Contributions
Abstract: P456
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration
Introduction: Cortical and subcortical brain gray matter (GM) atrophy occur early in the course of MS, but whether this underlies any early clinical dysfunction is unclear. Cervical spinal cord (SC) GM area and retinal ganglion cell layer (GCL) thickness are relatively easy to obtain, easy to quantitate and are promising means for assessing GM injury in MS. However, detailed assessments of these metrics and associations with disability metrics at the earliest disease stages have not been performed.
Objectives / aims: To investigate whether in early MS, GM atrophy can be detected in the retina and cervical SC, and whether it is associated with prior relapse and pathway specific or total disease related disability.
Methods: Sixty-four patients with median disease duration of 6 months (mean age 36.9 years, 20 men, median EDSS 2.0) and 42 matched healthy controls (HC) (mean age 36.9 years, 12 men) were investigated. SC GM and WM areas at C2/C3 (by PSIR imaging), GCL and retinal fiber nerve layer (RFNL) thickness (by SD-optic coherence tomography) were measured. Area and thickness differences betw. groups, and the associations between GM metrics and both focal (9-Hole Peg Test (9-HPT), 2.5% low contrast letter acuity (LCLA)) and global (Expanded Disability Status Score (EDSS), Symbol Digit Modalities Test (SDMT)) disability metrics were assessed using multivariable regression.
Results: SC GM areas and GCL were both sig. reduced in relapsing (p=0.0252, p=0.0030) and progressive patients (both p< 0.0001) compared to HC in the absence of sig. SC WM and RFNL reductions. SC GM and GCL atrophy were each also detected in subgroups of patients without prior SC relapse (p=0.0086) or optic neuritis (p=0.0095), respectively. Adjusting for age and sex, both SC and retinal GM metrics showed sig. associations with their corresponding focal disability metric (9-HPT: adj. R2=0.29, LCLA: adj. R2=0.30); associations with global disability metrics (EDSS: adj. R2=0.12, SDMT: adj. R2=0.07) were weak/non-sig.
Conclusions: At an early stage of MS, GM atrophy can be detected in the SC and retina in the absence of WM atrophy, even in patients without prior relapses in the corresponding functional system. Retinal and cervical SC GM atrophy correlate with focal disability metrics. This suggests that although GM is widespread at the earliest disease stages, it is not evenly distributed and provides evidence that GM injury underlies disability even very early in the disease.
Disclosure: R. Schlaeger: nothing to disclose
C. Cordano: nothing to disclose
N. Papinutto: nothing to disclose
E. Caverzasi: nothing to disclose
G. Kirkish: nothing to disclose
N. Baker: nothing to disclose
C. Bevan: nothing to disclose
A. Bischof reports speaker fees from Biogen and travel fees from Actelion.
R. Bove has received research support from the National Multiple Sclerosis Society, Hilton Foundation, California Initiative to Advance Precision Medicine, Doris Duke Award, Sherak Foundation, and Akili Interactive; and has received personal compensation for medical legal consulting and for consulting or serving on the advisory boards of F. Hoffmann-La Roche Ltd, Sanofi-Genzyme and Novartis.
E. Datta: nothing to disclose
M. Devereux: nothing to disclose
J. Gelfand: Research support from Genentech and MedDay. Consulting for Biogen. Personal compensation for medical legal consulting.
J. Graves: nothing to disclose
K. Jordan: nothing to disclose
A. Keshavan: nothing to disclose
W.A. Stern: nothing to disclose
M. Wilson receives research grant support from Roche and received a research speaking honorarium from Merck.
E. Waubant: nothing to disclose
A. Zhu: nothing to disclose
D. S. Goodin has participated a principal investigator in several clinical trials in MS and has given many public lectures regarding the epidemiology of MS and/or its treatment. These clinical trials and many of these lectures have been sponsored by various pharmaceutical companies including Biogen Idec, Bayer Schering, Novartis, EMD Serono, Genzyme, and Teva pharmaceuticals.
B.A.C. Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, Novartis and Shire. S. L. Hauser currently serves on the SAB of Symbiotix, Annexon, Bionure,
and Molecular Stethoscope and on the BOT of Neurona.
A. J. Green reports personal fees from Inception Sciences and Mylan, Pharmaceuticals and grants/awards from the National Multiple Sclerosis Society, Novartis, UCSF CTSI, and That Man May See as well as philanthropic support from the Rachelff Family and the Robert Dale Family. He also reported serving on an end point adjudication committees for Biogen and Medimmune. He serves on trial steering committees for Novartis and Scientific Advisory Board for Bionure.
R.G. Henry has received grants from Stem Cells Inc, and Roche, outside the submitted work.
