Optic neuritis and risk of MS: Differential diagnosis and management
ABSTRACTOptic neuritis, a cause of sudden vision loss, often heralds the onset of multiple sclerosis (MS) within the next few years. It is important to distinguish optic neuritis from other types of optic neuropathy so that treatment can be started promptly, possibly delaying the onset of MS.
KEY POINTS
- Optic neuritis is most common in women in their 20s and 30s, whereas ischemic optic neuropathy, which is more common, primarily affects older people.
- The diagnosis of optic neuritis is primarily clinical, but magnetic resonance imaging confirms the diagnosis and, more importantly, assesses the risk of MS.
- Intravenous methylprednisolone (Solu-Medrol) does not affect the long-term visual outcome, but it speeds visual recovery and reduces the risk of MS. Surprisingly, oral prednisone seems to increase the risk of recurrent optic neuritis and is therefore contraindicated.
- Early treatment with interferon beta reduces the risk of MS and should be considered in patients at high risk.
Inflammatory optic neuropathies
Inflammatory optic neuropathies can be caused by infections (eg, syphilis, cat scratch disease) or by noninfectious conditions (eg, sarcoidosis). Lyme disease is rarely a cause of retrobulbar optic neuritis but may cause papillitis.24 West Nile virus has also been reported to cause optic neuritis.25 Lupus may cause an optic neuropathy by inflammatory or ischemic mechanisms.26
Compressive optic neuropathies
Compressive optic neuropathies may be due to mass lesions, tumors, thyroid eye disease, or other orbital processes. MRI of the brain and orbits will confirm or rule out diagnoses associated with compressive optic neuropathy.
Genetic causes
Genetic causes of optic neuropathy include the Leber and Kjer hereditary optic neuropathies.
Leber optic neuropathy involves subacute and painless vision loss, with sequential involvement of both eyes over a period of weeks to months. This disorder predominantly affects men (80%–90% of patients) and is inherited from maternal mitochondrial DNA. The three most common mutations implicated in Leber optic neuropathy (located at base pairs 11,778, 3,460, and 14,484 in the mitochondrial DNA) are involved in more than 90% of cases. The prognosis for recovery varies depending on the genotype.27 These genes encode proteins that are part of complex I of the mitochondrial respiratory chain.28 Funduscopic examination most commonly shows circumpapillary telangiectasia, although up to one-third of patients can have a normal-appearing disc initially. Central vision is affected more severely than peripheral vision.29
Kjer autosomal-dominant optic atrophy is the most common hereditary optic neuropathy. This disease primarily affects children in the first decade of life with slowly progressive loss of vision. As with other optic neuropathies, there will eventually be pallor of the optic disc, a cecocentral scotoma, and loss of color perception. The OPA1 gene located on chromosome 3q28 has been implicated in most patients with dominant optic atrophy; a test is commercially available for diagnosis.30,31
Toxic and metabolic causes
Many agents can cause optic neuropathy. Toxins strongly associated with optic neuropathy include carbon monoxide, methanol, ethylene glycol, perchloroethylene, and tobacco. Drugs linked to optic neuropathy are ethambutol (Myambutol), clioquinol (Vioform), isoniazid (Nydrazid), amiodarone (Cordarone), linezolid (Zyvox), methotrexate, sildenafil (Viagra), oxymetazoline (contained in Afrin and other nasal sprays), and infliximab (Remicade).32–37 Additionally, several chemotherapeutic agents are known to cause optic atrophy, including vincristine (Oncovin), cisplatin (Platinol), carboplatin (Paraplatin), and paclitaxel (Abraxane, Onxol).
Nutritional deficiencies are presumed to have played a significant role in the endemics of optic neuropathy that have occurred in poor countries, such as in Cuba during the 1990s.38 Most nutritional optic neuropathies appear to be exacerbated by tobacco.39
MRI ASSESSES RISK OF MS
The diagnosis of optic neuritis is clinical, based on the history and physical findings.
However, MRI of the brain and orbits with gadolinium contrast has become the cornerstone of the evaluation in patients with optic neuritis. And MRI not only helps confirm the clinical diagnosis, but it also more importantly offers very strong prognostic information about the risk of future demyelinating events and MS.
Gadolinium-enhanced fat-saturated T1-weighted MRI of the orbits is the best sequence to show the inflammation of the optic nerve in optic neuritis (fat saturation is necessary to hide the bright signal of the orbital fat tissue).
Contrast-enhanced MRI can also help differentiate optic neuritis from nonarteritic anterior ischemic optic neuropathy. MRI of the orbits with gadolinium contrast shows enhancement of the affected optic nerve in approximately 95% of cases of optic neuritis, whereas optic nerve enhancement rarely occurs in nonarteritic anterior ischemic optic neuropathy.40
Brain MRI may show other white matter lesions (either hyperintensities on T2-weighted images or enhancement of T1-weighted images postcontrast), which denote a higher risk of developing MS. In 15-year follow-up data from the ONTT, monosymptomatic patients with no white matter lesions had a 25% risk of MS (defined at the time the ONTT was conducted as a second demyelinating event), while those with one lesion or more had a 72% risk.41
An earlier, prospective study in 102 Italian patients with optic neuritis found the risk of developing MS to be about 36% at 6 years and 42% at 8 years (using the Posner diagnostic criteria). When brain MRI data were analyzed, those with one or more lesions had a 52% risk of developing MS at 8 years, whereas those with no MRI lesions did not develop MS.42
Other studies have stratified the risk of MS in patients with clinically isolated syndromes (including not only optic neuritis, but also other neurologic symptoms such as brainstem, motor, or sensory deficits). At mean follow-ups ranging from 5 to 14 years, the risk of developing MS was 8% to 24% in patients with normal findings on brain MRI compared with 56% to 88% in those with abnormal MRI findings.43,44
Optic neuritis patients with atypical white matter lesions on brain MRI may benefit from lumbar puncture to look for oligoclonal bands, to measure the IgG index and the IgG synthesis rate, and to test for myelin basic protein in the cerebrospinal fluid. Of patients with acute optic neuritis, 79% have abnormalities in their cerebrospinal fluid. Oligoclonal bands are present in 69%, and for patients with oligoclonal bands, the 5-year probability of developing MS is estimated to be 65%, compared with 10% in those without bands. If the patient has no oligoclonal bands and has normal findings on brain MRI, he or she will not have MS 5 years later.45–47
Patients with optic neuritis who have no white matter lesions on brain MRI may be further risk-stratified on the basis of their clinical findings. In the ONTT 15-year follow-up, MS did not develop in any patient who had no brain lesions on baseline MRI, no prior optic neuritis in the contralateral eye, and no prior neurologic symptoms or signs, even if the patient had severe disc swelling (eg, peripapillary hemorrhage or retinal exudates) or if vision was reduced to no light perception.41
CASE CONTINUED: FINDINGS ON MRI
