Journal of the Neurological Sciences最新文献_第10页

Siponimod enhances brain-derived neurotrophic factor secretion from immune cells in multiple sclerosis: A longitudinal study 西ponimod促进多发性硬化症免疫细胞脑源性神经营养因子分泌：一项纵向研究。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-15 DOI: 10.1016/j.jns.2025.125699

Lior Fuchs , Roy Avizov , Arnon Karni , Maya Golan

Background

Siponimod is an approved drug for secondary progressive multiple sclerosis (SPMS), and may exert neuroprotective effects beyond its established immunomodulatory properties. Brain-derived neurotrophic factor (BDNF) is a key molecule supporting neuronal survival and plasticity, and its secretion by immune cells may contribute to neuroregeneration in MS. We studied the impact of long-term siponimod therapy on the secretion of BDNF and other neurotrophic factors by immune cells in MS patients.

Methods

Twenty patients diagnosed with relapsing-remitting MS (RRMS) or SPMS and receiving siponimod were assessed at baseline, 6 months, and 18 months. Peripheral blood mononuclear cells, CD3⁺ T cells, CD14⁺ monocytes, and B cell-enriched fractions were isolated and cultured ex vivo. Supernatants were analyzed for BDNF, nerve growth factor, glial cell line-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 levels.

Results

A significant increase in BDNF secretion was observed in PBMCs and T cells after 18 months of siponimod treatment. The other neurotrophins remained below detectable thresholds. Correlation of RRMS vs. SPMS analyses (age, sex, disease duration, baseline Expanded Disability Status Scale, and disease course), and multivariable regression modelling revealed no significant associations between them and treatment-induced changes in BDNF.

Conclusion

These findings suggest that prolonged siponimod therapy enhances BDNF secretion by immune cells, demonstrating a heretofore unreported neuroprotective mechanism contributing to siponimod's clinical efficacy in reducing disability progression in MS.

Key points

Our study found that long-term treatment with siponimod, a drug for multiple sclerosis MS, led to a significant increase in the release of a BDNF by immune cells. This effect was seen after 18 months and was not influenced by patients' age, disease type, or disability level. The findings suggest that siponimod may support neuroprotection and repair in MS through a newly identified mechanism beyond its known immune effects.

背景：西ponimod是一种被批准用于治疗继发性进行性多发性硬化症（SPMS）的药物，并且可能发挥神经保护作用，超出其既定的免疫调节特性。脑源性神经营养因子（Brain-derived neurotrophic factor， BDNF）是支持神经元存活和可塑性的关键分子，免疫细胞分泌BDNF可能有助于MS的神经再生。我们研究了长期西泊莫对MS患者免疫细胞分泌BDNF及其他神经营养因子的影响。方法：20例诊断为复发-缓解型多发性硬化（RRMS）或SPMS并接受西泊尼莫德治疗的患者在基线、6个月和18个月时进行评估。体外分离培养外周血单个核细胞、CD3+ T细胞、CD14+单核细胞和B细胞富集部分。分析上清液BDNF、神经生长因子、胶质细胞系来源的神经营养因子、神经营养因子-3和神经营养因子-4的水平。结果：西泊尼莫治疗18个月后，外周血单核细胞和T细胞BDNF分泌明显增加。其他神经营养因子仍低于可检测的阈值。RRMS与SPMS分析的相关性（年龄、性别、病程、基线扩展残疾状态量表和病程）和多变量回归模型显示，RRMS与治疗引起的BDNF变化之间没有显著关联。结论：这些研究结果表明，长期西波尼莫德治疗可增强免疫细胞分泌BDNF，证明了一种迄今未被报道的神经保护机制，有助于西波尼莫德在减少多发性硬化症MS残疾进展方面的临床疗效。重点：我们的研究发现，长期使用西波尼莫德治疗多发性硬化症MS，可导致免疫细胞释放BDNF显著增加。这种效果在18个月后观察到，不受患者年龄、疾病类型或残疾水平的影响。研究结果表明，西波尼莫德可能通过一种新发现的机制支持多发性硬化症的神经保护和修复，而不是通过其已知的免疫作用。

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引用次数: 0

Effectiveness and safety of prasugrel- versus clopidogrel-based dual antiplatelet therapy for acute ischemic stroke 普拉格雷与氯吡格雷双重抗血小板治疗急性缺血性卒中的有效性和安全性

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-11 DOI: 10.1016/j.jns.2025.125695

Saki Nakashima , Shotaro Aso , Hideo Yasunaga , Kenichiro Sato , Yoshiki Niimi , Toshiaki Isogai , Hiroki Matsui , Kiyohide Fushimi , Tatsushi Toda , Satoshi Kodama

Background

Although dual antiplatelet therapy (DAPT) prevents early recurrence of non-cardioembolic stroke, data on prasugrel-based DAPT are limited. We aimed to compare the effectiveness and safety of prasugrel- and clopidogrel-based DAPTs in acute atherothrombotic stroke.

