Sarchielli P, Presciutti O, Tarducci R, Gobbi G, Alberti A, Pelliccioli G P, Orlacchio A, Gallai V
Neurologic Clinic, University of Perugia, Italy.
J Neurol Neurosurg Psychiatry. 1998 Feb;64(2):204-12. doi: 10.1136/jnnp.64.2.204.
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) beta-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 beta treatment.
A 1H MRS study was performed on five patients with relapsing-remitting multiple sclerosis who were being treated with intramuscular IFN beta-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.
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 beta-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.
IFN beta-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 beta-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.
体内磁共振波谱（MRS）已被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所显示的代谢变化是该疾病免疫调节治疗效果的敏感指标。鉴于最近发现，在治疗的第一阶段接受β-1a干扰素（IFN）治疗的多发性硬化症患者疾病活动增加，因此采用氢质子磁共振波谱（1H MRS）进一步研究脑代谢指标的变化，尤其是在IFNβ治疗的第一阶段。
对5例正在接受肌肉注射β-1a干扰素（600万单位/周）治疗6个月的复发缓解型多发性硬化症患者以及5例未治疗的患者进行了1H MRS研究。两组患者的平均年龄、病程和扩展残疾状态评分（EDSS）相似。在研究开始时以及治疗的第1、3和6个月对患者进行评估。
在未治疗组中，整个研究期间多发性硬化症白质病变中的N-乙酰天门冬氨酸（NAA）、胆碱（Cho）、肌醇（Ins）和肌酸（Cr）峰均无显著变化。在治疗组中，与治疗前相比，第1个月Cho峰面积显著增加，且在第3和6个月持续增加（p<0.001）。在接受β-1a干扰素治疗的患者组中，正常外观白质中的Cho峰也有轻微但不显著的升高。与研究开始时相比，整个治疗期间Cho的增加以及Cr和NAA峰无显著变化导致Cho/Cr和Cho/NAA比值显著升高（分别为p<0.02和p<0.005）。在治疗组中，第1个月Ins峰有轻微但显著的增加（p<0.05），但在治疗的第3和6个月，Ins值恢复到治疗前范围。
β-1a干扰素对通过质子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比值的增加强化了以下观点，即它们是活跃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，表明在使用β-1a干扰素治疗的第一阶段疾病活动增加。另一方面，Cho峰的增加可能表明多发性硬化症病变中膜周转率的增加或斑块的重塑，这不一定是由于新的免疫介导的脱髓鞘所致。
