Richard Bedlack MD, PhD, Xiaoyan Li MD, PhD, Baggio Angelo Evangelista PhD, Maria E. Panzetta PhD, Justin Kwan MD, Lauren M. Gittings PhD, Rita Sattler PhD
There are no dramatically effective pharmacological treatments for most patients with amyotrophic lateral sclerosis, a complex disease with multiple underlying mechanisms, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, microbiome alteration, and antiretroviral activity. We sifted through 15 years of reviews by a group called ALSUntangled to identify 8 alternative and off-label treatments that target ≥1 of these mechanisms, and have ≥1 human trial suggesting meaningful benefits. Given the overlapping pathological mechanisms of the highlighted products, we suggest that combinations of these treatments targeting diverse mechanisms might be worthwhile for future amyotrophic lateral sclerosis therapy development. ANN NEUROL 2025;97:15–27
{"title":"The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis","authors":"Richard Bedlack MD, PhD, Xiaoyan Li MD, PhD, Baggio Angelo Evangelista PhD, Maria E. Panzetta PhD, Justin Kwan MD, Lauren M. Gittings PhD, Rita Sattler PhD","doi":"10.1002/ana.27126","DOIUrl":"10.1002/ana.27126","url":null,"abstract":"<p>There are no dramatically effective pharmacological treatments for most patients with amyotrophic lateral sclerosis, a complex disease with multiple underlying mechanisms, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, microbiome alteration, and antiretroviral activity. We sifted through 15 years of reviews by a group called ALSUntangled to identify 8 alternative and off-label treatments that target ≥1 of these mechanisms, and have ≥1 human trial suggesting meaningful benefits. Given the overlapping pathological mechanisms of the highlighted products, we suggest that combinations of these treatments targeting diverse mechanisms might be worthwhile for future amyotrophic lateral sclerosis therapy development. ANN NEUROL 2025;97:15–27</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"15-27"},"PeriodicalIF":8.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581143","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}
Cyprien A. Rivier MD, MSc, Daniela Renedo MD, Sandro Marini MD, Jessica R. Magid-Bernstein MD, PhD, Adam de Havenon MD, MS, Jonathan Rosand MD, MSc, Daniel F. Hanley MD, Wendy C. Ziai MD, MPH, Stephan A. Mayer MD, Daniel Woo MD, Lauren H. Sansing MD, MS, Kevin N. Sheth MD, Christopher D. Anderson MD, MMSc, Guido J. Falcone MD, ScD, MPH
Objective
The limited existing evidence on sex differences in the clinical characteristics of patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) comes from small, single-center studies. Here, we performed an individual patient data meta-analysis of 3 randomized clinical trials and 1 multi-ethnic observational study of ICH to investigate the impact of sex on ICH severity and outcome.
Methods
Inclusion criteria in our study were a neuroimaging-confirmed ICH. We evaluated whether sex was associated with ICH severity (hematoma volume and expansion) and poor functional outcomes (modified Rankin Scale >3) 3 or 6 months after the ICH.
Results
A total of 4,812 ICH patients were evaluated (mean age 62, 40% female). Males with ICH were younger, more likely to be smokers and have diabetes, and less likely to be on anticoagulants (all p < 0.05). In multivariable analyses, male sex was associated with non-lobar location (odds ratio [OR]: 1.63; 95% confidence interval [CI]: [1.39–1.92]; p < 0.001), larger hemorrhages (beta: 0.16 [0.08–0.23]; p < 0.001) and a higher risk of hematoma expansion (OR: 1.43 [1.20–1.71]; p < 0.001). Despite the larger hemorrhage volume and higher risk of expansion, male sex was associated with a 24% lower risk of poor outcomes (OR: 0.76 [0.64–0.90]; p = 0.002).
