Antibody Amalgam: Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Disease with Possible Rheumatological Component Anu Sehgal, MD, PGY-2 (Internal Medicine); Ramsha Bhutta, MD, Faculty - Neurology, St. Francis − Emory Healthcare, Columbus, GA.

Summary: Background: Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) is an inflammatory disorder of the central nervous system (CNS) characterized by immune-mediated demyelination. Unlike multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), where the first attack can lead to permanent neuronal damage, MOGAD often results in complete recovery after the initial event. This case illustrates the complexities associated with MOGAD, its potential overlap with other antibodies and ultimately, a potential overlap with rheumatological disorders. Case Presentation: A 46-year old woman with hypertension, anxiety, and chronic anemia presented to the ER with recurrent, episodic vision loss accompanied by slurred speech, agitation and gait instability—symptoms that had been waxing and waning for 3-4 months. The ophthalmologic symptomatology entailed color desaturation and sudden bilateral vision loss that improved to where the patient could identify hand movements. Patient did not report any nausea, dizziness, bowel/bladder incontinence, hearing or memory loss. Upon admission, differential diagnoses of vascular, spinal and ophthalmic conditions; heavy metal toxicity; and vitamin or mineral deficiencies failed to explain the etiology of her symptoms. CT angiogram and spinal MRI were unremarkable. A non-contrast, head CT indicated hypodensities in the thalamus, midbrain and pons. MRI Brain with contrast revealed restricted diffusion with post-contrast enhancement in the anterior limb of the right internal capsule, lateral right thalamus, midbrain, pons and right cerebellar peduncle. CSF analyses returned negative for infectious etiologies but reported varying results for MOG antibodies and Purkinje Cell Antibody 2 (PCA 2). Serum MOG antibody titer of 1:1000 was distinctly positive. A MOGAD diagnosis was considered based on the diagnostic workup. Treatment with PLEX, methyl prednisone and Rituximab achieved partial improvement and the patient had residual intermittent visual and gait deficits. Interestingly, residual symptoms persisted and the generalized pain and weakness remained unexplained. Discussion: The 2023 MOGAD diagnostic criteria were met based on a positive serum titer, optic neuritis, encephalopathy, agitation, cerebellar manifestations and exclusion of MS and NMOSD. Since the CSF initially tested positive for PCA 2 but subsequently demonstrated MOG antibodies, it could suggest a false positive PCA 2 test. Given the patient’s history of cigarette smoking, the relevance of PCA 2 in predicting small cell lung cancer assumes significance. Diagnosis of MOGAD hinges on identifying serum MOG-IgG via cell based assays; excluding alternative diagnosis; and assessing for a monophasic or relapsing demyelinating event. The criteria also suggest that MOGAD is typically associated with ADEM, optic neuritis or transverse myelitis and less often associated with cerebral cortical encephalitis, brainstem or cerebellar presentations. The criteria usually restrict radiologic imaging to cases with diagnostic uncertainty. Additionally, the MOG antibody titer is contingent upon the timing of sample collection and assay method used. This case depicted typical symptoms of optic neuritis mixed with relatively uncommon cerebellar signs. The occurrence of residual deficits, as seen here, is also uncommon in MOGAD along with generalized weakness and pain symptoms. Additionally, MOG antibodies are transient and clinical symptoms may be monophasic, in which case, MOGAD may evade detection. Currently, treatment regimens for MOGAD are not well established and have been adopted from those used to manage other demyelinating conditions. The prognosis and risk of relapse after treatment is also not well elucidated. This patient had partial improvement and outcomes could improve with better treatment regimens. Conclusion: Although MOGAD was considered here, ongoing systemic symptoms raise the possibility of alternative autoimmune or rheumatological diagnoses. Unlike MOGAD, some CNS demyelinating conditions such as Neuromyelitis Optica are associated with autoimmunity leading to rheumatoid arthritis or Hashimoto’s thyroiditis. Therefore, systemic symptoms could be atypical findings of a rare disease or the result of the combination of antibodies.