Ziccardi Stefano, Pisani Anna Isabella, Schiavi Gian Marco, Guandalini Maddalena, Crescenzo Francesco, Colombi Annalisa, Peloso Angela, Tamanti Agnese, Bertolazzo Maddalena, Marastoni Damiano, Calabrese Massimiliano
Neurology Section, Department of Neuroscience, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy.
Neurology Unit, Mater Salutis Hospital, Verona, Italy.
Eur J Neurol. 2023 May;30(5):1378-1388. doi: 10.1111/ene.15697. Epub 2023 Feb 19.
Although cognitive impairment (CI) is frequent in multiple sclerosis (MS) patients, few studies (and with conflicting results) have evaluated early predictors of CI in the long term. We aimed at determining associations between early clinical/neuroradiological variables with reference to CI after 20 years of MS.
We investigated in 170 MS patients the relationship between clinical/magnetic resonance imaging (MRI) data at diagnosis and cognitive status almost 20 years after MS onset. Among others, number and volume of both white matter lesions (WMLs) and cortical lesions (CLs) were evaluated at diagnosis and after 2 years. All MS patients were followed over time and underwent a comprehensive neuropsychological assessment at the end of study. Advanced statistical methods (unsupervised cluster analysis and random forest model) were conducted.
CI patients showed higher focal cortical pathology at diagnosis compared to cognitively normal subjects (p < 0.001). Volumes of both WMLs and CLs emerged as the MRI metrics most associated with long-term CI. Moreover, number of CLs (especially ≥3) was also strongly associated with long-term CI (≥3 CLs: odds ratio [OR] = 3.7, 95% confidence interval = 1.8-7.5, p < 0.001), more than number of WMLs; the optimal cutoff of three CLs (area under the curve = 0.67, specificity = 75%, sensitivity = 55%) was estimated according to the risk of developing CI.
These results highlight the impact of considering both white and gray matter focal damage from early MS stages. Given the low predictive value of WML number and the poor clinical applicability of lesion volume estimation in the daily clinical context, the evaluation of number of CLs could represent a reliable prognostic marker of CI.
尽管认知障碍（CI）在多发性硬化症（MS）患者中很常见，但很少有研究（且结果相互矛盾）评估CI的长期早期预测因素。我们旨在确定MS发病20年后早期临床/神经影像学变量与CI之间的关联。
我们调查了170例MS患者在诊断时的临床/磁共振成像（MRI）数据与MS发病近20年后的认知状态之间的关系。除其他外，在诊断时和2年后评估了白质病变（WML）和皮质病变（CL）的数量和体积。所有MS患者均接受长期随访，并在研究结束时进行全面的神经心理学评估。采用了先进的统计方法（无监督聚类分析和随机森林模型）。
与认知正常的受试者相比，CI患者在诊断时显示出更高的局灶性皮质病变（p < 0.001）。WML和CL的体积是与长期CI最相关的MRI指标。此外，CL的数量（尤其是≥3个）也与长期CI密切相关（≥3个CL：比值比[OR]=3.7，95%置信区间=1.8-7.5，p < 0.001），比WML的数量更相关；根据发生CI的风险估计，三个CL的最佳截断值（曲线下面积=0.67，特异性=75%，敏感性=55%）。
这些结果突出了从MS早期阶段就考虑白质和灰质局灶性损伤的影响。鉴于WML数量的预测价值较低，且病变体积估计在日常临床环境中的临床适用性较差，CL数量的评估可能是CI的可靠预后标志物。
