P.045 Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody Testing in Calgary: A Quality Improvement Review

Background: Despite the availability of cell-based assays for aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies provincially, outside confirmatory testing is often performed (typically Mayo Clinic Laboratories, USA) when results deviate from expected. It is unknown how often this costly undertaking (upwards of $1,200 CAN) alters diagnosis and management. Methods: We undertook a quality improvement project evaluating the concordance/discordance rate with select chart review in all patients who had cell-based AQP4 or MOG IgG antibody testing at Mitogen Diagnostics (MitogenDx; Calgary, Alberta) and subsequent testing at Mayo Clinic Laboratories from as early as 2010 to July 2020. Results: Preliminary review of data from January 2016 to July 2020 retrieved 145 paired tests; 10 of which were discordant (concordance rate: 93.1%). Chart review confirmed 9 truly discordant cases, often associated with AQP4 or MOG weak-positive results (7/9 cases) or presumed false negative AQP4 results in prototypical neuromyelitis optica spectrum disorder (2/9 cases). Conclusions: Discordant results were rare when comparing MitogenDx local AQP4/MOG antibody test results to those referred out to Mayo Clinic Laboratories, impacting diagnosis and treatment in only 3 patients out of the total. Our results suggest costly outside confirmatory testing of AQP4/MOG antibodies could be reduced.

MOG antibody-associated encephalitis secondary to Covid-19: case report

Background While Covid-19 predominantly affects the respiratory system, neurological manifestations including encephalitis occur in some patients, possibly affecting the course and outcome of the disease. Here, we describe a unique case of a young man with Covid-19 and transient MOG-positive encephalitis, with a benign course. Case presentation A 22-year-old male, with PCR confirmed Covid-19 infection was admitted because of persistent headache. The clinical examination was normal. Neuropsychological testing revealed distinct executive deficits. Brain MRI and cerebrospinal fluid (CSF) analysis were suggestive for encephalitis. Further laboratory examination revealed a serum MOG antibody titre. The headache improved with analgetic treatment and i.v. methylprednisolone. Consequently, the MOG antibody titer decreased and MRI lesions were resolving. The patient made a full recovery, with no signs of deterioration over the following months. Conclusions Covid-19 manifestations in the CNS include encephalitis with variable course and prognosis. This case highlights a possible association between inflammation due to COVID-19 and transient secondary autoimmunity with transient MOG antibodies and atypical clinical presentation.

Paraneoplastic encephalomyeloradiculits with multiple autoantibodies against ITPR-1, GFAP and MOG: case report and literature review

Background Recently, antibodies against the alpha isoform of the glial-fibrillary-acidic-protein (GFAPα) were identified in a small series of patients with encephalomyelitis. Coexisting autoantibodies (NMDA receptor, GAD65 antibodies) have been described in a few of these patients. We describe a patient with rapidly progressive encephalomyeloradiculitis and a combination of anti-ITPR1, anti-GFAP and anti-MOG antibodies. Case presentation and literature review A 44-year old caucasian woman with a flu-like prodrome presented with meningism, progressive cerebellar signs and autonomic symptoms, areflexia, quadriplegia and respiratory insufficiency. MRI showed diffuse bilateral T2w-hyperintense brain lesions in the cortex, white matter, the corpus callosum as well as a longitudinal lesion of the medulla oblongata and the entire spinal cord. Anti-ITPR1, anti-GFAP and anti-MOG antibodies were detected in cerebrospinal fluid along with lymphocytic pleocytosis. Borderline tumor of the ovary was diagnosed. Thus, the disease of the patient was deemed to be paraneoplastic. The patient was treated by surgical removal of tumor, steroids, immunoglobulins, plasma exchange and rituximab. Four months after presentation, the patient was still tetraplegic, reacted with mimic expressions to pain or touch and could phonate solitary vowels. An extensive literature research was performed. Conclusion Our case and the literature review illustrate that multiple glial and neuronal autoantibodies can co-occur, that points to a paraneoplastic etiology, above all ovarian teratoma or thymoma. Clinical manifestation can be a mixture of typically associated syndromes, e.g. ataxia associated with anti-ITPR1 antibodies, encephalomyelitis with anti-GFAPα antibodies and longitudinal extensive myelitis with anti-MOG antibodies.