Methods

Using the Diagnosis Procedure Combination database from April 2020 to March 2023, we identified patients admitted with atherothrombotic stroke who received aspirin plus clopidogrel or prasugrel. We compared a favorable functional outcome at discharge, hemorrhagic complications, seven-day mortality, and readmission for atherothrombotic stroke recurrence between the groups using propensity score overlap-weighting analyses. The number needed to treat (NNT) and harm (NNH) was calculated for each effectiveness and safety measure, respectively.

Results

Among 48,863 eligible patients (46,153 receiving clopidogrel and 2710 receiving prasugrel), the proportion of patients with a favorable functional outcome at discharge was higher in the prasugrel-based DAPT group (41.4 % vs. 40.0 %; adjusted risk difference [aRD], 1.4 %; 95 % confidence interval [CI], 0.4 %–2.4 %), corresponding to an NNT of 71. Overall hemorrhagic complications were more frequent in the prasugrel-based DAPT group (3.9 % vs. 2.4 %; aRD, 1.4 %; 95 % CI, 1.1 %–1.8 %), with an NNH of 67. No significant difference was observed in the seven-day mortality (0.50 % vs. 0.43 %; aRD, 0.07 %; 95 % CI, −0.06 %–0.21 %) or the proportion of 90-day readmissions for atherothrombotic stroke recurrence (0.91 % and 1.08 %; aRD, −0.17 %; 95 % CI, −0.37 %–0.03 %).

Conclusions

Prasugrel-based DAPT may improve outcomes without increasing early mortality, however, bleeding risk warrants caution. Careful patient selection is crucial for balancing ischemic benefits and bleeding risks, aiding acute-phase treatment decisions for high-risk patients.

虽然双重抗血小板治疗（DAPT）可以预防非心源性卒中的早期复发，但基于普拉格雷的DAPT的数据有限。我们的目的是比较基于普拉格雷和氯吡格雷的DAPTs治疗急性动脉粥样硬化性血栓性卒中的有效性和安全性。方法使用2020年4月至2023年3月的诊断程序组合数据库，我们确定了入院的动脉粥样硬化性卒中患者，他们服用阿司匹林加氯吡格雷或普拉格雷。我们使用倾向评分重叠加权分析比较了两组在出院、出血性并发症、7天死亡率和动脉粥样硬化血栓性卒中复发再入院方面的良好功能结局。分别计算每项有效和安全措施所需的治疗数（NNT）和危害数（NNH）。结果在48,863例符合条件的患者中（46,153例接受氯吡格雷治疗，2710例接受普拉格雷治疗），以普拉格雷为基础的DAPT组出院时功能预后良好的患者比例更高（41.4%比40.0%；调整后的风险差[aRD]， 1.4%； 95%可信区间[CI]， 0.4% - 2.4%），对应的NNT为71。以普拉格雷为基础的DAPT组总体出血性并发症更为频繁（3.9% vs. 2.4%; aRD, 1.4%; 95% CI, 1.1% - 1.8%）， NNH为67。7天死亡率（0.50% vs. 0.43%；平均寿命，0.07%;95% CI, - 0.06% - 0.21%）或动脉粥样硬化血栓性卒中复发的90天再入院比例（0.91%和1.08%；平均寿命，- 0.17%;95% CI, - 0.37% - 0.03%）无显著差异。结论：基于sprasugrel的DAPT可以改善预后，但不会增加早期死亡率，但出血风险值得警惕。谨慎的患者选择对于平衡缺血益处和出血风险至关重要，有助于高风险患者的急性期治疗决策。

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引用次数: 0

Ocrelizumab modulates the IL-2 signaling pathway and associated lncRNAs in multiple sclerosis Ocrelizumab调节多发性硬化症中IL-2信号通路和相关lncrna

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-11 DOI: 10.1016/j.jns.2025.125693

Fatemeh Rangani , Mohammad Ali Nahayati , Majid Pahlevan Kakhki , Seyed Hamid Aghaee-Bakhtiari

