Anti-MOG syndrome : two case reports

The last decades were marked by dramatic progress in understanding of the pathogenesis, diagnostics and treatment of demyelinating diseases. This interest is due to the important social role of multiple sclerosis, which is one of the most common causes of persistent disability of working age people. As our understanding of the pathogenesis of demyelinating diseases increases, it becomes apparent that they are a combination of various pathological processes, often overlapping. Examples include the opticospinal form of multiple sclerosis and neuromyelitis optica (Devic's disease) [1], the latter, however, in recent years has been regarded as a part of “neuromyelitis optica spectrum disorders” (NMOSD) [2]. In patients with optic neuritis and / or myelitis who do not have antibodies to aquaporin-4 (as well as people with other clinical manifestations of demyelinating diseases), the disease can be caused by the presence of antibodies to myelin oligodendrocyte glycoprotein (MOG), which can be phenotypically manifested in a number of conditions, including acute disseminated encephalomyelitis (ADEM), optic neuritis, myelitis (including severe transverse myelitis with a pronounced longitudinal lesion of the spinal cord [Longitudinally Extensive Transverse Myelitis, LETM]), and encephalitis [3]. Thus, in a large study by S. Mariotto et al. [4] involving 425 patients with demyelinating diseases, antibodies to MOG were detected in 22 subjects. In Russia, the research of anti-MOG syndrome was hampered by the fact that none of large laboratories performed tests for these antibodies as a routine practice, and only recently there has appeared an opportunity of their research at the Scientific Center of Neurology in patients over 18 years old, using ELISA type Sandwich method with reagents of CloudClone Corp (USA). We present a description of two clinical observations of anti-MOG syndrome. Male patient X., born in 1999, in 2014 after an acute respiratory viral infection presented with pain during the left eyeball movement and a sharp vision loss in the left eye. The history of this patient in the period of 2014–2015 was described in an earlier publication [5]. Following the left-sided optic neuritis, the patient developed myelitis, which did not meet the LETM criteria (Fig. 1, 2), and the analysis for antibodies to aquaporin-4 turned out to be negative. The diagnosis of multiple sclerosis was established, and interferon beta (IFNβ) was prescribed. With repeated MRI, performed at the age of 17, negative dynamics was observed in the form of the appearance of demyelination foci that did not accumulate a contrast agent in the white matter of the brain hemispheres (Fig. 3). Kotov A.S. M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia 61/2, Shchepkin St., Moscow 129110


C L I N I C A L O B S E R V A T I O N S
The last decades were marked by dramatic progress in understanding of the pathogenesis, diagnostics and treatment of demyelinating diseases. This interest is due to the important social role of multiple sclerosis, which is one of the most common causes of persistent disability of working age people. As our understanding of the pathogenesis of demyelinating diseases increases, it becomes apparent that they are a combination of various pathological processes, often overlapping. Examples include the opticospinal form of multiple sclerosis and neuromyelitis optica (Devic's disease) [1], the latter, however, in recent years has been regarded as a part of "neuromyelitis optica spectrum disorders" (NMOSD) [2]. In patients with optic neuritis and / or myelitis who do not have antibodies to aquaporin-4 (as well as people with other clinical manifestations of demyelinating diseases), the disease can be caused by the presence of antibodies to myelin oligodendrocyte glycoprotein (MOG), which can be phenotypically manifested in a number of conditions, including acute disseminated encephalomyelitis (ADEM), optic neuritis, myelitis (including severe transverse myelitis with a pronounced longitudinal lesion of the spinal cord [Longitudinally Extensive Transverse Myelitis, LETM]), and encephalitis [3].
Thus, in a large study by S. Mariotto et al. [4] involving 425 patients with demyelinating diseases, antibodies to MOG were detected in 22 subjects. In Russia, the research of anti-MOG syndrome was hampered by the fact that none of large laboratories performed tests for these antibodies as a routine practice, and only recently there has appeared an opportunity of their research at the Scientific Center of Neurology in patients over 18 years old, using ELISA type Sandwich method with reagents of Cloud-Clone Corp (USA).
We present a description of two clinical observations of anti-MOG syndrome.
Male patient X., born in 1999, in 2014 after an acute respiratory viral infection presented with pain during the left eyeball movement and a sharp vision loss in the left eye. The history of this patient in the period of 2014-2015 was described in an earlier publication [5]. Following the left-sided optic neuritis, the patient developed myelitis, which did not meet the LETM criteria ( Fig. 1, 2), and the analysis for antibodies to aquaporin-4 turned out to be negative.
