The chronic fatigue syndrome

Abstract:

CFIDS (chronic fatigue and immune disfunction syndrome) is also known as CFS (chronic fatigue syndrome), CEBV (chronic Epstein-Barr virus), M.E. (myalgic encephalomyelitis), yuppie flu and by other names.

It is a complex illness characterized by incapacitating fatigue (experienced as exhaustion and extremely poor stamina), neurological problems and a constellation of symptoms that can resemble many disorders, including; mononucleosis, multiple sclerosis, fibromyalgia, AIDS-related complex (ARC) and autoimmune diseases such as lupus. These symptoms tend to wax and wane, but any often severely debilitating and may last for many months or years. All sections of the population (including children) are at risk, but women under 45 seem to be most susceptible.

The investigators suggest that CFIDS results from dysfunction of the immune system. The exact nature of this dysfunction is not yet well defined, but it can generally be viewed as an unregulated or overactive state which is responsible for most of the symptoms. There is also evidence of some immune suppression in CFIDS. None of the treatments is consistently satisfactory, but some may be helpful: psychotherapy, physiotherapy, exercise programs, acupunctures, small doses of antidepressants, etc.

 

Source: Artsimovich NG, Chugunov VS, Kornev AV, Ivanova TM, Chugunov AV, Oprishchenko MA. The chronic fatigue syndrome. Zh Nevrol Psikhiatr Im S S Korsakova. 1994;94(5):47-50. [Article in Russian] http://www.ncbi.nlm.nih.gov/pubmed/7900453

 

Pathogenic tracks in fatigue syndromes

Abstract:

This review analyses the recent literature devoted to two related fatigue syndromes: chronic fatigue syndrome (CFS) and acute onset postviral fatigue syndrome (PVFS). The articles are grouped into five pathogenic tracks: infectious agents, immune system, skeletic muscle, hypothalamo-pituitary-adrenal (HPA) axis and psychiatric factors.

Although a particular infectious agent is unlikely to be responsible for all CFS cases, evidence is shown that host-parasite relationships are modified in a large proportion of patients with chronic fatigue. Antibody titres against infectious agents are often elevated and replication of several viruses could be increased.

Chronic activation of the immune system is also observed and could be due to the reactivation of persistent or latent infectious agents such as herpes viruses (i.e. HHV-6) or enteroviruses. It could also be favorised by an impaired negative feedback of the HPA axis on the immune system.

A model is proposed where the abnormalities of the HPA axis are primary events and are mainly responsible for a chronic activation of the immune system which in turn induces an increased replication of several viruses under the control of cellular transcription factors. These replicating viruses together with cytokines such as TNF-alpha would secondarily induce functional disorders of muscle and several aspects of asthenia itself.

 

Source: Moutschen M, Triffaux JM, Demonty J, Legros JJ, Lefèbvre PJ. Pathogenic tracks in fatigue syndromes. Acta Clin Belg. 1994;49(6):274-89. http://www.ncbi.nlm.nih.gov/pubmed/7871934

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214

 

 

Prevalence of fatigue and chronic fatigue syndrome in a primary care practice

Abstract:

BACKGROUND: Our goals were to determine the prevalence of unusual, debilitating fatigue and the frequency with which it was associated with the chronic fatigue syndrome (CFS) or other physical or psychological illness in an outpatient clinic population.

METHODS: We prospectively evaluated a cohort of 1000 consecutive patients in a primary care clinic in an urban, hospital-based general medicine practice. The study protocol included a detailed history, physical examination, and laboratory and psychiatric testing.

RESULTS: Five patients who came because of CFS studies were excluded. Of the remaining 995, 323 reported fatigue, and 271 (27%) complained of at least 6 months of unusual fatigue that interfered with their daily lives. Of the 271, self-report or record review revealed a medical or psychiatric condition that could have explained the fatigue in 186 (69%). Thus, 85 (8.5%) of 995 patients had a debilitating fatigue of at least 6 months’ duration, without apparent cause. Of these patients, 48 refused further evaluation, and 11 were unavailable for follow-up; 26 completed the protocol. Three of the 26 were hypothyroid, and one had a major psychiatric disorder. Of the remaining 22 patients, three met Centers for Disease Control and Prevention criteria for CFS, four met British criteria, and 10 met the Australian case definition. The point prevalences of CFS were thus 0.3% (95% confidence interval [CI], 0% to 0.6%), 0.4% (95% CI, 0% to 0.8%), and 1.0% (95% CI, 0.4% to 1.6%) using the Centers for Disease Control and Prevention, British, and Australian case definitions, respectively. These estimates were conservative, because they assumed that none of the patients who refused evaluation or were unavailable for follow-up would meet criteria for CFS.

