Design for the Next Trials of Neurodegeneration

  • P. Soelbergs Sørensen
Part of the Topics in Neuroscience book series (TOPNEURO)


During the past decade, several new medications have become available for the treatment of multiple sclerosis (MS). The main effect of these therapies, whether they are immunomodulatory or immunosuppressive types of treatment, has been their strong impact on the inflammatory component of the MS disease process. These anti-inflammatory therapies have, with various degrees of success, suppressed signs of inflammation as detected by magnetic resonance imaging (MRI) and have reduced the incidence of the clinical correlate to inflammation, i.e., the acute relapses [1, 2, 3, 4, 5, 6, 7], although they have had little effect on disease progression caused by permanent demyelination and axonal loss. Hence, it has been hypothesized that there are two different disease mechanisms at work in patients with MS: inflammation and neurodegeneration. The neurodegenerative disease process has been associated with the progressive phases of MS, either primary progressive (PP) MS or secondary progressive (SP) MS, during which the disease activity is thought to be driven by degenerative rather than inflammatory processes. However, recent studies have emphasized the presence of axonal damage early in the course of the disease [8], a fact that was already known by Charcot, as shown in his seminal studies of MS [9]. According to one theory, both inflammatory and degenerative disease processes are present from the onset of the disease and proceed independently; with inflammation being most prominent in the early phases of the disease, whereas neurodegeneration dominates during the later stages [10]. On the other hand, there are arguments for inflammation being the culprit for both acute relapses and disease progression [11, 12, 13]. Recent studies have indeed shown that inflammation is also prominent in patients with PPMS and SPMS, although this inflammation is thought to be compartmentalized within the CNS and is independent of the activation of T-cells in the peripheral bloodstream [14]. This low-burning, widespread inflammation is thought to be mediated by activated microglia that interact with T-and B-cells from infiltrates in the meninges and in the perivascular spaces, causing demyelination and axonal injury in plaques as well as diffusely in the white and gray matter of the brain [15, 16].


Multiple Sclerosis Expand Disability Status Scale Diffusion Tensor Magnetic Resonance Imaging Secondary Progressive Multiple Sclerosis Brain Parenchymal Fraction 
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Copyright information

© Springer-Verlag Italia 2007

Authors and Affiliations

  • P. Soelbergs Sørensen
    • 1
  1. 1.Danish Multiple Sclerosis Research Center Department of NeurologyCopenhaguen University HospitalCopenhaguenDenmark

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