Pub Date : 2024-08-01Epub Date: 2024-06-27DOI: 10.1016/S1474-4422(24)00173-X
Dario Pfyffer, Andrew C Smith, Kenneth A Weber, Andreas Grillhoesl, Orpheus Mach, Christina Draganich, Jeffrey C Berliner, Candace Tefertiller, Iris Leister, Doris Maier, Jan M Schwab, Alan Thompson, Armin Curt, Patrick Freund
<p><strong>Background: </strong>The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges-injury-spared neural tissue adjacent to the lesion-for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI.</p><p><strong>Methods: </strong>For this longitudinal study, we included patients with acute cervical SCI (vertebrae C1-C7) admitted to one of three trauma or rehabilitation centres: Murnau, Germany (March 18, 2010-March 1, 2021); Zurich, Switzerland (May 12, 2002-March 2, 2019); and Denver, CO, USA (Jan 12, 2010-Feb 16, 2017). Patients were clinically assessed at admission (baseline), at discharge (3 months), and at 12 months post SCI. Midsagittal tissue bridges were quantified from T2-weighted images assessed at 3-4 weeks post SCI. Fractional regression and unbiased recursive partitioning models, adjusted for age, sex, centre, and neurological level of injury, were used to assess associations between tissue bridge width and baseline-adjusted total motor score, pinprick score, and light touch scores at 3 months and 12 months. Patients were stratified into subgroups according to whether they showed better or worse predicted recovery.</p><p><strong>Findings: </strong>The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5-11.2), 8·6% (0·8) of maximal pinprick score (7·0-10·1), and 10·9% (0·8) of maximal light touch score (9·4-12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4-13·4), 5·7% (1·3) of maximal pinprick score (3·3-8·2), and 6·9% (1·4) of maximal light touch score (4·1-9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres.</p><p><strong>Interpretation: </strong>Tissue bridges, measured in the first few weeks after SCI, are associated with short-term and long-term clinical improvement. Thus, tissue bridges could potentially be used to guide rehabilitation decision making and to stratify patients into more homogeneous subgroups of recovery in regenerative and neuroprotective clinical trials.</p><p><strong>Funding: </strong>Wings for Life, International Foundation for Research in Paraplegia
{"title":"Prognostic value of tissue bridges in cervical spinal cord injury: a longitudinal, multicentre, retrospective cohort study.","authors":"Dario Pfyffer, Andrew C Smith, Kenneth A Weber, Andreas Grillhoesl, Orpheus Mach, Christina Draganich, Jeffrey C Berliner, Candace Tefertiller, Iris Leister, Doris Maier, Jan M Schwab, Alan Thompson, Armin Curt, Patrick Freund","doi":"10.1016/S1474-4422(24)00173-X","DOIUrl":"10.1016/S1474-4422(24)00173-X","url":null,"abstract":"<p><strong>Background: </strong>The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges-injury-spared neural tissue adjacent to the lesion-for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI.</p><p><strong>Methods: </strong>For this longitudinal study, we included patients with acute cervical SCI (vertebrae C1-C7) admitted to one of three trauma or rehabilitation centres: Murnau, Germany (March 18, 2010-March 1, 2021); Zurich, Switzerland (May 12, 2002-March 2, 2019); and Denver, CO, USA (Jan 12, 2010-Feb 16, 2017). Patients were clinically assessed at admission (baseline), at discharge (3 months), and at 12 months post SCI. Midsagittal tissue bridges were quantified from T2-weighted images assessed at 3-4 weeks post SCI. Fractional regression and unbiased recursive partitioning models, adjusted for age, sex, centre, and neurological level of injury, were used to assess associations between tissue bridge width and baseline-adjusted total motor score, pinprick score, and light touch scores at 3 months and 12 months. Patients were stratified into subgroups according to whether they showed better or worse predicted recovery.