Pub Date : 2024-04-12DOI: 10.1038/s41582-024-00955-x
Michael Khalil, Charlotte E. Teunissen, Sylvain Lehmann, Markus Otto, Fredrik Piehl, Tjalf Ziemssen, Stefan Bittner, Maria Pia Sormani, Thomas Gattringer, Samir Abu-Rumeileh, Simon Thebault, Ahmed Abdelhak, Ari Green, Pascal Benkert, Ludwig Kappos, Manuel Comabella, Hayrettin Tumani, Mark S. Freedman, Axel Petzold, Kaj Blennow, Henrik Zetterberg, David Leppert, Jens Kuhle
Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice. Neurofilaments have been validated as specific body fluid biomarkers of neuro-axonal injury. In this Review, Khalil and colleagues provide an update on the structure and function of neurofilaments, analytical approaches and challenges in different clinical contexts, and progress towards clinical application of neurofilaments as a biomarker in various neurological disorders.
{"title":"Neurofilaments as biomarkers in neurological disorders — towards clinical application","authors":"Michael Khalil, Charlotte E. Teunissen, Sylvain Lehmann, Markus Otto, Fredrik Piehl, Tjalf Ziemssen, Stefan Bittner, Maria Pia Sormani, Thomas Gattringer, Samir Abu-Rumeileh, Simon Thebault, Ahmed Abdelhak, Ari Green, Pascal Benkert, Ludwig Kappos, Manuel Comabella, Hayrettin Tumani, Mark S. Freedman, Axel Petzold, Kaj Blennow, Henrik Zetterberg, David Leppert, Jens Kuhle","doi":"10.1038/s41582-024-00955-x","DOIUrl":"10.1038/s41582-024-00955-x","url":null,"abstract":"Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice. Neurofilaments have been validated as specific body fluid biomarkers of neuro-axonal injury. In this Review, Khalil and colleagues provide an update on the structure and function of neurofilaments, analytical approaches and challenges in different clinical contexts, and progress towards clinical application of neurofilaments as a biomarker in various neurological disorders.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 5","pages":"269-287"},"PeriodicalIF":38.1,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550531","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 : 2024-04-12DOI: 10.1038/s41582-024-00960-0
Lisa Kiani
Nature Reviews Neurology is interviewing individuals who are driving efforts to address disparities in neurology through a broad spectrum of diversity, equity and inclusion initiatives. We spoke with neurosurgeon Sonia Mejía Pérez from Mexico about her work to address gaps in hospital care for individuals from minority groups, such as LGBT+ people.
{"title":"Addressing disparities in neurology by identifying gaps in hospital care","authors":"Lisa Kiani","doi":"10.1038/s41582-024-00960-0","DOIUrl":"10.1038/s41582-024-00960-0","url":null,"abstract":"Nature Reviews Neurology is interviewing individuals who are driving efforts to address disparities in neurology through a broad spectrum of diversity, equity and inclusion initiatives. We spoke with neurosurgeon Sonia Mejía Pérez from Mexico about her work to address gaps in hospital care for individuals from minority groups, such as LGBT+ people.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 5","pages":"253-254"},"PeriodicalIF":38.1,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547573","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 : 2024-04-10DOI: 10.1038/s41582-024-00959-7
Heather Wood
New data recently reported at the ACTRIMS Forum add to growing evidence of an aetiological role for Epstein–Barr virus infection in multiple sclerosis.
{"title":"EBV-specific T cells in multiple sclerosis","authors":"Heather Wood","doi":"10.1038/s41582-024-00959-7","DOIUrl":"10.1038/s41582-024-00959-7","url":null,"abstract":"New data recently reported at the ACTRIMS Forum add to growing evidence of an aetiological role for Epstein–Barr virus infection in multiple sclerosis.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 5","pages":"255-255"},"PeriodicalIF":38.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140541409","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 : 2024-04-10DOI: 10.1038/s41582-024-00958-8
Heather Wood
Findings of phase III trials of the Bruton’s tyrosine kinase inhibitor evobrutinib in patients with relapsing multiple sclerosis were recently presented at the ACTRIMS Forum.
布鲁顿酪氨酸激酶抑制剂 evobrutinib 用于复发性多发性硬化症患者的 III 期试验结果最近在 ACTRIMS 论坛上公布。
{"title":"BTK inhibitor falters in multiple sclerosis trials","authors":"Heather Wood","doi":"10.1038/s41582-024-00958-8","DOIUrl":"10.1038/s41582-024-00958-8","url":null,"abstract":"Findings of phase III trials of the Bruton’s tyrosine kinase inhibitor evobrutinib in patients with relapsing multiple sclerosis were recently presented at the ACTRIMS Forum.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 5","pages":"255-255"},"PeriodicalIF":38.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140541232","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 : 2024-04-05DOI: 10.1038/s41582-024-00956-w
Martijn P. van den Heuvel, Sara L. Seoane
A computational neuroimaging study has shed new light on the relationship between morphological changes in the brain in schizophrenia and the network architecture of the brain, providing evidence to support two network theories of the disorder.
