Bagnato Francesca, Mordin Margaret, Greene Nupur, Mahida Snehal, van Wingerden Janneke
Neuroimaging Unit, Neuorimmunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN.
RTI Health Solutions, Research Triangle Park, NC.
J Manag Care Spec Pharm. 2025 Jul;31(7):694-721. doi: 10.18553/jmcp.2025.24294. Epub 2025 May 13.
Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. Emerging evidence suggests that chronic disease processes within the central nervous system are important drivers of the ongoing disability accumulation in people with MS (pwMS). Chronic lesion activity driven by smoldering neuroinflammation is considered one of the neuropathological hallmarks of disease progression in worsening disability. Our understanding of the role of chronic active lesions (CALs) in MS pathology has expanded with improvements in imaging technology. Three in vivo imaging biomarkers of CALs are available to detect CALs: paramagnetic rim lesions (PRLs), 18 kDa translocator protein (TSPO)-positron emission tomography rim-positive lesions, and the magnetic resonance imaging (MRI)-defined slowly expanding lesions (SELs).
To evaluate associations between CALs and measures of worsening disability in pwMS.
A systematic literature search was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using PubMed, Embase, and the Cochrane Library on April 21, 2023. The review included randomized controlled trials, retrospective studies, and prospective cross-sectional and longitudinal studies conducted during 2010-2023 reporting the outcomes of interest. Studies evaluating people with any MS phenotype were included if they reported any associative analysis between CALs and clinical outcomes.
A total of 30 of 149 unique studies identified in the literature met the inclusion criteria. Of these 30 publications, 18 were based on PRLs, 9 on MRI-defined SELs, 1 on PRLs and MRI-defined SELs simultaneously, and 2 on TSPO-positive lesions. PRLs were associated with disability worsening in 17 studies, as measured by clinical disability scales. MRI-defined SELs were associated with worsening disability in 10 studies.
CALs are frequently associated with disease progression and disability accumulation. CALs may provide an indicator of disease severity and may assist with the assessment of treatment efficacy.
多发性硬化症（MS）是一种慢性神经炎症性和神经退行性疾病。新出现的证据表明，中枢神经系统内的慢性疾病过程是MS患者（pwMS）持续残疾积累的重要驱动因素。由隐匿性神经炎症驱动的慢性病灶活动被认为是疾病进展导致残疾恶化的神经病理学标志之一。随着成像技术的改进，我们对慢性活动性病灶（CALs）在MS病理学中的作用的理解有所扩展。有三种CALs的体内成像生物标志物可用于检测CALs：顺磁性边缘病灶（PRLs）、18 kDa转位蛋白（TSPO）-正电子发射断层扫描边缘阳性病灶，以及磁共振成像（MRI）定义的缓慢扩展病灶（SELs）。
评估CALs与pwMS患者残疾恶化指标之间的关联。
按照系统评价和Meta分析的首选报告项目指南，于2023年4月21日使用PubMed、Embase和Cochrane图书馆进行了系统文献检索。该综述纳入了2010年至2023年期间进行的随机对照试验、回顾性研究以及前瞻性横断面和纵向研究，这些研究报告了感兴趣的结果。如果研究报告了CALs与临床结果之间的任何关联分析，则纳入评估任何MS表型患者的研究。
文献中确定的149项独特研究中共有30项符合纳入标准。在这30篇出版物中，18篇基于PRLs，9篇基于MRI定义的SELs，1篇同时基于PRLs和MRI定义的SELs，2篇基于TSPO阳性病灶。根据临床残疾量表测量，17项研究中PRLs与残疾恶化相关。10项研究中MRI定义的SELs与残疾恶化相关。
CALs通常与疾病进展和残疾积累相关。CALs可能提供疾病严重程度的指标，并可能有助于评估治疗效果。
