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预期寿命正常的非进展性多发性硬化症患者的代表性队列。

A representative cohort of patients with non-progressive multiple sclerosis at the age of normal life expectancy.

机构信息

Department of Neuroscience and Physiology, University of Gothenburg, 413 45 Gothenburg, Sweden.

出版信息

Brain. 2012 Mar;135(Pt 3):900-11. doi: 10.1093/brain/awr336.

Abstract

Multiple sclerosis may have a non-progressive symptomatology for decades; however, it is not clear whether the disease activity may abate completely. We identified a cohort of patients, resident in Gothenburg at the time of disease onset, between the years 1950-64 (n = 307). These geographical and temporal restrictions, along with favourable conditions for a 'spider' epidemiological study, were optimal for an unbiased selection; this 15-year incidence cohort was essentially followed prospectively for 37-59 years after onset. The shortest follow-up time for patients without primary or secondary progression was 45 years. For patients with an initial relapsing-remitting course and multiple sclerosis diagnosis according to the Poser criteria (n = 202), the probability of non-progressive disease after 40 years was 22% (standard error 3.0%), and after 50 years it was 14% (standard error 3.2%). For attack onset including patients with possible multiple sclerosis, the corresponding probabilities after 40 and 50 years were 35% (standard error 3.3%) and 28% (standard error 3.5%), respectively. At the last follow-up in 2009-10, when patients reached the average age of the Swedish population life expectancy, only 13 patients from the multiple sclerosis diagnosis cohort, according to the Poser criteria, remained alive and non-progressive. Their annualized attack frequency diminished with time from 0.29 to 0.015. These patients had been functioning well socially. Nine patients had an Expanded Disability Status Scale score of 0-2.5, and four patients had a score of 3 or 3.5, with deficits dating back to attacks decades ago. Eight patients participated in a complete neuropsychological examination, which showed a slight difference (P < 0.01) concerning verbal memory and executive function compared to an age and socially matched reference group, whereas results for five other cognitive domains were within the normal range. Magnetic resonance images fulfilled the Barkhof-Tintoré criteria for multiple sclerosis in 10 of 11 patients, with conspicuously few subcortical lesions relative to extensive periventricular lesions and lesions extending from the inferior midline aspect of the corpus callosum. Prediction of the non-progressive stage was possible with moderate hazard ratios and low sensitivity. Early features that predicted a non-progressive course were complete remission of the onset attack, low or moderate initial relapse frequency and-when the patients with possible multiple sclerosis were included-dominating afferent symptoms. The clinical disease activity had abated in these 13 patients, with the caveat that transition to secondary progression continued to occur after four decades, albeit with decreasing risk.

摘要

多发性硬化症可能有数十年的非进展性症状;然而,目前尚不清楚疾病活动是否可能完全缓解。我们确定了一个队列的患者,在疾病发作时居住在哥德堡,时间在 1950-64 年之间(n=307)。这些地理和时间限制,以及进行“蜘蛛”式流行病学研究的有利条件,为进行无偏选择提供了最佳条件;这个 15 年的发病队列在发病后基本上进行了 37-59 年的前瞻性随访。没有原发性或继发性进展的患者最短随访时间为 45 年。对于根据 Poser 标准诊断为复发性缓解型多发性硬化症(n=202)的患者,40 年后无进展疾病的概率为 22%(标准误差 3.0%),50 年后为 14%(标准误差 3.2%)。对于包括可能患有多发性硬化症的患者在内的发病起始患者,40 年和 50 年后的相应概率分别为 35%(标准误差 3.3%)和 28%(标准误差 3.5%)。在 2009-10 年的最后一次随访中,当患者达到瑞典人口平均预期寿命时,根据 Poser 标准,多发性硬化症诊断队列中只有 13 名患者仍然存活且无进展。他们的年度发病频率随着时间的推移从 0.29 降至 0.015。这些患者的社会功能良好。9 名患者的扩展残疾状况量表评分为 0-2.5,4 名患者的评分为 3 或 3.5,这些缺陷可追溯到几十年前的发作。8 名患者参加了完整的神经心理学检查,与年龄和社会匹配的参考组相比,他们的言语记忆和执行功能存在明显差异(P<0.01),而其他五个认知领域的结果均在正常范围内。11 名患者中有 10 名的磁共振成像符合 Barkhof-Tintoré多发性硬化症标准,与广泛的脑室周围病变和从胼胝体中线下方延伸的病变相比,皮质下病变明显较少。使用中等危险比和低灵敏度可以预测非进展阶段。预测非进展性病程的早期特征是起始发作的完全缓解、低或中初始复发频率以及-当包括可能患有多发性硬化症的患者时-主导传入症状。这些患者的临床疾病活动已经消退,但需要注意的是,在四十年后仍会继续向继发性进展过渡,尽管风险降低。

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