Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis - Results of a longitudinal magnetic resonance spectroscopy study
Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis - Results of a longitudinal magnetic resonance spectroscopy study
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DOI：
10.1093/brain/121.8.1469
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发表时间：
1998-08-01
期刊：
影响因子：
14.5
通讯作者：
Arnold, DL
中科院分区：
文献类型：
--
作者：
De Stefano, N;Matthews, PM;Arnold, DL
多发性硬化症患者脑部T2加权病变体积与临床致残率之间的相关性一直很难建立，部分原因是MRI信号改变缺乏病理特异性。质子磁共振波谱研究表明，测量N-乙酰天冬氨酸(仅定位于成熟大脑中的神经元和神经元突起)的共振强度可以提供轴突损伤或功能障碍的特定指标。我们对29例有复发或继发进展期临床病程的多发性硬化症患者进行了30个月的纵向研究，每隔6-8个月进行常规脑MRI和单体素质子磁共振波谱检查，同时进行临床评估。在研究开始时，整个组患者的大脑N-乙酰天冬氨酸：肌酸共振强度比异常低(对照平均值=2.93±0.2，患者平均值=2.56+/-0.4，P<；0.005)。复发亚组和继发性进展亚组之间无显著差异。在随访期内，11名复发患者的大脑N-乙酰天冬氨酸/肌酸比值有下降的趋势(8%)，并且这组患者的大脑N-乙酰天冬氨酸：肌酸比值的变化与扩展的残疾程度评分之间存在显著的相关性(P<；0.001)。在30个月的随访中，这种相关性在临床相关复发的患者中更加明显(11名患者中有7名)。T-2加权病变体积的增加(整个组在30个月内增加了35%，P<；0.0001，没有亚组之间的差异)无论是在整个患者组还是在不同的亚组中都与残疾无关。我们得出结论，轴突损伤或丢失的指标，如脑N-乙酰天冬氨酸，可以提供与残疾相关的病理变化的具体衡量标准。总的T-2加权病变体积，虽然比脑N-乙酰天冬氨酸对时间的变化更敏感，但可能与了解残疾的进展不太相关。
It has been difficult to establish a strong correlation between total brain T-2-weighted lesion volume on MRI and clinical disability in multiple sclerosis, in part because of the lack of pathological specificity of T-2-weighted MRI signal changes. Proton magnetic resonance spectroscopy studies have shown that measurements of the resonance intensity of N-acetylaspartate (which is localized exclusively in neurons and neuronal processes in the mature brain) can provide a specific index of axonal damage or dysfunction. Here we report a 30-month longitudinal study of 29 patients with multiple sclerosis who had either a relapsing or a secondary progressive clinical course, Conventional brain MRI and single-voxel proton magnetic resonance spectroscopy examinations were obtained at intervals of 6-8 months with concurrent clinical evaluation. At the onset of the study, the brain N-acetylaspartate : creatine resonance intensity ratio was abnormally low for the whole group of patients (control mean = 2.93 +/- 0.2, patient mean = 2.56 +/- 0.4, P < 0.005). There were no significant differences between the relapsing and secondary progressive subgroups. Over the follow-up period, there was a trend towards a decrease (8%) in the brain N-acetylaspartate: creatine ratio for the 11 relapsing patients and a significant (P < 0.001) correlation between changes in the brain N-acetyl-aspartate : creatine ratio and expanded disability scale scores for the patients in this group. This correlation was even more evident for the patients who had clinically relevant relapses during the 30 months of follow-up (seven of 11 patients). Increases in T-2-weighted lesion volumes (35% in 30 months for the group as a whole, P < 0.0001, without differences between the subgroups) did not correlate with disability either in the group of patients as a whole or in the different subgroups. We conclude that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability. Total T-2-weighted lesion volumes, although more sensitive to changes with time than brain N-acetylaspartate, may be less relevant to understanding the progression of disability.