Pub Date : 2024-11-20DOI: 10.1016/s1474-4422(24)00424-1
Qingyuan Liu, Shaohua Mo, Jun Wu, Xianzeng Tong, Kaiwen Wang, Xu Chen, Shanwen Chen, Shuaiwei Guo, Xiong Li, Mingde Li, Lei Peng, Xinguo Sun, Yang Wang, Jianjun Sun, Jun Pu, Kaige Zheng, Jiaming Zhang, Yang Liu, Yi Yang, Zheng Wen, Pengjun Jiang
<h3>Background</h3>Patients with non-traumatic intracerebral haemorrhage have a substantial risk of major adverse cardiovascular and cerebrovascular events, including ischaemic stroke, after surgery. The optimal timing of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage in patients at high risk of postoperative ischaemic events has not been characterised. We aimed to investigate the safety and efficacy of early versus late initiation of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage.<h3>Methods</h3>This prospective, open-label, blinded-endpoint, randomised trial was done at eight stroke centres in China. Eligible patients were aged 18–70 years, undergoing surgery for the evacuation of spontaneous intracerebral haemorrhage, and had a high risk of postoperative ischaemic events. Using the minimisation method in an online randomisation system, patients were randomly assigned (1:1) to receive 100 mg acetylsalicylic acid once per day in either the early-start group (starting on the third day after surgery until the 90th day after surgery) or the late-start group (starting on the 30th day after surgery until the 90th day after surgery). Medication was taken orally or delivered via a feeding tube. The primary efficacy outcome was a composite of new major ischaemic cardiovascular, cerebrovascular, or peripheral vascular events within 90 days and the primary safety outcome was any intracranial bleeding within 90 days, both measured in the intention-to-treat population. The trial is registered at <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>NCT04820972</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 complete.<h3>Findings</h3>From May 1, 2021, to May 1, 2023, 7323 patients were screened, of whom 269 (4%) were enrolled and randomly assigned: 134 to the early-start group and 135 to the late-start group. 195 (72%) patients were male, 74 (28%) were female, and the median age was 60·2 years (IQR 52·0–66·5). Haematomas were supratentorial and deep in most (170 [63%] of 269) patients. Ischaemic major cardiovascular, cerebrovascular, or peripheral vascular events occurred within 90 days after surgery in 27 (20%) of 134 patients in the early-start group and 42 (31%) of 135 patients in the late-start group (odds ratio 0·56 [95% CI 0·32–0·98]; p=0·041). Intracranial bleeding occurred in one (1%) of 134 patients in the early-start group and four (3%) of 135 patients in the late-start group. Non-bleeding serious adverse events occurred in 57 (42%) of 134 patients in the early-start group and 57 (42%) of 135 patients in the late-start gro
{"title":"Safety and efficacy of early versus delayed acetylsalicylic acid after surgery for spontaneous intracerebral haemorrhage in China (E-start): a prospective, multicentre, open-label, blinded-endpoint, randomised trial","authors":"Qingyuan Liu, Shaohua Mo, Jun Wu, Xianzeng Tong, Kaiwen Wang, Xu Chen, Shanwen Chen, Shuaiwei Guo, Xiong Li, Mingde Li, Lei Peng, Xinguo Sun, Yang Wang, Jianjun Sun, Jun Pu, Kaige Zheng, Jiaming Zhang, Yang Liu, Yi Yang, Zheng Wen, Pengjun Jiang","doi":"10.1016/s1474-4422(24)00424-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00424-1","url":null,"abstract":"<h3>Background</h3>Patients with non-traumatic intracerebral haemorrhage have a substantial risk of major adverse cardiovascular and cerebrovascular events, including ischaemic stroke, after surgery. The optimal timing of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage in patients at high risk of postoperative ischaemic events has not been characterised. We aimed to investigate the safety and efficacy of early versus late initiation of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage.<h3>Methods</h3>This prospective, open-label, blinded-endpoint, randomised trial was done at eight stroke centres in China. Eligible patients were aged 18–70 years, undergoing surgery for the evacuation of spontaneous intracerebral haemorrhage, and had a high risk of postoperative ischaemic events. Using the minimisation method in an online randomisation system, patients were randomly assigned (1:1) to receive 100 mg acetylsalicylic acid once per day in either the early-start group (starting on the third day after surgery until the 90th day after surgery) or the late-start group (starting on the 30th day after surgery until the 90th day after surgery). Medication was taken orally or delivered via a feeding tube. The primary efficacy outcome was a composite of new major ischaemic cardiovascular, cerebrovascular, or peripheral vascular events within 90 days and the primary safety outcome was any intracranial bleeding within 90 days, both measured in the intention-to-treat population. The trial is registered at <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>NCT04820972</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 complete.<h3>Findings</h3>From May 1, 2021, to May 1, 2023, 7323 patients were screened, of whom 269 (4%) were enrolled and randomly assigned: 134 to the early-start group and 135 to the late-start group. 195 (72%) patients were male, 74 (28%) were female, and the median age was 60·2 years (IQR 52·0–66·5). Haematomas were supratentorial and deep in most (170 [63%] of 269) patients. Ischaemic major cardiovascular, cerebrovascular, or peripheral vascular events occurred within 90 days after surgery in 27 (20%) of 134 patients in the early-start group and 42 (31%) of 135 patients in the late-start group (odds ratio 0·56 [95% CI 0·32–0·98]; p=0·041). Intracranial bleeding occurred in one (1%) of 134 patients in the early-start group and four (3%) of 135 patients in the late-start group. Non-bleeding serious adverse events occurred in 57 (42%) of 134 patients in the early-start group and 57 (42%) of 135 patients in the late-start gro","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678246","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)00441-1
