Pub Date : 2024-09-01DOI: 10.1016/S1474-4422(24)00318-1
Vignan Yogendrakumar, Longting Lin, Robert L Medcalf, Mark W Parsons
{"title":"Improving thrombolysis efficiency for acute ischaemic stroke.","authors":"Vignan Yogendrakumar, Longting Lin, Robert L Medcalf, Mark W Parsons","doi":"10.1016/S1474-4422(24)00318-1","DOIUrl":"10.1016/S1474-4422(24)00318-1","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 9","pages":"853-855"},"PeriodicalIF":45.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996017","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 : 2024-09-01DOI: 10.1016/S1474-4422(24)00315-6
Jules Morgan
{"title":"Parkinson's disease is not just a tremor.","authors":"Jules Morgan","doi":"10.1016/S1474-4422(24)00315-6","DOIUrl":"10.1016/S1474-4422(24)00315-6","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 9","pages":"870"},"PeriodicalIF":45.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996021","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 : 2024-09-01DOI: 10.1016/S1474-4422(24)00330-2
Udani Samarasekera
{"title":"Andrew Singleton: from small island to \"Disneyland for doctors\".","authors":"Udani Samarasekera","doi":"10.1016/S1474-4422(24)00330-2","DOIUrl":"10.1016/S1474-4422(24)00330-2","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 9","pages":"865"},"PeriodicalIF":45.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996010","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 : 2024-09-01DOI: 10.1016/S1474-4422(24)00235-7
Tommaso Zoerle, Erta Beqiri, Cecilia A I Åkerlund, Guoyi Gao, Thomas Heldt, Gregory W J Hawryluk, Nino Stocchetti
Intracranial pressure monitoring enables the detection and treatment of intracranial hypertension, a potentially lethal insult after traumatic brain injury. Despite its widespread use, robust evidence supporting intracranial pressure monitoring and treatment remains sparse. International studies have shown large variations between centres regarding the indications for intracranial pressure monitoring and treatment of intracranial hypertension. Experts have reviewed these two aspects and, by consensus, provided practical approaches for monitoring and treatment. Advances have occurred in methods for non-invasive estimation of intracranial pressure although, for now, a reliable way to non-invasively and continuously measure intracranial pressure remains aspirational. Analysis of the intracranial pressure signal can provide information on brain compliance (ie, the ability of the cranium to tolerate volume changes) and on cerebral autoregulation (ie, the ability of cerebral blood vessels to react to changes in blood pressure). The information derived from the intracranial pressure signal might allow for more individualised patient management. Machine learning and artificial intelligence approaches are being increasingly applied to intracranial pressure monitoring, but many obstacles need to be overcome before their use in clinical practice could be attempted. Robust clinical trials are needed to support indications for intracranial pressure monitoring and treatment. Progress in non-invasive assessment of intracranial pressure and in signal analysis (for targeted treatment) will also be crucial.
{"title":"Intracranial pressure monitoring in adult patients with traumatic brain injury: challenges and innovations.","authors":"Tommaso Zoerle, Erta Beqiri, Cecilia A I Åkerlund, Guoyi Gao, Thomas Heldt, Gregory W J Hawryluk, Nino Stocchetti","doi":"10.1016/S1474-4422(24)00235-7","DOIUrl":"10.1016/S1474-4422(24)00235-7","url":null,"abstract":"<p><p>Intracranial pressure monitoring enables the detection and treatment of intracranial hypertension, a potentially lethal insult after traumatic brain injury. Despite its widespread use, robust evidence supporting intracranial pressure monitoring and treatment remains sparse. International studies have shown large variations between centres regarding the indications for intracranial pressure monitoring and treatment of intracranial hypertension. Experts have reviewed these two aspects and, by consensus, provided practical approaches for monitoring and treatment. Advances have occurred in methods for non-invasive estimation of intracranial pressure although, for now, a reliable way to non-invasively and continuously measure intracranial pressure remains aspirational. Analysis of the intracranial pressure signal can provide information on brain compliance (ie, the ability of the cranium to tolerate volume changes) and on cerebral autoregulation (ie, the ability of cerebral blood vessels to react to changes in blood pressure). The information derived from the intracranial pressure signal might allow for more individualised patient management. Machine learning and artificial intelligence approaches are being increasingly applied to intracranial pressure monitoring, but many obstacles need to be overcome before their use in clinical practice could be attempted. Robust clinical trials are needed to support indications for intracranial pressure monitoring and treatment. Progress in non-invasive assessment of intracranial pressure and in signal analysis (for targeted treatment) will also be crucial.