Contributions
Abstract: P537
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Objective: To assess the prevalence of brain magnetic resonance imaging (MRI) and subclinical abnormalities consistent with demyelination and axonal loss in asymptomatic individuals at risk for multiple sclerosis (MS).
Background: Subclinical inflammatory demyelination and neurodegeneration likely precede symptom onset in MS.
Methods: The Genes and Environment in Multiple Sclerosis (GEMS) is a prospective cohort study of MS first-degree family members that investigates risk factors and the sequence of events leading to MS onset. We assessed each subject"s risk for MS susceptibility using a weighted genetic and environmental risk score (GERS). Subjects 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.
Results: This study includes 100 subjects from higher-risk (n=41, 98% female) and lower-risk (n=59, 42% women) subgroups, with a mean age of 35.1 years. Given the unequal sex distribution between the two groups, we restricted analyses to women (n=65). Five women (8%) met the primary neuroimaging outcome of having brain T2-hyperintense brain lesions consistent with the 2010 MRI criteria for dissemination in space (4 higher-risk women and 1 lower-risk woman, 4:1 ratio). Further, a subset of these MS first-degree relatives harbor many different neuroimaging features that are associated with MS pathology, including perivenous T2 hyperintense lesions (22%) and focal leptomeningeal enhancement (6%), consistent with the idea that these individuals are at higher risk of developing MS than the general population. Interestingly, higher-risk women exhibited worse vibration sensitivity in distal lower extremities as detected by the Vibratron-II device (p=0.0082, after adjusting for age, smoking status, height, and testing date).
Conclusions: Asymptomatic family members at higher risk for MS manifest impaired vibration sensitivity, which may constitute evidence of myelitis, abnormal myelin structure / function and/or neurodegeneration and underscores the importance of early detection in high-risk individuals.
Disclosure:
Zongqi Xia: a recipient of the Clinician Scientist Development Award from the National Multiple Sclerosis Society and the American Academy of Neurology, research funding from NINDS (K08NS079493), research grant from DNAGenotek (not relevant to this abstract)
Sonya Steele: nothing to disclose
Anshika Bakshi: nothing to disclose
Sarah Clarkson: nothing to disclose
Matthew Schindler: nothing to disclose
Blake Dewey: nothing to disclose
Joan Ohayon: nothing to disclose
Lori Chibnik: nothing to disclose
Irene Cortese: nothing to disclose
Philip De Jager: a Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society, research funding from the National Multiple Sclerosis Society (RG5003A2), research grant from Biogen, Sanofi/Genzyme (none relevant to this abstract)
Daniel Reich: research funding from Intramural Research Program of NINDS, Myelin Repair Foundation, and Vertex Pharmaceuticals (none relevant to this abstract)
Abstract: P537
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Objective: To assess the prevalence of brain magnetic resonance imaging (MRI) and subclinical abnormalities consistent with demyelination and axonal loss in asymptomatic individuals at risk for multiple sclerosis (MS).
Background: Subclinical inflammatory demyelination and neurodegeneration likely precede symptom onset in MS.
Methods: The Genes and Environment in Multiple Sclerosis (GEMS) is a prospective cohort study of MS first-degree family members that investigates risk factors and the sequence of events leading to MS onset. We assessed each subject"s risk for MS susceptibility using a weighted genetic and environmental risk score (GERS). Subjects 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.
Results: This study includes 100 subjects from higher-risk (n=41, 98% female) and lower-risk (n=59, 42% women) subgroups, with a mean age of 35.1 years. Given the unequal sex distribution between the two groups, we restricted analyses to women (n=65). Five women (8%) met the primary neuroimaging outcome of having brain T2-hyperintense brain lesions consistent with the 2010 MRI criteria for dissemination in space (4 higher-risk women and 1 lower-risk woman, 4:1 ratio). Further, a subset of these MS first-degree relatives harbor many different neuroimaging features that are associated with MS pathology, including perivenous T2 hyperintense lesions (22%) and focal leptomeningeal enhancement (6%), consistent with the idea that these individuals are at higher risk of developing MS than the general population. Interestingly, higher-risk women exhibited worse vibration sensitivity in distal lower extremities as detected by the Vibratron-II device (p=0.0082, after adjusting for age, smoking status, height, and testing date).
Conclusions: Asymptomatic family members at higher risk for MS manifest impaired vibration sensitivity, which may constitute evidence of myelitis, abnormal myelin structure / function and/or neurodegeneration and underscores the importance of early detection in high-risk individuals.
Disclosure:
Zongqi Xia: a recipient of the Clinician Scientist Development Award from the National Multiple Sclerosis Society and the American Academy of Neurology, research funding from NINDS (K08NS079493), research grant from DNAGenotek (not relevant to this abstract)
Sonya Steele: nothing to disclose
Anshika Bakshi: nothing to disclose
Sarah Clarkson: nothing to disclose
Matthew Schindler: nothing to disclose
Blake Dewey: nothing to disclose
Joan Ohayon: nothing to disclose
Lori Chibnik: nothing to disclose
Irene Cortese: nothing to disclose
Philip De Jager: a Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society, research funding from the National Multiple Sclerosis Society (RG5003A2), research grant from Biogen, Sanofi/Genzyme (none relevant to this abstract)
Daniel Reich: research funding from Intramural Research Program of NINDS, Myelin Repair Foundation, and Vertex Pharmaceuticals (none relevant to this abstract)