Interpretation
Compared to females, males with ICH have larger bleeds and higher risk of hematoma expansion. Despite the larger bleeds and higher risk of hematoma expansion, males with ICH have lower risk of poor outcomes. Our results suggest that the biology and clinical trajectory are different in females and males with ICH, supporting sex-specific research in this condition. ANN NEUROL 2025;97:232–241
目的：关于自发性非外伤性脑内出血（ICH）患者临床特征的性别差异，现有的有限证据均来自小型单中心研究。在此，我们对 3 项随机临床试验和 1 项多种族 ICH 观察性研究的单个患者数据进行了荟萃分析，以研究性别对 ICH 严重程度和预后的影响：我们研究的纳入标准是神经影像学确诊的 ICH。我们评估了性别是否与 ICH 严重程度（血肿体积和扩大）和 ICH 3 个月或 6 个月后的不良功能预后（修正的 Rankin 量表>3）相关：共评估了 4812 名 ICH 患者（平均年龄 62 岁，女性占 40%）。男性 ICH 患者更年轻，更有可能是吸烟者和糖尿病患者，服用抗凝药物的可能性较低（均为 p）：与女性相比，男性 ICH 患者的出血量更大，血肿扩大的风险更高。尽管男性 ICH 患者出血量较大，血肿扩大的风险较高，但其不良预后的风险较低。我们的研究结果表明，女性和男性 ICH 患者的生物学特性和临床轨迹是不同的，这支持了针对这种疾病的性别特异性研究。ann neurol 2024.
{"title":"Sex Modifies the Severity and Outcome of Spontaneous Intracerebral Hemorrhage","authors":"Cyprien A. Rivier MD, MSc, Daniela Renedo MD, Sandro Marini MD, Jessica R. Magid-Bernstein MD, PhD, Adam de Havenon MD, MS, Jonathan Rosand MD, MSc, Daniel F. Hanley MD, Wendy C. Ziai MD, MPH, Stephan A. Mayer MD, Daniel Woo MD, Lauren H. Sansing MD, MS, Kevin N. Sheth MD, Christopher D. Anderson MD, MMSc, Guido J. Falcone MD, ScD, MPH","doi":"10.1002/ana.27123","DOIUrl":"10.1002/ana.27123","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The limited existing evidence on sex differences in the clinical characteristics of patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) comes from small, single-center studies. Here, we performed an individual patient data meta-analysis of 3 randomized clinical trials and 1 multi-ethnic observational study of ICH to investigate the impact of sex on ICH severity and outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Inclusion criteria in our study were a neuroimaging-confirmed ICH. We evaluated whether sex was associated with ICH severity (hematoma volume and expansion) and poor functional outcomes (modified Rankin Scale >3) 3 or 6 months after the ICH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 4,812 ICH patients were evaluated (mean age 62, 40% female). Males with ICH were younger, more likely to be smokers and have diabetes, and less likely to be on anticoagulants (all <i>p</i> < 0.05). In multivariable analyses, male sex was associated with non-lobar location (odds ratio [OR]: 1.63; 95% confidence interval [CI]: [1.39–1.92]; <i>p</i> < 0.001), larger hemorrhages (beta: 0.16 [0.08–0.23]; <i>p</i> < 0.001) and a higher risk of hematoma expansion (OR: 1.43 [1.20–1.71]; <i>p</i> < 0.001). Despite the larger hemorrhage volume and higher risk of expansion, male sex was associated with a 24% lower risk of poor outcomes (OR: 0.76 [0.64–0.90]; <i>p</i> = 0.002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Compared to females, males with ICH have larger bleeds and higher risk of hematoma expansion. Despite the larger bleeds and higher risk of hematoma expansion, males with ICH have lower risk of poor outcomes. Our results suggest that the biology and clinical trajectory are different in females and males with ICH, supporting sex-specific research in this condition. ANN NEUROL 2025;97:232–241</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"232-241"},"PeriodicalIF":8.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Carotid Stent Fracture","authors":"Ioana Maria Ion MD, Dimitri Renard MD","doi":"10.1002/ana.27127","DOIUrl":"10.1002/ana.27127","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"207-208"},"PeriodicalIF":8.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kevin van Veenhuijzen MD, Harold H.G. Tan MD, Abram D. Nitert MD, Michael A. van Es MD, PhD, Jan H. Veldink MD, PhD, Leonard H. van den Berg MD, PhD, Henk-Jan Westeneng MD, PhD
Objective
We prospectively studied asymptomatic C9orf72 mutation carriers, identifying those developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).
