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.

对肌萎缩侧索硬化症 （ALS） 和额颞叶痴呆之间的表型和生物学重叠的日益认识，以及不断发展的疾病症状前阶段的生物标志物证据以及观察到这个疾病阶段可能并不总是临床上无声的，正在挑战对这些疾病的传统看法。这些进展突出了调整这些临床综合征的根深蒂固的概念的必要性，以包括完整的表型连续体 - 从临床无症状到前驱，再到临床表现 - 以及包括ALS，额颞叶痴呆和一些运动障碍在内的扩展表型谱。更新后的临床范式还应与我们对这些疾病生物学的理解保持一致，反映在可测量的生物标志物中。迈阿密框架是在迈阿密举行的第二届国际症状前肌萎缩侧索硬化症研讨会（2023 年 2 月;与会者及其隶属关系的完整名单见补充信息）的讨论中提出的，它提出了一个基于以下基础的分类系统：首先，三个平行的表型轴——运动神经元、额颞叶和锥体外系——而不是将所有表型元素组合成一个临床实体的单一方法;其次，反映神经退行性病变潜在病理学和生物学不同方面的生物标志物。该框架将临床综合征与疾病的生物标志物证据分离，并建立在其他神经退行性疾病的经验之上，提供了一种统一的方法来指定疾病的多效性临床表现和描述新兴生物标志物的轨迹。