The clinical presentation is variable and largely dependent upon the overall clinical manifestation. The presence of anti-MOG autoantibodies has been described in association with the following conditions:
The most common presenting phenotypes are acute disseminated encephalomyelitis in children and optic neuritis in adults. Some of these phenotypes have been studied in detail:
Seronegative neuromyelitis optica
Anti-MOG antibodies have been described in some patients with NMOSD who were negative for the aquaporin 4 antibody. However, NMOSD is an astrocytopathy, whereas MOG antibody-associated disease is an oligodendrocytopathy, suggesting that these are two separate pathologic entities. Rare cases have been described of patients with antibodies against both AQP4 and MOG. These patients typically have MS-like brain lesions, multifocal spine lesions and optic nerve atrophy. However, the coexistence of both antibodies is still a matter of ongoing debate.
ADEM
The presence of anti-MOG antibodies is more common in children with ADEM.
The reason why anti-MOG auto-antibodies appear remains unknown. A post-infectious autoimmune process has been proposed as a possible pathophysiologic mechanism. Other reports point to molecular mimicry between MOG and some viruses as a possible etiology.
Histopathology
Demyelinating lesions of MOG-associated encephalomyelitis resemble more those observed in multiple sclerosis than NMO. They are similar to pattern-II multiple sclerosis with T-cells and macrophages surrounding blood vessels, preservation of oligodendrocytes and signs of complement system activation.
Diagnosis
Serum live cell-based assays are the gold standard for anti-MOG antibody testing. Cerebrospinal fluid analysis is less sensitive and specific compared to serum testing. Cerebrospinal fluidoligoclonal bands are uncommon. Proposed diagnostic criteria require serum positivity for MOG antibody, a clinical presentation consistent with an acquired demyelinating syndrome, and exclusion of an alternative diagnosis. In the young, MRI typically shows ADEM–like lesions and longitudinally extensive transverse myelitis, whereas optic neuritis and short transverse myelitis are more commonly seen in older patients. However, rare cases of symptomatic MRI-negative MOG-related disease have been described.
Clinical course
Two clinical courses have been described:
Monophasic
Relapsing
Prognosis
Residual disability develops in 50–80% of patients, with transverse myelitis at onset being the most significant predictor of long-term outcome.
Treatment
Acute therapy consists of high-dose corticosteroids, IVIG, or plasma exchange, and long-term immunosuppression may be necessary in recurrent cases. Anti-MOG positive patients should not be treated with interferons as these may worsen the disease course similar to those with NMOSD. There are also anecdotal reports against using fingolimod or Alemtuzumab.
Research
Animal models in experimental autoimmune encephalomyelitis, EAE, have shown that “MOG-specific EAE models display/mirror human multiple sclerosis" but EAE pathology is closer to NMO and ADEM than to the confluent demyelination observed in MS.
History
Reports describing the possible involvement of anti-MOG antibodies in multiple sclerosis and other demyelinating conditions first appeared in the literature in the late 1980s, but evidence to support their role in demyelinating disease was always weak and inconsistent. The turning point was in 2011, when Mader et al. developed a cell-based assay using HEK 293 cells which increased the detection rate of these antibodies in the serum. Reports about prevalence of anti-MOG in selected Multiple Sclerosis cases began to appear in 2016
