Department of Medical Radiation Physics in Linköping, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
PLoS One. 2024 Oct 21;19(10):e0309547. doi: 10.1371/journal.pone.0309547. eCollection 2024.
Multiple sclerosis (MS) is an inflammatory demyelinating disease with neurodegenerative features causing risk for neurologic irreversible disability over time. Examination of normal-appearing white matter (NAWM) changes in MS by proton magnetic resonance spectroscopy (1H-MRS), may detect diffuse white matter pathology that is associated with neurodegeneration.
In this observational study of in total twenty-six patients with MS, starting treatment with dimethyl fumarate (DMF), we measured the absolute concentration of metabolites in periventricular NAWM using 1H-MRS at baseline and after one and three years of treatment. Metabolite concentrations were analyzed both cross-sectionally, in relation to 10 controls and longitudinally in relation to disease activity.
Patients with MS had higher concentrations of myo-inositol (mIns) in NAWM at baseline compared with controls (mean 5.98 ± 1.37 (SD) and 4.32 ± 1.16 (SD), p<0.01, independent samples t-test). The disease duration was inversely correlated with concentrations of total N-acetylaspartate and N-acetylaspartylglutamate (tNA) (r = -0.62, p<0.01) in NAWM as well as positively to the ratio of mIns and tNA (r = 0.51, p = 0.03). Metabolite concentrations during one-year (n = 19) and three-years (n = 11) follow-up were generally stable. The dropouts were caused by treatment switch after one year, mainly due to new MRI activity. Cross-sectional analyses showed that there was an inverse correlation between concentrations of tNA and mIns at both baseline and at 1 and 3-years follow-up (r = -0.44 to -0.65, p = 0.04 to 0.004). Metabolite concentrations were stable during 1-year follow-up independently of disease activity.
Higher concentrations of the astrogliosis marker mIns in MS compared to controls, the inverse relation between MS disease duration and the neuroaxonal integrity marker tNA, as well as the consistent inverse relation between these two metabolites during follow-up, showed that non-lesional white matter pathology is present in this cohort of MS patients in early disease stages. However, metabolite concentrations during follow-up were generally stable and did not reflect differences in disease activity among patients.
多发性硬化症（MS）是一种具有神经退行性特征的炎症性脱髓鞘疾病，随着时间的推移，会导致神经系统不可逆转的残疾风险。通过质子磁共振波谱（1H-MRS）检查 MS 中正常表现的白质（NAWM）的变化，可能会检测到与神经退行性变相关的弥漫性白质病理学。
在这项共 26 例 MS 患者的观察性研究中，我们在开始使用二甲基富马酸（DMF）治疗时，使用 1H-MRS 在基线和治疗 1 年和 3 年后测量脑室周围 NAWM 中代谢物的绝对浓度。代谢物浓度进行了横断面分析，与 10 名对照者进行比较，并进行了纵向分析，与疾病活动度进行了比较。
与对照组相比，MS 患者的 NAWM 中肌醇（mIns）浓度更高（基线时分别为 5.98 ± 1.37（SD）和 4.32 ± 1.16（SD），p<0.01，独立样本 t 检验）。疾病持续时间与 NAWM 中总 N-乙酰天冬氨酸和 N-乙酰天门冬氨酸谷氨酸（tNA）的浓度呈负相关（r = -0.62，p<0.01），与 mIns 和 tNA 的比值呈正相关（r = 0.51，p = 0.03）。1 年（n = 19）和 3 年（n = 11）随访期间的代谢物浓度通常保持稳定。失访是由于治疗 1 年后的药物转换，主要是由于新的 MRI 活动。横断面分析显示，在基线时以及在 1 年和 3 年的随访时，tNA 和 mIns 的浓度之间均存在负相关（r = -0.44 至 -0.65，p = 0.04 至 0.004）。1 年随访期间，代谢物浓度保持稳定，与疾病活动无关。
与对照组相比，MS 患者的星形胶质细胞标记物 mIns 浓度较高，MS 疾病持续时间与神经轴突完整性标记物 tNA 之间呈负相关，以及在随访期间这两种代谢物之间存在一致的负相关，表明在这一队列的 MS 患者的早期疾病阶段存在非病灶性白质病理学。然而，随访期间的代谢物浓度总体上保持稳定，并未反映出患者之间疾病活动的差异。
