Assessment of Early Evidence of Multiple Sclerosis in a Prospective Study of Asymptomatic High-Risk Family Members.
Assessment of Early Evidence of Multiple Sclerosis in a Prospective Study of Asymptomatic High-Risk Family Members.
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DOI：
10.1001/jamaneurol.2016.5056
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发表时间：
2017-03-01
期刊：
影响因子：
29
通讯作者：
Reich DS
中科院分区：
文献类型：
--
作者：
Xia Z;Steele SU;Bakshi A;Clarkson SR;White CC;Schindler MK;Nair G;Dewey BE;Price LR;Ohayon J;Chibnik LB;Cortese IC;De Jager PL;Reich DS
Subclinical inflammatory demyelination and neurodegeneration likely precede symptom onset in multiple sclerosis (MS). To investigate the prevalence of brain magnetic resonance imaging (MRI) and subclinical abnormalities in asymptomatic individuals at risk for MS. The Genes and Environment in Multiple Sclerosis (GEMS) is a prospective cohort study of MS first-degree family members. We assessed each participant’s risk for MS using a weighted score comprising genetic burden and environmental exposures. Participants in the top and bottom 10% of the risk distribution underwent standard and quantitative neurological examination (including disability scale, visual, cognitive, motor, and sensory testing) as well as qualitative and quantitative neuroimaging with 3-tesla brain MRI and optical coherence tomography. This study included 100 participants: higher-risk (n=41, 98% women) and lower-risk (n=59, 42% women); mean age of 35.1 years. Given the unequal sex distribution between the two groups, we restricted analyses to women (n=65). When considering all measured outcomes, higher-risk women differed from lower-risk women (omnibus p-value=0.0125). We found the greatest difference in vibration sensation between the two groups: higher-risk women exhibited more impaired vibration perception in distal lower extremities as detected by the Vibratron-II device (p=0.0078, adjusting for age, height, and testing date). Further, five women (8%) met the primary neuroimaging outcome of having T2-hyperintense brain lesions consistent with the 2010 MS MRI criteria for dissemination in space (4 higher-risk; 1 lower-risk). A subset of participants harbor many different neuroimaging features associated with MS pathology, including perivenous T2-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 MS patients are more likely to have early manifestations of MS, which may constitute evidence of myelitis, abnormal myelin structure/function, and/or neurodegeneration. These findings underscore the importance of early detection in high-risk individuals. NCT01353547
