#ResearchSpeak: asymptomatic MS in siblings of MSers

How common is asymptomatic MS in siblings of MSers? #ResearchSpeak #MSBlog

The study below confirms that siblings of people with MS have a high incidence of sub-clinical, or asymptomatic, MS. Almost 1 in 10 siblings of pwMS have MRI features of MS. This confirms the findings of an earlier Sardinian study and other studies demonstrating that siblings of pwMS have early markers of MS. The NIH study only looked women, which will slightly bias the results as MS is commoner on women. 

We did a pilot study similar to this but had too few study subjects to pick-up a definite signal. What do we do with this information? We could use the information to power a prevention study in people at high-risk of MS. But what intervention would we use? Vitamin D? Anti-EBV drugs, for example rituximab or an small molecule antiviral? Should we be screening all siblings of people with MS and diagnosing them in the asymptomatic phase of the disease so we can intervene early with treatments? The latter is problematic as we don't have any evidence that intervening at the asymptomatic phase of the disease alters the long-term prognosis, but I suspect it will based on scientific principles underpinning treat-early and effectively. In addition, the current diagnostic criteria for MS don't allow neurologists to diagnose MS in the asymptomatic phase of the disease. This is important as payers, such as the NHS and health insurance companies, can't pay for treatments for a non-disease. I suspect it is only a matter of time until we extend the diagnostic criteria of MS into the asymptomatic phase. Once we do this we could then start clinical trials in the hope of preventing symptomatic disease later on (1st attack) and further damage.

Please note that if you are a sibling of someone with MS, or you have siblings, who are at high risk of MS you should probably be encouraging them to do what they can to lower  their risk of developing MS. At the moment this advice includes telling them not to smoke and to keep themselves vD replete.

Xia et al. Assessment of Early Evidence of Multiple Sclerosis in a Prospective Study of Asymptomatic High-Risk Family Members. JAMA Neurol. 2017 Jan 17.

IMPORTANCE: Subclinical inflammatory demyelination and neurodegeneration often precede symptom onset in multiple sclerosis (MS).

OBJECTIVE: 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.

MAIN OUTCOMES AND MEASURES: 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.

RESULTS: 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.

CONCLUSIONS AND RELEVANCE: 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.

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