Ocrelizumab, a CD20⁺ B cell-depleting monoclonal antibody, is widely used in multiple sclerosis (MS), yet its molecular impact on immune regulation remains incompletely defined. Given the importance of the interleukin-2 (IL-2) signaling axis in immune tolerance, we investigated the expression of key genes in this pathway, and their associated long non-coding RNAs in an Iranian cohort of relapsing-remitting MS patients. Peripheral Blood Mononuclear Cells (PBMC) from 20 untreated patients, 20 Ocrelizumab (Xacrel®)-treated stable RRMS patients for whom at least six months had passed since the last dose, and 20 healthy controls were analyzed by RT-PCR. Treatment resulted in reduced IL2RA and FOXP3 but not IL2 expression levels and normalization of FLICR and RP11-536 K7.5 levels in MS patients. Correlation analysis revealed a strong IL2RA-FOXP3 association and inverse IL2RA-RP11-536 K7.5 correlation in treated patients. Lower IL2RA and RP11-536 K7.5 levels correlated with higher EDSS scores. ROC analysis highlighted IL2, IL2RA, and FOXP3 as strong classifiers in treated patients, and RP11-536 K7.5 in untreated cases. FOXP3 expression positively correlates with the number of Ocrelizumab infusions, indicating reinforcement of regulatory T-cell activity with ongoing therapy. These findings highlight IL-2 pathway modulation and lncRNA regulation as therapeutic effects of Ocrelizumab.

Ocrelizumab是一种CD20+ B细胞消耗单克隆抗体，广泛用于多发性硬化症（MS），但其对免疫调节的分子影响仍未完全确定。鉴于白细胞介素-2 （IL-2）信号轴在免疫耐受中的重要性，我们在伊朗复发-缓解型MS患者队列中研究了该途径中关键基因及其相关长链非编码rna的表达。采用RT-PCR分析了20例未治疗患者、20例经Ocrelizumab （Xacrel®）治疗的稳定型RRMS患者（自最后一次给药以来至少已过去6个月）和20例健康对照的外周血单核细胞（PBMC）。治疗导致MS患者IL2RA和FOXP3降低，但IL2表达水平和FLICR和RP11-536 K7.5水平正常化未见改善。相关分析显示，治疗患者IL2RA-FOXP3相关性强，IL2RA-RP11-536 K7.5相关性逆。较低的IL2RA和RP11-536 K7.5水平与较高的EDSS评分相关。ROC分析强调，在治疗患者中，IL2、IL2RA和FOXP3是强分类因子，在未治疗患者中，RP11-536 K7.5是强分类因子。FOXP3表达与Ocrelizumab输注次数呈正相关，表明调节性t细胞活性随着治疗的进行而增强。这些发现强调了IL-2通路调节和lncRNA调节是Ocrelizumab的治疗作用。

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引用次数: 0

Poor outcome increase with baseline severity of lateral striatocapsular hemorrhages 不良预后随着侧纹状囊出血的基线严重程度而增加。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-08 DOI: 10.1016/j.jns.2025.125678

Ioan Avram , Clement Desjardins , Hugo Charles , Pierre Amarenco , Philippa C. Lavallee

Background

Intracranial hemorrhage (ICH) presents with varying outcomes based on location. Lateral striatocapsular hemorrhage (LSCH), located near the brain surface and outside the motor area, is surgically accessible, and evacuation may reduce mass effect and neurological sequelae. We aimed to determine prognosis and main predictors of poor outcomes in patients with acute LSCH.

Methods

We retrospectively analyzed LSCH patients admitted to our unit from January 2005 to October 2019. Factors associated with poor outcomes (mRS >2) were identified using logistic regression. The performance of identified predictors (alone and in combination) was assessed by calculating the area under the receiver operating characteristic curve (AUC) and its 95 % confidence intervals (CI).

Results

Of 224 patients with acute deep ICH, 84 (36.7 %) had LSCH. At 6 months, 41 (51.2 %) exhibited poor outcomes. Univariable analysis identified age, baseline NIHSS, hematoma volume, intraventricular hemorrhage, and midline deviation as factors associated with poor outcomes. In multivariable analysis, baseline NIHSS (OR for NIHSS>14: 5.82; 95 % CI 1.82–18.65; p = 0.003) and volume (OR per 10 mL increase: 1.94; 95 % CI 1.21–3.11; p = 0.0059) were significantly associated with mRS >2. The optimal cutoff for hematoma volume was 19.37 mL (AUC = 0.79), and for NIHSS, it was 13 (AUC = 0.86).

Conclusion

Half of LSCH patients had poor outcomes under medical treatment. Baseline NIHSS and hematoma volume accurately appeared as emergent predictor of poor outcomes and may be considered for risk stratification in this population.

