Contributions
Abstract: P1744
Type: Poster Sessions
Abstract Category: N/A
Importance: Inflammatory central nervous system (CNS) demyelinating disorders likely contain multiple pathogenetically distinct disease entities. Detection of anti-aquaporin (AQP)-4 antibodies defined neuromyelitis optica spectrum disorders (NMOSD) as a separate disease entity distinct from multiple sclerosis (MS). Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been associated with MS, acute disseminated encephalomyelitis (ADEM) or NMOSD. However, the exact pathological correlate of anti-MOG antibody-associated demyelination has not yet been defined.
Objective: To characterize the pathology of anti-MOG antibody-associated CNS lesions.
Design, setting and participants: This multi-center study included 15 brain biopsies from patients pathologically diagnosed with MS. CNS lesions from patients with serum anti-MOG antibodies (n=8) were compared to MS pattern II lesions without anti-MOG serum antibodies (n=7). We performed detailed morphological, immunohistochemical and quantitative analyses of the demyelination pattern, inflammatory infiltrates, oligodendrocytes, acute axonal damage and astrocytes.
Results: The quantification of inflammatory infiltrates, oligodendrocytes, axonal damage and astrocytes did not reveal significant differences between MOG antibody-positive cases and MS pattern II cases. The comparison between the perivascular and the parenchymal inflammatory infiltrates showed that (1) the MOG antibody-positive cases present more perivascular T cell inflammation than MS pattern II cases, and (2) the MS pattern II cases present more perivascular B cell/plasma cell inflammation than the MOG antibody-positive cases. Almost all MOG antibody-positive cases with periplaque white matter (PPWM) present in the tissue specimen (5/6) showed ADEM-like histological characteristics (perivascular demyelination) in the PPWM, which was completely absent in MS pattern II cases.
Conclusions: This study provides evidence that the MOG antibody-associated demyelination differs from pattern II MS lesions through a different distribution of inflammatory infiltrates and an ADEM-like demyelination pattern in the PPWM suggesting that anti-MOG antibody-associated demyelination may represent a disease entity separate from classic MS.
Disclosure: Theoni Maragkou: nothing to disclose
Imke Metz: Dr. Metz reports personal fees from BiogenIdec, Bayer Heathcare, TEVA, Serono, Novartis, Genzyme, Roche, grants from BiogenIdec, grants from N-RENNT 2 (Niedersachsen Research Network on Neuroinfectiology), outside the submitted work.
Christine Stadelmann: CS received honoraria for speaking and travel reimbursement from Novartis Pharma GmbH, Merck, Teva Pharmaceutical Industries Ltd., Biogen, and Bayer Health Care. She served on scientific advisory boards of Novartis, Merck, Roche, and Teva. She received research support from Teva. She is a member of the editoral board of Neurology: Neuroimmunology & Neuroinflammation.
Wolfgang Brück: WB was supported from the German Ministry of Education and Research (BMBF “German Competence Network Multiple Sclerosis (KKNMS)”). WB has received, outside the submitted work, honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Novartis and Genzyme. WB received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. WB serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.
Abstract: P1744
Type: Poster Sessions
Abstract Category: N/A
Importance: Inflammatory central nervous system (CNS) demyelinating disorders likely contain multiple pathogenetically distinct disease entities. Detection of anti-aquaporin (AQP)-4 antibodies defined neuromyelitis optica spectrum disorders (NMOSD) as a separate disease entity distinct from multiple sclerosis (MS). Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been associated with MS, acute disseminated encephalomyelitis (ADEM) or NMOSD. However, the exact pathological correlate of anti-MOG antibody-associated demyelination has not yet been defined.
Objective: To characterize the pathology of anti-MOG antibody-associated CNS lesions.
Design, setting and participants: This multi-center study included 15 brain biopsies from patients pathologically diagnosed with MS. CNS lesions from patients with serum anti-MOG antibodies (n=8) were compared to MS pattern II lesions without anti-MOG serum antibodies (n=7). We performed detailed morphological, immunohistochemical and quantitative analyses of the demyelination pattern, inflammatory infiltrates, oligodendrocytes, acute axonal damage and astrocytes.
Results: The quantification of inflammatory infiltrates, oligodendrocytes, axonal damage and astrocytes did not reveal significant differences between MOG antibody-positive cases and MS pattern II cases. The comparison between the perivascular and the parenchymal inflammatory infiltrates showed that (1) the MOG antibody-positive cases present more perivascular T cell inflammation than MS pattern II cases, and (2) the MS pattern II cases present more perivascular B cell/plasma cell inflammation than the MOG antibody-positive cases. Almost all MOG antibody-positive cases with periplaque white matter (PPWM) present in the tissue specimen (5/6) showed ADEM-like histological characteristics (perivascular demyelination) in the PPWM, which was completely absent in MS pattern II cases.
Conclusions: This study provides evidence that the MOG antibody-associated demyelination differs from pattern II MS lesions through a different distribution of inflammatory infiltrates and an ADEM-like demyelination pattern in the PPWM suggesting that anti-MOG antibody-associated demyelination may represent a disease entity separate from classic MS.
Disclosure: Theoni Maragkou: nothing to disclose
Imke Metz: Dr. Metz reports personal fees from BiogenIdec, Bayer Heathcare, TEVA, Serono, Novartis, Genzyme, Roche, grants from BiogenIdec, grants from N-RENNT 2 (Niedersachsen Research Network on Neuroinfectiology), outside the submitted work.
Christine Stadelmann: CS received honoraria for speaking and travel reimbursement from Novartis Pharma GmbH, Merck, Teva Pharmaceutical Industries Ltd., Biogen, and Bayer Health Care. She served on scientific advisory boards of Novartis, Merck, Roche, and Teva. She received research support from Teva. She is a member of the editoral board of Neurology: Neuroimmunology & Neuroinflammation.
Wolfgang Brück: WB was supported from the German Ministry of Education and Research (BMBF “German Competence Network Multiple Sclerosis (KKNMS)”). WB has received, outside the submitted work, honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Novartis and Genzyme. WB received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. WB serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.