Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis
Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis
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DOI：
10.1093/brain/awg038
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发表时间：
2003-02-01
期刊：
影响因子：
14.5
通讯作者：
Falini, A
中科院分区：
文献类型：
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作者：
Filippi, M;Bozzali, M;Falini, A
尽管轴突病理学被认为是多发性硬化症的主要病理特征之一，但尚不清楚它发生的时间有多早以及它与 MRI 可见病变负荷的关系。为了评估这种早期轴突病理学，我们量化了一组处于疾病最早临床阶段的患者的全脑 N-乙酰天冬氨酸 (WBNAA) 浓度，并将结果与健康对照的结果进行了比较。使用非定位质子磁共振波谱的传统脑部 MRI 和 WBNAA 从 31 名临床孤立综合征患者（提示多发性硬化症和空间传播的临床旁证据）和 16 名匹配对照中获得。 4-6个月后对所有患者进行额外的常规MRI扫描，以及时发现病变的扩散。与对照组相比，患者的平均 WBNAA 浓度显着降低 (P < 0.0001)。在基线 MRI 上有和没有增强病灶的患者之间，或者在时间上有和没有病灶扩散的患者之间没有显着差异。 WBNAA 浓度和病变体积之间没有发现相关性。即使在多发性硬化症的最早临床阶段，患者也会出现广泛的轴突病理，很大程度上与 MRI 可见的炎症无关，而且范围太广而无法完全逆转。这一发现削弱了当前概念的有效性，即多发性硬化症的轴突病理是反复炎症事件的终末期结果，并强烈支持早期神经保护干预。
Although axonal pathology is recognized as one of the major pathological features of multiple sclerosis, it is less clear how early in its course it occurs and how it correlates with MRI-visible lesion loads. To assess this early axonal pathology, we quantified the concentration of whole-brain N-acetylaspartate (WBNAA) in a group of patients at the earliest clinical stage of the disease and compared the results with those from healthy controls. Conventional brain MRI and WBNAA using unlocalized proton magnetic resonance spectroscopy were obtained from 31 patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis and paraclinical evidence of dissemination in space, and from 16 matched controls. An additional conventional MRI scan was obtained in all patients 4-6 months later to detect dissemination of lesions in time. The mean WBNAA concentration was significantly lower in patients compared with the controls (P < 0.0001). It was not significantly different between patients with and without enhancing lesions at the baseline MRI or between patients with and without lesion dissemination in time. No correlation was found between WBNAA concentrations and lesion volumes. Widespread axonal pathology, largely independent of MRI-visible inflammation and too extensive to be completely reversible, occurs in patients even at the earliest clinical stage of multiple sclerosis. This finding lessens the validity of the current concept that the axonal pathology of multiple sclerosis is the end-stage result of repeated inflammatory events, and argues strongly in favour of early neuroprotective intervention.