Group of Biomaterials, Aragon Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain; Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain.
Ophthalmology Department, Miguel Servet University Hospital, Zaragoza, Spain; GIMSO Research and Innovative Group, Aragon Institute for Health Research (IIS Aragón), Zaragoza, Spain.
Comput Biol Med. 2019 Aug;111:103357. doi: 10.1016/j.compbiomed.2019.103357. Epub 2019 Jul 15.
Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Many studies of MS patients have described axonal loss in the optic nerve of the retina, and specifically progressive thinning of the retinal nerve fiber layer (RNFL). We hypothesize that RNFL thinning involves the participation of 2 processes that cause CNS damage: autoimmune inflammation and axonal degeneration. To test this hypothesis, we developed a mathematical model based on ordinary differential equations to relate the evolution of RNFL thickness (measured by optical coherence tomography [OCT]) with that of the Expanded Disability Status Scale (EDSS) score in MS patients. Data were obtained from a longitudinal study of 114 MS patients who were followed-up for 10 years. After adjusting the parameters using a genetic algorithm, the model's prediction of the evolution of RNFL thickness accurately reflected the progression revealed by the 10-year clinical data. Our findings suggest that differences in the relative contributions of autoimmune inflammation and axonal degeneration can account for the complex dynamics of MS, which vary from one patient to the next. Moreover, our results show that CNS damage occurs cumulatively from the onset of MS and that most RNFL thinning occurs before the appearance of significant disability. RNFL thickness could therefore serve as a reliable biomarker of MS disease course. Our proposed methodology would enable the use of OCT data from new MS patients to predict the evolution of RNFL thinning and hence the progression of MS in individual patients, and to facilitate the selection of patient-specific therapies.
多发性硬化症 (MS) 是一种中枢神经系统 (CNS) 的神经退行性疾病。许多 MS 患者的研究都描述了视网膜视神经中的轴突丢失，特别是视网膜神经纤维层 (RNFL) 的进行性变薄。我们假设 RNFL 变薄涉及到导致 CNS 损伤的两个过程的参与：自身免疫炎症和轴突变性。为了验证这一假设，我们开发了一个基于常微分方程的数学模型，将 RNFL 厚度的演变（通过光学相干断层扫描 [OCT] 测量）与 MS 患者的扩展残疾状况量表 (EDSS) 评分的演变联系起来。数据来自对 114 名 MS 患者进行的纵向研究，这些患者随访了 10 年。使用遗传算法调整参数后，该模型对 RNFL 厚度演变的预测准确反映了 10 年临床数据揭示的进展。我们的发现表明，自身免疫炎症和轴突变性的相对贡献的差异可以解释 MS 的复杂动态，这种动态因患者而异。此外，我们的结果表明，CNS 损伤从 MS 发病开始就累积发生，并且大多数 RNFL 变薄发生在出现明显残疾之前。因此，RNFL 厚度可以作为 MS 病程的可靠生物标志物。我们提出的方法将使能够使用新的 MS 患者的 OCT 数据来预测 RNFL 变薄的演变，从而预测个体患者的 MS 进展，并有助于选择针对特定患者的治疗方法。
