Martina Absinta1, Hans Lassmann2, Bruce D Trapp3. 1. Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA. 2. Center for Brain Research, Medical University of Vienna, Wien, Austria. 3. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Abstract
PURPOSE OF REVIEW: In multiple sclerosis, currently approved disease-modifying treatments are effective in modulating peripheral immunity, and coherently, in reducing clinical/radiological relapses, but still, they perform poorly in preventing disease progression and overall disability accrual. This review provides an up-to-date overview of the neuropathology of progressive multiple sclerosis, including a summary of the main mechanisms of disease progression. RECENT FINDINGS: Clinical progression in multiple sclerosis is likely related to the accumulation of neuro-axonal loss in a lifelong inflammatory CNS environment (both adaptive and innate) and relative un-balance between damage, repair and brain functional reserve. A critical driver appears to be the T-cell and B-cell-mediated compartmentalized inflammation within the leptomeninges and within the parenchyma. Recent perspective highlighted also the role of the glial response to such lifelong inflammatory injury as the critical player for both pathological and clinical outcomes. SUMMARY: The neuropathological and biological understanding of disease progression in multiple sclerosis have progressed in the last few years. As a consequence, new therapeutic approaches are emerging outside the modulation of T-cell activity and/or the depletion of B cells.
PURPOSE OF REVIEW: In multiple sclerosis, currently approved disease-modifying treatments are effective in modulating peripheral immunity, and coherently, in reducing clinical/radiological relapses, but still, they perform poorly in preventing disease progression and overall disability accrual. This review provides an up-to-date overview of the neuropathology of progressive multiple sclerosis, including a summary of the main mechanisms of disease progression. RECENT FINDINGS: Clinical progression in multiple sclerosis is likely related to the accumulation of neuro-axonal loss in a lifelong inflammatory CNS environment (both adaptive and innate) and relative un-balance between damage, repair and brain functional reserve. A critical driver appears to be the T-cell and B-cell-mediated compartmentalized inflammation within the leptomeninges and within the parenchyma. Recent perspective highlighted also the role of the glial response to such lifelong inflammatory injury as the critical player for both pathological and clinical outcomes. SUMMARY: The neuropathological and biological understanding of disease progression in multiple sclerosis have progressed in the last few years. As a consequence, new therapeutic approaches are emerging outside the modulation of T-cell activity and/or the depletion of B cells.
Authors: Andrew S Mendiola; Kaira A Church; Sandra M Cardona; Difernando Vanegas; Shannon A Garcia; Wendy Macklin; Sergio A Lira; Richard M Ransohoff; Erzsebet Kokovay; Chin-Hsing Annie Lin; Astrid E Cardona Journal: J Neurochem Date: 2022-05-12 Impact factor: 5.546
Authors: Haritha L Desu; Placido Illiano; James S Choi; Maureen C Ascona; Han Gao; Jae K Lee; Roberta Brambilla Journal: Cells Date: 2021-07-15 Impact factor: 6.600