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Insular monoaminergic deficits in prodromal α-synucleinopathies. 前驱α-突触核蛋白病的岛叶单胺能缺陷
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-23 DOI: 10.1002/acn3.52151
Andrea Pilotto, Alice Galli, Cinzia Zatti, Fabio Placidi, Francesca Izzi, Enrico Premi, Silvia P Caminiti, Luca Presotto, Andrea Rizzardi, Marcello Catania, Alessandro Lupini, Leandro Purin, Maria P Pasolini, Nicola B Mercuri, Agostino Chiaravalotti, Mariana Fernandes, Carmen Calvello, Silvia Lucchini, Francesco Bertagna, Barbara Paghera, Daniela Perani, Daniela Berg, Alessandro Padovani, Claudio Liguori

Methods: This study assessed data from two cohorts of patients with alpha-synucleinopathies (University of Brescia and University of Rome Tor-Vergata cohorts). Consecutive participants with video-polysomnography-confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and 123I-FP-CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain 123 I-FP-CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls.

Results: The cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age-matched controls. Individuals with iRBD were categorized as RBD-DAT- (n = 32) and RBD-DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD-DAT- showed an early involvement of the left insula, which increased in RBD-DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18-10.27].

Interpretation: In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non-pharmacological interventions.

研究方法本研究评估了两个α-突触核蛋白病患者队列(布雷西亚大学队列和罗马托尔-韦尔加塔大学队列)的数据。经视频多导睡眠图证实患有 iRBD、帕金森病(PD)、路易体痴呆(DLB)的连续参与者和对照组接受了神经学、临床和 123I-FP-CIT SPECT 成像评估。对患有 iRBD 的患者进行纵向监测,以收集临床表现转化为 PD 或 DLB 的情况。主要结果是与对照组相比,确定反映各临床组单胺能缺陷的全脑123I-FP-CIT SPECT测量指标:组群(n = 184)包括 45 名 iRBD 患者、47 名 PD 患者、42 名 DLB 患者和 50 名年龄匹配的对照组。根据临床实践中使用的黑质评估方法,iRBD 患者被分为 RBD-DAT- 组(32 人)和 RBD-DAT+ 组(13 人)。与对照组相比,RBD-DAT-显示出左侧岛叶的早期受累,而RBD-DAT+则增加了左侧岛叶的受累,帕金森病和路易体痴呆患者也存在这种情况。纵向cox回归分析显示,iRBD和岛叶单胺能缺陷患者的表型转换风险更高[HR = 3.387; CI 95%: 1.18-10.27]:在这项研究中,iRBD的岛叶单胺能结合改变与表型转化为DLB或PD有关。这些发现可能为未来的药物或非药物干预提供了一种有用的分层方法。
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引用次数: 0
Heart meets brain: A 25-year-old with a constellation of neurologic symptoms and heart failure. 心脑交汇:一名患有神经系统症状和心力衰竭的 25 岁患者。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-23 DOI: 10.1002/acn3.52196
Noellie Rivera Torres, Rohini Samudralwar, Joseph Berger
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引用次数: 0
Visual Snow Syndrome is unstable: A longitudinal investigation of VSS symptoms in a Naïve population. 视觉雪综合征不稳定:对未患病人群 VSS 症状的纵向调查。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-23 DOI: 10.1002/acn3.52228
Amy Claire Thompson, Patrick T Goodbourn, Jason D Forte

Objective: This study aimed to investigate the nature of subclinical Visual Snow Syndrome (VSS). We sought to develop a means of recruiting naïve participants with subclinical VSS symptoms to participate in research; and to understand whether subclinical VSS symptoms are stable across time. VSS is a recently characterised neurological condition, whose primary symptom is visual snow (dynamic noise in the visual field). There is evidence that VSS may be common in the general population and that it is unnoticed by many who experience it. To fully characterise VSS, it is important to understand whether (and how) subclinical VSS progresses to a clinical form.

Methods: Here, we present two related studies: Study 1 develops and validates the Melbourne Visual Snow Questionnaire (MVSQ), a tool for screening the general population for VSS symptoms; and Study 2 investigates the stability of subclinical VSS. We developed the MVSQ based on the results of other recent work investigating undiagnosed cases of VSS, and a validated questionnaire designed to identify people with tinnitus for research participation. We then tested the MVSQ in a population with clinical VSS, including assessing face validity (i.e., the extent to which people with clinical VSS believed the questionnaire accurately captured their symptoms). In Study 2, we deployed the MVSQ in a naïve sample of 155 participants, who completed the MVSQ twice, 6 weeks apart.

Results: The results of Study 1 indicated that the MVSQ was a viable method of recruiting people who experience VSS symptoms for research participation. It was deemed to have appropriate face validity and to pose little burden to those who completed it. In Study 2, VSS symptoms changed substantially across a 6-week period. Cohen's weighted kappa for diagnosis was 0.56, 95% CI [0.43, 0.69]. However, the impact of perceptual experiences was low and did not change over time, rank ICC = 0.71, 95% CI [0.59, 0.82].

Interpretation: The MVSQ is appropriate for assessing perceptual experiences in the general population. Determining the exact time scale across which symptoms fluctuate is important for understanding both clinical and subclinical cases of VSS.

