TY - JOUR
T1 - Trans-Synaptic Degeneration Following Acute Optic Neuritis in Multiple Sclerosis
AU - Murphy, Olwen
AU - Sotirchos, Elias S.
AU - Kalaitzidis, Grigorios
AU - Vasileiou, Elena
AU - Ehrhardt, Henrik
AU - Lambe, Jeffrey
AU - Kwakyi, Ohemaa
AU - Nguyen, James
AU - Zambriczki Lee, Alexandra
AU - Button, Julia
AU - Dewey, Blake E.
AU - Newsome, Scott D.
AU - Mowry, Ellen M.
AU - Fitzgerald, Kathryn C.
AU - Prince, Jerry L.
AU - Calabresi, Peter A.
AU - Saidha, Shiv
N1 - Publisher Copyright:
© 2022 American Neurological Association.
PY - 2023/1
Y1 - 2023/1
N2 - Objective: To explore longitudinal changes in brain volumetric measures and retinal layer thicknesses following acute optic neuritis (AON) in people with multiple sclerosis (PwMS), to investigate the process of trans-synaptic degeneration, and determine its clinical relevance. Methods: PwMS were recruited within 40 days of AON onset (n = 49), and underwent baseline retinal optical coherence tomography and brain magnetic resonance imaging followed by longitudinal tracking for up to 5 years. A comparator cohort of PwMS without a recent episode of AON were similarly tracked (n = 73). Mixed-effects linear regression models were used. Results: Accelerated atrophy of the occipital gray matter (GM), calcarine GM, and thalamus was seen in the AON cohort, as compared with the non-AON cohort (−0.76% vs −0.22% per year [p = 0.01] for occipital GM, −1.83% vs −0.32% per year [p = 0.008] for calcarine GM, −1.17% vs −0.67% per year [p = 0.02] for thalamus), whereas rates of whole-brain, cortical GM, non-occipital cortical GM atrophy, and T2 lesion accumulation did not differ significantly between the cohorts. In the AON cohort, greater AON-induced reduction in ganglion cell+inner plexiform layer thickness over the first year was associated with faster rates of whole-brain (r = 0.32, p = 0.04), white matter (r = 0.32, p = 0.04), and thalamic (r = 0.36, p = 0.02) atrophy over the study period. Significant relationships were identified between faster atrophy of the subcortical GM and thalamus, with worse visual function outcomes after AON. Interpretation: These results provide in-vivo evidence for anterograde trans-synaptic degeneration following AON in PwMS, and suggest that trans-synaptic degeneration may be related to clinically-relevant visual outcomes. ANN NEUROL 2023;93:76–87.
AB - Objective: To explore longitudinal changes in brain volumetric measures and retinal layer thicknesses following acute optic neuritis (AON) in people with multiple sclerosis (PwMS), to investigate the process of trans-synaptic degeneration, and determine its clinical relevance. Methods: PwMS were recruited within 40 days of AON onset (n = 49), and underwent baseline retinal optical coherence tomography and brain magnetic resonance imaging followed by longitudinal tracking for up to 5 years. A comparator cohort of PwMS without a recent episode of AON were similarly tracked (n = 73). Mixed-effects linear regression models were used. Results: Accelerated atrophy of the occipital gray matter (GM), calcarine GM, and thalamus was seen in the AON cohort, as compared with the non-AON cohort (−0.76% vs −0.22% per year [p = 0.01] for occipital GM, −1.83% vs −0.32% per year [p = 0.008] for calcarine GM, −1.17% vs −0.67% per year [p = 0.02] for thalamus), whereas rates of whole-brain, cortical GM, non-occipital cortical GM atrophy, and T2 lesion accumulation did not differ significantly between the cohorts. In the AON cohort, greater AON-induced reduction in ganglion cell+inner plexiform layer thickness over the first year was associated with faster rates of whole-brain (r = 0.32, p = 0.04), white matter (r = 0.32, p = 0.04), and thalamic (r = 0.36, p = 0.02) atrophy over the study period. Significant relationships were identified between faster atrophy of the subcortical GM and thalamus, with worse visual function outcomes after AON. Interpretation: These results provide in-vivo evidence for anterograde trans-synaptic degeneration following AON in PwMS, and suggest that trans-synaptic degeneration may be related to clinically-relevant visual outcomes. ANN NEUROL 2023;93:76–87.
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U2 - 10.1002/ana.26529
DO - 10.1002/ana.26529
M3 - Article
C2 - 36218157
AN - SCOPUS:85140251637
SN - 0364-5134
VL - 93
SP - 76
EP - 87
JO - Annals of neurology
JF - Annals of neurology
IS - 1
ER -