Pub Date : 2025-12-10DOI: 10.1016/s1474-4422(25)00428-4
Raffaele Ferri, Maria Paola Mogavero
No Abstract
没有抽象的
{"title":"Advances in sleep research in 2025: translational connections","authors":"Raffaele Ferri, Maria Paola Mogavero","doi":"10.1016/s1474-4422(25)00428-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00428-4","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718028","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 : 2025-12-10DOI: 10.1016/s1474-4422(25)00386-2
Julia C Greenland, Kerry Dresser, Emma Cutting, Rachel Donegan, Simon Bond, Sarah J Crisp, Kirsten M Scott, Zanna J Voysey, Jonathan Holbrook, Lakmini Kahanawita, Reiss Pal, Marta Camacho, Alexander R D Peattie, Lennart R B Spindler, Young T Hong, Tim D Fryer, Caroline H Williams-Gray
Background
The immune system is implicated in Parkinson's disease aetiology and prognosis. Although there are effective symptomatic treatments for Parkinson's disease, there are currently no therapies that slow down disease progression. We aimed to investigate the clinical efficacy of the broadly acting peripheral immunosuppressant drug azathioprine for patients with early Parkinson's disease.
Methods
We did a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial at a single site (the Parkinson's Disease Research Clinic) in Cambridge, UK. Eligible participants were aged 50–80 years and were within 3 years of Parkinson's disease diagnosis (as per UK Parkinson's Disease Society Brain Bank Diagnostic Criteria). Participants were randomly assigned (1:1) using a web-based system to receive daily oral azathioprine 2 mg/kg or placebo for 12 months. The primary outcome was change from baseline Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) gait-axial score in the off-state at 12 months, assessed in the intention-to-treat population, which included all randomly assigned patients who completed the baseline visit. Safety was assessed in all participants who were screened for eligibility. Mixed model repeated measures analysis was used to assess treatment effects. This study was registered with ISRCTN, 14616801, and EudraCT, 2018-003089-14.
Findings
Between May 13, 2021, and July 28, 2022, 78 participants were screened, of whom 66 were randomly assigned to azathioprine (n=32) or placebo (n=34), and included in the intention-to-treat analysis. 23 (35%) of 66 patients were female and 43 (65%) were male. At 12 months, the mean change in MDS-UPDRS gait-axial score was 0·54 points (SD 2·43) in the azathioprine group and 0·13 points (2·09) in the placebo group (effect size 0·438 [95% CI –0·694 to 1·57]; p=0·78). 159 adverse events were reported in the azathioprine group and 156 in the placebo group. Eight participants had a serious adverse event in the azathioprine group (24%) and four patients in the placebo group (12%). The most common adverse events in both groups were infections (20 [61%] of 33 participants in the azathioprine group vs 26 [76%] of 34 participants in the placebo group) and gastrointestinal disorders (19 [58%] participants vs 17 [50%] participants).
Interpretation
Azathioprine was well-tolerated in this population; however, the primary outcome was not met. Exploratory analyses suggested effects of azathioprine on peripheral and central immune biomarkers and on motor symptoms. Potential clinical effects could be greater in females than males, warranting further exploration.
Funding
Cambridge Centre for Parkinson-Plus, Cure Parkinson's, National Institute for Health Research Biomedical Research Centre.
{"title":"Azathioprine for the treatment of early Parkinson's disease (AZA-PD): a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial","authors":"Julia C Greenland, Kerry Dresser, Emma Cutting, Rachel Donegan, Simon Bond, Sarah J Crisp, Kirsten M Scott, Zanna J Voysey, Jonathan Holbrook, Lakmini Kahanawita, Reiss Pal, Marta Camacho, Alexander R D Peattie, Lennart R B Spindler, Young T Hong, Tim D Fryer, Caroline H Williams-Gray","doi":"10.1016/s1474-4422(25)00386-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00386-2","url":null,"abstract":"<h3>Background</h3>The immune system is implicated in Parkinson's disease aetiology and prognosis. Although there are effective symptomatic treatments for Parkinson's disease, there are currently no therapies that slow down disease progression. We aimed to investigate the clinical efficacy of the broadly acting peripheral immunosuppressant drug azathioprine for patients with early Parkinson's disease.<h3>Methods</h3>We did a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial at a single site (the Parkinson's Disease Research Clinic) in Cambridge, UK. Eligible participants were aged 50–80 years and were within 3 years of Parkinson's disease diagnosis (as per UK Parkinson's Disease Society Brain Bank Diagnostic Criteria). Participants were randomly assigned (1:1) using a web-based system to receive daily oral azathioprine 2 mg/kg or placebo for 12 months. The primary outcome was change from baseline Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) gait-axial score in the off-state at 12 months, assessed in the intention-to-treat population, which included all randomly assigned patients who completed the baseline visit. Safety was assessed in all participants who were screened for eligibility. Mixed model repeated measures analysis was used to assess treatment effects. This study was registered with ISRCTN, 14616801, and EudraCT, 2018-003089-14.