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Relation to Multiple Sclerosis and Magnetic Resonance Imaging Findings

J. L. Frederiksen, MD; H. O. Madsen, MSc; L. P. Ryder, MSc; H. B. W. Larsson, MD, MSc; N. Morling, MD, MSc; A. Svejgaard, MD, MSc

Arch Neurol. 1997;54(1):76-80.

Abstract
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 (CDMS).

Design
Population-based cohort of patients with ON referred prospectively during 6 years by neurologists and ophthalmologists within 4 weeks of onset of ON.

Setting
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+CDMS), 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+CDMS (52%) and ON (47%) compared with control subjects (31%). The frequency of HLA-DR17 was almost equal in the ON + CDMS (18%), ON (23%), and control (23%) groups. The frequencies of HLA-DQA-1B (55% in ON+CDMS, 58% in ON) and HLA-DQB-1B (49% in ON+CDMS, 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+CDMS 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+CDMS, 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.

Author Affiliations
From the Department of Neurology, Glostrup University Hospital (Dr Frederiksen), Tissue Typing Laboratory, National University Hospital (Messrs Madsen and Ryder and Dr Svejgaard), Department of Magnetic Resonance Imaging, Hvidovre University Hospital (Dr Larsson), and University Department of Forensic Genetics (Dr Morling), Copenhagen, Denmark.

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