Mandrioli Jessica, Sola Patrizia, Bedin Roberta, Gambini Mariaelena, Merelli Elisa
Clinica Neurologica, Dept. of Neuroscience, University of Modena and Reggio Emilia, Nuovo Ospedale Civile S. Agostino Estense di Modena, Via Giardini 1355, 41100 Modena, Italy.
J Neurol. 2008 Jul;255(7):1023-31. doi: 10.1007/s00415-008-0827-5. Epub 2008 Jun 13.
The ability to predict the future progression of MS represents a key issue for the neurologist. The aim of the study was to create a multifactorial prognostic index (MPI) providing the probability of a severe MS course at diagnosis based on clinical and immunological CSF parameters.
64 clinically definite relapsing-remitting (RR)MS patients (38 benign, 26 severe MS) followed up for at least 10 years were included. Clinical and demographic details, EDSS after 5 and 10 years, progression index, relapse number and rate, time to a second relapse were assessed. CSF and serum samples collected at diagnosis were examined for CSF IgM and IgG oligoclonal bands (OB) and quantitative IgM and IgG determination.
Kaplan-Meier analysis showed that the probability of reaching an EDSS score of 3 or 4 was significantly influenced by the presence of IgMOB (p<0.01 and p<0.01, log-rank test) and by the symptoms at onset (p=0.04 and p=0.03, log-rank test). These results were confirmed at multivariate analysis (Cox model). Univariate logistic analysis showed that IgMOB presence predicted a severe MS course (OR=9.33, CI=2.92- 29.88), whereas sensory symptoms at onset predicted a benign MS course (OR=0.12, CI=0.02-0.56). Using multivariate logistic regression the factors found to be significant were: presence/absence of IgMOB (p<0.01), onset with sensory (p<0.01) and pyramidal symptoms (p=0.01), and first inter-attack interval (p=0.03). The individual probability of a severe evolution was thus estimated by a simple formula comprising clinical and biological markers of prognosis available at diagnosis (pyramidal and sensory symptoms, months to the 2nd episode, and IgMOB presence/absence), giving the probability of developing a severe MS course. Applied to the same patient cohort this formula showed a global error of 6/64 (9.37%). We then used another independent series of 65 RRMS patients to validate this model. In this second patient cohort, 4/45 BMS and 4/20 SMS patients were found to have been incorrectly classified (based on the formula), with a global error of 8/65 (12.31%).
For the first time we created a MPI, using clinical and biological markers to predict the clinical course of MS at diagnosis. This index can support the clinician in patient counselling, therapeutic choices, as well as in patient selection criteria for clinical trials.
预测多发性硬化症（MS）未来病情进展的能力是神经科医生面临的关键问题。本研究的目的是创建一个多因素预后指数（MPI），根据临床和免疫脑脊液参数提供诊断时严重MS病程的概率。
纳入64例临床确诊的复发缓解型（RR）MS患者（38例良性，26例严重MS），随访至少10年。评估临床和人口统计学细节、5年和10年后的扩展残疾状态量表（EDSS）、进展指数、复发次数和率、第二次复发时间。对诊断时采集的脑脊液和血清样本进行脑脊液IgM和IgG寡克隆带（OB）检测以及定量IgM和IgG测定。
Kaplan-Meier分析显示，IgM OB的存在（p<0.01和p<0.01，对数秩检验）和起病时的症状（p=0.04和p=0.03，对数秩检验）对达到EDSS评分为3或4的概率有显著影响。这些结果在多变量分析（Cox模型）中得到证实。单变量逻辑分析显示，IgM OB的存在预示着严重的MS病程（OR=9.33，CI=2.92-29.88），而起病时的感觉症状预示着良性的MS病程（OR=0.12，CI=0.02-0.56）。使用多变量逻辑回归，发现显著的因素为：IgM OB的存在与否（p<0.01）、起病时有感觉（p<0.01）和锥体束症状（p=0.01）以及首次发作间期（p=0.03）。因此，通过一个简单的公式估算严重病情进展的个体概率，该公式包含诊断时可用的预后临床和生物学标志物（锥体束和感觉症状、至第二次发作的月数以及IgM OB的存在与否），得出发生严重MS病程的概率。应用于同一患者队列，该公式显示总体误差为6/64（9.37%）。然后我们使用另一组65例RRMS患者的独立系列来验证该模型。在这第二个患者队列中，发现4/45例良性MS和4/20例严重MS患者被错误分类（基于该公式），总体误差为8/65（12.31%）。
我们首次创建了一个MPI，使用临床和生物学标志物来预测诊断时MS的临床病程。该指数可在患者咨询、治疗选择以及临床试验的患者选择标准方面为临床医生提供支持。