Methods
We enrolled 56 asymptomatic family members (AFM) with a C9orf72 mutation (AFM C9+), 132 non-carriers (AFM C9−), and 359 population-based controls. Using 3 T magnetic resonance imaging, we measured cortical thickness, gyrification, and subcortical volumes longitudinally. Linear mixed-effects models on non-converting AFM C9+ scans (n = 107) created a reference for these measurements, establishing individual atrophy patterns. Atrophy patterns from presymptomatic phenoconverters (n = 10 scans) served as a template for group comparisons and similarity assessments. Similarity with phenoconverters was quantified using Dice similarity coefficient (DSC) for cortical and Kullback–Leibler similarity (KLS) for subcortical measures. Using longitudinal similarity assessments, we predicted when participants would reach the average similarity level of phenoconverters at their first post-onset scan.
Results
Five AFM C9+ converted to ALS or ALS-FTD. Up to 6 years before symptoms, these phenoconverters exhibited significant atrophy in frontal, temporal, parietal, and cingulate cortex, along with smaller thalamus, hippocampus, and amygdala compared to other AFM C9+. Some non-converted AFM C9+ had high DSC and KLS, approaching values of phenoconverters, whereas others, along with AFM C9− and controls, had lower values. At age 80, we predicted 27.9% (95% confidence interval, 13.2–40.1%) of AFM C9+ and no AFM C9− would reach the same DSC as phenoconverters.
Interpretation
Distinctive atrophy patterns are visible years before symptom onset on presymptomatic scans of phenoconverters. Combining baseline and follow-up similarity measures may serve as a promising imaging biomarker for identifying those at risk of ALS or ALS-FTD. ANN NEUROL 2025;97:281–295
{"title":"Longitudinal Magnetic Resonance Imaging in Asymptomatic C9orf72 Mutation Carriers Distinguishes Phenoconverters to Amyotrophic Lateral Sclerosis or Amyotrophic Lateral Sclerosis With Frontotemporal Dementia","authors":"Kevin van Veenhuijzen MD, Harold H.G. Tan MD, Abram D. Nitert MD, Michael A. van Es MD, PhD, Jan H. Veldink MD, PhD, Leonard H. van den Berg MD, PhD, Henk-Jan Westeneng MD, PhD","doi":"10.1002/ana.27116","DOIUrl":"10.1002/ana.27116","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We prospectively studied asymptomatic <i>C9orf72</i> mutation carriers, identifying those developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 56 asymptomatic family members (AFM) with a <i>C9orf72</i> mutation (AFM C9+), 132 non-carriers (AFM C9−), and 359 population-based controls. Using 3 T magnetic resonance imaging, we measured cortical thickness, gyrification, and subcortical volumes longitudinally. Linear mixed-effects models on non-converting AFM C9+ scans (n = 107) created a reference for these measurements, establishing individual atrophy patterns. Atrophy patterns from presymptomatic phenoconverters (n = 10 scans) served as a template for group comparisons and similarity assessments. Similarity with phenoconverters was quantified using Dice similarity coefficient (DSC) for cortical and Kullback–Leibler similarity (KLS) for subcortical measures. Using longitudinal similarity assessments, we predicted when participants would reach the average similarity level of phenoconverters at their first post-onset scan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five AFM C9+ converted to ALS or ALS-FTD. Up to 6 years before symptoms, these phenoconverters exhibited significant atrophy in frontal, temporal, parietal, and cingulate cortex, along with smaller thalamus, hippocampus, and amygdala compared to other AFM C9+. Some non-converted AFM C9+ had high DSC and KLS, approaching values of phenoconverters, whereas others, along with AFM C9− and controls, had lower values. At age 80, we predicted 27.9% (95% confidence interval, 13.2–40.1%) of AFM C9+ and no AFM C9− would reach the same DSC as phenoconverters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Distinctive atrophy patterns are visible years before symptom onset on presymptomatic scans of phenoconverters. Combining baseline and follow-up similarity measures may serve as a promising imaging biomarker for identifying those at risk of ALS or ALS-FTD. ANN NEUROL 2025;97:281–295</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"281-295"},"PeriodicalIF":8.1,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563593","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}
Lan Gao PhD, Leonid Churilov PhD, Hannah Johns PhD, Deep Pujara MBBS, Ameer E. Hassan DO, Michael Abraham MD, Santiago Ortega-Gutierrez MD, Muhammad Shazam Hussain MD, Michael Chen MD, Spiros Blackburn MD, Clark W. Sitton MD, Florentina M. E. Pinckaers MD, Wim H. van Zwam MD, Georgios Tsivgoulis MD, Michael D. Hill MD, James C. Grotta MD, Scott Kasner MD, Marc Ribo MD, Bruce C Campbell PhD, Amrou Sarraj MD, For SELECT2 investigators
Objectives
Whereas highly cost-effective and cost-saving for patients with small infarcts, whether endovascular thrombectomy (EVT) remains cost-effective in patients with extensive ischemic injury is uncertain.
