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SOME FACTS ABOUT ME/PVFS/CFS

In the United Kingdom, CFS covers a number of conditions, including myalgic encephalopathy (ME) also known as post viral fatigue syndrome (PVFS). The latter is characterised by
fatiguability and slow recovery following minimal exertion, marked fluctuations in the severity of symptoms throughout the day, impaired circulation and the involvement of the CNS. Most patients who fulfil the British criteria for CFS appear to have disorders other than ME including undiagnosed hypothyroidism, masked depression, and problems related to lifestyle and
nutrition (e.g. deficiencies of vitamins D and B12). In America, the stricter criteria devised by the CDC (1988, 1992) select a more homogeneous population, so many cases of CFS so defined are probably the equivalent of ME/PVFS.

The prevalence of ME and strictly-defined CFS is about 1 per 1000; the prevalence of CFS selected using the British criteria may be as high as 2%.


Current Research Articles:
1. Researchers Identify A Key "Brake" Of The Immune Response
2. Challenges of the Chronic Fatigue Syndrome
3. Prescribed Medications for Fibromyalgia
4. SOME FACTS ABOUT ME/PVFS/CFS

The following papers generally refer to studies on ME/PVFS and strictly-defined CFS.

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Research into ME/PVFS/CFS has shown:

1. The presence of enteroviral particles in a significant number of muscle biopsies taken from ME/PVFS patients (e.g. Bowles et al, Gow et al). This was rare in healthy controls. Enteroviral specific sequences have also been detected in the serum of 41% of patients with post-infectious chronic fatigue (Clements et al). The proportion of positive results was significantly higher than that found in acutely ill patients with possible enteroviral
disease (27%) and in healthy controls (2%).

Bowles, NE., Bayston, TA., Zhang, H-Y., Doyle, D., Lane, RJM., Cunningham, L and Archard, LC. Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy. Journal of Medicine, 1993, 24, 145-160.


Clements, GB., McGarry, F., Nairn, C and Galbraith, DN. Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue. Journal of Medical Virology, 1995, 45, 156-161.

Gow, JW., Behan, WMH., Clements, GB., Woodall, C., Riding, M and Behan, PO. Enteroviral sequences detected by polymerase chain reaction in muscle biopsies of patients with postviral fatigue syndrome. British Medical Journal, 1991, 302, 692-6.


2. Abnormalities in muscle tissue. In a study on a fairly homogeneous population, 80% of the biopsies showed evidence of structural damage to the mitochondria.


Behan, WMH, More, IAR and Behan, PO.
Mitochondrial abnormalities in the postviral fatigue
syndrome. Acta Neuropathologica, 1991, 83, 61-65.


3. A deficiency in the levels of carnitine and serum acylcarnitine. Researchers believe that this may be involved in the muscular symptoms of ME and CFS.


Kuratsune, H., Yamaguti, K., Lindh, G., Evengard, B.,
Takahashi, M., Machii, T., Matsumura, K., Takaishi,
J., Kawata, S., Langstrom, B., Kanakura, Y., Kitani,
T., Watanabe, Y. Low levels of serum acylcarnitine in
chronic fatigue syndrome and chronic hepatitis type
C, but not seen in other diseases. International
Journal of Molecular Medicine, 1998, 2, 1, 51-56.

Majeed, T., De Simone, C., Famularo, G., Marcellini,
S and Behan, PO. Abnormalities of carnitine
metabolism in chronic fatigue syndrome. European
Journal of Neurology, 1995, 2, 425-428.


4. Abnormalities in muscle function have been found in a subgroup and do not seem to be related to inactivity (Lane et al). In people with ME, objective tests have found prolonged
recovery rates following exercise (Paul et al).


Lane, RJM., Barrett, MC., Woodrow, D., Moss, J.,
Fletcher, R and Archard, LC. Muscle fibre
characteristics and lactate responses to exercise in
chronic fatigue syndrome. Journal of Neurology,
Neurosurgery and Psychiatry, 1998, 64, 3, 362-367.

Paul, L., Wood, L., Behan, WMH and Maclaren,
WM. Demonstration of delayed recovery from
fatiguing exercise in chronic fatigue syndrome.
European Journal of Neurology, 1999, 6, 63-69.


5. MRI scans have revealed abnormalities in up to 80% of the patients in one study (Daugherty et al). According to researchers, these defects are probably caused by chronic viral encephalitis. There was a correlation between the areas involved and the symptoms experienced. Abnormalities on SPECT scans provide further objective evidence of CNS dysfunction. Studies published to date show patterns of reduced blood flow which are markedly different from those documented in major depression (Costa et al). Moreover, the number of defects are correlated with clinical status (e.g. Schwartz et al).


Buchwald, D., Cheyne, PR., Peterson, DL., Henry,
B., Wormsley, SB., Geiger, A., Ablashi, DV.,
Salahuddin, SZ., Saxinger, C., Biddle, R., Kikinis, R.,
Jolesz, FA., Folks, T., Balachandran, N., Peter, JB.,
Gallo, RC and Komaroff, AL. A chronic illness
characterised by fatigue, neurologic and
immunologic disorders, and active Human Herpes
Type 6 infection. Annals of Internal Medicine, 1992,
116, 2, 103-113.

Cook, DB., Lange, G., DeLuca, J and Natelson BH.
Relationship of brain MRI abnormalities and physical
functional status in chronic fatigue syndrome.
International Journal of Neuroscience, 2001, 107,
1-2, 1-6.