背景：颅内出血（ICH）表现为不同部位的不同结果。侧纹状囊出血（LSCH）位于脑表面附近和运动区外，可通过手术切除，排出可减少肿块效应和神经系统后遗症。我们的目的是确定急性LSCH患者的预后和不良预后的主要预测因素。方法：回顾性分析2005年1月至2019年10月在我科住院的LSCH患者。使用逻辑回归确定与不良预后相关的因素（mRS >2）。通过计算受试者工作特征曲线（AUC）下的面积及其95%置信区间（CI）来评估已确定的预测因子（单独或联合）的性能。结果：224例急性深部脑出血患者中，84例（36.7%）有LSCH。6个月时，41例（51.2%）表现为预后不良。单变量分析发现，年龄、基线NIHSS、血肿量、脑室内出血和中线偏差是与预后不良相关的因素。在多变量分析中，基线NIHSS （NIHSS>的比值为5.82;95% CI 1.82-18.65; p = 0.003）和体积（每10 mL增加的比值为1.94;95% CI 1.21-3.11; p = 0.0059）与mRS >2显著相关。血肿体积的最佳临界值为19.37 mL (AUC = 0.79)， NIHSS的最佳临界值为13 mL （AUC = 0.86）。结论：半数LSCH患者经药物治疗后预后较差。基线NIHSS和血肿量准确地出现为不良预后的紧急预测因子，并可考虑在该人群中进行风险分层。

{"title":"Poor outcome increase with baseline severity of lateral striatocapsular hemorrhages","authors":"Ioan Avram , Clement Desjardins , Hugo Charles , Pierre Amarenco , Philippa C. Lavallee","doi":"10.1016/j.jns.2025.125678","DOIUrl":"10.1016/j.jns.2025.125678","url":null,"abstract":"<div><h3>Background</h3><div>Intracranial hemorrhage (ICH) presents with varying outcomes based on location. Lateral striatocapsular hemorrhage (LSCH), located near the brain surface and outside the motor area, is surgically accessible, and evacuation may reduce mass effect and neurological sequelae. We aimed to determine prognosis and main predictors of poor outcomes in patients with acute LSCH.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed LSCH patients admitted to our unit from January 2005 to October 2019. Factors associated with poor outcomes (mRS >2) were identified using logistic regression. The performance of identified predictors (alone and in combination) was assessed by calculating the area under the receiver operating characteristic curve (AUC) and its 95 % confidence intervals (CI).</div></div><div><h3>Results</h3><div>Of 224 patients with acute deep ICH, 84 (36.7 %) had LSCH. At 6 months, 41 (51.2 %) exhibited poor outcomes. Univariable analysis identified age, baseline NIHSS, hematoma volume, intraventricular hemorrhage, and midline deviation as factors associated with poor outcomes. In multivariable analysis, baseline NIHSS (OR for NIHSS>14: 5.82; 95 % CI 1.82–18.65; <em>p</em> = 0.003) and volume (OR per 10 mL increase: 1.94; 95 % CI 1.21–3.11; <em>p</em> = 0.0059) were significantly associated with mRS >2. The optimal cutoff for hematoma volume was 19.37 mL (AUC = 0.79), and for NIHSS, it was 13 (AUC = 0.86).</div></div><div><h3>Conclusion</h3><div>Half of LSCH patients had poor outcomes under medical treatment. Baseline NIHSS and hematoma volume accurately appeared as emergent predictor of poor outcomes and may be considered for risk stratification in this population.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"480 ","pages":"Article 125678"},"PeriodicalIF":3.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Factors influencing the long-term maintenance of spasticity neurotoxin treatment 影响痉挛性神经毒素治疗长期维持的因素

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-04 DOI: 10.1016/j.jns.2025.125692

Mallory L. Hacker , Lucas Chang , Sheffield Sharp , Jack Slatton , Eli A. Abdou , Ariana Zarghami , Emily Butler , Kelly Harper , Ashley Eaves , Kevin Berry , C.J. Plummer , David Charles

Introduction

Spasticity is a motor disorder often impairing mobility, daily function, and quality of life. While botulinum neurotoxin (BoNT) is safe and effective for spasticity, treatment discontinuation is common. This study aimed to identify the factors influencing long-term BoNT therapy maintenance among spasticity patients.

Methods

Forty participants with spasticity who received at least five BoNT cycles completed a structured cross-sectional telephone interview. Interviews covered key dimensions of living with spasticity, such as impact on daily activities, experience of pain associated with spasticity, and the broader implications for quality of life. Data were summarized using descriptive statistics.

Results

The cohort (60 % male, aged 45.1 ± 14.8 years) featured multiple etiologies of spasticity, including cerebral palsy (35 %), stroke (20 %), and traumatic brain injury (20 %). Most were treated with onabotulinumtoxinA (36/40), three were receiving abobotulinumtoxinA, and one was treated with incobotulinumtoxinA. Primary reasons for maintaining BoNT treatment included reduction of symptoms (55 %), improvement in mobility/movement (27 %), and relief of pain or tension (12 %). A majority of subjects (95 %) stated their treatment met or exceeded their expectations. Over 90 % of participants maintained a strong relationship with their physician and were well-informed about the therapy, including what to expect from treatment (98 %), potential side effects (90 %), and treatment duration (90 %).

