Contributions
Abstract: P1114
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Neuro-axonal degeneration is considered to represent the substrate of permanent neurological disability in multiple sclerosis (MS) and can be indirectly quantified in vivo by use of brain MRI volumetric measures. Grey matter (GM) volume exhibits stronger correlations with disability than white matter (WM) volume and may predict future disability in MS. Subcortical GM structures, particularly the thalamus, have been shown to be affected at the earliest stages of MS and to exhibit faster atrophy rates than other GM regions, throughout the disease course. However, longitudinal studies of the relationship of GM substructure volumes and disability accrual in MS are limited, and mainly restricted to short-term follow-up.
Objective: To evaluate the clinical predictive utility of baseline whole brain and brain substructure volumes in people with MS.
Methods: An observational, prospective cohort of people with MS, followed with annual 3T brain MRI and biannual Expanded Disability Status Scale (EDSS), was evaluated. An automated MRI pipeline was utilized to obtain whole brain, cortical GM, subcortical GM (including the thalamus, putamen, caudate and globus pallidus), cerebral WM and T2 lesion volumes. Sustained disability progression was defined as a ≥1.5 point, ≥1-point or ≥0.5-point increase in EDSS score, if the baseline EDSS score was 0, < 5.5 or ≥5.5 respectively, confirmed on repeat evaluation after ≥6 months. Cox proportional hazards models were utilized to assess baseline brain substructure volumes as predictors of time-to-sustained disability progression, adjusting for age, sex, race, disease subtype and baseline EDSS.
Results: Data from 141 eligible participants were analyzed (median follow-up: 6.6 years). Sustained disability progression occurred in 35 participants (25%). In multivariable-adjusted models, baseline thalamic volume was an independent predictor of time-to-sustained disability progression (adjusted hazard ratio per one standard deviation decrease: 1.47; 95% CI: 1.05 to 2.05; p=0.025). Baseline whole brain, cortical GM, cerebral WM, other subcortical GM structures, and T2 lesion volumes were not associated with disability accrual during follow-up.
Conclusions: Decreased thalamic volume may independently identify individuals with MS at an increased risk of future, long-term disability progression.
Disclosure: This study was funded by the NIH (5R01NS082347 to P.A.C.; 5P41EB015909 to P.C.V.Z.), National MS Society (FP-1607-24999 to E.S.S.; RG-1606-08768 to S.S; TR 3760-A-3 to P.A.C; RG 4212-A-4 & RG-1507-05243 to D.L.P.), and Race to Erase MS (to S.S.).
Disclosures:
Elias Sotirchos is funded by a Sylvia Lawry physician fellowship award from the National Multiple Sclerosis Society (NMSS).
Natalia Gonzalez-Caldito has nothing to report.
Blake Dewey has nothing to report.
Kathryn Fitzgerald is funded by postdoctoral fellowships from the NMSS and Consortium of MS Centers (CMSC).
Angeliki Filippatou has nothing to report.
Jeffrey Glaister has nothing to report.
Dzung Pham has nothing to report.
Peter Van Zijl is a paid lecturer for Philips Healthcare and has technology licensed to Philips Healthcare; this arrangement has been approved by Johns Hopkins University in accordance with its Conflict of Interest policies.
Ellen Mowry has grants from Biogen and Genzyme, is site PI for studies sponsored by Biogen and Sun Pharma, has received free medication for a clinical trial from Teva and receives royalties for editorial duties from UpToDate.
Daniel Reich is supported by the Intramural Research Program of NINDS and has no disclosures relevant to the content of this article.
Jerry Prince is a founder of Sonovex, Inc. and serves on its Board of Directors.
Shiv Saidha has received consulting fees from Medical Logix for the development of CME programs in neurology and has served on scientific advisory boards for Biogen-Idec, Genzyme, Genentech Corporation, EMD Serono & Novartis. He is the PI of investigator-initiated studies funded by Genentech Corporation and Biogen Idec, and received support from the Race to Erase MS foundation. He has received equity compensation for consulting from JuneBrain LLC, a retinal imaging device developer. He is also the site investigator of a trial sponsored by MedDay Pharmaceuticals.
Peter Calabresi has received personal honorariums for consulting from Disarm Therapeutics. He is PI on research grants to Johns Hopkins from MedImmune, Annexon, and Genzyme.
