Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome

Abstract:

OBJECTIVE: We have investigated whether central activation failure (CAF) is increased during local muscle fatigue in chronic fatigue syndrome (CFS).

METHODS: Fourteen female CFS patients and 14 age-matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle. Before, during, and after sustained MVC, electrical endplate stimulation was applied. Force and 5 channel surface EMG (sEMG) were registered.

RESULTS: Although force responses upon stimulation during rest did not differ between patients and controls, MVC was significantly lower in patients. Already at the beginning of sustained MVC, CFS patients showed significantly larger CAF than controls (36.5+/-17.0% and 12.9+/-13.3%, respectively). For all individual patients mean CAF over the first 45 s was higher than 30%, while it was below 30% for all controls. Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction.

CONCLUSIONS: Central activation is diminished in CFS patients. Possible causes include changed perception, impaired concentration, reduced effort and physiologically defined changes, e.g. in the corticospinal excitability or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue.

SIGNIFICANCE: CFS patients show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined.

 

Source: Schillings ML, Kalkman JS, van der Werf SP, van Engelen BG, Bleijenberg G, Zwarts MJ. Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome. Clin Neurophysiol. 2004 Nov;115(11):2518-24. http://www.ncbi.nlm.nih.gov/pubmed/15465441

 

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

Abstract:

BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue.

METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects.

RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects.

CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue.

 

Source: Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N. Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol. 2004 Oct 4;4(1):14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524491/

 

Subjective and objective sleepiness in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

STUDY OBJECTIVE: To examine the association of chronic fatigue syndrome (CFS) with measures of objective and subjective sleepiness.

DESIGN: Monozygotic co-twin control study.

SETTING: Academic medical center.

PATIENTS AND PARTICIPANTS: Twenty monozygotic twin pairs discordant for CFS.

INTERVENTIONS: N/A.

MEASUREMENTS AND RESULTS: All twins completed an Epworth Sleepiness Scale (ESS), 4 Stanford Sleepiness Scales (SSS), and underwent a standard 4-nap multiple sleep latency test. We compared the ESS scores, average SSS scores, and average sleep latency in CFS and healthy twins. The CFS twins reported more sleepiness as measured by mean scores on the ESS (10.9 vs 8.2; 95% confidence interval [CI] = 0.3-5.5; P = .03) and the SSS (3.4 versus 2.1; 95% CI = 0.7-1.9; P < .001). The mean sleep latency on the Multiple Sleep Latency Test was not significantly different between the CFS and healthy twins (8.9 vs 10.0 minutes; 95% CI -4.4-1.7; P = .33). Mean SSS scores increased among the CFS twins and decreased among healthy twins from nap 1 to nap 4 (P < .001). The individual ESS scores and mean sleep latencies on the Multiple Sleep Latency Test were negatively correlated for all the twins (Pearson’s r = – 0.40; P = .01), with a slightly stronger association among the healthy twins (Pearson’s r = -0.42, P = .07) than the CFS twins (Pearson’s r = -0.36, P = .15).

CONCLUSIONS: CFS twins reported significantly more subjective sleepiness than their healthy co-twins despite similar nonpathologic mean sleep latencies on the Multiple Sleep Latency Test. Patients with CFS may mistake their chronic disabling fatigue for sleepiness.

 

Source: Watson NF, Jacobsen C, Goldberg J, Kapur V, Buchwald D. Subjective and objective sleepiness in monozygotic twins discordant for chronic fatigue syndrome. Sleep. 2004 Aug 1;27(5):973-7. http://www.ncbi.nlm.nih.gov/pubmed/15453557

 

Chronic fatigue syndrome impairs circadian rhythm of activity level

Abstract:

Some of the symptoms of chronic fatigue syndrome (CFS) are the same as for disrupted circadian rhythm. Activity level is frequently used to study circadian rhythm. Continuous waist activity measurements taken every minute 24 h/day for from 5 to 7 days in 10 controls and from 2 to 7 days in 8 patients with CFS yielded two primary findings: (a) lower daytime activity and (b) less regular activity-rest cycles in persons with CFS than in controls.

