Michael Benatar, Joanne Wuu, Edward D. Huey, Corey T. McMillan, Ronald C. Petersen, Ronald Postuma, Caroline McHutchison, Laynie Dratch, Jalayne J. Arias, Anita Crawley, Henry Houlden, Michael P. McDermott, Xueya Cai, Neil Thakur, Adam Boxer, Howard Rosen, Bradley F. Boeve, Penny Dacks, Stephanie Cosentino, Sharon Abrahams, Neil Shneider, Paul Lingor, Jeremy Shefner, Peter M. Andersen, Ammar Al-Chalabi, Martin R. Turner, Attendees of the Second International Pre-Symptomatic ALS Workshop
{"title":"The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology","authors":"Michael Benatar, Joanne Wuu, Edward D. Huey, Corey T. McMillan, Ronald C. Petersen, Ronald Postuma, Caroline McHutchison, Laynie Dratch, Jalayne J. Arias, Anita Crawley, Henry Houlden, Michael P. McDermott, Xueya Cai, Neil Thakur, Adam Boxer, Howard Rosen, Bradley F. Boeve, Penny Dacks, Stephanie Cosentino, Sharon Abrahams, Neil Shneider, Paul Lingor, Jeremy Shefner, Peter M. Andersen, Ammar Al-Chalabi, Martin R. Turner, Attendees of the Second International Pre-Symptomatic ALS Workshop","doi":"10.1038/s41582-024-00961-z","DOIUrl":null,"url":null,"abstract":"Increasing appreciation of the phenotypic and biological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, alongside evolving biomarker evidence for a pre-symptomatic stage of disease and observations that this stage of disease might not always be clinically silent, is challenging traditional views of these disorders. These advances have highlighted the need to adapt ingrained notions of these clinical syndromes to include both the full phenotypic continuum — from clinically silent, to prodromal, to clinically manifest — and the expanded phenotypic spectrum that includes ALS, frontotemporal dementia and some movement disorders. The updated clinical paradigms should also align with our understanding of the biology of these disorders, reflected in measurable biomarkers. The Miami Framework, emerging from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023; a full list of attendees and their affiliations appears in the Supplementary Information) proposes a classification system built on: first, three parallel phenotypic axes — motor neuron, frontotemporal and extrapyramidal — rather than the unitary approach of combining all phenotypic elements into a single clinical entity; and second, biomarkers that reflect different aspects of the underlying pathology and biology of neurodegeneration. This framework decouples clinical syndromes from biomarker evidence of disease and builds on experiences from other neurodegenerative diseases to offer a unified approach to specifying the pleiotropic clinical manifestations of disease and describing the trajectory of emergent biomarkers. In this Perspective, the authors propose a new classification system for amyotrophic lateral sclerosis and related neurodegenerative disorders that recognizes, in parallel, the clinical syndromes and the underlying biology of disease. The framework emerged from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023).","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 6","pages":"364-376"},"PeriodicalIF":28.2000,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Neurology","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41582-024-00961-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Increasing appreciation of the phenotypic and biological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, alongside evolving biomarker evidence for a pre-symptomatic stage of disease and observations that this stage of disease might not always be clinically silent, is challenging traditional views of these disorders. These advances have highlighted the need to adapt ingrained notions of these clinical syndromes to include both the full phenotypic continuum — from clinically silent, to prodromal, to clinically manifest — and the expanded phenotypic spectrum that includes ALS, frontotemporal dementia and some movement disorders. The updated clinical paradigms should also align with our understanding of the biology of these disorders, reflected in measurable biomarkers. The Miami Framework, emerging from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023; a full list of attendees and their affiliations appears in the Supplementary Information) proposes a classification system built on: first, three parallel phenotypic axes — motor neuron, frontotemporal and extrapyramidal — rather than the unitary approach of combining all phenotypic elements into a single clinical entity; and second, biomarkers that reflect different aspects of the underlying pathology and biology of neurodegeneration. This framework decouples clinical syndromes from biomarker evidence of disease and builds on experiences from other neurodegenerative diseases to offer a unified approach to specifying the pleiotropic clinical manifestations of disease and describing the trajectory of emergent biomarkers. In this Perspective, the authors propose a new classification system for amyotrophic lateral sclerosis and related neurodegenerative disorders that recognizes, in parallel, the clinical syndromes and the underlying biology of disease. The framework emerged from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023).
期刊介绍:
Nature Reviews Neurology aims to be the premier source of reviews and commentaries for the scientific and clinical communities we serve. We want to provide an unparalleled service to authors, referees, and readers, and we work hard to maximize the usefulness and impact of each article. The journal publishes Research Highlights, Comments, News & Views, Reviews, Consensus Statements, and Perspectives relevant to researchers and clinicians working in the field of neurology. Our broad scope ensures that the work we publish reaches the widest possible audience. Our articles are authoritative, accessible, and enhanced with clearly understandable figures, tables, and other display items. This page gives more detail about the aims and scope of the journal.