CNS Neuroscience & Therapeutics最新文献

Malignant Cells Beyond the Tumor Core: The Non-Negligible Factor to Overcome the Refractory of Glioblastoma

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-19 DOI: 10.1111/cns.70333

Yuyang Zhou, Qilin He, Guanglong Huang, Pei Ouyang, Hai Wang, Jiapeng Deng, Pengyu Chen, Xuan Liang, Zhisheng Hong, Xian Zhang, Songtao Qi, Yaomin Li

Background

Glioblastoma (GBM) is one of the most aggressive primary brain tumors in adults. Over 95% of GBM patients experience recurrence in the peritumoral brain tissue or distant regions, indicating the presence of critical factors in these areas that drive tumor recurrence. Current clinical treatments primarily focus on tumor cells from the tumor core (TC), while the role of neoplastic cells beyond the TC has been largely neglected.

Methods

We conducted a comprehensive review of existing literature and studies on GBM, focusing on the identification and characterization of questionable cells (Q cells). Advanced imaging techniques, such as diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET), were utilized to identify Q cells beyond the tumor core. We also analyzed the functional properties, cellular microenvironment, and physical characteristics of Q cells, as well as their implications for surgical resection.

Results

Our review revealed that Q cells exhibit unique functional attributes, including enhanced invasiveness, metabolic adaptations, and resistance mechanisms. These cells reside in a distinct cellular microenvironment and are influenced by physical properties such as solid stress and stiffness. Advanced imaging techniques have improved the identification of Q cells, enabling more precise surgical resection. Targeting Q cells in therapeutic strategies could significantly reduce the risk of GBM recurrence.

Conclusion

The presence of Q cells in the peritumoral brain zone (PBZ) and beyond is a critical factor in GBM recurrence. Current treatments, which primarily target tumor cells in the TC, are insufficient to prevent recurrence due to the neglect of Q cells. Future research should focus on understanding the mechanisms influencing Q cells and developing targeted therapies to improve patient outcomes.

背景胶质母细胞瘤（GBM）是成人中侵袭性最强的原发性脑肿瘤之一。超过 95% 的 GBM 患者会在瘤周脑组织或远处区域复发，这表明这些区域存在导致肿瘤复发的关键因素。目前的临床治疗主要针对肿瘤核心（TC）的肿瘤细胞，而TC以外的肿瘤细胞的作用在很大程度上被忽视。方法我们对有关 GBM 的现有文献和研究进行了全面回顾，重点关注问题细胞（Q 细胞）的鉴定和特征描述。我们利用弥散张量成像 (DTI)、磁共振波谱 (MRS) 和正电子发射断层扫描 (PET) 等先进的成像技术来识别肿瘤核心以外的 Q 细胞。我们还分析了 Q 细胞的功能特性、细胞微环境和物理特征，以及它们对手术切除的影响。结果我们的研究发现，Q 细胞表现出独特的功能特性，包括侵袭性增强、代谢适应性和抵抗机制。这些细胞驻留在独特的细胞微环境中，并受到固体应力和硬度等物理特性的影响。先进的成像技术提高了对 Q 细胞的识别能力，使手术切除更加精确。针对 Q 细胞的治疗策略可大大降低 GBM 复发的风险。结论 Q 细胞在瘤周脑区（PBZ）及以外区域的存在是 GBM 复发的关键因素。由于忽视了 Q 细胞，目前主要针对 TC 中肿瘤细胞的治疗不足以预防复发。未来的研究重点应放在了解影响 Q 细胞的机制和开发靶向疗法上，以改善患者的预后。

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引用次数: 0

Acute Restraint Stress Induces Long-Lasting Synaptic Enhancement by Inhibiting AMPK Activation in AD Model Mice

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-18 DOI: 10.1111/cns.70335

Ming Wang, Baoyuan Jin, Jihoon Jo

Background

Alzheimer's disease (AD) is characterized by a gradual synaptic loss. The progression of AD severely affects late-phase long-term potentiation (L-LTP), which is essential for long-term memory consolidation.

Aim

We have previously demonstrated the beneficial effects of acute restraint stress (ARS) on hippocampal LTP in AD mouse models. This study aimed to verify the effects and potential mechanisms of ARS on the maintenance of hippocampal L-LTP in two AD mouse models.