Conclusion

Results suggest spasticity patients are likely to continue treatment if they are properly educated on BoNT therapy, experience improvement in spasms and mobility, and have a strong physician-patient relationship. These findings highlight the importance of effective physician-patient relationships and proper education on BoNT therapy.

痉挛是一种运动障碍，常损害活动能力、日常功能和生活质量。虽然肉毒杆菌神经毒素（BoNT）对痉挛是安全有效的，但停止治疗是常见的。本研究旨在确定影响痉挛患者BoNT治疗长期维持的因素。方法40例接受至少5个BoNT周期治疗的痉挛患者完成了结构化的横断面电话访谈。访谈涵盖了痉挛患者生活的关键方面，如对日常活动的影响，痉挛相关的疼痛体验，以及对生活质量的更广泛影响。数据采用描述性统计进行汇总。结果该队列（60%为男性，年龄45.1±14.8岁）具有多种痉挛病因，包括脑瘫（35%）、中风（20%）和创伤性脑损伤（20%）。大多数用肉毒杆菌毒素治疗（36/40），3例用肉毒杆菌毒素治疗，1例用肉毒杆菌毒素治疗。维持BoNT治疗的主要原因包括减轻症状（55%），改善机动性/运动（27%），缓解疼痛或紧张（12%）。大多数受试者（95%）表示他们的治疗达到或超过了他们的预期。超过90%的参与者与他们的医生保持密切的关系，并充分了解治疗，包括治疗的预期（98%），潜在的副作用（90%）和治疗时间（90%）。结论痉挛患者如果接受BoNT治疗的适当教育，痉挛和活动能力得到改善，并有良好的医患关系，则可能继续治疗。这些发现强调了有效的医患关系和适当的BoNT治疗教育的重要性。

{"title":"Factors influencing the long-term maintenance of spasticity neurotoxin treatment","authors":"Mallory L. Hacker , Lucas Chang , Sheffield Sharp , Jack Slatton , Eli A. Abdou , Ariana Zarghami , Emily Butler , Kelly Harper , Ashley Eaves , Kevin Berry , C.J. Plummer , David Charles","doi":"10.1016/j.jns.2025.125692","DOIUrl":"10.1016/j.jns.2025.125692","url":null,"abstract":"<div><h3>Introduction</h3><div>Spasticity is a motor disorder often impairing mobility, daily function, and quality of life. While botulinum neurotoxin (BoNT) is safe and effective for spasticity, treatment discontinuation is common. This study aimed to identify the factors influencing long-term BoNT therapy maintenance among spasticity patients.</div></div><div><h3>Methods</h3><div>Forty participants with spasticity who received at least five BoNT cycles completed a structured cross-sectional telephone interview. Interviews covered key dimensions of living with spasticity, such as impact on daily activities, experience of pain associated with spasticity, and the broader implications for quality of life. Data were summarized using descriptive statistics.</div></div><div><h3>Results</h3><div>The cohort (60 % male, aged 45.1 ± 14.8 years) featured multiple etiologies of spasticity, including cerebral palsy (35 %), stroke (20 %), and traumatic brain injury (20 %). Most were treated with onabotulinumtoxinA (36/40), three were receiving abobotulinumtoxinA, and one was treated with incobotulinumtoxinA. Primary reasons for maintaining BoNT treatment included reduction of symptoms (55 %), improvement in mobility/movement (27 %), and relief of pain or tension (12 %). A majority of subjects (95 %) stated their treatment met or exceeded their expectations. Over 90 % of participants maintained a strong relationship with their physician and were well-informed about the therapy, including what to expect from treatment (98 %), potential side effects (90 %), and treatment duration (90 %).</div></div><div><h3>Conclusion</h3><div>Results suggest spasticity patients are likely to continue treatment if they are properly educated on BoNT therapy, experience improvement in spasms and mobility, and have a strong physician-patient relationship. These findings highlight the importance of effective physician-patient relationships and proper education on BoNT therapy.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"480 ","pages":"Article 125692"},"PeriodicalIF":3.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma neurofilament light chain to evaluate response during cladribine treatment in multiple sclerosis 血浆神经丝轻链评价克拉德滨治疗多发性硬化症的疗效

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-04 DOI: 10.1016/j.jns.2025.125681

Valerio Nicolella , Marco Varelli , Stefania Fasano , Enrico Cantone , Carmela Polito , Rosa Sirica , Evelina La Civita , Mariano Fiorenza , Federica Novarella , Giuseppe Corsini , Antonio Carotenuto , Maria Petracca , Roberta Lanzillo , Vincenzo Brescia Morra , Giuseppe Castaldo , Daniela Terracciano , Marcello Moccia

Introduction

Cladribine treatment in year 1 and 2 provides high efficacy on multiple sclerosis(MS) outcomes over 4 years. Use of biomarkers of neuro-axonal damage, such as plasma neurofilament light chain (pNfL), might support prognostication and treatment decisions.

