Optic Neuritis In Multiple Sclerosis

Background/Methods
One hundred and fifteen patients with Clinically Isolated Optic Neuritis underwent Magnetic Resonance Imaging (MRI) of the Brain and Spinal Cord within 3 months of the onset of symptoms.

Results
Eighty one (70%) patients had Brain lesions and 31 (27%) had Cord lesions. Cord lesions were seen in 12% with a normal Brain MRI, 21% with between one and eight Brain lesions, and 45% with nine or more Brain lesions.

When the new diagnostic criteria for MS were applied, MRI Cord imaging used for evidence of dissemination in time and space allowed a diagnosis of MS in only one additional asymptomatic patient at 1 year, two additional asymptomatic patients at 3 years.

Conclusions
Using existing criteria, Spinal Cord imaging rarely contributes to the diagnosis in patients with clinically isolated Optic Neuritis.

Using multivariate analyzes, individual risk of Clinically Definite Multiple Sclerosis (CDMS) after MonoSymptomatic Optic Neuritis (MON) was quantified in a prospective study with clinical MON onset during 1990-95 in Stockholm, Sweden.

During a mean follow-up time of 3.8 years, the presence of MS-like Brain Magnetic Resonance Imaging (MRI) lesions and OligoClonal ImmunoGlobulin (Ig) G bands in CerebroSpinal Fluid (CSF) were strong prognostic markers of CDMS.

With relative hazard ratios of 4.68 [95% confidence interval (CI) 2.21-9.91] and 5.39 (95% CI 1.56-18.61), respectively.

Age and season of clinical onset were also significant predictors, with relative hazard ratios of 1.76 (95% CI 1.02-3.04) and 2.21 (95% CI 1.13-3.98), respectively.

Based on the above two strong predictors, individual probability of CDMS development after MON was calculated in a three-quarter sample drawn from a cohort, with completion of follow-up at three years.

The highest probability, 0.66 (95% CI 0.48-0.80), was obtained for individuals presenting with three or more Brain MRI lesions and OligoClonal Bands in the CSF, and the lowest, 0.09 (95% CI 0.02-0.32), for those not presenting with these traits.

Medium values, 0.29 (95% CI 0.13-0.53) and 0.32 (95% CI 0.07-0.73), were obtained for individuals discordant for the presence of Brain MRI lesions and OligoClonal Bands in the CSF. These predictions were validated in an external one-quarter sample.

Background
In the Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS), intramuscular (IM) Interferon-ß-1a (IFN-ß-1a) delayed the development of Clinically Definite Multiple Sclerosis (CDMS).

In patients with a single DeMyelinating event who had Magnetic Resonance Imaging (MRI) evidence of previous subclinical disease activity (defined as > or = 2 T₂-weighted HyperIntense lesions, 1 of which was PeriVentricular or ovoid, on unenhanced MRI scans).

Objective
This post hoc analysis was conducted to assess the effects of IM IFN-ß-1a on delaying the development of CDMS in a subgroup of CHAMPS patients who met a more stringent definition of high risk than was used in that trial.

Methods
Patients from the overall CHAMPS population were included in the present analysis if they had > or = 9 T₂-weighted HyperIntense lesions and > or = 1 Gadolinium-enhanced lesion on the baseline MRI scan.

The cumulative probability of developing CDMS in each treatment group was calculated using the Kaplan-Meier product-limit method and compared using the log-rank test.

The actual proportions of patients who developed CDMS in each treatment group were calculated and compared using the chi-square test.

Results
Ninety-one patients met the more stringent definition of high risk and were included in the subgroup analysis.

Fifty-one patients (56.0%) received IFN-ß-1a 30 microg IM once weekly and 40 (44.0%) received placebo. Baseline demographic and clinical characteristics were similar between the 2 groups.

Seventy-four patients (81.3%) were female, 80 (87.9%) were white, and the mean age was 33.0 years.

Overall, IM IFN-ß-1a reduced the rate of development of CDMS by 66% compared with the placebo group (P = 0.002, log-rank test) over the 3-year follow-up period.

At 2 years, the Kaplan-Meier estimate of the cumulative probability of developing CDMS was 21% in the IM IFN-ß-1a group and 56% in the placebo group.

Representing a 63% reduction in risk for CDMS with IFN-ß-1a (P = 0.002, log-rank test). The results based on the actual proportions of patients developing CDMS were similar to the Kaplan-Meier estimates.

Conclusions
The results of this subgroup analysis are compatible with IM IFN-ß-1a reducing the risk of a second DeMyelinating event in patients meeting the more stringent definition of high risk.

