Clinical Neurology and Neurosurgery最新文献_第3页

“Eiffel-by-night” sign in hypertrophic pachymeningitis: Clinical and radiological correlates 肥厚性厚性脑膜炎的“夜间艾菲尔”征：临床和放射学相关性

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-24 DOI: 10.1016/j.clineuro.2025.109291

Daniela Ohlweiler Brescovit , Leandro Tavares Lucato , Luiz Henrique Martins Castro , Suely Kazue Nagahashi Marie , Guilherme Diogo Silva

Objective

To evaluate the clinical significance of the “Eiffel-by-night” (EBN) sign in hypertrophic pachymeningitis, focusing on its frequency, etiological associations, and prognostic value for recurrence, which improves diagnostic workflows, facilitating earlier, targeted therapeutic interventions.

Methods

We conducted a retrospective observational study at the Autoimmune Meningitis Outpatient Clinic at Hospital das Clínicas, Universidade de São Paulo (Brazil), from January 2024 to April 2025, including patients with HP confirmed by MRI dural thickening and enhancement, excluding infectious and neoplastic cases. Clinical, cerebrospinal fluid (CSF), and imaging data were obtained from medical records. Two independent raters assessed the presence of the EBN sign on post-contrast T1-weighted on baseline and follow-up MRIs, comparing EBN+ and EBN– groups.

Results

Forty-five patients fulfilled eligibility criteria; 8 (17.7 %) of whom were EBN+, mostly middle-aged women. EBN sign was more common in idiopathic HP (62.5 %), and less so in IgG4-related disease, neurosarcoidosis, and ANCA-associated vasculitis. Clinical and CSF profiles were similar between groups, except for two male EBN+ patients, with marked pleocytosis. Most EBN+ patients (75 %) had a relapsing disease course. The sign persisted in 86 % of cases on the last follow-up.

Conclusion

The EBN sign occurred in fewer than one-fifth of HP cases, primarily in idiopathic disease. Despite no clear clinical or CSF distinctions, its persistence correlated with frequent relapse.

目的探讨“夜间艾菲尔”（Eiffel-by-night， EBN）征象在肥厚性厚性脑膜炎中的临床意义，重点分析其出现频率、病因关联及复发的预后价值，以改善诊断流程，促进早期、有针对性的治疗干预。方法：研究人员于2024年1月至2025年4月在巴西圣保罗大学（Universidade de o Paulo） das医院Clínicas自身免疫性脑膜炎门诊进行回顾性观察研究，纳入经MRI硬膜增厚和增强确诊的HP患者，排除感染性和肿瘤性病例。临床、脑脊液（CSF）和影像学资料均来自医疗记录。两名独立评分者评估对比后基线和随访mri t1加权的EBN征象的存在，比较EBN+组和EBN -组。结果45例患者符合入选标准；EBN+ 8例（17.7 %），以中年妇女为主。EBN征象在特发性HP中更为常见（62.5 %），而在igg4相关疾病、神经结节病和anca相关血管炎中较少。除了2例男性EBN+ 患者有明显的多细胞增多外，两组患者的临床和脑脊液特征相似。大多数EBN+ 患者（75 %）有复发病程。在最后一次随访中，86 %的病例仍存在该症状。结论EBN征在HP病例中的发生率不到五分之一，主要见于特发性疾病。尽管没有明确的临床或脑脊液区别，但其持续存在与频繁复发相关。

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引用次数: 0

A comment on cohort structure in Chiari I malformation studies Chiari I型畸形研究中的队列结构评述

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-24 DOI: 10.1016/j.clineuro.2025.109295

Shiva A. Nischal, Shaan Patel, Jayaratnam Jayamohan

引用次数: 0

Occlusion of posterior communicating artery aneurysms with a ‘fetal’ type circulation treated with flow diversion 后交通动脉瘤合并“胎儿”型循环的分流治疗

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-23 DOI: 10.1016/j.clineuro.2025.109290

Kimberly Han, Aryan Wadhwa, Felipe Ramirez-Velandia, Alejandro Enriquez-Marulanda, Justin Granstein, Philipp Taussky, Christopher S. Ogilvy

Objective

The fetal-type posterior communicating artery is a circle of Willis variant. Previous studies report lower complete occlusion rates (0–20 %) for fetal-type PComA (fPComA) aneurysms treated with flow diversion than non-fPComA aneurysms (70–75 %). This study evaluated the efficacy of Pipeline embolization devices (PED) in treating fPComA aneurysms and identified predictors of obliteration.

