MOGAD is a rare, antibody-mediated inflammatory demyelinating disease of the central nervous system, which can occur at all ages and its clinical manifestations are age-dependent, with most children presenting with acute disseminated encephalomyelitis (ADEM) and adults presenting with optic neuritis, myelitis and brainstem encephalitis [6]. New clinical and imaging manifestations of atypical MOGAD are constantly being reported, and it is currently difficult to make a definitive diagnosis of MOGAD based on clinical presentation and imaging alone. Detection of anti-MOG-IgG in serum and CSF using a cell-based assay is important for the diagnosis of disease. The international diagnostic criteria for MOGAD require the presence of at least one core clinical demyelination event, as well as a positive MOG IgG test and exclusion of other diagnoses including multiple sclerosis and NMOSD [7]. To date, the exact pathogenesis of MOGAD remains unclear, and MOG expressed in the outer layer of the myelin sheath of nerve fibers in the central nervous system (CNS) is considered a potential target for autoimmune response during demyelination. There is no standard treatment protocol for MOGAD disease. Immunotherapy such as glucocorticoids and gammaglobulin in the acute phase and immunosuppressive agents such as azathioprine, motilmicronate and rituximab in the maintenance treatment in the remission phase have a good prognosis in most cases [8].
The imaging characteristics of MOGAD are diverse. Optic neuritis (ON) often manifests as bilateral simultaneous and longitudinal involvement of the optic nerve, enhancement of the optic nerve sheath around the nerve, and/or optic disc edema. Spinal cord inflammation often presents as extensive longitudinal involvement, central spinal cord position or axial H-sign on imaging, and/or involvement of the spinal cord cone. Brain, brainstem, or cerebral syndromes are often characterized by multiple poorly defined T2 high-intensity white matter lesions, involvement of deep gray matter, poorly defined T2 high-intensity signals involving the brainstem, cerebellar midfoot, or medulla oblongata, and/or the presence of cortical lesions [9]. The atypical imaging findings increase the diagnostic difficulty of MOGAD.
The previous reports indicate that after treating MOGAD with glucocorticoids and immunoglobulins, patients can achieve clinical and radiological improvement. In our case, the patient showed T2 hyperintensities in the medulla, midbrain, pons, and cerebellum. Although the patient's symptoms improved after glucocorticoid treatment, the lesions persisted. This suggests that the extent of radiological involvement may not necessarily be directly related to the severity of clinical symptoms. Therefore, further research is needed to clarify the relationship between MRI outcomes and the relapse-remission pattern of MOGAD, as well as its long-term prognosis.
Our case was initially thought to be CNS lymphoma, so the differential diagnosis of MOGAD and CNS lymphoma is important. CNS lymphoma is a rare and aggressive type of cancer that occurs in the lymphatic cells of the brain, spinal cord, or eyes, which is a form of non-Hodgkin lymphoma that is confined to the central nervous system without evidence of systemic disease [10]. CNS lymphoma typically presents on MRI as isointense to hypointense on T1-weighted images and isointense to hyperintense on T2-weighted images, with homogeneous, intense enhancement after gadolinium administration. Restricted diffusion on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) values are characteristic due to high cellularity. Lesions often involve periventricular white matter, basal ganglia, and corpus callosum, with minimal surrounding edema. CT shows hyperdense lesions, while FDG-PET reveals high metabolic activity. MR spectroscopy often demonstrates elevated choline and decreased NAA levels. These imaging features are critical for distinguishing CNS lymphoma from other intracranial pathologies. In contrast, MOGAD often shows variable, patchy enhancement, frequent involvement of the optic nerves and spinal cord, less pronounced diffusion restriction, and more extensive edema, with lesions that are more diffuse and poorly defined. These distinctions are crucial for accurate diagnosis and management. To sum up, myelin oligodendrocyte glycoprotein antibody disease can be misdiagnosed as CNS lymphoma due to several overlapping features. Both conditions may present with contrast-enhancing lesions on MRI, with MOGAD sometimes showing variable or patchy enhancement similar to the homogeneous enhancement seen in CNS lymphoma. They can also affect similar brain regions, such as the optic nerves and brainstem, leading to diagnostic confusion. Additionally, MOGAD lesions may appear ill-defined or diffuse and can exhibit restricted diffusion, albeit less pronounced than in CNS lymphoma. Extensive edema seen in MOGAD may further mimic the appearance of CNS lymphoma lesions. The lack of distinct imaging markers necessitates careful clinical evaluation and additional diagnostic testing to differentiate between these conditions accurately.
Our case presented with swallowing difficulties and nausea during the course of the disease and showed brainstem involvement on imaging, which cannot be ruled out as a manifestation of area postrema syndrome (APS). APS is characterized by severe nausea, vomiting and hiccups due to dysfunction of the area postrema in the medulla oblongata, which regulates the emetic reflex. APS can result from various underlying conditions, including demyelinating diseases, ischemic stroke, brainstem encephalitis, and tumors in the AP area (such as glioblastoma) [11–14]. APS is more common in NMOSD[14]. However, MOG-IgG-positive, AQP-4-negative patients have occasionally been reported with lesions in the area postrema (AP) and area postrema syndrome (APS), although this association is rare. In a study of 50 adult patients with MOG-IgG-positive optic neuritis and/or myelitis, 8 had lesions in the medulla oblongata, with only 2 near the fourth ventricle, and 1 presenting with APS [15]. Similarly, in a pediatric case series of 26 MOG-IgG-positive patients, only 1 had APS, compared to 4 out of 8 AQP-4-positive patients [16]. A study by Chen and colleagues also showed that 7 out of 200 MOG IgG positive patients had APS, while 47 out of 332 NMOSD patients had APS [14]. Rare APS manifestations make the diagnosis of MOGAD more challenging.
In summary, our case demonstrates that antibody testing is crucial for distinguishing between MOGAD and central nervous system tumors. We recommend incorporating antibody testing when imaging studies are inconclusive in diagnosing tumors or demyelinating diseases.