Costa, DC., Tannock, C and Brostoff, J. Brainstem
perfusion is impaired in patients with chronic fatigue
syndrome. Quarterly Journal of Medicine, 1995, 88,
767-773.

Daugherty, SA., Henry, BE., Peterson, DL., Swarts,
RL., Bastein, S and Thomas, RS. Chronic fatigue
syndrome in Northern Nevada. Reviews of Infectious
Diseases, 1991, 13, Suppl. 1. S39-44.

Schwartz, RB., Garada, BM., Komaroff, AL., Tice,
HM., Gleit, M., Jolesz, FA., Holman, BL. Detection of
intracranial abnormalities in patients with chronic
fatigue syndrome: comparison of MR imaging and
SPECT. American Journal of Roentgenology, 1994,
162, 4, 935-41.

Schwartz, RB., Komaroff, AL., Garada, BM., Gleit,
M., Doolittle, TH., Bates, DW., Vasile, RG and
Holman, B. SPECT imaging of the brain:
comparison of findings in patients with chronic
fatigue syndromes, AIDS, dementia complex and
major unipolar depression. American Journal of
Roentgenology, 1994, 162, 4, 943-51.


5a. The results on SPECT have been replicated using PET.


Tirelli, U., Chierichetti, F., Tavio, M., Simonelli, C.,
Bianchin, G., Zanco, P and Ferlin, G. Brain positron
emission tomography (PET) in chronic fatigue
syndrome: preliminary data. American Journal of
Medicine, 1998, 105, 3A, 54s-58s.


6. Enteroviral sequences have been detected in tissue samples taken from the hypothalamus and brain stem of a patient with ME. Such sequences were not found in samples from depressed patients who had not suffered from ME.


McGarry, F., Gow, J and Behan, PO. Enterovirus in
the chronic fatigue syndrome. Annals of Internal
Medicine, 1994, 120, 11, 972-973.


7. Several studies have found evidence of an overactive immune system. The abnormalities are generally more common in the severely affected, and are consistent with a persisting viral
infection. The disturbances of cell-mediated immunity in patients with ME and CFS differ in prevalence and magnitude from those which have been observed in people suffering from major
depression (e.g. Lloyd et al). There is also growing evidence implicating HHV-6 (e.g. Ablashi et al).


Bennett, AL., Chao, CC., Hu, S., Buchwald, D.,
Fagioli, LR., Schur, PH., Peterson, PK and
Komaroff, AL. Elevation of bioactive transforming
growth factor- in serum from patients with chronic
fatigue syndrome. Journal of Clinical Immunology,
1997, 17, 2, 160-166.

Cannon, JG., Angel, JB., Abad, LW., Vannier, E.,
Mileno, MD., Fagioli, L., Wolff, SM and Komaroff,
AL. Interleukin-1, interleukin-1 receptor antagonist,
and soluble interleukin-1 receptor type II secretion in
chronic fatigue syndrome. Journal of Clinical
Immunology, 1997, 17, 3, 253-261.

De Meirleir, K., Bisbal, C., Campine, I., De Becker,
P., Salehzada, T., Demettre, E and Lebleu, BA. 37
kDa 2-5A binding protein as a potential biochemical
marker for chronic fatigue syndrome. American
Journal of Medicine, 2000, 108, 2, 99-105.

Hassan, IS., Bannister, BA., Akbar, A., Weir, W and
Bofill, M. A study of the immunology of the chronic
fatigue syndrome: correlation of immunologic
parameters to health dysfunction. Clinical
Immunology and Immunopathology, 1998, 87, 1,
60-67.

Ho-Yen, DO., Billington, RW and Urquhart, J. Natural
killer cells and the post viral fatigue syndrome.
Scandinavian Journal of Infectious Diseases, 1991,
23, 711-716.

Kavelaars, A., Kuis, W., Knook, L., Sinnema, G and
Heijnen, CJ. Disturbed neuroendocrine-immune
interactions in chronic fatigue syndrome. Journal of
Clinical Endocrinology and Metabolism, 2000, 85, 2,
692-696.

Klimas, N.G., Salvato, F.R., Morgan, R and Fletcher,
M.A. Immunologic abnormalities in chronic fatigue
syndrome. Journal of Clinical Microbiology, 1990,
28, 1403-1410.

Landay, AL., Jessop, C., Lennette, ET and Levy, JA.
Chronic fatigue syndrome: clinical condition
associated with immune activation. Lancet, 1991,
338, 707-712.

Lloyd, A., Hickie, I., Hickie, C., Dwyer, J and
Wakefield, D. Cell-mediated immunity in patients
with chronic fatigue syndrome, healthy control
subjects and patients with depression. Clinical and
Experimental Immunology, 1992, 87, 76-79.

Natelson, BH., Denny, T., Zhou, XD., LaManca, JJ.,
Ottenweller, JE., Tiersky, L., DeLuca, J and Gause,
WC. Is depression associated with immune
activation? Journal of Affective Disorders, 1999, 53,
2, 179-184.

Patarca, R., Klimas, NG., Garcia, MN., Walters, MJ.,
Dombroski, D., Pons, H and Fletcher, MA.
Dysregulated expression of soluble immune
mediator receptors in a subset of patients with
chronic fatigue syndrome: cross-sectional
categorization of patients by immune status. Journal
of Chronic Fatigue Syndrome, 1995, 1, 1, 81-96.