研究目的本研究旨在调查亚临床视觉雪症候群(VSS)的性质。我们试图开发一种方法,招募具有亚临床 VSS 症状的天真参与者参与研究;并了解亚临床 VSS 症状在不同时期是否稳定。VSS是一种新近定性的神经系统疾病,其主要症状是视觉雪花(视野中的动态噪音)。有证据表明,VSS 在普通人群中可能很常见,而且许多患者并没有注意到这一症状。为了全面描述 VSS 的特征,了解亚临床 VSS 是否(以及如何)发展为临床形式非常重要:研究 1 开发并验证了墨尔本视觉雪盲问卷(MVSQ),这是一种用于筛查普通人群 VSS 症状的工具;研究 2 调查了亚临床 VSS 的稳定性。我们开发 MVSQ 的依据是近期调查未确诊 VSS 病例的其他工作的结果,以及为确定耳鸣患者是否参与研究而设计的有效问卷。然后,我们在临床 VSS 患者中测试了 MVSQ,包括评估表面效度(即临床 VSS 患者认为问卷准确反映其症状的程度)。在研究 2 中,我们对 155 名新样本参与者进行了 MVSQ 测试,他们两次完成 MVSQ,每次间隔 6 周:研究 1 的结果表明,MVSQ 是招募有 VSS 症状的人参与研究的可行方法。它被认为具有适当的表面效度,对填写者造成的负担很小。在研究 2 中,VSS 症状在 6 周内发生了很大变化。诊断的科恩加权卡帕值为 0.56,95% CI [0.43,0.69]。然而,感知体验的影响较低,且不随时间变化,等级 ICC = 0.71,95% CI [0.59, 0.82]:MVSQ适用于评估普通人群的感性经验。确定症状波动的确切时间范围对于了解 VSS 的临床和亚临床病例非常重要。
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引用次数: 0
Matched oligoclonal bands: Diagnostic utility and clinical characteristics. 匹配的寡克隆带:诊断效用和临床特征。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-22 DOI: 10.1002/acn3.52162
Yoji Hoshina, Justin R Abbatemarco, Stefanie J Rodenbeck, Jason T Poon, Suzanne C Liu, M Mateo Paz Soldan, John E Greenlee, John W Rose, Lisa K Peterson, Lisa Johnson, Alen Delic, Tammy L Smith, Stacey L Clardy

Objective: To describe patient clinical characteristics associated with matched oligoclonal bands (OCB).

Methods: A retrospective review at the University of Utah examined patients with matched OCB from 2015 to 2020. Clinical data, diagnosis, and outcomes were collected. Patients were classified with either multiple sclerosis (MS), other inflammatory neurologic disorder (other-IND), or noninflammatory neurologic disorder (NIND).

Results: Of 539 identified patients, 436 (53.4% female) were matched-only, while 103 (43.7% female) were matched + unique. Patients with matched-only bands were older (57.4 ± 16 vs. 52 ± 14.2, p < 0.001) and more likely to have a history of autoimmune disease (40.1% vs. 28.2%, p = 0.024) and/or cancer (28.7% vs. 16.5%, p = 0.012). Patients with matched + unique bands were more likely to have CSF pleocytosis (52.4% vs. 25.9%, p < 0.001), high IgG index (52.2% vs. 7.6%, p < 0.001), and an abnormal MRI (86.9% vs. 63.1%, p < 0.001). More than two-thirds of matched-only patients had NIND, while 33% and 41.7% of matched + unique patients had MS and other-IND, respectively. Patients exhibiting matched-only bands and a high IgG index demonstrated a significantly higher incidence of other-IND compared to those with matched-only bands and a normal IgG index (55.6% vs. 30.4%, p = 0.013). While Kaplan-Meier survival curves demonstrated higher mortality in the matched-only cohort compared to the matched + unique cohort (p = 0.02), multivariable Cox regression analysis showed this difference was not statistically significant when adjusting for various factors. A history of cancer was the significant predictor of increased mortality risk (Hazard ratio = 3.147, 95% CI [2.196, 4.51]).

Interpretation: Patients with matched only versus matched + unique OCB have distinct clinical profiles.

目的:描述与匹配寡克隆带(OCB)相关的患者临床特征:描述与匹配的寡克隆带(OCB)相关的患者临床特征:犹他大学的一项回顾性研究对2015年至2020年的匹配OCB患者进行了检查。收集了临床数据、诊断和结果。患者被分为多发性硬化症(MS)、其他炎症性神经系统疾病(other-IND)或非炎症性神经系统疾病(NIND):在 539 名已确认的患者中,436 人(53.4% 为女性)为纯匹配患者,103 人(43.7% 为女性)为匹配 + 唯一患者。仅有匹配带的患者年龄较大(57.4 ± 16 vs. 52 ± 14.2,P 解释:仅有匹配带的患者与匹配 + 唯一带的患者相比,年龄更大:仅配型与配型+独特的 OCB 患者具有不同的临床特征。
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引用次数: 0
Dried blood spot improves global access to aquaporin-4-IgG testing for neuromyelitis optica. 干血斑提高了全球神经脊髓炎视网膜病变水肿素-4-IgG 检测的可及性。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-15 DOI: 10.1002/acn3.52178
Nisa Vorasoot, Yahya J Abdulrahman, Farrah Mateen, James P Fryer, Vyanka Redenbaugh, Jessica A Sagen, Abdu K Musubire, Sarah M Jenkins, Amy P Gorsh, John J Chen, Anastasia Zekeridou, Andrew McKeon, Eoin P Flanagan, John R Mills, Sean J Pittock

Objective: This study aimed to evaluate the diagnostic accuracy of dried blood spot (DBS) compared with conventional serum Aquaporin-4-IgG (AQP4-IgG) testing.

