An Eye on Brain Integrity: Acute Optic Neuritis Affects Resting State Functional Connectivity.
Currently, the ability for imaging to capture brain adaptations to injury that occurs in multiple sclerosis
(MS) is limited. In particular, how the brain initially contends with
the earliest clinical manifestations of white matter injury has yet to
be defined. The purpose of this study is to determine the impact of
acute optic neuritis (ON) on resting state functional connectivity
magnetic resonance imaging (rs-fcMRI).
patients with a clinically isolated syndrome of acute ON were evaluated
at an academic center in a prospective study. Subjects were assessed
with structural and functional vision measures, including optical
coherence tomography (OCT), high and low contrast letter acuity testing,
visual fields and the quality of life measures (VFQ-25). rs-fcMRI was
compared to age and gender matched healthy controls.
observed reduced functional connectivity within the visual system and a
loss of anti-correlations between the visual system and non-visual
networks. Stronger functional connectivity between visual regions
correlated with better quality of life, as measured by the VFQ-25, and
better acuity scores for both high and low contrast testing in the
functional connectivity changes within (intra-network) and between
(inter-network) resting state networks occur after acute ON indicating
immediate cortical responses to focal inflammatory demyelination. Thus,
focal white matter injury in the central nervous system acutely results
in widespread network alterations that may lead to functional neurologic
changes seen in MS.
We already know that optic neuritis is the result of focal inflammation affecting the optic nerves. So how does as these researcher suggest, does focal white matter injury lead to a dysfunction in the perception of vision (i.e. a higher order cortical dysfunction)?
It seems that disruption of the anterior visual pathways also leads to similar structural changes in the rest of the brain with wider network effects that reach beyond the visual center of the brain (see figure below). Moreover, there appears to be a reduction in brain connectivity even at the earliest stages of MS.
Functional connectivity in with the primary visual cortex is disrupted in acute optic neuritis. Top row looks at the connection between the left visual cortex and the rest of the brain in healthy controls. The middle row is the same connections, but this time in acute optic neuritis. The bottom row is the difference (HC – ON) showing the reduction in functional connectivity.
Interestingly, the brain connectivity changes correlated with retinal nerve fibre layer thickness (the optic nerve fans out a nerve fibre layer at the back of the eye to serve the whole retina) following acute optic neuritis. And even more interestingly, this change correlated with RNFL thickness even in the unaffected eye. It is therefore not surprising that even MSers who have not experienced even a single episode of acute optic neuritis, still have a thinner RNFL layer compared to healthy controls!
I feel this research is clear indication that we should be treating early at the CIS (clinically isolated syndrome) stage. As neurologists we need to push the boundaries of our comfort zone and realize that we need to act!!