The two differential diagnoses in our patient were demyelinating optic neuritis and ocular toxoplasmosis with papillary involvement. Making the correct diagnosis had significant therapeutic implications. High-dose corticosteroids may improve the course of a demyelinating optic neuritis, but may exacerbate toxoplasmosis. Moreover, a patient with demyelinating optic neuritis with IgG bands in the cerebrospinal fluid and a demyelinating lesion in the brain would have been advised to begin long-term immunomodulatory therapy to prevent conversion to MS. Although the symptoms, as well as the MRI and cerebrospinal fluid findings all pointed to demyelinating disease, ophthalmological findings suggested ocular toxoplasmosis. Normal findings on MRI of the optic nerve and a normal VEP test also supported the diagnosis of toxoplasmosis, as did positive serology (3, 6, 10, 11).
T. gondii is a very common parasite worldwide, especially in warmer climates (12). Cats are the primary host of the parasite (12), which releases eggs that can be ingested by birds and most mammals, including humans. Infection occurs through consumption of undercooked meat or unwashed fruits and vegetables, or through contact with faeces from infected cats. Infections are usually asymptomatic or mild, but immunocompromised individuals may develop serious manifestations such as encephalitis (12). Infection during pregnancy can lead to miscarriage or serious birth defects such as hydrocephalus, vision loss and mental retardation (12).
Ocular toxoplasmosis is essentially a clinical diagnosis. T. gondii-IgG is usually present (6, 10), but the disease may also be the result of a past infection. While the prevalence of ocular toxoplasmosis is relatively low in Norway, a population-based study detected T. gondii-IgG in 10 % of pregnant women (13). A positive T. gondii-IgM test supports the diagnosis, but is not always seen because acute disease can also result from reactivation (2, 6, 10). T. gondii-IgG avidity testing can be used to distinguish between acute, chronic and past toxoplasma infections. Avidity is a measure of the functional affinity, or total binding strength, between an antibody and antigen (9). IgG avidity typically increases over time, and high IgG avidity therefore rules out an acute toxoplasma infection (infection during the last 3–4 months) with a high degree of certainty (9). Our patient had low IgG avidity, which together with the high IgM/IgG ratio, indicated an acute infection (9).
There is a lack of consensus over the optimal treatment for ocular toxoplasmosis (2, 6, 10). Antiparasitic treatment is recommended in cases with involvement of the optic disc, macula or retinal vessels, or where there are multiple or large lesions (2, 10). International recommendations favour the use of oral sulfadiazine and pyrimethamine, with the addition of corticosteroids if indicated (6, 10).
Sulfadiazine and pyrimethamine are not marketed in Norway and are rarely used because of their side effect profiles, and because of the teratogenicity of pyrimethamine (2). The Norwegian Ophthalmological Society instead recommends oral clindamycin and azithromycin, with the addition of corticosteroids in cases of more pronounced vitritis (2). The duration of treatment is determined by the clinical presentation. For recurrent infections, long-term systemic therapy may be required, such as a trimethoprim-sulfonamide combination (2). Intravitreal clindamycin, which was used in the current patient, is also likely to be effective (14, 15), but the evidence base is relatively limited (2, 10). The treatment may cause retinal toxicity and should be administered in collaboration with an ophthalmologist with relevant experience (10).
Ocular toxoplasmosis can affect both immunocompetent and immunodeficient individuals (6, 10). Toxoplasmosis is relatively common in immunocompetent individuals worldwide (16), and our patient had no immune deficiency.
Demyelinating optic neuritis is a frequent manifestation of multiple sclerosis. The condition is usually retrobulbar and is often without ophthalmoscopic findings in the acute stages (mild optic disc swelling is present in about one-third of cases): as the old adage goes, "the patient sees nothing, and the doctor sees nothing" (17). Demyelinating optic neuritis occurs most frequently in women aged 18–50 years. Typical early symptoms are mild to moderate retrobulbar pain exacerbated by eye movements, and the onset of blurred vision over hours to days. Examination often reveals vision loss with deficits in colour vision (dyschromatopsia), accompanied by a relative afferent pupillary defect (1, 18). The natural disease course is usually gradual spontaneous improvement. Red flags that may indicate an alternative aetiology are general malaise, young or advanced age, insidious onset, progressive course, pronounced pain or no pain at all, bilateral involvement, severe optic disc swelling and, as in the current patient, concomitant uveitis or neuroretinitis (1, 18, 19).
No definite association has been established between multiple sclerosis and toxoplasmosis (20), but the two conditions do share certain similarities, in that both can result in uveitis and optic neuritis (10, 21). The Norwegian ophthalmologist Marius Haarr was among the first to describe the association between multiple sclerosis and retinal periphlebitis. In 1951, he defended the first Norwegian doctoral thesis on the topic (22, 23). However, MS-associated uveitis is uncommon and rarely affects the posterior vitreous and optic disc, whereas both were affected in our patient (21).
This case history is an example of how a brain MRI can reveal signs of demyelinating disease in patients without clinical symptoms. This phenomenon, known as radiologically isolated syndrome, poses a significant therapeutic dilemma because about one-third of these patients will experience an episode of MS within five years (23). The presence of lesions in the spinal cord or oligoclonal IgG bands in the cerebrospinal fluid increases this risk significantly (24). Our patient did not fulfil the radiological McDonald criteria (dissemination in time and place) for multiple sclerosis, either initially or upon subsequent examination, and nor did she have spinal cord lesions. We chose therefore to continue with observation without initiating immunomodulatory therapy.
Atypical optic neuritis has been discussed in several previous case reports (1, 19, 25) and in a review article in the Journal of the Norwegian Medical Association (18). This case report illustrates the importance of remaining vigilant to possible differential diagnoses and of thorough interdisciplinary assessment, including in patients with symptoms and findings from MRI and cerebrospinal fluid analysis that may indicate demyelinating optic neuritis.