Cerebral white matter blood flow and energy metabolism in multiple sclerosis.

Background: Cerebral blood flow (CBF) is reduced in normal-appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but the underlying mechanism is unknown.

Objective: The objective of this article is to assess the relationship between reduced NAWM CBF and both axonal mitochondrial metabolism and astrocytic phosphocreatine (PCr) metabolism.

Methods: Ten healthy controls and 25 MS subjects were studied with 3 Tesla magnetic resonance imaging.

Reduced creatine kinase B activity in multiple sclerosis normal appearing white matter.

Background: Two studies using (31)P-magnetic resonance spectroscopy (MRS) reported enhanced phosphocreatine (PCr) levels in normal appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but this finding could not be properly explained.

Methodology/principal Findings: We performed (31)P-MRS and (1)H-MRS in the NAWM in 36 subjects, including 17 with progressive MS, 9 with benign MS, and 10 healthy controls. Compared to controls, PCr/beta-ATP and PCr/total (31)P ratios were significantly increased in subjects with progressive MS, but not with benign MS.

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.