 1.09-1.68, p = 0.006). Furthermore, the mortality rate was significantly lower in the IVT + EVT group than in the direct EVT group (25% vs. 30%; OR = 0.70, 95% CI 0.55-0.89, p = 0.003), with low heterogeneity observed (I ² = 0.0%, p = 0.78). However, there were no significant differences between the groups regarding the rates of sICH (5% vs. 6%; OR = 0.85, 95% CI: 0.52-1.39, p = 0.53), SAH (3% vs. 3%; OR = 0.93, 95% CI: 0.39-2.22, p = 0.87), perforation (2% vs. 3%; OR = 0.71, 95% CI 0.26-1.95, p = 0.51), and dissection (3% vs. 2%; OR = 0.97, 95% CI: 0.13-7.14, p = 0.98).

Conclusion: Bridging IVT in conjunction with EVT was associated with better functional outcomes and reduced mortality rates in patients with acute ischemic stroke (AIS) due to BAO compared to EVT alone, without an increased risk of sICH, SAH, perforation, and dissection. In addition, the benefit of bridging IVT to EVT appeared to be more pronounced in European patients than in Asian patients compared to EVT alone. However, the conclusions of this study are not definitive and require validation through large-scale randomized controlled trials (RCTs) to draw more robust conclusions.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024531363.

Background: Environmental contaminants may play a significant role in the development of migraine. Perchlorate, nitrate, and thiocyanate were selected for this study due to their known impact on thyroid function, which is closely linked to neurological processes. Disruptions in thyroid function have been associated with various neurological disorders, including migraines. However, there is currently no evidence linking exposure to these specific chemicals to migraine. The study aims to evaluate the association between urinary concentrations of perchlorate, nitrate, and thiocyanate with the prevalence of severe headache or migraine in U.S. adults.

Methods: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. Utilizing electrospray tandem mass spectrometry in conjunction with ion chromatography, urinary concentrations of perchlorate, nitrate, and thiocyanate urine were measured. Multiple logistic regression models were employed to evaluate the linear correlation between perchlorate, nitrate, and thiocyanate exposure and severe headache or migraine. The non-linear relationship is described analytically using a fitted smoothing curve and a two-piecewise regression model. Subgroup analyses were used to further clarify the stability of this relationship across different populations.

Results: There were 1,446 participants in this population-based study, ranging in age from 20 to 85. After adjusting for potential confounding variables, the multiple logistic regression findings demonstrated that thiocyanate was significantly positively associated with the prevalence of migraine (odds ratio [OR] = 1.18; [1.06, 1.30]; p < 0.001). There was consistency in this connection across different subgroups (p for interaction >0.05). Furthermore, there was a non-linear correlation between urinary thiocyanate and migraine. Using a fitted smoothing curve and a two-piecewise regression model, it was found that the correlation between urinary thiocyanate and migraine was U-shaped (p for Log-likelihood ratio = 0.002). According to the findings of the multiple regression analysis, there was no significant correlation between urinary perchlorate and nitrate and migraine (both p > 0.05).

Conclusion: We should limit our exposure to thiocyanate by keeping it within a reasonable range, as indicated by the U-shaped correlation between urinary thiocyanate and migraine.

Background: Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity. The phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate, total number of gadolinium-enhancing (Gd+) T1 lesions, and total number of new or enlarging T2 at Week 96, as well as improvement in the proportion of participants with no evidence of disease activity (NEDA) from Weeks 24-96 with ublituximab vs. teriflunomide.

Methods: In ULTIMATE I (NCT03277261; www.clinicaltrials.gov) (N = 549) and II (NCT03277248; www.clinicaltrials.gov) (N = 545), participants with relapsing multiple sclerosis received ublituximab 450 mg intravenous infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks. Pooled post hoc analyses evaluated NEDA by treatment epoch and participant subtype: age ( ≤ 38 or >38 years), early or later disease (<3 or ≥3 years following diagnosis), treatment history (treatment naïve or previously treated), 0 or ≥1 Gd+ T1 lesions at baseline, and Expanded Disability Status Scale score ≤ 3.5 or >3.5 at baseline. NEDA was defined as no confirmed relapses, no Gd+ T1 lesions, no new or enlarging T2 lesions, and no disability progression confirmed for ≥12 weeks.

