Pub Date : 2024-12-18DOI: 10.1016/s1474-4422(24)00490-3
No Abstract
{"title":"Bridging the diagnostic gap in Alzheimer's disease","authors":"","doi":"10.1016/s1474-4422(24)00490-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00490-3","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-18DOI: 10.1016/s1474-4422(24)00485-x
Patricia Pozo-Rosich
No Abstract
{"title":"Headache research in 2024: new data on migraine prevention","authors":"Patricia Pozo-Rosich","doi":"10.1016/s1474-4422(24)00485-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00485-x","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-02DOI: 10.1016/s1474-4422(24)00430-7
Jennifer V Gettings, Fatemeh Mohammad Alizadeh Chafjiri, Archana A Patel, Simon Shorvon, Howard P Goodkin, Tobias Loddenkemper
Status epilepticus is a common neurological emergency that is characterised by prolonged or recurrent seizures without recovery between episodes and associated with substantial morbidity and mortality. Prompt recognition and targeted therapy can reduce the risk of complications and death associated with status epilepticus, thereby improving outcomes. The most recent International League Against Epilepsy definition considers two important timepoints in status epilepticus: first, when the seizure does not self-terminate; and second, when the seizure can have long-term consequences, including neuronal injury. Recent advances in our understanding of the pathophysiology of status epilepticus indicate that changes in neurotransmission as status epilepticus progresses can increase excitatory seizure-facilitating and decrease inhibitory seizure-terminating mechanisms at a cellular level. Effective clinical management requires rapid initiation of supportive measures, assessment of the cause of the seizure, and first-line treatment with benzodiazepines. If status epilepticus continues, management should entail second-line and third-line treatment agents, supportive EEG monitoring, and admission to an intensive care unit. Future research to study early seizure detection, rescue protocols and medications, rapid treatment escalation, and integration of fundamental scientific and clinical evidence into clinical practice could shorten seizure duration and reduce associated complications. Furthermore, improved recognition, education, and treatment in patients who are at risk might help to prevent status epilepticus, particularly for patients living in low-income and middle-income countries.
{"title":"Diagnosis and management of status epilepticus: improving the status quo","authors":"Jennifer V Gettings, Fatemeh Mohammad Alizadeh Chafjiri, Archana A Patel, Simon Shorvon, Howard P Goodkin, Tobias Loddenkemper","doi":"10.1016/s1474-4422(24)00430-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00430-7","url":null,"abstract":"Status epilepticus is a common neurological emergency that is characterised by prolonged or recurrent seizures without recovery between episodes and associated with substantial morbidity and mortality. Prompt recognition and targeted therapy can reduce the risk of complications and death associated with status epilepticus, thereby improving outcomes. The most recent International League Against Epilepsy definition considers two important timepoints in status epilepticus: first, when the seizure does not self-terminate; and second, when the seizure can have long-term consequences, including neuronal injury. Recent advances in our understanding of the pathophysiology of status epilepticus indicate that changes in neurotransmission as status epilepticus progresses can increase excitatory seizure-facilitating and decrease inhibitory seizure-terminating mechanisms at a cellular level. Effective clinical management requires rapid initiation of supportive measures, assessment of the cause of the seizure, and first-line treatment with benzodiazepines. If status epilepticus continues, management