Journal of the Neurological Sciences最新文献_第9页

Is there a causal nexus between norovirus infection and Guillain-Barré syndrome: The lessons learnt from GBS outbreak in Pune, India, 2025 诺如病毒感染与格林-巴- <s:1>综合征之间是否存在因果关系：从2025年印度浦那爆发的吉兰-巴-综合征中吸取的教训

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-17 DOI: 10.1016/j.jns.2025.125696

Babasaheb V. Tandale, Rajlakshmi Vishwanathan, Mallika Lavania, Naveen Kumar

In January 2025, a significant outbreak of Guillain-Barré Syndrome (GBS) affected over 200 individuals in Southwest Pune. GBS, a rare neurological disorder triggered by infections, was linked in this case to antecedent illnesses, primarily acute diarrheal disease (ADD). Molecular screening for 19 pathogens revealed Campylobacter jejuni a known GBS trigger in nearly 50 % of cases, and norovirus in over 20 %. Contaminated drinking water emerged as the primary source of infection, with both pathogens also detected in poultry, suggesting a possible zoonotic link and highlighting the role of foodborne transmission.

The outbreak was contained by March 2025 through urgent improvements to local water and sanitation systems. However, the event exposed critical public health shortcomings, including delayed diagnosis, limited access to specialized care, and weak disease surveillance. These factors contributed to the outbreak's severity and duration. Many patients required prolonged hospitalization and rehabilitation, placing a significant strain on healthcare resources and causing economic hardship for affected families.

This outbreak underscores the need to recognize infection-associated GBS as a public health priority. It highlights the importance of cross-sector collaboration in clinical care, epidemiology, environmental health, and policy. Key actions include strengthening surveillance, ensuring safe water and food sources, improving clinical capacity for early GBS detection and management, and enhancing coordination between health systems. Addressing the infection-neurological disorder nexus is vital for effective prevention and timely response. This incident serves as both a warning and an opportunity to build more resilient public health infrastructure in rapidly urbanizing areas.

2025年1月，普那西南部爆发了严重的格林-巴- 综合征（GBS），影响了200多人。GBS是一种由感染引发的罕见神经系统疾病，在本病例中与先前的疾病有关，主要是急性腹泻病（ADD）。对19种病原体的分子筛选显示，在近50%的病例中，空肠弯曲杆菌是已知的吉兰-巴氏综合征的诱因，在20%以上的病例中，诺如病毒是诱因。受污染的饮用水成为主要感染源，在家禽中也检测到这两种病原体，这表明可能存在人畜共患病的联系，并突出了食源性传播的作用。到2025年3月，通过紧急改善当地供水和卫生系统，疫情得到了控制。然而，这一事件暴露了严重的公共卫生缺陷，包括诊断延误、获得专业护理的机会有限以及疾病监测薄弱。这些因素促成了疫情的严重程度和持续时间。许多病人需要长期住院和康复，给医疗资源造成很大压力，并给受影响家庭造成经济困难。此次疫情突出表明，需要将与感染相关的吉兰-巴雷综合征视为公共卫生重点。它强调了在临床护理、流行病学、环境卫生和政策方面进行跨部门合作的重要性。关键行动包括加强监测，确保安全的饮用水和食物来源，提高早期发现和管理吉兰-巴雷综合征的临床能力，以及加强卫生系统之间的协调。解决感染与神经系统疾病之间的联系对于有效预防和及时反应至关重要。这一事件既是一个警告，也是一个在快速城市化地区建设更具抵御力的公共卫生基础设施的机会。

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引用次数: 0

The impact of enlarged perivascular spaces on the association among peripheral inflammation, disease progression and motor symptoms in Parkinson's disease 血管周围空间增大对帕金森病外周炎症、疾病进展和运动症状相关性的影响

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-17 DOI: 10.1016/j.jns.2025.125698

Mingchao Shi , Huihui Zhao , Yue Zhu , Min Chen , Haibo Jiang , Zonghui Chen , Meijiang Feng

Background

The glymphatic system and peripheral inflammation are involved in Parkinson's disease (PD), but the underlying mechanisms remain unclear. We studied enlarged perivascular spaces (EPVSs) to investigate the interactions among glymphatic system, peripheral inflammation, disease progression and motor symptoms in PD patients.