Although, the treatment effect of IFN-ß-1a was significant in both the overall CHAMPS population (44% risk reduction vs placebo; P = 0.002) and in this high-risk subgroup (66%).

The results of the present analysis suggest that the magnitude of treatment benefit with IFN-ß-1a may be greater in patients with more disease activity, as measured by MRI parameters.

We retrospectively reviewed 27 cases diagnosed as idiopathic Optic Neuritis between 1992 and 2001 at Kaohsiung Veterans General Hospital.

To assess the clinical features, Visual prognosis, NeuroImaging, laboratory studies, and development of Multiple Sclerosis in Chinese patients with Optic Neuritis.

Patient age ranged from 13 to 54 years (mean, 35.8 +/- 11.3 years). Five cases presented as BiLateral Optic Neuritis and 22 as UniLateral.

Visual function improved gradually from 2 weeks after treatment. Twelve (44.4%) cases showed Disc swelling and Ocular pain was also noted in 44.4% of patients.

All cases that underwent Visual Field and Visual Evoked Potential tests showed abnormality in lesion Eyes.

Of the 23 cases that underwent NeuroImaging studies, including computerized tomography (17 patients) and Magnetic Resonance Imaging (6 patients), 10 revealed Optic Nerve thickening. Four cases (14.8%) developed Multiple Sclerosis during follow-up (mean, 4.3 years).

The incidence of Disc swelling was higher than that reported by the Optic Neuritis Treatment Trial.

But the incidence of initial Ocular Pain, the presence of PeriVentricular plaques, and the development of Multiple Sclerosis were lower in our study. The UniLateral group had significantly better Visual outcome than the BiLateral group.

Objective
To determine clinical characteristics of patients with Optic Neuritis and Visual outcome after IntraVenous MethylPrednisolone treatment.

Method
A total of 81 patients with Optic Neuritis were reviewed retrospectively with regard to their clinical characteristics by dividing into two groups as follows:

Group I had Isolated Optic Neuritis and Group II had Optic Neuritis with DeMyelinative Disease. The Visual outcome in these patients before and after IntraVenous MethylPrednisolone treatment was analyzed.

Results
Of 81 patients with Optic Neuritis, 63 patients (77.8%) had Isolated Optic Neuritis and 18 (22.2%) patients were Optic Neuritis with DeMyelinative Disease.

The ages of the patients ranged from 16 to 59 years (mean = 35.3 years) in patients with Isolated Optic Neuritis and from 16 to 73 years of age (mean = 35.8 years) in patients with Optic Neuritis with DeMyelinative Disease.

After treatment, 45 patients (52 eyes) with Isolated Optic Neuritis and 14 patients (25 eyes) with Optic Neuritis with DeMyelinative Disease who were followed-up for more than 10 days were studied.

After treatment, 60 per cent of the Isolated Optic Neuritis patients and 24 per cent of the Optic Neuritis patients with DeMyelinative Disease had a Visual Acuity of 6/12 or better respectively.

The Isolated Optic Neuritis who had an onset interval to treatment of less than 8 days had a Visual Acuity better than 6/9 in 75 per cent.

Conclusion
The final Visual outcome in patients with Isolated Optic Neuritis who received earlier treatment was better than those who received treatment later.

Purpose
To review the clinical features, natural history, potential pathogenic mechanisms, differential diagnosis, and management of Optic Neuritis in Multiple Sclerosis.

Methods
Relevant literature regarding Optic Neuritis in Multiple Sclerosis from 1970 to the present was reviewed.

Results
Optic Neuritis is an Acute Inflammatory Optic Neuropathy. It is the most common type of Optic Neuropathy causing Acute Visual Loss in young adults (peak age at 30-40 years), especially among women.

Patients usually present with an acute reduction of Visual Acuity, Orbital Pain exacerbated by Eye movements, DysChroMatopsia, and an Afferent Papillary Defect, with or without swelling of the Optic Nerve Head.

Visual Field Testing most often reveals Central defects, but others, such as Centrocecal, can also occur. Magnetic Resonance Image (MRI) scanning of the Brain should be undertaken in all cases of acute Optic Neuritis for diagnostic and prognostic purposes.

The Brain lesions of Multiple Sclerosis are commonly seen as T₂ ovoid high-signal White Matter lesions on MRI scans of the Brain located in PeriVenular regions perpendicular to Ventricles with variable enhancement.

For atypical presentations of Optic Neuritis, additional laboratory tests, such as CerebroSpinal Fluid analysis, Serologic Tests, and Visual Evoked Potentials, prove to be useful in the diagnosis and subsequent management of the patient.

