{"doi":"10.1002/ana.26529","title":"Trans‐Synaptic Degeneration Following Acute Optic Neuritis in Multiple Sclerosis","abstract":"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.","journal":"Annals of Neurology","year":2022,"id":252124,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9226,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":241641,"name":"Elias S. Sotirchos","orcid":"0000-0002-8812-1637","position":1,"is_corresponding":false},{"id":492664,"name":"Grigorios Kalaitzidis","orcid":"0000-0001-7680-3609","position":2,"is_corresponding":false},{"id":492665,"name":"Eleni S. Vasileiou","orcid":"0000-0002-8639-8405","position":3,"is_corresponding":false},{"id":492667,"name":"Henrik Ehrhardt","orcid":"0000-0003-3246-6609","position":4,"is_corresponding":false},{"id":492666,"name":"Jeffrey Lambe","orcid":"0000-0002-3306-0988","position":5,"is_corresponding":false},{"id":896081,"name":"Ohemaa Kwakyi","orcid":"0000-0002-6034-0686","position":6,"is_corresponding":false},{"id":575978,"name":"James Nguyen","orcid":"0000-0002-9972-6252","position":7,"is_corresponding":false},{"id":896598,"name":"Alexandra Zambriczki Lee","orcid":null,"position":8,"is_corresponding":false},{"id":800650,"name":"Julia Button","orcid":null,"position":9,"is_corresponding":false},{"id":420040,"name":"Blake E. Dewey","orcid":"0000-0003-4554-5058","position":10,"is_corresponding":false},{"id":615362,"name":"Scott D. Newsome","orcid":"0000-0002-5284-4681","position":11,"is_corresponding":false},{"id":241643,"name":"Ellen M. Mowry","orcid":"0000-0003-0623-5188","position":12,"is_corresponding":false},{"id":241632,"name":"Kathryn C. Fitzgerald","orcid":"0000-0003-3137-0322","position":13,"is_corresponding":false},{"id":249467,"name":"Jerry L. Prince","orcid":"0000-0002-6553-0876","position":14,"is_corresponding":false},{"id":241645,"name":"Peter A. Calabresi","orcid":"0000-0002-7776-6472","position":15,"is_corresponding":false},{"id":280480,"name":"Shiv Saidha","orcid":"0000-0001-6387-0714","position":16,"is_corresponding":false},{"id":250707,"name":"Olwen C. Murphy","orcid":"0000-0001-7880-8948","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T00:24:46.226372Z","pmid":"36218157","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}