Corti Stefania, Ottoboni Linda, Sansone Valeria
Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), Università Degli Studi Di Milano, Milan, Italy.
SC Neurology Unit, Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
J Neurol. 2025 Sep 2;272(9):605. doi: 10.1007/s00415-025-13314-7.
With the advent of survival motor neuron (SMN)-enhancing therapies, the natural course of spinal muscular atrophy (SMA) has been reshaped, unveiling new patient phenotypes. As therapeutic options expand, there is an increasing demand for robust biomarkers to enhance prognostic accuracy, anticipate treatment response, track disease progression, and support personalized clinical decision-making. This narrative review critically examines the literature and discusses the role and appropriate application of key biomarkers across different age groups, ranging from presymptomatic newborns to adults with chronic disease. Genetic testing remains the diagnostic gold standard, with SMN2 copy number serving as the strongest prognostic indicator. However, substantial phenotypic variability exists among individuals with the same SMN2 copy number. Neurophysiological measures, including compound muscle action potential (CMAP) and motor unit number estimation (MUNE), accurately inform about motor neuron integrity, often anticipating clinical changes and potentially predicting treatment responsiveness. Circulating neurofilaments (NF) are increasingly recognized as sensitive biomarkers of active neurodegeneration. While NF holds promise in infants and younger children, its relevance in adolescents and adults remains limited. Conversely, quantitative muscle imaging techniques, such as MRI and ultrasound, may be valuable tools in adolescent and adult patients, capturing long-term muscle structural changes. By reviewing the current evidence across age groups, we provide an overview of biomarker application in newborns, children and adolescents/adults for diagnostic, prognostic, predictive, and monitoring purposes to help advance individualized management across all SMA stages.
随着存活运动神经元（SMN）增强疗法的出现，脊髓性肌萎缩症（SMA）的自然病程已被重塑，展现出了新的患者表型。随着治疗选择的不断扩展，对强大的生物标志物的需求日益增加，以提高预后准确性、预测治疗反应、追踪疾病进展并支持个性化临床决策。这篇叙述性综述批判性地审视了相关文献，并讨论了关键生物标志物在不同年龄组（从无症状新生儿到患有慢性疾病的成年人）中的作用及适当应用。基因检测仍然是诊断的金标准，SMN2拷贝数是最强的预后指标。然而，具有相同SMN2拷贝数的个体之间存在显著的表型差异。神经生理学测量，包括复合肌肉动作电位（CMAP）和运动单位数量估计（MUNE），能够准确反映运动神经元的完整性，常常先于临床变化并可能预测治疗反应性。循环神经丝（NF）越来越被认为是活跃神经退行性变的敏感生物标志物。虽然NF在婴儿和年幼儿童中具有应用前景，但其在青少年和成年人中的相关性仍然有限。相反，定量肌肉成像技术，如MRI和超声，可能是青少年和成年患者的有价值工具，可捕捉长期的肌肉结构变化。通过回顾各年龄组的现有证据，我们概述了生物标志物在新生儿、儿童和青少年/成年人中的诊断、预后、预测和监测应用，以帮助推进所有SMA阶段的个体化管理。
