Neuroprotection for acute optic neuritis-Can it work?

Optic neuritis is a common manifestation of MS and the acute inflammatory lesion in the optic nerve resembles demyelinating plaques elsewhere in the CNS. As with other MS relapses, treatment with corticosteroids has little or no impact on the extent to which vision eventually recovers after an attack of optic neuritis. Neuroaxonal loss is now recognised as a major cause of permanent disability. Imaging of the retinal nerve fibre layer with optical coherence tomography (OCT) and of the optic nerve with MRI both demonstrate significant volume loss which correlates with impaired visual function. The extent of axonal loss correlates with the magnitude of inflammation and there is robust evidence that excessive accumulation of sodium ions within axons in an inflammatory environment leads to axonal degeneration. Partial blockade of sodium channels protects against axonal loss and improves clinical outcome in experimental models of MS. The recent randomised placebo-controlled trial of lamotrigine in secondary progressive MS did not demonstrate a protective effect on brain atrophy, and indeed the opposite effect was observed during the first year of treatment. Despite this, there were some positive treatment signals. Specifically the rate of decline of walking speed was halved in the active group compared to placebo and the treatment compliant group had a significantly lower serum concentration of neurofilament. The limitiations in the design of the lamotrigine trial have been addressed in the ongoing trial of neuroprotection with phenytoin in acute optic neuritis. Specifically, treatment will be tested in an early inflammatory lesion and the readout will be timed beyond the lag in development of atrophy in the optic nerve and retina and after any treatment related volume changes have subsided. If the treatment is successful, this form of neuroprotection should improve the recovery from relapses in general, since the pathophysiology of optic neuritis resembles that of other MS relapses.

RCT Entities:   Population Interventions Outcomes