The Lancet Neurology最新文献

{"title":"Navigating the use of generative AI in peer review","authors":"Laura Hart","doi":"10.1016/s1474-4422(25)00041-9","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00041-9","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451631","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":"Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: from genetics to therapeutics","authors":"Sarah Mizielinska, Guillaume M Hautbergue, Tania F Gendron, Marka van Blitterswijk, Orla Hardiman, John Ravits, Adrian M Isaacs, Rosa Rademakers","doi":"10.1016/s1474-4422(25)00026-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00026-2","url":null,"abstract":"GGGGCC repeat expansions in <em>C9orf72</em> are a common genetic cause of amyotrophic lateral sclerosis in people of European ancestry; however, substantial variability in the penetrance of the mutation, age at disease onset, and clinical presentation can complicate diagnosis and prognosis. The repeat expansion is bidirectionally transcribed in the sense and antisense directions into repetitive RNAs and translated into dipeptide repeat proteins, and both accumulate in the cortex, cerebellum, and the spinal cord. Furthermore, neuropathological aggregates of phosphorylated TDP-43 are observed in motor cortex and other cortical regions, and in the spinal cord of patients at autopsy. <em>C9orf72</em> repeat expansions can also cause frontotemporal dementia. The GGGGCC repeat induces a complex interplay of loss-of-function and gain-of-function pathological mechanisms. Clinical trials using antisense oligonucleotides to target the GGGGCC repeat RNA have not been successful, potentially because they only target a single gain-of-function mechanism. Novel therapeutic approaches targeting the DNA repeat expansion, multiple repeat-derived RNA species, or downstream targets of TDP-43 dysfunction are, however, on the horizon, together with the development of diagnostic and prognostic biomarkers.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451489","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":"Clinical insights in enzyme replacement therapy for metabolic storage disorders: lessons from Pompe disease","authors":"Nadine A M E van der Beek, Maudy T M Theunissen, Johanna M P van den Hout, Wilhelmus W M Pijnappel, Benedikt Schoser, Pascal Laforêt, Giancarlo Parenti, Pieter A van Doorn, Ans T van der Ploeg","doi":"10.1016/s1474-4422(24)00518-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00518-0","url":null,"abstract":"Metabolic storage disorders, including lysosomal storage disorders, pose complex challenges in management due to their progressive and life-threatening nature. Although enzyme replacement therapy has substantially improved outcomes for patients with lysosomal storage disorders, limitations of this therapy have become apparent throughout two decades of use. New clinical features of these diseases have emerged as patients live longer, leading to unresolved questions regarding ongoing treatment and long-term care. Innovative therapies are emerging that aim to improve targeting of tissues, particularly for previously inaccessible areas such as the CNS. These next-generation treatments hold promise for enhancing patient outcomes beyond what enzyme replacement therapy can do. Continued exploration of novel therapeutic strategies will be crucial for providing more effective and personalised care for these complex diseases.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451487","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":"Autoinflammatory encephalopathy due to PTPN1 haploinsufficiency: a case series","authors":"Gaofeng Zhu, Blaise Didry-Barca, Luis Seabra, Gillian I Rice, Carolina Uggenti, Moncef Touimy, Mathieu P Rodero, Rolando Hernandez Trapero, Vincent Bondet, Darragh Duffy, Philippe Gautier, Katie Livingstone, Fraser J H Sutherland, Pierre Lebon, Mélanie Parisot, Christine Bole-Feysot, Cécile Masson, Nicolas Cagnard, Patrick Nitschké, Glenn Anderson, Alice Lepelley","doi":"10.1016/s1474-4422(24)00526-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00526-x","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Through the agnostic screening of patients with uncharacterised disease phenotypes for an upregulation of type I interferon (IFN) signalling, we identified a cohort of individuals heterozygous for mutations in &lt;em&gt;PTPN1&lt;/em&gt;, encoding the protein-tyrosine phosphatase 1B (PTP1B). We aimed to describe the clinical phenotype and molecular and cellular pathology of this new disease.&lt;h3&gt;Methods&lt;/h3&gt;In this case series, we identified patients and collected clinical and neuroradiological data through collaboration with paediatric neurology and clinical genetics colleagues across Europe (Czechia, France, Germany, Italy, Slovenia, and the UK) and Israel. Variants in &lt;em&gt;PTPN1&lt;/em&gt; were identified by exome and directed Sanger sequencing. The expression of IFN-stimulated genes was determined by quantitative (q) PCR or NanoString technology. Experiments to assess RNA and protein expression and to investigate type 1 IFN signalling were undertaken in patient fibroblasts, hTERT-immortalised BJ-5ta fibroblasts, and RPE-1 cells using CRISPR–Cas9 editing and standard cell biology techniques.&lt;h3&gt;Findings&lt;/h3&gt;Between Dec 20, 2013, and Jan 11, 2023, we identified 12 patients from 11 families who were heterozygous for mutations in &lt;em&gt;PTPN1&lt;/em&gt;. We found ten novel or very rare variants in &lt;em&gt;PTPN1&lt;/em&gt; (frequency on gnomAD version 4.1.0 of &lt;1·25 × 10:sup&gt;–6). Six variants were predicted as STOP mutations, two involved canonical splice-site nucleotides, and two were missense substitutions. In three patients, the variant occurred de novo, whereas in nine affected individuals, the variant was inherited from an asymptomatic parent. The clinical phenotype was characterised by the subacute onset (age range 1–8 years) of loss of motor and language skills in the absence of seizures after initially normal development, leading to spastic dystonia and bulbar involvement. Neuroimaging variably demonstrated cerebral atrophy (sometimes unilateral initially) or high T2 white matter signal. Neopterin in CSF was elevated in all ten patients who were tested, and all probands demonstrated an upregulation of IFN-stimulated genes in whole blood. Although clinical stabilisation and neuroradiological improvement was seen in both treated and untreated patients, in six of eight treated patients, high-dose corticosteroids were judged clinically to result in an improvement in neurological status. Of the four asymptomatic parents tested, IFN signalling in blood was normal (three patients) or minimally elevated (one patient). Analysis of patient blood and fibroblasts showed that tested &lt;em&gt;PTPN1&lt;/em&gt; variants led to reduced levels of &lt;em&gt;PTPN1&lt;/em&gt; mRNA and PTP1B protein, and in-vitro assays demonstrated that loss of PTP1B function was associated with impaired negative regulation of type 1 IFN signalling.