A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome

Abstract:

OBJECTIVE: To provide a preliminary assessment of the efficacy and safety of fludrocortisone acetate treatment of chronic fatigue syndrome.

DESIGN: A placebo-controlled, double-blind, random-allocation crossover trial of 6 weeks of fludrocortisone.

SETTING: An outpatient clinical trials unit.

PATIENTS: Twenty-five participants with chronic fatigue syndrome (mean age, 40 years; 19 [76%] women; mean duration of illness, 7.0 years) were recruited from a research and clinic registry. Five patients withdrew from the trial.

INTERVENTIONS: All participants were scheduled to receive fludrocortisone acetate (0.1-0.2 mg) or a placebo for 6 weeks in each treatment.

MAIN OUTCOME MEASURES: Self-administered questionnaires were completed at the beginning and end of each treatment arm that asked patients to rate the severity of their symptoms on a visual analogue scale. The Medical Outcomes Study 36-Item Short-Form Health Survey, a reaction time test, and a treadmill exercise test were used to assess functional status. Blood pressure, heart rate, and plasma norepinephrine levels were obtained at baseline. Blood pressure and heart rate were recorded at the end of the exercise test and monitored at all subsequent visits.

RESULTS: At baseline, the study participants reported symptom severity greater than 5 for most symptoms, and all had evidence of marked functional impairments. No improvement was observed in the severity of any symptom or in any test of function for the 20 participants who completed both arms of the trial. Blood pressure and heart rate readings were unaffected by treatment, and plasma norepinephrine levels did not differ from those of a healthy control group. The incidence of adverse experiences was similar in the fludrocortisone and placebo arms of the trial.

CONCLUSION: Low-dose fludrocortisone does not provide sufficient benefit to be evident in a preliminary blinded trial of unselected patients with chronic fatigue syndrome.

Comment in: Treatment for chronic fatigue syndrome. [Arch Intern Med. 1998]

 

Source: Peterson PK, Pheley A, Schroeppel J, Schenck C, Marshall P, Kind A, Haugland JM, Lambrecht LJ, Swan S, Goldsmith S. A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome. Arch Intern Med. 1998 Apr 27;158(8):908-14. http://www.ncbi.nlm.nih.gov/pubmed/9570178

Fibromyalgia, chronic fatigue syndrome, and myofascial pain

Abstract:

Epidemiologic studies continue to provide evidence that fibromyalgia is part of a spectrum of chronic widespread pain. The prevalence of chronic widespread pain is several times higher than fibromyalgia as defined by the 1990 American College of Rheumatology guidelines. There is now compelling evidence of a familial clustering of fibromyalgia cases in female sufferers; whether this clustering results from nature or nature remains to be elucidated. A wide spectrum of fibromyalgia-associated symptomatology and syndromes continues to be described.

During the past year the association with interstitial cystitis has been explored, and neurally mediated hypotension has been documented in both fibromyalgia and chronic fatigue syndrome. Abnormalities of the growth hormone-insulin-like growth factor-1 axis have been also documented in both fibromyalgia and chronic fatigue syndrome. The commonly reported but anecdotal association of fibromyalgia with whiplash-type neck trauma was validated in a report from Israel. However, unlike North America, 100% of Israeli patients with posttraumatic fibromyalgia returned to work.

Basic research in fibromyalgia continues to pinpoint abnormal sensory processing as being integral to understanding fibromyalgia pain. Drugs such as ketamine, which block N-methyl-D-aspartate receptors (which are often upregulated in central pain states) were shown to benefit fibromyalgia pain in an experimental setting. The combination of fluoxetine and amitriptyline was reported to be more beneficial than either drug alone in patients with fibromyalgia.

A high prevalence of autoantibodies to cytoskeletal and nuclear envelope proteins was found in chronic fatigue syndrome, and an increased prevalence of antipolymer antibodies was found in symptomatic silicone breast implant recipients who often have fibromyalgia.

