Optic Neuritis & Multiple Sclerosis

Purpose
Magnetic Resonance Imaging is able to depict lesions in the Optic Nerve in the acute stage of MonoSymptomatic Optic Neuritis.

Most patients have lesions located IntraOrbitally, IntraCanalicularly, and/or IntraCranially. The goal of this study is to determine whether these lesions resolve after Visual recovery, change in length or localization, or could be correlated to the Visual function.

Methods
Between 1987 and 1992, the authors examined 22 patients with Acute Optic Neuritis using Magnetic Resonance Imaging short-time inversion recovery sequences.

Additionally, the authors determined Visual Acuity, Visual Field, Color Vision, Contrast Sensitivity, and Visual-Evoked Responses. All patients were re-examined between 1993 and 1994 in the same manner.

Visual recovery in the re-examination was divided into three groups:

1. Complete Visual Recovery
   • Visual Acuity better than 20/25
2. Incomplete Recovery
   • Visual Acuity better than 20/25 but
     Defect in at least one of the other tests:
     • Visual Field, Color Vision, and Contrast Sensitivity
3. Partial Recovery
   • Visual Acuity remained less than 20/25
     • Defect in all the other tests

Results
All group 1 patients initially had lesions less than 17.5 mm, group 2 patients had lesions greater than 17.5 mm (44%) and/or Lesions located IntraCanalicularly (66%), and most of group 3 patients initially had lesions greater than 17.5 mm (79%).

Conclusion
Eyes with lesions less than 17.5 mm in the Optic Nerve in Acute Optic Neuritis have a good prognosis for Visual recovery.

Lesions greater than 17.5 mm or lesions involving the IntraCanalicular portion of the Optic Nerve lead to incomplete or partial Visual recovery.

Background
Optic Neuritis is often the first clinical manifestation of Multiple Sclerosis, but little is known about the effect of CorticoSteroid treatment for Optic Neuritis on the subsequent risk of Multiple Sclerosis.

Methods
We conducted a multicenter study in which 389 patients with Acute Optic Neuritis (and without known Multiple Sclerosis) were randomly assigned to receive IntraVenous MethylPrednisolone (250 mg every six hours) for 3 days followed by Oral Prednisone (1 mg per kilogram of body weight) for 11 days, Oral Prednisone (1 mg per kilogram) alone for 14 days, or placebo for 14 days.

Neurologic status was assessed over a period of two to four years. The patients in the first group were hospitalized for three days; the others were treated as outpatients.

Results
Definite Multiple Sclerosis developed within the first two years in 7.5 percent of the IntraVenous MethylPrednisolone group (134 patients), 14.7 percent of the Oral Prednisone group (129 patients), and 16.7 percent of the placebo group (126 patients).

The adjusted rate ratio for the development of definite Multiple Sclerosis within two years in the IntraVenous MethylPrednisolone group was 0.34 (95 percent confidence interval, 0.16 to 0.74) as compared with the placebo group and 0.38 (95 percent confidence interval, 0.17 to 0.83) as compared with the oral-Prednisone group.

The beneficial effect of the IntraVenous Steroid regimen appeared to lessen after the first two years of follow-up.

Signal abnormalities on Magnetic Resonance Imaging (MRI) of the Brain were a strong indication of risk for the development of definite Multiple Sclerosis (adjusted rate ratio in patients with three or more lesions, 5.53; 95 percent confidence interval, 2.41 to 12.66).

The beneficial effect of treatment was most apparent in patients with abnormal MRI scans at entry.

Conclusions
In patients with Acute Optic Neuritis, treatment with a three-day course of high-dose IntraVenous MethylPrednisolone (followed by a short course of Prednisone) reduces the rate of development of Multiple Sclerosis over a two-year period.

Objective
To determine the efficacy of CorticoSteroids as treatment for Acute DeMyelinative Optic Neuritis after completion of 1 year of patient follow-up in the Optic Neuritis Treatment Trial.

Design
Randomized placebo controlled multicenter clinical trial. Fifteen university or hospital-based centers throughout the United States.

Four hundred fifty-seven patients with Acute DeMyelinative Optic Neuritis between 18 and 46 years of age.

Intervention
Either IntraVenous MethylPrednisolone Sodium Succinate (250 mg every 6 hours) for 3 days followed by Oral Prednisone (1 mg/kg per day) for 11 days, Oral Prednisone (1 mg/kg per day) for 14 days, or oral placebo for 14 days.

The first two regimens were followed by a short taper of CorticoSteroid therapy.

Main Outcome Measures
Visual Acuity, Visual Field, Contrast Sensitivity, and Color Vision.

Results
Visual Acuity at 1 year was 20/40 or better in 95% of the placebo group, 94% of the IntraVenous group, and 91% of the Oral Prednisone group.

Comparing each CorticoSteroid group with the placebo group, there were no statistically significant differences in the distributions of any of the four measures of Visual Function.

Patients in the Oral Prednisone group suffered a higher rate of new attacks of Optic Neuritis than patients in either of the other two groups.

Conclusions
The visual benefit from treating acute Optic Neuritis with IntraVenous followed by Oral CorticoSteroids is short term, limited to an accelerated rate of recovery.

