Optic Nerve Diffusion Tensor Imaging after Acute Optic Neuritis Predicts Axonal and Visual Outcomes

Abstract

BackgroundEarly markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS). ObjectivesTo assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months. MethodsThirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction. ResultsAffected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated. ConclusionsThese results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.

Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system

“…After an initial decrease, AD values gradually increased back to normal AD values after a median of 18 weeks in MS ON patients. Longer AD normalization times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months [111]. These findings suggest that optic nerve DTI AD values at ON baseline and the initial course of decreased AD values gradually increasing back to normal levels are biomarker candidates in MS patients to predict functional disability and putative recovery after acute ON.…”

“…On the other hand, FA values were reported to be initially normal and then to decrease over time [111,112]. These findings suggest simultaneous demyelination and axonal loss as well as possible reorganization processes to be present in the optic nerve after ON.…”

“…Two studies consistently showed initial AD decrease at baseline [112] and after 1 month [111] to predict other visual outcome parameters -i.e. OCT RNFL thinning, full-field VEP latency delay -and visual acuity measures after 6 months [112] as well as OCT RNFL and multifocal VEP changes after 12 months [111]. After an initial decrease, AD values gradually increased back to normal AD values after a median of 18 weeks in MS ON patients.…”

Axonal degeneration in multiple sclerosis: can we predict and prevent permanent disability?

“…In fact, region-specific DTI measurements in MS patients have indicated a greater correlation of DTI changes in motor tracts with EDSS [20]. Importantly, it has been recently proposed that a reduction in axial diffusivity measurements of DTI correlate to extensive neuroinflammatorymediated axonal damage within the optic nerve following acute optic neuritis, often a primary indicator of MS [21]. Moreover, these investigators demonstrated that protracted reduction in axial diffusivity measurements correlated with pronounced retinal nerve fiber layer (RNFL) thinning and multifocal visual evoked potential (mfVEP) amplitude loss at 12 months.…”

Evaluation of the Areas Involved in Visual Cortex in Parkinson's Disease Using Diffusion Tensor Imaging

“…Among numerous advanced MR techniques Diusion-weighted image (DWI) and diusion tensor imaging Multiple system atrophy and progressive supranuclear palsy [5]. So far, DTI has been widely practical for the quantitative evaluation in many types of brain disease, including amyotrophic lateral sclerosis [6], schizophrenia [7], Parkinson's disease [8], NMO [9], and multiple sclerosis [10],and it has also been used in the quantitative evaluation of the optic nerves in normal brain [11], idiopathic demyelinating optic neuritis [12],and indirect traumatic optic neuropathy [13].…”