Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a very strong autoimmune component. Its name is a descriptive term and originates from the observation of multifocal lesions/plaques in the CNS. These lesions of variable size usually involve the white matter of the brain (myelinated axons) but can extend to gray matter too (where the neuronal cell bodies are found) According to WHO the global incidence and prevalence are estimated to be 2.5 per 100,000 person-‐years and 30 per 100,000 persons respectively. MS is a very complex disease with tremendous variability both in its presentation (as any brain areas can be affected potentially giving rise to any neurological symptom) and its clinical course. Its aetiology and pathogenesis is not well understood but, as twin studies have shown, genetic factors may account for 25 to 75% and this leads to the hypothesis that environmental triggers may be implicated in the pathogenesis of MS in susceptible individuals carrying certain genes.
This post is based on an essay I wrote for my course in 2012. It explores the differences between myelinated and non-myelinated axons, the consequences of demyelination and possible therapeutic strategies targeting certain potassium channels.
The integrity of multiple
sclerosis (MS) as a single nosological entity is threatened with strong evidence
highlighting its pathophysiological and clinical heterogeneity. The
pathogenesis of MS is not well understood and its classification as an
autoimmune disease has also been questioned (Kornek,
Lassmann 2003, Ludwin 2006, Ludwin, Raine 2008) The recognition of four immunohistologically
distinct patterns in addition to the recognized variable response to immunomodulatory
therapy, indicates the need for therapies directed to either the potentially
variable underlying pathophysiology or the ubiquitously detrimental effects of
demyelination. Despite the fact that many aspects of MS pathophysiology need to
be elucidated, MS can still be defined as “a
chronic inflammatory disease of the central nervous system (CNS)” characterized
by focal demyelination and partial axonal sparing (Kornek,
Lassmann 2003). The
role of ion and especially potassium channels in both axonal failure and T-cell
activation is pivotal and could provide a basis for the treatment of MS and
other neuroinflammatory or demyelinating diseases. Hence, this essay is going
to be focused on the neurophysiology of action potential (AP) conduction and
the potential of potassium channels as therapeutic targets.
