Abstract
Purpose
To describe the clinical, radiological, immunological and electrophysiological features of a myelin oligodendrocyte glycoprotein (MOG)-IgG positive girl with five prior episodes of idiopathic bilateral optic neuritis (ON).
Observations
We report a Danish girl who has been followed by pediatricians and pediatric neurologists since the age of 10 with recurrent episodes of idiopathic bilateral ON. Since the age of 15 there has been no recurrence of ON, and the patient has been thoroughly investigated for Multiple Sclerosis (MS) several times, but with negative findings. At the age of 19 the patient was referred to the Clinic of Optic Neuritis where she was tested seropositive for antibodies against MOG (MOG- IgG) on a conventionally cell-based assay. Despite 5 previous episodes of ON, the latency and amplitude signals of pattern-reversal visual evoked potentials (pVEP) including multifocal VEP were detected within the normal range.
Conclusion
The clinical implications of MOG- IgG are not yet clear, but in cases where the diagnosis of MS is less likely and where ON is the main symptom, testing for both IgG antibodies against AQP4 and MOG while having atypical optic neuropathies in mind is important. MOG-IgG positive patients may have a good prognosis with regards to visual function.
1
Introduction
The myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein expressed on the outer membrane of myelin in the central nervous system (CNS). Neuroinflammatory autoimmune diseases involving IgG antibodies against MOG (MOG-IgG) are termed MOG-IgG associated disease [MOG-AD] or MOG-IgG associated encephalomyelitis and is considered as a distinct disease entity from both multiple sclerosis (MS) and aquaporin-4 antibody (AQP4-IgG)- neuromyelitis optica spectrum disorders (NMOSD). Detection of antibodies to the astrocytic AQP4 water channel is currently considered as a highly sensitive and specific diagnostic biomarker in NMOSD, but up to 42% of the NMOSD patients who are tested seronegative for the AQP4-IgG are tested positive for MOG-IgG.
Here we present a case report of a Caucasian girl with a long pediatric history of recurrent episodes of idiopathic bilateral ON who is finally tested positive for MOG-IgG.
2
Case report
In April 2016 a 19-year-old girl is referred to the Clinic of Optic Neuritis and Multiple Sclerosis for an investigation of demyelinating disease. The patient has been followed by pediatricians and pediatric neurologists since the age of 10 with recurrent episodes of idiopathic bilateral optic neuritis (rON). Previous ophthalmologic examinations showed a best-corrected visual acuity (VA) of 0.08 in the left eye and 1.2 in the right eye with a positive relative afferent pupillary defect (RAPD) in the left eye. Superior and inferior temporal visual field defects were confirmed in the left eye using perimetry tests, whereas the visual field was normal in the right eye. Initially a 3- days course of methylprednisolone was given intravenously (1000 mg/day) followed by 2 months of daily oral prednisolone until tapering off during another 4 months (5 mg–2.5 mg). In the beginning, the patient experienced relapses of ON when steroids were tapered down but at the end the patient had good recovery (i.e. normal VA and visual fields). Since the age of 15 no recurrence of ON and the patient had several times been thoroughly investigated for MS, but with negative findings. The suspicion of MS arises again because the patient experienced progressive paraesthesia in the left extremities for 2–3 weeks.
During hospitalization magnetic resonance imaging (MRI) scanning (1.5T Siemens) of the central nervous system (CNS) was performed, and it revealed only a cervical demyelinating lesion, extending above C3 and down to C6/C7. The radiological diagnosis was acute transverse myelitis. The chest X-ray was normal and lumbar puncture (the patient had not been given any treatment in two months) showed normal conditions with regard to leukocytes, protein, glucose, oligoclonal bands, immunoglobulin G index, borrelia and herpes viruses. The patient was screened extensively with blood samples including the complete blood count with differential, common electrolytes and liver functions tests, glucose and coagulation factors, thyroid stimulating hormone (TSH), folate, 25-hydroxy vitamin D test, cobalamin, immunoglobulins, antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), IgM-Rheumatoid Factor, Sjögren’s Syndrome-B Extractable Nuclear Antibodies, angiotensin converting enzyme test (to exclude sarcoidosis). The above blood tests were all normal including negative test for IgG autoantibodies against aquaporin-4 (AQP4-IgG), but with a weak positive test for IgG autoantibodies against the myelin oligodendrocyte glycoprotein (MOG-IgG). MOG-IgG analysis were performed with a cell based assay (CBA) which is an internationally recognized assay method for detecting MOG-IgG. The technique indirectly detects immunofluorescence on live transfected CBA and results are recorded on a semiquantitative scale (negative, grey‐zone, weak positive, medium positive, or strong positive). A standard 1:10 dilution was used.
Due to the symptoms of paraesthesia the patient was treated with a 5- days course of methylprednisolone (given intravenously 1000 mg/day). Two months later, the pattern-reversal visual evoked potentials (pVEP) and multifocal VEP showed normal latency and amplitude in both eyes ( Fig. 2 ). VA was 1.2 in both eyes and the visual fields of both eyes were normal and the pupils did not show a RAPD. Optical coherence tomography (OCT) was also performed using the Cirrus HD-OCT, model 4000, software V.7.0.1.290 and it showed bilateral loss of the peripapillary retinal nerve fiber layer (RNFL) (i.e. the average RNFL thickness was 69 μm in the right eye and 54 μm in the left eye). Furthermore OCT showed bilateral loss of the ganglion cell layer (GCL) with an average GCL thickness of 70 μm in the right eye and 64 μm in the left eye (see Fig. 1 ). MOG-IgG was again measured by the same method and this time the test was strong positive. The paraesthesia in the extremities was no longer present and a signal intensity decrease was observed on T2-weighted images of the cervical spine on MRI (extending from C3 to C6/C7).