Abstract: P1114
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Neuro-axonal degeneration is considered to represent the substrate of permanent neurological disability in multiple sclerosis (MS) and can be indirectly quantified in vivo by use of brain MRI volumetric measures. Grey matter (GM) volume exhibits stronger correlations with disability than white matter (WM) volume and may predict future disability in MS. Subcortical GM structures, particularly the thalamus, have been shown to be affected at the earliest stages of MS and to exhibit faster atrophy rates than other GM regions, throughout the disease course. However, longitudinal studies of the relationship of GM substructure volumes and disability accrual in MS are limited, and mainly restricted to short-term follow-up.
Objective: To evaluate the clinical predictive utility of baseline whole brain and brain substructure volumes in people with MS.
Methods: An observational, prospective cohort of people with MS, followed with annual 3T brain MRI and biannual Expanded Disability Status Scale (EDSS), was evaluated. An automated MRI pipeline was utilized to obtain whole brain, cortical GM, subcortical GM (including the thalamus, putamen, caudate and globus pallidus), cerebral WM and T2 lesion volumes. Sustained disability progression was defined as a ≥1.5 point, ≥1-point or ≥0.5-point increase in EDSS score, if the baseline EDSS score was 0, < 5.5 or ≥5.5 respectively, confirmed on repeat evaluation after ≥6 months. Cox proportional hazards models were utilized to assess baseline brain substructure volumes as predictors of time-to-sustained disability progression, adjusting for age, sex, race, disease subtype and baseline EDSS.
Results: Data from 141 eligible participants were analyzed (median follow-up: 6.6 years). Sustained disability progression occurred in 35 participants (25%). In multivariable-adjusted models, baseline thalamic volume was an independent predictor of time-to-sustained disability progression (adjusted hazard ratio per one standard deviation decrease: 1.47; 95% CI: 1.05 to 2.05; p=0.025). Baseline whole brain, cortical GM, cerebral WM, other subcortical GM structures, and T2 lesion volumes were not associated with disability accrual during follow-up.
Conclusions: Decreased thalamic volume may independently identify individuals with MS at an increased risk of future, long-term disability progression.
Disclosure: This study was funded by the NIH (5R01NS082347 to P.A.C.; 5P41EB015909 to P.C.V.Z.), National MS Society (FP-1607-24999 to E.S.S.; RG-1606-08768 to S.S; TR 3760-A-3 to P.A.C; RG 4212-A-4 & RG-1507-05243 to D.L.P.), and Race to Erase MS (to S.S.).
Disclosures:
Elias Sotirchos is funded by a Sylvia Lawry physician fellowship award from the National Multiple Sclerosis Society (NMSS).
Natalia Gonzalez-Caldito has nothing to report.
Blake Dewey has nothing to report.
Kathryn Fitzgerald is funded by postdoctoral fellowships from the NMSS and Consortium of MS Centers (CMSC).
Angeliki Filippatou has nothing to report.
Jeffrey Glaister has nothing to report.
Dzung Pham has nothing to report.
Peter Van Zijl is a paid lecturer for Philips Healthcare and has technology licensed to Philips Healthcare; this arrangement has been approved by Johns Hopkins University in accordance with its Conflict of Interest policies.
Ellen Mowry has grants from Biogen and Genzyme, is site PI for studies sponsored by Biogen and Sun Pharma, has received free medication for a clinical trial from Teva and receives royalties for editorial duties from UpToDate.
Daniel Reich is supported by the Intramural Research Program of NINDS and has no disclosures relevant to the content of this article.
Jerry Prince is a founder of Sonovex, Inc. and serves on its Board of Directors.
Shiv Saidha has received consulting fees from Medical Logix for the development of CME programs in neurology and has served on scientific advisory boards for Biogen-Idec, Genzyme, Genentech Corporation, EMD Serono & Novartis. He is the PI of investigator-initiated studies funded by Genentech Corporation and Biogen Idec, and received support from the Race to Erase MS foundation. He has received equity compensation for consulting from JuneBrain LLC, a retinal imaging device developer. He is also the site investigator of a trial sponsored by MedDay Pharmaceuticals.
Peter Calabresi has received personal honorariums for consulting from Disarm Therapeutics. He is PI on research grants to Johns Hopkins from MedImmune, Annexon, and Genzyme.