 

Source: Tryon WW, Jason L, Frankenberry E, Torres-Harding S. Chronic fatigue syndrome impairs circadian rhythm of activity level. Physiol Behav. 2004 Oct 15;82(5):849-53. http://www.ncbi.nlm.nih.gov/pubmed/15451649

 

Improving the diagnostic criteria and procedures for chronic fatigue syndrome

Abstract:

Since the publication of the case definition for chronic fatigue syndrome (CFS) in 1988 the diagnostic criteria have been revised twice in the U.S. None of the case definitions were derived empirically. As a result, there is concern regarding the sensitivity, specificity, and reliability of the criteria.

The goal of the present study was to identify methods for improving the diagnostic criteria for CFS. Three groups of 15 participants each were recruited: participants with (1) CFS, (2) major depressive disorder (MDD), and (3) healthy controls.

Using statistical procedures, three methods for improving the diagnostic criteria were explored: identification of new diagnostic symptoms, the use of severity ratings for symptomatology, and the identification of standardized measures that differentiate cases of CFS from other conditions. Results of the present study suggest that these three methods hold promise for improving the sensitivity, specificity, and reliability of the diagnostic criteria for CFS.

 

Source: King C, Jason LA. Improving the diagnostic criteria and procedures for chronic fatigue syndrome. Biol Psychol. 2005 Feb;68(2):87-106. http://www.ncbi.nlm.nih.gov/pubmed/15450690

 

Regional prevalence of fatiguing illnesses in the United States before and after the terrorist attacks of September 11, 2001

Abstract:

OBJECTIVE: Stress or emotional traumas are considered risk factors for unexplained fatiguing illnesses. From July to December 2001, the Centers for Disease Control and Prevention conducted a multigeographical pilot study to test the feasibility of a survey to estimate the prevalence of fatiguing illnesses in the United States. We used data obtained during this survey to estimate the effect of the coincidentally occurring terrorist attacks of September 11, 2001, on the regional prevalence of fatiguing illnesses.

METHODS: Identified by random-digit dialing, 2,728 households in eight regional strata were interviewed, and 7,317 respondents were screened for severe fatigue of at least 1 month duration. Identified fatigued people of age 18 to 69 years (N = 440) and a sample of nonfatigued people of the same age range (N = 444) were interviewed in detail concerning fatigue, other symptoms, and medical and psychiatric histories.

RESULTS: Weighted prevalence estimates based on interviews performed after the attacks were significantly lower compared with estimates based on interviews performed before the attacks (prolonged fatigue: 5,450 vs. 1,530/100,000, p =.010; chronic fatigue: 18,510 vs. 10,070/100,000, p =.002; chronic fatigue syndrome-like illness: 2,510 vs. 960/100,000, p =.014).

CONCLUSION: Our findings suggest decreased regional prevalence of fatiguing illnesses in the aftermath of the terrorist attacks. The causes of this effect are unknown but might involve acute psychological and physiological adaptations that modify the perception or manifestation of fatigue. Future studies should be specifically designed to scrutinize the relationship between stress and fatiguing illnesses and the mediating mechanisms of such a relationship.

 

Source: Heim C, Bierl C, Nisenbaum R, Wagner D, Reeves WC. Regional prevalence of fatiguing illnesses in the United States before and after the terrorist attacks of September 11, 2001. Psychosom Med. 2004 Sep-Oct;66(5):672-8. http://www.ncbi.nlm.nih.gov/pubmed/15385690

 

Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome

Abstract:

OBJECTIVE: To compare effectiveness of oral therapy with reduced nicotinamide adenine dinucleotide (NADH) to conventional modalities of treatment in patients with chronic fatigue syndrome (CFS).

BACKGROUND: CFS is a potentially disabling condition of unknown etiology. Although its clinical presentation is associated to a myriad of symptoms, fatigue is a universal and essential finding for its diagnosis. No therapeutic regimen has proven effective for this condition.

