Cerebral degeneration predicts survival in amyotrophic lateral sclerosis

Cerebral degeneration predicts survival in amyotrophic lateral sclerosis
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脑退化预测肌萎缩侧索硬化症患者的生存

DOI:
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发表时间:
2006
影响因子:
11
通讯作者:
D. Arnold
D. Arnold
中科院分区:
医学1区
文献类型:
--
作者:
Sanjay Kalra;A. Vitale;Neil R. Cashman;A. Genge;D. Arnold

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目的:探讨肌萎缩侧索硬化(ALS)患者脑变性与生存的关系。研究方法:1996年7月至2002年5月,可能或确定的ALS患者接受了脑部磁共振波谱成像(MRSI),并前瞻性随访至2004年3月。肌酸(Cr),胆碱(Cho)和神经元标记物N-乙酰天冬氨酸(NAA)在运动皮层中的比例进行定量。结果:63例患者与18例健康人比较,NAA/Cho降低13%(p<0.001),NAA/Cr降低5%(p = 0.01),Cho/Cr升高8%(p = 0.01)。    NAA/Cho用于生存分析,因为它具有更大的效应量和更高的上级测试准确性(敏感性为67%,特异性为83%)。MRSI后的中位生存期为24个月。多变量分析显示,较低的NAA/Cho(风险比(HR)0.24,95%置信区间(CI)0.08至0.72,p = 0.01)、年龄较大(HR 1.03,95% CI 1.00至1.06,p = 0.04)和症状持续时间较短(HR 0.96,95% CI 0.93至0.99,p = 0.01)会降低生存率。      NAA/Cho <2.11的患者的生存期缩短为19.4个月vs 31.9个月(HR 2.05,95% CI 1.12至4.03,p = 0.02)。  结论:脑变性是ALS患者生存率降低的预测因素。
Objective: To determine the relationship of cerebral degeneration with survival in amyotrophic lateral sclerosis (ALS). Methods: Patients with probable or definite ALS underwent magnetic resonance spectroscopic imaging (MRSI) of the brain between July 1996 and May 2002, and were followed prospectively until March 2004. Creatine (Cr), choline (Cho) and the neuronal marker N-acetylaspartate (NAA) were quantified as ratios in the motor cortex. Results: In 63 patients compared with 18 healthy people, NAA/Cho was reduced by 13% (p<0.001), NAA/Cr was reduced by 5% (p = 0.01) and Cho/Cr was increased by 8% (p = 0.01). NAA/Cho was used for survival analysis, given its larger effect size and superior test accuracy (a sensitivity of 67% and a specificity of 83%). Median survival after MRSI was 24 months. Multivariate analysis showed reduced survival for lower NAA/Cho (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.08 to 0.72, p = 0.01), older age (HR 1.03, 95% CI 1.00 to 1.06, p = 0.04) and shorter symptom duration (HR 0.96, 95% CI 0.93 to 0.99, p = 0.01). Patients with NAA/Cho <2.11 had a reduced survival of 19.4 v 31.9 months (HR 2.05, 95% CI 1.12 to 4.03, p = 0.02). Conclusions: Cerebral degeneration is predictive of reduced survival in ALS.