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.
INTRAVENOUS METHYLPREDNISOLONE OUTDOES ORAL PREDNISONE
Patients in the ONTT were randomized to receive one of three treatments:
- Oral prednisone 1 mg/kg/day for 14 days and then tapered over 4 days
- Intravenous methylprednisolone (Solu-Medrol) 250 mg four times per day for 3 days followed by oral prednisone 1 mg/kg/day for 11 days and then tapered for 4 days
- Oral placebo for 14 days.
The primary visual outcomes measured were visual acuity and contrast sensitivity.48
Patients who received intravenous methylprednisolone recovered their visual function faster, although the visual outcomes after 6 months were no better with methylprednisolone than with placebo or oral prednisone. Intravenous methylprednisolone also reduced the risk of MS within the first 2 years in patients with high-risk brain MRIs.
Surprisingly, patients in the oral prednisone group had a higher risk of recurrent optic neuritis in both eyes than did patients given intravenous methylprednisolone or placebo (30% at 2 years with oral prednisone vs 16% with placebo and 13% with intravenous methylprednisolone).48 At 10 years, the risk of recurrent optic neuritis was still higher in the oral prednisone group (44%) than in the intravenous methylprednisolone group (29%) (P = .03). However, the difference between the oral prednisone and placebo groups was no longer statistically significant (P = .07).49 Oral prednisone alone is therefore contraindicated in the treatment of typical unilateral demyelinating optic neuritis.
Many patients can now be treated with intravenous infusions of methylprednisolone at home for episodes of optic neuritis.
Risks vs benefits of corticosteroid therapy
When deciding whether to treat an individual patient who has optic neuritis with intravenous corticosteroids, one should consider all the benefits and risks.
Corticosteroids do not affect long-term visual outcome, although they do hasten recovery. Patients with mild vision loss (visual acuity better than 20/40), no significant visual field loss, and no enhancing lesions on brain MRI can forgo therapy with intravenous corticosteroids.
On the other hand, we strongly favor intravenous corticosteroid treatment in patients who have both acute optic neuritis and high signal abnormalities on brain MRI, since it may delay the onset of MS. In addition, patients with severe vision loss should receive intravenous corticosteroids to hasten their recovery. In the rare circumstance in which intravenous corticosteroids are not available, high-dose oral methyl-prednisolone (500 mg daily for 5 days and then tapered over 10 days) may be acceptable.50
The side effects of corticosteroids are minimal when they are given for a brief time in otherwise healthy patients. The most common side effects are mood changes, facial flushing, sleep perturbations, weight gain, and dyspepsia.48
IMMUNOGLOBUL IN: LITTLE BENEFIT
In a double-blind, randomized trial, patients were treated with intravenous immunoglobulin 0.4 g/kg or placebo on days 0, 1, 2, 30, and 60. No difference was found in the primary outcomes of contrast sensitivity, visual acuity, or color vision from 1 week up to 6 months. There was also no significant difference in MRI outcomes between the two groups. The number of relapses was similar between both groups after 6 months.51,52
PLASMA EXCHANGE: FEW DATA
Data on plasma exchange are too scarce for us to make any recommendations. In one trial in 10 patients with severe optic neuritis, 3 patients appeared to benefit from plasma exchange. All patients had already received two doses of intravenous steroids.53
IMMUNOMODULATORY THERAPY MAY PREVENT MULTIPLE SCLEROSIS IN SOME
The most important clinical decision to make in patients with optic neuritis is whether to begin immunomodulatory therapy. Patients who may benefit the most from immunomodulatory therapy are those with abnormal white matter lesions on brain MRI, as they are at higher risk of developing MS.
Collectively, data from three studies indicate that early treatment in patients with clinically isolated syndromes, such as optic neuritis, reduces the rate of MS to 35% (from 50% without treatment) and reduces the number of new active lesions on MRI by approximately 50%.54–56
In addition, the Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) trial57 found that at 3 years the rate of disability was 40% lower in patients who started immunomodulatory therapy (interferon beta-1b; Betaseron) early vs later. (Early treatment meant starting within 60 days of the clinically isolated syndrome; late treatment began 2 years later.) This study suggests that early treatment may reduce future disability, although these results need to be confirmed in prospective trials.
Therefore, once the diagnosis is secure, patients with optic neuritis should be referred to a neurologist with experience in treating MS to begin treatment with immunomodulatory therapy, such as glatiramer acetate (Copaxone), interferon beta-1a (Avonex, Refib), or interferon beta-1b (Betaseron).
Patients who have a normal MRI of the brain may consider deferring therapy, since they are at low risk of developing MS. These patients should undergo surveillance MRI (at least annually at first) to look for the development of white matter lesions, as the ONTT showed even this cohort has a 22% risk of developing MS.
If neuromyelitis optica is suspected (ie, in patients with severe unilateral or bilateral vision loss, recurrent optic neuritis, paraplegia, or quadriplegia), the serum neuromyelitis optic antibody can be tested, keeping in mind that 30% to 40% of patients with neuromyelitis optica will be seronegative for this antibody. Other tests supporting the diagnosis of neuromyelitis optica may include an MRI of the spine showing longitudinally extensive transverse myelitis, a polymorphonuclear pleocytosis in the cerebrospinal fluid, absent oligoclonal bands in the cerebrospinal fluid, and normal MRI of the brain (with some possible signal abnormalities in the periaqueductal gray matter and around the diencephalon).
Because neuromyelitis optica is believed to be mediated primarily by the humoral immune system, immunomodulatory therapy is not a first-line treatment. Patients with neuromyelitis optica can be treated initially with corticosteroids, intravenous immunoglobulin therapy, plasma exchange, or immunosuppressive agents such as azathioprine (Imuran), rituximab (Rituxan), or cyclophosphamide (Cytoxan). The choice of medication should be deferred to a neurologist familiar with treatment of this disorder.
The risk of MS may be lower in children than in adults. One large, retrospective study found the cumulative risk of developing MS (the study predated the McDonald criteria) was 13% at 10 years and 19% by 20 years.58 More recently, a large series from Toronto reported a higher rate of MS development in children with optic neuritis (36% at two years).59 By comparison, studies of adults with unilateral optic neuritis found a 38% to 39% risk of converting to MS at 10 years.5,41 The use of immunomodulatory therapies to reduce the risk of MS has not been well studied in children, since the prevalence is low in this age group.
The most common side effects of the beta-interferons are flulike symptoms (fatigue, myalgia), injection site reactions, and elevations of aminotransferase levels. Most patients are able to tolerate the side effects if the beta-interferon is taken with acetaminophen (Tylenol) or with over-the-counter nonsteroidal anti-inflammatory drugs.
Glatiramer acetate does not cause flulike symptoms or elevate aminotransferases, but it does require more frequent injections. Rarely, it may cause an idiosyncratic panic-like attack.
CASE CONTINUED
The best therapeutic regimen for this patient would be intravenous methylprednisolone, and subsequently a disease-modifying, immunomodulatory agent (interferon beta or glatiramer acetate). Our patient chose to start therapy with interferon beta-1a 30 μg intramuscularly once a week. She has been tolerating the medication well and has had no new neurologic or visual symptoms for the past 2 years.
