Journal of the Neurological Sciences最新文献_第7页

Effects of surgical therapies on cognitive function in patients with essential tremor 手术治疗对特发性震颤患者认知功能的影响

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-20 DOI: 10.1016/j.jns.2025.125697

Vibhash D. Sharma , Diane S. Berry , Stephanie Cosentino , Elan D. Louis

Background

Essential tremor (ET) is associated with increased risk of cognitive decline, particularly with advancing age. Surgical therapies, such as deep brain stimulation (DBS) and MR-guided focused ultrasound (MRgFUS), are effective treatment options for tremor, but their long-term cognitive effects remain unclear. This is the first study to compare ET patients who underwent surgery to those who had not.

Objective

We assessed cognitive outcomes in ET patients who underwent surgical therapies and compared them to non-surgical controls.

Methods

We identified both surgical (n = 12) and non-surgical ET cases (n = 188) from a large prospective longitudinal study and compared their cognitive function. Cognitive function was assessed prior to and following surgery, over the course of 36- and 54-month intervals. Mixed model analyses of covariance were used to assess cognitive changes over time, controlling for age, global cognitive scores, years of education, and study visit.

Results

Although both groups showed modest cognitive decline over time, few significant differences were observed between the surgical and non-surgical groups. Significant group × time interactions were observed for several tests, with the surgical group demonstrating greater decline in some subdomains of Memory and Executive Function.

Conclusion

Surgical therapies such as DBS and MRgFUS do not appear to broadly impact global cognitive function in older ET patients. However, specific cognitive domains may be more susceptible to decline.

特发性震颤（ET）与认知能力下降的风险增加有关，尤其是随着年龄的增长。外科治疗，如深部脑刺激（DBS）和磁共振引导聚焦超声（MRgFUS），是治疗震颤的有效选择，但其长期认知效果尚不清楚。这是第一个比较接受手术和未接受手术的ET患者的研究。目的：我们评估接受手术治疗的ET患者的认知结局，并将其与非手术对照进行比较。方法我们从一项大型前瞻性纵向研究中选择手术（n = 12）和非手术（n = 188） ET病例，并比较他们的认知功能。在手术前后以36个月和54个月为间隔评估认知功能。使用协方差的混合模型分析来评估随时间的认知变化，控制年龄、整体认知评分、受教育年限和研究访问。结果虽然两组随着时间的推移都表现出适度的认知能力下降，但在手术组和非手术组之间没有观察到明显的差异。在几项测试中观察到显著的组与时间相互作用，手术组在记忆和执行功能的某些子域表现出更大的下降。手术治疗如DBS和MRgFUS似乎不会广泛影响老年ET患者的整体认知功能。然而，特定的认知领域可能更容易衰退。

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引用次数: 0

Serological testing patterns among individuals newly diagnosed with myasthenia gravis 重症肌无力患者的血清学检测模式

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-20 DOI: 10.1016/j.jns.2025.125700

A. Pesa Jacqueline , N. Liberman Joshua , D. Darer Jonathan , Yang Xiaoyun , A. Jackson Louis , Sergenyenko Artem , Campbell Nolan , J. Nowak Richard

Serologic antibody testing supports myasthenia gravis (MG) diagnosis and informs appropriate treatment. The research objective was to evaluate real-world MG serostatus testing patterns in the United States. Using insurance claims linked to serological test results, a retrospective, observational cohort study was conducted among adults with newly diagnosed MG between 01-January-2018 and 30-June-2022. Serostatus tests included acetylcholine receptor (anti-AChR), muscle-specific kinase (anti-MuSK), and low-density lipoprotein receptor-related protein 4 (anti-LRP4) antibodies. Of 5788 cases, 2590 (44.7 %) had at least one valid serology test result: 1453 (56.3 %) seronegative, 1094 (42.4 %) anti-AChR+, 28 (1.1 %) anti-MuSK+, and 5 (0.2 %) anti-LRP4+. Among the seronegative, 56.6 % were only tested for anti-AChR antibodies, 33.7 % tested both anti-AChR and anti-MuSK antibodies, and 5.0 % tested all three antibodies. Of the seronegative and untested populations, 40.9 % and 37.4 % initiated ≥2 unique MG treatments, with 699 (69.4 %) and 1267 (64.7 %) initiating acetylcholinesterase inhibitor. Factors associated with a higher likelihood of obtaining serologic testing included diagnosis by neurology, presence of MG-associated symptoms, residence in large metropolitan areas, fewer comorbidities, and Medicare insurance (vs. commercial or Medicaid). Variation in MG serologic testing, including infrequent MuSK and LRP4 autoantibody testing among seronegative patients, highlights a potential need to promote best practices in patient care.