Materials and Methods

5xFAD and Tg2576 mice underwent a 30-min body immobilization protocol to induce ARS, followed by electrophysiological recordings of L-LTP (> 3 h) in the CA1 region of thehippocampus.

Results

The ARS-exposed group exhibited significantly enhanced L-LTP compared to the control group. Maintenance of L-LTP requires new protein synthesis and signaling via the mammalian target of rapamycin (mTOR) pathway. Our findings revealed that ARS increased hippocampal adenosine triphosphate (ATP) production and reduced AMPK activity. Inactivation of AMPK and subsequent activation of the mTOR pathway were strongly associated with the ARS-facilitated enhancement of L-LTP. Furthermore, our experiments using the mTOR inhibitor rapamycin demonstrated that it effectively prevented the enhancement of L-LTP following ARS, underscoring the pivotal role of mTOR in this process.

Conclusion

ARS may significantly modify AMPK activation and mTOR regulation in L-LTP, potentially triggering the mechanisms of long-term memory consolidation in AD mouse model mice. Identifying these underlying mechanisms could help promote the development of novel pharmaceutical agents for the treatment of AD.

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引用次数: 0

Incidence, Characteristics, and Risk Factors of Post-Radiosurgery Headaches: A Prospective Observational Study 放射手术后头痛的发生率、特征和风险因素：前瞻性观察研究

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-18 DOI: 10.1111/cns.70344

Shaobo Xiao, Jiayi Liu, Yunmo Liu, Guangshuang Lu, Yan Chang, Jinjing Zhao, Wenjie Su, Xinghao Guo, Nan Gao, Xiufen Zhang, Ke Liu, Zhen Zhang, Shengyuan Yu, Longsheng Pan, Ruozhuo Liu

Aims

This prospective observational study aimed to characterize the incidence, clinical features, and risk factors of headaches following CyberKnife radiosurgery (CKRS) in patients with intracranial pathologies.

Methods

In a prospective observational study conducted from January 2022 to January 2023, we enrolled consecutive patients who underwent CKRS. Patients completed headache-related questionnaires developed based on the International Classification of Headache Disorders (ICHD-3) guidelines at 24 h, 1 week, and 3 months post-radiosurgery. The incidence of CKRS-related headaches was determined, and the link between risk factors and outcomes was analyzed.

Results

Of 153 patients (female 58.2%; mean age 47.7 ± 14.8 years), all completed a 3-month follow-up. Among 153 patients, 61 (39.9%) developed post-CKRS headaches, with 83.6% reporting peak intensity within 2 weeks post-procedure. Fifty (32.7%) developed headaches within 2 weeks, resolving within 3 months. A strong temporal association between headache onset and CKRS supports a causal relationship. Multivariate Cox regression analysis identified female sex (HR = 2.16, 95% CI = 1.14–4.11, p = 0.019), younger age (HR = 0.97 per year, p = 0.006), absence of prior craniocerebral surgery (HR = 0.55, p = 0.046), and multiple lesions (HR = 2.28, p = 0.047) as independent risk factors. Although headaches were more frequently observed following radiation targeting the basal ganglia and thalamus, this association lacked statistical significance (p > 0.05).

Conclusions

Headaches attributed to brain radiosurgery constitute a significant yet overlooked clinical issue, warranting increased focus from surgical teams to deliver improved and tailored treatment.

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引用次数: 0

The Role of TCD in Assessing Postoperative Collateral Development and Long-Term Clinical Outcome in Moyamoya Disease

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-18 DOI: 10.1111/cns.70245

Shuangfeng Huang, Songtao Pei, Yiqin Han, Jiali Xu, Lanjing Wang, Heguan Fu, Changhong Ren, Xunming Ji, Sijie Li, Cong Han

Aims

To explore the role of transcranial Doppler (TCD) parameters after encephaloduroarteriosynangiosis (EDAS) to identify collateral development in moyamoya disease (MMD) and assess the relationship between these collateral formations and long-term postoperative cerebrovascular events.

Methods

A retrospective analysis of 91 MMD patients who underwent EDAS. Patients were categorized into rich or poor collateral groups based on postoperative angiography. TCD was used to monitor changes in hemodynamic parameters pre-and post-surgery. The association between clinical outcome, TCD parameters, and the degree of collateral development was investigated.

