Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Department of Neurology with Institute for Translational Neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster, Germany.
Ann Neurol. 2022 Feb;91(2):268-281. doi: 10.1002/ana.26281. Epub 2022 Jan 4.
A major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS).
From a single-center observational study, all RRMS (n = 360) and SPMS (n = 47) patients and 80 matched controls were evaluated. RRMS patient subsets who converted to SPMS (n = 54) or silently progressed (n = 159), respectively, during the 12-year observation period were compared to clinically matched RRMS patients remaining RRMS (n = 54) or stable (n = 147), respectively. From brain MRI, we assessed the value of brain and spinal cord measures to predict silent progression and SPMS conversion.
Patients who developed SPMS showed faster cord atrophy rates (-2.19%/yr) at least 4 years before conversion compared to their RRMS matches (-0.88%/yr, p < 0.001). Spinal cord atrophy rates decelerated after conversion (-1.63%/yr, p = 0.010) towards those of SPMS patients from study entry (-1.04%). Each 1% faster spinal cord atrophy rate was associated with 69% (p < 0.0001) and 53% (p < 0.0001) shorter time to silent progression and SPMS conversion, respectively.
Silent progression and conversion to secondary progressive disease are predominantly related to cervical cord atrophy. This atrophy is often present from the earliest disease stages and predicts the speed of silent progression and conversion to Progressive MS. Diagnosis of SPMS is rather a late recognition of this neurodegenerative process than a distinct disease phase. ANN NEUROL 2022;91:268-281.
多发性硬化症（MS）研究中的一个主要挑战是理解无症状进展和进展型 MS。我们采用一种新方法，从传统的脑部 MRI 扫描中准确地捕捉上颈髓区域，旨在研究脊髓和脑萎缩在无症状进展和向继发性进展型疾病（SPMS）转化中的作用。
我们对来自单中心观察性研究的所有 RRMS（n=360）和 SPMS（n=47）患者以及 80 名匹配的对照者进行了评估。在 12 年的观察期内，分别将转化为 SPMS（n=54）或无症状进展（n=159）的 RRMS 患者亚组与临床上匹配的 RRMS 患者（分别为 n=54）或稳定的 RRMS 患者（分别为 n=147）进行比较。我们从脑部 MRI 评估了脑和脊髓测量值预测无症状进展和 SPMS 转化的价值。
与 RRMS 匹配者相比（-0.88%/yr，p<0.001），发生 SPMS 的患者在转化前至少 4 年就显示出更快的脊髓萎缩率（-2.19%/yr）。转化后，脊髓萎缩率减慢（-1.63%/yr，p=0.010），向研究入组时的 SPMS 患者的脊髓萎缩率（-1.04%）靠拢。脊髓萎缩率每增加 1%，与无症状进展和 SPMS 转化的时间分别缩短 69%（p<0.0001）和 53%（p<0.0001）相关。
无症状进展和向继发性进展型疾病的转化主要与颈髓萎缩有关。这种萎缩通常从疾病的最早阶段就存在，可预测无症状进展和向进展型多发性硬化症转化的速度。SPMS 的诊断与其说是一个明确的疾病阶段，不如说是对这种神经退行性过程的晚期认识。