The recommended treatment for Optic Neuritis is intravenous Steroids, as shown in the Optic Neuritis Treatment Trial (ONTT).

Conclusion
Optic Neuritis is often the initial presentation of Multiple Sclerosis. Recent advances in the understanding of the Immune basis for Multiple Sclerosis has led to earlier and more effective treatment of this disease.

We evaluated 190 patients in the placebo group of the CHAMPS trial in order to assess factors associated with short-term Clinical and Brain Magnetic Resonance Imaging (MRI) outcomes.

In, patients with a first clinical DeMyelinating event involving the Optic Nerve, Spinal Cord, or BrainStem/Cerebellum, and SubCinical DeMyelination on Brain MRI.

The two study outcomes were 1) development of Clinically Definite Multiple Sclerosis (CDMS) and 2) development of CDMS or two or more new or enlarging Brain MRI T₂ lesions.

The presence of Gadolinium (Gd)-enhancing lesions on the baseline scan was the only MRI characteristic associated with a higher risk of both the clinical and combined outcomes (p = 0.003 and < 0.001, respectively).

The only demographic or clinical characteristic associated with an increased risk of these outcomes was younger age (p < 0.001 for both outcomes). The lowest risk subgroups we could define had a 30% risk of CDMS and a 65% risk of the combined clinical/MRI outcome.

Our results indicate that all patients presenting with a first DeMyelinating event who also have Brain MRI evidence of SubClinical DeMyelination have at least a moderate risk of short-term disease activity.

This finding provides support for initiating disease-modifying therapy at the time of the first DeMyelinating event in patients meetng the CHAMPS enrollment criteria.

The objective of this study was to evaluate the risk of Visual outcome after acute Optic Neuritis (ON) in relation to clinical and MRI findings.

Fifty cases of acute ON within one month were retrospectively studied. MRI with Short Tau Inversion Recovery (STIR) sequence of the Optic Nerve were obtained with a median time onset of 9 days after ON.

Mean age of patients was 32.8 years, mean initial Visual Acuity was 3/10 and Orbital Pain was present in 86 percent100 of patients. The STIR sequence revealed lesion in 88 percent 100 of acutely symptomatic Optic Nerves.

An initial low Visual Acuity (less than 2/10), the absence of Orbital Pain and involvement of the IntraCanalicular portion of the Optic Nerve on STIR sequence were statistically correlated with a poorer Visual outcome (respectively p=0.0041, p=0.035 and p=0.011).

Purpose
To evaluate the effect of treatment with Interferon-ß-1a (Avonex) initiated at the time of a first episode of Optic Neuritis in patients at high risk for Multiple Sclerosis (MS).

Design, Methods & Setting
Randomized clinical, prospective trial in fifty clinical centers throughout the US and Canada.

Study Population
After the onset of a first episode of Optic Neuritis treated with intravenous and oral CorticoSteroids,

192 patients with Brain Magnetic Resonance Imaging (MRI) evidence of SubClinical DeMyelination were randomly assigned to receive weekly intramuscular injections of 30 microg interferon-ß-1a or placebo.

Main Outcome Measure
The study outcomes were the development of Clinically Definite MS within 3 years of follow-up and Brain MRI changes at 6, 12, and 18 months.

Results
The rates of Clinically Definite MS and of a combined MS/MRI outcome were lower in the Interferon-ß-1a group than in the placebo group (adjusted rate ratios 0.58, 95% confidence interval 0.34 to 1.00; and 0.50, 95% confidence interval 0.34 to 0.73, respectively).

Compared with the placebo group, on the 18-month Brain MRI the Interferon-ß-1a group had a smaller change from baseline in T₂ lesion volume (P =.02), fewer new or enlarging T₂ lesions (P < .001), and a lower frequency of Gd-enhancing lesions (P < .001).

Conclusion
The clinical and Brain MRI results of this trial support initiating Interferon-ß-1a treatment at the time of a first episode of Optic Neuritis.

Occurring in patients at high risk for MS based on the presence of SubClinical Brain MRI lesions.

Background
Optic PeriNeuritis is an uncommon variety of Orbital Inflammatory Disease that is distinct from DeMyelinating Optic Neuritis.

Objective
To describe the clinical and radiographic features of idiopathic Optic PeriNeuritis, with particular emphasis on those features that help to distinguish this condition from Optic Neuritis.

Methods
We reviewed the medical records of 14 patients with Optic PeriNeuritis who were seen in 2 NeuroOphthalmology clinics.