should entail second-line and third-line treatment agents, supportive EEG monitoring, and admission to an intensive care unit. Future research to study early seizure detection, rescue protocols and medications, rapid treatment escalation, and integration of fundamental scientific and clinical evidence into clinical practice could shorten seizure duration and reduce associated complications. Furthermore, improved recognition, education, and treatment in patients who are at risk might help to prevent status epilepticus, particularly for patients living in low-income and middle-income countries.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<h3>Background</h3>Intra-arterial prourokinase has been shown to be a promising thrombolytic agent in patients with acute ischaemic stroke. Given the global shortage of thrombolytics, we aimed to assess the non-inferiority of intravenous recombinant human prourokinase compared with alteplase in patients with acute ischaemic stroke who were ineligible for or who refused endovascular thrombectomy.<h3>Methods</h3>PROST-2 was a phase 3, open-label, non-inferiority, randomised controlled trial conducted at 61 hospitals in China. Patients older than 18 years with acute ischaemic stroke, who were ineligible for or who refused endovascular thrombectomy, were randomly assigned in a 1:1 ratio within 4·5 h of stroke onset to receive intravenous recombinant human prourokinase (15 mg bolus followed by 20 mg infusion within 30 min) or intravenous alteplase (0·9 mg per kg, maximum dose 90 mg; 10% bolus followed by remainder as infusion over 60 min). The primary efficacy outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days, assessed via masked review in the intention-to-treat population, with a non-inferiority margin for the risk ratio of 0·93. The primary safety outcome was the incidence of symptomatic intracranial haemorrhage within 36 h. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (<span><span>NCT05700591</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>) and is now completed.<h3>Findings</h3>Between Jan 29, 2023, and March 14, 2024, 1552 patients were randomly assigned: 775 received recombinant human prourokinase and 777 received alteplase. The primary outcome of a modified Rankin Scale score of 0 or 1 at 90 days was reached by 558 (72·0%) of 775 patients in the recombinant human prourokinase group versus 534 (68·7%) of 777 in the alteplase group (risk ratio 1·04 [95% CI 0·98 to 1·10]; p<0·0001 for non-inferiority). The frequency of symptomatic intracranial haemorrhage within 36 h was lower in the recombinant human prourokinase group than in the alteplase group (two [0·3%] of 770 patients <em>vs</em> ten [1·3%] of 775, risk difference –1·0 percentage points [95% CI –2·1 to –0·1]; p=0·021), as was the incidence of major bleeding at 7 days (four [0·5%] vs 16 [2·1%]; –1·5 percentage points (–2·8 to –0·4); p=0·0072). All-cause mortality within 7 days did not differ between groups (five [0·6%] deaths in the recombinant human prourokinase group <em>vs</em> 13 [1·7%] in the alteplase group; risk difference –1·0 percentage points; 95% CI –2·3 to 0·1]; p=0·060).<h3>Interpretation</h3>In our trial, recombinant human prourokinase was shown t
{"title":"Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4·5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial","authors":"Shuya Li, Hong-Qiu Gu, Baoyu Feng, Hao Li, Xuechun Wang, Qiang Dong, Dongsheng Fan, Yun Xu, Suiqiang Zhu, Hongguo Dai, Yan Wei, Ziran Wang, Guozhi Lu, Yutong Ma, Zixiao Li, Yilong Wang, Xia Meng, Xingquan Zhao, Liping Liu, Yongjun Wang","doi":"10.1016/s1474-4422(24)00436-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00436-8","url":null,"abstract":"<h3>Background</h3>Intra-arterial prourokinase has been shown to be a promising thrombolytic agent in patients with acute ischaemic stroke. Given the global shortage of thrombolytics, we aimed to assess the non-inferiority of intravenous recombinant human prourokinase compared with alteplase in patients with acute ischaemic stroke who were ineligible for or who refused endovascular thrombectomy.