Methods: Prospective multicenter diagnostic study was conducted between April 2018 and October 2023 across medical centers in the United States, Uganda, and the Republic of Guinea. Neuromyelitis optica spectrum disorder (NMOSD) patients and controls collected blood on filter paper cards along with concurrent serum samples. These samples underwent analysis using flow cytometric live-cell-based assays (CBA) and enzyme-linked immunosorbent assay (ELISA) to determine AQP4 serostatus. The accuracy of AQP4-IgG detection between DBS and serum (gold standard) was compared.

Results: Among 150 participants (47 cases, 103 controls), there was a strong correlation between DBS and serum samples (Spearman's correlation coefficient of 0.82). The AUC was 0.97 (95% CI: 0.92-0.99). AQP4-IgG detection through DBS showed 87.0% sensitivity (95% CI: 0.74-0.95) and 100% specificity (95% CI: 0.96-1.00) using CBA, and 65.2% sensitivity (95% CI: 0.43-0.84) and 95.2% specificity (95% CI: 0.76-0.99) using ELISA. Serum ELISA demonstrated 69.6% sensitivity (95% CI: 0.47-0.87) and 98.4% specificity (95% CI: 0.91-0.99). The stability of DBS in detecting AQP4-IgG persisted over 24 months for most cases.

Interpretation: The DBS represents a viable alternative for detecting AQP4-IgG in resource-limited settings to diagnose NMOSD, offering high sensitivity and specificity comparable to serum testing. Moreover, DBS has low shipping costs, is easy to administer, and is suitable for point-of-care testing.

目的本研究旨在评估干血斑(DBS)与传统血清Aquaporin-4-IgG(AQP4-IgG)检测相比的诊断准确性:2018年4月至2023年10月期间,在美国、乌干达和几内亚共和国的医疗中心开展了前瞻性多中心诊断研究。神经脊髓炎视网膜频谱障碍(NMOSD)患者和对照组在滤纸卡上采集血液,同时采集血清样本。这些样本通过流式细胞活细胞检测法(CBA)和酶联免疫吸附法(ELISA)进行分析,以确定 AQP4 血清状态。比较了 DBS 和血清(金标准)检测 AQP4-IgG 的准确性:在 150 名参与者(47 名病例,103 名对照组)中,DBS 与血清样本之间存在很强的相关性(斯皮尔曼相关系数为 0.82)。AUC为0.97(95% CI:0.92-0.99)。使用 CBA 通过 DBS 检测 AQP4-IgG 的灵敏度为 87.0%(95% CI:0.74-0.95),特异度为 100%(95% CI:0.96-1.00);使用 ELISA 的灵敏度为 65.2%(95% CI:0.43-0.84),特异度为 95.2%(95% CI:0.76-0.99)。血清 ELISA 的灵敏度为 69.6%(95% CI:0.47-0.87),特异度为 98.4%(95% CI:0.91-0.99)。在大多数病例中,DBS 检测 AQP4-IgG 的稳定性持续了 24 个月:在资源有限的环境中,DBS是检测AQP4-IgG以诊断NMOSD的可行替代方法,其灵敏度和特异性均可媲美血清检测。此外,DBS 的运输成本较低,易于管理,适合进行床旁检测。
{"title":"Dried blood spot improves global access to aquaporin-4-IgG testing for neuromyelitis optica.","authors":"Nisa Vorasoot, Yahya J Abdulrahman, Farrah Mateen, James P Fryer, Vyanka Redenbaugh, Jessica A Sagen, Abdu K Musubire, Sarah M Jenkins, Amy P Gorsh, John J Chen, Anastasia Zekeridou, Andrew McKeon, Eoin P Flanagan, John R Mills, Sean J Pittock","doi":"10.1002/acn3.52178","DOIUrl":"https://doi.org/10.1002/acn3.52178","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate the diagnostic accuracy of dried blood spot (DBS) compared with conventional serum Aquaporin-4-IgG (AQP4-IgG) testing.</p><p><strong>Methods: </strong>Prospective multicenter diagnostic study was conducted between April 2018 and October 2023 across medical centers in the United States, Uganda, and the Republic of Guinea. Neuromyelitis optica spectrum disorder (NMOSD) patients and controls collected blood on filter paper cards along with concurrent serum samples. These samples underwent analysis using flow cytometric live-cell-based assays (CBA) and enzyme-linked immunosorbent assay (ELISA) to determine AQP4 serostatus. The accuracy of AQP4-IgG detection between DBS and serum (gold standard) was compared.</p><p><strong>Results: </strong>Among 150 participants (47 cases, 103 controls), there was a strong correlation between DBS and serum samples (Spearman's correlation coefficient of 0.82). The AUC was 0.97 (95% CI: 0.92-0.99). AQP4-IgG detection through DBS showed 87.0% sensitivity (95% CI: 0.74-0.95) and 100% specificity (95% CI: 0.96-1.00) using CBA, and 65.2% sensitivity (95% CI: 0.43-0.84) and 95.2% specificity (95% CI: 0.76-0.99) using ELISA. Serum ELISA demonstrated 69.6% sensitivity (95% CI: 0.47-0.87) and 98.4% specificity (95% CI: 0.91-0.99). The stability of DBS in detecting AQP4-IgG persisted over 24 months for most cases.</p><p><strong>Interpretation: </strong>The DBS represents a viable alternative for detecting AQP4-IgG in resource-limited settings to diagnose NMOSD, offering high sensitivity and specificity comparable to serum testing. Moreover, DBS has low shipping costs, is easy to administer, and is suitable for point-of-care testing.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Comparison of intraepidermal nerve fiber density and confocal corneal microscopy for neuropathy. 表皮内神经纤维密度与共聚焦角膜显微镜在神经病变方面的比较。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-12 DOI: 10.1002/acn3.52218
Evan L Reynolds, Fallon Koenig, Maya Watanabe, Alyssa Kwiatek, Melissa A Elafros, Amro Stino, Don Henderson, David N Herrmann, Eva L Feldman, Brian C Callaghan

