Difference between revisions of "Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling"

== Demyelinating Diseases ==

There are a large number of demyelinating diseases affecting both the PNS (Figure 1) and CNS (Figure 2). The etiologies are heterogeneous, ranging from genetic disorders to metabolic, infectious or autoimmune mechanisms. Multiple sclerosis (MS) is the most prevalent of these disorders, with an estimated 3 million patients worldwide. Its underlying cause is uncertain but is thought to involve genetic predisposition to environmental agents<ref name=":0">Trapp B.D., Nave K.A. Multiple sclerosis: An immune or neurodegenerative disorder? Annu. Rev. Neurosci. 2008;31:247–69. doi: 10.1146/annurev.neuro.30.051606.094313. [PubMed] [CrossRef] [Google Scholar]</ref><ref name=":1">Compston A., Coles A. Multiple sclerosis. Lancet. 2008;372:1502–1517. doi: 10.1016/S0140-6736(08)61620-7. [PubMed] [CrossRef] [Google Scholar]</ref> and can involve immunological, responsiveness to trauma, biophysical, genetic and/or metabolic components.<ref name=":1" /> The symptoms and lesions must be multiple in both time and space. That is, there must be multiple episodes in time, involving disconnected parts of the central nervous system. It is not clear whether inflammatory demyelination is a primary or secondary event within the disease process.<ref name=":0" /><ref>Ostermann P.O., Westerberg C.E. Paroxysmal attacks in multiple sclerosis. Brain. 1975;98:189–202. doi: 10.1093/brain/98.2.189. [PubMed] [CrossRef] [Google Scholar]</ref><ref>Twomey J.A., Espir M.L. Paroxysmal symptoms as the first manifestations of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 1980;43:296–304. doi: 10.1136/jnnp.43.4.296. [PMC free article] [PubMed] [CrossRef] [Google Scholar]</ref> Most treatments target the immune system or the blood-brain barrier, but managing neurological symptoms through modulation of axonal excitability also plays an important role (see below).

Figure 1