Contributions
Abstract: 109
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
Background: Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD with AQP4-IgG) is an autoimmune astrocytopathic disease pathologically characterized by massive destruction and regeneration of astrocytes. However, the temporal changes of NMOSD lesions have been defined by the activity of inflammatory demyelination due to lack of the staging of astrocytopathy.
Objective: To verify the usefulness of our astrocytopathy staging in NMOSD with AQP4-IgG.
Methods: Eight autopsied cases of NMOSD with AQP4-IgG, diagnosed by the 2015 international consensus criteria, were analyzed. Presence of AQP4-IgG was confirmed in life. We classified the astrocytopathy into the following four stages by means of the astrocytic morphology and immunostaining pattern of glial fibrillary acidic protein (GFAP), (a) Destruction; extensive loss of astrocytes with fragmented and/or dust-like particles. (b) Progenitor; loss of astrocytes except small nucleated cells with GFAP-positive fiber-forming foot processes. (c) Proto-Gliosis; insufficient density of star-shaped astrocytes. (d) Gliosis; lesions covered with mature astrocytes. These lesions were compared with clinical stage as well as demyelination, oligodendrocyte damage, cellular inflammation and complement deposition.
Result: Along with loss of AQP4 and myelin-associated glycoprotein, Destruction and Progenitor stages were the major findings in clinically acute cases (within 2 months after the last recurrence), but only Destruction was accompanied by depositions of activated complements and granulocyte infiltration, the hallmark of acute NMOSD lesions (Destruction vs Progenitor vs Proto-Gliosis vs Gliosis = 98.4% vs 1.6% vs 0% vs 0%). On the other hand, depositions of fragmented complement (C3d) were observed even in the Gliosis stage. Oligodendrocytes were severely decreased and axonal swellings were seen in Destruction, but the activity of inflammatory demyelination assessed by the number of myelin-laden macrophages was more evident in Progenitor than in Destruction. Activity of demyelination was mild in Proto-Gliosis and Gliosis stages.
Conclusion: Our staging of astrocytopathy is useful to understand the temporal changes of the unique pathology of NMOSD with AQP4-IgG.
Disclosure:
Dr. Takai Y has received research support from a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Dr. Misu T has received speaker honoraria from Bayer Schering Pharma, Biogen Idec Japan, Mitsubishi Tanabe Pharma Corporation, Asahi Kasei Medical Co., and Astellas Pharma Inc. and has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Kuraray Medical Co., The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Teijin Pharma, and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labor and Welfare of Japan.
Dr. Suzuki H reports no disclosures.
Dr. Ogawa K reports no disclosures.
Dr. Kaneko K reports no disclosures.
Dr. Shuhei Nishiyama has received research support from a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Dr. Kuroda H has received research support from a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Dr. Takahashi T reports no disclosures.
Dr. Nakashima I has received funding for travel and received speaker honoraria from Tanabe Mitsubishi Pharma Corporation and has received research funding from LSI Medience Corporation and the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Prof. Fujihara K serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Merck Serono, Alexion Pharmaceuticals, Medimmune and Medical Review; has received funding for travel and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co., Daiichi Sankyo, and Nihon Pharmaceutical; serve as an editorial board member of Clinical and Experimental Neuroimmunology (2009-present) and an advisory board member of Sri Lanka journal of Neurology; has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, and Genzyme Japan; is funded by the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Grants-in-Aid for Scientific Research from the Ministry of Health, Welfare and Labor of Japan.
Prof. Aoki M has received research support from Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labor and Welfare of Japan.
Abstract: 109
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 12 Pathology
Background: Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD with AQP4-IgG) is an autoimmune astrocytopathic disease pathologically characterized by massive destruction and regeneration of astrocytes. However, the temporal changes of NMOSD lesions have been defined by the activity of inflammatory demyelination due to lack of the staging of astrocytopathy.
Objective: To verify the usefulness of our astrocytopathy staging in NMOSD with AQP4-IgG.
Methods: Eight autopsied cases of NMOSD with AQP4-IgG, diagnosed by the 2015 international consensus criteria, were analyzed. Presence of AQP4-IgG was confirmed in life. We classified the astrocytopathy into the following four stages by means of the astrocytic morphology and immunostaining pattern of glial fibrillary acidic protein (GFAP), (a) Destruction; extensive loss of astrocytes with fragmented and/or dust-like particles. (b) Progenitor; loss of astrocytes except small nucleated cells with GFAP-positive fiber-forming foot processes. (c) Proto-Gliosis; insufficient density of star-shaped astrocytes. (d) Gliosis; lesions covered with mature astrocytes. These lesions were compared with clinical stage as well as demyelination, oligodendrocyte damage, cellular inflammation and complement deposition.
Result: Along with loss of AQP4 and myelin-associated glycoprotein, Destruction and Progenitor stages were the major findings in clinically acute cases (within 2 months after the last recurrence), but only Destruction was accompanied by depositions of activated complements and granulocyte infiltration, the hallmark of acute NMOSD lesions (Destruction vs Progenitor vs Proto-Gliosis vs Gliosis = 98.4% vs 1.6% vs 0% vs 0%). On the other hand, depositions of fragmented complement (C3d) were observed even in the Gliosis stage. Oligodendrocytes were severely decreased and axonal swellings were seen in Destruction, but the activity of inflammatory demyelination assessed by the number of myelin-laden macrophages was more evident in Progenitor than in Destruction. Activity of demyelination was mild in Proto-Gliosis and Gliosis stages.
Conclusion: Our staging of astrocytopathy is useful to understand the temporal changes of the unique pathology of NMOSD with AQP4-IgG.
Disclosure:
Dr. Takai Y has received research support from a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Dr. Misu T has received speaker honoraria from Bayer Schering Pharma, Biogen Idec Japan, Mitsubishi Tanabe Pharma Corporation, Asahi Kasei Medical Co., and Astellas Pharma Inc. and has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Kuraray Medical Co., The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Teijin Pharma, and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labor and Welfare of Japan.
Dr. Suzuki H reports no disclosures.
Dr. Ogawa K reports no disclosures.
Dr. Kaneko K reports no disclosures.
Dr. Shuhei Nishiyama has received research support from a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Dr. Kuroda H has received research support from a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Dr. Takahashi T reports no disclosures.
Dr. Nakashima I has received funding for travel and received speaker honoraria from Tanabe Mitsubishi Pharma Corporation and has received research funding from LSI Medience Corporation and the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Prof. Fujihara K serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Merck Serono, Alexion Pharmaceuticals, Medimmune and Medical Review; has received funding for travel and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co., Daiichi Sankyo, and Nihon Pharmaceutical; serve as an editorial board member of Clinical and Experimental Neuroimmunology (2009-present) and an advisory board member of Sri Lanka journal of Neurology; has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, and Genzyme Japan; is funded by the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Grants-in-Aid for Scientific Research from the Ministry of Health, Welfare and Labor of Japan.
Prof. Aoki M has received research support from Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labor and Welfare of Japan.