</p><p><strong>Findings: </strong>The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5-11.2), 8·6% (0·8) of maximal pinprick score (7·0-10·1), and 10·9% (0·8) of maximal light touch score (9·4-12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4-13·4), 5·7% (1·3) of maximal pinprick score (3·3-8·2), and 6·9% (1·4) of maximal light touch score (4·1-9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres.</p><p><strong>Interpretation: </strong>Tissue bridges, measured in the first few weeks after SCI, are associated with short-term and long-term clinical improvement. Thus, tissue bridges could potentially be used to guide rehabilitation decision making and to stratify patients into more homogeneous subgroups of recovery in regenerative and neuroprotective clinical trials.</p><p><strong>Funding: </strong>Wings for Life, International Foundation for Research in Paraplegia","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"816-825"},"PeriodicalIF":46.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469169","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}
Pub Date : 2024-08-01Epub Date: 2024-06-06DOI: 10.1016/S1474-4422(24)00255-2
Udani Samarasekera
{"title":"Caring for the carers: the power of personal stories.","authors":"Udani Samarasekera","doi":"10.1016/S1474-4422(24)00255-2","DOIUrl":"10.1016/S1474-4422(24)00255-2","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"774"},"PeriodicalIF":46.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296368","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}
Pub Date : 2024-08-01Epub Date: 2024-06-12DOI: 10.1016/S1474-4422(24)00175-3
Mads Hjortdal Grønhøj, Thorbjørn Søren Rønn Jensen, Rares Miscov, Ann Kathrine Sindby, Birgit Debrabant, Torben Hundsholt, Carsten Reidies Bjarkam, Bo Bergholt, Kåre Fugleholm, Frantz Rom Poulsen
<p><strong>Background: </strong>Postoperative drainage after surgical evacuation of chronic subdural haematoma reduces the risk of recurrence, but the optimum drainage time is uncertain. We aimed to investigate the shortest possible drainage time without increasing the haematoma recurrence rate.</p><p><strong>Methods: </strong>We conducted a randomised, multi-arm and multistage non-inferiority trial at four neurosurgical centres in Denmark. We enrolled adult patients (aged ≥18 years) with symptomatic chronic subdural haematoma. All patients were treated according to the national standard practice with a burr hole above the maximum width of the haematoma. Patients were randomly assigned in a 1:1:1 ratio via a centralised web server to receive 6 h, 12 h, or 24 h of postoperative passive subdural drainage. Randomisation was done by an independent on-call neurosurgeon and was masked until 6 h after surgery. The primary outcome was symptomatic haematoma recurrence at 3 months after surgery; the rate of recurrence was assessed in a regression model for non-inferiority testing, with no missing data. Personnel assessing the primary outcome were masked to group allocation. Non-inferiority was assessed with a prespecified margin of 7%, in a modified intention-to-treat population-defined as patients with randomly assigned treatment excluding those withdrawing from study participation after randomisation, or experiencing acute rebleedings or accidental drain removal. This trial is registered with ISRCTN (number 15186366); the trial was stopped after the first interim analysis on the advice of an independent safety advisory committee.