De Stefano Nicola, Narayanan Sridar, Francis Simon J, Smith Steve, Mortilla Marzia, Tartaglia M Carmela, Bartolozzi Maria L, Guidi Leonello, Federico Antonio, Arnold Douglas L
Institute of Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
Arch Neurol. 2002 Oct;59(10):1565-71. doi: 10.1001/archneur.59.10.1565.
Although in situ pathological studies and in vivo magnetic resonance (MR) investigations have shown that axonal injury can be significant in the early stages of multiple sclerosis (MS), diffuse axonal injury is generally considered a secondary event. Cerebral axonal damage can be specifically assessed in vivo by measuring levels of brain N-acetylaspartate (NAA, a specific index of axonal integrity detected by MR spectroscopy). Other new MR measurements such as magnetization transfer ratio (MTr) or computed estimation of brain volume can provide less specific indexes of tissue damage.
To determine whether diffuse axonal and tissue injury is present in patients with definite MS who do not show clinically significant disability.
We measured brain NAA levels (normalized to creatine [Cr]), MTr values, and cerebral volumes in patients with definite MS who had low T2-weighted MR imaging lesion volumes and no clinical disability, and also in age-matched healthy control subjects.
Values of central brain NAA/Cr and MTr in normal-appearing white matter were significantly lower in the MS patients than in controls (P<.001). In contrast, total brain volumes were not significantly different between these groups. Similar results were found for MS patients with early disease (duration, <3 years) and with a particularly low cerebral T2-weighted MR imaging lesion load (< or = 2 cm(3)).
Cerebral NAA/Cr and MTr values are diffusely decreased in MS patients with early disease, low demyelinating lesion load, and no significant disability. This suggests that axonal and/or tissue injury begins very early in the course of MS and might be at least partially independent of cerebral demyelination.
尽管原位病理学研究和体内磁共振（MR）研究表明，轴突损伤在多发性硬化症（MS）的早期阶段可能很显著，但弥漫性轴突损伤通常被认为是继发性事件。通过测量脑内N-乙酰天门冬氨酸（NAA，一种通过磁共振波谱检测到的轴突完整性的特异性指标）水平，可以在体内特异性评估脑轴突损伤。其他新的MR测量方法，如磁化传递率（MTr）或脑容量的计算估计，可提供特异性较低的组织损伤指标。
确定在无明显临床残疾的确诊MS患者中是否存在弥漫性轴突和组织损伤。
我们测量了T2加权MR成像病变体积较小且无临床残疾的确诊MS患者以及年龄匹配的健康对照者的脑NAA水平（以肌酸[Cr]标准化）、MTr值和脑容量。
MS患者正常白质中的脑中央NAA/Cr和MTr值显著低于对照组（P<0.001）。相比之下，这些组之间的全脑体积没有显著差异。在疾病早期（病程<3年）且脑T2加权MR成像病变负荷特别低（≤2 cm³）的MS患者中也发现了类似结果。
在疾病早期、脱髓鞘病变负荷低且无明显残疾的MS患者中，脑NAA/Cr和MTr值普遍降低。这表明轴突和/或组织损伤在MS病程中很早就开始了，并且可能至少部分独立于脑脱髓鞘。
