Chronic fatigue syndrome: probable pathogenesis and possible treatments

Abstract:

Chronic fatigue syndrome (CFS) belongs in the medically unexplained illnesses. It affects approximately 0.2-0.7% of the population in Western countries. It is characterised by unexplained fatigue, lasting 6 months or more, impairment of neurocognitive functions and quality of sleep, and of somatic symptoms, such as recurrent sore throat, muscle aches, arthralgias, headache and postexertional malaise. No link between infections and CFS has been clearly established but the immune system is activated, there are aberrations in several hypothalamic-pituitary axes and involvement of other parts of the central nervous system. No specific treatment has been found. Cognitive behavioural therapy is established to be of value to improve quality of life. More effective treatment should result, as advances in biomedical as well as psychological research continue.

 

Source: Evengård B, Klimas N. Chronic fatigue syndrome: probable pathogenesis and possible treatments. Drugs. 2002;62(17):2433-46. http://www.ncbi.nlm.nih.gov/pubmed/12421101

 

Dysautonomias: clinical disorders of the autonomic nervous system

Abstract:

The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities.

In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after “patchy” autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops.

Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with beta-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology.

 

Source: Goldstein DS, Robertson D, Esler M, Straus SE, Eisenhofer G. Dysautonomias: clinical disorders of the autonomic nervous system. Ann Intern Med. 2002 Nov 5;137(9):753-63. http://www.ncbi.nlm.nih.gov/pubmed/12416949

 

Health and functional status of twins with chronic regional and widespread pain

Erratum in: J Rheumatol. 2002 Dec;29(12):2667. Buchwald, Dedra [corrected to Buchwald, Debra].

 

Abstract:

OBJECTIVE: To examine the independent effects of chronic regional and widespread pain syndromes on health and functional status after accounting for comorbid chronic fatigue using a co-twin control design.

METHODS: We identified 95 twin pairs discordant for pain in which one twin had chronic regional or widespread pain and the other denied chronic pain. Demographic data, functional and psychological status, health behaviors, and symptoms based on the 1994 criteria for chronic fatigue syndrome (CFS) were assessed by questionnaire. Psychiatric diagnoses were based on structured interview. Random effects regression modeling estimated associations between chronic regional and widespread pain and each health measure with and without adjustment for CFS.

RESULTS: Significant differences (p </= 0.05) were found within twin pairs discordant for chronic regional and widespread pain, for general health perception, and physical and mental health functioning as measured by summary scores from the Short Form-36. In addition, differences were observed within pain discordant pairs in psychological distress as measured by the General Health Questionnaire as well as the number of psychiatric diagnoses. Adjustment for CFS eliminated the association between chronic pain and mental health, but the association between chronic pain and poor general health, physical functioning, and sleep quality persisted (p </= 0.01). Only the intra-pair difference in physical functioning distinguished twins with regional vs widespread pain (p </= 0.05).

CONCLUSION: Both chronic regional and widespread pain exact debilitating effects on perceived general health, physical functioning, and sleep quality independent of CFS. However, the psychological and psychiatric influence of chronic pain appears closely tied to CFS. Research should examine the additive role of CFS-like illnesses in patients with chronic pain, and its influence on treatment and outcome.

 

Source: Aaron LA, Arguelles LM, Ashton S, Belcourt M, Herrell R, Goldberg J, Smith WR, Buchwald D. Health and functional status of twins with chronic regional and widespread pain. J Rheumatol. 2002 Nov;29(11):2426-34. http://www.ncbi.nlm.nih.gov/pubmed/12415604

 

Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain

Abstract:

Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation.

Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate.

When we studied the cerebral uptake of acetylcarnitine by using [2-(11)C]acetyl-L-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmann’s area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum.

These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.

 

Source: Kuratsune H, Yamaguti K, Lindh G, Evengård B, Hagberg G, Matsumura K, Iwase M, Onoe H, Takahashi M, Machii T, Kanakura Y, Kitani T, Långström B, Watanabe Y. Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage. 2002 Nov;17(3):1256-65. http://www.ncbi.nlm.nih.gov/pubmed/12414265

 

Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome–a randomised controlled trial

Abstract:

We have previously conducted a small treatment study on staphylococcus toxoid in fibromyalgia (FM) and chronic fatigue syndrome (CFS). The aim of the present study was to further assess the efficacy of the staphylococcus toxoid preparation Staphypan Berna (SB) during 6 months in FM/CFS patients.

