Contributions
Abstract: EP1573
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: The pathophysiological and clinical role of antibodies to myelin-oligodendrocyte-glycoprotein (MOG-abs) is still not fully understood. In this context we report the case of a 61-year-old patient presenting with neurological symptoms and positive serum IgM MOG-abs.
Case report: A 61-year-old female patient developed episodes of vertigo, which worsened significantly along with double vision, lack of coordination and weight loss. Primary assessment included MRI and CSF analysis. MRI showed unspecific white matter lesions with focus in the pons and cerebellar peduncles without gadolinium enhancement. CSF analysis revealed a mild lymphoplasmacellular pleocytosis without detection of any tumour cells. As an inflammatory demyelinating disorder appeared possible a screening for MOG-abs complemented the diagnostic approach. Serum MOG-ab were detected with an initial titer of 1:160, however, this MOG-ab-response was mainly of the IgM isotype (1:2560), most likely also detected by the IgG(H+L) secondary antibody used, whereas no IgG(Fc) specific response was detected. After alternating periods of improvement due to high-dose methylprednisolone and relapses with brainstem symptoms, the therapeutic regime was changed to continuous, oral low-dose corticosteroids. As MRI was repeated a new, strongly gadolinium enhancing lesion in the basal ganglia, highly suspicious for CNS lymphoma was revealed, which was verified by biopsy and histopathology. The following therapy with rituximab, azathioprine and methotrexate was unfortunately not successful, thus palliative treatment was decided.
Conclusion: The present case challenged by its differential diagnoses, which included inflammatory, like CLIPPERS-syndrome, and neoplastic disorders. The exclusive IgM-isotype MOG-ab-response might be a false positive result, which fits well to the resent observation, that secondary antibodies to human IgG can also detect IgM-abs. While the absence of demyelination in the biopsy argues against a pathophysiological role, the clinical relevance of MOG-ab response is unclear. Finally, we have analysed 10 additional patients with CNS lymphoma for MOG-abs, but all of them were negative for IgG MOG-abs, whereas two were positive for IgM MOG-abs.
This case report demonstrates the possible pitfalls of MOG-ab testing and indicates that borderline positive MOG-ab results should be confirmed by a second immunoassay using either human IgG(Fc) or IgG1 specific secondary antibodies.
Disclosure: Klaus Berek: nothing to disclose.
Franziska Di Pauli has received speaking honoraria from Biogen-Idec and Sanofi-Aventis Austria.
Paul Rhomberg: nothing to disclose.
Kathrin Schanda: nothing to disclose.
Guenther Stockhammer: nothing to disclose.
Romana Höftberger received speakers honoraria from Euroimmun AG and travel support from Novartis.
Markus Reindl was supported by a research grant from the Austrian Science Promotion Agency (FFG). The University Hospital and Medical University of Innsbruck (Austria; M.R.) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Lübeck, Germany).
Thomas Berger has received research grants (“BIG-WIG MS”,Austrian Federal Ministry of Science, Research and Economy; Austrian Multiple Sclerosis Research Society) and his institution receives payments for antibody assays (AQP4 and anti-neuronal antibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Germany).
Abstract: EP1573
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: The pathophysiological and clinical role of antibodies to myelin-oligodendrocyte-glycoprotein (MOG-abs) is still not fully understood. In this context we report the case of a 61-year-old patient presenting with neurological symptoms and positive serum IgM MOG-abs.
Case report: A 61-year-old female patient developed episodes of vertigo, which worsened significantly along with double vision, lack of coordination and weight loss. Primary assessment included MRI and CSF analysis. MRI showed unspecific white matter lesions with focus in the pons and cerebellar peduncles without gadolinium enhancement. CSF analysis revealed a mild lymphoplasmacellular pleocytosis without detection of any tumour cells. As an inflammatory demyelinating disorder appeared possible a screening for MOG-abs complemented the diagnostic approach. Serum MOG-ab were detected with an initial titer of 1:160, however, this MOG-ab-response was mainly of the IgM isotype (1:2560), most likely also detected by the IgG(H+L) secondary antibody used, whereas no IgG(Fc) specific response was detected. After alternating periods of improvement due to high-dose methylprednisolone and relapses with brainstem symptoms, the therapeutic regime was changed to continuous, oral low-dose corticosteroids. As MRI was repeated a new, strongly gadolinium enhancing lesion in the basal ganglia, highly suspicious for CNS lymphoma was revealed, which was verified by biopsy and histopathology. The following therapy with rituximab, azathioprine and methotrexate was unfortunately not successful, thus palliative treatment was decided.
Conclusion: The present case challenged by its differential diagnoses, which included inflammatory, like CLIPPERS-syndrome, and neoplastic disorders. The exclusive IgM-isotype MOG-ab-response might be a false positive result, which fits well to the resent observation, that secondary antibodies to human IgG can also detect IgM-abs. While the absence of demyelination in the biopsy argues against a pathophysiological role, the clinical relevance of MOG-ab response is unclear. Finally, we have analysed 10 additional patients with CNS lymphoma for MOG-abs, but all of them were negative for IgG MOG-abs, whereas two were positive for IgM MOG-abs.
This case report demonstrates the possible pitfalls of MOG-ab testing and indicates that borderline positive MOG-ab results should be confirmed by a second immunoassay using either human IgG(Fc) or IgG1 specific secondary antibodies.
Disclosure: Klaus Berek: nothing to disclose.
Franziska Di Pauli has received speaking honoraria from Biogen-Idec and Sanofi-Aventis Austria.
Paul Rhomberg: nothing to disclose.
Kathrin Schanda: nothing to disclose.
Guenther Stockhammer: nothing to disclose.
Romana Höftberger received speakers honoraria from Euroimmun AG and travel support from Novartis.
Markus Reindl was supported by a research grant from the Austrian Science Promotion Agency (FFG). The University Hospital and Medical University of Innsbruck (Austria; M.R.) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Lübeck, Germany).
Thomas Berger has received research grants (“BIG-WIG MS”,Austrian Federal Ministry of Science, Research and Economy; Austrian Multiple Sclerosis Research Society) and his institution receives payments for antibody assays (AQP4 and anti-neuronal antibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Germany).