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Action for ME
InterActions Monthly Update
August 2000
From InterAction 34, August 2000 issue
To subscribe, contact Action for M.E. at info@afme.org.uk or call (0)1749 670799; website at www.afme.org.uk
Research Update
Brain MRI abnormalities exist in a subset of patients with CFS
Researchers from New Jersey studied the MRI scans of three groups: 21 patients with CFS (modified CDC criteria' 94) but no psychiatric disorder (CFS-No Psych); 18 people with CFS plus a psychiatric disorder (CFS-Psych), and 19 sedentary healthy controls (HC).
MRI scans show the structure of the brain, not how it functions.
The CFS-No Psych group had a significantly larger number of brain abnormalities than the CFS-Psych and HC groups, particularly in the white matter and more specifically, in the frontal lobes. These findings could explain the "more severe cognitive impairment previously reported in this subset of CFS patients". No differences were found when both the CFS groups were combined and compared to the controls.
The results are consistent with earlier reports of structural abnormalities in some patients with CFS (e.g. Buchwald et al). They also support the view that further studies should focus on subgroups, rather than mixed samples.
Lange G et al. Journal of the Neurological Sciences, 1999, 171, 1, 3-7.
Verbal memory problems in CFS
The same team reported the findings of a study involving 51 patients with CFS, of whom 22 had a psychiatric illness and 29 did not. They were compared with two control groups: 30 healthy persons and 19 people with rheumatoid arthritis. Verbal memory was assessed using a word list learning task.
The results indicate that the two CFS groups required more trials to learn the word list than the healthy controls. During recall, the CFS patients without psychiatric disorders performed more poorly than the healthy controls. There were no significant group differences for recognition.
The results imply that verbal memory impairment in CFS is caused by problems in acquisition. The patients without psychiatric disorders also exhibited deficient retrieval from long-term storage (memory). In other words, the problems with memory are specific, not global, and again, it's clearly worth studying subgroups.
Christodoulou, C et al. Archives of Clinical Neuropsychology, 1999, 14, 8, 652
Perfectionist myth put to rest
A recent study on 101 patients with CFS (Oxford and CDC criteria '94) and 45 people with rheumatoid arthritis (RA) has found no difference on measures such as perfectionism, attitudes to mental illness, 'harm avoidance' and depression..
According to the researchers, the findings fail to support ‘media and self-help stereotypes’ of the ‘high-achieving, over-dedicated sufferer with high personal standards’ and hostility towards all things psychiatric. They also note that depressive disorders in their CFS clinic ‘have been decreasing over time’, which they attribute to better recognition and treatment by GPs (rather than improved diagnosis of CFS by researchers.)
Wood, B and Wessely, S. Journal of Psychosomatic Research, 1999, 47, 4, 385-397
Searching for findings unique to CFS
Past studies on the blood of patients with CFS have revealed abnormalities in the antiviral, ribonuclease L pathway*. The most recent study has just been published by Prof. De Meirleir and his colleagues from Belgium. They tested 57 patients with acute or subacute post-viral onset CFS (CDC criteria '88 and '94) and 53 control subjects (28 healthy subjects and 25 patients with depression or fibromyalgia). A unique 37 kDa form of RNase L was found in 88% of the patients with CFS and 28% of the controls (p<0.01). When present, the amount of the 37 kDa form was very low in the control groups. The ratio of 37 kDa to the normal 80 kDa form of RNase L was high in 72% of CFS patients compared with 11% of the controls and none of the people with fibromyalgia or depression. In other words, by calculating the ratio of the low molecular weight RNase L to the normal 80 kDa RNase L, people with CFS can be distinguished from healthy controls and patients with depression or fibromyalgia with significant accuracy.
De Meirleir, K et al. American Journal of Medicine, 2000, 108, 2, 99-105
*See below for a beginners’ guide to the RNaseL pathway
Dr Ellen Goudsmit comments: These results are consistent with the theory that most patients with strictly-defined CFS are suffering from an ongoing chronic viral infection. (The abnormalities are not limited to recent onset cases; some of those tested had been ill for 19 years). In his editorial on this study, Prof Komaroff speculates about ‘a chronic low-level “war” with the immune system attempting in vain to rid the body of infection.’