Objectives

To:1)investigate pNfL variations over time in people with MS(pwMS) treated with cladribine;2)compare pNfL levels during cladribine treatment to age- and sex-matched controls;3) assess pNfL prediction on clinical and radiological outcomes.

Methods

This retrospective analysis of longitudinally-collected data included 258 pwMS treated with cladribine and 304 age and sex-matched controls. During follow-up,in pwMS,we collected evidence of disease activity (EDA3).

Results

When compared with pNfL before or in the first 3 months of treatment,pNfL was lower between 3 and 12 months(Coeff = −182.05; 95 %CI = -303.73, -60.36; p = 0.004), between 12 and 24 months (Coeff = −149.98; 95 %CI = -272.41, -27.55; p = 0.017) and after 24 months from the first cladribine dosing (Coeff = −280.32; 95 %CI = -280.32,-29.86; p = 0.016). When compared with controls,pNfL was higher in pwMS before or in the first 3 months of cladribine treatment(Coeff = 7.43; 95 %CI = 2.45, 12.40; p = 0.004), but was similar between 3 and 12 months(Coeff = −1.04; 95 %CI = -3.36, 1.27; p- = 0.376), between 12 and 24 months(Coeff = 1.48; 95 %CI = -0.60, 3.55; p = 0.162) and after 24 months(Coeff = 2.23; 95 %CI = -0.47, 5.08; p = 0.103). We observed no significant associations between baseline pNfL and EDA(11 patients,4.26 %).

Conclusions

Cladribine significantly reduced pNfL levels, which stabilized at values comparable to matched healthy controls, confirming its strong efficacy with minimal disease activity during follow-up.

介绍：cladribine治疗1年和2年对多发性硬化症（MS）的疗效超过4年。使用神经轴突损伤的生物标志物，如血浆神经丝轻链（pNfL），可能支持预后和治疗决策。目的：1)研究克拉德滨治疗多发性硬化症（pwMS）患者pNfL随时间的变化；2)比较克拉德滨治疗期间与年龄和性别匹配对照组的pNfL水平；3)评估pNfL对临床和放射预后的预测。方法回顾性分析纵向收集的资料，包括258例接受克拉德滨治疗的pwMS患者和304例年龄和性别匹配的对照组。在随访期间，在pwMS中，我们收集了疾病活动的证据（EDA3）。结果与治疗前或治疗前3个月的pNfL相比，治疗后3 ~ 12个月（Coeff = - 182.05; 95% CI = -303.73, -60.36; p = 0.004）、12 ~ 24个月（Coeff = - 149.98; 95% CI = -272.41, -27.55; p = 0.017）和治疗后24个月（Coeff = -280.32; 95% CI = -280.32,-29.86; p = 0.016） pNfL均降低。与对照组相比，在克拉西滨治疗前或前3个月，pwMS患者的pNfL较高（Coeff = 7.43; 95% CI = 2.45, 12.40; p = 0.004），但在3 - 12个月（Coeff = - 1.04; 95% CI = -3.36, 1.27; p = 0.376）、12 - 24个月（Coeff = 1.48; 95% CI = -0.60, 3.55; p = 0.162）和24个月后（Coeff = 2.23; 95% CI = -0.47, 5.08; p = 0.103）之间的pNfL相似。我们观察到基线pNfL和EDA之间无显著关联（11例，4.26%）。结论克拉比滨可显著降低pNfL水平，稳定在与匹配健康对照相当的值，证实其在随访期间疾病活动度最小的情况下具有很强的疗效。

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引用次数: 0

Is segmental/multifocal onset a distinct presentation of idiopathic adult-onset dystonia? 节段性/多灶性发作是特发性成人肌张力障碍的独特表现吗？

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-04 DOI: 10.1016/j.jns.2025.125691

Vittorio Velucci , Carmen Terranova , Francesco Bono , Giovanna Squintani , Marcello Esposito , Laura Avanzino , Daniele Belvisi , Roberta Pellicciari , Carlo Alberto Artusi , Maria Concetta Altavista , Anna Castagna , Cesa Lorella Maria Scaglione , Maria Sofia Cotelli , Christian Lettieri , Roberto Erro , Martina Petracca , Tommaso Schirinzi , Roberto Ceravolo , Angelo Fabio Gigante , Nicola Tambasco , Giovanni Defazio

Background

Idiopathic adult-onset dystonia (IAOD) is classically considered to begin focally, although segmental or multifocal onset has been reported in retrospective series. Whether this reflects a true early presentation or recall bias remains uncertain.