Objective: Compare the diagnostic characteristics of intraepidermal nerve fiber density (IENFD) and confocal corneal microscopy (CCM) for distal symmetric polyneuropathy (DSP) and small fiber neuropathy (SFN).

Methods: Participants with obesity were recruited from bariatric surgery clinics and testing was performed prior to surgery. DSP and SFN were determined using the Toronto consensus definitions of probable neuropathy. IENFD was assessed from 3 mm punch biopsies of the distal leg and proximal thigh. CCM was performed on both eyes with manual and automated counting. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was also completed. Diagnostic capability was determined using areas under the receiver operating characteristics curve (AUC) from logistic regression.

Results: We enrolled 140 participants (mean [standard deviation [SD]] age: 50.3 years [7.1], 77.1% female, BMI: 44.4 kg/m2 [6.7]). In this population, 22.9% had DSP and 14.3% had SFN. Distal leg IENFD had the largest AUC (95% confidence interval) for DSP (0.78, 0.68-0.89) and SFN (0.85, 0.75-0.96). Proximal thigh IENFD (DSP: AUC: 0.59, 0.48-0.69, SFN: AUC: 0.59, 0.46-0.73) and CCM metrics (DSP: AUC range: 0.55-0.60, SFN: AUC range: 0.45-0.62) had poorer diagnostic capability than distal leg IENFD for DSP/SFN (P < 0.05). MNSIq had similar diagnostic capability to distal leg IENFD for both DSP/SFN (DSP: AUC: 0.76, 0.68-0.85, SFN: AUC: 0.81, 0.73-0.88). More participants (52%) preferred skin biopsies to CCM.

Interpretation: Distal leg IENFD was the best quantitative measure of DSP/SFN. CCM had poor diagnostic characteristics and fewer patients preferred this test to IENFD. The MNSIq had similar diagnostic characteristics to distal leg IENFD, indicating its value as a diagnostic tool in the clinical setting.

Clinical trial registration: clinicaltrials.gov: NCT03617185.