<h3>Findings</h3>Between May 13, 2021, and July 28, 2022, 78 participants were screened, of whom 66 were randomly assigned to azathioprine (n=32) or placebo (n=34), and included in the intention-to-treat analysis. 23 (35%) of 66 patients were female and 43 (65%) were male. At 12 months, the mean change in MDS-UPDRS gait-axial score was 0·54 points (SD 2·43) in the azathioprine group and 0·13 points (2·09) in the placebo group (effect size 0·438 [95% CI –0·694 to 1·57]; p=0·78). 159 adverse events were reported in the azathioprine group and 156 in the placebo group. Eight participants had a serious adverse event in the azathioprine group (24%) and four patients in the placebo group (12%). The most common adverse events in both groups were infections (20 [61%] of 33 participants in the azathioprine group <em>vs</em> 26 [76%] of 34 participants in the placebo group) and gastrointestinal disorders (19 [58%] participants <em>vs</em> 17 [50%] participants).<h3>Interpretation</h3>Azathioprine was well-tolerated in this population; however, the primary outcome was not met. Exploratory analyses suggested effects of azathioprine on peripheral and central immune biomarkers and on motor symptoms. Potential clinical effects could be greater in females than males, warranting further exploration.<h3>Funding</h3>Cambridge Centre for Parkinson-Plus, Cure Parkinson's, National Institute for Health Research Biomedical Research Centre.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718033","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 : 2025-12-10DOI: 10.1016/s1474-4422(25)00453-3
Terence J O'Brien
No Abstract
没有抽象的
{"title":"Epilepsy research in 2025: sudden unexpected death in epilepsy, artifical intelligence and seizure classification","authors":"Terence J O'Brien","doi":"10.1016/s1474-4422(25)00453-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00453-3","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718276","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 : 2025-12-10DOI: 10.1016/s1474-4422(25)00434-x
Andrew S C Rice, David L H Bennett, Angelika Lampert
No Abstract
没有抽象的
{"title":"Advances in pain research in 2025 illuminate the complexities of neuropathic pain","authors":"Andrew S C Rice, David L H Bennett, Angelika Lampert","doi":"10.1016/s1474-4422(25)00434-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00434-x","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718029","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}
Epilepsy surgery, the treatment of choice for drug-resistant focal epilepsy, is evolving rapidly. This progress is driven by a growing interest in the network theory of epilepsy, advances in data-driven models, and a focus on personalised treatment approaches. As a result, treatment options have expanded to include minimally invasive procedures, neurostimulation devices, and network-based interventions. Predicting surgical outcomes—such as seizure freedom and neuropsychological effects—remains challenging but is improving through advances in computational technology and molecular research, paving the way for more precise surgery. Despite these advancements, disparities in access to treatments persist, particularly in resource-scarce settings, highlighting the need for systemic solutions to improve access. Emerging research into genetic and multi-omic markers might assist in tailoring treatments and improving the prediction of outcomes. Future directions include integrating minimally invasive techniques, refining neuromodulation strategies, and leveraging molecular and computational tools to optimise patient care. Multidisciplinary collaboration will be essential to overcome challenges, reduce disparities, and advance surgical outcomes for patients with drug-resistant epilepsy worldwide.
{"title":"Emerging technologies and strategies in epilepsy surgery: toward personalised medicine","authors":"Ruta Yardi, Dario J Englot, Chengyuan Wu, Kathryn Davis, Sallie Baxendale, Manjari Tripathi, Lara Jehi","doi":"10.1016/s1474-4422(25)00380-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00380-1","url":null,"abstract":"Epilepsy surgery, the treatment of choice for drug-resistant focal epilepsy, is evolving rapidly. This progress is driven by a growing interest in the network theory of epilepsy, advances in data-driven models, and a focus on personalised treatment approaches. As a result, treatment options have expanded to include minimally invasive procedures, neurostimulation devices, and network-based interventions. Predicting surgical outcomes—such as seizure freedom and neuropsychological effects—remains challenging but is improving through advances in computational technology and molecular research, paving the way for more precise surgery. Despite these advancements, disparities in access to treatments persist, particularly in resource-scarce settings, highlighting the need for systemic solutions to improve access. Emerging research into genetic and multi-omic markers might assist in tailoring treatments and improving the prediction of outcomes. Future directions include integrating minimally invasive techniques, refining neuromodulation strategies, and leveraging molecular and computational tools to optimise patient care. Multidisciplinary collaboration will be essential to overcome challenges, reduce disparities, and advance surgical outcomes for patients with drug-resistant epilepsy worldwide.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718279","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 : 2025-12-10DOI: 10.1016/s1474-4422(25)00424-7