One hundred consecutively referred patients fulfilling the ACR criteria for FM and the 1994 CDC criteria for CFS were randomised to receive active drug or placebo. Treatment included weekly injections containing 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.6 ml, 0.8 ml, 0.9 ml, and 1.0 ml SB or coloured sterile water, followed by booster doses given 4-weekly until endpoint.

Main outcome measures were the proportion of responders according to global ratings and the proportion of patients with a symptom reduction of > or =50% on a 15-item subscale derived from the comprehensive psychopathological rating scale (CPRS). The treatment was well tolerated. Intention-to-treat analysis showed 32/49 (65%) responders in the SB group compared to 9/49 (18%) in the placebo group (P<0.001). Sixteen patients (33%) in the SB group reduced their CPRS scores by at least 50% compared to five patients (10%) in the placebo group (P< 0.01). Mean change score on the CPRS (95% confidence interval) was 10.0 (6.7-13.3) in the SB group and 3.9 (1.1-6.6) in the placebo group (P<0.01). An increase in CPRS symptoms at withdrawal was noted in the SB group.

In conclusion, treatment with staphylococcus toxoid injections over 6 months led to significant improvement in patients with FM and CFS. Maintenance treatment is required to prevent relapse.

 

Source: Zachrisson O, Regland B, Jahreskog M, Jonsson M, Kron M, Gottfries CG. Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome–a randomised controlled trial. Eur J Pain. 2002;6(6):455-66. http://www.ncbi.nlm.nih.gov/pubmed/12413434

 

The treatment of small intestinal bacterial overgrowth with enteric-coated peppermint oil: a case report

Abstract:

Recent investigations have shown that bacterial overgrowth of the small intestine is associated with a number of functional somatic disorders, including irritable bowel syndrome (IBS), fibromyalgia, and chronic fatigue syndrome.

A number of controlled studies have shown that enteric-coated peppermint oil (ECPO) is of benefit in the treatment of IBS. However, despite evidence of strong antimicrobial activity, ECPO has not been specifically investigated for an effect on small intestinal bacterial overgrowth (SIBO).

A case report of a patient with SIBO who showed marked subjective improvement in IBS-like symptoms and significant reductions in hydrogen production after treatment with ECPO is presented. While further investigation is necessary, the results in this case suggest one of the mechanisms by which ECPO improves IBS symptoms is antimicrobial activity in the small intestine.

Comment in: Treatment with enteric-coated peppermint oil reduced small-intestinal bacterial overgrowth in a patient with irritable bowel syndrome. [Altern Med Rev. 2003]

 

Source: Logan AC, Beaulne TM. The treatment of small intestinal bacterial overgrowth with enteric-coated peppermint oil: a case report. Altern Med Rev. 2002 Oct;7(5):410-7. http://www.altmedrev.com/publications/7/5/410.pdf (Full article)

 

Intravenous nutrient therapy: the “Myers’ cocktail”

Abstract:

Building on the work of the late John Myers, MD, the author has used an intravenous vitamin-and-mineral formula for the treatment of a wide range of clinical conditions. The modified “Myers’ cocktail,” which consists of magnesium, calcium, B vitamins, and vitamin C, has been found to be effective against acute asthma attacks, migraines, fatigue (including chronic fatigue syndrome), fibromyalgia, acute muscle spasm, upper respiratory tract infections, chronic sinusitis, seasonal allergic rhinitis, cardiovascular disease, and other disorders. This paper presents a rationale for the therapeutic use of intravenous nutrients, reviews the relevant published clinical research, describes the author’s clinical experiences, and discusses potential side effects and precautions.