Objectives

To determine whether segmental/multifocal onset represents a distinct presentation of IAOD and to assess whether these patients differ from those with focal onset.

Methods

We analyzed dystonia body distribution at first neurological evaluation in 863 patients from the Italian Dystonia Registry, all examined by expert neurologists within one year of symptom onset to minimize recall bias.

Results

Segmental or multifocal onset occurred in 10 % of cases. This proportion remained stable across increasing intervals between symptom onset and first evaluation, arguing against recall bias. Patients with segmental/multifocal onset did not differ from those with focal onset in sex, age at onset, family history of dystonia, frequency of thyroid disease, or subsequent spread to additional body regions.

Conclusions

IAOD can present with segmental or multifocal onset, and this is unlikely to reflect recall bias. Moreover, patients with segmental/multifocal onset do not differ in factors potentially linked to disease initiation or subsequent spread compared with those with focal onset. These findings may have implications for prognostic counseling in IAOD.

背景：虽然在回顾性研究中也曾报道过节段性或多灶性肌张力障碍（IAOD）的发病，但一般认为是局部发病。这是否反映了一个真正的早期陈述或回忆偏见仍然不确定。目的确定节段性/多灶性发作是否代表IAOD的独特表现，并评估这些患者是否与灶性发作的患者不同。方法：我们分析了863例意大利肌张力障碍登记患者首次神经评估时的肌张力障碍体分布，所有患者均在症状出现一年内由神经科专家检查，以尽量减少回忆偏差。结果节段性或多灶性发病占10%。这一比例在症状发作和首次评估之间的时间间隔增加时保持稳定，反驳了回忆偏差。节段性/多局灶性发病患者与局灶性发病患者在性别、发病年龄、肌张力障碍家族史、甲状腺疾病发生频率或随后扩散到其他身体部位等方面没有差异。结论siaod可表现为节段性或多灶性发病，不太可能反映回忆偏倚。此外，与局灶性发病的患者相比，节段性/多灶性发病的患者在与疾病开始或随后的传播相关的潜在因素方面没有差异。这些发现可能对IAOD的预后咨询具有启示意义。

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引用次数: 0

A combined approach of Interleukin-8 and magnetic resonance neurography to differentiate Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy 白细胞介素-8联合磁共振神经造影鉴别格林-巴勒综合征和慢性炎性脱髓鞘性多发性神经病。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-04 DOI: 10.1016/j.jns.2025.125675

Jianru Xiao , Yunfei Bai , Xiaoran Bu , Jiaxiang Xin , Jinfan Zheng , Yi Shan , Wei Li , Yuying Zhao , Chuanzhu Yan , Anning Li , Qinzhou Wang

Background and objectives

Early differentiation between Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) is often difficult due to overlapping clinical features. This study investigates cerebrospinal fluid (CSF) interleukin-8 (IL-8) levels and magnetic resonance neurography (MRN) findings as potential diagnostic biomarkers for distinguishing GBS from CIDP.

Methods

This retrospective study included 130 patients, comprising 73 with GBS and 57 with CIDP. CSF samples were obtained at initial presentation, and IL-8 concentrations were quantified using flow cytometry. MRN was performed with maximum intensity projection to reconstruct the lumbosacral plexus, and cross-sectional areas (CSA) of lumbar nerve roots were measured. Statistical analyses involved independent t-tests, Wilcoxon rank-sum tests, Pearson's correlation coefficients, and receiver operating characteristic (ROC) curve analysis to assess diagnostic performance.

Results

CSF IL-8 levels were significantly higher in GBS patients compared with CIDP patients. An optimal IL-8 cutoff value yielded 67.1 % sensitivity and 75.4 % specificity for distinguishing GBS from CIDP. MRN demonstrated significantly enlarged lumbar nerve root CSA in CIDP, particularly at the L4 root, with 76.1 % sensitivity and 92.5 % specificity. Combining CSF IL-8 levels with L4 nerve root CSA further improved diagnostic performance, achieving 89.0 % sensitivity and 80.7 % specificity.

Conclusion

The integration of CSF IL-8 measurement with MRN-based assessment of the lumbosacral plexus provides a clinically applicable approach to enhance the differentiation of GBS from CIDP, facilitating earlier diagnosis and guiding timely therapeutic decision-making.