<h3>Methods</h3>PROST-2 was a phase 3, open-label, non-inferiority, randomised controlled trial conducted at 61 hospitals in China. Patients older than 18 years with acute ischaemic stroke, who were ineligible for or who refused endovascular thrombectomy, were randomly assigned in a 1:1 ratio within 4·5 h of stroke onset to receive intravenous recombinant human prourokinase (15 mg bolus followed by 20 mg infusion within 30 min) or intravenous alteplase (0·9 mg per kg, maximum dose 90 mg; 10% bolus followed by remainder as infusion over 60 min). The primary efficacy outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days, assessed via masked review in the intention-to-treat population, with a non-inferiority margin for the risk ratio of 0·93. The primary safety outcome was the incidence of symptomatic intracranial haemorrhage within 36 h. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT05700591</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and is now completed.<h3>Findings</h3>Between Jan 29, 2023, and March 14, 2024, 1552 patients were randomly assigned: 775 received recombinant human prourokinase and 777 received alteplase. The primary outcome of a modified Rankin Scale score of 0 or 1 at 90 days was reached by 558 (72·0%) of 775 patients in the recombinant human prourokinase group versus 534 (68·7%) of 777 in the alteplase group (risk ratio 1·04 [95% CI 0·98 to 1·10]; p<0·0001 for non-inferiority). The frequency of symptomatic intracranial haemorrhage within 36 h was lower in the recombinant human prourokinase group than in the alteplase group (two [0·3%] of 770 patients <em>vs</em> ten [1·3%] of 775, risk difference –1·0 percentage points [95% CI –2·1 to –0·1]; p=0·021), as was the incidence of major bleeding at 7 days (four [0·5%] vs 16 [2·1%]; –1·5 percentage points (–2·8 to –0·4); p=0·0072). All-cause mortality within 7 days did not differ between groups (five [0·6%] deaths in the recombinant human prourokinase group <em>vs</em> 13 [1·7%] in the alteplase group; risk difference –1·0 percentage points; 95% CI –2·3 to 0·1]; p=0·060).<h3>Interpretation</h3>In our trial, recombinant human prourokinase was shown t","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"196 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-25DOI: 10.1016/s1474-4422(24)00438-1
Nyika D Kruyt, Paul J Nederkoorn, Else Charlotte Sandset, Patrick Lyden, Lili Song, Craig S Anderson
No Abstract
无摘要
{"title":"A cautionary view on blood pressure lowering in patients with acute ischaemic stroke receiving reperfusion therapy","authors":"Nyika D Kruyt, Paul J Nederkoorn, Else Charlotte Sandset, Patrick Lyden, Lili Song, Craig S Anderson","doi":"10.1016/s1474-4422(24)00438-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00438-1","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/s1474-4422(24)00445-9
Wendy C Ziai, Santosh B Murthy, Christopher P Kellner
No Abstract
无摘要
{"title":"Antiplatelet therapy after intracerebral haemorrhage","authors":"Wendy C Ziai, Santosh B Murthy, Christopher P Kellner","doi":"10.1016/s1474-4422(24)00445-9","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00445-9","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/s1474-4422(24)00395-8
Yihua Ma, Carly M Farris, Sandrina Weber, Sebastian Schade, Hieu Nguyen, Alexandra Pérez-Soriano, Darly M Giraldo, Manel Fernández, Marta Soto, Ana Cámara, Celia Painous, Esteban Muñoz, Francesc Valldeoriola, Maria J Martí, Jordi Clarimon, Pekka Kallunki, Thong Chi Ma, Roy N Alcalay, Bárbara Fernandez Gomes, Kaj Blennow, Luis Concha-Marambio