&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;em&gt;PTPN1&lt;/em&gt; haploinsufficiency causes a type 1 IFN-driven autoinflammatory encephalopathy. Notably, some patients demonstrated stabilisation, ","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"81 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451552","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":"Direct oral anticoagulants for cerebral venous thrombosis","authors":"Ana-Lucia Garcia Guarniz, Thalia S Field, Shadi Yaghi","doi":"10.1016/s1474-4422(25)00035-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00035-3","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462525","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":"Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study","authors":"Anita van de Munckhof, Mayte Sánchez van Kammen, Turgut Tatlisumak, Katarzyna Krzywicka, Sanjith Aaron, Florina Antochi, Antonio Arauz, Miguel A Barboza, Adriana B Conforto, Daniel Galdames Contreras, Mirjam R Heldner, Maria Hernández-Pérez, Sini Hiltunen, Xunming Ji, Wayneho Kam, Timothy J Kleinig, Espen S Kristoffersen, Ronen R Leker, Robin Lemmens, Sven Poli, Marialuisa Zedde","doi":"10.1016/s1474-4422(24)00519-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00519-2","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;There is an unmet need for high-quality data from prospective studies on the safety and effectiveness of direct oral anticoagulants (DOACs) for the treatment of cerebral venous thrombosis (CVT). We aimed to compare the safety and effectiveness of DOACs versus vitamin K antagonists (VKAs) for the treatment of CVT in a setting that reflects daily clinical practice.&lt;h3&gt;Methods&lt;/h3&gt;DOAC-CVT was an international, prospective, observational cohort study done in 65 hospitals in 23 countries across five continents. Eligible patients were adults (aged ≥18 years) with radiologically confirmed CVT starting oral anticoagulant treatment with either DOACs or VKAs, as per local practice, within 30 days after diagnosis. Exclusion criteria were previous use of anticoagulants at the time of CVT diagnosis or an absolute contraindication to DOACs (eg, pregnancy and lactation, or severe renal or liver disease). Data were collected during routine clinical visits or telephone consultations at CVT diagnosis (baseline) and at 3 months, 6 months, and 12 months after CVT diagnosis. The primary endpoint was a composite of symptomatic venous thromboembolism and major bleeding events (International Society on Thrombosis and Haemostasis criteria) at 6 months. Main outcomes were adjusted for the confounders age, renal function, active cancer, CNS infections, concomitant antiplatelet use, country of inclusion's income status, Glasgow Coma Scale score, intracranial haemorrhage, antiphospholipid antibodies, previous major bleeding, and previous venous thromboembolism using inverse probability-of-treatment weighting. This study is registered at &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt; (&lt;span&gt;&lt;span&gt;NCT04660747&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;) and is ongoing.&lt;h3&gt;Findings&lt;/h3&gt;Between Jan 27, 2021, and Jan 15, 2024, 619 patients were included; 401 (65%) patients started DOAC treatment, and 218 (35%) patients started VKA treatment. 390 (63%) of 619 patients were female and 229 (37%) of 619 patients were male. Patients’ median age was 41 years (IQR 28–51). 6-month follow-up data were available for 617 (&gt;99%) of 619 patients. 12 (3%) of 401 patients in the DOAC group and seven (3%) of 218 patients in the VKA group had a primary outcome event (weighted odds ratio [OR] 0·99 [95% CI 0·37–3·38]). Three (1%) of 401 patients in the DOAC group died versus three (1%) of 218 patients in the VKA group (weighted OR 0·55 [95% CI 0·11–2·80]).&lt;h3&gt;Interpretation&lt;/h3&gt;The rate of recurrent thrombosis and major bleeding did not differ between patients with CVT treated with DOACs versus VKAs. This study adds to","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451490","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":"Maria Trojano: advocate for real-world multiple sclerosis studies","authors":"Udani Samarasekera","doi":"10.1016/s1474-4422(25)00043-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00043-2","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451481","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":"For brain health, one drink a day is not better than none","authors":"Sanjula D Singh, Jasper R Senff, Christopher D Anderson, Jonathan Rosand","doi":"10.1016/s1474-4422(25)00028-6","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00028-6","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451482","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":"Thank you to The Lancet Neurology's peer reviewers in 2024","authors":"","doi":"10.1016/s1474-4422(25)00042-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00042-0","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451633","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":"The unyielding voice: the story of Celine Dion","authors":"Rui Araújo","doi":"10.1016/s1474-4422(24)00455-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00455-1","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451485","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}