Outcomes

Ninety-one patients were assessed, with 45 (49.0%) exhibiting rich collaterals and 46 (51.0%) showing poor collaterals. Over 2 years, the rich collateral group experienced significantly fewer cerebrovascular events than the poor collateral group (p = 0.041). Postoperative evaluations demonstrated significant improvements in hemodynamic parameters within the rich collateral group, including increases in peak-systolic velocity (PSV), end-diastolic velocity (EDV), and mean velocity (MV), alongside decreases in resistance index (RI) and pulsatility index (PI) (p < 0.05). An EDV cutoff of > 16.62 cm/s in the superficial temporal artery (STA) effectively identified collateral development, yielding an area under the curve (AUC) of 0.907. Additionally, multivariate analysis revealed a strong association between preoperative MV of the STA and collateral formation.

Conclusion

TCD sonography is a non-invasive modality essential for assessing cerebral hemodynamics after revascularization in MMD. Collateral development shown on angiography corresponds to hemodynamic changes reflected in TCD. The postoperative EDV of the STA was a vital indicator of effective collaterals. Patients with well-developed collaterals were at a lower risk of long-term cerebrovascular events post-surgery.

{"title":"The Role of TCD in Assessing Postoperative Collateral Development and Long-Term Clinical Outcome in Moyamoya Disease","authors":"Shuangfeng Huang, Songtao Pei, Yiqin Han, Jiali Xu, Lanjing Wang, Heguan Fu, Changhong Ren, Xunming Ji, Sijie Li, Cong Han","doi":"10.1111/cns.70245","DOIUrl":"https://doi.org/10.1111/cns.70245","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the role of transcranial Doppler (TCD) parameters after encephaloduroarteriosynangiosis (EDAS) to identify collateral development in moyamoya disease (MMD) and assess the relationship between these collateral formations and long-term postoperative cerebrovascular events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis of 91 MMD patients who underwent EDAS. Patients were categorized into rich or poor collateral groups based on postoperative angiography. TCD was used to monitor changes in hemodynamic parameters pre-and post-surgery. The association between clinical outcome, TCD parameters, and the degree of collateral development was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Outcomes</h3>\u0000 \u0000 <p>Ninety-one patients were assessed, with 45 (49.0%) exhibiting rich collaterals and 46 (51.0%) showing poor collaterals. Over 2 years, the rich collateral group experienced significantly fewer cerebrovascular events than the poor collateral group (<i>p</i> = 0.041). Postoperative evaluations demonstrated significant improvements in hemodynamic parameters within the rich collateral group, including increases in peak-systolic velocity (PSV), end-diastolic velocity (EDV), and mean velocity (MV), alongside decreases in resistance index (RI) and pulsatility index (PI) (<i>p</i> < 0.05). An EDV cutoff of > 16.62 cm/s in the superficial temporal artery (STA) effectively identified collateral development, yielding an area under the curve (AUC) of 0.907. Additionally, multivariate analysis revealed a strong association between preoperative MV of the STA and collateral formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TCD sonography is a non-invasive modality essential for assessing cerebral hemodynamics after revascularization in MMD. Collateral development shown on angiography corresponds to hemodynamic changes reflected in TCD. The postoperative EDV of the STA was a vital indicator of effective collaterals. Patients with well-developed collaterals were at a lower risk of long-term cerebrovascular events post-surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prevalence of Aspirin or Clopidogrel Pharmacological Resistance in Ischemic Stroke: A Step Toward Precision Medicine

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-18 DOI: 10.1111/cns.70343

Samantha Cencer, Laurel Packard, Alan Davis, Asad Ahrar, Malgorzata Miller, Nadeem Khan, Nabil Wees, Jiangyong Min

Background and Objectives

Currently, there is not sufficient data regarding the prevalence of resistance or inadequate platelet function inhibition with the use of antiplatelet therapy in patients with noncardioembolic stroke. This study was designed to evaluate the prevalence of antiplatelet inactivity to aspirin and clopidogrel in the setting of chronic use and presentation with primary or recurrent stroke.

