Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
San Camillo-Forlanini Hospital, Rome, Italy.
Ann Clin Transl Neurol. 2021 Mar;8(3):623-630. doi: 10.1002/acn3.51302. Epub 2021 Feb 3.
To assess the dynamics of "pseudo-atrophy," the accelerated brain volume loss observed after initiation of anti-inflammatory therapies, in patients with multiple sclerosis (MS).
Monthly magnetic resonance imaging (MRI) data of patients from the IMPROVE clinical study (NCT00441103) comparing relapsing-remitting MS patients treated with interferon beta-1a (IFNβ-1a) for 40 weeks versus those receiving placebo (16 weeks) and then IFNβ-1a (24 weeks) were used to assess percentage of gray (PGMVC) and white matter (PWMVC) volume changes. Comparisons of PGMVC and PWMVC slopes were performed with a mixed effect linear model. In the IFNβ-1a-treated arm, a quadratic term was included in the model to evaluate the plateauing effect over 40 weeks.
Up to week 16, PGMVC was -0.14% per month in the placebo and -0.27% per month in treated patients (P < 0.001). Over the same period, the decrease in PWMVC was -0.067% per month in the placebo and -0.116% per month in treated patients (P = 0.27). Similar changes were found in the group originally randomized to placebo when starting IFNβ-1a treatment (week 16-40, reliability analysis). In the originally treated group, over 40 weeks, the decrease in PGMVC showed a significant (P < 0.001) quadratic component, indicating a plateauing at week 20.
Findings reported here add new insights into the complex mechanisms of pseudo-atrophy and its relation to the compartmentalized inflammation occurring in the GM of MS patients. Ongoing and forthcoming clinical trials including MRI-derived GM volume loss as an outcome measure need to account for potentially significant GM volume changes as part of the initial treatment effect.
评估多发性硬化症（MS）患者在开始抗炎治疗后观察到的“假性萎缩”（加速脑体积损失）的动态变化。
使用 IMPROVE 临床研究（NCT00441103）中每月的磁共振成像（MRI）数据，比较接受干扰素β-1a（IFNβ-1a）治疗 40 周的复发缓解型 MS 患者与接受安慰剂（16 周）然后接受 IFNβ-1a（24 周）治疗的患者的灰质（PGMVC）和白质（PWMVC）体积变化的百分比。使用混合效应线性模型比较 PGMVC 和 PWMVC 斜率的变化。在 IFNβ-1a 治疗组中，模型中包含二次项以评估 40 周内的稳定期效应。
在第 16 周之前，安慰剂组的 PGMVC 为每月-0.14%，治疗组为每月-0.27%（P<0.001）。在同一时期，安慰剂组的 PWMVC 减少量为每月-0.067%，治疗组为每月-0.116%（P=0.27）。当开始 IFNβ-1a 治疗时，最初随机分配到安慰剂组的患者也出现了类似的变化（第 16-40 周，可靠性分析）。在最初接受治疗的组中，40 周后，PGMVC 的减少呈现出显著的（P<0.001）二次成分，表明在第 20 周时达到稳定期。
这里报告的发现为假性萎缩的复杂机制及其与 MS 患者 GM 中分隔性炎症的关系提供了新的见解。正在进行和即将进行的临床试验，包括 MRI 衍生的 GM 体积损失作为结果测量，需要考虑到潜在的显著 GM 体积变化作为初始治疗效果的一部分。
