233例肌萎缩侧索硬化患者起病部位与顺序的临床研究

发布时间：2018-09-08 21:25

【摘要】：背景:肌萎缩侧索硬化(Amyotrophic Lateral Sclerosis,以下简称ALS)是一种累及上运动神经元和下运动神经元的神经系统变性疾病,临床首发症状通常为某一局部或某个肢体受累,逐渐影响四肢、球部以及呼吸肌,也有少数患者首发症状为球部受累,表现为构音障碍、饮水呛咳及吞咽困难等。有关起病部位和顺序的研究国外虽有报告,但国内在起病顺序方面的研究相对较少。目的:通过对北京协和医院诊治的233例散发型ALS患者的数据进行分析,探索散发型ALS患者起病部位和顺序的临床特点及与生存预后的关系。方法:本研究收集了 2013年12月到2016年12月在北京协和医院神经科诊治的233名ALS患者的性别、起病年龄、发病到确诊时间、就诊时ALSFRS-R量表评分、起病顺序等信息,每年进行至少1次电话随访评估生存情况直至死亡或者气管切开,使用Kaplan-Meier分析法和Cox回归分析对生存数据进行统计。结果:233例ALS患者男女比例1.38:1,平均起病年龄52.6±10.7岁,发病至确诊平均时间为14.4±8.1个月,中位时间为12个月。起病部位方面,球部、上肢(颈段)、下肢(腰段)起病患者比例分别为24.5%、51.9%、23.6%;不同起病部位患者在生存预后上差异无统计学意义。肢体起病患者第二进展部位以对侧肢体为主,比例为56.2%(上肢起病)/69.1%(下肢起病);在上肢起病患者中,性别对第二进展部位有影响(p0.05),第二进展部位为球部的患者预后最差。起病顺序方面,连续型(进展至相邻功能区)和跳跃型(进展至非相邻功能区)患者比例分别为90.1%和9.9%,连续型起病患者中比例由高到低依次为球颈腰型(21.5%)、颈腰球型(21.0%)、腰颈球型(17.6%)、肢体折返型(指受累顺序为单侧上/下肢→相邻功能区→对侧上/下肢)(15.5%)、颈球腰型(14.6%),跳跃型起病患者中比例由高到低依次为肢体交叉型(指受累顺序为单侧上肢→对侧下肢或相反)(5.6%)、球腰型(3.0%)、腰球型(1.3%);连续型和跳跃型起病患者在生存预后上的差异无统计学意义;连续型起病患者中,颈腰球型患者预后最好,颈球腰型患者预后最差,二者差异具有统计学意义(p=0.044),校正起病年龄、发病到确诊时间、性别因素后颈球腰型患者死亡风险为颈腰球型的2.76倍(p=0.031),球颈腰型、腰颈球型、肢体折返型患者预期生存期介于上述二者之间,差异无统计学意义。在Cox回归分析中,对预后有影响的因素还包括起病年龄、发病到确诊时间、疾病进展率(从发病到就诊期间每月ALSFRS-R量表评分下降的平均值),未观察到性别对生存预后的影响。结论:1.不同起病部位患者在生存时间上的差异无统计学意义;2.肢体起病患者第二进展部位以对侧肢体最常见;3.起病顺序以连续型模式最多,连续型和跳跃型起病患者在生存时间上的差异无统计学意义,连续型起病模式中颈球腰型患者预后最差,颈腰球型预后最好,二者差异有统计学意义;4.起病年龄越大、发病到确诊时间越短、疾病早期ALSFRS-R评分下降速度越快患者的死亡风险越高。
[Abstract]:BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder involving both upper and lower motor neurons. The first clinical symptom is usually a local or a limb involvement that gradually affects the extremities, bulbs, and respiratory muscles. In a few patients, the first symptom is the bulb. Objective: To analyze the data of 233 sporadic ALS patients treated in Peking Union Medical College Hospital, and to explore the onset site and sequence of sporadic ALS patients. Methods: From December 2013 to December 2016, 233 patients with ALS in the Department of Neurology, Peking Union Medical College Hospital were collected for sex, onset age, onset time, ALSFRS-R score, onset order and so on. The survival data were analyzed by Kaplan-Meier analysis and Cox regression analysis until death or tracheotomy. Results: The male-female ratio of 233 patients with ALS was 1.38:1, the average age of onset was 52.6+10.7 years, the average time from onset to diagnosis was 14.4+8.1 months, and the median time was 12 months. The incidence of lumbar disease was 24.5%, 51.9% and 23.6% respectively. There was no significant difference in survival and prognosis between patients with different onset sites. The prognosis of the patients with the second progressive site was the worst. Type I (referring to unilateral upper/lower extremities adjacent functional areas contralateral upper/lower extremities) (15.5%), Cervical-Lumbar type (14.6%) and jumping type (from high to low) were in the order of limb crossing type (referring to unilateral upper extremities contralateral lower extremities or the contrary) (5.6%), ball-lumbar type (3.0%) and lumbar type (1.3%); continuous type and jumping type (1.3%). There was no significant difference in survival and prognosis between patients with continuous onset of Cervical-Lumbar type and those with continuous onset of Cervical-Lumbar type. In Cox regression analysis, the factors influencing prognosis included age at onset, time from onset to diagnosis, and disease progression rate (mean monthly decrease in ALSFRS-R scores from onset to consultation). Conclusion: 1. There was no significant difference in survival time between patients with different onset sites; 2. Contralateral limbs were the most common site of secondary progression in patients with limb onset; 3. The sequence of onset was the most continuous type; and there was no significant difference in survival time between patients with continuous and jumping onset. In the continuous onset model, the prognosis of patients with Cervical-Lumbar type was the worst, and the prognosis of patients with Cervical-Lumbar type was the best, the difference was statistically significant; 4. The older the onset age, the shorter the time from onset to diagnosis, the higher the risk of death of patients with ALSFRS-R score decreased faster in the early stage of disease.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R744.8

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