Ablashi, DV., Eastman, HB., Owen, CB., Roman,
MM., Friedman, J., Zabriskie, JB., Peterson, DL.,
Pearson, GR and Whitman, JE. Frequent HHV-6
reactivation in multiple sclerosis (MS) and chronic
fatigue syndrome (CFS) patients. Journal of Clinical
Virology, 2000, 16, 3, 179-191.


8. Some symptoms of CFS may be related to due to an inflammatory process. Findings from experiments in mice are consistent with the notion that fatigue could be due to "cytokine
production within the CNS".


Sheng, WS., Hu, SX., Lamkin, A., Peterson, PK and
Chao, CC. Susceptibility to immunologically
mediated fatigue in C57BL/6 versus Balb/c mice.
Clinical Immunology and Immunopathology, 1996,
81, 2, 161-167.


9. Research has revealed a number of disturbances in the function of the hypothalamic-pituitary-adrenal axis. Some of these are different from the abnormalities documented in patients suffering from depression (e.g. Demitrack et al, Scott et al).


Bakheit, AMO., Behan, PO., Dinan, TG., Gray, CE
and O'Keane, VO. Possible upregulation of
hypothalamic 5-hydroxytryptamine receptors in
patients with postviral fatigue syndrome. British
Medical Journal, 1992, 304, 1010-2.

Behan, PO and Bakheit, AMO. Clinical spectrum of
postviral fatigue syndrome. British Medical Bulletin,
1991, 47, 4, 793-808.

Cleare, AJ., Bearn, J., Allain, T., McGregor, A.,
Wessely, S., Murray, RM and O'Keane, V.
Contrasting neuroendocrine responses in
depression and chronic fatigue syndrome. Journal
of Affective Disorders, 1995, 35, 283-289.

Demitrack, MA, Dale, JK, Straus, SE., Laue, L.,
Listwalk, SJ., Kruesi, MJP., Chrousos, GP and Gold,
PW. Evidence for impaired activation of the
hypothalamic-pituitary-adrenal axis in patients with
chronic fatigue syndrome. Journal of Clinical
Endocrinology and Metabolism, 1991, 73,
1224-1234.
Himmel, PB and Seligman, TM. A pilot study
employing dehydroepiandrosterone (DHEA) in the
treatment of chronic fatigue syndrome. Journal of
Clinical Rheumatology, 1999, 5, 2, 56-59.

Majeed, T., Dinan, TG., Thakore, J., Gray, C and
Behan, PO. Defective dexamethasone induced
growth hormone release in chronic fatigue syndrome:
evidence for glucocorticoid receptor resistance and
lack of plasticity? Journal of the Irish Colleges of
Physicians and Surgeons, 1995, 24, 1, 20-24.

Richardson, J. Disturbance of hypothalamic function
and evidence for persistent enteroviral infection in
patients with chronic fatigue syndrome. Journal of
Chronic Fatigue Syndrome, 1995, 1, 2, 59-66.

Scott, LV., Salahuddin, F., Cooney, J., Svec, F and
Dinan, TG. Differences in adrenal steroid profile in
chronic fatigue syndrome, in depression and in
health. Journal of Affective Disorders, 1999, 54, 1-2,
129-137.


10. Neuropsychological tests on patients with ME/PVFS and strictly-defined CFS have revealed abnormalities which are consistent with an organic brain disorder (e.g. Daugherty et al).
The deficits have been found in both community and hospital samples and they were not the result of psychiatric disorders, such as depression (e.g. Smith, DeLuca et al).


Daugherty, SA., Henry, BE., Peterson, DL., Swarts,
RL., Bastein, S and Thomas, RS. Chronic fatigue
syndrome in Northern Nevada. Reviews of Infectious
Diseases, 1991, 13, Suppl. 1. S39-44.

Riccio, M., Thompson, C., Wilson, B, Morgan, DJR
and Lant, AF. Neuropsychological and psychiatric
abnormalities in myalgic encephalomyelitis: A
preliminary report. British Journal of Clinical
Psychology, 1992, 31, 111-120.

Smith, AP. Chronic fatigue syndrome and
performance. In AP Smith and D Jones (eds),
Handbook of Human Performance, Vol. 2. London:
Academic Press. 1992, p. 261-278.

Marcel, B., Komaroff, AL., Fagioli, LR., Kornish, RJ
and Albert, MS. Cognitive deficits in patients with
chronic fatigue syndrome. Biological Psychiatry,
1996, 40, 535-541.

DeLuca, J., Johnson, SK., Ellis, SP and Natelson,
BH. Cognitive functioning in patients with chronic
fatigue syndrome devoid of psychiatric disease.
Journal of Neurology, Neurosurgery, and Psychiatry,
1997, 62, 151-155.

Scholey, A., McCue, P and Wesnes, KA. A
comparison of the cognitive deficits seen in myalgic
encephalomyelitis to Alzheimer's Disease.
Proceedings of the British Psychological Society,
1999, January, 12.


10a. Exercise has an adverse effect on cognitive functioning.


LaManca, JJ., Sisto, SA., DeLuca., Johnson, SK.,
Lange, G., Pareja, J., Cook, S and Natelson, BH.
Influence of exhaustive treadmill exercise on
cognitive functioning in chronic fatigue syndrome.
American Journal of Medicine, 1998, 105, 3A,
59s-65s.