Methods

Patients who were taking aspirin, clopidogrel, or both at the time of presentation for stroke were selected in this study. Those with confirmed stroke on MRI or clinically determined TIA and age > 18 years were included. A standard laboratory test, VerifyNow aspirin or P2Y12 assay, was utilized to assess the responsiveness to the platelet inhibitors. A total of 158 patients were identified, 52 presenting with primary stroke and 106 with recurrent stroke. Data were analyzed using chi-squared or Fisher's exact as well as t-test analysis.

Results

Of the primary stroke population, 4% of patients demonstrated resistance to aspirin and 30% to clopidogrel. Of the patients presenting with recurrent stroke, 13% demonstrated resistance to aspirin and 38% to clopidogrel. The data also suggest increased resistance to aspirin and clopidogrel in Caucasians compared to minorities, with 11% versus 8% in regard to aspirin and 33% versus 17% to clopidogrel. Additionally, this study demonstrated 17% resistance to aspirin in males compared to 4% in females and 13% in males compared to 36% in females, respectively, regarding resistance to clopidogrel. No difference in inactivity to either aspirin or clopidogrel was detected between patients with stroke mechanisms of small or large vessel disease.

Conclusions

The present result demonstrated that a sizeable portion of the population has inefficacious activity in the setting of specific antiplatelet agents. Additionally, sex and ethnicity differences in responsiveness to aspirin or clopidogrel have been noted. Determining a patient's response to medications could provide opportunities to individualize treatment and better prevent future strokes. Further studies of a larger scale are indeed needed to apply this information to pursue individualized treatment.

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引用次数: 0

Quantitative EEG Insights Into A Hundred Adult ADHD Patients: A Deep Dive Into Test of Variables of Attention (TOVA) Correlations and Attention Dynamics

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-18 DOI: 10.1111/cns.70304

Elvan Ciftci, Zeynep Betul Alp

<div> <section> <h3> Objective</h3> <p>This study aimed to enhance the diagnostic accuracy of attention-deficit/hyperactivity disorder (ADHD) by integrating quantitative electroencephalography (qEEG) power bands with the test of variables of attention (TOVA) and self-reported psychiatric symptoms. We examined the relationship between TOVA scores, qEEG findings—particularly the theta-beta ratio—and comorbid psychiatric conditions to assess their role in refining ADHD diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).</p> </section> <section> <h3> Method</h3> <p>A total of 100 participants were assessed using TOVA, qEEG, and psychological scales, including the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Maudsley Obsessive-Compulsive Inventory (MOCI), and the Mood Disorder Questionnaire (MDQ). Participants were categorized into groups based on their Attention Comparison Scores (ACS) above or below the zero threshold. Mann–Whitney <i>U</i>-tests, correlation analyses, and predictive modeling using automatic linear modeling (ALM) were conducted to evaluate group differences, age-related changes, and predictor variables for attention performance.</p> </section> <section> <h3> Results</h3> <p>All participants met the diagnostic criteria for ADHD. Among them, 37% exhibited anxiety, 60% depression, 26% obsessive-compulsive, and 35% mood disorder symptoms. The group with ACS above zero was significantly older (<i>p</i> = 0.034) and performed better on all Tests of Variables of Attention (TOVA) measures (<i>p</i> < 0.05). Age negatively correlated with attention scores (<i>r</i> = −0.371, <i>p</i> < 0.001), response time variability (<i>r</i> = −0.241, <i>p</i> = 0.016), and response time (<i>r</i> = −0.311, <i>p</i> = 0.002). qEEG showed significant age-related changes in theta-to-beta and delta-to-beta ratios (<i>p</i> < 0.005). TOVA and qEEG ratios, particularly beta and delta activity, predicted attention and response time variability, with adjusted <i>R</i><sup>2</sup> values between 71.5% and 87.1%.</p> </section> <section> <h3> Conclusion</h3> <p>The findings highlight that attention performance in ADHD is shaped by age, neuropsychological factors, and qEEG-measured brain activity. Higher attention scores correlate with better TOVA results, particularly in response time and error rates. Age-related declines in attention align with reductions in theta-to-beta and delta-to-beta ratios. Predictive modeling underscores the value of combining TOVA and qEEG to identify key pred