 

Source: Bennett R. Fibromyalgia, chronic fatigue syndrome, and myofascial pain. Curr Opin Rheumatol. 1998 Mar;10(2):95-103. http://www.ncbi.nlm.nih.gov/pubmed/9567202

 

Chronic fatigue syndrome: a literature review from a physiatric perspective

Abstract:

To examine the literature on chronic fatigue syndrome (CFS), especially as it relates to cognitive deficits and exercise, more than 200 articles related to CFS were selected from computer-based research as well as pertinent articles noted in the references of individual articles. All were relevant articles on CFS, although articles in a foreign language were excluded. CFS is a controversial diagnosis of exclusion, but certain subgroups do appear to exist. It may represent multiple diseases or multiple stages of the same disease. Although cognitive deficits are commonly reported, the measured impairments are relatively subtle and are in the area of complex information processing speed, or efficiency.

Magnetic resonance imaging, single-photon emission computer tomography, and neuroendocrine studies present preliminary evidence suggestive of the cerebral involvement primarily in the white matter. The weakness and fatigue may be the result of alterations in the central nervous system, not in the peripheral muscles. However, it is hard to separate the documented weakness and endurance deficits from deconditioning.

Autonomic symptoms such as orthostatic intolerance and a predisposition to neurally mediated syncope may be explained by cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or both. The review points out the need for more carefully designed studies of CFS that focus on the relationship between neuropathology, psychopathology and neuropsychologic functioning. The role of exercise as a stimulus for exacerbation or in treatment needs to be further studied using clear diagnostic criteria as well as control groups that carefully match the activity level.

 

Source: Jain SS, DeLisa JA. Chronic fatigue syndrome: a literature review from a physiatric perspective. Am J Phys Med Rehabil. 1998 Mar-Apr;77(2):160-7. http://www.ncbi.nlm.nih.gov/pubmed/9558019

 

31P-mr spectroscopy of peripheral skeletal musculature under load: demonstration of normal energy metabolites compared with metabolic muscle diseases

Abstract:

PURPOSE: 31P-MR spectroscopy of skeletal muscle under exercise was used to obtain the range of normal variation and comparison was made for different neuromuscular diseases.

METHODS: 41 examinations of 24 volunteers and 41 investigations in 35 patients were performed on 1.5 T MR systems (Gyroscan 515 und S15/ACSII, Philips). Localised 31P-MR spectra of the calf muscle were obtained in time series with a resolution of 12 s.

RESULTS: Two types of muscle energy metabolism were identified from the pattern of spectroscopic time course in volunteers: While the first group was characterised by a remarkable decline to lower pH values during exercise, the second group showed only small pH shifts (minimum pH: 6.48 +/- 0.13 vs 6.87 +/- 0.07, p < 10(-6)) although comparable workload conditions were maintained. The pH-values correlated well with blood lactate analysis. Patients with metabolic disorders and chronic fatigue syndrome (CFS) showed decreased resting values of PCr/(PCr + Pi) and increased pH levels during exercise. PCr recovery was significantly delayed (0.31 vs 0.65 min-1, p < 0.00005) in metabolic muscle disorders but was normal in CFS patients.

CONCLUSION: Findings in volunteers indicate utilisation of different metabolic pathways which seems to be related to the fibre type composition of muscle. Reduced resting levels for PCr/(PCr + Pi), altered pH time courses, and decreased PCr recovery seem to be helpful indicators for diagnosis of metabolic muscle disorders.

Source: Block W, Träber F, Kuhl CK, Keller E, Lamerichs R, Karitzky J, Rink H, Schild HH. 31P-mr spectroscopy of peripheral skeletal musculature under load: demonstration of normal energy metabolites compared with metabolic muscle diseases. Rofo. 1998 Mar;168(3):250-7. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/9551111

Putting the rest cure to rest—again

Go home and rest” is still the advice given to many patients who complain of chronic fatigue. The refrain is echoed in self help books and magazines and adopted by many patients. What are the origins of rest as a treatment, does it work, and what evidence is there on which to base our advice to patients?