11. The depression experienced by patients with ME/PVFS and strictly defined CFS is different from that reported by psychiatric patients and closely related to the severity of the other
symptoms. Some patients report more anxiety (Lindal et al).


Hickie, I, Lloyd, A, Wakefield, D and Parker, G. The
psychiatric status of patients with the chronic fatigue
syndrome. British Journal of Psychiatry, 1990, 156,
534-540.

Hickie, I., Lloyd, A and Wakefield, D. Chronic fatigue
syndrome and depression. Lancet, 1991, 337, 992.

Landay, AL., Jessop, C., Lennette, ET and Levy, JA.
Chronic fatigue syndrome: clinical condition
associated with immune activation. Lancet, 1991,
338, 707-712.

Lindal E., Bergmann S., Thorlacius S and
Stefansson, JG. Anxiety disorders: A result of
long-term chronic fatigue - the psychiatric
characteristics of the sufferers of Iceland disease.
Acta Neurologica Scandinavica, 1997, 96, 3,
158-162.


12. ME/PVFS affects people of all ages and backgrounds.


Ho-Yen, DO and McNamara, I. General
practitioners' experience of the chronic fatigue
syndrome. British Journal of General Practice, 1991,
41, 324-326.


13. ME/PVFS and strictly-defined CFS are different from
fibromyalgia, a rheumatic condition.


Bennett, AL., Mayes, DM., Fagioli, LR., Guerriero, R
and Komaroff, AL. Somatomedin C (insulin-like
growth factor 1) levels in patients with chronic fatigue
syndrome. Journal of Psychiatric Research, 1997,
31, 1, 91-96.

Wysenbeek, AJ., Shapira, Y and Leibovici, L.
Primary fibromyalgia and the chronic fatigue
syndrome. Rheumatology International, 1991, 10,
227-230.


14. The fatigue reported by patients with ME/PVFS and strictly-defined CFS is very different from that experienced by the general population. Scores on fatigue scales are more like
those of people with M.S.


Krupp, LB., Mendelson, WB and Friedman, R. An
overview of chronic fatigue syndrome. Journal of
Clinical Psychiatry, 1991, 52, 10, 403-410.

Ray, C., Weir, WRC., Phillips, S and Cullen, S.
Development of a measure of symptoms in chronic
fatigue syndrome: the profile of fatigue-related
symptoms (PFRS). Psychology and Health, 1992, 7,
27-43.

Schwartz, JE., Jandorf, L and Krupp, LB. The
measurement of fatigue: a new instrument. Journal
of Psychosomatic Research, 1993, 37, 7, 753-762.


15. The fatigue is not due to a lack of motivation or effort.


Lloyd, A, Gandevia, S. and Hales, J. Muscle
performance, voluntary activation, twitch properties
and perceived effort in normal subjects and patients
with chronic fatigue syndrome. Brain, 1991, 114,
85-98.


16. Recent evidence indicates that most patients with CFS do not spend the whole of the daytime resting. A number of coping strategies are used, some of which are associated with a
positive outcome (e.g. Saltzstein et al).


Packer, TL., Foster, DM and Brouwer, B. Fatigue
and activity patterns of people with chronic fatigue
syndrome. The Occupational Therapy Journal of
Research, 1997, 17, 3, 186-199.

Knussen, C and Lee, D. Chronic fatigue syndrome:
symptoms, appraisal and ways of coping. British
Journal of Health Psychology, 1998, 3, 111-121.

Lovell, DM. Chronic fatigue syndrome among
overseas development workers: a qualitative study.
Journal of Travel Medicine, 1999, 6, 16-23.

Saltzstein, BJ., Wyshak, G., Hubbuch, JT and Perry,
JC. A naturalistic study of the chronic fatigue
syndrome among women in primary care. General
Hospital Psychiatry, 1998, 20, 5, 307-316.
16a. Patients with CFS are no different from other
medically ill groups in terms of personality.

Johnson, SK., Lange, G., Tiersky, L., DeLuca, J and
Natelson, BH. Health-related personality variables in
chronic fatigue syndrome and multiple sclerosis.
Journal of Chronic Fatigue Syndrome, 2001, 8, 3/4,
41-52.


17. Longitudinal studies using appropriate measures have shown that physical attributions do not affect outcome (e.g. Lawrie et al). Moreover, research on patients with ME indicated
that a belief in a biological cause was not associated with avoidance behaviour or poor mental health.


Lawrie, SM., Manders, DN., Geddes, JR and Pelosi,
AJ. A population-based incidence study of chronic
fatigue. Psychological Medicine, 1997, 27, 343-353.

Ray, C., Jefferies, S and Weir, WRC. Coping and
other predictors of outcome in chronic fatigue
syndrome: A 1-year follow-up. Journal of
Psychosomatic Research, 1997, 43, 4, 405-415.

Deale, A., Chalder, T and Wessely, S. Illness beliefs
and treatment outcome in chronic fatigue syndrome.
Journal of Psychosomatic Research, 1998, 45, 1,
77-83.

Heijmans, MJWM. Coping and adaptive outcome in
chronic fatigue syndrome: importance of illness
cognitions. Journal of Psychosomatic Research,
1998, 45, 1, 39-51.


18. Exercise does not lead to a major reduction in activity levels (Sisto et al, Van der Werf et al). There is no evidence for the phobic avoidance of activity amongst the majority of patients with CFS, or support for the view that deconditioning plays a major role in the perpetuation of fatigue (Bazelmans et al, Sargent et al).