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 9","pages":"938-950"},"PeriodicalIF":45.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996018","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 : 2024-09-01Epub Date: 2024-07-18DOI: 10.1016/S1474-4422(24)00270-9
Wolfgang Grisold, David W Dodick, Alla Guekht, Steven L Lewis, Tissa Wijeratne
{"title":"World Brain Day 2024: a focus on brain health and prevention.","authors":"Wolfgang Grisold, David W Dodick, Alla Guekht, Steven L Lewis, Tissa Wijeratne","doi":"10.1016/S1474-4422(24)00270-9","DOIUrl":"10.1016/S1474-4422(24)00270-9","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"863-864"},"PeriodicalIF":45.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734515","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 : 2024-09-01Epub Date: 2024-07-23DOI: 10.1016/S1474-4422(24)00216-3
Leonard H van den Berg, Jeffrey D Rothstein, Pamela J Shaw, Suma Babu, Michael Benatar, Robert C Bucelli, Angela Genge, Jonathan D Glass, Orla Hardiman, Vincenzo Libri, Theodore Mobach, Björn Oskarsson, Gary L Pattee, John Ravits, Christopher E Shaw, Markus Weber, Lorne Zinman, Paymaan Jafar-Nejad, Frank Rigo, Luan Lin, Toby A Ferguson, Anthony L Gotter, Danielle Graham, Michael Monine, Jennifer Inra, Susie Sinks, Satish Eraly, Steve Garafalo, Stephanie Fradette
<p><strong>Background: </strong>Hexanucleotide repeat expansion of C9orf72 is a common genetic cause of amyotrophic lateral sclerosis (ALS). No C9orf72-targeted treatments are available. BIIB078 is an investigational antisense oligonucleotide targeting C9orf72 sense RNA. We aimed to assess the safety, tolerability, and pharmacokinetics of BIIB078 in participants with C9orf72-associated ALS.</p><p><strong>Methods: </strong>This phase 1, randomised controlled trial was done at 22 sites in six countries (Canada, Ireland, Netherlands, Switzerland, UK, and USA). Adults with ALS and a pathogenic repeat expansion in C9orf72 were randomly assigned within six cohorts, via Interactive Response Technology in a 3:1 ratio per cohort, to receive BIIB078 (5 mg, 10 mg, 20 mg, 35 mg, 60 mg, or 90 mg in cohorts 1-6, respectively) or placebo, via an intrathecal bolus injection. The treatment period consisted of three loading doses of study treatment, administered approximately once every 2 weeks, followed by monthly maintenance doses during a treatment period of about 3 months for cohorts 1-3 and about 6 months for cohorts 4-6. Patients and investigators were masked to treatment assignment. The primary endpoint was the incidence of adverse events and serious adverse events. This trial was registered with ClinicalTrials.gov (NCT03626012) and is completed.</p><p><strong>Findings: </strong>Between Sept 10, 2018, and Nov 17, 2021, 124 patients were screened for inclusion in the study. 18 patients were excluded and 106 participants were enrolled and randomly assigned to receive 5 mg (n=6), 10 mg (n=9), 20 mg (n=9), 35 mg (n=19), 60 mg (n=18), or 90 mg (n=18) of BIIB078, or placebo (n=27). 58 (55%) of 106 patients were female. All patients received at least one dose of study treatment and were included in all analyses. All participants had at least one adverse event; most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. The most common adverse events in BIIB078-treated participants were falls, procedural pain, headache, and post lumbar puncture syndrome. 14 (18%) of 79 patients who received any dose of BIIB078 reported serious adverse events, compared with nine (33%) of 27 patients who received placebo. Five participants who received BIIB078 and three participants who received placebo had fatal adverse events: respiratory failure in a participant who received 10 mg BIIB078, ALS worsening in two participants who received 35 mg BIIB078, traumatic intracerebral haemorrhage in one participant who received 35 mg BIIB078, pulmonary embolism in one participant who received 60 mg BIIB078, and respiratory failure in three participants who received placebo. All deaths were assessed as not related to the study treatment by the reporting investigator.</p><p><strong>Interpretation: </strong>On the basis of these phase 1 study results, including secondary and exploratory findings showing no reduction in neurofilament levels and no benefit