目的:比较表皮内神经纤维密度(IENFD)和共聚焦角膜显微镜(CCM)对远端对称性多发性神经病(DSP)和小纤维神经病(SFN)的诊断特征:从减肥手术诊所招募肥胖症患者,在手术前进行测试。DSP和SFN是根据多伦多共识的可能神经病变定义确定的。根据腿远端和大腿近端 3 毫米冲孔活检组织对 IENFD 进行评估。对双眼进行手动和自动计数。还填写了密歇根神经病变筛查工具问卷(MNSIq)。使用逻辑回归的接收者操作特征曲线下面积(AUC)确定诊断能力:我们共招募了 140 名参与者(平均[标准差[SD]]年龄:50.3 岁[7.1],77.1% 为女性,体重指数:44.4 kg/m2 [6.7])。其中 22.9% 患有 DSP,14.3% 患有 SFN。腿远端 IENFD 对 DSP(0.78,0.68-0.89)和 SFN(0.85,0.75-0.96)的 AUC(95% 置信区间)最大。就 DSP/SFN 而言,大腿近端 IENFD(DSP:AUC:0.59,0.48-0.69;SFN:AUC:0.59,0.46-0.73)和 CCM 指标(DSP:AUC 范围:0.55-0.60;SFN:AUC 范围:0.45-0.62)的诊断能力比腿部远端 IENFD 差(P 解释:腿远端 IENFD 是 DSP/SFN 的最佳定量测量指标。CCM 的诊断特性较差,较少患者选择该检测而非 IENFD。MNSIq的诊断特征与腿部远端IENFD相似,表明其在临床环境中作为诊断工具的价值。临床试验注册:clinicaltrials.gov:临床试验注册:clinicaltrials.gov:NCT03617185。
{"title":"Comparison of intraepidermal nerve fiber density and confocal corneal microscopy for neuropathy.","authors":"Evan L Reynolds, Fallon Koenig, Maya Watanabe, Alyssa Kwiatek, Melissa A Elafros, Amro Stino, Don Henderson, David N Herrmann, Eva L Feldman, Brian C Callaghan","doi":"10.1002/acn3.52218","DOIUrl":"https://doi.org/10.1002/acn3.52218","url":null,"abstract":"<p><strong>Objective: </strong>Compare the diagnostic characteristics of intraepidermal nerve fiber density (IENFD) and confocal corneal microscopy (CCM) for distal symmetric polyneuropathy (DSP) and small fiber neuropathy (SFN).</p><p><strong>Methods: </strong>Participants with obesity were recruited from bariatric surgery clinics and testing was performed prior to surgery. DSP and SFN were determined using the Toronto consensus definitions of probable neuropathy. IENFD was assessed from 3 mm punch biopsies of the distal leg and proximal thigh. CCM was performed on both eyes with manual and automated counting. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was also completed. Diagnostic capability was determined using areas under the receiver operating characteristics curve (AUC) from logistic regression.</p><p><strong>Results: </strong>We enrolled 140 participants (mean [standard deviation [SD]] age: 50.3 years [7.1], 77.1% female, BMI: 44.4 kg/m<sup>2</sup> [6.7]). In this population, 22.9% had DSP and 14.3% had SFN. Distal leg IENFD had the largest AUC (95% confidence interval) for DSP (0.78, 0.68-0.89) and SFN (0.85, 0.75-0.96). Proximal thigh IENFD (DSP: AUC: 0.59, 0.48-0.69, SFN: AUC: 0.59, 0.46-0.73) and CCM metrics (DSP: AUC range: 0.55-0.60, SFN: AUC range: 0.45-0.62) had poorer diagnostic capability than distal leg IENFD for DSP/SFN (P < 0.05). MNSIq had similar diagnostic capability to distal leg IENFD for both DSP/SFN (DSP: AUC: 0.76, 0.68-0.85, SFN: AUC: 0.81, 0.73-0.88). More participants (52%) preferred skin biopsies to CCM.</p><p><strong>Interpretation: </strong>Distal leg IENFD was the best quantitative measure of DSP/SFN. CCM had poor diagnostic characteristics and fewer patients preferred this test to IENFD. The MNSIq had similar diagnostic characteristics to distal leg IENFD, indicating its value as a diagnostic tool in the clinical setting.</p><p><strong>Clinical trial registration: </strong>clinicaltrials.gov: NCT03617185.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Prediction of stroke severity: systematic evaluation of lesion representations. 中风严重程度的预测:病变表征的系统评估。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-11 DOI: 10.1002/acn3.52215
Anna K Bonkhoff, Alexander L Cohen, William Drew, Michael A Ferguson, Aaliya Hussain, Christopher Lin, Frederic L W V J Schaper, Anthony Bourached, Anne-Katrin Giese, Lara C Oliveira, Robert W Regenhardt, Markus D Schirmer, Christina Jern, Arne G Lindgren, Jane Maguire, Ona Wu, Sahar Zafar, John Y Rhee, Eyal Y Kimchi, Maurizio Corbetta, Natalia S Rost, Michael D Fox

Objective: To systematically evaluate which lesion-based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets.

Methods: We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N1 = 109, N2 = 638, N3 = 794) to statistically predict acute stroke severity (NIHSS) based on lesion volume, lesion location, and structural and functional disconnection with the lesion location using normative connectomes.

Results: We found that prediction models trained on small single-center datasets could perform well using within-dataset cross-validation, but results did not generalize to independent datasets (median R2 N1 = 0.2%). Performance across independent datasets improved using large single-center training data (R2 N2 = 15.8%) and improved further using multicenter training data (R2 N3 = 24.4%). These results were consistent across lesion attributes and prediction models. Including either structural or functional disconnection in the models outperformed prediction based on volume or location alone (P < 0.001, FDR-corrected).

Interpretation: We conclude that (1) prediction performance in independent datasets of patients with acute stroke cannot be inferred from cross-validated results within a dataset, as performance results obtained via these two methods differed consistently, (2) prediction performance can be improved by training on large and, importantly, multicenter datasets, and (3) structural and functional disconnection allow for improved prediction of acute stroke severity.