Sisto, SA., Tapp, WN., LaManca, JJ., Ling, W., Korn,
LR., Nelson, AJ and Natelson, BH. Physical activity
before and after exercise in women with chronic
fatigue syndrome. Quarterly Journal of Medicine,
1998, 91, 7, 465-473.

Van der Werf, SP., Prins, JB., Vercoulen, JHMM.,
van der Meer, JWM and Bleijenberg, G. Identifying
physical activity patterns in chronic fatigue syndrome
using actigraphic assessment. Journal of
Psychosomatic Research, 2000, 49, 5, 373-379.

Bazelmans E, Bleijenberg, G., van der Meer, JWM
and Folgering, H. Is physical deconditioning a
perpetuating factor in chronic fatigue syndrome? A
controlled study on maximal exercise performance
and relations with fatigue, impairment and physical
activity. Psychological Medicine, 2001, 31, 107-114.

Sargent., C, Scroop, GC., Nemeth, PM., Burnet, RB
and Buckley JD. Maximal oxygen uptake and lactate
metabolism are normal in chronic fatigue syndrome.
Medicine and Science in Sports and Exercise, 2002,
34, 1, 51-56.


19. Graded exercise, where activity is increased according to a plan irrespective of symptoms, is not appropriate for all patients with CFS (Friedberg and Krupp, Jason et al). Indeed,
overexertion can lead to relapse (eg Lapp). Although cognitive behavioural therapy is not superior to counselling for CFS in general (Ridsdale et al), it may be helpful for a subgroup, for example, those who are particularly anxious and depressed, those with inadequate coping strategies or where activity levels are largely determined by a fear of symptom flare-ups.
Follow-up studies suggest that improvements are often limited and transient (e.g. Akagi et al). There are no follow-up studies indicating benefits for those with somatic symptoms (cf. Deale et al).


Akagi, H., Klimas, I and Bass, C. Cognitive
behavioral therapy for chronic fatigue syndrome in a
general hospital - feasible and effective. General
Hospital Psychiatry, 2001, 23, 254-260.

Deale, A., Husain, K., Chalder, T and Wessely, S.
Long-term outcome of cognitive behavior therapy
versus relaxation therapy for chronic fatigue
syndrome: a 5-year follow-up study. American
Journal of Psychiatry, 2001, 158, 2038-2042.

Friedberg, F and Krupp, LB. A comparison of
cognitive behavioral treatment for chronic fatigue
syndrome and primary depression. Clinical
Infectious Diseases, 1994, 18, (Suppl.1),
S105-S110.

Jason, LA., Richman, JA., Friedberg, F., Wagner, L.,
Taylor, R and Jordan, KM. Politics, science, and the
emergence of a new disease. The case of chronic
fatigue syndrome. American Psychologist, 1997, 52,
9, 973-983.

Lloyd, AR., Hickie, I., Brockman, A., Hickie, C.,
Wilson, A., Dwyer, J and Wakefield, D. Immunologic
and psychologic therapy for patients with chronic
fatigue syndrome: a double-blind, placebo-controlled
trial. American Journal of Medicine, 1993, 94,
197-203.

Lapp, C. Exercise limits in chronic fatigue
syndrome. American Journal of Medicine, 1997,
103, 83-84.

Ridsdale, L., Godfrey, E., Chalder, T., Seed, P.,
King, M., Wallace, P and Wessely, S. Chronic
fatigue in general practice: is counselling as good as
cognitive behaviour therapy? A UK randomised trial.
British Journal of General Practice, 2001, 51, 462,
19-24.


20. Symptoms indicative of autonomic nervous system dysfunction are not related to psychiatric disorder and can not be fully explained by deconditioning.


Freeman, R and Komaroff, AL. Does the chronic
fatigue syndrome involve the autonomic nervous
system? American Journal of Medicine, 1997, 102,
4, 357-364.


21. CFS remains a research diagnosis. A number of subgroups have been identified. These appear to have different causes, different rates of psychiatric disorders, may have different prognoses and probably require different treatments.


Friedberg, F. A subgroup analysis of
cognitive-behavioral treatment studies. Journal of
Chronic Fatigue Syndrome, 1999, 5, 3/4, 149-159.

Levine, PH., Snow, PG., Ranum, BA., Paul, C and
Holmes, MJ. Epidemic neuromyasthenia and
chronic fatigue syndrome in West Otago, New
Zealand: a 10-year follow-up. Archives of Internal
Medicine, 1997, 157, 7, 750-754.

DeLuca, J., Johnson, SK., Ellis, SP and Natelson,
BH. Sudden versus gradual onset of chronic fatigue
syndrome differentiates individuals on cognitive and
psychiatric measures. Journal of Psychiatric
Research, 1997, 31, 1, 83-90.

DeLuca, J., Johnson, SK., Ellis, SP and Natelson,
BH. Cognitive functioning in patients with chronic
fatigue syndrome devoid of psychiatric disease.
Journal of Neurology, Neurosurgery, and Psychiatry,
1997, 62, 151-155.

Lerner, AM., Zervos, M., Dworkin, HJ., Chang, CH.,
Fitzgerald, T., Goldstein, J et al. New
cardiomyopathy: pilot study of intravenous
ganciclovir in a subset of the chronic fatigue
syndrome. Infectious Diseases in Clinical Practice,
1997, 6, 110-117.


