[Analysis of disease progression rate and related factors in amyotrophic lateral sclerosis patients at initial visit].

Objective: To find out the relationship of the progression rate of amyotrophic lateral sclerosis (ALS) patients with relevant clinical indicators at initial visit so as to enrich the knowledge of ALS at its early stage. Methods: The clinical data of 282 patients diagnosed with ALS at Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to March 2021 were collected in order to make a retrospective analysis of the dynamic change of the progression rate (ΔFS) and influencing factors, and thus a classification of the progression rate will be summarized. Results: Among 282 patients, 164 were males and 118 were females. The age of onset was (53±11) years old. The ΔFS had a negative exponential relationship with delay time of diagnosis no matter what kinds of onset the patients experienced (upper limb onset, lower limb onset or bulbar onset). The ΔFS for the limb function sub-group had a similar functional relationship with diagnostic delay in patients with either upper limb onset or lower limb onset. The statistical model indicated that the disease progression rate of ALS at initial visit can be classified into three types (high speed type: ΔFS≥1.0 score/month; moderate speed type: 0.5≤ΔFS<1.0 score/month; low speed type: ΔFS<0.5 score/month). The critical values of the three types in patients with upper limb onset were 8 and 20 months, while 9 and 24 months for lower limb onset patients, and 9 and 36 months for bulbar onset patients. At initial visit, there were significant statistical differences among these three types in age at onset (P=0.008), diagnostic delay (P<0.001), ALS functional rating scale-revised (ALSFRS-R) score (P<0.001) and onset site (P=0.006). The age at onset in moderate speed type was significantly greater than that of the slow speed type [(54.9±10.4) years vs (50.2±9.6) years, P=0.002]. The diagnostic delay in high speed type [6 (4, 10) months] was significantly shorter than that in moderate speed type [12 (8, 19) months, P<0.001] and low speed type [22 (14, 36) months, P<0.001], and the moderate speed type was shorter in comparison with low speed type (P<0.001). As for the ALSFRS-R score, the high speed type [36(32, 39)] was significantly lower than the moderate speed type [39 (36, 42), P<0.001] and low speed type [42 (39, 44), P<0.001], and the moderate speed type was lower in comparison with low speed type (P=0.002). The proportion of cases with upper limb onset in high speed type (20.3%) was significantly lower than that in low speed type (42.2%, P<0.001) and moderate speed type (37.5%, P=0.014). By contrast, the proportion of cases with lower limb onset in high speed type (39.2%) was significantly higher than that in low speed type (28.9%, P=0.023), however no difference was shown between the fast speed type and moderate speed type (32.0%, P=0.061). There was no difference among these three progression types in patients with bulbar onset. Conclusions: The disease progression rate of ALS at initial visit can be classified into three types including high speed, moderate speed and low speed. At early stage of ALS, ΔFS is affected by onset age, onset site, diagnostic delay and ALSFRS-R score.目的： 探讨肌萎缩侧索硬化（ALS）患者初次就诊时病情进展速率与临床指标的关系，提高对ALS早期疾病特点的认识。 方法： 收集解放军总医院第一医学中心神经内科在2016年6月至2021年3月的282例ALS患者的资料，总结疾病进展速率的主要类型，分析疾病进展速率（ΔFS）的特点及主要影响因素。 结果： 282例患者中，男164例，女118例，发病年龄（53±11）岁。无论是上肢、下肢或球部起病，ΔFS与诊断延迟病程之间均满足非线性指数函数关系；上肢和下肢起病的运动功能亚组ΔFS与诊断延迟病程满足相同的函数关系。统计模型揭示在初次就诊时，可将ALS分为快速（ΔFS≥1.0分/月）、中速（ΔFS<1.0~≥0.5分/月）和慢速（ΔFS<0.5分/月）三种进展类型，上肢、下肢和球部起病的界值分别为发病8个月和20个月、9个月和24个月以及9个月和36个月。初次就诊时，发病年龄（P=0.008）、诊断延迟病程（P<0.001）、临床功能评分（ALSFRS-R）（P<0.001）、发病部位（P=0.006）在不同进展型患者间差异有统计学意义。中速进展型发病年龄明显高于慢速进展型［（54.9±10.4）岁比（50.2±9.6）岁，P=0.002］。在诊断延迟病程上，快速进展型［M （Q1， Q3），6（4，10）月］明显短于中速进展型［12（8，19）月，P<0.001］和慢速进展型［22（14，36）月，P<0.001）］，中速进展型明显短于慢速进展型（P<0.001）。ALSFRS-R指标中快速进展型［36（32，39）分］明显低于中速进展型［39（36，42）分，P<0.001］和慢速进展型［42（39，44）分，P<0.001］，中速进展型则明显低于慢速进展型（P=0.002）。在上肢起病患者比例中，快速进展型（20.3%）显著低于慢速进展型（42.2%，P<0.001）和中速进展型（37.5%，P=0.014）。相反，在下肢起病患者比例中，快速进展型（39.2%）则显著高于慢速进展型（28.9%，P=0.023），但与中速进展型（32.0%，P=0.061）没有差异。不同进展型球部起病患者比例比较差异无统计学意义（均P>0.05）。 结论： 初次就诊时，ALS可分为快速、中速和慢速三种进展类型。在ALS早期，ΔFS受发病年龄、起病部位、诊断延迟病程和临床功能评分的影响。.