Visual Pathway Neurodegeneration And Prediction Of Brain Structure Changes In Neuromyelitis Optica Spectrum Disorder

Objective: Neuromyelitis optica spectrum disorder(NMOSD)is an inflammatory demyelinating condition of the central nervous system CNS with a predilection for attacking the optic nerves and spinal cord.The interplay between inflammation and neurodegeneration plays an important role over the entire course of pathogenesis in NMOSD.1.For the neurodegeneration,anterograde(damage from optic nerve to the OR and visual cortex)and retrograde(damage from optic nerve to the retina)trans-synaptic degeneration in the visual pathway remain unclear in NMOSD patients.2.For the inflammation,various cytokines and chemokines are involved in the regulation of immune responses by recruitment and activation of different cell types,interleukin-1?(IL-1?),IL-6 and IL-17 A are vital cytokine in the NMOSD pathogenesis.However,the relationship between clinical disability,MRI measurements and cytokine levels remains largely unknown.Therefore,the study consists of two sections.For the first section,the aim is whether bidirectional degeneration occurs within the visual pathway and,if so,the extent of such changes in NMOSD.For the second section,the aim is to investigate a potential relationship between clinical and MRI outcomes and plasma IL-1?,IL-6,IL-17 A levels in NMOSD.Methods: For the first section,in total,36 NMOSD and 24 healthy controls(HC)were enrolled.Three-dimensional T1-weighted magnetic resonance imaging(MRI)and diffusion tensor imaging(DTI)were used to analyze damage to the posterior visual pathway.Damage to the anterior visual pathway was measured by optical coherence tomography.For the second section,Forty NMOSD patients and 31 matched HC were enrolled.IL-1?,IL-6 and IL-17 A measurements were performed by ELISA.Routine brain and spinal cord MRI,3D brain high resolution T1-weighted MRI and DTI were obtained to assess brain and spinal cord lesions,atrophy and brain white matter integrity.A longitudinal follow up of a subgroup(7 patients)was used to investigate the dynamic changes.Results: For the first section,in total,24 NMOSD with prior optic neuritis(NMOON) patients showed significant reduction of peripapillary retinal nerve fiber layer,inner and outer retinal thickness,lateral geniculate nucleus volume,primary visual cortex volume,and decreased integrity of optic radiations,compared with 12 NMOSD without prior optic neuritis(NMONON)patients and 24 HCs.In NMONON,only the inner retinal thickness and the integrity of optic radiations were significantly reduced in comparison with HCs.Moreover,patients with optic neuritis showed severe bidirectional degeneration,the loss of the RNFL was greater than the atrophy of V1.For the second section,Plasma IL-1? and IL-6 levels were significantly higher in NMOSD patients when compared with HC.IL-1? levels were correlated with the brain white matter volume(WMV)and mean upper cervical cord area(MUCCA)and associated with brain diffusion measurements in NMOSD.Plasma IL-1? was positively correlated with the EDSS score in the NMOSD patients.A 2 years follow up study of 7 patients showed decreased IL-1? levels were correlated with increased brain WMV.Conclusion: Our study indicated that 1)the presence of trans-synaptic degeneration in NMOSD.Damage to the inner retina and optic radiations can be observed even in NMONON.After an episode of optic neuritis,the anterior visual pathway damage is greater than the posterior visual pathway damage.2)Plasma IL-1? levels were elevated in patients with NMOSD and correlated with structural MRI alterations and clinical disability.Our findings suggest that plasma IL-1? can be valuable to monitor NMOSD and serves as a possible treatment target.