Piervincenzi Claudia, Petsas Nikolaos, De Giglio Laura, Carmellini Maurizio, Giannì Costanza, Tommasin Silvia, Pozzilli Carlo, Pantano Patrizia
Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
Department of Radiology, IRCCS NEUROMED, Pozzilli, Italy.
Front Neurol. 2021 Mar 5;12:632917. doi: 10.3389/fneur.2021.632917. eCollection 2021.
Only a few studies have evaluated the brain functional changes associated with disease-modifying therapies (DMTs) in multiple sclerosis (MS), though none used a composite measure of clinical and MRI outcomes to evaluate DMT-related brain functional connectivity (FC) measures predictive of short-term outcome. Therefore, we investigated the following: (1) baseline FC differences between patients who showed evidence of disease activity after a specific DMT and those who did not; (2) DMT-related effects on FC, and; (3) possible relationships between DMT-related FC changes and changes in performance. We used a previously analyzed dataset of 30 relapsing MS patients who underwent fingolimod treatment for 6 months and applied the "no evidence of disease activity" (NEDA-3) status as a clinical response indicator of treatment efficacy. Resting-state fMRI data were analyzed to obtain within- and between-network FC measures. After therapy, 14 patients achieved NEDA-3 status (hereinafter NEDA), while 16 did not (EDA). The two groups significantly differed at baseline, with the NEDA group having higher within-network FC in the anterior and posterior default mode, auditory, orbitofrontal, and right frontoparietal networks than the EDA. After therapy, NEDA showed significantly reduced within-network FC in the posterior default mode and left frontoparietal networks and increased between-network FC in the posterior default mode/orbitofrontal networks; they also showed PASAT improvement, which was correlated with greater within-network FC decrease in the posterior default mode network and with greater between-network FC increase. No significant longitudinal FC changes were found in the EDA. Taken together, these findings suggest that NEDA status after fingolimod is related to higher within-network FC at baseline and to a consistent functional reorganization after therapy.
仅有少数研究评估了与多发性硬化症（MS）疾病修正治疗（DMTs）相关的脑功能变化，不过尚无研究使用临床和MRI结果的综合指标来评估预测短期结果的DMT相关脑功能连接（FC）指标。因此，我们进行了以下研究：（1）在接受特定DMT治疗后出现疾病活动迹象的患者与未出现该迹象的患者之间的基线FC差异；（2）DMT对FC的影响；（3）DMT相关FC变化与性能变化之间的可能关系。我们使用了一个先前分析过的数据集，该数据集包含30名复发型MS患者，他们接受了6个月的芬戈莫德治疗，并将“无疾病活动证据”（NEDA-3）状态作为治疗效果的临床反应指标。对静息态功能磁共振成像（fMRI）数据进行分析，以获得网络内和网络间的FC指标。治疗后，14名患者达到NEDA-3状态（以下简称NEDA），而16名患者未达到（EDA）。两组在基线时存在显著差异，NEDA组在前、后默认模式、听觉、眶额和右侧额顶叶网络中的网络内FC高于EDA组。治疗后，NEDA组在后默认模式和左侧额顶叶网络中的网络内FC显著降低，在后默认模式/眶额网络中的网络间FC增加；他们的PASAT也有所改善，这与后默认模式网络中更大的网络内FC降低以及更大的网络间FC增加相关。EDA组未发现显著的纵向FC变化。综上所述，这些发现表明，芬戈莫德治疗后的NEDA状态与基线时较高的网络内FC以及治疗后一致的功能重组有关。