Sanjay M Sisodiya, Mark A Maslin, Marina Romanello, Michael G Hanna
No Abstract
无摘要
{"title":"Effects of climate change on the brain: an environmental neurology perspective – Authors’ reply","authors":"Sanjay M Sisodiya, Mark A Maslin, Marina Romanello, Michael G Hanna","doi":"10.1016/s1474-4422(24)00441-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00441-1","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"252 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678239","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)00431-9
Jacques Reis, Alain Buguet, Manny W Radomski, Gustavo C Román, Peter S Spencer
No Abstract
无摘要
{"title":"Effects of climate change on the brain: an environmental neurology perspective","authors":"Jacques Reis, Alain Buguet, Manny W Radomski, Gustavo C Román, Peter S Spencer","doi":"10.1016/s1474-4422(24)00431-9","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00431-9","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678242","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)00450-2
Maria Francisca Rocha, Rosa Maria Rodrigues, Arpan R Mehta
No Abstract
无摘要
{"title":"The legacy of Egas Moniz","authors":"Maria Francisca Rocha, Rosa Maria Rodrigues, Arpan R Mehta","doi":"10.1016/s1474-4422(24)00450-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00450-2","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678241","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)00402-2
Gerard Mayà, Alex Iranzo, Carles Gaig, Raquel Sánchez-Valle, Monica Serradell, Laura Molina-Porcel, Joan Santamaria, Ellen Gelpi, Iban Aldecoa
<h3>Background</h3>Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) is thought to be an early stage of α-synuclein-related neurodegenerative diseases. Nevertheless, the definitive identification of its biological substrate can be determined only by post-mortem neuropathology. We aimed to describe the post-mortem neuropathology of individuals with IRBD who developed or did not develop a neurodegenerative disease before death.<h3>Methods</h3>In this case series at the Hospital Clinic de Barcelona, Barcelona, Spain, we examined post-mortem brain tissue and spinal cords from individuals diagnosed with IRBD by video polysomnography who became donors to the Neurological Tissue Bank between May 28, 2005, and March 23, 2023. We performed post-mortem neuropathology to assess the presence and distribution of neuronal loss, gliosis, and protein aggregates using antibodies against α-synuclein, amyloid β, phosphorylated tau, three-repeat and four-repeat tau isoforms, and TDP-43. Comparative statistical analyses were not done because of the small sample size, but differences observed across the nuclei and brain structures were described.<h3>Findings</h3>The brains and spinal cords of 20 individuals with IRBD were examined (19 [95%] men, one [5%] woman). Their clinical antemortem diagnoses were of IRBD without any other neurological disorder in three (15%), Parkinson's disease without dementia in two (10%), Parkinson's disease dementia (PDD) in three (15%), and dementia with Lewy bodies (DLB) in 12 (60%) individuals. Post-mortem neuropathological diagnoses were Lewy body disease in 19 (95%) and multiple system atrophy (MSA) in one (5%). All participants with Lewy body disease and MSA showed neuronal loss, gliosis, and α-synuclein deposits in neurons and astrocytes. In all participants, α-synuclein was found in the structures that regulate REM sleep atonia (eg, subcoeruleus nucleus, gigantocellular reticular nucleus, laterodorsal tegmentum, and amygdala). Coexistent pathologies were found in all participants, including Alzheimer's disease pathology (amyloid β plaques and neurofibrillary tangles) in 14 (70%), ageing-related tau astrogliopathy in 12 (60%), cerebral amyloid angiopathy in 11 (55%), argyrophilic grain disease in four (20%), limbic-predominant age-related TDP-43 encephalopathy in four (20%), and early changes indicative of progressive supranuclear palsy in three (15%). In individuals with IRBD without any other neurological disorder and in those who developed Parkinson's disease without dementia, α-synuclein was found in the brainstem and limbic system and rarely in the cortex, whereas coexisting proteinopathies were few and showed mild pathological burden. In contrast, in individuals who developed PDD or DLB, α-synuclein had diffuse distribution in the brainstem, limbic system, and cortex, and multiple comorbid pathologies were common, particularly those related to Alzheimer's disease.<h3>Interpretation</h3>Although limited by a re