…However, the study raises several questions. Firstly, not every patient tested had an upregulated RNase L pathway. Why not? Were they misdiagnosed? Were they recovering? Secondly, if the antiviral pathway is activated, why have so few studies identified viruses in patients with CFS? Is the pathway responding to the presence of an infectious agent or is there something wrong with the mechanism that's supposed to switch it off?
Psychiatrists will no doubt wonder whether the abnormalities are the result of chronic stress. If that were the case, one should have observed the same changes in the majority of patients with fibromyalgia which is also a major stressor, like CFS. Still, a study involving patients with 'burn-out' may be interesting.
Future research should also compare CFS patients with people suffering from diseases like hepatitis, to confirm that the abnormalities are related to an ongoing viral infection. Similarly, it might be worth replicating the study using people with broadly-defined CFS (selected using the Oxford criteria). If the definition matters, then fewer of these patients will have the 37 kDa form of RNase L.
To conclude, scientists have found a reproducible enzyme defect which is linked to the health status of patients. However, it's early days so the findings should be regarded as 'preliminary'.
Box:
A beginner's guide to the RNase L pathway
Viral infections stimulate the production of cytokines, including the interferons. Interferons control the way in which cells respond to a virus through their effect on a group of inter-related enzymes that make up an antiviral defense pathway. The status of the RNase L pathway, as I'll refer to it here, is measured in humans by taking a sample of blood and separating the lymphocytes (white blood cells). RNase L is the key enzyme. It's 'turned on' by a small molecule, 2-5A. This changes the enzyme from its inactive state to its active state. When active, RNase inhibits the synthesis of viral protein and thereby prevents the virus from replicating.
Research in the States has found that several parts of the pathway are clearly not functioning properly in many patients with CFS. For instance, people who became ill during the epidemic at Lake Tahoe (and developed ME) had a dramatically increased level of RNase L activity (as much as 1500 times above normal). Conversely, as their symptoms improved, their RNase L activity decreased.
Blood samples from patients with CFS have also revealed other abnormalities, for instance, a significant increase in 2-5A, (the molecule that 'turns on' RNase L), and a second enzyme involved in the pathway. However, the most striking finding has been the discovery of a unique form of RNase L.
The size of the normal form of RNase L is 80 kilodaltons (kDa). However, patients with CFS often have another form with a lower molecular weight: 37 kDa. Despite its smaller size, it's more potent than the 80 kDa form.
Finally, the research so far has shown that the three abnormalities in the antiviral pathway (RNase L, the levels of 2-5A, and the low molecular form of RNase L) are all linked to a lower state of general health. In other words, these findings are of clinical significance!
*While the antiviral pathway is active, it consumes adenosine triphosphate (ATP), the cells' energy source, which could lead to some of the symptoms of CFS.
With thanks to Nancy Reichenbach, CFS Research Review, 2000, 1, 1, 1-3.
Dr Goudsmit’s research extracts and comments are reproduced with kind permission from Axford’s Abode, a website containing articles and research updates on ME and CFS: http://freespace.virgin.net/david.axford/me/me.htm
Other useful sources of research information include:
The CFIDS Association, (producers of the excellent CFS Research Review). Check out their website at www.cfids.org or write to PO Box 220398, Charlotte NC, 28222-3437 USA (tel. 001 704 364 0016)
The CFIDS and FMS Health Resource, who provide regular free e-mail bulletins and a newsletter, ‘HEALTHwatch’ with the latest research on CFIDS and fibromyalgia. Go to www.immunesupport.com or write to PO Box 280, 1187 Coast Village Road, Santa Barbara, CA 93108, USA (tel. 001 805 564 3064)
Action for M.E., Po Box 1302, Wells, Somerset, BA5 1YE, UK
tel. (0)1749 670799
fax. (0)1749 672561
website: www.afme.org.uk
e-mail info@afme.org.uk
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