{"title":"Quantitative EEG Insights Into A Hundred Adult ADHD Patients: A Deep Dive Into Test of Variables of Attention (TOVA) Correlations and Attention Dynamics","authors":"Elvan Ciftci, Zeynep Betul Alp","doi":"10.1111/cns.70304","DOIUrl":"https://doi.org/10.1111/cns.70304","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to enhance the diagnostic accuracy of attention-deficit/hyperactivity disorder (ADHD) by integrating quantitative electroencephalography (qEEG) power bands with the test of variables of attention (TOVA) and self-reported psychiatric symptoms. We examined the relationship between TOVA scores, qEEG findings—particularly the theta-beta ratio—and comorbid psychiatric conditions to assess their role in refining ADHD diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A total of 100 participants were assessed using TOVA, qEEG, and psychological scales, including the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Maudsley Obsessive-Compulsive Inventory (MOCI), and the Mood Disorder Questionnaire (MDQ). Participants were categorized into groups based on their Attention Comparison Scores (ACS) above or below the zero threshold. Mann–Whitney <i>U</i>-tests, correlation analyses, and predictive modeling using automatic linear modeling (ALM) were conducted to evaluate group differences, age-related changes, and predictor variables for attention performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All participants met the diagnostic criteria for ADHD. Among them, 37% exhibited anxiety, 60% depression, 26% obsessive-compulsive, and 35% mood disorder symptoms. The group with ACS above zero was significantly older (<i>p</i> = 0.034) and performed better on all Tests of Variables of Attention (TOVA) measures (<i>p</i> < 0.05). Age negatively correlated with attention scores (<i>r</i> = −0.371, <i>p</i> < 0.001), response time variability (<i>r</i> = −0.241, <i>p</i> = 0.016), and response time (<i>r</i> = −0.311, <i>p</i> = 0.002). qEEG showed significant age-related changes in theta-to-beta and delta-to-beta ratios (<i>p</i> < 0.005). TOVA and qEEG ratios, particularly beta and delta activity, predicted attention and response time variability, with adjusted <i>R</i><sup>2</sup> values between 71.5% and 87.1%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings highlight that attention performance in ADHD is shaped by age, neuropsychological factors, and qEEG-measured brain activity. Higher attention scores correlate with better TOVA results, particularly in response time and error rates. Age-related declines in attention align with reductions in theta-to-beta and delta-to-beta ratios. Predictive modeling underscores the value of combining TOVA and qEEG to identify key pred","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Effect of Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex on the Amyotrophic Lateral Sclerosis Patients With Cognitive Impairment: A Double-Blinded, Randomized, and Sham Control Trial

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-18 DOI: 10.1111/cns.70316

Wensi Zheng, Xiaojie Zhang, Jingjiong Chen, Xinghua Luan, Jijun Wang, Liren Zhang, Kun Liu, Yuwu Zhao, Zhouwei Xu

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. A large number of ALS patients have cognitive impairment. In this double-blinded, randomized, and sham-controlled study, we aimed to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on ALS patients with cognitive impairment.

Methods

A total of 90 ALS patients with cognitive impairment were recruited from two cohorts; 80 participants were randomly assigned in a 1:1 ratio to receive 10 Hz rTMS or sham treatment on the bilateral dorsolateral prefrontal cortices (DLPFC) for 4 consecutive weeks. The patients were assessed by ECAS and ALSFRS-R scales. The Zarit care burden scale was administered to caregivers of ALS patients. The primary outcome measured was the rate of decline in the total ECAS score between pretreatment, 6 months post-treatment, and 12 months post-treatment. Secondary outcomes included the group difference in the slope of the Zarit score, ALSFRS-R total score, and the neurofilament light chain plasma levels.

Results

The ECAS total score in the intention-to-treat population significantly changed from 79.74 ± 6.39 to 81.98 ± 6.51 and 79.22 ± 6.50 with rTMS intervention at the 6-month and 12-month follow-ups, respectively (p = 0.031, p = 0.042). The Zarit score also significantly decreased from 57.65 ± 3.42 to 52.24 ± 3.34 and 56.42 ± 3.41 at the 3-month and 6-month post-treatment time points, respectively (p = 0.003, p = 0.014). No significant differences were observed between the groups for other secondary endpoints. However, there was a trend of decreasing NF-L level rates in the treatment group over the first 6 months' follow-up.