</p><p><strong>Findings: </strong>Between March 1, 2021, and June 30, 2022, 347 patients were enrolled and 331 were followed up to 3 months, 105 were assigned to 6 h of drainage, 111 to 12 h of drainage, and 115 to 24 h of drainage. At admission, 83 (25%) participants were women and 248 (75%) were men, mean age was 75·7 years (SD 10·5), median modified Rankin Scale score was 4 (IQR 3-5), and median Glasgow Coma Scale score was 15 (IQR 14-15). At 3 months after surgery, haematoma recurrence was reported in 28 (27%) of 105 patients who were assigned to 6 h drainage (predicted haematoma recurrence rate 27·0%, 95% CI 18·5 to 35·4), 22 (20%) of 111 assigned to 12 h drainage (19·5%, 12·0 to 27·0), and 12 (10%) of 115 assigned to 24 h drainage (10·4%, 4·8 to 16·0). The risk of haematoma recurrence was increased by 16·5 percentage points (95% CI 6·5 to 26·6) in patients drained for 6 h compared with 24 h, and by 9·1 percentage points (-0·4 to 18·5) in patients drained for 12 h compared with 24 h. Therefore, non-inferiority of 6 h and 12 h of drainage to 24 h of drainage was not established. 20 patients had died by 3 months, seven in the 6 h group, eight in the 12 h group, and five in the 24 h group. The most frequent known causes of death were haematoma recurrence (three in 12 h group), comorbidity (three in 12 h group), and pneumonia (o
{"title":"Optimal drainage time after evacuation of chronic subdural haematoma (DRAIN TIME 2): a multicentre, randomised, multiarm and multistage non-inferiority trial in Denmark.","authors":"Mads Hjortdal Grønhøj, Thorbjørn Søren Rønn Jensen, Rares Miscov, Ann Kathrine Sindby, Birgit Debrabant, Torben Hundsholt, Carsten Reidies Bjarkam, Bo Bergholt, Kåre Fugleholm, Frantz Rom Poulsen","doi":"10.1016/S1474-4422(24)00175-3","DOIUrl":"10.1016/S1474-4422(24)00175-3","url":null,"abstract":"<p><strong>Background: </strong>Postoperative drainage after surgical evacuation of chronic subdural haematoma reduces the risk of recurrence, but the optimum drainage time is uncertain. We aimed to investigate the shortest possible drainage time without increasing the haematoma recurrence rate.</p><p><strong>Methods: </strong>We conducted a randomised, multi-arm and multistage non-inferiority trial at four neurosurgical centres in Denmark. We enrolled adult patients (aged ≥18 years) with symptomatic chronic subdural haematoma. All patients were treated according to the national standard practice with a burr hole above the maximum width of the haematoma. Patients were randomly assigned in a 1:1:1 ratio via a centralised web server to receive 6 h, 12 h, or 24 h of postoperative passive subdural drainage. Randomisation was done by an independent on-call neurosurgeon and was masked until 6 h after surgery. The primary outcome was symptomatic haematoma recurrence at 3 months after surgery; the rate of recurrence was assessed in a regression model for non-inferiority testing, with no missing data. Personnel assessing the primary outcome were masked to group allocation. Non-inferiority was assessed with a prespecified margin of 7%, in a modified intention-to-treat population-defined as patients with randomly assigned treatment excluding those withdrawing from study participation after randomisation, or experiencing acute rebleedings or accidental drain removal. This trial is registered with ISRCTN (number 15186366); the trial was stopped after the first interim analysis on the advice of an independent safety advisory committee.</p><p><strong>Findings: </strong>Between March 1, 2021, and June 30, 2022, 347 patients were enrolled and 331 were followed up to 3 months, 105 were assigned to 6 h of drainage, 111 to 12 h of drainage, and 115 to 24 h of drainage. At admission, 83 (25%) participants were women and 248 (75%) were men, mean age was 75·7 years (SD 10·5), median modified Rankin Scale score was 4 (IQR 3-5), and median Glasgow Coma Scale score was 15 (IQR 14-15). At 3 months after surgery, haematoma recurrence was reported in 28 (27%) of 105 patients who were assigned to 6 h drainage (predicted haematoma recurrence rate 27·0%, 95% CI 18·5 to 35·4), 22 (20%) of 111 assigned to 12 h drainage (19·5%, 12·0 to 27·0), and 12 (10%) of 115 assigned to 24 h drainage (10·4%, 4·8 to 16·0). The risk of haematoma recurrence was increased by 16·5 percentage points (95% CI 6·5 to 26·6) in patients drained for 6 h compared with 24 h, and by 9·1 percentage points (-0·4 to 18·5) in patients drained for 12 h compared with 24 h. Therefore, non-inferiority of 6 h and 12 h of drainage to 24 h of drainage was not established. 