Methods

Retrospective analysis was performed on fPComA and non-fPComA aneurysms in patients treated from 2013 to 2023 with PED in the internal carotid artery covering the PComA origin. Demographic, fetal-type anatomy morphology, aneurysm characteristics, intervention technique, and outcome data (e.g., occlusion status at one year, complications, and retreatment rate) was collected. Aneurysm occlusion was assessed during angiographic follow-up. Univariate statistical analysis was performed to compare aneurysm occlusion rates.

Results

Among 96 patients treated for PComA aneurysms, 19 patients with a mean age of 61.6 ± 16.3 years had a fetal variant. Three patients were lost to follow-up. Flow diversion achieved complete or near-complete occlusion (>90 % angiographic obliteration) in 12 fetal variant cases (75 %) at one year, matching PED-treated non-fPComA aneurysm occlusion rate (75 %). Two patients with fPComA aneurysms experienced in-stent thrombosis resulting in minor strokes without permanent deficits. Distal PED tip placement in the proximal M1 segment was significantly associated with complete fPComA aneurysm occlusion (p = 0.049).

Conclusion

PED treatment for fPComA aneurysms in our cohort demonstrates a 75 % occlusion rate, exceeding rates of prior studies and matching non-fPComA cases. PED placement technique was significantly associated with this high occlusion rate. These findings highlight PED as a potentially safe and effective intervention for these aneurysms.

目的胎儿型后交通动脉是一种环状Willis变异型动脉。先前的研究报告，胎儿型PComA （fPComA）动脉瘤经分流治疗的完全闭塞率（0-20 %）低于非fPComA动脉瘤（70-75 %）。本研究评估了管道栓塞装置（PED）治疗fPComA动脉瘤的疗效，并确定了栓塞的预测因素。方法回顾性分析2013 ~ 2023年在覆盖PComA起源的颈内动脉内发生PED的fPComA和非fPComA患者。收集人口统计学、胎儿型解剖形态、动脉瘤特征、介入技术和结局数据（如一年的闭塞状况、并发症和再治疗率）。在血管造影随访期间评估动脉瘤闭塞。采用单变量统计分析比较动脉瘤闭塞率。结果96例PComA动脉瘤患者中有19例存在胎儿变异，平均年龄为61.6 ± 16.3岁。3例患者失访。在12例胎儿变异病例（75 %）中，血流转移在一年内实现了完全或接近完全闭塞（血管造影闭塞）（>90 %），与ped治疗的非fpcoma动脉瘤闭塞率（75 %）相当。两名患有fPComA动脉瘤的患者在支架内形成血栓，导致轻微中风，但没有永久性缺陷。远端PED尖端放置在近端M1段与完全fPComA动脉瘤闭塞显著相关（p = 0.049）。结论：在我们的队列中，ped治疗fPComA动脉瘤的闭塞率为75% %，超过了先前的研究，并与非fPComA病例相匹配。PED放置技术与高闭塞率显著相关。这些发现强调了PED作为治疗这些动脉瘤的潜在安全有效的干预手段。

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引用次数: 0

Predicting dementia severity changes after shunt surgery for idiopathic normal-pressure hydrocephalus: Role of the tap test and cognitive assessments 预测特发性常压脑积水分流手术后痴呆严重程度的变化：tap测试和认知评估的作用。

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-16 DOI: 10.1016/j.clineuro.2025.109288

Fuyuki Koizumi , Hideki Kanemoto , Takashi Suehiro , Shunsuke Sato , Yuto Satake , Daiki Taomoto , Kenji Yoshiyama , Koichi Hosomi , Haruhiko Kishima , Manabu Ikeda

Objective

To determine the most appropriate assessment scale and timing of the tap test for predicting improvements in dementia severity after shunt surgery in patients with idiopathic normal-pressure hydrocephalus (iNPH).

Methods

Data were extracted from an observational study that followed patients with iNPH as follows: Patients diagnosed with possible iNPH and scheduled for a tap test were enrolled. Patients diagnosed with probable iNPH by the tap test underwent shunting and followed up for 3 months after shunting. Patients with missing data in the tap test assessment items (gait speed: 3 consecutive days before tapping and 3 consecutive days after tapping; cognition: before tapping, 1 day after tapping and 1 week after tapping; and urinary dysfunction: before tapping and 1 week after tapping) or in the Clinical Dementia Rating (CDR) assessed before tapping and 3 months after shunting were excluded from this study.