背景与目的：吉兰-巴勒综合征（GBS）和慢性炎症性脱髓鞘性多神经病变（CIDP）由于临床特征重叠，往往难以早期鉴别。本研究探讨脑脊液（CSF）白介素-8 （IL-8）水平和磁共振神经成像（MRN）结果作为区分GBS和CIDP的潜在诊断生物标志物。方法：本回顾性研究纳入130例患者，其中73例为GBS， 57例为CIDP。在初次呈现时获得脑脊液样本，并使用流式细胞术定量IL-8浓度。采用最大强度投影MRN重建腰骶神经丛，测量腰神经根的横截面积（CSA）。统计分析包括独立t检验、Wilcoxon秩和检验、Pearson相关系数和受试者工作特征（ROC）曲线分析来评估诊断效果。结果：GBS患者CSF IL-8水平明显高于CIDP患者。最佳IL-8临界值为区分GBS和CIDP的敏感性为67.1%，特异性为75.4%。MRN显示CIDP的腰神经根CSA明显扩大，特别是在L4根，敏感性为76.1%，特异性为92.5%。结合CSF IL-8水平与L4神经根CSA进一步提高了诊断性能，达到89.0%的敏感性和80.7%的特异性。结论：将CSF IL-8检测与腰骶神经丛mri评估相结合，为增强GBS与CIDP的鉴别提供了一种临床适用的方法，有助于早期诊断，指导及时的治疗决策。

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引用次数: 0

Steroid-sparing in myasthenia gravis: How much is efgartigimod, and How much is carryover? 重症肌无力的类固醇节约：多少是有效的，多少是遗留的？

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-03 DOI: 10.1016/j.jns.2025.125688

Christian Messina

引用次数: 0

Comparison of outcomes among generations in endovascular treatment for unruptured intracranial aneurysms: insights from a single-center study 未破裂颅内动脉瘤血管内治疗的代际结果比较：来自单中心研究的见解

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-02 DOI: 10.1016/j.jns.2025.125679

Hidetoshi Matsukawa , Kiyoshi Kazekawa , Masahiro Yasaka , Yoshimasa Fukui , Kosei Maruyama , Takashi Fujii , Kosuke Takigawa , Noriaki Tashiro , Yoshiya Hashiguchi , Hiroshi Aikawa , Yoshinori Go

Background

The relationship between age and 90-day outcome in unruptured intracranial aneurysm (UIA) patients with endovascular treatment (EVT) remains uncertain.

Methods

This retrospective study was conducted between April 2017 and April 2022. Patients were stratified into four groups by age: < 50, 50–64, 65–79, and ≥ 80 years. The primary outcome was neurological deterioration, defined as an increase of 1 or more in the modified Rankin Scale (mRS) score at 90 days after EVT compared with the preoperative score. A multivariate logistic regression model (using age < 50 years as the reference) was constructed for the outcome, adjusting for sex, dyslipidemia, diabetes mellitus, wide neck, aneurysm location, and EVT technique. Subgroups for the primary outcome were analyzed using multivariate logistic regression models with the same adjustments.

Results

A total of 756 cases were included. Of these, 155 patients (20.5 %) were < 50 years, 225 (29.8 %) were 50–64 years, 298 (39.4 %) were 65–79 years, and 78 (10.3 %) were ≥ 80 years. Neurological deterioration occurred in 33 patients (4.4 %). Age ≥ 80 years was not significantly related to neurological deterioration (adjusted odds ratio 4.59, 95 %CI 0.80–26.2). The relationship between age 80 years or older and neurological decline did not differ significantly between subgroups.

Conclusion

No significant differences in odds of neurological deterioration were observed among the four age groups. EVT appears to be a viable treatment option for UIAs, including in elderly patients aged ≥80 years.

背景：未破裂颅内动脉瘤（UIA）患者接受血管内治疗（EVT）时，年龄与90天预后的关系尚不确定。方法回顾性研究于2017年4月至2022年4月进行。患者按年龄分为4组：50岁、50 - 64岁、65-79岁和≥80岁。主要结局是神经功能恶化，定义为EVT后90天改良兰金量表（mRS）评分较术前评分增加1或更多。在性别、血脂异常、糖尿病、宽颈、动脉瘤位置和EVT技术等因素的影响下，构建多因素logistic回归模型（以年龄50岁为参考）。主要结局的亚组采用相同调整的多变量逻辑回归模型进行分析。结果共纳入病例756例。其中，50岁155例（20.5%），50 - 64岁225例（29.8%），65-79岁298例（39.4%），≥80岁78例（10.3%）。33例（4.4%）患者出现神经功能恶化。年龄≥80岁与神经功能恶化无显著相关性（校正优势比4.59,95% CI 0.80-26.2）。80岁及以上年龄与神经功能衰退之间的关系在亚组之间没有显著差异。结论4个年龄组神经功能恶化发生率无显著差异。EVT似乎是uia的可行治疗选择，包括≥80岁的老年患者。

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引用次数: 0