Optic Neuritis In Multiple Sclerosis

Thirty-one patients were followed-up, at 3-month intervals for the first year and at 6-month intervals for the second year, after an episode of Optic Neuritis.

The object was to confirm previous evidence for a progressive shortening of Visual Evoked Potential (VEP) latencies and to determine whether this is associated with any change in the clinical Ocular examination, Visual fields or Contrast Sensitivity.

VEP latencies were found to decrease significantly during both the first and (less strikingly) the second year.

The most marked changes occurring between 3 and 6 months. Contrast sensitivity improved during the first 9 months, but subsequently tended (non-significantly) to deteriorate.

A similarly transient improvement in Central Visual Field sensitivity was seen in a subgroup of patients with clinically overt Multiple Sclerosis.

In the data from the acutely unaffected fellow eyes, no significant changes in VEP parameters or functional indices were observed.

The findings extend those of a previous study which showed significant shortening of VEP latencies between 6 months and 3 years without significant functional improvement.

Over this period, a significant prolongation of VEP latencies occurred in the asymptomatic fellow eye, accompanied by Contrast Sensitivity Deterioration.

Taken in conjunction, the two studies suggest that recovery processes involving ReMyelination or, possibly, Ion Channel reorganization proceed for at least 2 years.

The concurrent effects of insidious DeMyelination and/or Axonal Degeneration (also occurring in the fellow Optic Nerve) are initially masked by the recovery process, but gradually become more evident.

The functional benefits of the long-term recovery process are relatively minor and are usually reversed within a few years.

Nevertheless, it is suggested that long-term ReMyelination may perform an important role in protecting DeMyelinated Axons from degeneration.

Understanding the factors which promote long-term ReMyelination may have significant implications for therapy in Multiple Sclerosis.

Objective
To study the association of Brain Magnetic Resonance Imaging (MRI) findings and HLA findings to clarify the relationship between MonoSymptomatic Optic Neuritis (ON) and ON as part of Clinically Definite Multiple Sclerosis (CD/MS).

Design & Setting
Population-based cohort of patients with ON referred prospectively during 6 years by Neurologists and Ophthalmologists within 4 weeks of onset of ON. Referral center in the general community of greater Copenhagen (Denmark) (population, 1.5 million).

Patients
A consecutive sample of 199 patients aged 12 to 59 years with ON (133 with idiopathic ON, 66 with ON+CD/MS), ethnically matched with 192 healthy volunteers.

Main Outcome Measures
Relation between the HLA-DR15, -DR17, -DQA-1B, and -DQB-1B PolyMorphisms as defined by restriction fragment length PolyMorphism analysis, and presence of Plaques on T₂-weighted Brain MRI.

Results
The frequency of HLA-DR15 was significantly increased in patients with ON+CD/MS (52%) and ON (47%) compared with control subjects (31%). The frequency of HLA-DR17 was almost equal in the ON+CD/MS (18%), ON (23%), and control (23%) groups.

The frequencies of HLA-DQA-1B (55% in ON+CD/MS, 58% in ON) and HLA-DQB-1B (49% in ON+CD/MS, 59% in ON) were significantly increased compared with control subjects (41%, HLA-DQA-1B; 37%, HLA-DQB-1B).

Brain MRI was abnormal in 48 of 56 examined patients with ON+CD/MS (Poser's Criteria) and in 64 of 120 examined patients with ON (P<.001).

In contrast, the frequencies of HLA alleles did not differ between patients with and without DeMyelinating lesions. However, patients with ON and normal MRI findings did not show association with HLA-DR15.

Conclusions
The frequencies of alleles were similar in patients with ON and ON+Clinically Definite Multiple Sclerosis (CD/MS, confirming that they are not 2 ImmunoGenetically distinct disease entities.

The Heterogeneity within the group of patients with ON suggests that the HLA-DR15 molecule is involved in susceptibility to initial DeMyelinating Lesion formation.

In the present study the relation between Human Leukocyte Antigen (HLA), Optic Neuritis (ON) and Multiple Sclerosis (MS) has been investigated in 56 Iranian patients (46 females and 10 males).

HLA-A and -B typing by MicroLymphoCytoToxicity method and HLA-DRB, DQA and DQB by polymerase chain reaction based on sequence specific primers method was performed for the selected patients with ON.

The diagnosis of clinically defined MS (CDMS) was confirmed in 15 of them (26.7%) during their follow-up. HLA-A24 was significantly higher in ON patients, while A23, A26, and A30 showed a significant decrease in these patients.

HLA-A10 and A26 were absent in CDMS patients and A2 and A11 were significantly decreased in ON and CDMS patients.

HLA-B5, B51, B38, B27, and B35 were significantly increased in ON patients compared with control subjects. HLA-B44, B16 and B38 alleles were not present in CDMS patients.

Regarding DR locus, the frequency of HLA-DRB1*15 and DRB1*04 has been increased in CDMS patients, while the frequency of HLA-DRB1*07 and *11 was much higher in ON patients.

In DQA region, the most frequent allele in the MS patients was DQA1*0102, which was significantly higher than ON patients, and control group. The frequency of DQA1*0103 was significantly increased in both patients group.

In DQB1, the frequency of DQB1*0602 increased significantly in the MS patients. In conclusion existence of common genetic basis for early manifestations of MS could be suggested.