 

Source: Gaby AR. Intravenous nutrient therapy: the “Myers’ cocktail”. Altern Med Rev. 2002 Oct;7(5):389-403. http://www.altmedrev.com/publications/7/5/389.pdf (Full article)

 

On the history of the concept neurasthenia and its modern variants chronic-fatigue-syndrome, fibromyalgia and multiple chemical sensitivities

Abstract:

This article deals with the history of the terminological and nosological development of the concept neurasthenia introduced in 1869 by George Miller Beard and in particular with its reappearance in western medicine in the 1980 s. Beginning with its predecessors in antiquity and continuing with hypochondria, which became a fashionable disease in the 18 th century, the concept neurasthenia reached a high point and world-wide medical acceptance at the end of the 19 th/beginning of the 20 th century. However, between the 1930 s and 1960 s it declined in popularity and gradually disappeared until finally it only had a rudimentary nosological role in the term “pseudoneurasthenia”. In the countries of the Far East, on the contrary, the concept of neurasthenia has been in continual use since its importation in the first decades of the last century. In the 1980 s, when an interest in the symptoms of chronic fatigue was reawakened in western medicine, the concept neurasthenia reappeared, this time to define the particular form of a neurotic disorder.

Parallel to these developments increasing importance was attached to clinical descriptions of illnesses which on account of their similarity to the symptoms of neurasthenia could be termed modern variants of the concept neurasthenia. These are “Chronic-Fatigue-Syndrome”, “Fibromyalgia” and “Multiple Chemical Sensitivities” which have more or less adopted the organic inheritance of Beard’s former concept of neurasthenia, despite the fact that so far the question of organicity could not be decisively answered in a single case. In order to clarify possible influences on the development of the concept neurasthenia and its variants, the theories and ideas of E. Shorter, medical historian at the University of Toronto, are discussed in the final part of the article, whereby the particular cultural background in each case has a decisive influence on the manifestation of the psychosomatic symptoms.

 

Source: Schäfer ML. On the history of the concept neurasthenia and its modern variants chronic-fatigue-syndrome, fibromyalgia and multiple chemical sensitivities. Fortschr Neurol Psychiatr. 2002 Nov;70(11):570-82. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/12410427

 

Role of fatigue in limiting physical activities in humans with neuromuscular diseases

Abstract:

New methods of examining both central and peripheral fatigue are now available. A broader understanding of the mechanisms of fatigue in healthy human subjects has begun to emerge. The mechanisms of fatigue in patients with various neuromuscular diseases are even more complex than in healthy persons. Examples of both central and peripheral fatigue in various neuromuscular diseases and other disorders are presented, including metabolic myopathy, chronic fatigue syndrome, postpolio syndrome, and amyotrophic lateral sclerosis.

 

Source: Miller RG. Role of fatigue in limiting physical activities in humans with neuromuscular diseases. Am J Phys Med Rehabil. 2002 Nov;81(11 Suppl):S99-107. http://www.ncbi.nlm.nih.gov/pubmed/12409815

 

Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review

Abstract:

Infectious mononucleosis is usually an acute, transiently incapacitating condition, but for some sufferers it precipitates chronic illness. It is unclear which patients are at risk of a prolonged state of illness following onset of infectious mononucleosis and if there are any useful preventive measures that would facilitate recovery. The aim of this study was to review all cohort studies and intervention trials that provide information on: (a) the longitudinal course of ill health subsequent to the onset of infectious mononucleosis; (b) the relationship between psychosocial and clinical factors and recovery rate; and (c) the effect of interventions on recovery.

A systematic review was conducted, based on a search of the PSYCHINFO, MEDLINE, EMBASE and CINHAL databases up to October 2001, and ISI Science and Social Sciences Citation Indices up to 22 November 2001. Eight papers were identified that gave data on illness following onset of infectious mononucleosis. The best evidence concluded that there is a distinct fatigue syndrome after infectious mononucleosis. Eight papers explored risk factors for prolonged illness following acute infectious mononucleosis.

Results varied on the association of acute illness characteristics and psychological features with prolonged ill health. Poor physical functioning, namely lengthy convalescence and being less fit or active, consistently predicted chronic ill health. Three trials reported on interventions that aimed to shorten the time taken to resolve symptoms after uncomplicated infectious mononucleosis. None of the drug trials found any evidence that drug therapy shortens recovery time. The trial that compared the effect of activity with imposed bed rest, found that those patients allowed out of bed as soon as they felt able reported a quicker recovery. More information is needed on the course of ill health subsequent to the onset of infectious mononucleosis. Certain risk factors associated with delay may be amenable to a simple intervention in primary care.

 

Source: Candy B, Chalder T, Cleare AJ, Wessely S, White PD, Hotopf M. Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review. Br J Gen Pract. 2002 Oct;52(483):844-51. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1316091/ (Full article)