Methods
We conducted a model-based cost-effectiveness analysis from the United States, Australian, and Spanish societal perspectives, using a 7-state Markov model, with each state defined by the modified Rankin Scale (mRS) score. Initial probabilities at 3 months were derived from the SELECT2 trial. All other model inputs, including transition probabilities, health care and non-health care costs, and utility weights, were sourced from published literature and government websites. Our analysis included extensive sensitivity and subgroup analyses.
Results
EVT in patients with large ischemic stroke improved health outcomes and was associated with lower costs from a societal viewpoint. EVT was cost-effective with a mean between-group difference of 1.24 quality-adjusted life years (QALYs), and a cost-saving of $23,409 in the United States, $10,691 in Australia, and $30,036 in Spain, in addition to uncosted benefits in productivity for patients and carers. Subgroup analyses were directionally consistent with the overall population, notably with preserved cost-effectiveness in older patients (≥ 70 years) and those with more severe strokes (National Institutes of Health Stroke Scale [NIHSS] ≥ 20). Sensitivity analyses were largely consistent with the base-case results.
Interpretation
EVT demonstrated cost-effectiveness in patients with large core across different settings in the United States, Australia, and Spain, including older patients and those with more severe strokes. These results further support adaptation of systems of care to accommodate the expansion of thrombectomy eligibility to patients with large cores and maximize EVT benefits. ANN NEUROL 2025;97:222–231
{"title":"Cost-Effectiveness of Endovascular Thrombectomy in Patients with Large Ischemic Stroke","authors":"Lan Gao PhD, Leonid Churilov PhD, Hannah Johns PhD, Deep Pujara MBBS, Ameer E. Hassan DO, Michael Abraham MD, Santiago Ortega-Gutierrez MD, Muhammad Shazam Hussain MD, Michael Chen MD, Spiros Blackburn MD, Clark W. Sitton MD, Florentina M. E. Pinckaers MD, Wim H. van Zwam MD, Georgios Tsivgoulis MD, Michael D. Hill MD, James C. Grotta MD, Scott Kasner MD, Marc Ribo MD, Bruce C Campbell PhD, Amrou Sarraj MD, For SELECT2 investigators","doi":"10.1002/ana.27119","DOIUrl":"10.1002/ana.27119","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Whereas highly cost-effective and cost-saving for patients with small infarcts, whether endovascular thrombectomy (EVT) remains cost-effective in patients with extensive ischemic injury is uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a model-based cost-effectiveness analysis from the United States, Australian, and Spanish societal perspectives, using a 7-state Markov model, with each state defined by the modified Rankin Scale (mRS) score. Initial probabilities at 3 months were derived from the SELECT2 trial. All other model inputs, including transition probabilities, health care and non-health care costs, and utility weights, were sourced from published literature and government websites. Our analysis included extensive sensitivity and subgroup analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>EVT in patients with large ischemic stroke improved health outcomes and was associated with lower costs from a societal viewpoint. EVT was cost-effective with a mean between-group difference of 1.24 quality-adjusted life years (QALYs), and a cost-saving of $23,409 in the United States, $10,691 in Australia, and $30,036 in Spain, in addition to uncosted benefits in productivity for patients and carers. Subgroup analyses were directionally consistent with the overall population, notably