Jennifer V Gettings, Fatemeh Mohammad Alizadeh Chafjiri, Archana A Patel, Simon Shorvon, Howard P Goodkin, Tobias Loddenkemper
{"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}
{"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}
Nyika D Kruyt, Paul J Nederkoorn, Else Charlotte Sandset, Patrick Lyden, Lili Song, Craig S Anderson
{"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}
Wendy C Ziai, Santosh B Murthy, Christopher P Kellner
{"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}
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
{"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}
{"title":"Creative neurorehabilitation: the art of intervention","authors":"Jules Morgan","doi":"10.1016/s1474-4422(24)00480-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00480-0","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678227","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}
{"title":"Correction to Lancet Neurol 2024; 23: 961–62","authors":"","doi":"10.1016/s1474-4422(24)00452-6","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00452-6","url":null,"abstract":"<em>Monfrini E, Minardi R, Valzania F, Calandra-Buonaura G, Mandich P, Di Fonzo A.</em> RAB32 <em>mutation in Parkinson's disease. Lancet Neurol 2024; <strong>23:</strong> 961–62</em>—The appendix has been updated to include a list of ParkNet Study Group members who were involved in this project. This correction has been made as of Nov 20, 2024.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678240","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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