Abstract: P456
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration
Introduction: Cortical and subcortical brain gray matter (GM) atrophy occur early in the course of MS, but whether this underlies any early clinical dysfunction is unclear. Cervical spinal cord (SC) GM area and retinal ganglion cell layer (GCL) thickness are relatively easy to obtain, easy to quantitate and are promising means for assessing GM injury in MS. However, detailed assessments of these metrics and associations with disability metrics at the earliest disease stages have not been performed.
Objectives / aims: To investigate whether in early MS, GM atrophy can be detected in the retina and cervical SC, and whether it is associated with prior relapse and pathway specific or total disease related disability.
Methods: Sixty-four patients with median disease duration of 6 months (mean age 36.9 years, 20 men, median EDSS 2.0) and 42 matched healthy controls (HC) (mean age 36.9 years, 12 men) were investigated. SC GM and WM areas at C2/C3 (by PSIR imaging), GCL and retinal fiber nerve layer (RFNL) thickness (by SD-optic coherence tomography) were measured. Area and thickness differences betw. groups, and the associations between GM metrics and both focal (9-Hole Peg Test (9-HPT), 2.5% low contrast letter acuity (LCLA)) and global (Expanded Disability Status Score (EDSS), Symbol Digit Modalities Test (SDMT)) disability metrics were assessed using multivariable regression.
Results: SC GM areas and GCL were both sig. reduced in relapsing (p=0.0252, p=0.0030) and progressive patients (both p< 0.0001) compared to HC in the absence of sig. SC WM and RFNL reductions. SC GM and GCL atrophy were each also detected in subgroups of patients without prior SC relapse (p=0.0086) or optic neuritis (p=0.0095), respectively. Adjusting for age and sex, both SC and retinal GM metrics showed sig. associations with their corresponding focal disability metric (9-HPT: adj. R2=0.29, LCLA: adj. R2=0.30); associations with global disability metrics (EDSS: adj. R2=0.12, SDMT: adj. R2=0.07) were weak/non-sig.
Conclusions: At an early stage of MS, GM atrophy can be detected in the SC and retina in the absence of WM atrophy, even in patients without prior relapses in the corresponding functional system. Retinal and cervical SC GM atrophy correlate with focal disability metrics. This suggests that although GM is widespread at the earliest disease stages, it is not evenly distributed and provides evidence that GM injury underlies disability even very early in the disease.
Disclosure: R. Schlaeger: nothing to disclose
C. Cordano: nothing to disclose
N. Papinutto: nothing to disclose
E. Caverzasi: nothing to disclose
G. Kirkish: nothing to disclose
N. Baker: nothing to disclose
C. Bevan: nothing to disclose
A. Bischof reports speaker fees from Biogen and travel fees from Actelion.
R. Bove has received research support from the National Multiple Sclerosis Society, Hilton Foundation, California Initiative to Advance Precision Medicine, Doris Duke Award, Sherak Foundation, and Akili Interactive; and has received personal compensation for medical legal consulting and for consulting or serving on the advisory boards of F. Hoffmann-La Roche Ltd, Sanofi-Genzyme and Novartis.
E. Datta: nothing to disclose
M. Devereux: nothing to disclose
J. Gelfand: Research support from Genentech and MedDay. Consulting for Biogen. Personal compensation for medical legal consulting.
J. Graves: nothing to disclose
K. Jordan: nothing to disclose
A. Keshavan: nothing to disclose
W.A. Stern: nothing to disclose
M. Wilson receives research grant support from Roche and received a research speaking honorarium from Merck.
E. Waubant: nothing to disclose
A. Zhu: nothing to disclose
D. S. Goodin has participated a principal investigator in several clinical trials in MS and has given many public lectures regarding the epidemiology of MS and/or its treatment. These clinical trials and many of these lectures have been sponsored by various pharmaceutical companies including Biogen Idec, Bayer Schering, Novartis, EMD Serono, Genzyme, and Teva pharmaceuticals.
B.A.C. Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, Novartis and Shire. S. L. Hauser currently serves on the SAB of Symbiotix, Annexon, Bionure,
and Molecular Stethoscope and on the BOT of Neurona.
A. J. Green reports personal fees from Inception Sciences and Mylan, Pharmaceuticals and grants/awards from the National Multiple Sclerosis Society, Novartis, UCSF CTSI, and That Man May See as well as philanthropic support from the Rachelff Family and the Robert Dale Family. He also reported serving on an end point adjudication committees for Biogen and Medimmune. He serves on trial steering committees for Novartis and Scientific Advisory Board for Bionure.
R.G. Henry has received grants from Stem Cells Inc, and Roche, outside the submitted work.