Epilepsy in patients with MOG antibody disease

Introduction. MOG (anti-myelin oligodendrocyte glycoprotein) antibody disease is a group of demyelinating disorders of the central nervous system, in which antibodies attack the glycoproteins on the oligodendrocyte myelin membrane. The aim of the study was to evaluate the course of the disease in patients with MOG antibody disease with epilepsy. Materials and methods. We examined 11 patients (5 men and 6 women) with MOG antibody disease aged from 2 months to 46 years. Three case studies were described when patients with MOG antibody disease had epileptic seizures. Results and discussion. Epileptic seizures preceded the diagnosis of MOG antibody disease in the first patient. The disease presented as right-sided optic neuritis in the second patient. Seven years later, an epileptic seizure occurred after childbirth, when the BBB could have become permeable to circulating MOG antibodies. The disease presented with headache in the third patient. Right-sided optic neuritis and ataxia developed after an acute viral respiratory infection. Myelitis was diagnosed, and an epileptic seizure occurred one year later. The patient had a combination of CADASIL syndrome with MOG antibody disease. Conclusion. Epileptic seizures are common in patients with MOG antibody disease. In addition to antiepileptic therapy, treatment of MOG antibody disease is crucial. This leads to good seizure control and a favourable prognosis.

Rate of Leptomeningeal Enhancement in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody–Associated Encephalomyelitis

Introduction: Myelin oligodendrocyte glycoprotein antibodies (MOG-abs) are associated with demyelinating diseases. Leptomeningeal enhancement occurs in 6% of adult MOG-abs patients but rates in pediatric MOG-abs patients are unknown. Methods: Retrospective review of pediatric MOG-abs patients was performed. Results: Twenty-one patients (7 boys, 14 girls) were included with an average age of 8.6 years (range 2-15 years). Seven of 21 (33%) pediatric MOG-abs patients had leptomeningeal enhancement. Two patients’ relapses were manifested by leptomeningeal enhancement alone and another patient presented with seizures, encephalopathy, and aseptic meningitis without demyelinating lesions. Cerebrospinal fluid pleocytosis was seen in both leptomeningeal (4/7 patients) and nonleptomeningeal enhancement (10/14 patients). Interestingly, 3 patients with leptomeningeal enhancement had normal cerebrospinal fluid white blood cell count. Cortical edema was more likely in patients with leptomeningeal enhancement ( P = .0263). Conclusion: We expand the clinical spectrum of anti-MOG antibody–associated disorder. Patients with recurrent leptomeningeal enhancement without demyelinating lesions should be tested for MOG antibodies.

Anti-MOG autoantibody–associated schizophreniform psychosis

Objective: Autoimmune mechanisms are related to disease development in a subgroup of patients with psychosis. The contribution of immunoglobulin G (IgG) antibodies against myelin oligodendrocyte glycoprotein (MOG) is mainly unclear in this context. Methods: Therefore, two patients with psychosis and anti-MOG antibodies—detected in fixed cell-based and live cell-based assays—are presented. Results: Patient 1 suffered from late-onset psychosis with singular white matter lesions in MRI and intermittent EEG slowing. Patient 2 suffered from a chronic paranoid-hallucinatory disorder with intermittent confusional states, non-specific white matter alterations on MRI, a disorganized alpha rhythm on EEG and elevated cerebrospinal-fluid protein. Both patients had anti-MOG antibody titers of 1:320 in serum (reference<1:20). Conclusion: The arguments for and against a causal role for anti-MOG antibodies are discussed. The antibodies could be relevant, but due to moderate titers, they may have caused a rather “subtle clinical picture” consisting of psychosis instead of “classical” MOG encephalomyelitis.