N.B. The immunological changes documented in ME/PVFS and
strictly-defined CFS are related to the severity of the illness and
correlated with the presence of cognitive dysfunction


Cheney, PR. Evidence for T-cell activation by
soluble IL-2-R and T8-R in the chronic fatigue
syndrome. In Hyde, B., Goldstein, J and Levine, P
(Eds). The Clinical and Scientific Basis of Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome.
Ottawa: Nightingale Research Foundation. 1992.

Lutgendorf, S., Klimas, NG., Antoni, M., Brickman, A
and Fletcher, MA. Relationships of cognitive
difficulties to immune measures, depression and
illness burden in chronic fatigue syndrome. Journal
of Chronic Fatigue Syndrome, 1995, 1, 2, 23-41.


The immunological changes are not the same as those
documented in depression (Landay et al 1991, Lloyd et al 1992,
as above).

22. The documented links between CFS and psychiatric disorders may reflect the use of broader diagnostic criteria and the researcher's choice of measures. More psychiatric morbidity is diagnosed using the DIS than the SCID.


Jason, LA., Richman, JA., Friedberg, F., Wagner, L.,
Taylor, R and Jordan, KM. Politics, science, and the
emergence of a new disease. The case of chronic
fatigue syndrome. American Psychologist, 1997, 52,
9, 973-983.


23. There is growing evidence of oxidative damage in CFS.


Fulle, S., Mecocci, P., Fano, G., Vecchiet, I.,
Vecchini, A., Racciotti, D, Cherubini, A., Pizzigallo,
E., Vecchiet, L., Senin, U and Beal MF. Specific
oxidative alterations in vastus lateralis muscle of
patients with the diagnosis of chronic fatigue
syndrome. Free Radical Biology and Medicine,
2000, 29, 12, 1252-1259

Richards, RS., Roberts, TK., Mathers, D., Dunstan,
RH., McGregor, NR and Butt, HL. Investigation of
erythrocyte oxidative damage in rheumatoid arthritis
and chronic fatigue syndrome. Journal of Chronic
Fatigue Syndrome, 2000, 6, 1, 37-46.


24. A significant minority of patients with CFS as currently defined may have been wrongly diagnosed. More specific criteria should improve accuracy.


Cox DL and Findley, LJ. Severe and very severe
patients with chronic fatigue syndrome: perceived
outcome following an inpatient programme. Journal
of Chronic Fatigue Syndrome, 2000, 7, 3, 33-47.

Jason, LA., King, CP., Taylor RR and Kennedy, C.
Defining chronic fatigue syndrome: methodological
challenges. Journal of Chronic Fatigue Syndrome,
2000, 7, 3, 17-32.


25. Evidence supports the differentiation of CFS from functional somatic syndromes.


Taylor, RR., Taylor, LA and Schoeny, ME. Evaluating
latent variable models of functional somatic distress
in a community-based sample. Journal of Mental
Health, 2001, 10, 335-349.


26. Patients selected using the 1988 definition appear to be more symptomatic and impaired than people selected using the 1994 criteria. This is not explained by psychiatric reasons.


De Becker, P., McGregor, N and De Meirleir, K. A
definition-based analysis of symptoms in a large
cohort of patients with chronic fatigue syndrome.
Journal of Internal Medicine, 2001, 250, 3, 234-240.

Jason, LA., Torres-Harding, SR., Taylor, RR and
Carrico, AW. A comparison of the 1988 and 1994
diagnostic criteria for chronic fatigue syndrome.
Journal of Clinical Psychology in Medical Settings,
2001, 8, 4, 337-343.



Copyright.

February 2002

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Additional reading list

Ablashi, DV et al. Frequent HHV-6 reactivation in multiple
sclerosis (MS) and chronic fatigue syndrome (CFS) patients.
Journal of Clinical Virology, 2000, 16, 3, 179-191.

Behan, WMH and Behan, PO. The role of viral infection in
polymyositis, dermatomyositis and chronic fatigue syndrome.
Bailliere's Clinical Neurology, 1993, 2, 3, 637-657.

Blenkiron, P et al. Associations between perfectionism, mood,
and fatigue in chronic fatigue syndrome. A pilot study. Journal of
Nervous and Mental Disease, 1999, 187, 9, 566-570.

Boda, WL et al. Gait abnormalities in chronic fatigue syndrome.
Journal of the Neurological Sciences, 1995, 156-161.

Bou-Holaigah, I et al. The relationship between neurally
mediated hypotension and the chronic fatigue syndrome. JAMA,
1995, 274, 961-967.

Buckley, L et al. Personality dimensions in chronic fatigue
syndrome and depression. Journal of Psychosomatic Research,
1999, 46, 4, 395-400.

Chaudhuri, A et al. Chronic fatigue syndrome. Proceedings of
the Royal College of Physicians of Edinburgh, 1998, 28,
150-163. Up-to-date review plus personal comments.

Cunningham, L et al. Persistence of enteroviral RNA in chronic
fatigue syndrome is associated with abnormal production of
equal amounts of positive and negative strands of enteroviral
RNA. Journal of General Virology, 1990, 71, 1399-1402.

Daly, E. et al. Neuropsychological function in patients with
chronic fatigue syndrome, multiple sclerosis, and depression.
Applied Neuropsychology, 2001, 8, 1, 12-22.

Denz-Penhey, H and Murdoch, JC. Service delivery for people
with chronic fatigue syndrome: a pilot action research study.
Family Practice, 1993, 10, 14-18.