Methods

This study included 85 PD patients and 87 healthy controls (HCs). Based on MDS-UPDRS score, patients were divided into tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subgroups. The disease stage was assessed using the Hoehn–Yahr (H-Y) scale. We evaluated EPVS number in basal ganglia (BG) and centrum semiovale (CSO), collected serum leukocyte counts and their derived ratios, explored their potential effects on motor symptoms and H-Y stage.

Results

The numbers of BG-EPVSs and CSO-EPVSs were significantly greater in PD patients than in HCs. Furthermore, the numbers of BG-EPVSs and CSO-EPVSs were positively correlated with leukocyte, neutrophil, neutrophil-to-lymphocyte ratio (NLR), systemic immune–inflammation index (SII), H-Y stage, and motor symptoms and negatively correlated with lymphocyte and lymphocyte-to-monocyte ratio (LMR). However, motor symptoms were positively associated only with neutrophil, NLR, SII, and H-Y stage. Multiple regression analysis confirmed that neutrophil, NLR, SII, and H-Y stage significantly influenced BG-EPVSs numbers, CSO-EPVSs numbers, and MDS-UPDRS III score. Mediation analysis showed that EPVS numbers mediated the relationships among peripheral inflammation, disease progression, and motor symptoms.

Conclusions

The EPVS number is associated with peripheral inflammation and may mediate the effects of peripheral inflammation and disease progression on motor symptoms in PD. EPVSs may serve as an effective indicator of glymphatic system dysfunction.

背景：淋巴系统和外周炎症与帕金森病（PD）有关，但其潜在机制尚不清楚。我们研究了扩大的血管周围间隙（EPVSs），以探讨淋巴系统、外周炎症、疾病进展和PD患者运动症状之间的相互作用。方法：本研究纳入85例PD患者和87例健康对照。根据MDS-UPDRS评分，将患者分为震颤主导型（TD）亚组和姿势不稳定及步态困难（PIGD）亚组。采用Hoehn-Yahr （H-Y）量表评估疾病分期。我们评估了基底神经节（BG）和半瓣膜中心（CSO）的EPVS数量，收集了血清白细胞计数及其衍生比率，探讨了它们对运动症状和H-Y分期的潜在影响。结果：PD患者的BG-EPVSs和CSO-EPVSs数量明显高于hcc患者。此外，BG-EPVSs和CSO-EPVSs的数量与白细胞、中性粒细胞、中性粒细胞与淋巴细胞比值（NLR）、全身免疫炎症指数（SII）、H-Y分期和运动症状呈正相关，与淋巴细胞和淋巴细胞与单核细胞比值（LMR）呈负相关。然而，运动症状仅与中性粒细胞、NLR、SII和H-Y期呈正相关。多元回归分析证实，中性粒细胞、NLR、SII和H-Y分期显著影响BG-EPVSs、CSO-EPVSs和MDS-UPDRS III评分。中介分析显示EPVS数量介导了外周炎症、疾病进展和运动症状之间的关系。结论：EPVS数量与外周炎症有关，并可能介导外周炎症和疾病进展对PD运动症状的影响。EPVSs可作为淋巴系统功能障碍的有效指标。

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引用次数: 0

Transcranial Doppler pulsatility index variability association with clinical outcome after aneurysmal subarachnoid hemorrhage 动脉瘤性蛛网膜下腔出血后经颅多普勒脉搏指数变异性与临床预后的关系。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-17 DOI: 10.1016/j.jns.2025.125694

Jason J. Chang , David Kepplinger , Siqi Wei , Julia Alexander , Maya Shah , Alexander Kim , Josef Williams , Charles Withington , Ehsan Dowlati , Rizwan Tahir , Daniel R. Felbaum , Jeffrey C. Mai , Rocco A. Armonda , Yongwoo Kim

Background

Transcranial Doppler mean flow velocity (MFV) and pulsatility index (PI) are used for ancillary monitoring in aneurysmal subarachnoid hemorrhage (SAH). We evaluated PI and MFV variables in the middle cerebral arteries (MCA) for potential associations with delayed cerebral ischemia (DCI) and clinical outcome.

