Risk Factors and Prediction of Chronic Postsurgical Pain Among Patients With Distal Lower Extremity Fracture: Cohort Analysis.

Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous neuromuscular disorder (NMD) characterized by reduced levels of the survival motor neuron (SMN) protein, leading to the loss of spinal and bulbar motor neurons (MNs) and muscle mass. While severe early-onset forms (Type I) are mechanistically well-characterized, the pathomechanisms underlying late-onset forms, such as SMA Type III, remain poorly understood. Spinal muscular atrophy (SMA) was historically divided into five clinical types (0–IV) based on symptom onset and the highest motor milestone achieved. This pre-therapy classification reflected the natural disease range from severe prenatal (Type 0) to mild adult-onset (Type IV) forms. With SMN-enhancing treatments and newborn screening, these categories have become less predictive, as early treated patients often surpass expected milestones. Disease severity now correlates more with copy number, treatment timing, and achieved motor function. Similarly, the expanding therapeutic landscape and phenotypic variability call for re-evaluating how we classify and choose SMA mouse models for specific research aims. Importantly, although SMN-enhancing therapies, including antisense oligonucleotides (nusinersen), small molecules (risdiplam), and gene addition therapy (onasemnogene abeparvovec), have markedly improved patient outcomes, individuals with late-onset SMA often experience only partial motor recovery. Nevertheless, improvements in less quantifiable aspects, such as daily functioning and quality of life, remain highly meaningful for patients.