McKay Kyla A, Manouchehrinia Ali, Berrigan Lindsay, Fisk John D, Olsson Tomas, Hillert Jan
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
JAMA Neurol. 2019 Sep 1;76(9):1028-1034. doi: 10.1001/jamaneurol.2019.1546.
Cognitive impairment in multiple sclerosis (MS) can lead to reduced quality of life, social functioning, and employment. Few studies have investigated cognitive outcomes among patients with pediatric-onset MS (POMS) over the long term.
To compare long-term information-processing efficiency between patients with POMS and adult-onset MS (AOMS).
DESIGN, SETTING, AND PARTICIPANTS: This population-based longitudinal cohort study accessed the Swedish MS Registry (SMSreg), which collates information from all 64 neurology clinics in Sweden. Registered cases with definite MS in the SMSreg with an onset before April 15, 2018, and at least 2 Symbol Digit Modalities Test (SDMT) scores recorded were included. Only persons aged 18 to 55 years and with duration of disease of less than 30 years at the time of SDMT administration were included, to ensure comparable ranges between patients with POMS and AOMS. Of 8247 persons with an SDMT recorded in the SMSreg, 5704 met inclusion criteria, 300 (5.3%) of whom had POMS. Data were collected from April 1, 2006, through April 15, 2018 and analyzed from April through August 2018.
Pediatric-onset MS (onset <18 years of age) vs AOMS (onset ≥18 years of age).
Information-processing efficiency measured every 6 or 12 months by the SDMT. Linear mixed-effects models were used to compare all available SDMT scores between patients with POMS and those with AOMS. Persons with cognitive impairment (ever vs never) were identified using regression-based norms and compared between POMS and AOMS groups using logistic regression.
Of the 5704 participants, 4015 were female (70.4%), and 5569 had a relapsing-onset disease course (97.6%). Most participants were exposed to a disease-modifying therapy (DMT) during follow-up (98.8%). Median age at baseline for the POMS group was 25.6 years (interquartile range, 21.0-31.7 years) and for the AOMS group, 38.3 years (interquartile range, 31.4-45.2 years). A total of 46 429 unique SDMT scores were analyzed. After adjustment for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and DMT exposure, the SDMT score for patients with POMS was significantly lower than that of patients with AOMS (β coefficient, -3.59 [95% CI, -5.56 to -1.54]). The SDMT score for patients with POMS declined faster than that of patients with AOMS (β coefficient, -0.30 [95% CI, -0.42 tp -0.17]). The odds of cognitive impairment were also significantly elevated in the POMS group (odds ratio, 1.44; 95% CI, 1.06-1.98).
In adulthood, patients with POMS demonstrated a more rapid reduction in information-processing efficiency over time and were more likely to experience cognitive impairment than patients with AOMS, independent of age or disease duration. Further investigation is required to understand the mechanisms by which early MS onset influences cognitive outcomes.
多发性硬化症(MS)中的认知障碍会导致生活质量、社交功能和就业能力下降。很少有研究长期调查儿童期发病的多发性硬化症(POMS)患者的认知结局。
比较POMS患者和成人期发病的多发性硬化症(AOMS)患者的长期信息处理效率。
设计、背景和参与者:这项基于人群的纵向队列研究访问了瑞典多发性硬化症登记处(SMSreg),该登记处整理了瑞典所有64家神经科诊所的信息。纳入SMSreg中确诊为MS且发病时间在2018年4月15日之前且至少记录了2次符号数字模式测验(SDMT)分数的病例。仅纳入年龄在18至55岁之间且在进行SDMT测试时疾病病程少于30年的人,以确保POMS患者和AOMS患者之间有可比范围。在SMSreg中记录了SDMT的8247人中,5704人符合纳入标准,其中300人(5.3%)患有POMS。数据收集时间为2006年4月1日至2018年4月15日,并于2018年4月至8月进行分析。
儿童期发病的多发性硬化症(发病年龄<18岁)与AOMS(发病年龄≥18岁)。
每6或12个月通过SDMT测量信息处理效率。使用线性混合效应模型比较POMS患者和AOMS患者之间所有可用的SDMT分数。使用基于回归的标准确定有认知障碍(曾经有过与从未有过)的人,并使用逻辑回归比较POMS组和AOMS组。
在5704名参与者中,4015名是女性(70.4%),5569名有复发型病程(97.6%)。大多数参与者在随访期间接受了疾病修饰治疗(DMT)(98.8%)。POMS组基线时的中位年龄为25.6岁(四分位间距,21.0 - 31.7岁),AOMS组为38.3岁(四分位间距,31.4 - 45.2岁)。共分析了46429个独特的SDMT分数。在对性别、年龄、疾病病程、疾病类型、完成的SDMT总数、口头或视觉SDMT形式以及DMT暴露进行调整后,POMS患者的SDMT分数显著低于AOMS患者(β系数,-3.59 [95%置信区间,-5.56至-1.54])。POMS患者的SDMT分数下降速度比AOMS患者快(β系数,-0.30 [95%置信区间,-0.42至-0.17])。POMS组出现认知障碍的几率也显著升高(优势比,1.44;95%置信区间,1.06 - 1.98)。
在成年期,POMS患者的信息处理效率随时间下降得更快,并且比AOMS患者更有可能出现认知障碍,这与年龄或疾病病程无关。需要进一步研究以了解MS早期发病影响认知结局的机制。