1H-MRS in patients with multiple sclerosis undergoing treatment with interferon β-1a: results of a preliminary study
1H-MRS in patients with multiple sclerosis undergoing treatment with interferon β-1a: results of a preliminary study
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接受干扰素 β-1a 治疗的多发性硬化症患者的 1H-MRS：初步研究结果
DOI：
10.1136/jnnp.64.2.204
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
V. Gallai†
中科院分区：
文献类型：
--
作者：
P. Sarchielli;O. Presciutti;R. Tarducci;G. Gobbi;A. Alberti;G. Pelliccioli;A. Orlacchio;V. Gallai†
背景技术体内磁共振波谱(MRS)已广泛用于评估多发性硬化症患者白质脱髓鞘病变中发生的生化变化。有人提出，MRS 证明的代谢变化是免疫调节治疗对该疾病效果的敏感指标。 鉴于最近发现多发性硬化症患者接受干扰素（IFN）β-1a治疗的第一阶段疾病活动性增加，利用1H MRS进一步研究脑代谢指标的改变，特别是在IFN β治疗的第一阶段。方法 对五名复发缓解型多发性硬化症患者和五名未经治疗的患者进行 1H MRS 研究，这些患者正在接受肌内 IFN β-1a（600 万单位/周）治疗六个月。两组的平均年龄、病程和扩展残疾状态评分（EDSS）相似。在研究开始以及治疗的第一、第三和六个月时对患者进行评估。结果 在多发性硬化症白质病变中，未经治疗组的 N-乙酰天冬氨酸 (NAA)、胆碱 (Cho)、肌醇 (Ins) 和肌酸 (Cr) 峰值在整个研究期间没有显着变化。与治疗前相比，治疗组第一个月的 Cho 峰面积显着增加，并且这种增加在第三个月和第六个月持续存在（p<0.001）。在接受 IFN β-1a 治疗的患者组中，正常白质中也发现 Cho 峰略有但不显着升高。与研究开始时相比，Cho 的增加以及 Cr 和 NAA 峰值没有显着变化导致整个治疗期间 Cho/Cr 和 Cho/NAA 比率显着升高（分别为 p<0.02 和 p<0.005）。 在治疗组中，第一个月的 Ins 峰值略有但显着增加 (p<0.05)，但在治疗的第三个月和第六个月，Ins 值恢复到治疗前范围。结论 IFN β-1a 对质子 MRS 测量的多发性硬化症病变中的代谢物浓度有影响。多发性硬化症病变中 Cho、Cho/NAA 和 Cho/Cr 比率的增加强化了这样的观点，即它们是活动性或近期脱髓鞘的指标，并且可以支持临床、神经放射学和免疫学证据，显示在 IFN β-1a 治疗的第一阶段期间疾病活动性增加。另一方面，Cho 峰的增加可能表明多发性硬化症病变中膜更新的增加或斑块的重塑，这不一定是由于从头免疫介导的脱髓鞘作用。
BACKGROUND In vivo magnetic resonance spectroscopy (MRS) has been widely used to assess biochemical changes which occur in demyelinating lesions in white matter of patients with multiple sclerosis. It has been suggested that metabolic variations evidenced by MRS are sensitive indicators of the effects of immunomodulatory treatments in this disease. Given the recent finding of an increase in the disease activity in patients with multiple sclerosis treated with interferon (IFN) β-1a in the first period of treatment,1H MRS was used to investigate further the modification in brain metabolic indices, particularly in the first phase of IFN β treatment. METHODS A 1H MRS study was performed on five patients with relapsing-remitting multiple sclerosis who were being treated with intramuscular IFN β-1a (6 million units/week) for six months and on five untreated patients. The mean age, duration of the disease, and expanded disability status scores (EDSS) of the two groups were similar. Patients were evaluated at the beginning of the study and in the first, third, and sixth months of treatment. RESULTS In the multiple sclerosis white matter lesions, N-acetylaspartate (NAA), choline (Cho), inositol (Ins), and creatine (Cr) peaks did not vary significantly over the entire period of the study in the untreated group. In the treated group there was a significant increase in the Cho peak area at the first month compared with the pretreatment period, and this increase continued in the third and sixth months (p<0.001). A slight but not significant rise in the Cho peak was also found in normal appearing white matter in the patient group undergoing treatment with IFN β-1a. The increase in Cho and the lack of significant changes in Cr and NAA peaks induced a significant rise in Cho/Cr and Cho/NAA ratios over the entire period of treatment compared with those at the beginning of the study (p<0.02 and p<0.005 respectively). In the treated group there was a slight but significant increase in the Ins peak in the first month (p<0.05) but in the third and sixth months of treatment the Ins values returned to the pretreatment range. CONCLUSIONS IFN β-1a has an impact on metabolite concentrations in multiple sclerosis lesions measured by proton MRS. The increase in Cho, Cho/NAA, and Cho/Cr ratios in multiple sclerosis lesions reinforces the view that they are an index of active or recent demyelination and could support the clinical, neuroradiological and immunological evidence showing an increase in disease activity during the first period of treatment with IFN β-1a. On the other hand, the increase in the Cho peak could be indicative of a rise in membrane turnover in multiple sclerosis lesions or a remodelling of plaques which is not necessarily due to a de novo immune mediated demyelination.