Innovations In Clinical Neuroscience

HOTTOP Multiple Sclerosis DEC 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

Issue link:

Contents of this Issue


Page 18 of 27

R E V I E W 19 Hot Topics in Multiple Sclerosis [December 2017] prophylaxis" to reduce the incidence of MS. 23 BET TER UNDERSTANDING, BET TER TREATMENT Despite our increasing knowledge and better understanding of the underlying mechanisms, many questions remain open. Accumulating evidences support considering PPMS as a part of the MS spectrum. However, there is no solid explanation of what exactly drives the development of the clinical phenotypes. In our opinion, the core of MS might be a slowly progressive low-degree inflammatory process driven by autoreactive apoptosis- resistant EBV-infected B cells that manifests itself clinically in genetically predisposed individuals only after a specific age threshold is exceeded. In the presence of other factors (like vitamin D deficiency), a superimposed fluctuating high-grade inflammatory process appears in younger age and manifests itself in the form of recurrent exacerbations. Evidences supporting this hypothesis are 1 more than half of MS patients suffer from PMS (either as PPMS from the beginning or SPMS), 2 the striking clinical and pathological similarities between PP and SPMS, 3 the almost universal positive EBV status in MS patients, 4 the presence of EBV- infected B cells in brain and meninges of MS patients, perivascular spaces, and parenchyma, 5 the well-known change in age-dependent host response to latent EBV infection, 6 the success of B cell- depleting agents in RRMS and PPMS, 7 the "preliminary" success of T-cell-based therapy against EBV-infected B cells in SPMS, 8 the presence of vitamin D deficiency in RRMS but not patients with PPMS and its well-described effect on the relapse rate but not disease progression, and finally, 9 almost all pathological aspects of the progressive phase like MiA, iron accumulation, mitochondrial dysfunction, involvement of the NAWM and NAGM, cortical and cerebral atrophy, as well as meningeal infiltration can be detected very early in the disease course even in CIS patients. 55,90–93 Further work is needed to prove the exact role of EBV in PMS forms, to characterize the BAuto population, and how do they differentiate, and at last to explain the role of different risk factors in PMS and their interactions in different populations. The current therapy options for PPMS are promisingly increasing with upcoming possibilities of targeting different aspects of the disease (Figure 3). A combination of different treatments might be a viable approach in the future, considering the suboptimal effect of every single treatment alone so far. SUMMARY PPMS is considered a relatively rare but very challenging phenotype in the care of patients with MS. Our current knowledge supports an underlying inflammatory-driven neurodegenerative process. Autoreactive EBV-infected B cells are essential to drive the progressive TABLE 1. Overview of the major clinical trials in primary progressive multiple sclerosis.

Articles in this issue

Archives of this issue

view archives of Innovations In Clinical Neuroscience - HOTTOP Multiple Sclerosis DEC 2017