with preserved cost-effectiveness in older patients (≥ 70 years) and those with more severe strokes (National Institutes of Health Stroke Scale [NIHSS] ≥ 20). Sensitivity analyses were largely consistent with the base-case results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>EVT demonstrated cost-effectiveness in patients with large core across different settings in the United States, Australia, and Spain, including older patients and those with more severe strokes. These results further support adaptation of systems of care to accommodate the expansion of thrombectomy eligibility to patients with large cores and maximize EVT benefits. ANN NEUROL 2025;97:222–231</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"222-231"},"PeriodicalIF":8.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmed Alkhiri MBBS, Aser F. Alamri MBBS, Ahmed A. Almaghrabi MBBS, Fahad Alturki MBBS, Basil A. Alghamdi MBBS, Abdullah Alharbi MBBS, Hassan K. Salamatullah MBBS, Mohamed Alzawahmah MD, Faisal Al-Otaibi MD, Abdulrahman Y. Alturki MBBS, Dar Dowlatshahi MD, PhD, Andrew M. Demchuk MD, Wendy C. Ziai MD, Christopher P. Kellner MD, Adel Alhazzani MD, Fahad S. Al-Ajlan MD
Objectives
Spontaneous intracerebral hemorrhage (ICH) poses high mortality and morbidity rates with limited evidence-based therapeutic approaches. We aimed to evaluate the current evidence for the role of minimally invasive surgery (MIS) in the management of ICH.
Methods
This systematic review and meta-analysis followed recommended guidelines and protocols. Medline, Embase, Scopus, and the Cochrane Library were searched from inception up to April 12, 2024. The inclusion was restricted to randomized clinical trials (RCTs) of high quality, ensuring they were not deemed to have a high risk of bias in any of the Cochrane risk of bias tool (RoB2) domains. Primary outcomes were good functional outcome (modified Rankin scale, 0–3) and mortality beyond 90 days. Secondary outcomes were early mortality within 30 days and rebleeding rates. We pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using random-effects models.
Results
Fourteen high-quality RCTs were included. There were 3,027 patients with ICH (1,475 randomized to MIS, and 1,452 randomized to medical management or craniotomy). Of included patients, 1,899 (62.7%) were males. MIS resulted in higher odds of achieving long-term good functional outcome (OR, 1.51 [95% CI, 1.25–1.82]), lower odds of long-term mortality (OR, 0.72 [95% CI, 0.57–0.90]) and lower odds of early mortality (OR, 0.73 [95% CI, 0.56–0.95]). Rebleeding rates were similar (OR, 1.10 [95% CI, 0.55–2.19]). The treatment effect of MIS was consistent across multiple sensitivity and subgroup analyses, including individuals with deep ICH.
Interpretation
This meta-analysis provides high-quality clinical trial evidence supporting the use of MIS as a primary treatment strategy in the management of ICH. ANN NEUROL 2025;97:185–194
目的：自发性脑内出血（ICH）的死亡率和发病率都很高，而循证治疗方法却很有限。我们旨在评估微创手术（MIS）在治疗 ICH 中的作用的现有证据：本系统综述和荟萃分析遵循推荐的指南和协议。对 Medline、Embase、Scopus 和 Cochrane 图书馆进行了检索，检索时间从开始到 2024 年 4 月 12 日。纳入的研究仅限于高质量的随机临床试验（RCT），确保这些试验在Cochrane偏倚风险工具（RoB2）的任何一个领域中都不存在高偏倚风险。主要结果是良好的功能预后（改良Rankin量表，0-3）和90天后的死亡率。次要结果是 30 天内的早期死亡率和再出血率。我们使用随机效应模型汇总了几率比（OR）及相应的 95% 置信区间（CI）：结果：共纳入了 14 项高质量的 RCT。共有 3,027 名 ICH 患者（1,475 名随机接受 MIS 治疗，1,452 名随机接受药物治疗或开颅手术治疗）。在纳入的患者中，1,899 名（62.7%）为男性。MIS术后获得长期良好功能预后的几率更高（OR，1.51 [95% CI，1.25-1.82]），长期死亡率较低（OR，0.72 [95% CI，0.57-0.90]），早期死亡率较低（OR，0.73 [95% CI，0.56-0.95]）。再出血率相似（OR，1.10 [95% CI，0.55-2.19]）。在多项敏感性分析和亚组分析中，MIS的治疗效果是一致的，包括深部ICH患者：这项荟萃分析提供了高质量的临床试验证据，支持将 MIS 作为治疗 ICH 的主要治疗策略。ann neurol 2024.
