Neurosciences Research Australia, Randwick, Sydney, Australia.
J Pediatr. 2013 Jan;162(1):155-9. doi: 10.1016/j.jpeds.2012.05.067. Epub 2012 Jul 17.
To examine the natural history of spinal muscular atrophy (SMA) to gain further insight into the clinical course and pathogenesis.
Survival pattern, age of onset, and ambulatory status were retrospectively analyzed in 70 patients with SMA with deletions of the survival motor neuron 1 genes that presented to a specialized neuromuscular clinic. The Kaplan-Meier method was used to obtain survival curves. Hammersmith Functional Motor Scale-Expanded and abductor pollicis brevis compound muscle action potential amplitudes were assessed in 25 of the surviving cohort and correlated with survival motor neuron 2 copy number.
Survival probabilities at ages 1, 2, 4, 10, 20, and 40 years were 40%, 25%, 6%, and 0%, respectively, for patients with SMA type 1; 100%, 100%, 97%, 93%, 93%, and 52% for patients with SMA type 2 and all patients with SMA type 3 were alive (age range 7-33 years). There were significant associations between age of onset and long-term outcome, specifically survival in SMA type 1 (P < .01) and Hammersmith Functional Motor Scale-Expanded (P < .0001), and compound muscle action potential (P = .001) in SMA types 2 and 3. Motor function in patients with long-standing SMA reduced over prolonged periods or remained stable. Survival motor neuron 2 copy number related to continuing changes in motor function with age.
The natural history of SMA suggests considerable early loss of motor neurons, with severity related to differences in the number of remaining motor neurons. As the ensuing chronic course in milder phenotypes suggests relative stability of remaining motor neurons, the maximal therapeutic window presents early.
研究脊髓性肌萎缩症（SMA）的自然病史，以进一步了解其临床过程和发病机制。
对 70 例生存运动神经元 1 基因缺失的 SMA 患者的生存模式、发病年龄和步行状态进行回顾性分析，这些患者曾在专门的神经肌肉诊所就诊。使用 Kaplan-Meier 法获得生存曲线。对存活队列中的 25 例患者进行了 Hammersmith 功能性运动量表扩展和拇短展肌复合肌肉动作电位幅度的评估，并与运动神经元 2 拷贝数相关。
1 岁、2 岁、4 岁、10 岁、20 岁和 40 岁时 SMA 1 型患者的生存率分别为 40%、25%、6%和 0%；SMA 2 型患者的生存率为 100%、100%、97%、93%、93%和 52%，所有 SMA 3 型患者均存活（年龄范围为 7-33 岁）。发病年龄与长期预后，特别是 SMA 1 型患者的生存率（P<0.01）和 Hammersmith 功能性运动量表扩展（P<0.0001）以及 SMA 2 型和 3 型的复合肌肉动作电位（P=0.001）有显著相关性。长期 SMA 患者的运动功能随着时间的推移而逐渐下降或保持稳定。运动神经元 2 拷贝数与年龄相关的运动功能变化有关。
SMA 的自然病史表明早期运动神经元大量丢失，严重程度与剩余运动神经元数量的差异有关。由于轻度表型的后续慢性病程表明剩余运动神经元相对稳定，因此最大的治疗窗口较早出现。
