Primary Progressive Multiple Sclerosis: Putting Together the Puzzle
The focus of multiple sclerosis research has recently turned to the relatively rare and clearly more challenging condition of primary progressive multiple sclerosis (PPMS). Many risk factors such as genetic susceptibility, age, and Epstein–Barr virus (EBV) infection may interdepend on various levels...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2017.00234/full |
| _version_ | 1818285568062128128 |
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| author | Ahmed Abdelhak Martin S. Weber Martin S. Weber Hayrettin Tumani Hayrettin Tumani |
| author_facet | Ahmed Abdelhak Martin S. Weber Martin S. Weber Hayrettin Tumani Hayrettin Tumani |
| author_sort | Ahmed Abdelhak |
| collection | DOAJ |
| description | The focus of multiple sclerosis research has recently turned to the relatively rare and clearly more challenging condition of primary progressive multiple sclerosis (PPMS). Many risk factors such as genetic susceptibility, age, and Epstein–Barr virus (EBV) infection may interdepend on various levels, causing a complex pathophysiological cascade. Variable pathological mechanisms drive disease progression, including inflammation-associated axonal loss, continuous activation of central nervous system resident cells, such as astrocytes and microglia as well as mitochondrial dysfunction and iron accumulation. Histological studies revealed diffuse infiltration of the gray and white matter as well as of the meninges with inflammatory cells such as B-, T-, natural killer, and plasma cells. While numerous anti-inflammatory agents effective in relapsing remitting multiple sclerosis basically failed in treatment of PPMS, the B-cell-depleting monoclonal antibody ocrelizumab recently broke the dogma that PPMS cannot be treated by an anti-inflammatory approach by demonstrating efficacy in a phase 3 PPMS trial. Other treatments aiming at enhancing remyelination (MD1003) as well as EBV-directed treatment strategies may be promising agents on the horizon. In this article, we aim to summarize new advances in the understanding of risk factors, pathophysiology, and treatment of PPMS. Moreover, we introduce a novel concept to understand the nature of the disease and possible treatment strategies in the near future. |
| first_indexed | 2024-12-13T01:10:46Z |
| format | Article |
| id | doaj.art-ca42ddcc4f9b4d689b8a41f5f5bbcd6d |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-13T01:10:46Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-ca42ddcc4f9b4d689b8a41f5f5bbcd6d2022-12-22T00:04:28ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-05-01810.3389/fneur.2017.00234242738Primary Progressive Multiple Sclerosis: Putting Together the PuzzleAhmed Abdelhak0Martin S. Weber1Martin S. Weber2Hayrettin Tumani3Hayrettin Tumani4Department of Neurology, Ulm University, Ulm, GermanyDepartment of Neuropathology, University Medical Center, Georg August University, Göttingen, GermanyDepartment of Neurology, University Medical Center, Georg August University, Göttingen, GermanyDepartment of Neurology, Ulm University, Ulm, GermanySpecialty Clinic of Neurology Dietenbronn, Schwendi, GermanyThe focus of multiple sclerosis research has recently turned to the relatively rare and clearly more challenging condition of primary progressive multiple sclerosis (PPMS). Many risk factors such as genetic susceptibility, age, and Epstein–Barr virus (EBV) infection may interdepend on various levels, causing a complex pathophysiological cascade. Variable pathological mechanisms drive disease progression, including inflammation-associated axonal loss, continuous activation of central nervous system resident cells, such as astrocytes and microglia as well as mitochondrial dysfunction and iron accumulation. Histological studies revealed diffuse infiltration of the gray and white matter as well as of the meninges with inflammatory cells such as B-, T-, natural killer, and plasma cells. While numerous anti-inflammatory agents effective in relapsing remitting multiple sclerosis basically failed in treatment of PPMS, the B-cell-depleting monoclonal antibody ocrelizumab recently broke the dogma that PPMS cannot be treated by an anti-inflammatory approach by demonstrating efficacy in a phase 3 PPMS trial. Other treatments aiming at enhancing remyelination (MD1003) as well as EBV-directed treatment strategies may be promising agents on the horizon. In this article, we aim to summarize new advances in the understanding of risk factors, pathophysiology, and treatment of PPMS. Moreover, we introduce a novel concept to understand the nature of the disease and possible treatment strategies in the near future.http://journal.frontiersin.org/article/10.3389/fneur.2017.00234/fullprimary progressive multiple sclerosispathophysiologytreatmentEpstein–Barr virusrisk factors |
| spellingShingle | Ahmed Abdelhak Martin S. Weber Martin S. Weber Hayrettin Tumani Hayrettin Tumani Primary Progressive Multiple Sclerosis: Putting Together the Puzzle Frontiers in Neurology primary progressive multiple sclerosis pathophysiology treatment Epstein–Barr virus risk factors |
| title | Primary Progressive Multiple Sclerosis: Putting Together the Puzzle |
| title_full | Primary Progressive Multiple Sclerosis: Putting Together the Puzzle |
| title_fullStr | Primary Progressive Multiple Sclerosis: Putting Together the Puzzle |
| title_full_unstemmed | Primary Progressive Multiple Sclerosis: Putting Together the Puzzle |
| title_short | Primary Progressive Multiple Sclerosis: Putting Together the Puzzle |
| title_sort | primary progressive multiple sclerosis putting together the puzzle |
| topic | primary progressive multiple sclerosis pathophysiology treatment Epstein–Barr virus risk factors |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2017.00234/full |
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