From the Department of Neurology (C.C., N.P., E.C., A.A., F.C.O., A.B.-R., A.S., S.S., D.J.B., A.G., S.L.H., B.A.C.C., R.G.H., A.J.G.), UCSF Weill Institute for Neurosciences, University of California, San Francisco; Department of Neurology (B.N.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biology (H.H.Y.), University of Maryland, College Park; Department of Pathology (C.J.S.), University of California, San Diego, La Jolla; and Department of Neurosciences (R.M.), Biomedicine and Movement Sciences, University of Verona, Italy.
Neurology. 2022 Oct 11;99(15):e1685-e1693. doi: 10.1212/WNL.0000000000200977. Epub 2022 Aug 29.
The timing of neurodegeneration in multiple sclerosis (MS) remains unclear. It is critical to understand the dynamics of neuroaxonal loss if we hope to prevent or forestall permanent disability in MS. We therefore used a deeply phenotyped longitudinal cohort to assess and compare rates of neurodegeneration in retina and brain throughout the MS disease course.
We analyzed 597 patients with MS who underwent longitudinal optical coherence tomography imaging annually for 4.5 ± 2.4 years and 432 patients who underwent longitudinal MRI scans for 10 ± 3.4 years, quantifying macular ganglion cell-inner plexiform layer (GCIPL) volume and cortical gray matter (CGM) volume. The association between the slope of decline in the anatomical structure and the age of entry in the cohort (categorized by the MRI cohort's age quartiles) was assessed by hierarchical linear models.
The rate of CGM volume loss declined with increasing age of study entry (1.3% per year atrophy for the age of entry in the cohort younger than 35 years; 1.1% for older than 35 years and younger than 41; 0.97% for older than 41 years and younger than 49; 0.9% for older than 49 years) while the rate of GCIPL thinning was highest in patients in the youngest quartile, fell by more than 50% in the following age quartile, and then stabilized (0.7% per year thinning for the age of entry in the cohort younger than 35 years; 0.29% for age older than 35 and younger than 41 years; 0.34% for older than 41 and younger than 49 years; 0.33% for age older than 49 years).
An age-dependent reduction in retinal and cortical volume loss rates during relapsing-remitting MS suggests deceleration in neurodegeneration in the earlier period of disease and further indicates that the period of greatest adaptive immune-mediated inflammatory activity is also the period with the greatest neuroaxonal loss.
多发性硬化症(MS)的神经退行性变时间仍不清楚。如果我们希望预防或阻止 MS 患者出现永久性残疾,那么了解神经轴突丢失的动态至关重要。因此,我们使用经过深度表型分析的纵向队列来评估和比较 MS 病程中视网膜和大脑的神经退行性变速度。
我们分析了 597 例接受了每年 1 次的纵向光学相干断层扫描成像检查,共持续了 4.5±2.4 年,以及 432 例接受了每年 1 次的纵向 MRI 扫描,共持续了 10±3.4 年,以量化黄斑神经节细胞-内丛状层(GCIPL)容积和皮质灰质(CGM)容积。通过分层线性模型评估解剖结构下降斜率与队列入组年龄(按 MRI 队列的年龄四分位数分类)之间的关联。
CGM 容积丢失率随入组年龄的增加而降低(入组年龄小于 35 岁的患者每年萎缩 1.3%;入组年龄大于 35 岁且小于 41 岁的患者每年萎缩 1.1%;入组年龄大于 41 岁且小于 49 岁的患者每年萎缩 0.97%;入组年龄大于 49 岁的患者每年萎缩 0.9%),而 GCIPL 变薄率在最年轻的四分位组中最高,在随后的年龄四分位组中下降超过 50%,然后稳定(入组年龄小于 35 岁的患者每年变薄 0.7%;入组年龄大于 35 岁且小于 41 岁的患者每年变薄 0.29%;入组年龄大于 41 岁且小于 49 岁的患者每年变薄 0.34%;入组年龄大于 49 岁的患者每年变薄 0.33%)。
复发缓解型 MS 中视网膜和皮质容积丢失率随年龄的降低表明神经退行性变速度在疾病早期减慢,进一步表明适应性免疫介导的炎症活动最活跃的时期也是神经轴突丢失最严重的时期。