The diagnosis of multiple sclerosis was established, and interferon beta (IFNβ) was prescribed. With repeated MRI, performed at the age of 17, negative dynamics was observed in the form of the appearance of demyelination foci that did not accumulate a contrast agent in the white matter of the brain hemispheres (Fig. 3  The patient continued treatment with IFNβ, but at the age of 18 new exacerbation occurred with a clinical picture of optic neuritis and myelitis. After methylprednisolone pulse therapy, the patient was tested for MOG antibodies; the test was positive (15.3 pg/ml; normal range 0-15 pg/ml).
In the second patient, the disease course was less typical, the symptoms of demyelinating process superimposed on other neurological and somatic symptoms, which led to a prolonged and unproductive evaluation before establishing the correct diagnosis.  Female patient V., born in 1991, from childhood was diagnosed with stomatitis 1-3 times a year, at the age of 15 years "blindness in the right eye", in Helmholtz Moscow Research Institute of Eye Diseases she was diagnosed with retrobulbar neuritis in the right eye, and a standard treatment was carried out, which, however, did not lead to the reversal of the symptoms. Atrophy of the right optic nerve developed, which was further confirmed by optical coherence tomography (OCT, Fig. 4).
From the age of 15 to 23 years old, there were no significant changes in the patient's neurological status, although she was observed at V.A. Nasonova Institute of Rheumatology for bilateral uveitis and recurrent joint pain (a rheumatic disease was suspected); she was also observed by a dermatologist for psoriasis. Based on these data, as well as the negative dynamics of neurological changes, the rheumatologist suggested that the patient had Behcet's disease with the CNS damage, which was not confirmed by subsequent findings, including the negative pathergy test. At the age of 23, persistent numbness appeared in the left half of the body, and, after a few months, an epileptic seizure occurred with a focal beginning in the left extremities and a subsequent secondary generalization. The brain MRI revealed a demyelinating disease with gliosis in the right hemisphere (Fig. 5).
Later, from the age of 23 to 27 years, an increase in left-sided spastic hemiparesis was observed, as well as rare (1-2 times a year) epileptic seizures with a focal onset in the left extremities and secondary generalization (Fig. 6). Such disease course in anti-MOG syndrome is extremely rare [6]; the debut of epileptic seizures in children with ADEM is more typical [7].
During the observation and treatment in our clinic (from the age of 23 to 27), numerous laboratory studies (tests for antineuronal antibodies, antinuclear factor, M and G class antibodies to cardiolipin, type of oligoclonal antibody synthesis, antibodies to aquaporin-4, anti-erythrocyte antibodies, rheumatoid factor, lupus anticoagulant, HLA phenotypes, antibodies to the NMDA receptor, as well as clinical and biochemical analyzes of blood and cerebrospinal fluid, urinalysis, coagulogram, etc.) did not reveal a definite pathology.
A rheumatic disease was also rejected, taking into account the normal picture of the peripheral blood and the absence of pathological changes in the joints according to numerous radiographic studies and MRI scans.
The patient was consulted in absentia by one of the world's leading experts on demyelinating diseases, Professor F. Fazekas from Austria. It was recommended that antibodies to MOG be tested, and the test turned out to be positive (20 pg/ml; normal range 0-15 pg/ml).
Discussion. Detection of anti-MOG syndrome is very important because a number of drugs used in treatment of multiple sclerosis may be ineffective, or even exacerbate the severity of clinical symptoms in patients with optic neuritis and / or myelitis, among which there may be patients with anti-MOG [8,9].
Anti-MOG syndrome should be suspected in patients with a clinical picture of optic neuritis and/or myelitis and a negative test for the presence of antibodies to aquaporin-4 [10,11].
The first line treatment for the syndrome is pulse therapy with intravenous methylprednisolone, but over time, the effectiveness of such therapy may decrease. Intravenous human immunoglobulin or plasmapheresis can be an adjunct or alterna-  tive. If the disease is relapsing, or recovery of patients is too slow, the second-line therapy should be considered, including mycophenolate mofetil or azathioprine, and the third line -rituximab [12]. However, it should be emphasized that not only the therapy scheme, but also the diagnostic algorithm and even the taxonomic position of this syndrome in the classification of demyelinating diseases [13] are not fully developed. Obviously, further research is needed to solve these problems.
Article received 22.10.2018