{"title":"Post-mortem neuropathology of idiopathic rapid eye movement sleep behaviour disorder: a case series","authors":"Gerard Mayà, Alex Iranzo, Carles Gaig, Raquel Sánchez-Valle, Monica Serradell, Laura Molina-Porcel, Joan Santamaria, Ellen Gelpi, Iban Aldecoa","doi":"10.1016/s1474-4422(24)00402-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00402-2","url":null,"abstract":"<h3>Background</h3>Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) is thought to be an early stage of α-synuclein-related neurodegenerative diseases. Nevertheless, the definitive identification of its biological substrate can be determined only by post-mortem neuropathology. We aimed to describe the post-mortem neuropathology of individuals with IRBD who developed or did not develop a neurodegenerative disease before death.<h3>Methods</h3>In this case series at the Hospital Clinic de Barcelona, Barcelona, Spain, we examined post-mortem brain tissue and spinal cords from individuals diagnosed with IRBD by video polysomnography who became donors to the Neurological Tissue Bank between May 28, 2005, and March 23, 2023. We performed post-mortem neuropathology to assess the presence and distribution of neuronal loss, gliosis, and protein aggregates using antibodies against α-synuclein, amyloid β, phosphorylated tau, three-repeat and four-repeat tau isoforms, and TDP-43. Comparative statistical analyses were not done because of the small sample size, but differences observed across the nuclei and brain structures were described.<h3>Findings</h3>The brains and spinal cords of 20 individuals with IRBD were examined (19 [95%] men, one [5%] woman). Their clinical antemortem diagnoses were of IRBD without any other neurological disorder in three (15%), Parkinson's disease without dementia in two (10%), Parkinson's disease dementia (PDD) in three (15%), and dementia with Lewy bodies (DLB) in 12 (60%) individuals. Post-mortem neuropathological diagnoses were Lewy body disease in 19 (95%) and multiple system atrophy (MSA) in one (5%). All participants with Lewy body disease and MSA showed neuronal loss, gliosis, and α-synuclein deposits in neurons and astrocytes. In all participants, α-synuclein was found in the structures that regulate REM sleep atonia (eg, subcoeruleus nucleus, gigantocellular reticular nucleus, laterodorsal tegmentum, and amygdala). Coexistent pathologies were found in all participants, including Alzheimer's disease pathology (amyloid β plaques and neurofibrillary tangles) in 14 (70%), ageing-related tau astrogliopathy in 12 (60%), cerebral amyloid angiopathy in 11 (55%), argyrophilic grain disease in four (20%), limbic-predominant age-related TDP-43 encephalopathy in four (20%), and early changes indicative of progressive supranuclear palsy in three (15%). In individuals with IRBD without any other neurological disorder and in those who developed Parkinson's disease without dementia, α-synuclein was found in the brainstem and limbic system and rarely in the cortex, whereas coexisting proteinopathies were few and showed mild pathological burden. In contrast, in individuals who developed PDD or DLB, α-synuclein had diffuse distribution in the brainstem, limbic system, and cortex, and multiple comorbid pathologies were common, particularly those related to Alzheimer's disease.<h3>Interpretation</h3>Although limited by a re","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678250","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)00396-x
Florian Krismer, Alessandra Fanciulli, Wassilios G Meissner, Elizabeth A Coon, Gregor K Wenning
Multiple system atrophy is an adult-onset, sporadic, and progressive neurodegenerative disease. People with this disorder report a wide range of motor and non-motor symptoms. Overlap in the clinical presentation of multiple system atrophy with other movement disorders (eg, Parkinson's disease and progressive supranuclear palsy) is a concern for accurate and timely diagnosis. Over the past 5 years, progress has been made in understanding key pathophysiological events in multiple system atrophy, including the seeding of α-synuclein inclusions and the detection of disease-specific α-synuclein strains. Diagnostic criteria were revised in 2022 with the intention to improve the accuracy of a diagnosis of multiple system atrophy, particularly for early disease stages. Early signals of efficacy in clinical trials have indicated the potential for disease-modifying therapies for multiple system atrophy, although no trial has yet provided unequivocal evidence of neuroprotection in this rare disease. The advances in pathophysiology could play a part in biomarker discovery for early diagnosis as well as in the development of disease-modifying therapies.
{"title":"Multiple system atrophy: advances in pathophysiology, diagnosis, and treatment","authors":"Florian Krismer, Alessandra Fanciulli, Wassilios G Meissner, Elizabeth A Coon, Gregor K Wenning","doi":"10.1016/s1474-4422(24)00396-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00396-x","url":null,"abstract":"Multiple system atrophy is an adult-onset, sporadic, and progressive neurodegenerative disease. People with this disorder report a wide range of motor and non-motor symptoms. Overlap in the clinical presentation of multiple system atrophy with other movement disorders (eg, Parkinson's disease and progressive supranuclear palsy) is a concern for accurate and timely diagnosis. Over the past 5 years, progress has been made in understanding key pathophysiological events in multiple system atrophy, including the seeding of α-synuclein inclusions and the detection of disease-specific α-synuclein strains. Diagnostic criteria were revised in 2022 with the intention to improve the accuracy of a diagnosis of multiple system atrophy, particularly for early disease stages. Early signals of efficacy in clinical trials have indicated the potential for disease-modifying therapies for multiple system atrophy, although no trial has yet provided unequivocal evidence of neuroprotection in this rare disease. The advances in pathophysiology could play a part in biomarker discovery for early diagnosis as well as in the development of disease-modifying therapies.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678317","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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