Program in Translational Neuropsychiatric Genomics and Partners Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts3Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts4Program in Translational Neurology and Neuroinflammation, Pittsburgh Institute of Neurodegenerative Diseases and Institute of Multiple Sclerosis Care and Research, Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
JAMA Neurol. 2017 Mar 1;74(3):293-300. doi: 10.1001/jamaneurol.2016.5056.
Subclinical inflammatory demyelination and neurodegeneration often precede symptom onset in multiple sclerosis (MS).
To investigate the prevalence of brain magnetic resonance imaging (MRI) and subclinical abnormalities among asymptomatic individuals at risk for MS.
DESIGN, SETTING, AND PARTICIPANTS: The Genes and Environment in Multiple Sclerosis (GEMS) project is a prospective cohort study of first-degree relatives of people with MS. Each participant's risk for MS was assessed using a weighted score (Genetic and Environmental Risk Score for Multiple Sclerosis Susceptibility [GERSMS]) comprising an individual's genetic burden and environmental exposures. The study dates were August 2012 to July 2015.
Participants in the top and bottom 10% of the risk distribution underwent standard and quantitative neurological examination, including disability status, visual, cognitive, motor, and sensory testing, as well as qualitative and quantitative neuroimaging with 3-T brain MRI and optical coherence tomography.
This study included 100 participants at risk for MS, with 41 at higher risk (40 women [98%]) and 59 at lower risk (25 women [42%]), at a mean (SD) age of 35.1 (8.7) years. Given the unequal sex distribution between the 2 groups, the analyses were restricted to women (n = 65). When considering all measured outcomes, higher-risk women differed from lower-risk women (P = .01 by omnibus test). Detailed testing with a vibration sensitivity testing device in a subgroup of 47 women showed that higher-risk women exhibited significantly poorer vibration perception in the distal lower extremities (P = .008, adjusting for age, height, and testing date). Furthermore, 5 of 65 women (8%) (4 at higher risk and 1 at lower risk) met the primary neuroimaging outcome of having T2-weighted hyperintense brain lesions consistent with the 2010 McDonald MRI criteria for dissemination in space. A subset of participants harbor many different neuroimaging features associated with MS, including perivenous T2-weighted hyperintense lesions and focal leptomeningeal enhancement, consistent with the hypothesis that these individuals are at higher risk of developing clinical symptoms of MS than the general population.
Higher-risk asymptomatic family members of patients with MS are more likely to have early subclinical manifestations of MS. These findings underscore the importance of early detection in high-risk individuals.
clinicaltrials.gov Identifier: NCT01353547.
在多发性硬化症（MS）中，亚临床炎症性脱髓鞘和神经退行性变通常先于症状出现。
研究有 MS 风险的无症状个体中脑磁共振成像（MRI）和亚临床异常的患病率。
设计、设置和参与者：多发性硬化症的基因和环境（GEMS）项目是一项对 MS 患者一级亲属的前瞻性队列研究。每位参与者的 MS 风险均使用加权评分（多发性硬化症易感性的遗传和环境风险评分 [GERSMS]）进行评估，该评分包括个体的遗传负担和环境暴露。研究日期为 2012 年 8 月至 2015 年 7 月。
风险分布前 10%和后 10%的参与者接受了标准和定量神经检查，包括残疾状况、视觉、认知、运动和感觉测试，以及使用 3-T 脑部 MRI 和光学相干断层扫描进行定性和定量神经影像学检查。
这项研究包括 100 名有 MS 风险的参与者，其中 41 名处于高风险（40 名女性[98%]），59 名处于低风险（25 名女性[42%]），平均（SD）年龄为 35.1（8.7）岁。由于两组之间的性别分布不均，因此分析仅限于女性（n=65）。考虑到所有测量结果，高风险女性与低风险女性不同（通过总检验 P=0.01）。在 47 名女性的亚组中使用振动敏感测试设备进行详细测试表明，高风险女性在下肢远端的振动感知明显较差（P=0.008，调整年龄、身高和测试日期）。此外，65 名女性中有 5 名（8%）（4 名高风险，1 名低风险）符合 2010 年 McDonald MRI 标准的 T2 加权高信号脑病变，提示这些女性发生 MS 临床症状的风险高于一般人群。亚组的一部分参与者具有许多与 MS 相关的不同神经影像学特征，包括静脉周围 T2 加权高信号病变和局灶性软脑膜强化，这与假设这些个体比一般人群更容易出现 MS 的临床症状一致。
MS 患者的高风险无症状家庭成员更有可能出现 MS 的早期亚临床表现。这些发现强调了在高危个体中进行早期检测的重要性。
clinicaltrials.gov 标识符：NCT01353547。