<h3>Background</h3>The pathological hallmarks of multiple system atrophy and Parkinson's disease are, respectively, misfolded-α-synuclein-laden glial cytoplasmic inclusions and Lewy bodies. CSF-soluble misfolded α-synuclein aggregates (seeds) are readily detected in people with Parkinson's disease by α-synuclein seed amplification assay (synSAA), but identification of seeds associated with multiple system atrophy for diagnostic purposes has proven elusive. We aimed to assess whether a novel synSAA could reliably distinguish seeds from Lewy bodies and glial cytoplasmic inclusions.<h3>Methods</h3>In this multicentre cohort study, a novel synSAA that multiplies and detects seeds by fluorescence was used to analyse masked CSF and brain samples from participants with either clinically diagnosed or pathology-confirmed multiple system atrophy, Parkinson's disease, dementia with Lewy bodies, isolated rapid eye movement sleep behaviour disorder (IRBD), disorders that were not synucleinopathies, or healthy controls. Participants were from eight available cohorts from seven medical centres in four countries: New York Brain Bank, New York, USA (NYBB); University of Pennsylvania, Philadelphia, PA, USA (UPENN); Paracelsus-Elena-Klinik, Kassel, Germany (DeNoPa and KAMSA); Hospital Clinic Barcelona, Spain (BARMSA); Universität Tübingen, Tübingen, Germany (EKUT); Göteborgs Universitet, Göteborgs, Sweden (UGOT); and Karolinska Institutet, Stockholm, Sweden (KIMSA). Clinical cohorts were classified for expected diagnostic accuracy as either research (longitudinal follow-up visits) or real-life (single visit). Sensitivity and specificity were estimated according to pathological (gold standard) and clinical (reference standard) diagnoses.<h3>Findings</h3>In 23 brain samples (from the NYBB cohort), those containing Lewy bodies were synSAA-positive and produced high fluorescence amplification patterns (defined as type 1); those containing glial cytoplasmic inclusions were synSAA-positive and produced intermediate fluorescence (defined as type 2); and those without α-synuclein pathology produced below-threshold fluorescence and were synSAA-negative. In 21 pathology-confirmed CSF samples (from the UPENN cohort), those with Lewy bodies were synSAA-positive type 1; those with glial cytoplasmic inclusions were synSAA-positive type 2; and those with four-repeat tauopathy were synSAA-negative. In the DeNoPa research cohort (which had no samples from people with multiple system atrophy), the novel synSAA had sensitivities of 95% (95% CI 88–99) for 80 participants with Parkinson's disease and 95% (76–100) for 21 participants with IRBD, and a specificity of 95% (86–99) for 60 healthy controls. Overall (combining BARMSA, EKUT, KAMSA, UGOT, and KIMSA cohorts that were enriched for cases of multiple system atrophy), the novel synSAA had 87% sensitivity for multiple system atrophy (95% CI 80–93) and specificity for type 2 seeds was 77% (67–85). For participants with multiple system
背景多系统萎缩症和帕金森病的病理特征分别是含有错误折叠的α-突触核蛋白的胶质细胞质包涵体和路易体。通过α-突触核蛋白种子扩增试验（synSAA）可以很容易地在帕金森病患者体内检测到 CSF 溶性错误折叠的α-突触核蛋白聚集体（种子），但要鉴定出与多系统萎缩相关的种子以用于诊断却很难。我们的目的是评估新型突触核蛋白种子扩增试验能否可靠地将种子与路易体和胶质细胞质包涵体区分开来。方法在这项多中心队列研究中，我们使用了一种能通过荧光增殖和检测种子的新型同步分析仪来分析来自临床诊断或病理确诊的多系统萎缩、帕金森病、路易体痴呆、孤立性眼球快速运动睡眠行为障碍（IRBD）、非突触核蛋白病的患者或健康对照组的遮蔽脑脊液和脑样本。参与者来自四个国家七个医疗中心的八个队列：美国纽约的纽约脑库（NYBB）、美国宾夕法尼亚州费城的宾夕法尼亚大学（UPENN）、德国卡塞尔的Paracelsus-Elena-Klinik（DeNoPa和KAMSA）、西班牙巴塞罗那医院诊所（BARMSA）、德国图宾根的图宾根大学（EKUT）、瑞典哥德堡大学（UGOT）和瑞典斯德哥尔摩的卡罗林斯卡医学院（KIMSA）。临床队列根据预期诊断准确性分为研究队列（纵向随访）和实际队列（单次随访）。根据病理诊断（金标准）和临床诊断（参考标准）估算灵敏度和特异性。研究结果在23份脑样本（来自NYBB队列）中，含有路易体的样本呈synSAA阳性，并产生高荧光扩增模式（定义为1型）；含有胶质细胞质包涵体的样本呈synSAA阳性，并产生中等荧光（定义为2型）；无α-突触核蛋白病理变化的样本产生低于阈值的荧光，呈synSAA阴性。在21份病理确诊的脑脊液样本（来自UPENN队列）中，有路易体的样本为synSAA阳性1型；有胶质细胞质包涵体的样本为synSAA阳性2型；有四重复tauopathy的样本为synSAA阴性。在DeNoPa研究队列（没有多系统萎缩患者样本）中，新型synSAA对80名帕金森病患者和21名IRBD患者的灵敏度分别为95%（95% CI 88-99）和95%（76-100），对60名健康对照者的特异性为95%（86-99）。总体而言（结合 BARMSA、EKUT、KAMSA、UGOT 和 KIMSA 队列，这些队列富含多系统萎缩病例），新型 synSAA 对多系统萎缩的灵敏度为 87%（95% CI 80-93），对 2 型种子的特异性为 77%（67-85）。对于研究队列（BARMSA 和 EKUT）中患有多系统萎缩的参与者，新型 synSAA 的灵敏度为 84%（95% CI 71-92），对 2 型种子的特异性为 87%（74-95），而现实队列（KAMSA、KIMSA 和 UGOT）中的病例灵敏度为 91%（95% CI 80-97），但对 2 型种子的特异性下降至 68%（53-81）。释义新型 synSAA 产生的扩增模式可识别潜在的α-突触核蛋白病理变化，其显示的两种荧光水平与突触核蛋白病的不同病理特征相对应。synSAA 可用于临床试验中突触核蛋白病的早期诊断，并有可能用于临床，但还需要更多的正式验证工作。