Conclusions

rTMS could yield short-term positive effects on the ALS patients subgroup with cognitive impairment and alleviate caregivers' burden. No improvement was observed in the severity of ALS and ALS plasma biomarkers.

{"title":"The Effect of Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex on the Amyotrophic Lateral Sclerosis Patients With Cognitive Impairment: A Double-Blinded, Randomized, and Sham Control Trial","authors":"Wensi Zheng, Xiaojie Zhang, Jingjiong Chen, Xinghua Luan, Jijun Wang, Liren Zhang, Kun Liu, Yuwu Zhao, Zhouwei Xu","doi":"10.1111/cns.70316","DOIUrl":"https://doi.org/10.1111/cns.70316","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. A large number of ALS patients have cognitive impairment. In this double-blinded, randomized, and sham-controlled study, we aimed to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on ALS patients with cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 90 ALS patients with cognitive impairment were recruited from two cohorts; 80 participants were randomly assigned in a 1:1 ratio to receive 10 Hz rTMS or sham treatment on the bilateral dorsolateral prefrontal cortices (DLPFC) for 4 consecutive weeks. The patients were assessed by ECAS and ALSFRS-R scales. The Zarit care burden scale was administered to caregivers of ALS patients. The primary outcome measured was the rate of decline in the total ECAS score between pretreatment, 6 months post-treatment, and 12 months post-treatment. Secondary outcomes included the group difference in the slope of the Zarit score, ALSFRS-R total score, and the neurofilament light chain plasma levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ECAS total score in the intention-to-treat population significantly changed from 79.74 ± 6.39 to 81.98 ± 6.51 and 79.22 ± 6.50 with rTMS intervention at the 6-month and 12-month follow-ups, respectively (<i>p</i> = 0.031, <i>p</i> = 0.042). The Zarit score also significantly decreased from 57.65 ± 3.42 to 52.24 ± 3.34 and 56.42 ± 3.41 at the 3-month and 6-month post-treatment time points, respectively (<i>p</i> = 0.003, <i>p</i> = 0.014). No significant differences were observed between the groups for other secondary endpoints. However, there was a trend of decreasing NF-L level rates in the treatment group over the first 6 months' follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>rTMS could yield short-term positive effects on the ALS patients subgroup with cognitive impairment and alleviate caregivers' burden. No improvement was observed in the severity of ALS and ALS plasma biomarkers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intranasal Administration of a Novel ApoE-Mimetic Peptide-Coated Gold Nanoparticles as Therapy for Ischemic Stroke

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-18 DOI: 10.1111/cns.70263

Ming-Yan Yang, Ya-Wen Yu, Da-Lei Li, Teng Liu, Zhi-Xia Wang, Bai-Fang Gong, Xin-Xin Bai, Ya-Ping He, Hai-Yue Liang, Hua-Ying Fan

Background

Discovering new drugs for ischemic stroke is an effective intervention that may address the significant unmet clinical need of stroke. There is increasing evidence indicating that apolipoprotein E (ApoE) can be a potential candidate for the treatment of ischemic stroke. A short ApoE peptide could maintain the anti-inflammation and neuroprotection of the intact protein. Herein, we synthetized a novel ApoE memetic peptide, referred to as CS15, and explored its efficacy and neuroprotection of its innovative formulation of gold nanoparticles (GNPs) in transient focal ischemia in rat.

Methods

We examined anti-inflammatory activities of CS15 using LPS-induced inflammatory response in BV2 cells and in mice. GNPs were prepared by citrate reduction method and surface modified with CS15 to generate CS15-coated GNPs (CS15-GNPs). The accumulation and distribution of CS15-GNPs in the brain were confirmed by detecting the gold amount and fluorescent intensity. The neuroprotection of CS15 and CS15-GNPs was evaluate using middle cerebral artery occlusion (MCAO) model.

Results

The results showed that CS15 exhibited more potent anti-inflammation than COG1410. GNPs are capable of transporting CS15 to the brain, expanding its duration of action. Intranasal administration of CS15-GNPs notably reduced infarct size and neuronal damage, improved neurological function and inhibited cerebral inflammation in transient focal ischemia in rat, which had much higher efficiency than free CS15.

