Anatomical wiring and functional networking changes in the visual system following optic neuritis

Yael Backner, Joseph Kuchling, Said Massarwa, Timm Oberwahrenbrock, Carsten Finke, Judith Bellmann-Strobl, Klemens Ruprecht, Alexander U. Brandt, Hanna Zimmermann, Noa Raz, Friedemann Paul, Netta Levin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


IMPORTANCE Clinical outcome in multiple sclerosis was suggested to be driven by not only remyelination but also adaptive reorganization. This mechanism needs to be further understood. OBJECTIVE To explore anatomical and functional visual networks in patients with optic neuritis (ON) to assess the relative weight of each connectivity modality to expedite visual recovery. DESIGN, SETTING, AND PARTICIPANTS Between March 11, 2011, and May 26, 2014, 39 patients with either clinically isolated syndrome (CIS) ON (n = 18) or other CIS (non-ON) (n = 21) were recruited 1 to 28 months following an initial clinical event. These patients enrolled in an ongoing prospective cohort study (107 participants at the time of this present study) about the disease course of CIS and multiple sclerosis. Inclusion criteria were an age of 18 to 65 years, the suggestive clinical and paraclinical diagnosis of CIS or multiple sclerosis after relevant differential diagnoses have been ruled out, the existence of complete imaging data, and no ocular comorbidities. Anatomical connectivity was evaluated by diffusion tensor imaging, and functional connectivity was evaluated by resting-state functional magnetic resonance imaging. The visual pathways, including optic tracts, optic radiations, and splenial fibers, were delineated, and the resting-state visual networks were detected. Data analysis took place from September 1, 2015, to December 1, 2015. MAIN OUTCOMES AND MEASURES Connectivity changeswere quantified and compared to determine the association of ON with the visual network. RESULTS This study included 18 patients with CIS ON, 11 (61%) of whom were women with a mean (SD) age of 32.83 (8.53) years, and 21 patients with CIS non-ON (11 [52%] of whom were women with a mean [SD] age of 30.86 [7.54] years). With the use of diffusion tensor imaging, reduced diffusivity (mean [SD] fractional anisotropy, 0.35 [0.03] vs 0.38 [0.03]; P < .01) was evident along the optic tracts of patients with ON, suggesting the extension of axonal injury from the damaged optic nerve. Neither the optic radiations nor the splenial fibers showed evidence of loss of integrity. Yet, in the presence of an intact postgeniculate anatomical network, the functional connectivity within the visual network was higher in the ON cohort. Functional connectivity observed in cortical motion-related areas was inversely correlated with the visual evoked potential-measured conduction velocity (r =-0.59; P < .05). CONCLUSIONS AND RELEVANCE In this cohort, local optic nerve demyelinating damage does not affect distant wiring, but even in the presence of an intact anatomical network, functional modification may occur. These functional network changesmay be part of the recovery process, but further research is needed to elucidate this process.

Original languageAmerican English
Pages (from-to)287-295
Number of pages9
JournalJAMA Neurology
Issue number3
StatePublished - Mar 2018
Externally publishedYes

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