Results

54 patients were included in the analysis. The change in CDR-Sum of Boxes (CDR-SoB) score after shunt surgery was significantly correlated with the change in Mini-Mental State Examination (MMSE) score (β = −0.417, p < 0.001) and Frontal Assessment Battery (FAB) score (β = −0.379, p = 0.002) 3 months after shunt surgery after adjusting for age and sex. The change in MMSE score after shunt surgery was correlated with the change in MMSE score 1 day after tapping (β = 0.411, p = 0.001), the change in the minimum Timed Up and Go test score across repeated tests after tapping (β = −0.376, p = 0.004) and attention/concentration in Wechsler Memory Scale-Revised 1 day after tapping (β = −0.289, p = 0.024). The change in FAB score after shunt surgery was correlated with the change in the maximum FAB score across repeated tests after tapping (β = 0.523, p < 0.001).

Conclusion

Combining MMSE and FAB assessments during the tap test may yield more useful information in assessing cognitive impairment than using either MMSE or FAB alone.

目的：确定特发性常压脑积水（iNPH）患者分流术后痴呆严重程度改善的tap试验的最合适评估量表和时间。方法：从一项观察性研究中提取数据，该研究对iNPH患者进行如下随访：诊断为可能的iNPH并计划进行tap测试的患者入组。通过tap试验诊断为可能的iNPH的患者接受分流治疗，并在分流后随访3个月。在叩击测试评估项目（步态速度：叩击前连续3天、叩击后连续3天；认知能力：叩击前、叩击后1 天、叩击后1周；泌尿功能障碍：叩击前、叩击后1周）或叩击前、分流后3个月临床痴呆评分（CDR）数据缺失的患者排除在本研究之外。结果：54例患者纳入分析。分流手术后CDR-Sum of Boxes （CDR-SoB）评分的变化与Mini-Mental State Examination （MMSE）评分的变化具有显著相关性（β = -0.417, p ）。结论：tap试验中结合MMSE和FAB评估可能比单独使用MMSE或FAB更能提供评估认知功能障碍的有用信息。

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引用次数: 0

Clinical significance of thalamic FASI finding in neurofibromatosis type 1: Deepening the cognitive relevance with advanced approaches 1型神经纤维瘤病丘脑FASI发现的临床意义：与先进方法加深认知相关性

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-16 DOI: 10.1016/j.clineuro.2025.109287

Gül Yücel , Nur Yücel Ekici

引用次数: 0

Relative influence of paraspinal muscularity and underlying bone quality on proximal junctional kyphosis and failure mode in patients undergoing thoracolumbar instrumented fusion 椎旁肌肉和潜在骨质量对胸腰椎内固定融合患者近端关节后凸和失败模式的相对影响。

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-15 DOI: 10.1016/j.clineuro.2025.109286

Zach Pennington , Anthony L. Mikula , Abdelrahman Hamouda , Derrick Obiri-Yeboah , Michael L. Martini , Andrew J. Grossbach , Gabriella L. Paganucci , Ahmad N. Nassr , Brett A. Freedman , Arjun Sebastian , Jeremy L. Fogelson , Benjamin D. Elder

Objective

To assess paraspinal muscularity and bone quality contribution to PJK risk.

Methods

Defining PJK as ≥ 10° increase in proximal junctional angle from first upright radiograph, thoracolumbopelvic fusion patients experiencing PJK were compared to controls. Baseline radiographic parameters, bone quality in CT Hounsfield units (HU), and paraspinal musculature cross-sectional area (CSA) at L3 and the UIV. Patients were subdivided into type 1–3 PJK based upon the Yagi-Boachie scale. Time-dependent analyses with univariable Cox proportional hazards model were performed.

Results

206 patients were included (59.7 % female; median age 67.1); 26.9 % experienced PJK – 52.5 % type 1, 27.8 % type 2, and 19.7 % type 3. Univariable comparisons showed PJK patients had lower HU at the UIV (137 vs 151; p = 0.047) and UIV+ 1 (137 vs 151; p = 0.028); mean multifidus CSA (p = 0.21) was also nonsignificantly smaller. Average HU were lower in type 2 PJK patients relative to non-PJK and type 1 PJK (p < 0.001). Type 2 failure was predicted by UIV/UIV+ 1, UIV, and UIV+ 1 average HU (all p < 0.01) while type 1 failure was predicted by UIV multifidus CSA (p = 0.03); average HU did not predict type 1 failure.

