Early Relapses, Onset of Progression, and Late Outcome in Multiple Sclerosis
Early Relapses, Onset of Progression, and Late Outcome in Multiple Sclerosis
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DOI：
10.1001/jamaneurol.2013.599
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发表时间：
2013-02-01
期刊：
影响因子：
29
通讯作者：
Ebers, George C.
中科院分区：
文献类型：
--
作者：
Scalfari, Antonio;Neuhaus, Anneke;Ebers, George C.
目的：调查前2年内发作之间的关系（早期复发）、继发性进展（SP）和晚期残疾的多发性硬化症（MS）。设计：随访28年的队列研究。设置：转诊MS中心。患者：根据Poser标准诊断的复发缓解型MS患者（N = 730），来自伦敦多发性硬化症诊所（London，安大略）的数据库，加拿大.主要结果测量：高（>= 3次发作）和早期（在疾病的前2年内）复发频率患者的长期演变。在总SP人群和按早期复发数量分组的患者中，我们评估了进展潜伏期（至SP的时间）对达到手杖要求（残疾状态量表评分为6 [DSS 6]）和卧床不起状态（DSS 8）的预测作用。尽管103例（65.2%）患者迅速转为SP MS（中位持续时间为5年），并迅速达到DSS 6和DSS 8评分（分别为7年和17年），但其余患者（n = 55）未进入SP期，尽管存在不良的早期复发特征。在总SP人群中，较长的进展潜伏期与达到DSS 6的概率较低（5年和15年潜伏期的比值比分别为0.76 [95%CI，0.69-0.84]和0.44 [95%CI，0.37-0.52]）和至重度残疾的时间较长相关。即使在与早期发作次数相匹配的患者中，也观察到SP发作时间与晚期结局之间存在相同的相关性。然而，复发缓解期的持续时间没有影响的时间从SP发病DSS levels.Conclusions：我们的研究结果表明早期炎症发作和发病的SP阶段和进一步的问题之间的分离复发频率作为一个替代标记晚期残疾。在频繁早期复发的组中，我们观察到结果的大变异性，从一个极端到相反。JAMA Neurol. 2013;70（2）：214-222。2012年11月19日在线发布。doi：10.1001/jamaneurol.2013.599
Objectives: To investigate the relationship among attacks in the first 2 years (early relapses), secondary progression (SP), and late disability in multiple sclerosis (MS).Design: Cohort study with follow-up of 28 years.Setting: Referral MS center.Patients: Patients (N = 730) with relapsing-remitting MS diagnosed according to Poser criteria, from the database of the London Multiple Sclerosis Clinic, London, Ontario, Canada.Main Outcome Measure: Long-term evolution of patients with high (>= 3 attacks) and early (within the first 2 years of the disease) frequency of relapses. In the total SP population and in patients grouped by numbers of early relapses, we assessed the predictive effect of latency to progression (time to SP) on times to attain cane requirement (Disability Status Scale score of 6 [DSS 6]) and bed-ridden status (DSS 8).Results: Among the group with frequent early relapses (n = 158), outcomes were variable. Although 103 (65.2%) experienced rapid conversion to SP MS (median duration, 5 years) and rapidly attained DSS 6 and DSS 8 scores (7 and 17 years, respectively), the remainder (n = 55) did not enter the SP phase, despite adverse early relapse features. Among the total SP population, longer latency to progression was associated with lower probability of attaining DSS 6 (odds ratio, 0.76 [95% CI, 0.69-0.84] and 0.44 [95% CI, 0.37-0.52] for 5- and 15-year latency, respectively) and longer times to severe disability. The same association between time to onset of SP and late outcomes was observed even in patients matched by number of early attacks. However, duration of the relapsing-remitting phase did not influence the times from SP onset to DSS levels.Conclusions: Our results indicate dissociation between early inflammatory attacks and onset of the SP phase and further question the validity of relapse frequency as a surrogate marker for late disability. Among the group with frequent early relapses, we observed a large variability of outcomes, ranging from one extreme to the opposite. JAMA Neurol. 2013;70(2):214-222. Published online November 19, 2012. doi:10.1001/jamaneurol.2013.599