Dowsett, EG and Welsby, PD. Conversation Piece.
Postgraduate Medical Journal, 1992, 68, 63-65.
Dowsett, E.G., Ramsay, A.M., McCartney, R.A. and Bell, E.J.
Myalgic encephalomyelitis - a persistent enteroviral infection?
Postgraduate Medical Journal, 1990, 66, 526-530.

Dyer, C. Cardiologist admits research misconduct. British
Medical Journal, 1997, 314, 1501. (Contains information to
consider in relation to the hyperventilation theory).

English, TL. Skeptical of skeptics. Journal of the American
Medical Association, 1991, 265, 8, 964.

Fukuda, K., Straus, SE., Hickie, I., Sharpe, MC., Dobbins, JG.,
Komaroff, A and the International Chronic Fatigue Syndrome
Study Group. The chronic fatigue syndrome: a comprehensive
approach to its definition and study. Annals of Internal Medicine,
1994, 121, 953-959. (Latest American diagnostic criteria for
CFS).

Galbraith, DN., Nairn, C and Clements, GB. Phylogenetic
analysis of short enteroviral sequences from patients with
chronic fatigue syndrome. Journal of General Virology, 1995,
76, 1701-1707.

Gilliam, AG. Epidemiological study of an epidemic, diagnosed
as poliomyelitis, occurring among the personnel of the Los
Angeles County General Hospital during the Summer of 1934.
Public Health Bulletin, US Treasury Dept. no. 240. Washington:
United States Government Printing Office 1938.

Goudsmit, E. Response to Stainton Rogers. Health Psychology
Update, 2002, 11, 1, 60-64. (Letter responding to an earlier
article by Stainton Rogers (ibid, 10, 4, 29-32) and covering issue
of bias in journals).

Gow, JW et al. Antiviral pathway activation in patients with
chronic fatigue syndrome and acute infection. Journal of
Infectious Diseases, 2001, 33, 12, 2080-2081. E-CID:
www.journals.uchicago.edu/CID/journal/rapid.html

Harvey, WT. A flight surgeon's personal view of an emerging
illness. Aviation, Space, and Environmental Medicine, 1989, 60,
1199-201.

Hedrick, TE. Chronic fatigue syndrome. Quarterly Journal of
Medicine, 1997, 90, 723-725 (letter challenging the
psychologisation of CFS).
Hickie, I et al. Can the chronic fatigue syndrome be defined by
distinct clinical features? Psychological Medicine, 1995, 25,
925-935.

Hilgers, A and Frank, J. Chronic fatigue immundysfunction
syndrome bei 103 patienten: diagnostik, befunde und therapie.
Zeitschrift fur Klinische Medizin, 1992, 47, 152-164.

Hill, NF et al. Natural history of severe chronic fatigue syndrome.
Archives of Physical Medicine and Rehabilitation, 1999, 80, 9,
1090-1094.

Innes, S.B.G. Encephalomyelitis resembling benign myalgic
encephalomyelitis. Lancet, 1970, 1: 969-971. (Evidence of
inflammation within the CNS).

Iriarte, J et al. Modalities of fatigue in multiple sclerosis:
correlation with clinical and biological factors. Multiple
Sclerosis, 2000, 6, 2, 124-130. (Indicates the complexity of
fatigue and its links with immune system).

Jason, LA et al. A community-based study of chronic fatigue
syndrome. Archives of Internal Medicine, 1999, 159, 2129-2137.

Johnson, SK et al. Assessing somatization disorder in the
chronic fatigue syndrome. Psychosomatic Medicine, 1996, 58,
50-57.

Keller, RH et al. Association between HLA Class II antigens and
the chronic fatigue immune dysfunction syndrome. Clinical
Infectious Diseases (1994), 18, (Suppl.1), S154-S156.

Komaroff, AL et al. Health status in patients with chronic fatigue
syndrome and in general population and disease comparison
groups. American Journal of Medicine, 1996, 101, 3, 281-290.
(This shows that the level of disability associated with CFS is
higher than that documented in several medically-ill groups).

LaManca JJ et al. Cardiovascular response during head-up tilt in
chronic fatigue syndrome. Clinical Physiology, 1999, 19, 2,
111-120. (OI may be due to inactivity).

Lane, RJM et al. Exercise responses and psychiatric disorder in
chronic fatigue syndrome. BMJ, 1995, 311, 544-5.

Lange, G et al. Quantitative assessment of cerebral ventricular
volumes in chronic fatigue syndrome. Applied Neuropsychology,
2001, 8, 1, 23-30.

Levine, S. Prevalence in the cerebrospinal fluid of the following
infectious agents in a cohort of 12 CFS subjects: human herpes
virus-6 and 8; chlamydia species; mycoplasma species; EBV;
CMV; and Coxsackievirus. Journal of Chronic Fatigue
Syndrome, 2001, 9, 1/2, 41-51.

Levine, S et al. Prevalence of IgM and IgG antibody to HHV-6
and HHV-8 and results of plasma PCR to HHV-6 and HHV-7 in a
group of CFS patients and healthy donors. Journal of Chronic
Fatigue Syndrome, 2001, 9, 1/2, 31-40.

Lieberman, J and Bell, DS. Serum angiotensin-converting
enzyme as a marker for the chronic fatigue immune dysfunction
syndrome: a comparison to serum angiotensin-converting
enzyme in sarcoidosis. American Journal of Medicine, 1993,
95, 4, 407-412.