Conclusions

Poor bone quality may be the strongest predictor of PJK; however, subanalysis by PJK type suggests it only increases the odds of bony or implant/bone interface failure. Decreased multifidus CSA appears to confer risk for type 1 (discoligamentous) PJK, suggesting PJK failure mode is dictated by the interplay of UIV bony and soft tissue integrity.

目的：评价椎旁肌肉和骨质量对PJK风险的影响。方法：将PJK定义为第一次直立x线片近端关节角增加≥ 10°，将经历PJK的胸腰盂融合患者与对照组进行比较。基线x线摄影参数，CT Hounsfield单元（HU）的骨质量，L3和UIV的棘旁肌肉横截面积（CSA）。根据Yagi-Boachie量表将患者细分为1-3型PJK。采用单变量Cox比例风险模型进行时间相关分析。结果：纳入206例患者（59.7 %为女性，中位年龄67.1岁）；26.9 %经历PJK， 52.5 % 1型，27.8 % 2型，19.7 % 3型。单变量比较显示，PJK患者在UIV时的HU较低（137 vs 151, p = 0.047）和UIV+ 1 (137 vs 151, p = 0.028)；平均多裂肌CSA （p = 0.21）也无显著性差异。2型PJK患者的平均HU低于非PJK和1型PJK （p ）结论：骨质量差可能是PJK的最强预测因子；然而，PJK类型的亚分析表明，它只会增加骨或种植体/骨界面失效的几率。多裂肌CSA降低似乎会增加1型（双韧带）PJK的风险，这表明PJK的失败模式是由紫外线照射下骨和软组织完整性的相互作用决定的。

{"title":"Relative influence of paraspinal muscularity and underlying bone quality on proximal junctional kyphosis and failure mode in patients undergoing thoracolumbar instrumented fusion","authors":"Zach Pennington , Anthony L. Mikula , Abdelrahman Hamouda , Derrick Obiri-Yeboah , Michael L. Martini , Andrew J. Grossbach , Gabriella L. Paganucci , Ahmad N. Nassr , Brett A. Freedman , Arjun Sebastian , Jeremy L. Fogelson , Benjamin D. Elder","doi":"10.1016/j.clineuro.2025.109286","DOIUrl":"10.1016/j.clineuro.2025.109286","url":null,"abstract":"<div><h3>Objective</h3><div>To assess paraspinal muscularity and bone quality contribution to PJK risk.</div></div><div><h3>Methods</h3><div>Defining PJK as ≥ 10° increase in proximal junctional angle from first upright radiograph, thoracolumbopelvic fusion patients experiencing PJK were compared to controls. Baseline radiographic parameters, bone quality in CT Hounsfield units (HU), and paraspinal musculature cross-sectional area (CSA) at L3 and the UIV. Patients were subdivided into type 1–3 PJK based upon the Yagi-Boachie scale. Time-dependent analyses with univariable Cox proportional hazards model were performed.</div></div><div><h3>Results</h3><div>206 patients were included (59.7 % female; median age 67.1); 26.9 % experienced PJK – 52.5 % type 1, 27.8 % type 2, and 19.7 % type 3. Univariable comparisons showed PJK patients had lower HU at the UIV (137 vs 151; p = 0.047) and UIV+ 1 (137 vs 151; p = 0.028); mean multifidus CSA (p = 0.21) was also nonsignificantly smaller. Average HU were lower in type 2 PJK patients relative to non-PJK and type 1 PJK (p < 0.001). Type 2 failure was predicted by UIV/UIV+ 1, UIV, and UIV+ 1 average HU (all p < 0.01) while type 1 failure was predicted by UIV multifidus CSA (p = 0.03); average HU did not predict type 1 failure.</div></div><div><h3>Conclusions</h3><div>Poor bone quality may be the strongest predictor of PJK; however, subanalysis by PJK type suggests it only increases the odds of bony or implant/bone interface failure. Decreased multifidus CSA appears to confer risk for type 1 (discoligamentous) PJK, suggesting PJK failure mode is dictated by the interplay of UIV bony and soft tissue integrity.</div></div>","PeriodicalId":10385,"journal":{"name":"Clinical Neurology and Neurosurgery","volume":"261 ","pages":"Article 109286"},"PeriodicalIF":1.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Influence of surgical technique, interbody characteristics, and radiographic parameters on fusion rates across the disc space and posterolateral elements following transforaminal lumbar interbody fusion 手术技术、椎间特征和影像学参数对经椎间孔腰椎椎间融合术后椎间盘间隙和后外侧元素融合率的影响