{"title":"Sensitivity and specificity of a seed amplification assay for diagnosis of multiple system atrophy: a multicentre cohort study","authors":"Yihua Ma, Carly M Farris, Sandrina Weber, Sebastian Schade, Hieu Nguyen, Alexandra Pérez-Soriano, Darly M Giraldo, Manel Fernández, Marta Soto, Ana Cámara, Celia Painous, Esteban Muñoz, Francesc Valldeoriola, Maria J Martí, Jordi Clarimon, Pekka Kallunki, Thong Chi Ma, Roy N Alcalay, Bárbara Fernandez Gomes, Kaj Blennow, Luis Concha-Marambio","doi":"10.1016/s1474-4422(24)00395-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00395-8","url":null,"abstract":"<h3>Background</h3>The pathological hallmarks of multiple system atrophy and Parkinson's disease are, respectively, misfolded-α-synuclein-laden glial cytoplasmic inclusions and Lewy bodies. CSF-soluble misfolded α-synuclein aggregates (seeds) are readily detected in people with Parkinson's disease by α-synuclein seed amplification assay (synSAA), but identification of seeds associated with multiple system atrophy for diagnostic purposes has proven elusive. We aimed to assess whether a novel synSAA could reliably distinguish seeds from Lewy bodies and glial cytoplasmic inclusions.<h3>Methods</h3>In this multicentre cohort study, a novel synSAA that multiplies and detects seeds by fluorescence was used to analyse masked CSF and brain samples from participants with either clinically diagnosed or pathology-confirmed multiple system atrophy, Parkinson's disease, dementia with Lewy bodies, isolated rapid eye movement sleep behaviour disorder (IRBD), disorders that were not synucleinopathies, or healthy controls. Participants were from eight available cohorts from seven medical centres in four countries: New York Brain Bank, New York, USA (NYBB); University of Pennsylvania, Philadelphia, PA, USA (UPENN); Paracelsus-Elena-Klinik, Kassel, Germany (DeNoPa and KAMSA); Hospital Clinic Barcelona, Spain (BARMSA); Universität Tübingen, Tübingen, Germany (EKUT); Göteborgs Universitet, Göteborgs, Sweden (UGOT); and Karolinska Institutet, Stockholm, Sweden (KIMSA). Clinical cohorts were classified for expected diagnostic accuracy as either research (longitudinal follow-up visits) or real-life (single visit). Sensitivity and specificity were estimated according to pathological (gold standard) and clinical (reference standard) diagnoses.<h3>Findings</h3>In 23 brain samples (from the NYBB cohort), those containing Lewy bodies were synSAA-positive and produced high fluorescence amplification patterns (defined as type 1); those containing glial cytoplasmic inclusions were synSAA-positive and produced intermediate fluorescence (defined as type 2); and those without α-synuclein pathology produced below-threshold fluorescence and were synSAA-negative. In 21 pathology-confirmed CSF samples (from the UPENN cohort), those with Lewy bodies were synSAA-positive type 1; those with glial cytoplasmic inclusions were synSAA-positive type 2; and those with four-repeat tauopathy were synSAA-negative. In the DeNoPa research cohort (which had no samples from people with multiple system atrophy), the novel synSAA had sensitivities of 95% (95% CI 88–99) for 80 participants with Parkinson's disease and 95% (76–100) for 21 participants with IRBD, and a specificity of 95% (86–99) for 60 healthy controls. Overall (combining BARMSA, EKUT, KAMSA, UGOT, and KIMSA cohorts that were enriched for cases of multiple system atrophy), the novel synSAA had 87% sensitivity for multiple system atrophy (95% CI 80–93) and specificity for type 2 seeds was 77% (67–85). For participants with multiple system ","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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