Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance.
Multiple sclerosis (MS) is a disease of the central nervous system characterized by patchy areas of demyelination, inflammation, axonal loss and gliosis, and a diffuse axonal degeneration throughout the so-called normal-appearing white matter (NAWM). A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss. The reduced perfusion of the NAWM in MS might be caused by a widespread astrocyte dysfunction, possibly related to a deficiency in astrocytic beta(2)-adrenergic receptors and a reduced formation of cAMP, resulting in a reduced uptake of K(+) at the nodes of Ranvier and a reduced release of K(+) in the perivascular spaces. Pathologic and imaging studies suggest that ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions), and there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.
De Keyser
Jacques
J
Department of Neurology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium. jacquesdekeyser@gmail.com
Steen
Christel
C
Mostert
Jop P
JP
Koch
Marcus W
MW
D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002560:Cerebrovascular Circulation; D006801:Humans; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*