Imaging axonal damage of normal-appearing white matter in multiple sclerosis
Imaging axonal damage of normal-appearing white matter in multiple sclerosis
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DOI：
10.1093/brain/121.1.103
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发表时间：
1998-01-01
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：
Fu, L;Matthews, PM;Arnold, DL
本研究旨在确定N-乙酰天冬氨酸（NAA）（轴突损伤的标志物）减少在多发性硬化患者病变和正常白色物质之间的相对分布，并测试这些隔间中NAA与肌酸/磷酸肌酸（NAA：Cr）比值变化与残疾变化之间的相关性。数据收集自28例患者的30个月纵向研究，其中11例患者为复发病程伴部分缓解且发作间无进展（复发/缓解），17例患者为复发/缓解期疾病后进行性增加的残疾病程（继发性进行性）。每6-8个月进行一次质子磁共振波谱成像（MRSI）和常规MRI检查，同时进行残疾的临床评估。一般线性模型用于检验MRSI、MRI、病变体积和临床数据之间的关联。分析证实，病变中NAA：Cr比低于正常外观的白色物质（复发/缓解型多发性硬化为-15.3%，继发性进展型多发性硬化为-8.8%）。较低的NAA：先前观察到的继发性进展患者相对于复发/缓解患者的每单位病变体积的Cr比率被发现是由于正常外观的白色物质中的较低比率（8.2%，P < 0.01），而不是由于病变内的任何差异。在研究期间，复发/缓解患者脑中NAA：Cr比值下降15.6%（P < 0.001），其中大部分是由于正常白色物质中NAA：Cr比值下降所致，这进一步强调了正常白色物质变化的重要性。NAA的降低：在复发/缓解亚组中，外观正常的白色物质中的Cr比率与残疾变化密切相关（P < 0.001）。这些结果补充了提示轴突损伤或缺失可能是多发性硬化症功能障碍的原因的数据。继发性轴索损伤在正常白色物质中的积累对于理解这种疾病的慢性残疾可能具有特别重要的意义。
The current study was designed to determine the relative distribution of decreases of N-acetylaspartate (NAA), a marker of axonal damage, between lesions and normal-appearing white matter of patients with established multiple sclerosis and to test for associations between changes in the ratio of NAA to creatine/phosphocreatine (NAA : Cr) in those compartments and changes in disability. Data were collected from a 30-month longitudinal study of 28 patients with either a relapsing course with partial remissons and no progression between attacks (relapsing/remitting) (11 patients) or a course of progressively increasing disability, following a period of relapsing/remitting disease (secondary progressive) (17 patients). Proton magnetic resonance spectroscopic imaging (MRSI) and conventional MRI examinations were performed at 6-8-month intervals with concurrent clinical assessments of disability. General linear models were used to test associations between MRSI, MRI, lesion volume and clinical data. Analysis confirmed that the NAA : Cr ratio is lower in lesions than in the normal-appearing white matter (-15.3% in relapsing/remitting multiple sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower NAA : Cr ratio per unit lesion volume previously observed for secondary progressive relative to relapsing/remitting patients was found to result from a lower ratio (8.2%, P < 0.01) in the normal-appearing white matter rather than from any differences within lesions. The importance of changes in the normal-appearing white matter was emphasized further with the observation that the NAA : Cr ratio in the normal-appearing white matter accounted for most of the observed 15.6% (P < 0.001) decrease in the NAA : Cr ratio in the brains of relapsing/remitting patients over the period of study. The decrease in the NAA : Cr ratio in normal-appearing white matter correlated strongly (P < 0.001) with changes in disability in the relapsing/remitting subgroup. These results add to data suggesting that axonal damage or loss may be responsible for functional impairments in multiple sclerosis. The accumulation of secondary axonal damage in the normal-appearing white matter may be of particular significance for understanding chronic disability in this disease.