SEATTLE—Vision is typically restored following an attack of optic neuritis, despite persistent abnormal nerve conduction and axonal loss. The key to visual recovery is the recruitment of additional cortical connections outside the visual cortex, according to a study presented at the 124th Annual Meeting of the American Neurological Association.

"A remarkable feature of demyelinating diseases is their capacity for complete functional recovery, despite the persistence of structural damage and conduction abnormalities in affected pathways. In optic neuritis, an excellent recovery is usually observed, despite the frequent occurrence of retinal fiber layer loss and visual evoked potential delay. This raises the possibility that the central nervous system has somehow adapted to compensate for a persistently abnormal input pattern," said David J. Werring, MD, and his colleagues from the Institute of Neurology, University College London, UK.

A WIDER ACTIVATION PATTERN

In patients who had recovered from optic neuritis, visual stimulation activated parts of the frontal, temporal, and parietal cortices, as well as the visual cortex. This wider activation pattern, the researchers suggested, might compensate for the anatomic and physiologic abnormalities that remain after optic neuritis, permitting restoration of almost normal visual information processing. In control subjects receiving the same visual stimulation, activation was confined to the visual cortex.

Dr. Werring and colleagues used functional magnetic resonance imaging (fMRI) to map cerebral responses to visual stimulation in a sample of 14 subjects. Seven (three men, four women; mean age, 37.8) had presented with isolated unilateral optic neuritis but had recovered their vision—with normal acuity and color perception—by the time the study began. Five of these patients had abnormal structural damage to the affected optic nerve, while two had definite evoked potential delay. The other seven participants (three men, four women; mean age, 31.0) were normal controls. Patients with evidence of demyelination outside the optic nerve were excluded.

Neuroimaging was conducted during eight-minute sessions while the 14 subjects received 20-second epochs of monocular stimulation, alternating with equal periods of darkness. The subjects were studied twice in random order, while each eye was stimulated separately with a flashing red light. Also under investigation was the link between volume of abnormal extraoccipital activation and visual evoked latency.

Normally, visual stimulation of either eye will exclusively activate areas of the visual cortex. Stimulating the clinically unaffected eye in the recovered optic neuritis patients, however, caused additional activation in the right insula-claustrum. Stimulating the recovered eye caused further extensive bilateral activation in the insula-claustrum, lateral temporal cortex, posterior parietal cortex, orbitofrontal cortex, corpus striatum, and thalamus. This extraoccipital activation was observed in all seven patients who had recovered from optic neuritis. The putative multimodal sensory areas, which have extensive visual connections, showed peak fMRI signal change during the dark (baseline) phase. Findings were similar in studies using 40-second periods of darkness and monocular stimulation.

The fMRI maps of two patients with definite evoked potential delay showed an even greater extent of extraoccipital activation. There was a graded relationship of extraoccipital volume with visual evoked potential latency, suggesting that compensatory changes are likely to occur in the synaptic relays within the cerebral cortex. "The phase of periodic fMRI signal change in the extraoccipital areas activated only by patients was delayed relative to the phase of response to photic stimulation in visual cortex," the researchers explained.

ENDURING CHANGES?

The new findings provide compelling evidence that temporary visual loss from optic nerve damage can produce long-term changes in brain activation patterns. "Whether and how these changes might contribute to the recovery process and its maintenance remains to be determined," the researchers said. "An important next step will be to determine the time course of the changes and their relationship to clinical and electrophysiological measures in serial studies from symptom onset," they added. Confirmation that cortical reorganization enhances the recovery process could have substantial implications for the development and monitoring of rehabilitation strategies, the researchers concluded—not only for recovery from optic neuritis, but for other manifestations of demyelinating disease as well.

-Janis Kelly
Contributing Writer

Suggested Reading
Werring DJ, Clark CA, Parker GJ, et al. A direct demonstration of both structure and function in the visual system: Combining diffusion tensor imaging with functional magnetic resonance imaging. Neuroimage. 1999;9:352-361.

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