{"title":"Minimally Invasive Surgery for Spontaneous Intracerebral Hemorrhage: Meta-Analysis of High-Quality Randomized Clinical Trials","authors":"Ahmed Alkhiri MBBS, Aser F. Alamri MBBS, Ahmed A. Almaghrabi MBBS, Fahad Alturki MBBS, Basil A. Alghamdi MBBS, Abdullah Alharbi MBBS, Hassan K. Salamatullah MBBS, Mohamed Alzawahmah MD, Faisal Al-Otaibi MD, Abdulrahman Y. Alturki MBBS, Dar Dowlatshahi MD, PhD, Andrew M. Demchuk MD, Wendy C. Ziai MD, Christopher P. Kellner MD, Adel Alhazzani MD, Fahad S. Al-Ajlan MD","doi":"10.1002/ana.27107","DOIUrl":"10.1002/ana.27107","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Spontaneous intracerebral hemorrhage (ICH) poses high mortality and morbidity rates with limited evidence-based therapeutic approaches. We aimed to evaluate the current evidence for the role of minimally invasive surgery (MIS) in the management of ICH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This systematic review and meta-analysis followed recommended guidelines and protocols. Medline, Embase, Scopus, and the Cochrane Library were searched from inception up to April 12, 2024. The inclusion was restricted to randomized clinical trials (RCTs) of high quality, ensuring they were not deemed to have a high risk of bias in any of the Cochrane risk of bias tool (RoB2) domains. Primary outcomes were good functional outcome (modified Rankin scale, 0–3) and mortality beyond 90 days. Secondary outcomes were early mortality within 30 days and rebleeding rates. We pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using random-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fourteen high-quality RCTs were included. There were 3,027 patients with ICH (1,475 randomized to MIS, and 1,452 randomized to medical management or craniotomy). Of included patients, 1,899 (62.7%) were males. MIS resulted in higher odds of achieving long-term good functional outcome (OR, 1.51 [95% CI, 1.25–1.82]), lower odds of long-term mortality (OR, 0.72 [95% CI, 0.57–0.90]) and lower odds of early mortality (OR, 0.73 [95% CI, 0.56–0.95]). Rebleeding rates were similar (OR, 1.10 [95% CI, 0.55–2.19]). The treatment effect of MIS was consistent across multiple sensitivity and subgroup analyses, including individuals with deep ICH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This meta-analysis provides high-quality clinical trial evidence supporting the use of MIS as a primary treatment strategy in the management of ICH. ANN NEUROL 2025;97:185–194</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"185-194"},"PeriodicalIF":8.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saoussen Cherif PhD, Nicolas Tempier, Mathieu Yeche, Gizem Temiz PhD, Julia Perrière, Marco Romanato PhD, Déborah Ziri PhD, Sara Fernandez-Vidal PhD, Elodie Hainque MD, PhD, David Maltête MD, PhD, Stéphane Derrey MD, PhD, Eric Bardinet PhD, Brian Lau PhD, Carine Karachi MD, PhD, Marie-Laure Welter MD, PhD
Objective
To investigate the effects of directional subthalamic deep brain stimulation (STN-dDBS) on gait and balance disorders, including freezing of gait (FOG), in patients with advanced Parkinson's disease (PD).