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-14 DOI: 10.1016/j.clineuro.2025.109285

Zach Pennington , Abdelrahman Hamouda , Omar Hafz , Anthony L. Mikula , Michelle J. Clarke , William E. Krauss , Brett A. Freedman , Melvin D. Helgeson , Ahmad N. Nassr , Arjun S. Sebastian , Jeremy L. Fogelson , Benjamin D. Elder

Objective

To evaluate predictors of fusion across the disc space and posterolaterally following transforaminal lumbar interbody fusion (TLIF).

Methods

Patients who underwent 1- or 2-level TLIF for degenerative pathologies were examined for fusion across the disc space, posterolateral fusion, and circumferential radiographic fusion. Multivariable logistic regression was used to identify independent predictors of the primary and secondary outcomes.

Results

278 unique patients (328 unique levels) were included (median age 66.2 yr; 58.3 % female) 25.9 % had complete circumferential fusion, 69.6 % had fusion across the disc space and 71 % had unilateral posterolateral fusion. Fusion across the disc space was less likely with a minimally invasive [versus open] approach (OR 0.39; 95 % CI [0.16, 0.95]; p = 0.04) or bullet [versus banana] cage (OR 0.18; [0.09, 0.38]; p < 0.001). Posterolateral fusion was also less likely with an MIS approach (OR 0.10; [0.03, 0.30]; p < 0.001) or bullet cage (OR 0.14; [0.06, 0.30]; p < 0.001) but was significantly more likely with BMP use (OR 2.97; [1.14, 7.74]; p = 0.026). Circumferential fusion was predicted by BMP use (OR 3.29; [1.48; 7.35]; p = 0.004), use of a bullet cage (OR 0.19; [0.04, 0.87] p = 0.033), and use of a longer interbody device (OR 1.15; [1.01, 1.30]; p = 0.032). Cage material was not predictive in any of the multivariable analyses.

Conclusion

The minority of patients experience circumferential fusion following TLIF. Use of a minimally invasive approach or a bullet-type cage lowers the odds of successful fusion both posterolaterally and across the disc space. BMP increases fusion odds due to improved odds of posterolateral fusion.

目的：评价经椎间孔腰椎椎体间融合术（TLIF）后跨椎间盘间隙和后外侧融合的预测因素。方法：因退行性病变接受1或2节段TLIF的患者检查椎间盘间隙融合、后外侧融合和周向放射融合。采用多变量逻辑回归来确定主要和次要结局的独立预测因子。结果：278例独特的患者（328个独特的水平）被纳入研究（中位年龄66.2 岁；58.3% %女性），25.9 %为全周融合术，69.6 %为跨椎间盘间隙融合术，71 %为单侧后外侧融合术。微创[与开放]入路相比（OR 0.39; 95 % CI [0.16, 0.95]; p = 0.04）或子弹[与香蕉]笼子相比(OR 0.18; [0.09, 0.38]； p 结论：少数患者在TLIF后经历了周向融合。采用微创入路或子弹式椎笼可降低后外侧和整个椎间盘间隙成功融合的几率。由于后外侧融合几率的提高，BMP增加了融合几率。

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引用次数: 0

ABCC2 as a drug target for post-stroke recovery: Evidence from Mendelian randomization and colocalization analyses ABCC2作为脑卒中后恢复的药物靶点：来自孟德尔随机化和共定位分析的证据。

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-11 DOI: 10.1016/j.clineuro.2025.109284

Jiawei Gui , Zhanghua Qi , Keqi Wan , Xiangli Dong , Guohua Yu , Lang Shuai , Jun Wang , Weiming Sun

Background

Ischemic stroke imposes a substantial burden due to long-term neurological disability and high mortality. Despite advancements in acute treatment, therapeutic strategies for post-stroke recovery remain limited.

