Contributions
Abstract: P647
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Introduction: Functional impairment in MS reflects a composite of white matter (WM) and grey matter (GM) damage. Estimation of axonal conduction velocity (ACV) within demyelinated white matter (WM) lesions could be used to elucidate the relative contribution of focal structural pathology within WM bundles in the CNS. While an ACV of approximately 2.72mm/ms has been reported in brainstem MS lesions1, cerebral WM tracts have not been similarly interrogated. We used a combination of MRI and multi-focal visual evoked potentials (mfVEP) to probe the impact of focal WM pathology on visual pathway function in patients with MS.
Objective: To estimate the ACV in demyelinated segments of the optic radiation (OR) in vivo.
Methods: Fifty patients with RRMS were enrolled in the study. mfVEP recording from eyes without a clinical history of optic neuritis (ON) were included, and analyzed for each visual hemi-field, corresponding to left and right ORs. 3DT1, FLAIR and 64-dir dMRI were acquired with a 3.0T MRI scanner. ORs were delineated using probabilistic tractography and lesion length along each OR computed. Patients without lesions in both ORs or with active gadolinium-enhancing lesions (GELs) in either OR were excluded. The onset latency differences (Δτ) and corresponding lesion length differences (Δλ) between visual hemifields were modelled with linear regression, and the absolute ACV calculated based on Δτ/Δλ= 1/ACVlesion -1/ACVnormal, where ACVnormal was assumed starting at approximately 32mm/ms1.
Results: Twenty patients remained in the study after excluding those with bilateral ON, OR Gad+ lesions, and those without OR lesions on either side. Linear regression predicted lesion length difference between left and right OR based on the onset latency differences (F(1,19)=12.44,p=0.002, R2=0.40). ACVlesion were estimated at approximately 1.70 mm/ms.
Conclusion: The estimation of ACVlesion ~ 1.70 mm/ms in demyelinated OR aligns with the ACV previously reported in the demyelinated medial longitudinal fasciculus; and represents a composite MRI-mfVEP biomarker that discerns the relative contribution of WM and GM pathology to functional impairment in MS.
References: Wang C, et al. Axonal conduction in multiple sclerosis: A combined magnetic resonance imaging and electrophysiological study of the medial longitudinal fasciculus. Mult Scler2015;21(7):1-11.
Disclosure: This study was partially funded by Novartis Pharma AG, Basel, Switzerland.
Chenyu Wang declared no conflict of interest.
Joshua Barton declared no conflict of interest.
Alexander Klistorner declared no conflict of interest.
Linda Ly declared no conflict of interest.
Heidi N Beadnall has received compensation for education travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck and Sanofi-Genzyme.
Stephen Reddel has received payments for grant support from Biogen, CSL, Novartis and Sanofi-Genzyme, travel support from Merck, Sanofi-Genzyme and Teva, membership on advisory councils from Biogen, Merck, Sanofi-Genzyme and Teva, speaker's bureau from Biogen, Novartis, and Sanofi-Genzyme, and is a shareholder in Medical Safety Systems P/L Australia.
Matthew C Kiernan is Editor-in-Chief of Journal of Neurology, Neurosurgery & Psychiatry.
Michael Barnett has received institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche and Sanofi Genzyme. Dr Barnett is a research consultant at Medical Safety Systems and research director for the Sydney Neuroimaging Analysis Centre.
Abstract: P647
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Introduction: Functional impairment in MS reflects a composite of white matter (WM) and grey matter (GM) damage. Estimation of axonal conduction velocity (ACV) within demyelinated white matter (WM) lesions could be used to elucidate the relative contribution of focal structural pathology within WM bundles in the CNS. While an ACV of approximately 2.72mm/ms has been reported in brainstem MS lesions1, cerebral WM tracts have not been similarly interrogated. We used a combination of MRI and multi-focal visual evoked potentials (mfVEP) to probe the impact of focal WM pathology on visual pathway function in patients with MS.
Objective: To estimate the ACV in demyelinated segments of the optic radiation (OR) in vivo.
Methods: Fifty patients with RRMS were enrolled in the study. mfVEP recording from eyes without a clinical history of optic neuritis (ON) were included, and analyzed for each visual hemi-field, corresponding to left and right ORs. 3DT1, FLAIR and 64-dir dMRI were acquired with a 3.0T MRI scanner. ORs were delineated using probabilistic tractography and lesion length along each OR computed. Patients without lesions in both ORs or with active gadolinium-enhancing lesions (GELs) in either OR were excluded. The onset latency differences (Δτ) and corresponding lesion length differences (Δλ) between visual hemifields were modelled with linear regression, and the absolute ACV calculated based on Δτ/Δλ= 1/ACVlesion -1/ACVnormal, where ACVnormal was assumed starting at approximately 32mm/ms1.
Results: Twenty patients remained in the study after excluding those with bilateral ON, OR Gad+ lesions, and those without OR lesions on either side. Linear regression predicted lesion length difference between left and right OR based on the onset latency differences (F(1,19)=12.44,p=0.002, R2=0.40). ACVlesion were estimated at approximately 1.70 mm/ms.
Conclusion: The estimation of ACVlesion ~ 1.70 mm/ms in demyelinated OR aligns with the ACV previously reported in the demyelinated medial longitudinal fasciculus; and represents a composite MRI-mfVEP biomarker that discerns the relative contribution of WM and GM pathology to functional impairment in MS.
References: Wang C, et al. Axonal conduction in multiple sclerosis: A combined magnetic resonance imaging and electrophysiological study of the medial longitudinal fasciculus. Mult Scler2015;21(7):1-11.
Disclosure: This study was partially funded by Novartis Pharma AG, Basel, Switzerland.
Chenyu Wang declared no conflict of interest.
Joshua Barton declared no conflict of interest.
Alexander Klistorner declared no conflict of interest.
Linda Ly declared no conflict of interest.
Heidi N Beadnall has received compensation for education travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck and Sanofi-Genzyme.
Stephen Reddel has received payments for grant support from Biogen, CSL, Novartis and Sanofi-Genzyme, travel support from Merck, Sanofi-Genzyme and Teva, membership on advisory councils from Biogen, Merck, Sanofi-Genzyme and Teva, speaker's bureau from Biogen, Novartis, and Sanofi-Genzyme, and is a shareholder in Medical Safety Systems P/L Australia.
Matthew C Kiernan is Editor-in-Chief of Journal of Neurology, Neurosurgery & Psychiatry.
Michael Barnett has received institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche and Sanofi Genzyme. Dr Barnett is a research consultant at Medical Safety Systems and research director for the Sydney Neuroimaging Analysis Centre.