Manu, P et al. Idiopathic chronic fatigue: depressive symptoms
and functional somatic complaints. In, MA Demitrack and SE
Abbey (Eds.) Chronic Fatigue Syndrome. NY: Guildford Press.
1996.

Mengshoel, AM et al. Pain and fatigue induced by exercise in
fibromyalgia patients and sedentary healthy subjects. Clinical
and Experimental Rheumatology, 1995, 13, 477-482.

Nairn, C et al. Comparison of Coxsackie B neutralisation and
enteroviral PCR in chronic fatigue patients. Journal of Medical
Virology, 1995, 46, 310-313.

Natelson, BH et al. Reducing heterogeneity in chronic fatigue
syndrome: a comparison with depression and multiple sclerosis.
Clinical Infectious Diseases, 1995, 21, 5, 1204-1210.

Patarca, R et al. Dysregulated expression of tumor necrosis
factor in chronic fatigue syndrome: intercorrelations with cellular
sources and patterns of soluble immune mediator expression.
Clinical Infectious Diseases (1994), 18, (Suppl.1), S147-S153.

Plioplys, AV., Plioplys, S and Davis, JS. Meeting the frustrations
of chronic fatigue syndrome. Hospital Practice, 1997, 32, 6,
147-166. (Good on diagnosis).

Preedy, VR et al. Biochemical and muscle studies in patients
with acute onset post-viral fatigue syndrome. Journal of Clinical
Pathology, 1993, 46, 722-726.

Regland, B et al. Increased concentrations of homocysteine in
the cerebrospinal fluid in patients with fibromyalgia and chronic
fatigue syndrome. Scandinavian Journal of Rheumatology,
1997, 26, 301-307.

Reyes, M et al. Chronic fatigue syndrome progression and
self-defined recovery: evidence from the CDC Surveillance
System. Journal of Chronic Fatigue Syndrome, 1999, 5, 1,
17-27.

Richardson, J. Four cases of pesticide poisoning, presenting as
"ME", treated with a choline and ascorbic acid mixture. Journal
of Chronic Fatigue Syndrome, 2000, 6, 2, 11-21.

Scholey, A et al. Cognitive defects in chronic fatigue syndrome
are reversed by oxygen administration. Paper presented at the
BPS conference, Belfast, April 8-11th, 1999. Proceedings of the
British Psychological Society, 1999, 7, 2, 137.

Schweitzer, R et al. Quality of life in chronic fatigue syndrome.
Social Science and Medicine, 195, 41, 1367-1372.

Scott, LV et al. Small adrenal glands in chronic fatigue
syndrome: a preliminary computer tomography study.
Psychoneuroendocrinology, 1999, 24, 7, 759-768.

Shanks, MF and Ho-Yen, DO. A clinical study of chronic fatigue
syndrome. British Journal of Psychiatry, 1995, 166, 798-801.

Sigurdsson, B and Gudmundsson, KR. Clinical findings six
years after outbreak of Akureyri disease. Lancet, 1956, 1
766-767.

Simon, TR., Cowden. E., Seastrunk, JW., Weiner, E and Hickie,
DC. Chronic fatigue syndrome: flow and functional abnormalities
seen with SPECT. Radiology, 1991, 181, Suppl. 173.

Teitelbaum, J and Bird, B. Effective treatment of severe chronic
fatigue: a report of a series of 64 patients. Journal of
Musculoskeletal Pain, 1995, 3, 4, 91-110.

Trigwell, P et al. 'Abnormal' illness behaviour in chronic fatigue
syndrome and multiple sclerosis. BMJ, 1995, 311, 15-18.

Vercoulen, JHMM., Bazelmans, E., Swanink, CMA., Fennis, JFM
et al. Physical activity in chronic fatigue syndrome: Assessment
and its role in fatigue. Journal of Psychiatric Research, 1997, 31,
6, 661-673.

Vojdani, A et al. Elevated apoptotic cell population in patients
with chronic fatigue syndrome: the pivotal role of protein kinase
RNA. Journal of Internal Medicine, 1997, 242, 6, 465-478

Wood, B and Wessely, S. Personality and social attitudes in
chronic fatigue syndrome. Journal of Psychosomatic Research ,
1999, 47, 4, 385-397.

Woodward, RV et al. Diagnosis in chronic illness: disabling or
enabling - the case of chronic fatigue syndrome. Journal of the
Royal Society of Medicine, 1995, 88, 325-329.


Copyright EM Goudsmit
February 2002


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Suggested criteria for ME (based on the work of Dr MA
Ramsay):


1. Generalised or localised muscle fatigue following
minimal exertion with prolonged recovery time.

2. Neurological disturbances and variable
involvement of cardiac and other bodily systems.

3. Impaired circulation.

4. Marked variability of symptoms in the course of a
day and from day to day.

5. An extended relapsing course with a tendency to
chronicity.


ME can be diagnosed immediately. For research purposes
however, a minimum duration of six months may help to
differentiate ME from more common, transient post-viral
syndromes.

The criteria for ME differ from the American and Oxford
definitions for CFS in three ways. Firstly, the latter do not require
evidence of central nervous system dysfunction. Secondly, they
do not include any references to the fluctuation of symptoms or
the close links between symptoms and exertion. Thirdly, the
older CDC criteria place a much greater emphasis on
infection-related symptoms such as mild fever, sore throat (which
are counted twice) and tender glands compared to the
definitions of ME.

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