CONCLUSIONS: While chronic, debilitating fatigue is common in medical outpatients, CFS is relatively uncommon. Prevalence depends substantially on the case definition used.

 

Source: Bates DW, Schmitt W, Buchwald D, Ware NC, Lee J, Thoyer E, Kornish RJ, Komaroff AL. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med. 1993 Dec 27;153(24):2759-65. http://www.ncbi.nlm.nih.gov/pubmed/8257251

 

A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome

Abstract:

Two neuroradiologists compared the brain MR scans of 52 patients with the CDC criteria for the chronic fatigue syndrome (CFS) with those of 52 age and sex matched controls who had undergone imaging because of histories of head trauma or headache.

CFS patients had significantly more abnormal scans than controls–27% vs 2%. Abnormalities seen were foci of increased white matter T2 signal in 9 CFS patients and one control and ventricular or sulcal enlargement in 5 CFS patients. Follow up of patients with subcortical signal hyperintensities revealed 3 who had symptoms suggestive of other known medical causes of what appeared to be CFS.

The data indicate that some CFS patients have some organic problem manifesting itself on neuroimaging. But, finding MR abnormalities should warn the physician that the patient’s symptoms may be secondary to some other medical illness and not simply primary CFS.

 

Source: Natelson BH, Cohen JM, Brassloff I, Lee HJ. A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome. J Neurol Sci. 1993 Dec 15;120(2):213-7. http://www.ncbi.nlm.nih.gov/pubmed/8138812

 

Serum folate and chronic fatigue syndrome

Abstract:

We assayed serum folate levels of 60 patients with chronic fatigue syndrome (CFS) and found that 50% had values below 3.0 micrograms/l. Some patients with CFS are deficient in folic acid.

Comment in: Folate and chronic fatigue syndrome. [Neurology. 1994]

 

Source: Jacobson W, Saich T, Borysiewicz LK, Behan WM, Behan PO, Wreghitt TG. Serum folate and chronic fatigue syndrome. Neurology. 1993 Dec;43(12):2645-7. http://www.ncbi.nlm.nih.gov/pubmed/8255470

 

Post-viral fatigue syndrome. A longitudinal assessment in varsity athletes

Abstract:

Maximal oxygen uptake, anaerobic threshold (AT), isometric strength of the elbow flexor and knee extensor muscles, isometric strength endurance exhaustion time (prolonged contraction at 66% of maximal isometric strength), uphill sprinting exhaustion time were longitudinally studied in eight varsity endurance runners with post-viral fatigue syndrome (PVFS).

Prolonged impairment of exercise performance is evident during the course of PVFS. Although maximal oxygen uptake (VO2max) had returned to pre-infection values 13 months after the viral illness (4.160 vs 4.0 L.min-1), AT was still significantly reduced [52 ml.kg-1.min-1, 18.6 km.hr-1, 176 bpm, and 82% of VO2max vs. 49.1 ml.kg-1.min-1 (p < 0.05), 175 bpm (NS), 17.2 km.hr-1 (p < 0.01) and 79% of VO2max (NS)].

Maximal isometric contraction strength of the upper limb remained constant (282 N vs. 274 N), while knee extensor muscles strength decreased significantly (730 N vs. 701 N, p < 0.05). Strength endurance was still significantly reduced by the end of the study (arm average pre-infection: 46.2 sec; end of study: 29.3 sec, p < 0.001; leg average pre-infection: 66.4 sec; end of study: 49.1 sec, p < 0.01). Up hill sprinting time was similarly reduced by the end of the study period (29.3 sec vs. 16.2 sec, p < 0.01).

Both aerobic and anaerobic exercise variables are seriously affected by post-viral fatigue syndrome, and one year may not be sufficient to fully recover.

