Contributions
Abstract: 92
Type: Oral
The basic pathology of multiple sclerosis has already been defined more than 100 years ago. However, a systematic account of the pathology of the disease in relation to recent progress in the understanding of basic mechanism of inflammation and tissue injury in the central nervous system has provided important new insights into the pathophysiology of the disease. On a structural basis these studies show that in addition to the well-defined focal inflammatory demyelinating lesions additional brain changes are of key importance in particular in the progressive stage of the disease. They include grey matter demyelination, expansion of pre-existing white and grey matter lesions and global neurodegeneration in the entire brain and spinal cord. Pathological studies further confirm the inflammatory nature of the disease and provide new insights on the functional phenotypic of brain infiltrating T- and B-lymphocytes or plasma cells. They further show that the formation of large confluent lesions of primary demyelination is specific for multiple sclerosis and is not a mere consequence of the inflammatory reaction in the CNS. Such demyelination lesions appear to be a driven by soluble factors, produced by inflammatory cells, which initiate demyelination either directly or indirectly through microglia activation. Oxidative injury with subsequent mitochondrial damage are central mediators of tissue injury, resulting in a state of energy deficiency (“virtual hypoxia”), which in patients with progressive disease is amplified by age related mechanisms of neurodegeneration and vascular comorbidities. The new account of MS pathology is consistent with the results of recent therapeutic trials in patients with relapsing and progressive disease. Experimental models are essential to define new potentially relevant pathophysiological mechanisms of inflammation, demyelination and neurodegeneration in MS, but their relevance for the human disease process has to be validated in depth by molecular pathology and immunopathology.
Disclosure: Hans Lassmann received honoraria from Novartis, Biogen, Roch and Sanofi Aventis
Abstract: 92
Type: Oral
The basic pathology of multiple sclerosis has already been defined more than 100 years ago. However, a systematic account of the pathology of the disease in relation to recent progress in the understanding of basic mechanism of inflammation and tissue injury in the central nervous system has provided important new insights into the pathophysiology of the disease. On a structural basis these studies show that in addition to the well-defined focal inflammatory demyelinating lesions additional brain changes are of key importance in particular in the progressive stage of the disease. They include grey matter demyelination, expansion of pre-existing white and grey matter lesions and global neurodegeneration in the entire brain and spinal cord. Pathological studies further confirm the inflammatory nature of the disease and provide new insights on the functional phenotypic of brain infiltrating T- and B-lymphocytes or plasma cells. They further show that the formation of large confluent lesions of primary demyelination is specific for multiple sclerosis and is not a mere consequence of the inflammatory reaction in the CNS. Such demyelination lesions appear to be a driven by soluble factors, produced by inflammatory cells, which initiate demyelination either directly or indirectly through microglia activation. Oxidative injury with subsequent mitochondrial damage are central mediators of tissue injury, resulting in a state of energy deficiency (“virtual hypoxia”), which in patients with progressive disease is amplified by age related mechanisms of neurodegeneration and vascular comorbidities. The new account of MS pathology is consistent with the results of recent therapeutic trials in patients with relapsing and progressive disease. Experimental models are essential to define new potentially relevant pathophysiological mechanisms of inflammation, demyelination and neurodegeneration in MS, but their relevance for the human disease process has to be validated in depth by molecular pathology and immunopathology.
Disclosure: Hans Lassmann received honoraria from Novartis, Biogen, Roch and Sanofi Aventis