Recurrent Bilateral Optic Neuritis
I am treating a 44-year-old woman with a history of 4 episodes of optic neuritis. The first episode caused blindness in her left eye, and the right eye acuity is now about 20/100. Her MRI results demonstrate about 4 small, circular white matter lesions, although none contrast enhancing. There is also a cavernous hemangioma in the right caudate head, with both recent and old bleeding. A spinal tap has been performed and showed no abnormal findings. What treatment options would you suggest?

Wladimir Kummer de Paula, MD

This is indeed an intriguing question, and it sounds clinically like recurrent bilateral optic neuritis. Although the MRI is reported to show "a few circular lesions," one would want to know if they are subcortical, callosal, or periventricular, whether their shape is compatible with demyelinating lesions (eg, ovoid), and whether their size varies.

I will assume that the cerebrospinal fluid (CSF) showing "no abnormality" means in fact there were no cells, protein was normal, the immunoglobulin G (IgG) index was not elevated, and no evidence of oligoclonal banding was found using an immunoblotting technique. A negative CSF result with only 4 small MRI lesions raises some doubts about a demyelinating etiology of the optic nerve problems. It is also important to ensure that there is no other explanation for the recurrent optic neuritis. One must also rule out systemic lupus erythematosus, sarcoid, infectious (eg, Lyme) or ischemic causes, and rarer entities such as Susac's syndrome. Furthermore, appropriate blood testing and careful history should exclude systemic disorders, particularly any endocrinopathies. In such circumstances, an important step would be to have a proper assessment by an ophthalmologist or neuro-ophthalmologist.

If the diagnosis favors demyelination by default, then the question remains as to whether this is demyelination due to multiple sclerosis (MS) or some other entity. Bilateral optic neuritis has been associated with Devic's syndrome or neuromyelitis optica (NMO), but this case lacks any myelopathic features or pleocytosis in the CSF. There are some cases of "autoimmune optic neuritis," but many of these case descriptions predated the MRI era, and long-term follow-up of such cases was not performed to determine whether patients subsequently developed MS. I believe the cavernoma here can be considered a bit of a "red herring."

As for treatment, some of the older literature suggests a trial of high-dose intravenous steroids, but cases often required maintenance prednisone and cytotoxic agents such as cyclophosphamide. In some cases of NMO, the combination of azathioprine and prednisone has been effective. There is really nothing more than anecdotal data to support the use of interferons. Similarly, some use intravenous immunoglobulin (IVIG) monthly, or more widely spaced infusions of 1 g/kg every 2 to 3 months has also been advocated. I favor the latter given monthly, given the few cases of autoimmune-induced visual loss that I have seen improve on this regimen.

In summary, it is not clear that this patient has MS, and therefore treatment needs to address the main problem of visual loss, which is bordering on complete blindness. Regardless of a diagnosis of MS, some form of immunosuppression or immunomodulation (eg, IVIG) should be considered to protect the optic nerves from further damage.