Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy; Siena Imaging SRL, 53100 Siena, Italy.
MS Center Amsterdam, Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1118, 1081 HZ Amsterdam, the Netherlands.
Neuroimage Clin. 2023;38:103397. doi: 10.1016/j.nicl.2023.103397. Epub 2023 Apr 5.
White matter (WM) lesions and brain atrophy are present early in multiple sclerosis (MS). However, their spatio-temporal relationship remains unclear.
Yearly magnetic resonance images were analysed in 387 patients with a first clinical demyelinating event (FCDE) from the 5-year REFLEXION study. Patients received early (from baseline; N = 258; ET) or delayed treatment (from month-24; N = 129; DT) with subcutaneous interferon beta-1a. FSL-SIENA/VIENA were used to provide yearly percentage volume change of brain (PBVC) and ventricles (PVVC). Yearly total lesion volume change (TLVC) was determined by a semi-automated method. Using linear mixed models and voxel-wise analyses, we firstly investigated the overall relationship between TLVC and PBVC and between TLVC and PVVC in the same follow-up period. Analyses were then separately performed for: the untreated period of DT patients (first two years), the first year of treatment (year 1 for ET and year 3 for DT), and a period where patients had received at least 1 year of treatment (stable treatment; ET: years 2, 3, 4, and 5; DT: years 4 and 5).
Whole brain: across the whole study period, lower TLVC was related to faster atrophy (PBVC: B = 0.046, SE = 0.013, p < 0.001; PVVC: B = -0.466, SE = 0.118, p < 0.001). Within the untreated period of DT patients, lower TLVC was related to faster atrophy (PBVC: B = 0.072, SE = 0.029, p = 0.013; PVVC: B = -0.917, SE = 0.306, p = 0.003). A similar relationship was found within the first year of treatment of ET patients (PBVC: B = 0.081, SE = 0.027, p = 0.003; PVVC: B = -1.08, SE = 0.284, p < 0.001), consistent with resolving oedema and pseudo-atrophy. Voxel-wise: overall, higher TLVC was related to faster ventricular enlargement. Lower TLVC was related to faster widespread atrophy in year 1 in both ET (first year of treatment) and DT (untreated) patients. In the second untreated year of DT patients and within the stable treatment period of ET patients (year 4), faster periventricular and occipital lobe atrophy was associated with higher TLVC.
WM lesion changes and atrophy occurred simultaneously in early MS. Spatio-temporal correspondence of these two processes involved mostly the periventricular area. Within the first year of the study, in both treatment groups, faster atrophy was linked to lower lesion volume changes, consistent with higher shrinking and disappearing lesion activity. This might reflect the pseudo-atrophy phenomenon that is probably related to the therapy driven (only in ET patients, as they received treatment from baseline) and "natural" (both ET and DT patients entered the study after a FCDE) resolution of oedema. In an untreated period and later on during stable treatment, (real) atrophy was related to higher lesion volume changes, consistent with increased new and enlarging lesion activity.
在多发性硬化症（MS）中，早期就存在白质（WM）病变和脑萎缩。然而，它们的时空关系仍不清楚。
对 REFLEXION 研究中首次出现临床脱髓鞘事件（FCDE）的 387 例患者进行了每年的磁共振成像分析。患者接受了皮下注射干扰素 beta-1a 的早期（从基线开始；N=258；ET）或延迟治疗（从第 24 个月开始；N=129；DT）。FSL-SIENA/VIENA 用于提供每年脑（PBVC）和脑室（PVVC）的百分比体积变化。通过半自动方法确定每年总病变体积变化（TLVC）。使用线性混合模型和体素分析，我们首先研究了 TLVC 与 PBVC 以及 TLVC 与 PVVC 在同一随访期内的总体关系。然后分别对以下情况进行了分析：DT 患者未治疗期（前两年）、第一年治疗（ET 年 1 和 DT 年 3）以及患者接受至少 1 年治疗的时期（稳定治疗；ET：第 2、3、4 和 5 年；DT：第 4 和 5 年）。
全脑：在整个研究期间，较低的 TLVC 与较快的萎缩相关（PBVC：B=0.046，SE=0.013，p<0.001；PVVC：B=-0.466，SE=0.118，p<0.001）。在 DT 患者未治疗期间，较低的 TLVC 与较快的萎缩相关（PBVC：B=0.072，SE=0.029，p=0.013；PVVC：B=-0.917，SE=0.306，p=0.003）。在 ET 患者治疗的第一年也发现了类似的关系（PBVC：B=0.081，SE=0.027，p=0.003；PVVC：B=-1.08，SE=0.284，p<0.001），这与水肿和假性萎缩的消退有关。体素分析：整体而言，较高的 TLVC 与更快的脑室扩大有关。在 ET（第一年治疗）和 DT（未治疗）患者的第一年中，较低的 TLVC 与更广泛的快速萎缩有关。在 DT 患者的第二年未治疗期和 ET 患者的稳定治疗期（第 4 年）内，更快的脑室周围和枕叶萎缩与更高的 TLVC 相关。
WM 病变变化和萎缩在早期 MS 中同时发生。这两个过程的时空对应主要涉及脑室周围区域。在研究的第一年，在两个治疗组中，较快的萎缩与较低的病变体积变化相关，这与较高的收缩和消失病变活性一致。这可能反映了假性萎缩现象，这可能与治疗驱动（仅在 ET 患者中，因为他们从基线开始接受治疗）和“自然”（ET 和 DT 患者均在 FCDE 后进入研究）水肿消退有关。在未治疗期间和随后的稳定治疗期间，（真正的）萎缩与更高的病变体积变化有关，这与新病变和扩大病变的活性增加有关。
