Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis
Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis
复制标题
DOI：
10.1001/jamaneurol.2022.1025
复制
发表时间：
2022-05-16
期刊：
影响因子：
29
通讯作者：
Granziera, Cristina
中科院分区：
文献类型：
--
作者：
Cagol, Alessandro;Schaedelin, Sabine;Granziera, Cristina
复发性多发性硬化症(RMS)神经变性和脑萎缩的驱动机制尚不完全清楚。目的确定复发性多发性硬化症(RMS)患者中与复发活动无关的残疾进展(PIRA)是否与加速的脑组织丢失有关。设计、设置和参与者进行了这项观察性纵向队列研究，中位数(IQR)为3.2年(2.0-4.9)，数据从2012年1月到2019年9月在一个由三级大学和非大学转诊医院组成的联合体中获得。如果患者有定期的临床随访和至少2次适合进行容量分析的脑磁共振成像(MRI)扫描，则包括在内。分析2020年1月至2021年3月的数据。根据整个观察期间的临床演变，患者被分类为(1)仅有复发活动，(2)仅有PIRA发作。(3)混合活动度，或(4)临床稳定性。MAIN结果和测量是指在倾向性得分匹配后计算的组之间脑体积/皮质厚度的年百分比变化(MD-APC)的差异。结果516例RMS患者(女性占67.4%；平均[SD]年龄41.4[11.1]岁；[IQR]扩展残疾状态量表评分2.0[1.5-30])共1904次脑部MRI扫描。排除质量不足的扫描(n=19)。放射性炎症活动与几个脑室萎缩的增加有关，而年化复发率的增加与深层灰质(GM)体积的加速丢失有关。与临床稳定的患者相比，PIRA患者的脑体积丢失率增加(MD-APC，-0.36；95%CI，-0.60至-0.12；P=0.02)，主要由大脑皮层GM的丢失所致。与临床稳定的患者相比，复发患者的全脑萎缩增加(MD-APC，-0.18；95%CI，-0.34至-0.02；P=0.04)，大脑皮层和深层GM均加速丢失。PIRA患者和复发活动者之间的脑萎缩率没有差异。结论和相关性我们的研究表明，RMS和PIRA患者表现出加速的脑萎缩，尤其是大脑皮层。这些结果表明，有必要在临床实践中认识到PIRA的潜在表现，并在临床试验中进一步评估PIRA患者的治疗策略。
IMPORTANCE The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood.OBJECTIVE To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss.DESIGN, SETTING, AND PARTICIPANTS In this observational, longitudinal cohort study with median (IQR) follow-up of 3.2 years (2.0-4.9), data were acquired from January 2012 to September 2019 in a consortium of tertiary university and nonuniversity referral hospitals. Patients were included if they had regular clinical follow-up and at least 2 brain magnetic resonance imaging (MRI) scans suitable for volumetric analysis. Data were analyzed between January 2020 and March 2021.EXPOSURES According to the clinical evolution during the entire observation, patients were classified as those presenting (1) relapse activity only, (2) PIRA episodes only. (3) mixed activity, or (4) clinical stability.MAIN OUTCOMES AND MEASURES Mean difference in annual percentage change (MD-APC) in brain volume/cortical thickness between groups, calculated after propensity score matching. Brain atrophy rates, and their association with the variables of interest, were explored with linear mixed-effect models.RESULTS Included were 1904 brain MRI scans from 516 patients with RMS (67.4% female; mean [SD] age, 41.4 [11.1] years; median [IQR] Expanded Disability Status Scale score, 2.0 [1.5-30]). Scans with insufficient quality were excluded (n = 19). Radiological inflammatory activity was associated with increased atrophy rates in several brain compartments, while an increased annualized relapse rate was linked to accelerated deep gray matter (GM) volume loss. When compared with clinically stable patients, patients with PIRA had an increased rate of brain volume loss (MD-APC, -0.36; 95% CI, -0.60 to -0.12; P = .02), mainly driven by GM loss in the cerebral cortex. Patients who were relapsing presented increased whole brain atrophy (MD-APC, -0.18; 95% CI, -0.34 to -0.02; P = .04) with respect to clinically stable patients, with accelerated GM loss in both cerebral cortex and deep GM. No differences in brain atrophy rates were measured between patients with PIRA and those presenting relapse activity.CONCLUSIONS AND RELEVANCE Our study shows that patients with RMS and PIRA exhibit accelerated brain atrophy, especially in the cerebral cortex. These results point to the need to recognize the insidious manifestations of PIRA in clinical practice and to further evaluate treatment strategies for patients with PIRA in clinical trials.