Conclusion

CS15-GNPs exhibited favorable neuroprotection and biosafety. This study develops an innovative ApoE-mimetic peptide-capped GNPs, which provides a potential strategy for the treatment of ischemic stroke.

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引用次数: 0

Early Prediction of the Evolution of Self-Limited Epilepsy With Centrotemporal Spikes to Epileptic Encephalopathy With Spike-and-Wave Activation in Sleep: A Prediction Model Construction Based on Quantitative Electroencephalography Characteristics 早期预测伴有中心颞区棘波的自限性癫痫向伴有睡眠中棘波激活的癫痫性脑病的演变：基于定量脑电图特征的预测模型构建

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-18 DOI: 10.1111/cns.70268

Zimeng He, Linghui Zhu, Zaifen Gao, Yumei Li, Xiaoyu Zhao, Xiaofan Yang, Lili Tong, Guijuan Jia, Dongqing Zhang, Baomin Li

Aims

To predict the progression of children with self-limited epilepsy with centrotemporal spikes (SeLECTS) to epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS).

Methods

We conducted a retrospective analysis of early clinical and electroencephalography (EEG) data. Clinical parameters included demographic and epilepsy-related characteristics. EEG were qualitatively (localization, lateralization, synchrony, non-Rolandic discharges, nondipole spikes, multiple spikes, focal slow-wave activity) and quantitatively (spike–wave index [SWI], spike–wave frequency [SWF], power spectral density [PSD], phase-locking value [PLV], phase lag index [PLI], weighted phase lag index [wPLI], characteristic path length [CPL], clustering coefficient [CC], small-worldness [Sigma]) analyzed. A logistic regression-based prediction model was further formulated and evaluated.

Results

This study included 50 children with seizure-free typical SeLECTS and 76 who developed EE-SWAS. Multivariable logistic regression revealed that early EEG features—SWF, relative PSD in the alpha band, wPLI and CPL in the delta band—were associated with the risk of encephalopathic transformation. The model demonstrated good performance with an area under the curve of 0.817 (95% confidence interval 0.736–0.898). The model showed a good fit and clinical benefit.

Conclusion

Initial quantitative EEG characteristics of SeLECTS can predict the development of EE-SWAS, suggesting distinct disease characteristics and pathogeneses in children at risk of encephalopathic transformation.

{"title":"Early Prediction of the Evolution of Self-Limited Epilepsy With Centrotemporal Spikes to Epileptic Encephalopathy With Spike-and-Wave Activation in Sleep: A Prediction Model Construction Based on Quantitative Electroencephalography Characteristics","authors":"Zimeng He, Linghui Zhu, Zaifen Gao, Yumei Li, Xiaoyu Zhao, Xiaofan Yang, Lili Tong, Guijuan Jia, Dongqing Zhang, Baomin Li","doi":"10.1111/cns.70268","DOIUrl":"https://doi.org/10.1111/cns.70268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To predict the progression of children with self-limited epilepsy with centrotemporal spikes (SeLECTS) to epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective analysis of early clinical and electroencephalography (EEG) data. Clinical parameters included demographic and epilepsy-related characteristics. EEG were qualitatively (localization, lateralization, synchrony, non-Rolandic discharges, nondipole spikes, multiple spikes, focal slow-wave activity) and quantitatively (spike–wave index [SWI], spike–wave frequency [SWF], power spectral density [PSD], phase-locking value [PLV], phase lag index [PLI], weighted phase lag index [wPLI], characteristic path length [CPL], clustering coefficient [CC], small-worldness [Sigma]) analyzed. A logistic regression-based prediction model was further formulated and evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study included 50 children with seizure-free typical SeLECTS and 76 who developed EE-SWAS. Multivariable logistic regression revealed that early EEG features—SWF, relative PSD in the alpha band, wPLI and CPL in the delta band—were associated with the risk of encephalopathic transformation. The model demonstrated good performance with an area under the curve of 0.817 (95% confidence interval 0.736–0.898). The model showed a good fit and clinical benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Initial quantitative EEG characteristics of SeLECTS can predict the development of EE-SWAS, suggesting distinct disease characteristics and pathogeneses in children at risk of encephalopathic transformation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the Role of Protein Posttranslational Modifications in Glioma Prognosis

