Contributions
Abstract: EP1768
Type: ePoster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: In multiple sclerosis (MS) treatment, a personalized approach is pursued to account for the clinical and histopathological heterogeneity. Four different histological patterns of brain lesions were identified: subtypes I and II are characterized by T-cell infiltration without and with antibody involvement, respectively, whereas subtype III and IV reveal a distal or general oligodendrocytopathy, respectively. Apart from pattern II lesions, which have been identified to be predictive for a therapeutic response to apheresis therapies, knowledge about the correlation of histological subtypes and efficacy of treatment regimens is sparse.
Objectives: Description of the successful treatment of a MS patient with pattern III lesions.
Methods: Case report. Histological and immunocytochemical analysis.
Results: A 53-years old male developed atactic gait disorder, dysarthria, and sensory disturbance. Moreover, saccadic pursuits, pallhypaesthesia, and pyramidal tract signs were evident. His first MRI exposed a large, contrast enhancing lesion in the left middle cerebellar peduncle, disseminated supratentorial T2 lesions and a thoracic spinal lesion. Cerebrospinal fluid oligoclonal bands were present. Stereotactic cerebellar biopsy revealed perivascular T cell, macrophage, and plasma cell infiltration, along with demyelination, all compatible with MS. By evidence of oligodendrocyte apoptosis and a significant reduction of myelin-associated glycoprotein (MAG) expression, the lesion was classified as pattern III according to Lucchinetti, Brück, and Lassmann 2000. Treatment with high dose intravenous steroids and 180 mg triamcinolone intrathecally led to recovery of the atactic gait. After immunosuppressive therapy with four cycles of mitoxantrone (12 mg/m² body surface) every 2-3 months, his clinical condition and MRI findings further improved.
Conclusions: Distal oligodendrocytopathy, MAG loss, and increased hypoxia inducible factor-1α are common findings in MS with pattern III lesions, but also in virus-induced demyelination and acute white matter stroke lesions. This might indicate a common mechanism based on hypoxia-induced metabolic injury. The treatment response of pattern III lesions to classical immunomodulatory MS therapy is unknown. Since in pattern III lesions a small vessel vasculitis is suspected, immunosuppressive therapies such as mitoxantrone might be more effective and should be considered as therapeutic option.
Disclosure:
Thomas Grüter received a travel reimbursement from Sanofi Genzyme.
Wolfgang Brück serves on the editorial boards of Neuropathology and Applied Neurobiology ans, Multiple Sclerosis International. Dr. Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva, Genzyme, Roche and Novartis and is a member of scientific advisory boards for Teva, Biogen, Novartis, MedDay and Genzyme. He received funding for research projects by Teva, Biogen, Novartis, MedDay and Genzyme.
Anna Gahlen received a travel reimbursement from Sanofi Genzyme.
Janine Kneiphof: nothing to disclose.
Ralf Gold serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis, none related to this manuscript.
Ingo Kleiter received honoraria for consultancy or speaking and travel reimbursement from Bayer Healthcare, Chugai, Merck, Roche, and Shire, and grant support from Affectis, Biogen, Chugai and Diamed, all not related to the presented work.
Abstract: EP1768
Type: ePoster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: In multiple sclerosis (MS) treatment, a personalized approach is pursued to account for the clinical and histopathological heterogeneity. Four different histological patterns of brain lesions were identified: subtypes I and II are characterized by T-cell infiltration without and with antibody involvement, respectively, whereas subtype III and IV reveal a distal or general oligodendrocytopathy, respectively. Apart from pattern II lesions, which have been identified to be predictive for a therapeutic response to apheresis therapies, knowledge about the correlation of histological subtypes and efficacy of treatment regimens is sparse.
Objectives: Description of the successful treatment of a MS patient with pattern III lesions.
Methods: Case report. Histological and immunocytochemical analysis.
Results: A 53-years old male developed atactic gait disorder, dysarthria, and sensory disturbance. Moreover, saccadic pursuits, pallhypaesthesia, and pyramidal tract signs were evident. His first MRI exposed a large, contrast enhancing lesion in the left middle cerebellar peduncle, disseminated supratentorial T2 lesions and a thoracic spinal lesion. Cerebrospinal fluid oligoclonal bands were present. Stereotactic cerebellar biopsy revealed perivascular T cell, macrophage, and plasma cell infiltration, along with demyelination, all compatible with MS. By evidence of oligodendrocyte apoptosis and a significant reduction of myelin-associated glycoprotein (MAG) expression, the lesion was classified as pattern III according to Lucchinetti, Brück, and Lassmann 2000. Treatment with high dose intravenous steroids and 180 mg triamcinolone intrathecally led to recovery of the atactic gait. After immunosuppressive therapy with four cycles of mitoxantrone (12 mg/m² body surface) every 2-3 months, his clinical condition and MRI findings further improved.
Conclusions: Distal oligodendrocytopathy, MAG loss, and increased hypoxia inducible factor-1α are common findings in MS with pattern III lesions, but also in virus-induced demyelination and acute white matter stroke lesions. This might indicate a common mechanism based on hypoxia-induced metabolic injury. The treatment response of pattern III lesions to classical immunomodulatory MS therapy is unknown. Since in pattern III lesions a small vessel vasculitis is suspected, immunosuppressive therapies such as mitoxantrone might be more effective and should be considered as therapeutic option.
Disclosure:
Thomas Grüter received a travel reimbursement from Sanofi Genzyme.
Wolfgang Brück serves on the editorial boards of Neuropathology and Applied Neurobiology ans, Multiple Sclerosis International. Dr. Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva, Genzyme, Roche and Novartis and is a member of scientific advisory boards for Teva, Biogen, Novartis, MedDay and Genzyme. He received funding for research projects by Teva, Biogen, Novartis, MedDay and Genzyme.
Anna Gahlen received a travel reimbursement from Sanofi Genzyme.
Janine Kneiphof: nothing to disclose.
Ralf Gold serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis, none related to this manuscript.
Ingo Kleiter received honoraria for consultancy or speaking and travel reimbursement from Bayer Healthcare, Chugai, Merck, Roche, and Shire, and grant support from Affectis, Biogen, Chugai and Diamed, all not related to the presented work.