目的系统评估哪些基于病灶的成像特征和方法可在独立数据集上对卒中后功能障碍进行最佳统计预测:我们利用来自三个独立数据集的急性卒中患者(N1 = 109、N2 = 638、N3 = 794)的成像和临床数据,根据病变体积、病变位置以及与病变位置的结构和功能断开情况,使用常模连接组对急性卒中严重程度(NIHSS)进行统计预测:我们发现,使用数据集内交叉验证,在小型单中心数据集上训练的预测模型表现良好,但结果不能推广到独立数据集(中位数 R2 N1 = 0.2%)。使用大型单中心训练数据时,独立数据集的性能有所提高(R2 N2 = 15.8%),使用多中心训练数据时性能进一步提高(R2 N3 = 24.4%)。这些结果在不同的病变属性和预测模型中都是一致的。将结构性或功能性断开纳入模型的预测结果优于仅基于体积或位置的预测结果(P 解释:我们的结论是:(1) 急性卒中患者独立数据集的预测性能不能从数据集内的交叉验证结果推断,因为通过这两种方法得到的性能结果始终存在差异;(2) 预测性能可以通过在大型数据集(重要的是,多中心数据集)上进行训练得到改善;(3) 结构性和功能性断开可改善急性卒中严重程度的预测。
{"title":"Prediction of stroke severity: systematic evaluation of lesion representations.","authors":"Anna K Bonkhoff, Alexander L Cohen, William Drew, Michael A Ferguson, Aaliya Hussain, Christopher Lin, Frederic L W V J Schaper, Anthony Bourached, Anne-Katrin Giese, Lara C Oliveira, Robert W Regenhardt, Markus D Schirmer, Christina Jern, Arne G Lindgren, Jane Maguire, Ona Wu, Sahar Zafar, John Y Rhee, Eyal Y Kimchi, Maurizio Corbetta, Natalia S Rost, Michael D Fox","doi":"10.1002/acn3.52215","DOIUrl":"https://doi.org/10.1002/acn3.52215","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate which lesion-based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets.</p><p><strong>Methods: </strong>We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N<sub>1</sub> = 109, N<sub>2</sub> = 638, N<sub>3</sub> = 794) to statistically predict acute stroke severity (NIHSS) based on lesion volume, lesion location, and structural and functional disconnection with the lesion location using normative connectomes.</p><p><strong>Results: </strong>We found that prediction models trained on small single-center datasets could perform well using within-dataset cross-validation, but results did not generalize to independent datasets (median R<sup>2</sup> <sub>N1</sub> = 0.2%). Performance across independent datasets improved using large single-center training data (R<sup>2</sup> <sub>N2</sub> = 15.8%) and improved further using multicenter training data (R<sup>2</sup> <sub>N3</sub> = 24.4%). These results were consistent across lesion attributes and prediction models. Including either structural or functional disconnection in the models outperformed prediction based on volume or location alone (P < 0.001, FDR-corrected).</p><p><strong>Interpretation: </strong>We conclude that (1) prediction performance in independent datasets of patients with acute stroke cannot be inferred from cross-validated results within a dataset, as performance results obtained via these two methods differed consistently, (2) prediction performance can be improved by training on large and, importantly, multicenter datasets, and (3) structural and functional disconnection allow for improved prediction of acute stroke severity.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Gait speed after mild stroke/transient ischemic attack was associated with long-term adverse outcomes: A cohort study. 轻度中风/短暂性脑缺血发作后的步速与长期不良预后有关:一项队列研究。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-11 DOI: 10.1002/acn3.52222
Ning Li, Jia Zhang, Yang Du, Jing Li, Anxin Wang, Xingquan Zhao

Objective: The association between gait speed and adverse outcomes after stroke has not been fully illustrated. This study aimed to explore the association of gait speed on long-term outcomes in minor stroke or transient ischemic attack (TIA).

Methods: We performed a longitudinal study with acute minor stroke or TIA based on a subgroup of the Third China National Stroke Registry data. The gait speed was evaluated using a 10-meter walking test at discharge and 3 months after the stroke onset. The primary outcomes were poor functional outcomes at 1 year, defined by a modified Rankin Score (mRS) of 2-6. Additional outcomes included all-cause death, ambulate dependency (mRS score 4-6), cognitive impairment (Montreal Cognitive Assessment <26), stroke recurrence, and composite vascular events.

Results: The study sample included a total of 1542 stroke patients with a median age of 60 (53-68). At 1-year follow-up, 140 (9.20%) patients experienced poor functional outcomes. Faster gait speed at discharge was associated with lower incidence of poor functional outcome (OR = 0.89; 95% CI, 0.84-0.94), cognitive impairment (OR = 0.93; 95% CI, 0.89-0.96), ischemic stroke recurrence (HR = 0.92; 95% CI, 0.87-0.98), and composite vascular events (HR =0.94; 95% CI, 0.89-0.99) at 1 year. Faster gait speed at 3 months was associated with lower incidence of poor functional outcome (OR = 0.90; 95% CI, 0.85-0.95), ambulate dependency (OR = 0.86; 95% CI, 0.77-0.97), and cognitive impairment (OR = 0.92; 95% CI, 0.88-0.95) at 1 year.

Interpretation: Our findings indicated that slow gait speed after minor stroke or TIA may be an independent predictor for long-term poor outcomes. Gait speed may be considered as a vital sign during follow-up in post-stroke patients.