{"title":"Support for network theories of schizophrenia","authors":"Martijn P. van den Heuvel, Sara L. Seoane","doi":"10.1038/s41582-024-00956-w","DOIUrl":"10.1038/s41582-024-00956-w","url":null,"abstract":"A computational neuroimaging study has shed new light on the relationship between morphological changes in the brain in schizophrenia and the network architecture of the brain, providing evidence to support two network theories of the disorder.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 7","pages":"381-382"},"PeriodicalIF":28.2,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349578","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 : 2024-04-04DOI: 10.1038/s41582-024-00951-1
In this issue of Nature Reviews Neurology, we launch a Series to highlight the importance of diversity, equity and inclusion in efforts to improve global brain health. This month, Nature Reviews Neurology launches a Series to highlight the importance of diversity, equity and inclusion in the neurology community and in neurological care to address health disparities and thereby to improve global brain health.
{"title":"Diversity, equity and inclusion in neurology","authors":"","doi":"10.1038/s41582-024-00951-1","DOIUrl":"10.1038/s41582-024-00951-1","url":null,"abstract":"In this issue of Nature Reviews Neurology, we launch a Series to highlight the importance of diversity, equity and inclusion in efforts to improve global brain health. This month, Nature Reviews Neurology launches a Series to highlight the importance of diversity, equity and inclusion in the neurology community and in neurological care to address health disparities and thereby to improve global brain health.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 4","pages":"199-199"},"PeriodicalIF":38.1,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41582-024-00951-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140345842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-04DOI: 10.1038/s41582-024-00952-0
Lisa Kiani
Nature Reviews Neurology is interviewing individuals who are driving efforts to address disparities in neurology through a broad spectrum of diversity, equity and inclusion initiatives. We spoke with stroke neurologist Nirali Vora from the USA about her work to build neurology capacity in low and middle-income countries.
{"title":"Addressing disparities in neurology by building the workforce in LMICs","authors":"Lisa Kiani","doi":"10.1038/s41582-024-00952-0","DOIUrl":"10.1038/s41582-024-00952-0","url":null,"abstract":"Nature Reviews Neurology is interviewing individuals who are driving efforts to address disparities in neurology through a broad spectrum of diversity, equity and inclusion initiatives. We spoke with stroke neurologist Nirali Vora from the USA about her work to build neurology capacity in low and middle-income countries.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 4","pages":"200-201"},"PeriodicalIF":38.1,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41582-024-00952-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140345870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-03DOI: 10.1038/s41582-024-00954-y
Matthew Pease, Kunal Gupta, Solomon L. Moshé, Daniel J. Correa, Aristea S. Galanopoulou, David O. Okonkwo, Jorge Gonzalez-Martinez, Lori Shutter, Ramon Diaz-Arrastia, James F. Castellano
Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies. The incidence of PTE after traumatic brain injury (TBI) depends on the severity of injury, approaching one in three in groups with the most severe injuries. The repeated seizures that characterize PTE impair neurological recovery and increase the risk of poor outcomes after TBI. Given this high risk of recurrent seizures and the relatively short latency period for their development after injury, PTE serves as a model disease to understand human epileptogenesis and trial novel anti-epileptogenic therapies. Epileptogenesis is the process whereby previously normal brain tissue becomes prone to recurrent abnormal electrical activity, ultimately resulting in seizures. In this Review, we describe the clinical course of PTE and highlight promising research into epileptogenesis and treatment using animal models of PTE. Clinical, imaging, EEG and fluid biomarkers are being developed to aid the identification of patients at high risk of PTE who might benefit from anti-epileptogenic therapies. Studies in preclinical models of PTE have identified tractable pathways and novel therapeutic strategies that can potentially prevent epilepsy, which remain to be validated in humans. In addition to improving outcomes after TBI, advances in PTE research are likely to provide therapeutic insights that are relevant to all epilepsies. Post-traumatic epilepsy is a major driver of disability associated with traumatic brain injury. This article reviews the epidemiology and clinical features of post-traumatic epilepsy and discusses how an understanding of the underlying epileptogenic mechanisms might inform the development of anti-epileptogenic medications.