血清学抗体测试支持重症肌无力（MG）的诊断和告知适当的治疗。研究目的是评估美国真实世界MG血清状态检测模式。利用与血清学检测结果相关的保险索赔，在2018年1月1日至2022年6月30日期间对新诊断为MG的成年人进行了一项回顾性观察性队列研究。血清状态检测包括乙酰胆碱受体（抗achr）、肌肉特异性激酶（抗musk）和低密度脂蛋白受体相关蛋白4（抗lrp4）抗体。5788例患者中，2590例（44.7%）至少有一项有效血清学检测结果：血清阴性1453例（56.3%），抗achr + 1094例（42.4%），抗musk + 28例（1.1%），抗lrp4 + 5例（0.2%）。血清阴性患者中，仅检测抗achr抗体的占56.6%，同时检测抗achr和抗musk抗体的占33.7%，三种抗体均检测的占5.0%。在血清阴性和未检测的人群中，40.9%和37.4%的人开始了≥2种独特的MG治疗，其中699人（69.4%）和1267人（64.7%）开始使用乙酰胆碱酯酶抑制剂。与获得血清学检测的可能性较高相关的因素包括神经学诊断、mg相关症状的存在、居住在大城市地区、合并症较少以及医疗保险（与商业或医疗补助相比）。MG血清学检测的差异，包括在血清阴性患者中罕见的MuSK和LRP4自身抗体检测，突出了促进患者护理最佳实践的潜在需求。

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引用次数: 0

Global, regional and national burden of Parkinson's disease, 1990–2021: Update from the GBD 2021 study 1990-2021年全球、区域和国家帕金森病负担：GBD 2021研究的最新进展

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-18 DOI: 10.1016/j.jns.2025.125703

Rong Yang , Mou Sun , Wen Chen , Hao Feng , Bing Chen , Yi Liu , Qiuguo He , Lin Wang , Chengong Zou , Xiaoquan Luo , Zhou Li , Anhui Fu , Fei Qiao , Hui Tang , Jing Yang , Haibo Ren

Background and objective

Parkinson's disease (PD) poses an escalating global health burden. This study evaluates PD burden, key drivers, and health system implications.

Methods

Using Global Burden of Disease 2021 data, we analyzed incidence, prevalence, mortality, and DALYs and their age-standardized rates (ASRs) for PD across 204 countries from 1990 to 2021, examining spatial and demographic patterns. Decomposition analysis identified burden drivers, and relationship between socio-demographic index (SDI) and health workforce density with DALYs were assessed.

Results

In 2021, PD caused 1.335 million (95 % UI: 1.200 to 1.490) incident cases, 11.767 million (95 % UI: 10.400 to 13.400) prevalent cases, 0.388 million (95 %UI: 0.347 to 0.417 million) deaths, and 7.472 million (95 %UI: 6.740 to 8.140 million) DALYs globally. ASR for all indicators increased significantly since 1990, with the Average Annual Percent Changes exceeding 0 for each (P > 0.01). Burden heterogeneity was marked, with the highest in East Asia. Males bear a higher overall burden, though females exceeded them above age 90. Population growth and aging were primary drivers. DALYs correlated non-linearly with SDI, and weakly with health workforce density (|r| < 0.20).

Conclusion

From 1990 to 2021, the burden of PD intensified globally, with notable spatial and demographic disparities, primarily driven by population growth and aging. The current alignment between healthcare workforce allocation and disease burden is weak, indicating that the health system requires targeted reinforcement of its response capabilities.

