Centre for Neuroscience, Division of Experimental Medicine, Imperial College London, London, England.
JAMA Neurol. 2013 Feb;70(2):214-22. doi: 10.1001/jamaneurol.2013.599.
To investigate the relationship among attacks in the first 2 years (early relapses), secondary progression (SP), and late disability in multiple sclerosis (MS).
Cohort study with follow-up of 28 years.
Referral MS center.
Patients (N=730) with relapsing-remitting MS diagnosed according to Poser criteria, from the database of the London Multiple Sclerosis Clinic, London, Ontario, Canada.
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 bedridden status (DSS 8).
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.
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.
研究多发性硬化症（MS）首发 2 年内的发作（早期复发）、继发进展（SP）和晚期残疾之间的关系。
28 年随访的队列研究。
安大略省伦敦多发性硬化症诊所的转诊 MS 中心。
730 例符合 Poser 标准的复发性缓解型 MS 患者，来自加拿大安大略省伦敦的伦敦多发性硬化症诊所数据库。
高（≥ 3 次）和早（疾病首发 2 年内）发作频率患者的长期演变。在总 SP 人群和按早期复发次数分组的患者中，我们评估了进展潜伏期（进展至 SP 的时间）对达到使用手杖要求的时间（残疾状况量表评分 6 [DSS 6]）和卧床状态（DSS 8）的预测作用。
在频繁发生早期复发的患者中（n=158），结局存在差异。尽管 103 例（65.2%）迅速进展为 SP MS（中位时间为 5 年），且迅速达到 DSS 6 和 DSS 8 评分（分别为 7 年和 17 年），但其余 55 例（34.8%）尽管存在早期复发的不良特征，但并未进入 SP 阶段。在总 SP 人群中，进展潜伏期较长与达到 DSS 6 的可能性较低相关（优势比分别为 0.76 [95%CI，0.69-0.84]和 0.44 [95%CI，0.37-0.52]，分别为 5 年和 15 年潜伏期），且达到严重残疾的时间也较长。即使在按早期发作次数匹配的患者中，SP 发病与晚期结局之间也存在相同的关联。然而，缓解-复发期的持续时间并不影响从 SP 发病到 DSS 水平的时间。
我们的结果表明，早期炎症发作与 SP 阶段的发病之间存在差异，进一步质疑复发频率作为晚期残疾替代标志物的有效性。在频繁发生早期复发的患者中，我们观察到结局存在很大的变异性，从一个极端到另一个极端。
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