Methods
We included 10 participants who underwent STN-DBS and presented severe preoperative FOG, in a randomized, double-blind, crossover study. We used segmented DBS electrodes to investigate whether directing the predicted volume of tissue activated (VTA) to overlap the central STN preferentially improved gait and balance disorders compared to directional DBS applied in the more posterior STN (sensorimotor). We also assessed non-directional (ring-mode) STN-DBS. Our primary outcome was gait and balance control measured using instrumented gait recordings. Each patient had a pre-operative structural and diffusion-weighted imaging to model individual VTAs and to examine cortico-subthalamic connectivity. We used linear mixed-effects models to contrast the effects of central STN-dDBS, posterior STN-dDBS, and ring-mode STN-DBS.
Results
Central STN-dDBS produced significantly better improvement in gait and balance control compared to posterior STN-dDBS (p = 0.027), with fewer FOG episodes (p < 0.001). Conversely, ring-mode STN-DBS resulted in worsened postural control compared to central STN-dDBS (p = 0.009). The cortico-subthalamic connectivity with the STN VTAs involved mostly primary sensorimotor, premotor, and medial frontal cortices, with a higher overall cortico-STN connectivity with ring-mode STN-DBS.
Interpretation
Central STN-dDBS represents the best option to improve gait and balance disorders in PD patients, including FOG. Our findings raise the possibility of reprogramming STN-DBS toward the central area in selected patients with disabling FOG and/or postural instability after surgery. ANN NEUROL 2025;97:149–162
{"title":"Directional Subthalamic Deep Brain Stimulation Better Improves Gait and Balance Disorders in Parkinson's Disease Patients: A Randomized Controlled Study","authors":"Saoussen Cherif PhD, Nicolas Tempier, Mathieu Yeche, Gizem Temiz PhD, Julia Perrière, Marco Romanato PhD, Déborah Ziri PhD, Sara Fernandez-Vidal PhD, Elodie Hainque MD, PhD, David Maltête MD, PhD, Stéphane Derrey MD, PhD, Eric Bardinet PhD, Brian Lau PhD, Carine Karachi MD, PhD, Marie-Laure Welter MD, PhD","doi":"10.1002/ana.27099","DOIUrl":"10.1002/ana.27099","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the effects of directional subthalamic deep brain stimulation (STN-dDBS) on gait and balance disorders, including freezing of gait (FOG), in patients with advanced Parkinson's disease (PD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 10 participants who underwent STN-DBS and presented severe preoperative FOG, in a randomized, double-blind, crossover study. We used segmented DBS electrodes to investigate whether directing the predicted volume of tissue activated (VTA) to overlap the central STN preferentially improved gait and balance disorders compared to directional DBS applied in the more posterior STN (sensorimotor). We also assessed non-directional (ring-mode) STN-DBS. Our primary outcome was gait and balance control measured using instrumented gait recordings. Each patient had a pre-operative structural and diffusion-weighted imaging to model individual VTAs and to examine cortico-subthalamic connectivity. We used linear mixed-effects models to contrast the effects of central STN-dDBS, posterior STN-dDBS, and ring-mode STN-DBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Central STN-dDBS produced significantly better improvement in gait and balance control compared to posterior STN-dDBS (<i>p</i> = 0.027), with fewer FOG episodes (<i>p</i> < 0.001). Conversely, ring-mode STN-DBS resulted in worsened postural control compared to central STN-dDBS (<i>p</i> = 0.009). The cortico-subthalamic connectivity with the STN VTAs involved mostly primary sensorimotor, premotor, and medial frontal cortices, with a higher overall cortico-STN connectivity with ring-mode STN-DBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Central STN-dDBS represents the best option to improve gait and balance disorders in PD patients, including FOG. Our findings raise the possibility of reprogramming STN-DBS toward the central area in selected patients with disabling FOG and/or postural instability after surgery. ANN NEUROL 2025;97:149–162</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"149-162"},"PeriodicalIF":8.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542309","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}
The effects of seizure control on outcomes in persons with dementia (PWD) remain unclear. Our study aimed to investigate the impact of seizure control on mortality, function, cognition, and mood among PWD.