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-03-16 DOI: 10.1111/cns.70330

Zhipeng Jiang, Hanxue Huang, Youwei Guo, Zihan Wang, Hailong Huang, Wen Yin, Haoxuan Huang, Lei Wang, Weidong Liu, Xingjun Jiang, Caiping Ren

Background

Gliomas represent the most aggressive malignancies of the central nervous system, with posttranslational modifications (PTMs) emerging as critical regulators of oncogenic processes through dynamic protein functional modulation. Despite their established role in tumor biology, the systematic characterization of PTM-mediated molecular mechanisms driving glioma progression remains unexplored. This study aims to uncover the molecular mechanisms of glioma, with a focus on the role of PTMs.

Methods

We analyzed the PTM pathway to classify glioma patients into distinct clusters. Comprehensive analyses compared intercluster differences in clinical outcomes, mutational landscapes, and immune microenvironment profiles. Differentially expressed genes (DEGs) were identified to construct a robust prognostic prediction model with machine learning approaches. Among the genes included in the model, TOM1L1 (Target of Myb1 Like 1 Membrane Trafficking Protein) was selected for in vitro experimental validation to assess its role in glioma progression.

Results

PTMs were found to influence glioma prognosis significantly. Dysregulation in specific pathways, such as glutathionylation and citrullination, was correlated with more aggressive clinical features. The prognostic model, comprising DEGs such as TOM1L1, demonstrated high predictive accuracy (c-index = 0.867)—the scores derived from the model strongly correlated with glioma progression indicators. In vitro experiments revealed that TOM1L1 facilitates malignant progression by modulating PTM pathways, confirming its functional role in glioma.

Conclusion

Our study establishes the first comprehensive PTM atlas in gliomas, revealing subtype-specific modification patterns with clinical and therapeutic implications. TOM1L1 emerges as a promising prognostic biomarker and a potential therapeutic intervention target. Targeting PTM pathways may offer novel strategies for glioma treatment, enhancing patient outcomes.

{"title":"Unveiling the Role of Protein Posttranslational Modifications in Glioma Prognosis","authors":"Zhipeng Jiang, Hanxue Huang, Youwei Guo, Zihan Wang, Hailong Huang, Wen Yin, Haoxuan Huang, Lei Wang, Weidong Liu, Xingjun Jiang, Caiping Ren","doi":"10.1111/cns.70330","DOIUrl":"https://doi.org/10.1111/cns.70330","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gliomas represent the most aggressive malignancies of the central nervous system, with posttranslational modifications (PTMs) emerging as critical regulators of oncogenic processes through dynamic protein functional modulation. Despite their established role in tumor biology, the systematic characterization of PTM-mediated molecular mechanisms driving glioma progression remains unexplored. This study aims to uncover the molecular mechanisms of glioma, with a focus on the role of PTMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed the PTM pathway to classify glioma patients into distinct clusters. Comprehensive analyses compared intercluster differences in clinical outcomes, mutational landscapes, and immune microenvironment profiles. Differentially expressed genes (DEGs) were identified to construct a robust prognostic prediction model with machine learning approaches. Among the genes included in the model, <i>TOM1L1</i> (Target of Myb1 Like 1 Membrane Trafficking Protein) was selected for in vitro experimental validation to assess its role in glioma progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PTMs were found to influence glioma prognosis significantly. Dysregulation in specific pathways, such as glutathionylation and citrullination, was correlated with more aggressive clinical features. The prognostic model, comprising DEGs such as <i>TOM1L1</i>, demonstrated high predictive accuracy (c-index = 0.867)—the scores derived from the model strongly correlated with glioma progression indicators. In vitro experiments revealed that TOM1L1 facilitates malignant progression by modulating PTM pathways, confirming its functional role in glioma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study establishes the first comprehensive PTM atlas in gliomas, revealing subtype-specific modification patterns with clinical and therapeutic implications. <i>TOM1L1</i> emerges as a promising prognostic biomarker and a potential therapeutic intervention target. Targeting PTM pathways may offer novel strategies for glioma treatment, enhancing patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0