目的:步态速度与脑卒中后不良预后之间的关系尚未得到充分说明。本研究旨在探讨步速与轻微脑卒中或短暂性脑缺血发作(TIA)长期预后的关系:方法:我们基于第三届中国全国卒中登记数据的一个亚组,对急性轻微卒中或 TIA 患者进行了一项纵向研究。在卒中患者出院时和卒中发生后 3 个月,我们使用 10 米步行测试对其步速进行了评估。主要研究结果为1年后的不良功能预后,即改良Rankin评分(mRS)为2-6分。其他结果包括全因死亡、行动依赖(mRS 评分 4-6 分)、认知障碍(蒙特利尔认知评估结果):研究样本共包括 1542 名中风患者,中位年龄为 60 岁(53-68 岁)。在 1 年的随访中,有 140 名(9.20%)患者出现功能障碍。出院时步速越快,1 年后不良功能预后(OR = 0.89;95% CI,0.84-0.94)、认知障碍(OR = 0.93;95% CI,0.89-0.96)、缺血性卒中复发(HR = 0.92;95% CI,0.87-0.98)和复合血管事件(HR = 0.94;95% CI,0.89-0.99)的发生率越低。3个月时较快的步态速度与1年后较低的不良功能预后(OR = 0.90; 95% CI, 0.85-0.95)、行走依赖(OR = 0.86; 95% CI, 0.77-0.97)和认知障碍(OR = 0.92; 95% CI, 0.88-0.95)发生率相关:我们的研究结果表明,轻微卒中或 TIA 后步速缓慢可能是长期不良预后的独立预测因素。我们的研究结果表明,轻微卒中或 TIA 后步态速度缓慢可能是长期不良预后的独立预测因素,步态速度可被视为卒中后患者随访期间的重要体征。
{"title":"Gait speed after mild stroke/transient ischemic attack was associated with long-term adverse outcomes: A cohort study.","authors":"Ning Li, Jia Zhang, Yang Du, Jing Li, Anxin Wang, Xingquan Zhao","doi":"10.1002/acn3.52222","DOIUrl":"https://doi.org/10.1002/acn3.52222","url":null,"abstract":"<p><strong>Objective: </strong>The association between gait speed and adverse outcomes after stroke has not been fully illustrated. This study aimed to explore the association of gait speed on long-term outcomes in minor stroke or transient ischemic attack (TIA).</p><p><strong>Methods: </strong>We performed a longitudinal study with acute minor stroke or TIA based on a subgroup of the Third China National Stroke Registry data. The gait speed was evaluated using a 10-meter walking test at discharge and 3 months after the stroke onset. The primary outcomes were poor functional outcomes at 1 year, defined by a modified Rankin Score (mRS) of 2-6. Additional outcomes included all-cause death, ambulate dependency (mRS score 4-6), cognitive impairment (Montreal Cognitive Assessment <26), stroke recurrence, and composite vascular events.</p><p><strong>Results: </strong>The study sample included a total of 1542 stroke patients with a median age of 60 (53-68). At 1-year follow-up, 140 (9.20%) patients experienced poor functional outcomes. Faster gait speed at discharge was associated with lower incidence of poor functional outcome (OR = 0.89; 95% CI, 0.84-0.94), cognitive impairment (OR = 0.93; 95% CI, 0.89-0.96), ischemic stroke recurrence (HR = 0.92; 95% CI, 0.87-0.98), and composite vascular events (HR =0.94; 95% CI, 0.89-0.99) at 1 year. Faster gait speed at 3 months was associated with lower incidence of poor functional outcome (OR = 0.90; 95% CI, 0.85-0.95), ambulate dependency (OR = 0.86; 95% CI, 0.77-0.97), and cognitive impairment (OR = 0.92; 95% CI, 0.88-0.95) at 1 year.</p><p><strong>Interpretation: </strong>Our findings indicated that slow gait speed after minor stroke or TIA may be an independent predictor for long-term poor outcomes. Gait speed may be considered as a vital sign during follow-up in post-stroke patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Clinical relevance of paramagnetic rim lesion heterogeneity in multiple sclerosis. 多发性硬化症顺磁边缘病变异质性的临床意义。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-09 DOI: 10.1002/acn3.52220
Anna Stölting, Colin Vanden Bulcke, Serena Borrelli, Céline Bugli, Renaud Du Pasquier, Vincent van Pesch, Pietro Maggi

Objective: Previous studies reveal heterogeneity in terms of paramagnetic rim lesions (PRL) associated tissue damage. We investigated the physiopathology and clinical implications of this heterogeneity.

Methods: In 103 MS patients (72 relapsing and 31 progressive), brain lesions were manually segmented on 3T 3D-FLAIR and rim visibility was assessed with a visual confidence level score (VCLS) on 3D-EPI phase. Using T1 relaxation time maps, lesions were categorized in long-T1 and short-T1. Lesion age was calculated from time of first gadolinium enhancement (N = 84 lesions). Results on clinical scores were validated in an extended cohort of 167 patients using normalized T1w-MPRAGE lesion values.

Results: Rim visibility (VCLS analysis) was associated with increasing lesional T1 (P/PFDR < 0.001). Of 1680 analyzed lesions, 427 were categorized as PRL. Long-T1 PRL were older than short-T1 PRL (average 0.8 vs. 2.0 years, P/PFDR = 0.005/0.008), and featured larger lesional volume (P/PFDR < 0.0001) and multi-shell diffusion-measured axonal damage (P/PFDR < 0.0001). The total volume of long-T1-PRL versus PRL showed 2× predictive power for both higher MS disability (EDSS; P/PFDR = 0.003/0.005 vs. P/PFDR = 0.042/0.057) and severity (MSSS; P/PFDR = 0.0006/0.001 vs. P/PFDR = 0.004/0.007). In random forest, having ≥1 long-T1-PRL versus ≥4 PRL showed 2-4× higher performance to predict a higher EDSS and MSSS. In the validation cohort, long-T1 PRL outperformed (~2×) PRL in predicting both EDSS and MSSS.

Interpretation: PRL show substantial heterogeneity in terms of intralesional tissue damage. More destructive, likely older, long-T1 PRL improve the association with MS clinical scales. This PRL heterogeneity characterization was replicated using standard T1w MRI, highlighting its potential for clinical translation.

