TY - JOUR
T1 - The Miami Framework for ALS and related neurodegenerative disorders
T2 - an integrated view of phenotype and biology
AU - Attendees of the Second International Pre-Symptomatic ALS Workshop
AU - Benatar, Michael
AU - Wuu, Joanne
AU - Huey, Edward D.
AU - McMillan, Corey T.
AU - Petersen, Ronald C.
AU - Postuma, Ronald
AU - McHutchison, Caroline
AU - Dratch, Laynie
AU - Arias, Jalayne J.
AU - Crawley, Anita
AU - Houlden, Henry
AU - McDermott, Michael P.
AU - Cai, Xueya
AU - Thakur, Neil
AU - Boxer, Adam
AU - Rosen, Howard
AU - Boeve, Bradley F.
AU - Dacks, Penny
AU - Cosentino, Stephanie
AU - Abrahams, Sharon
AU - Shneider, Neil
AU - Lingor, Paul
AU - Shefner, Jeremy
AU - Andersen, Peter M.
AU - Al-Chalabi, Ammar
AU - Turner, Martin R.
AU - Zinman, Lorne
AU - Weydt, Patrick
AU - Uspenskaya, Olga
AU - Thompson, Alexander
AU - Stanislaw, Christine
AU - Mozaffar, Tahseen
AU - Levy, Oren
AU - Lewis, Travis
AU - Lawrence, Karen
AU - Hesterlee, Sharon
AU - Heiman-Patterson, Terry
AU - Harms, Matthew
AU - Gubitz, Amelie
AU - Grignon, Anne Laure
AU - Granit, Volkan
AU - Fradette, Stephanie
AU - Dave, Kuldip
AU - Champney, Thomas
AU - Caress, James
AU - Carberry, Nathan
AU - Buczyner, Jennifer
AU - Bruijn, Lucie
AU - Bradbury, Meg
AU - Appel, Stanley
N1 - Publisher Copyright:
© Springer Nature Limited 2024. corrected publication 2024.
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
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U2 - 10.1038/s41582-024-00961-z
DO - 10.1038/s41582-024-00961-z
M3 - Article
C2 - 38769202
AN - SCOPUS:85195328165
SN - 1759-4758
VL - 20
SP - 364
EP - 376
JO - Nature Reviews Neurology
JF - Nature Reviews Neurology
IS - 6
ER -