Research Update

 

Blood vessel abnormalities in CFS

 Introduction

In my last research update (Winter 2002), I described how neuroimaging studies have demonstrated reduced cerebral blood flow and increased choline levels in parts of the brain in CFS patients. Recent work from Scotland has also raised intriguing questions about blood flow and abnormal choline metabolism in the blood vessels of the skin. The Vascular Research Group at Dundee Medical School have approached this problem by studying the vascular endothelium.

The Vascular Endothelium

The vascular endothelium is a layer of cells forming the inner surface of the blood vessels. It is involved in local control of blood flow, by constriction and dilation of the small vessels in the periphery. One of the mediators of vasodilatation is Acetylcholine (ACh - a chemical that also has a well-known function as a neurotransmitter in the central and peripheral nervous system).

The first Dundee study (Spence at al, 2000) showed enhanced blood flow in response to ACh applied to the peripheral vascular endothelium of the skin vessels of CFS patients compared to normal controls. They recently (Khan et al, 2003a) replicated this result in a second group of patients, and further demonstrated that this response is prolonged and may be due to abnormally slow clearance of Ach, perhaps mediated by reduced levels of the naturally occurring enzyme Acetylcholinesterase.

What is the significance of these finding? They may be related to systemic blood flow defects that contribute to one of the aspects of CFS – the development of symptoms when upright, e.g. orthostatic intolerance.

Gulf War Syndrome & OP induced illness

There are many clinical similarities between CFS and Gulf War Syndrome (GWS), and both resemble conditions associated with impaired cholinergic mechanisms. GWS has been linked to exposure to cholinesterase inhibitors and insecticides, and a similar illness has recently been described in people exposed to cholinesterase inhibitors contained in organophosphate (OP) insecticides.

So the question arises, is the abnormal vascular response in CFS also present in GWS and OP? A third Dundee study (Khan et al, 2003b) set out to test this idea. Comparing a group of CFS patients to those with GWS and OP illness, they found that latter two groups have a normal response to ACh. It therefore seems that the endothelial cholinergic abnormalities are unique to CFS, which suggests that these illnesses have different aetiologies (causes). This is reinforced by evidence obtained previously by other researchers using brain scanning techniques, which demonstrates increased levels of choline in some brain areas in CFS, whereas they are normal or decreased in GWS.

The future

Work on vascular and other aspects of CFS continues apace in Dundee, and hopes are high that they will shed more light on the biology of this illness. It is worth pointing out that their work has been entirely supported by charity, mainly from MERGE, with no financial aid from government bodies.

Dr John Breward

October 2003

References

Spence, V. A., Khan, K. and Belch, J. J. F. (2000) Enhanced sensitivity of the peripheral cholinergic vascular response in patients with chronic fatigue syndrome. Am. J. Med. 108, 736–739

Khan, F., Spence, V., Kennedy, G. and Belch, J. J. F. (2003a) Prolonged acetylcholine induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome. Clin. Physiol. Funct. Imaging 23, 282–285

Khan F, Kennedy G, Spence VA, Newton DJ, Belch JJ. (2003b) Peripheral cholinergic function in humans with chronic fatigue syndrome, gulf war syndrome, and with illness following organophosphate exposure. Clin Sci (Lond). Sep 23