目的:以往的研究显示,与顺磁边缘病变(PRL)相关的组织损伤具有异质性。我们研究了这种异质性的生理病理和临床意义:在 103 名多发性硬化症患者(72 名复发患者和 31 名进行性患者)中,通过 3T 3D-FLAIR 对脑部病变进行人工分割,并通过 3D-EPI 相的视觉置信度评分(VCLS)评估边缘可见度。通过 T1 松弛时间图,病变被分为长 T1 和短 T1 两类。病变年龄从首次钆增强的时间开始计算(N = 84 个病变)。使用归一化 T1w-MPRAGE 病灶值对 167 名患者的临床评分结果进行了验证:结果:边缘可见度(VCLS 分析)与病变 T1 增加相关(P/PFDR FDR = 0.005/0.008),病变体积(P/PFDR FDR FDR = 0.003/0.005 vs. P/PFDR = 0.042/0.057)和严重程度(MSSS;P/PFDR = 0.0006/0.001 vs. P/PFDR = 0.004/0.007)较大。在随机森林中,≥1个长T1-PRL与≥4个PRL相比,预测较高的EDSS和MSSS的性能高出2-4倍。在验证队列中,长T1 PRL在预测EDSS和MSSS方面的表现优于PRL(约2倍):PRL在组织内部损伤方面显示出很大的异质性。更具破坏性、可能更老、长T1的PRL提高了与多发性硬化症临床量表的关联性。使用标准 T1w MRI 复制了这种 PRL 异质性特征,突出了其临床应用的潜力。
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引用次数: 0
CHA2DS2-VASc score and prior oral anticoagulant use on endovascular treatment for acute ischemic stroke. 急性缺血性脑卒中血管内治疗的 CHA2DS2-VASc 评分和既往口服抗凝剂使用情况。
IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-09 DOI: 10.1002/acn3.52217
Yukihiro Imaoka, Nice Ren, Soshiro Ogata, Hirotoshi Imamura, Yasuyuki Kaku, Koichi Arimura, Shogo Watanabe, Eri Kiyoshige, Kunihiro Nishimura, Syoji Kobashi, Masafumi Ihara, Kenji Kamiyama, Masafumi Morimoto, Tsuyoshi Ohta, Hidenori Endo, Yuji Matsumaru, Nobuyuki Sakai, Takanari Kitazono, Shigeru Fujimoto, Kuniaki Ogasawara, Koji Iihara

Objective: We evaluated the effect of CHA2DS2-VASc score and prior use of oral anticoagulants (OACs) on endovascular treatment (EVT) in patients with acute ischemic stroke and atrial fibrillation (AF).

Methods: Patients with AF who received EVT in 353 centers in Japan (2018-2020) were included. The outcomes were symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, functional independence, and successful and complete reperfusion. The effects of CHA2DS2-VASc score, its components, and prior use of OACs were assessed via a multiple logistic regression model.

Results: Of the 6984 patients, 780 (11.2%) used warfarin and 1168 (16.7%) used direct oral anticoagulants (DOACs) before EVT. Based on the CHA2DS2-VASc score, 6046 (86.6%) presented a high risk (≥2 for males and ≥3 for females) while 938 (13.4%) had intermediate to low risks. Higher CHA2DS2-VASc scores were associated with increased sICH, in-hospital mortality, and decreased functional independence, regardless of prior OACs. For patients with a high-risk category, prior DOACs increased the odds of successful and complete reperfusion (adjusted odds ratio [95% confidence interval (CI)], 1.27 [1.00-1.61] and 1.30 [1.10-1.53]). For those with integrated intermediate to low risks, neither prior warfarin nor DOAC affected the outcomes. Regardless of total CHA2DS2-VASc scores, patients with congestive heart failure or left ventricular dysfunction, hypertension, age >75 years, or female benefited similarly from prior DOAC use.

Interpretation: Prior DOAC use for patients with high- and selected intermediate-risk CHA2DS2-VASc scores increased prevalence of successful and complete reperfusion. These findings may provide supplemental evidence to introduce preventive DOAC for patients with AF.

目的我们评估了CHA2DS2-VASc评分和既往使用口服抗凝药(OACs)对急性缺血性卒中合并心房颤动(AF)患者血管内治疗(EVT)的影响:纳入在日本 353 个中心接受 EVT 的房颤患者(2018-2020 年)。研究结果为症状性脑出血(sICH)、院内死亡率、功能独立性以及成功和完全再灌注。通过多元逻辑回归模型评估了CHA2DS2-VASc评分、其组成部分和先前使用OACs的影响:在 6984 例患者中,780 例(11.2%)在 EVT 前使用过华法林,1168 例(16.7%)使用过直接口服抗凝药(DOAC)。根据 CHA2DS2-VASc 评分,6046 名患者(86.6%)属于高风险(男性≥2,女性≥3),938 名患者(13.4%)属于中低风险。无论之前是否使用过 OAC,CHA2DS2-VASc 评分越高,sICH、院内死亡率和功能独立性越差。对于高风险患者,既往使用过 DOACs 会增加成功和完全再灌注的几率(调整后的几率比 [95% 置信区间 (CI)],1.27 [1.00-1.61] 和 1.30 [1.10-1.53])。对于中低综合风险的患者,既往服用过华法林也服用过 DOAC 都不会影响结果。无论CHA2DS2-VASc总评分如何,充血性心力衰竭或左心室功能障碍、高血压、年龄大于75岁或女性患者均可从既往使用DOAC中获益:高危和部分中危CHA2DS2-VASc评分患者事先使用DOAC可增加成功和完全再灌注的发生率。这些发现为房颤患者引入预防性 DOAC 提供了补充证据。
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引用次数: 0
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Annals of Clinical and Translational Neurology
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