Victorian physicians diagnosed them as neurasthenia and routinely prescribed rest. This approach was typified by Silas Weir Mitchell’s “rest cure,” which was so popular as to be described as “the greatest advance of which practical medicine can boast in the last quarter of the century.” Despite such accolades, the popularity of the rest cure was short lived. By the turn of the century the same private clinics that once provided it were changing to more active treatments and to the newer psychotherapies. The years that followed saw the end of the rest cure; Karl Menninger poured scorn on the lack of psychological sophistication shown by its proponents, while Richard Asher drew attention to the “the dangers of going to bed.”

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1112768/

Comment in:

Treating chronic fatigue with exercise. Exercise improves mood and sleep. [BMJ. 1998]

Treating chronic fatigue with exercise. Exercise, and rest, should be tailored to individual needs. [BMJ. 1998]

Treating chronic fatigue with exercise. Results are contradictory for patients meeting different diagnostic criteria. [BMJ. 1998]

 

Source: Sharpe M, Wessely S. Putting the rest cure to rest—again. BMJ. 1998 Mar 14;316(7134):796. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1112768/ (Full article)

 

Lack of seasonal variation of symptoms in patients with chronic fatigue syndrome

Abstract:

Several of the symptoms involved in chronic fatigue syndrome (CFS) such as fatigue, hypersomnia, hyperphagia, weight gain, and mood show seasonal variations in the general population. The aim of this study was to investigate whether patients with CFS experience seasonal fluctuations in these symptoms as well.

Seasonal variation of symptoms was assessed in a group of 41 patients with CFS and 41 controls closely matched for age, gender, and city of residence. Participants were recruited across the US and were asked to complete the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Profile of Mood States (POMS). CFS patients showed significantly lower scores on multiple SPAQ-derived measures as compared with controls. These included seasonal variation in energy, mood, appetite, weight, and sleep length.

Patients also reported a significantly reduced sensitivity toward sunny, dry, and long days than controls. No association was noted between intensity of seasonal changes and severity of depressive symptoms. Patients with CFS exhibit an abnormally reduced seasonal variation in mood and behavior and would not be expected to benefit from light therapy.

 

Source: García-Borreguero D, Dale JK, Rosenthal NE, Chiara A, O’Fallon A, Bartko JJ, Straus SE. Lack of seasonal variation of symptoms in patients with chronic fatigue syndrome. Psychiatry Res. 1998 Feb 9;77(2):71-7. http://www.ncbi.nlm.nih.gov/pubmed/9541142

 

Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome

Abstract:

OBJECTIVES: To examine the proportions of type 1 and type 2 muscle fibres and the degree of muscle fibre atrophy and hypertrophy in patients with chronic fatigue syndrome in relation to lactate responses to exercise, and to determine to what extent any abnormalities found might be due to inactivity.

METHODS: Quadriceps needle muscle biopsies were obtained from 105 patients with chronic fatigue syndrome and the proportions of type 1 and 2 fibres and fibre atrophy and hypertrophy factors were determined from histochemical preparations, using a semiautomated image analysis system. Forty one randomly selected biopsies were also examined by electron microscopy. Lactate responses to exercise were measured in the subanaerobic threshold exercise test (SATET).

RESULTS: Inactivity would be expected to result in a shift to type 2 fibre predominance and fibre atrophy, but type 1 predominance (23%) was more common than type 2 predominance (3%), and fibre atrophy was found in only 10.4% of cases. Patients with increased lactate responses to exercise did have significantly fewer type 1 muscle fibres (p<0.043 males, p<0.0003 females), but there was no evidence that this group was less active than the patients with normal lactate responses. No significant ultrastructural abnormalities were found.