Methods

We conducted a two-sample Mendelian randomization (MR) using summary statistics of post-stroke functional outcome from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) network and cis-expression quantitative trait loci (cis-eQTLs) of druggable genes from the eQTLGen Consortium. Bayesian colocalization analysis was performed to assess the shared genetic architecture between gene expression and post-stroke functional outcome. Follow-up analyses included phenome-wide association analysis, collider bias evaluation, protein-protein interaction (PPI) network construction, functional enrichment analysis, and drug candidate prediction via Connectivity Map (CMap) analysis.

Results

Two-sample MR identified 15 genes associated with post-stroke functional outcome, of which five were validated in unadjusted models. Summary-data-based MR (SMR) analysis further confirmed three genes, with ABCC2 demonstrating strong colocalization evidence (PPH4 = 0.843) with post-stroke functional outcome. Results of phenome-wide association analysis showed that ABCC2 was associated with direct bilirubin. Functional analyses showed that ABCC2 expression signatures were enriched in coagulation regulation and lipid efflux pathways. CMap analysis predicted candidate drugs that modulate ABCC2-related gene expression signatures.

Conclusions

This study provides genetic evidence supporting ABCC2 as a druggable target for post-stroke recovery. Our findings offer insights into the underlying mechanisms and highlight the potential for drug repurposing, providing a scientific basis for future therapeutic development in ischemic stroke rehabilitation.

背景：缺血性脑卒中由于长期的神经功能障碍和高死亡率，给患者带来了沉重的负担。尽管在急性治疗方面取得了进展，但中风后恢复的治疗策略仍然有限。方法：我们使用来自缺血性卒中功能结局遗传（GISCOME）网络的脑卒中后功能结局和来自eQTLGen联盟的可用药基因的顺式表达数量性状位点（顺式- eqtls）的汇总统计数据进行了两样本孟德尔随机化（MR）。采用贝叶斯共定位分析来评估基因表达与脑卒中后功能预后之间的共享遗传结构。随访分析包括全现象关联分析、对撞机偏倚评估、蛋白蛋白相互作用（PPI）网络构建、功能富集分析和通过连接图（CMap）分析预测候选药物。结果：双样本MR鉴定出15个与卒中后功能结局相关的基因，其中5个在未调整的模型中得到验证。基于汇总数据的MR （SMR）分析进一步证实了三个基因，其中ABCC2表现出强大的共定位证据（PPH4 = 0.843）与卒中后功能结局有关。全表型关联分析结果显示ABCC2与胆红素直接相关。功能分析表明，ABCC2在凝血调节和脂质外排途径中表达特征丰富。CMap分析预测了调节abcc2相关基因表达特征的候选药物。结论：本研究为ABCC2作为脑卒中后恢复的药物靶点提供了遗传学证据。我们的发现提供了对潜在机制的见解，并强调了药物再利用的潜力，为未来缺血性卒中康复治疗的发展提供了科学基础。

{"title":"ABCC2 as a drug target for post-stroke recovery: Evidence from Mendelian randomization and colocalization analyses","authors":"Jiawei Gui , Zhanghua Qi , Keqi Wan , Xiangli Dong , Guohua Yu , Lang Shuai , Jun Wang , Weiming Sun","doi":"10.1016/j.clineuro.2025.109284","DOIUrl":"10.1016/j.clineuro.2025.109284","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke imposes a substantial burden due to long-term neurological disability and high mortality. Despite advancements in acute treatment, therapeutic strategies for post-stroke recovery remain limited.</div></div><div><h3>Methods</h3><div>We conducted a two-sample Mendelian randomization (MR) using summary statistics of post-stroke functional outcome from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) network and cis-expression quantitative trait loci (cis-eQTLs) of druggable genes from the eQTLGen Consortium. Bayesian colocalization analysis was performed to assess the shared genetic architecture between gene expression and post-stroke functional outcome. Follow-up analyses included phenome-wide association analysis, collider bias evaluation, protein-protein interaction (PPI) network construction, functional enrichment analysis, and drug candidate prediction via Connectivity Map (CMap) analysis.</div></div><div><h3>Results</h3><div>Two-sample MR identified 15 genes associated with post-stroke functional outcome, of which five were validated in unadjusted models. Summary-data-based MR (SMR) analysis further confirmed three genes, with ABCC2 demonstrating strong colocalization evidence (PPH4 = 0.843) with post-stroke functional outcome. Results of phenome-wide association analysis showed that ABCC2 was associated with direct bilirubin. Functional analyses showed that ABCC2 expression signatures were enriched in coagulation regulation and lipid efflux pathways. CMap analysis predicted candidate drugs that modulate ABCC2-related gene expression signatures.</div></div><div><h3>Conclusions</h3><div>This study provides genetic evidence supporting ABCC2 as a druggable target for post-stroke recovery. Our findings offer insights into the underlying mechanisms and highlight the potential for drug repurposing, providing a scientific basis for future therapeutic development in ischemic stroke rehabilitation.</div></div>","PeriodicalId":10385,"journal":{"name":"Clinical Neurology and Neurosurgery","volume":"261 ","pages":"Article 109284"},"PeriodicalIF":1.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Re-calculated idiopathic intracranial hypertension prevalence rates with corrected age-filtering techniques 用校正年龄过滤技术重新计算特发性颅内高压患病率。