Results
Patients ranged in age from 24 to 60 years; 5 were older than 50 years. All patients had Visual Loss, Eye Pain, or both. The Visual Acuity was 20/20 or better in 8 of the 15 eyes.

The results of Visual Field testing were normal in 2 eyes, and a ParaCentral Scotoma or an Arcuate Defect was seen in 7.

Magnetic Resonance Imaging scans demonstrated circumferential enhancement around the Optic Nerve, sometimes with IntraOrbital extension. Response to CorticoSteroids was dramatic; however, 4 patients had a relapse with lowering of the dose.

Conclusions
In contrast to those with Optic Neuritis, patients with Optic PeriNeuritis are often older at onset and are more likely to show sparing of Central Vision.

Magnetic Resonance Imaging scans demonstrate enhancement around, rather than within, the Optic Nerve. Response to CorticoSteroids is more dramatic than in patients with Optic Neuritis, and patients are more likely to experience recurrence after stopping treatment.

Optic Neuritis presentations are thought to have a better prognosis. The aim of our study was to compare conversion to Multiple Sclerosis on the different topographies of CISs.

We prospectively evaluated 320 patients with CISs (123 with Optic Neuritis, 78 with BrainStem Syndromes, 89 with Spinal Cord Syndromes, and 30 with other topographies).

They were observed for a median of 39 months, patients underwent Brain MRI within 3 months of their first attack and again 12 months later.

Conversion to Multiple Sclerosis determined either clinically or by MRI was evaluated according to topography.

Baseline MRI was normal in 49.2% of patients with Optic Neuritis compared with 24% in BrainStem Syndromes, 24% in Spinal Cord Syndromes, and 18.5% in other Syndromes.

Optic Neuritis behaved differently from the other CISs for lower conversion to Clinically Definite Multiple Sclerosis and smaller proportion of patients fulfilling MRI Dissemination in Space, Time, or both.

Nevertheless, when only patients with abnormal Cranial MRI results at baseline were selected, no differences for clinical or MRI conversion were found.

Optic Neuritis has a smaller risk for conversion to Multiple Sclerosis. Nevertheless, MRI at baseline, not CIS topography, appears to be the crucial issue at Multiple Sclerosis presentation.

Ann Neurol 2005;57:210-215.

This study assessed Optic Nerve Mean Area on serial MRI in a cohort of patients with a first episode of Acute UniLateral Optic Neuritis to assess the effects of a single acute Inflammatory DeMyelinating lesion.

Twenty-nine patients with a median delay from onset of Visual symptoms of 13 days (range 7-24 days) were recruited.

After a clinical examination and Visual Evoked Potential (VEP) measurement, each patient had their Optic Nerves imaged with a Coronal Fat-Saturated Short Echo fast Fluid-Attenuated Inversion Recovery sequence.

Twenty-one patients had serial examinations after 2, 4, 8, 12, 26 and 52 weeks. In addition, 32 control subjects had their Optic Nerves imaged up to three times.

The Mean Cross-Sectional Area of the Intra-Orbital portion of each Optic Nerve was calculated by a blinded observer using a computer-assisted contouring technique.

At baseline, the Mean Area of diseased Optic Nerves was 16.1 mm2 compared with 13.4 mm2 for healthy ContraLateral Optic Nerves (20.1% higher, P < 0.0001) and 13.6 mm2 for controls (18.4% higher, P = 0.0003).

The diseased Optic Nerve Mean Area declined over time, from initial swelling to later Atrophy. The mean decline at 52 weeks was -0.0018 mm2/day (95% confidence interval -0.0038 to -0.00051).

At 52 weeks, the Mean Area of diseased Optic Nerves was 11.3 mm2 compared with 12.8 mm2 for healthy ContraLateral Optic Nerves (11.7% lower, P = 0.032) and 13.1 mm2 for controls (13.7% lower, P = 0.008).

There was an association between baseline Optic Nerve Mean Area and logMAR Visual Acuity (rS = 0.46, P = 0.012) and Visual Field mean deviation (rS = -0.55, P = 0.002).

But, there was no evidence of an association between 1 year Mean Area and Visual outcome.

There was no evidence of association between baseline, rates of decline or 1 year diseased Optic Nerve Mean Areas and any of the baseline, 1 year or time-averaged VEP variables.

The present study shows a consistent pattern of changes associated with individual Inflammatory DeMyelinating lesions in the Optic Nerve.

Acutely, there was swelling, consistent with the presence of acute inflammation, which was related to Visual Impairment.

Over the longer term, there was loss of tissue. The lack of association between 1 year Optic Nerve Mean Area and Visual outcome may reflect a mild loss of tissue, redundancy or remodelling of function.