Eng-King Tan
{"title":"The role of the exposome in Parkinson's disease","authors":"Eng-King Tan","doi":"10.1016/s1474-4422(25)00424-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00424-7","url":null,"abstract":"","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730692","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 : 2025-12-10DOI: 10.1016/s1474-4422(25)00438-7
Laurent Servais
{"title":"2025 for neuromuscular diseases: a year of multiple advances","authors":"Laurent Servais","doi":"10.1016/s1474-4422(25)00438-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00438-7","url":null,"abstract":"","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730698","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 : 2025-12-10DOI: 10.1016/s1474-4422(25)00435-1
Bruce James Brew
{"title":"Neuroinfectious diseases in 2025: pathogens old and new","authors":"Bruce James Brew","doi":"10.1016/s1474-4422(25)00435-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00435-1","url":null,"abstract":"","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731603","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 : 2025-11-22DOI: 10.1016/s1474-4422(25)00379-5
Philippe Ryvlin, Margaux Huot, Luc Valton, Louis Maillard, Fabrice Bartolomei, Philippe Derambure, Edouard Hirsch, Véronique Michel, Francine Chassoux, Jérôme Petit, Arielle Crespel, Arnaud Biraben, Vincent Navarro, Philippe Kahane, Bertrand De Toffol, Pierre Thomas, Sarah Rosenberg, Adriano Bernini, Anne-Laure Charlois, Laura Craciun, Fatima Chorfa, Pauline Ducouret, Axel Ferreira, Mathilde Leclercq, Manon Marty, Blanca Mercedes Alvarez, Milena Sampaio, Antoine Spahr, Noémie Timestit-Kurland, Maylis Touya, Pascal Roy, Sylvain Rheims, C Adam, N Andre-Obadia, S Aubert, F Bartolomei, J Biberon, A Biraben, FB Bonini, S Boulogne, V Bourg, H Catenoix, F Chassoux, A Crespel, JC Curot, MD Damiano, M De Montaudouin, B De Toffol, M Denuelle, P Derambure, S Dupont, V Eid, V Frazzini, P Gelisse, E Hirsch, J Isnard, AS Job, J Jung, P Kahane, SL Lagarde, E Landre, P Latour, L Maillard, C Marchal, A Mc Gonigal, V Michel, L Minotti, A Montavont, V Navarro, VH Nguyen-Michel, A Nica, J Petit, FP Pizzo, S Rheims, SR Rosenberg, FR Rulquin, P Ryvlin, CS Sabourdy, M Sampaio, W Szurhaj, P Thomas, D Tourniaire, AT Trébuchon, L Tyvaert, MP Valenti, L Valton, L Vercueil, JP Vignal
{"title":"Seizure-related biomarkers of sudden unexpected death in epilepsy (SUDEP) in drug-resistant focal epilepsy (REPO2MSE): a prospective, multicentre case–control study","authors":"Philippe Ryvlin, Margaux Huot, Luc Valton, Louis Maillard, Fabrice Bartolomei, Philippe Derambure, Edouard Hirsch, Véronique Michel, Francine Chassoux, Jérôme Petit, Arielle Crespel, Arnaud Biraben, Vincent Navarro, Philippe Kahane, Bertrand De Toffol, Pierre Thomas, Sarah Rosenberg, Adriano Bernini, Anne-Laure Charlois, Laura Craciun, Fatima Chorfa, Pauline Ducouret, Axel Ferreira, Mathilde Leclercq, Manon Marty, Blanca Mercedes Alvarez, Milena Sampaio, Antoine Spahr, Noémie Timestit-Kurland, Maylis Touya, Pascal Roy, Sylvain Rheims, C Adam, N Andre-Obadia, S Aubert, F Bartolomei, J Biberon, A Biraben, FB Bonini, S Boulogne, V Bourg, H Catenoix, F Chassoux, A Crespel, JC Curot, MD Damiano, M De Montaudouin, B De Toffol, M Denuelle, P Derambure, S Dupont, V Eid, V Frazzini, P Gelisse, E Hirsch, J Isnard, AS Job, J Jung, P Kahane, SL Lagarde, E Landre, P Latour, L Maillard, C Marchal, A Mc Gonigal, V Michel, L Minotti, A Montavont, V Navarro, VH Nguyen-Michel, A Nica, J Petit, FP Pizzo, S Rheims, SR Rosenberg, FR Rulquin, P Ryvlin, CS Sabourdy, M Sampaio, W Szurhaj, P Thomas, D Tourniaire, AT Trébuchon, L Tyvaert, MP Valenti, L Valton, L Vercueil, JP Vignal","doi":"10.1016/s1474-4422(25)00379-5","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00379-5","url":null,"abstract":"","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567316","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 : 2025-11-22DOI: 10.1016/s1474-4422(25)00423-5
Daniel Friedman
{"title":"Advances in understanding sudden unexpected death in people with drug-resistant epilepsy","authors":"Daniel Friedman","doi":"10.1016/s1474-4422(25)00423-5","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00423-5","url":null,"abstract":"","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567740","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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