 

Source: Maffulli N, Testa V, Capasso G. Post-viral fatigue syndrome. A longitudinal assessment in varsity athletes. J Sports Med Phys Fitness. 1993 Dec;33(4):392-9. http://www.ncbi.nlm.nih.gov/pubmed/8035588

 

Prevalence of chronic fatigue syndrome-related symptoms among nurses

Abstract:

Chronic Fatigue Syndrome is an illness that is characterized by debilitating fatigue and a group of other related symptoms. Few epidemiological studies have been conducted, and none have focused on a nursing population. The present study is the first to assess the prevalence of Chronic Fatigue Syndrome-related symptoms in a sample of nurses. Demographic characteristics, symptoms, and possible prevalence rates are presented and discussed. When using both narrow and more inclusive criteria to define this symptom complex, higher rates of this disorder were found than in previous epidemiological studies. The implications of these findings are discussed.

 

Source: Jason LA, Taylor SL, Johnson S, Goldston SE, Salina D, Bishop P, Wagner L. Prevalence of chronic fatigue syndrome-related symptoms among nurses. Eval Health Prof. 1993 Dec;16(4):385-99. http://www.ncbi.nlm.nih.gov/pubmed/10130552

 

Repetitively negative changing T waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome. Left ventricular dysfunction in a cohort

Abstract:

This study surveys the occurrence of repetitively negative to flat T waves, alternating with normal upright T waves in 24-h electrocardiographic recordings from a subspecialty infectious diseases outpatient practice during the years 1982 to 1990. Patients with normal resting electrocardiogram in the assayed leads, but with repetitively inverted to isoelectric abnormal T waves at Holter monitors, were considered to have abnormal readings.

A total of 300 patients had undergone a 24-h Holter monitor. This group included 24 individuals with chronic fatigue syndrome (CFS). This population was restricted to individuals 50 years old or younger, and the patients with CFS are compared with the patients without CFS.

One of the more striking differences between the two groups was the difference in abnormal Holter readings. The patients with CFS all had abnormal Holter readings, while 22.4 percent patients without CFS had abnormal readings (p < 0.01). We further report the occurrence of mild left ventricular dysfunction in 8 of 60 patients in continuing studies of this population with CFS, younger than 50 years old, and with no risk factors for coronary artery disease.

All 60 patients with CFS showed repetitively flat to inverted T waves alternating with normal T waves. Stress multiple gated acquisitions (MUGAs) (labeled erythrocytes with stannous pyrophosphate) were abnormal in eight patients with CFS. Although resting ejection fractions (EFs) were normal (mean, 60 percent), with increasing work loads (Kilopon meters [Kpms]), gross left ventricular dysfunction occurred. The fatigue of patients with CFS may be related to subtle cardiac dysfunction occurring at work loads common to ordinary living.

 

Source: Lerner AM, Lawrie C, Dworkin HS. Repetitively negative changing T waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome. Left ventricular dysfunction in a cohort. Chest. 1993 Nov;104(5):1417-21. http://www.ncbi.nlm.nih.gov/pubmed/8222798

 

Chronic fatigue in primary care attenders

Abstract:

From 686 patients attending primary care physicians, 77 were identified by a screening procedure as having chronic fatigue. Of these, 65 were given a comprehensive psychological, social and physical evaluation.

Seventeen cases (26%) met criteria for the chronic fatigue syndrome. Forty-seven (72%) received an ICD-9 diagnosis of whom 23 had neurotic depression, with a further 5 meeting criteria for neurasthenia.

Forty-nine were ‘cases’ as defined by the revised Clinical Interview Schedule (CIS-R), and 42 if the fatigue item was excluded. Psychiatric morbidity was more related to levels of social stresses than was severity of fatigue.

The main difference between these subjects and those examined in hospital settings is that the former are less liable to attribute their symptoms to wholly physical causes, including viruses, as opposed to social or psychological factors. Identification and management of persistent fatigue in primary care may prevent the secondary disabilities seen in patients with chronic fatigue syndromes.

 

Source: McDonald E, David AS, Pelosi AJ, Mann AH. Chronic fatigue in primary care attenders. Psychol Med. 1993 Nov;23(4):987-98. http://www.ncbi.nlm.nih.gov/pubmed/8134522