Methods
This longitudinal, multicenter study is based on 39 Alzheimer's disease centers (ADCs) in the United States from September 2005 to December 2021. PWD were grouped by seizure status into recurrent (seizures in the past year), remote (prior seizures but none in the past year), and no seizures (controls). The primary outcome was all-cause mortality among seizure groups. We used Weibull survival analysis to assess the mortality risks by seizure status after adjusting for age, sex, education, race, ethnicity, hypertension, diabetes, hyperlipidemia, degree of cognitive impairment, dominant Alzheimer's disease (AD) mutation, brain trauma, stroke, Parkinson's disease, alcohol abuse, and depression. Cognition (Clinical Dementia Rating), function (physical dependence and nursing home residence), day-to-day activities (Functional Assessment Scores), and mood (Geriatric Depression Scale) were compared among seizure groups after adjusting for dementia duration and age.
Results
Among 26,501 participants, 374 (1.4%) had recurrent seizures and 510 (1.9%) had remote seizures. In multivariable survival analysis, recurrent seizures were associated with a higher mortality risk than remote and no seizures (adjusted hazard ratio [aHR], 95% confidence interval [95% CI]; recurrent aHR = 1.79, 95% CI = 1.51 to 2.12; remote aHR = 1.17, 95% CI = 0.98 to 1.38). Median time-to-death for recurrent, remote, and no seizures was 2.4, 4.0, and 4.7 years, respectively. People with recurrent seizures had worse cognition, day-to-day function, and physical dependence than those with remote seizures and controls.
Interpretation
PWD with poorly controlled recurrent seizures have worse mortality, functional, and cognitive outcomes than PWD with remote and no seizures. These findings underscore the need for timely identification and management of ongoing seizures in PWD. ANN NEUROL 2025;97:358–368
{"title":"Association of Seizure Control with Mortality, Cognition, and Function in People With Dementia","authors":"Ifrah Zawar MD, MS-CR, Mark Quigg MD, MSc, Soutik Ghosal PhD, Vineet Punia MD, MSc, Yamile Calle-Lopez MD, Carol Manning PhD, Jaideep Kapur MD, PhD","doi":"10.1002/ana.27125","DOIUrl":"10.1002/ana.27125","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The effects of seizure control on outcomes in persons with dementia (PWD) remain unclear. Our study aimed to investigate the impact of seizure control on mortality, function, cognition, and mood among PWD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This longitudinal, multicenter study is based on 39 Alzheimer's disease centers (ADCs) in the United States from September 2005 to December 2021. PWD were grouped by seizure status into recurrent (seizures in the past year), remote (prior seizures but none in the past year), and no seizures (controls). The primary outcome was all-cause mortality among seizure groups. We used Weibull survival analysis to assess the mortality risks by seizure status after adjusting for age, sex, education, race, ethnicity, hypertension, diabetes, hyperlipidemia, degree of cognitive impairment, dominant Alzheimer's disease (AD) mutation, brain trauma, stroke, Parkinson's disease, alcohol abuse, and depression. Cognition (Clinical Dementia Rating), function (physical dependence and nursing home residence), day-to-day activities (Functional Assessment Scores), and mood (Geriatric Depression Scale) were compared among seizure groups after adjusting for dementia duration and age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 26,501 participants, 374 (1.4%) had recurrent seizures and 510 (1.9%) had remote seizures. In multivariable survival analysis, recurrent seizures were associated with a higher mortality risk than remote and no seizures (adjusted hazard ratio [aHR], 95% confidence interval [95% CI]; recurrent aHR = 1.79, 95% CI = 1.51 to 2.12; remote aHR = 1.17, 95% CI = 0.98 to 1.38). Median time-to-death for recurrent, remote, and no seizures was 2.4, 4.0, and 4.7 years, respectively. People with recurrent seizures had worse cognition, day-to-day function, and physical dependence than those with remote seizures and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>PWD with poorly controlled recurrent seizures have worse mortality, functional, and cognitive outcomes than PWD with remote and no seizures. These findings underscore the need for timely identification and management of ongoing seizures in PWD. ANN NEUROL 2025;97:358–368</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 2","pages":"358-368"},"PeriodicalIF":8.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542307","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号