CONCLUSION: Muscle histometry in patients with chronic fatigue syndrome generally did not show the changes expected as a result of inactivity. However, patients with abnormal lactate responses to exercise had a significantly lower proportion of mitochondria rich type 1 muscle fibres.

 

Source: Lane RJ, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC. Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):362-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169994/ (Full article)

 

Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue

Abstract:

97 patients (25 per cent males, ages ranging from 14 to 73 years, median 38 years) with complaints of chronic fatigue (chronic fatigue syndrome, fibromyalgia or/and spasmophilia) have been enrolled in a prospective study to evaluate the Mg status and the dietary intake of Mg. An IV loading test (performed following the Ryzen protocol) showed a Mg deficit in 44 patients.

After Mg supplementation in 24 patients, the loading test showed a significant decrease (p = 0.0018) in Mg retention. Mean values of serum Mg, red blood cell Mg and magnesuria showed no significant difference between patients with or without Mg deficiency.

No association was found between Mg deficiency, CFS or FM. However serum Mg level was significantly lower in the patients with spasmophilia than in the other patients.

 

Source: Moorkens G, Manuel y Keenoy B, Vertommen J, Meludu S, Noe M, De Leeuw I. Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue. Magnes Res. 1997 Dec;10(4):329-37. http://www.ncbi.nlm.nih.gov/pubmed/9513929

 

 

 

 

Core body temperature is normal in chronic fatigue syndrome

Abstract:

BACKGROUND: Subjects with chronic fatigue syndrome (CFS) frequently report symptoms of subnormal body temperature and low-grade fever. We conducted a study to determine whether CFS subjects manifest any abnormality of core body temperature (CBT) that might help explain their fatigue.

METHODS: Continuous 24-hour recordings of CBT measured every 5 min were performed in 7 subjects meeting the Centers for Disease Control definition of CFS. Three additional groups were studied: normal controls, subjects with seasonal allergy, and subjects with major depression. Subjects (n = 7) in each group were age-, sex-, and weight-matched to the CFS group and had normal basal metabolic rates, thyroid function, and 24-hour urinary free cortisol excretions. CBT was measured with an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. Each pill was factory-calibrated to +/- 0.1 degree C and field-calibrated with a water bath calibration prior to use.

RESULTS: The 24-hour mean calibration-adjusted CBTs of each group were not significantly different (control: 37.00 +/- 0.17 degrees C; CFS: 37.04 +/- 0.31 degrees C; allergy: 37.15 +/- 0.18 degrees C; depression: 37.16 +/- 0.18 degrees C). Similarly, the mean peak and trough circadian temperatures were not statistically different. The mean 24-hour profile of CBT for each group showed a similar circadian rhythm. In simultaneously collected blood samples, each group showed a similar circadian profile of serum cortisol with a peak occurring at 08:00.

CONCLUSIONS: Subjects with CFS have normal CBT despite frequent self-reports of subnormal body temperature and low-grade fever.

 

Source: Hamilos DL, Nutter D, Gershtenson J, Redmond DP, Clementi JD, Schmaling KB, Make BJ, Jones JF. Core body temperature is normal in chronic fatigue syndrome. Biol Psychiatry. 1998 Feb 15;43(4):293-302. http://www.ncbi.nlm.nih.gov/pubmed/9513740

 

Chronic fatigue syndrome: an update

Abstract:

Among the many patients who seek medical care for the complaint of fatigue, a small number suffer from chronic fatigue syndrome (CFS). CFS is a poorly understood condition characterized by debilitating fatigue and associated symptoms lasting at least six months. Studies indicate that the illness is not simply a manifestation of an underlying psychiatric disorder, but rather is an illness characterized by activation of the immune system, various abnormalities of several hypothalamic-pituitary axes, and reactivation of certain infectious agents.

 

Source: Komaroff AL, Buchwald DS. Chronic fatigue syndrome: an update. Annu Rev Med. 1998;49:1-13. http://www.ncbi.nlm.nih.gov/pubmed/9509246