The decision whether to prescribe this regimen for Optic Neuritis, or to prescribe no treatment, must be made for each patient on an individual basis.

Oral Prednisone alone, in the dose range used in the Optic Neuritis Treatment Trial, should not be prescribed.

Sixteen patients with Acute Optic Neuritis were studied, and randomized into two groups of treatment.

Group I was assigned to in hospital treatment with IntraVenous MethylPrednisolone 500 mg Q8 hours for 10 doses, followed by Oral Prednisone for two weeks and tapering doses thereafter.

Group II was treated with Oral Prednisone one mg per kilogram of body weight for two weeks followed by tapering doses. All patients had examination of Visual Acuity, Visual Field at baseline and repeated on weeks two, four and sixteen.

Two patients in group I were lost to follow up, and three patients (two in group I and one in group II) had previous established diagnosis of Multiple Sclerosis and the onset of acute Optic Neuritis was considered a recurrence of the disease.

There was no statistical difference between the groups with regards to clinical outcome, Visual Acuity And Visual Field examination (p = 0.329) Fisher test.

A randomized double-blind placebo-controlled trial of IntraVenous MethylPrednisolone versus Oral MethylPrednisolone at equivalent high dose was carried out on 35 patients with an acute relapse of Multiple Sclerosis (MS).

After baseline evaluation each was randomly allocated to oral treatment and intravenous placebo or intravenous treatment and oral placebo, receiving 500 mg of MethylPrednisolone for five consecutive days and with re-assessment at days five and twenty-eight.

There was no significant difference in response when disability or functional scores were compared in the two groups. Adverse effects were minor and equally distributed.

In this study Oral treatment with MethylPrednisolone was as effective as IntraVenous treatment in acute relapse of MS.

Optic Neuritis is frequently the first clinical sign of Multiple Sclerosis (MS). Study results indicate that MethylPrednisolone pulse therapy reduces the rate of development of MS over a two year period.

Patients also experience quicker recovery of vision. This short duration therapy presents immediate and intense nursing care challenges.

Coordination of care between three departments at the Univ of Michigan Medical Center enables many patients to complete IV [IntraVenous] pulse therapy at home.

Although coordination is challenging for providers, ambulatory care and home care benefit patients and their families with potential healthcare cost savings.

Eighty-one patients with a first attack of Isolated Optic Neuritis, 40 with Uhthoff's Symptom (Group 1) and 41 without (Group 2), were studied.

All had a NeuroVisual examination, 74 of 81 patients had the pattern Visual Evoked Potential recorded at rest, and 43 had MRI Brain scans.

The pattern Visual Evoked Potential P100 latency was prolonged, Group 1 with a mean of 136 +/- 19 msec. Group 2 with a mean of 131 +/- 19 msec (control subjects, 102 +/- 5 msec; n = 84), and the P100 amplitude was reduced, without significant difference between the groups.

Abnormal MRI scans were present in significantly more patients in Group 1 (p less than 0.025).

Treatment of Optic Neuritis with CorticoSteroids had no effect on the evolution or duration of Uhthoff's Syndrome.

Overall, 35 of 81 (43%) patients, followed for a mean of 3.5 years, developed Multiple Sclerosis.

The incidence was significantly greater in Group 1 (p less than 0.01). Uhthoff's Symptom also correlated with a higher incidence of recurrent Optic Neuritis.

We conclude that Uhthoff's Symptom is a prognostic indicator for the early development of Multiple Sclerosis.

CorticoSteroids have a firm place in the treatment of MS, but as yet no generally accepted regimen of this therapy exists. It is not known either, how to achieve the greatest effectiveness of these drugs and avoid side effects.

Many clinicians advocate high IntraVenous doses of MethylPrednisolone in a short time of 5-7 days. This method is more effective and leads to less adverse effects.

The studied patients received Prednisone (Encorton Polfa) in short course of 3 days every month. The dose of Encorton in each course depended on the clinical condition but never exceeded 200 mg.

The regimen was used in 18 patients who were followed up at least one year. Evident improvement or stabilization was obtained in 11 cases. No adverse effects were noted.

These results are comparable to those achieved with MethylPrednisolone. It may be supposed that every regimen of Corticoid treatment in MS is usefull if it causes no adverse effects.

The treatment by method of long-term pulse therapy with Corticoids is applicable in outpatients.

The diagnosis of Optic Neuritis is based on clinical signs and symptoms.

Ancillary testing is of little medical value, but helpful to evaluate the risk of developing Multiple Sclerosis and for proper counseling of the patient.

The visual field defects caused by Optic Neuritis are less often central, but most often altitudinal or sectorial, and thus of little help to differentiate between Papillitis and Anterior Ischemic Optic Neuropathy.

In contrast to common belief, the usual therapy with Oral Prednisone at an initial dose of 100 mg/day may be harmful.

This therapy does not accelerate recovery of Visual function and does not lead to a better final result but increases the risk of new episodes of Neuritis and may favor the development of Multiple Sclerosis.

In the case of severe visual loss (Visual Acuity < or = 0.1) a megadose-therapy with 1000 mg MethylPrednisolone/day accelerates the recovery of Visual function.

Side effects of the megadose therapy are infrequent and not severe.

In the case of moderate visual loss (Visual Acuity > or = 0.5) no therapy is advocated.