{"title":"Insights into epileptogenesis from post-traumatic epilepsy","authors":"Matthew Pease, Kunal Gupta, Solomon L. Moshé, Daniel J. Correa, Aristea S. Galanopoulou, David O. Okonkwo, Jorge Gonzalez-Martinez, Lori Shutter, Ramon Diaz-Arrastia, James F. Castellano","doi":"10.1038/s41582-024-00954-y","DOIUrl":"10.1038/s41582-024-00954-y","url":null,"abstract":"Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies. The incidence of PTE after traumatic brain injury (TBI) depends on the severity of injury, approaching one in three in groups with the most severe injuries. The repeated seizures that characterize PTE impair neurological recovery and increase the risk of poor outcomes after TBI. Given this high risk of recurrent seizures and the relatively short latency period for their development after injury, PTE serves as a model disease to understand human epileptogenesis and trial novel anti-epileptogenic therapies. Epileptogenesis is the process whereby previously normal brain tissue becomes prone to recurrent abnormal electrical activity, ultimately resulting in seizures. In this Review, we describe the clinical course of PTE and highlight promising research into epileptogenesis and treatment using animal models of PTE. Clinical, imaging, EEG and fluid biomarkers are being developed to aid the identification of patients at high risk of PTE who might benefit from anti-epileptogenic therapies. Studies in preclinical models of PTE have identified tractable pathways and novel therapeutic strategies that can potentially prevent epilepsy, which remain to be validated in humans. In addition to improving outcomes after TBI, advances in PTE research are likely to provide therapeutic insights that are relevant to all epilepsies. Post-traumatic epilepsy is a major driver of disability associated with traumatic brain injury. This article reviews the epidemiology and clinical features of post-traumatic epilepsy and discusses how an understanding of the underlying epileptogenic mechanisms might inform the development of anti-epileptogenic medications.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 5","pages":"298-312"},"PeriodicalIF":38.1,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343270","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 : 2024-04-03DOI: 10.1038/s41582-024-00957-9
Sylvia Boesch, Elisabetta Indelicato
The recent approval of omaveloxolone for the treatment of Friedreich ataxia in the USA and Europe represents an important milestone in the field of rare neurological diseases. However, many challenges lie ahead, including the translation of trial results into clinical practice, and the management of patients’ expectations.
{"title":"Approval of omaveloxolone for Friedreich ataxia","authors":"Sylvia Boesch, Elisabetta Indelicato","doi":"10.1038/s41582-024-00957-9","DOIUrl":"10.1038/s41582-024-00957-9","url":null,"abstract":"The recent approval of omaveloxolone for the treatment of Friedreich ataxia in the USA and Europe represents an important milestone in the field of rare neurological diseases. However, many challenges lie ahead, including the translation of trial results into clinical practice, and the management of patients’ expectations.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 6","pages":"313-314"},"PeriodicalIF":38.1,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343417","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 : 2024-04-03DOI: 10.1038/s41582-024-00953-z
Jesse Dawson, Azmil H. Abdul-Rahim, Teresa J. Kimberley
Neurostimulation, the use of electrical stimulation to modulate the activity of the nervous system, is now commonly used for the treatment of chronic pain, movement disorders and epilepsy. Many neurostimulation techniques have now shown promise for the treatment of physical impairments in people with stroke. In 2021, vagus nerve stimulation was approved by the FDA as an adjunct to intensive rehabilitation therapy for the treatment of chronic upper extremity deficits after ischaemic stroke. In 2024, pharyngeal electrical stimulation was conditionally approved by the UK National Institute for Health and Care Excellence for neurogenic dysphagia in people with stroke who have a tracheostomy. Many other approaches have also been tested in pivotal device trials and a number of approaches are in early-phase study. Typically, neurostimulation techniques aim to increase neuroplasticity in response to training and rehabilitation, although the putative mechanisms of action differ and are not fully understood. Neurostimulation techniques offer a number of practical advantages for use after stroke, such as precise dosing and timing, but can be invasive and costly to implement. This Review focuses on neurostimulation techniques that are now in clinical use or that have reached the stage of pivotal trials and show considerable promise for the treatment of post-stroke impairments. Various neurostimulation techniques are being explored for the treatment of physical impairments in people with stroke. This Review summarizes our current knowledge of the techniques that are now in clinical use or have reached the stage of pivotal trials alongside emerging techniques and highlights the need for further studies.
{"title":"Neurostimulation for treatment of post-stroke impairments","authors":"Jesse Dawson, Azmil H. Abdul-Rahim, Teresa J. Kimberley","doi":"10.1038/s41582-024-00953-z","DOIUrl":"10.1038/s41582-024-00953-z","url":null,"abstract":"Neurostimulation, the use of electrical stimulation to modulate the activity of the nervous system, is now commonly used for the treatment of chronic pain, movement disorders and epilepsy. Many neurostimulation techniques have now shown promise for the treatment of physical impairments in people with stroke. In 2021, vagus nerve stimulation was approved by the FDA as an adjunct to intensive rehabilitation therapy for the treatment of chronic upper extremity deficits after ischaemic stroke. In 2024, pharyngeal electrical stimulation was conditionally approved by the UK National Institute for Health and Care Excellence for neurogenic dysphagia in people with stroke who have a tracheostomy. Many other approaches have also been tested in pivotal device trials and a number of approaches are in early-phase study. Typically, neurostimulation techniques aim to increase neuroplasticity in response to training and rehabilitation, although the putative mechanisms of action differ and are not fully understood. Neurostimulation techniques offer a number of practical advantages for use after stroke, such as precise dosing and timing, but can be invasive and costly to implement. This Review focuses on neurostimulation techniques that are now in clinical use or that have reached the stage of pivotal trials and show considerable promise for the treatment of post-stroke impairments. Various neurostimulation techniques are being explored for the treatment of physical impairments in people with stroke. This Review summarizes our current knowledge of the techniques that are now in clinical use or have reached the stage of pivotal trials alongside emerging techniques and highlights the need for further studies.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 5","pages":"259-268"},"PeriodicalIF":38.1,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343341","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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