Methods

We retrospectively evaluated patients with SAH over a six-year period. Poor outcome was defined as a three-month Modified Rankin Scale (Rajajee et al., 2012; Bellner et al., n.d.; Chang et al., 2023), and DCI was defined by presence of vascular infarcts on brain imaging. Serial PI and MFV values for each patient were compiled to obtain four PI and MFV variables, including maximum absolute change in daily PI values (AbsΔPI). Multivariate logistic regression was performed to identify subsets of variables that maximized area under curve-receiver operating characteristic (AUC-ROC) for clinical outcome. Multivariate logistic regression analysis using clinical outcome and DCI was generated using PI variables, MFV variables, and demographic variables.

Results

268 patients met inclusion criteria and were evaluated. PI, MFV, and demographic variables yielded an AUC-ROC value of 0.84 for clinical outcome. Multivariate logistic regression analysis showed that AbsΔPI (p = 0.01), older age (p < 0.001), Hunt Hess score (p < 0.001), and Fisher score (p = 0.05) were significant predictors for poor clinical outcome. No MFV variable had significant associations with clinical outcome.

Conclusion

We found that PI variability in the MCAs had a significant association with clinical outcome in patients with SAH: every 0.1 variability in PI resulted in 1.4-times higher odds of poor clinical outcome. Further studies are needed for confirmation.

背景：经颅多普勒平均血流速度（MFV）和脉搏指数（PI）用于动脉瘤性蛛网膜下腔出血（SAH）的辅助监测。我们评估了大脑中动脉（MCA）的PI和MFV变量与延迟性脑缺血（DCI）和临床结果的潜在关联。方法：我们回顾性评估SAH患者6年的时间。不良预后定义为三个月修正Rankin量表（Rajajee et al., 2012; Bellner et al., n.d; Chang et al., 2023）， DCI定义为脑成像上是否存在血管梗死。收集每位患者的PI和MFV序列值，获得PI和MFV 4个变量，包括每日PI值的最大绝对变化（AbsΔPI）。进行多变量logistic回归，以确定对临床结果影响最大的曲线下面积-受试者工作特征（AUC-ROC）变量子集。采用PI变量、MFV变量和人口统计变量，对临床结果和DCI进行多因素logistic回归分析。结果：268例患者符合纳入标准并进行了评估。PI、MFV和人口学变量对临床结果的AUC-ROC值为0.84。多因素logistic回归分析显示AbsΔPI (p = 0.01)，年龄更大(p)。结论：我们发现MCAs的PI变异性与SAH患者的临床结局有显著相关：PI每0.1个变异性导致不良临床结局的几率增加1.4倍。需要进一步的研究来证实。

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引用次数: 0

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。

{"title":"Siponimod enhances brain-derived neurotrophic factor secretion from immune cells in multiple sclerosis: A longitudinal study","authors":"Lior Fuchs , Roy Avizov , Arnon Karni , Maya Golan","doi":"10.1016/j.jns.2025.125699","DOIUrl":"10.1016/j.jns.2025.125699","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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<sup>+</sup> T cells, CD14<sup>+</sup> 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div><div><h3>Key points</h3><div>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.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"480 ","pages":"Article 125699"},"PeriodicalIF":3.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774466","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

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。

{"title":"Ocrelizumab modulates the IL-2 signaling pathway and associated lncRNAs in multiple sclerosis","authors":"Fatemeh Rangani , Mohammad Ali Nahayati , Majid Pahlevan Kakhki , Seyed Hamid Aghaee-Bakhtiari","doi":"10.1016/j.jns.2025.125693","DOIUrl":"10.1016/j.jns.2025.125693","url":null,"abstract":"<div><div>Ocrelizumab, a CD20<sup>+</sup> 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 <em>IL2RA</em> and <em>FOXP3</em> but not <em>IL2</em> expression levels and normalization of <em>FLICR</em> and <em>RP11-536</em> <em>K7.5</em> levels in MS patients. Correlation analysis revealed a strong <em>IL2RA-FOXP3</em> association and inverse <em>IL2RA-RP11-536</em> <em>K7.5</em> correlation in treated patients. Lower <em>IL2RA</em> and <em>RP11-536</em> <em>K7.5</em> levels correlated with higher EDSS scores. ROC analysis highlighted <em>IL2</em>, <em>IL2RA</em>, and <em>FOXP3</em> as strong classifiers in treated patients, and <em>RP11-536</em> <em>K7.5</em> in untreated cases. <em>FOXP3</em> 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.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"480 ","pages":"Article 125693"},"PeriodicalIF":3.2,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735212","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

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。

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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