Results: NEDA rates in the ublituximab vs. teriflunomide cohorts by treatment epoch were: Weeks 0-96, 44.6% vs. 12.4% (3.6 × improvement); Weeks 24-96 (re-baselined), 82.1% vs. 22.5% (3.6 × improvement); and Weeks 48-96 (re-baselined), 88.2% vs. 30.4% (2.9 × improvement) (all p < 0.0001). The primary driver of disease activity in ublituximab-treated participants was new or enlarging T2 lesions during Weeks 0-24. 41.8% of ublituximab-treated participants who had evidence of disease activity in the first year (Weeks 0-48) experienced NEDA in the second year of treatment (Weeks 48-96) compared with 17.3% of teriflunomide-treated participants. At Weeks 24-96 (re-baselined), rates of NEDA were significantly higher with ublituximab than teriflunomide in all participant subtypes (all p < 0.0001).

Conclusions: ULTIMATE I and II pooled post hoc analyses demonstrated a consistent NEDA benefit among ublituximab-treated participants across treatment epochs and key participant subpopulations.

Introduction: Knowledge of the natural and temporal course of a disease is important when deciding if an intervention is appropriate. In the case of Ménière's disease (MD), there is some evidence that attacks diminish over time, but the topic remains controversial. A conservative approach to surgery is usually followed in northern Europe, and leads to strict patient selection before considering surgery. Here, we describe the evolution of vertigo attacks among a group of intractable MD patients in whom surgery was considered.

Methods: Retrospective cohort study in a Ménière's disease expert center. Patients with definite unilateral Ménière's disease and persisting vertigo attacks despite treatment with intratympanic steroid injections were included. All patients had been waitlisted for participation in a planned trial assessing non-ablative surgery. They were waitlisted between June 2016 and June 2021 without undergoing the surgical intervention. In September 2022, data were collected from patient's files and follow-up telephone interviews were conducted to assess the evolution of their vertigo attacks.

Results: Thirty-five patients (54% male, mean age of onset 52 years, 51% right sided) were included in the analysis. Twenty-five patients (71%) eventually declined surgery. Of the 33 patients with complete information on vertigo attacks, 21 (64%) were free of vertigo attacks upon data collection, after a median disease duration of 5.3 years. Patients who did undergo surgery, had longer duration of disease than patients who did not.

Discussion: Even in a population with intractable MD, most patients will experience relief of symptoms over time. On one hand, active treatment may accelerate relief of symptoms, but on the other hand, non-ablative therapies are of debatable effect and ablative intervention carries a risk of life long side effects. Therefore, any active intervention should be carefully considered.

Cochlear outer hair cells (OHCs) play a fundamental role in the hearing sensitivity and frequency selectivity of mammalian hearing and are especially vulnerable to noise-induced damage. The OHCs depend on Ca²⁺ homeostasis, which is a balance between Ca²⁺ influx and extrusion, as well as Ca²⁺ buffering by proteins and organelles. Alterations in OHC Ca²⁺ homeostasis is not only an immediate response to noise, but also associated with impaired auditory function. However, there is little known about the contribution of Ca²⁺ buffering proteins and organelles to the vulnerability of OHCs to noise. In this study, we used a knockout (KO) mouse model where oncomodulin (Ocm), the major Ca²⁺ binding protein preferentially expressed in OHCs, is deleted. We show that Ocm KO mice were more susceptible to noise induced hearing loss compared to wildtype (WT) mice. Following noise exposure (106 dB SPL, 2 h), Ocm KO mice had higher threshold shifts and increased OHC loss and TUNEL staining, compared to age-matched WT mice. Mitochondrial morphology was significantly altered in Ocm KO OHCs compared to WT OHCs. Before noise exposure, Ocm KO OHCs showed decreased mitochondrial abundance, volume, and branching compared to WT OHCs, as measured by immunocytochemical staining of outer mitochondrial membrane protein, TOM20. Following noise exposure, mitochondrial proteins were barely visible in Ocm KO OHCs. Using a mammalian cell culture model of prolonged cytosolic Ca²⁺ overload, we show that OCM has protective effects against changes in mitochondrial morphology and apoptosis. These experiments suggest that disruption of Ca²⁺ buffering leads to an increase in noise vulnerability and mitochondrial-associated changes in OHCs.