20 patients had died by 3 months, seven in the 6 h group, eight in the 12 h group, and five in the 24 h group. The most frequent known causes of death were haematoma recurrence (three in 12 h group), comorbidity (three in 12 h group), and pneumonia (o","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"787-796"},"PeriodicalIF":46.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327535","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}
Pub Date : 2024-08-01Epub Date: 2024-06-13DOI: 10.1016/S1474-4422(24)00206-0
Mark W Parsons, Vignan Yogendrakumar, Leonid Churilov, Carlos Garcia-Esperon, Bruce C V Campbell, Michelle L Russell, Gagan Sharma, Chushuang Chen, Longting Lin, Beng Lim Chew, Felix C Ng, Akshay Deepak, Philip M C Choi, Timothy J Kleinig, Dennis J Cordato, Teddy Y Wu, John N Fink, Henry Ma, Thanh G Phan, Hugh S Markus, Carlos A Molina, Chon-Haw Tsai, Jiunn-Tay Lee, Jiann-Shing Jeng, Daniel Strbian, Atte Meretoja, Juan F Arenillas, Brian H Buck, Michael J Devlin, Helen Brown, Ken S Butcher, Billy O'Brien, Arman Sabet, Tissa Wijeratne, Andrew Bivard, Rohan S Grimley, Smriti Agarwal, Sunil K Munshi, Geoffrey A Donnan, Stephen M Davis, Ferdinand Miteff, Neil J Spratt, Christopher R Levi
<p><strong>Background: </strong>Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging.</p><p><strong>Methods: </strong>This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed.</p><p><strong>Findings: </strong>Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed p<sub>non-inferiority</sub>=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed p<sub>non-inferiority</sub>=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk differe
背景：静脉注射替奈普酶可增加灌注成像显示有可挽救脑组织的患者的再灌注，作为缺血性卒中的溶栓药物，它可能比阿替普酶更具优势。我们旨在评估替奈普酶与阿替普酶对通过灌注成像筛选出的患者的临床疗效的非劣效性：这项国际多中心、开放标签、平行分组、随机临床非劣效性试验招募了来自 8 个国家 35 家医院的患者。参试者年龄在 18 岁或以上，缺血性中风发病或最后一次已知病程在 4-5 小时之内，未考虑进行血管内血栓切除术，并符合脑灌注成像的靶点不匹配标准。患者通过中央网络服务器随机分配（1:1）至静脉注射替奈普酶（0-25 毫克/千克）或阿替普酶（0-90 毫克/千克）。主要结果是患者在3个月后无残疾（改良Rankin量表0-1）的比例，在意向治疗和按协议治疗人群中均通过蒙面审查进行评估。我们的目标是招募 832 名参与者，以获得 90% 的力量（单侧α=0-025）来检测 0-08 的风险差异，绝对非劣效差为-0-03。该试验已在澳大利亚-新西兰临床试验注册中心（ACTRN12613000243718）和欧盟临床试验注册中心（EudraCT编号2015-002657-36）注册，目前已完成：结果：在其他试验结果显示替奈普酶与阿替普酶相比无劣效性后，招募工作提前停止。2014年3月21日至2023年10月20日期间，680名患者入组并被随机分配到替奈普酶（n=339）和阿替普酶（n=341），所有患者均纳入意向治疗分析（对5名患者缺失的主要结果数据采用多重归因）。74名参与者违反了协议，因此按协议治疗的患者有601人（替奈替普酶组295人，阿替普酶组306人）。参与者的中位年龄为 74 岁（IQR 为 63-82），美国国立卫生研究院卒中量表基线评分为 7 分（4-11），260 人（38%）为女性。在意向治疗分析中，335名接受替奈普酶治疗的患者中有191人（57%）出现了主要结果，340名接受阿替普酶治疗的患者中有188人（55%）出现了主要结果（标准化风险差异[SRD]=0-03 [95% CI -0-033 to 0-10]，单尾p非劣效性=0-031）。在按协议分析中，295名接受替奈普酶治疗的患者中有173人（59%）出现了主要结果，306名接受阿替普酶治疗的患者中有171人（56%）出现了主要结果（SRD 0-05 [-0-02 to 0-12]，单尾p非劣效性=0-01）。替奈普酶组337名患者中有9人（3%）和阿替普酶组340名患者中有6人（2%）出现症状性颅内出血（未调整风险差异=0-01 [95% CI -0-01 to 0-03]），335名患者中有23人（7%）和340名患者中有15人（4%）在开始治疗后90天内死亡（SRD 0-02 [95% CI -0-02 to 0-05]）：我们的研究结果进一步证明了替奈普酶不劣于阿替普酶，尤其是在使用灌注成像确定符合再灌注条件的卒中患者时。虽然在按协议治疗人群中达到了非劣效性，但在意向治疗分析中却没有达到，这可能是由于样本量的限制。尽管如此，在早期时间窗大规模实施灌注CT以帮助选择静脉溶栓患者的做法已被证明是可行的：澳大利亚国家健康医学研究委员会；勃林格殷格翰公司。