{"title":"Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study.","authors":"Leonard H van den Berg, Jeffrey D Rothstein, Pamela J Shaw, Suma Babu, Michael Benatar, Robert C Bucelli, Angela Genge, Jonathan D Glass, Orla Hardiman, Vincenzo Libri, Theodore Mobach, Björn Oskarsson, Gary L Pattee, John Ravits, Christopher E Shaw, Markus Weber, Lorne Zinman, Paymaan Jafar-Nejad, Frank Rigo, Luan Lin, Toby A Ferguson, Anthony L Gotter, Danielle Graham, Michael Monine, Jennifer Inra, Susie Sinks, Satish Eraly, Steve Garafalo, Stephanie Fradette","doi":"10.1016/S1474-4422(24)00216-3","DOIUrl":"10.1016/S1474-4422(24)00216-3","url":null,"abstract":"<p><strong>Background: </strong>Hexanucleotide repeat expansion of C9orf72 is a common genetic cause of amyotrophic lateral sclerosis (ALS). No C9orf72-targeted treatments are available. BIIB078 is an investigational antisense oligonucleotide targeting C9orf72 sense RNA. We aimed to assess the safety, tolerability, and pharmacokinetics of BIIB078 in participants with C9orf72-associated ALS.</p><p><strong>Methods: </strong>This phase 1, randomised controlled trial was done at 22 sites in six countries (Canada, Ireland, Netherlands, Switzerland, UK, and USA). Adults with ALS and a pathogenic repeat expansion in C9orf72 were randomly assigned within six cohorts, via Interactive Response Technology in a 3:1 ratio per cohort, to receive BIIB078 (5 mg, 10 mg, 20 mg, 35 mg, 60 mg, or 90 mg in cohorts 1-6, respectively) or placebo, via an intrathecal bolus injection. The treatment period consisted of three loading doses of study treatment, administered approximately once every 2 weeks, followed by monthly maintenance doses during a treatment period of about 3 months for cohorts 1-3 and about 6 months for cohorts 4-6. Patients and investigators were masked to treatment assignment. The primary endpoint was the incidence of adverse events and serious adverse events. This trial was registered with ClinicalTrials.gov (NCT03626012) and is completed.</p><p><strong>Findings: </strong>Between Sept 10, 2018, and Nov 17, 2021, 124 patients were screened for inclusion in the study. 18 patients were excluded and 106 participants were enrolled and randomly assigned to receive 5 mg (n=6), 10 mg (n=9), 20 mg (n=9), 35 mg (n=19), 60 mg (n=18), or 90 mg (n=18) of BIIB078, or placebo (n=27). 58 (55%) of 106 patients were female. All patients received at least one dose of study treatment and were included in all analyses. All participants had at least one adverse event; most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. The most common adverse events in BIIB078-treated participants were falls, procedural pain, headache, and post lumbar puncture syndrome. 14 (18%) of 79 patients who received any dose of BIIB078 reported serious adverse events, compared with nine (33%) of 27 patients who received placebo. Five participants who received BIIB078 and three participants who received placebo had fatal adverse events: respiratory failure in a participant who received 10 mg BIIB078, ALS worsening in two participants who received 35 mg BIIB078, traumatic intracerebral haemorrhage in one participant who received 35 mg BIIB078, pulmonary embolism in one participant who received 60 mg BIIB078, and respiratory failure in three participants who received placebo. All deaths were assessed as not related to the study treatment by the reporting investigator.</p><p><strong>Interpretation: </strong>On the basis of these phase 1 study results, including secondary and exploratory findings showing no reduction in neurofilament levels and no benefit","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"901-912"},"PeriodicalIF":45.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766471","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 : 2024-09-01DOI: 10.1016/S1474-4422(24)00272-2
Harmen R Moes, Erik Buskens, Teus van Laar
{"title":"Continuous subcutaneous levodopa-carbidopa infusion for Parkinson's disease.","authors":"Harmen R Moes, Erik Buskens, Teus van Laar","doi":"10.1016/S1474-4422(24)00272-2","DOIUrl":"10.1016/S1474-4422(24)00272-2","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 9","pages":"856-857"},"PeriodicalIF":45.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996013","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}
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