**2. Fundamental pathogenesis factors change during the progression of the demyelinating disorders**

As MS disease progressed, two fundamental changes occurred [29]. First, the activity of the adaptive immune system decreases leading clinically to a decrease in the incidence of clinically detectable relapses. It is currently unclear why the adaptive (and perhaps also innate) immune system becomes less active as the disease progresses, but immunosenescence likely plays an important role [30].

### *Experimental* in Vitro *and* in Vivo *Models of Demyelinating Disorders DOI: http://dx.doi.org/10.5772/intechopen.100163*

Second, the slow-burning degenerative process reaches a certain threshold and becomes clinically apparent.

Two possible mechanisms play a role in the retarding clinical performance [31]. One of them is a compensation of damaged or degenerated neurons by nearby neurons known as neural plasticity. Another one is the destruction of neurons without obvious clinical signs and symptoms [32]. Likely, this condition can be seen in 80% of Parkinson's patients. Many dopaminergic neurons in their brain may be lost before any clinical deficits [33]. For example, imagine that across from you is a container with 1,000 bullets. If someone removes a single bullet, it is not likely that it will be recognized. However, if only two bullets remain, most people will certainly recognize if another bullet has left the container. At the RRMS disease stage, the initial loss of neuronal structures is neither recognized by the patient nor, in the other words, does not lead to obvious clinical deficits [34]. Subsequently, during the disease, when numerous neurons are already dying at the transition phase from RRMS to SPMS, evident clinical deficits can be seen obviously [35].
