Contributions
Abstract: P573
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Multiple sclerosis (MS) is a demyelinating disease that predominantly affects the white matter (WM). However, WM lesion load exhibits only modest correlation with clinical disability, an observation known as the clinico-radiologic paradox. Accelerated brain atrophy occurs in MS and grey matter (GM) atrophy is present early in the disease course and exhibits stronger correlations with clinical measures than WM measures. The exact cause of GM atrophy is unclear but proposed mechanisms include primary GM damage, retrograde degeneration following axonal transection and trans-synaptic degeneration (TSD), a process which involves neuronal loss following damage to a pre- or post-synaptic neuron, termed anterograde and retrograde TSD respectively. The visual pathway provides an excellent model to study TSD. Cross-sectional and limited longitudinal studies have suggested that TSD may occur in the visual pathway in MS.
Objective: To evaluate for presence of anterograde TSD following acute optic neuritis (AON).
Methods: 38 patients within 45 days of onset of AON (AON cohort) and 32 relapsing-remitting MS patients without a history of prior AON (non-AON cohort) were followed with annual 3T brain MRI and regular optical coherence tomography (OCT) scans (Median follow-up: 4.2 years). Validated segmentation algorithms developed at our institution were utilized to obtain volumes of cortical/subcortical regions from MRI scans and retinal layer measurements from OCT scans. Analyses were performed with mixed-effects linear regression.
Results: In the AON and non-AON cohorts calcarine cortex atrophy was observed during follow-up but the rate of decline did not differ between the two cohorts (AON:-0.81%/year; non-AON:-0.67%/year; p=0.76). Thalamic atrophy occurred across cohorts but was significantly accelerated in the AON vs. non-AON cohort (AON:-0.95%/year; non-AON:-0.40%/year; p=0.001). Global atrophy occurred in both groups as evidenced by significant decreases in cerebral volume fraction, but this did not differ between the two cohorts (AON:-0.39%/year; non-AON:-0.37%/year; p=0.78).
Conclusions: Accelerated thalamic atrophy occurs following AON, despite similar rates of global atrophy in AON and non-AON patients, raising potential support for anterograde TSD. However, calcarine atrophy was observed at similar rates in AON and non-AON MS patients. Future study should assess the clinical significance of accelerated thalamic atrophy following AON.
Funding:
National Institutes of Health (5R01NS082347-02 to P.A.C.)
National MS Society (RG-1606-08768 to SS)
Disclosure:
E. Sotirchos, N. Gonzalez Caldito, B. Dewey, J. Glaister, K. Fitzgerald, A. Rothman, E. Ogbuokiri, J. Nguyen, J. Prince: Nothing to disclose
P. Calabresi: Has received personal honorara for consulting from Biogen and Vertex. He is PI on research grants to Johns Hopkins from Novartis, Teva, MedImmune, Annexon, and Biogen.
S. Saidha: Has received consulting fees from Medical Logix for the development of CME programs in neurology, consulting fees from Axon Advisors LLC, speaking honoraria from the National Association of Managed Care Physicians, Family Medicine Foundation of West Virginia, and Advanced Studies in Medicine and served on scientific advisory boards for Biogen-Idec, Genzyme, Genentech Corporation & Novartis. He receives research support from Genentech Corporation and the National MS Society, and received support from the Race to Erase MS foundation. He is a member of the working committee of the International Multiple Sclerosis Visual System (IMSVISUAL) Consortium.
Abstract: P573
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Multiple sclerosis (MS) is a demyelinating disease that predominantly affects the white matter (WM). However, WM lesion load exhibits only modest correlation with clinical disability, an observation known as the clinico-radiologic paradox. Accelerated brain atrophy occurs in MS and grey matter (GM) atrophy is present early in the disease course and exhibits stronger correlations with clinical measures than WM measures. The exact cause of GM atrophy is unclear but proposed mechanisms include primary GM damage, retrograde degeneration following axonal transection and trans-synaptic degeneration (TSD), a process which involves neuronal loss following damage to a pre- or post-synaptic neuron, termed anterograde and retrograde TSD respectively. The visual pathway provides an excellent model to study TSD. Cross-sectional and limited longitudinal studies have suggested that TSD may occur in the visual pathway in MS.
Objective: To evaluate for presence of anterograde TSD following acute optic neuritis (AON).
Methods: 38 patients within 45 days of onset of AON (AON cohort) and 32 relapsing-remitting MS patients without a history of prior AON (non-AON cohort) were followed with annual 3T brain MRI and regular optical coherence tomography (OCT) scans (Median follow-up: 4.2 years). Validated segmentation algorithms developed at our institution were utilized to obtain volumes of cortical/subcortical regions from MRI scans and retinal layer measurements from OCT scans. Analyses were performed with mixed-effects linear regression.
Results: In the AON and non-AON cohorts calcarine cortex atrophy was observed during follow-up but the rate of decline did not differ between the two cohorts (AON:-0.81%/year; non-AON:-0.67%/year; p=0.76). Thalamic atrophy occurred across cohorts but was significantly accelerated in the AON vs. non-AON cohort (AON:-0.95%/year; non-AON:-0.40%/year; p=0.001). Global atrophy occurred in both groups as evidenced by significant decreases in cerebral volume fraction, but this did not differ between the two cohorts (AON:-0.39%/year; non-AON:-0.37%/year; p=0.78).
Conclusions: Accelerated thalamic atrophy occurs following AON, despite similar rates of global atrophy in AON and non-AON patients, raising potential support for anterograde TSD. However, calcarine atrophy was observed at similar rates in AON and non-AON MS patients. Future study should assess the clinical significance of accelerated thalamic atrophy following AON.
Funding:
National Institutes of Health (5R01NS082347-02 to P.A.C.)
National MS Society (RG-1606-08768 to SS)
Disclosure:
E. Sotirchos, N. Gonzalez Caldito, B. Dewey, J. Glaister, K. Fitzgerald, A. Rothman, E. Ogbuokiri, J. Nguyen, J. Prince: Nothing to disclose
P. Calabresi: Has received personal honorara for consulting from Biogen and Vertex. He is PI on research grants to Johns Hopkins from Novartis, Teva, MedImmune, Annexon, and Biogen.
S. Saidha: Has received consulting fees from Medical Logix for the development of CME programs in neurology, consulting fees from Axon Advisors LLC, speaking honoraria from the National Association of Managed Care Physicians, Family Medicine Foundation of West Virginia, and Advanced Studies in Medicine and served on scientific advisory boards for Biogen-Idec, Genzyme, Genentech Corporation & Novartis. He receives research support from Genentech Corporation and the National MS Society, and received support from the Race to Erase MS foundation. He is a member of the working committee of the International Multiple Sclerosis Visual System (IMSVISUAL) Consortium.