{"title":"Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial.","authors":"Mark W Parsons, Vignan Yogendrakumar, Leonid Churilov, Carlos Garcia-Esperon, Bruce C V Campbell, Michelle L Russell, Gagan Sharma, Chushuang Chen, Longting Lin, Beng Lim Chew, Felix C Ng, Akshay Deepak, Philip M C Choi, Timothy J Kleinig, Dennis J Cordato, Teddy Y Wu, John N Fink, Henry Ma, Thanh G Phan, Hugh S Markus, Carlos A Molina, Chon-Haw Tsai, Jiunn-Tay Lee, Jiann-Shing Jeng, Daniel Strbian, Atte Meretoja, Juan F Arenillas, Brian H Buck, Michael J Devlin, Helen Brown, Ken S Butcher, Billy O'Brien, Arman Sabet, Tissa Wijeratne, Andrew Bivard, Rohan S Grimley, Smriti Agarwal, Sunil K Munshi, Geoffrey A Donnan, Stephen M Davis, Ferdinand Miteff, Neil J Spratt, Christopher R Levi","doi":"10.1016/S1474-4422(24)00206-0","DOIUrl":"10.1016/S1474-4422(24)00206-0","url":null,"abstract":"<p><strong>Background: </strong>Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging.</p><p><strong>Methods: </strong>This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed.</p><p><strong>Findings: </strong>Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed p<sub>non-inferiority</sub>=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed p<sub>non-inferiority</sub>=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk differe","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"775-786"},"PeriodicalIF":46.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331365","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}
Pub Date : 2024-08-01Epub Date: 2024-06-13DOI: 10.1016/S1474-4422(24)00258-8
Kazunori Toyoda
{"title":"Tenecteplase versus alteplase in stroke thrombolysis: the last piece of the puzzle?","authors":"Kazunori Toyoda","doi":"10.1016/S1474-4422(24)00258-8","DOIUrl":"10.1016/S1474-4422(24)00258-8","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"750-751"},"PeriodicalIF":46.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331366","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}
Pub Date : 2024-08-01Epub Date: 2024-06-21DOI: 10.1016/S1474-4422(24)00264-3
Joanna M Roy, Stavropoula Tjoumakaris
{"title":"Bailout angioplasty or stenting for large vessel occlusion.","authors":"Joanna M Roy, Stavropoula Tjoumakaris","doi":"10.1016/S1474-4422(24)00264-3","DOIUrl":"10.1016/S1474-4422(24)00264-3","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"753-754"},"PeriodicalIF":46.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446478","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}
Pub Date : 2024-07-01DOI: 10.1016/S1474-4422(24)00225-4
Jennifer G Goldman, Bradley F Boeve, Doug Galasko, James E Galvin, James B Leverenz, John-Paul Taylor
{"title":"Concerns with the new biological research criteria for synucleinopathy.","authors":"Jennifer G Goldman, Bradley F Boeve, Doug Galasko, James E Galvin, James B Leverenz, John-Paul Taylor","doi":"10.1016/S1474-4422(24)00225-4","DOIUrl":"10.1016/S1474-4422(24)00225-4","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 7","pages":"660-661"},"PeriodicalIF":46.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321127","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}
Pub Date : 2024-07-01DOI: 10.1016/S1474-4422(24)00213-8
Bradley F Boeve, Albert A Davis, Yo-El Ju, Kejal Kantarci, Wolfgang Singer, Aleks Videnovic
{"title":"Concerns with the new biological research criteria for synucleinopathy.","authors":"Bradley F Boeve, Albert A Davis, Yo-El Ju, Kejal Kantarci, Wolfgang Singer, Aleks Videnovic","doi":"10.1016/S1474-4422(24)00213-8","DOIUrl":"10.1016/S1474-4422(24)00213-8","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 7","pages":"659-660"},"PeriodicalIF":6.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321122","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}
Pub Date : 2024-07-01DOI: 10.1016/S1474-4422(24)00215-1
Jacques Reis, Christine Tranchant, Roberto G Lucchini, Peter S Spencer
{"title":"Concerns with the new biological research criteria for synucleinopathy.","authors":"Jacques Reis, Christine Tranchant, Roberto G Lucchini, Peter S Spencer","doi":"10.1016/S1474-4422(24)00215-1","DOIUrl":"10.1016/S1474-4422(24)00215-1","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 7","pages":"663"},"PeriodicalIF":46.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321124","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}
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