背景与目的：帕金森病（PD）造成了日益严重的全球健康负担。本研究评估帕金森病负担、主要驱动因素和卫生系统影响。方法：使用2021年全球疾病负担数据，我们分析了1990年至2021年204个国家PD的发病率、患病率、死亡率、DALYs及其年龄标准化率（ASRs），并检查了空间和人口模式。分解分析确定了负担驱动因素，并评估了社会人口统计指数（SDI）和卫生人力密度与DALYs之间的关系。结果：2021年全球PD发病133.5万例（95% UI: 1200 ~ 1490），流行1176.7万例（95% UI: 10400 ~ 13400），死亡338.8万例（95% UI: 0.347 ~ 0.417万），DALYs 747.2万例（95% UI: 6740 ~ 814万）。自1990年以来，各指标的ASR均显著增加，年均变化百分比均超过0 （P < 0.01）。负担异质性明显，东亚负担最重。男性的总体负担更高，但90岁以上的女性负担更重。人口增长和老龄化是主要驱动因素。结论：1990 - 2021年，PD负担在全球范围内呈加重趋势，且存在显著的空间和人口差异，主要受人口增长和老龄化的驱动。目前卫生保健人力配置与疾病负担之间的一致性较弱，这表明卫生系统需要有针对性地加强其应对能力。

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引用次数: 0

Clinical safety of ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis: Open-label extension of a phase 2/3 randomized controlled study 超高剂量甲基钴胺素治疗肌萎缩性侧索硬化症的临床安全性：一项2/3期随机对照研究的开放标签扩展

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences

Pub Date : 2025-12-18 DOI: 10.1016/j.jns.2025.125701

Ryuji Kaji , Yurie Nishi , Takayuki Ishida , Takao Takase , Tamotsu Ueda , Takaya Maeda , Yuishin Izumi , on behalf of the Methylcobalamin 762 study group

Objective

To develop combined therapies for amyotrophic lateral sclerosis (ALS), we investigated the long-term safety of ultra-high-dose methylcobalamin (50-mg intramuscular, twice weekly) in patients with advanced ALS.

Methods

As an open-label extension of a multicenter, randomized, double-blind, placebo-controlled phase 2/3 study, patients were enrolled and administered methylcobalamin 50 mg intramuscularly twice weekly for up to 52 weeks.

Results

In total, 144 patients (mean age, 62.1 years; 61.1 % male) were included, and the overall disease duration was 53.2 ± 17.9 months, with 85.4 % of patients having an ALS severity stage ≥3. The incidence of adverse events was 94.4 %, and adverse drug reactions occurred in 3.5 % of patients, which included proteinuria (2.1 %) and single cases of supraventricular arrhythmia, increased blood urea, and hypertension (0.7 % each). None led to discontinuation or death. The survival rate at 52 weeks was 85.7 %, and as shown for the following patient subgroups: by ALS severity (stage 1–2, 100 %; 3, 85.3 %; 4, 82.8 %; 5, 82.0 %) and by presence of tracheostomy (with, 88.8 %; without, 84.1 %). The median change in the ALS functional rating scale total score from baseline to 52 weeks was −1.0.

Conclusion

There were no particular safety issues as reported in the phase 2/3 study and no clear deterioration in survival rate or physical function when ultra-high-dose methylcobalamin was administered intramuscularly in patients with advanced ALS. This regimen could be a candidate for initial therapy with further add-on to overcome ALS in the future.

目的：为了开发治疗肌萎缩性侧索硬化症（ALS）的联合疗法，我们研究了超高剂量甲基钴胺素（50 mg肌肉注射，每周两次）在晚期ALS患者中的长期安全性。方法：作为一项多中心、随机、双盲、安慰剂对照2/3期研究的开放标签延伸，患者入组，每周两次肌肉注射甲钴胺50 mg，持续52周。结果：共纳入144例患者，平均年龄62.1岁，男性占61.1%，总病程53.2±17.9个月，85.4%的患者ALS严重程度≥3期。不良事件发生率为94.4%，药物不良反应发生率为3.5%，包括蛋白尿（2.1%）、单例室上性心律失常、尿素升高、高血压（0.7%）。没有一个导致停产或死亡。52周存活率为85.7%，以下患者亚组显示：ALS严重程度（1-2期，100%;3,85.3%;4,82.8%;5,82.0%）和存在气管切开术（有，88.8%；无，84.1%）。从基线到52周，ALS功能评定量表总分的中位数变化为-1.0。结论：在2/3期研究中没有报道的特别的安全性问题，在晚期ALS患者中肌肉注射超高剂量甲基钴胺素没有明显的生存率或身体功能恶化。该方案可能成为未来治疗渐冻症的初始治疗方案，并有进一步的附加治疗。

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引用次数: 0

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。

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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