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-07 DOI: 10.1016/j.clineuro.2025.109283

Guei-Chiuan Chen, Joshua Wang

引用次数: 0

Bone modifying agents and multikinase inhibitors as treatments for chordoma: A TriNetX-based retrospective cohort study 骨修饰剂和多激酶抑制剂治疗脊索瘤：一项基于trinetx的回顾性队列研究

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Clinical Neurology and Neurosurgery

Pub Date : 2025-12-03 DOI: 10.1016/j.clineuro.2025.109282

Kamal Shaik , Spencer Rasmussen , Rudy Rahme , Michael Karsy

Introduction

Chordomas are rare malignant tumors arising from embryonic remnants of the notochord, most commonly affecting the axial skeleton. Although advances have been made in surgical resection and radiation therapy, systemic treatment options remain limited. Bone-modifying agents (BMAs), including zoledronic acid and denosumab, as well as multikinase inhibitors (MKIs) like lenvatinib and cabozantinib, have emerged as potential targeted therapies based on preclinical models. However, comparative real-world data evaluating their outcomes in chordoma patients is lacking.

Methods

A retrospective cohort study was conducted using the TriNetX Research Network. Patients with chordoma (ICD-10-CM C41.0, C41.2, C41.4) were stratified into treatment groups based on receipt of zoledronic acid, denosumab, or multikinase inhibitors (MKIs). Propensity score matching was used to adjust for baseline confounders. Outcomes evaluated at 5 years post-diagnosis included all-cause mortality, pathologic fracture, spinal cord compression, and osteonecrosis. Risk ratios with 95 % confidence intervals were calculated.

Results

Compared to denosumab, zoledronic acid was associated with a higher 5-year mortality risk, but a lower osteonecrosis risk. Comparisons involving MKIs showed no difference in mortality. No pathologic fractures were reported across cohorts. Spinal cord compression was not different among treatments.

Conclusion

This study highlights potential differences in survival and skeletal-related outcomes among chordoma patients treated with BMAs, specifically denosumab and MKIs. These preliminary findings underscore the need for prospective studies to better define optimal systemic therapies for this rare malignancy.

脊索瘤是一种罕见的恶性肿瘤，起源于脊索的胚胎残余，最常影响中轴骨骼。尽管在手术切除和放射治疗方面取得了进展，但全身治疗的选择仍然有限。骨修饰剂（bma），包括唑来膦酸和地诺单抗，以及多激酶抑制剂（MKIs），如lenvatinib和cabozantinib，已经成为基于临床前模型的潜在靶向治疗方法。然而，评估其在脊索瘤患者中的结果的比较真实世界的数据是缺乏的。方法采用TriNetX研究网络进行回顾性队列研究。脊索瘤患者（ICD-10-CM C41.0, C41.2, C41.4）根据接受唑来膦酸，地诺单抗或多激酶抑制剂（MKIs）分为治疗组。倾向评分匹配用于调整基线混杂因素。诊断后5年评估的结果包括全因死亡率、病理性骨折、脊髓压迫和骨坏死。计算了95% %置信区间的风险比。结果与地诺单抗相比，唑来膦酸与更高的5年死亡风险相关，但与更低的骨坏死风险相关。涉及mki的比较显示死亡率没有差异。所有队列均未报告病理性骨折。不同治疗间脊髓压迫无差异。结论：本研究强调了脊索瘤患者接受bma治疗（特别是denosumab和MKIs）在生存和骨骼相关结局方面的潜在差异。这些初步发现强调需要前瞻性研究来更好地确定这种罕见恶性肿瘤的最佳全身治疗方法。

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引用次数: 0