METHODS: A total of 31 patients fulfilling the Centers for Disease Control criteria for CFS, were randomly assigned to either NADH or nutritional supplements and psychological therapy for 24 months. A thorough medical history, physical examination and completion of a questionnaire on the severity of fatigue and other symptoms were performed each trimester of therapy. In addition, all of them underwent evaluation in terms of immunological parameters and viral antibody titers. Statistical analysis was applied to the demographic data, as well as to symptoms scores at baseline and at each trimester of therapy.

RESULTS: The twelve patients who received NADH had a dramatic and statistically significant reduction of the mean symptom score in the first trimester (p < 0.001). However, symptom scores in the subsequent trimesters of therapy were similar in both treatment groups. Elevated IgG and Ig E antibody levels were found in a significant number of patients.

CONCLUSIONS: Observed effectiveness of NADH over conventional treatment in the first trimester of the trial and the trend of improvement of that modality in the subsequent trimesters should be further assessed in a larger patient sample.

 

Source: Santaella ML, Font I, Disdier OM. Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. P R Health Sci J. 2004 Jun;23(2):89-93. http://www.ncbi.nlm.nih.gov/pubmed/15377055

 

The feeling of fatigue–fatigue severity by unidimensional versus composite questionnaires

Abstract:

The authors’ purpose in this study was to compare the perception of fatigue severity as measured by different fatigue questionnaires. The authors evaluated 3 groups of patients in a cross-sectional study: chronic fatigue syndrome (CFS, n = 20), non-CFS fatigue (n = 20), and familial Mediterranean fever (FMF n = 25). In addition, the authors tracked 7 patients with CFS longitudinally for severity of fatigue.

The severity of fatigue-related symptoms was assessed with 2 questionnaires: the unidimensional Chalder’s Fatigue Severity Scale (CH) and the composite Fatigue Impact Scale (FI) which has 3 subscales–cognitive, physical, and social–and a total score.

In the cross-sectional study, correlations between CH and FI cognitive scores were r = .78 (p < .0001), CH versus FI physical scores r = .603 (p < .0001), CH versus FI social scores r = .66 (p < .0001), and CH versus FI total scores r = .74 (p < .0001).

In the longitudinal survey of CFS patients, the authors compared 30 questionnaires revealing correlations of CH versus FI cognitive scores r = .64 (p = .0004), CH versus FI physical r = .68 (p = .0001), CH versus FI social r = .87 (p < .0001), and CH versus FI total r = .90 (p < .0001).

Fatigue severity as assessed by the unidimensional CH scale and the composite FI scale is comparable. The simple CH scale may be adequate for the assessment of the feeling of fatigue, in general, and for monitoring the severity of fatigue in CFS, in particular.

 

Source: Naschitz JE, Rozenbaum M, Shaviv N, Fields MC, Enis S, Babich JP, Manor H, Yeshurun D, Sabo E, Rosner I. The feeling of fatigue–fatigue severity by unidimensional versus composite questionnaires. Behav Med. 2004 Winter;29(4):167-72. http://www.ncbi.nlm.nih.gov/pubmed/15369197

 

Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome

Abstract:

We reported unique incomplete herpesvirus (Epstein-Barr Virus (EBV) and/or nonstructural (HCMV) cytomegalovirus) multiplication in 2 distinct subsets of CFS patients. The CFS subsets were identified by: a) presence of IgM serum antibodies to HCMV nonstructural gene products p52 and CM2 (UL44 and UL57), and/or b) IgM serum antibodies to Epstein-Barr virus viral capsid antigen (EBV, VCA IgM).

Diagnostic IgM serum antibodies were found in two independent blinded studies involving 49 CFS patients, but the same antibodies were absent in 170 control patients (p<0.05). Abnormal 24 Hr-electrocardiographic monitoring, tachycardias at rest and, in severe chronic cases, abnormal cardiac wall motion (ACWM) were seen in these same CFS patients.

We now report a prospective consecutive case control study from 1987–1999 of cardiac dynamics as measured by radionuclide ventriculography in 98 CFS patients from 1987–1999. Controls were patients with various malignancies who were evaluated in protocols requiring radionuclide ventriculography before initiation of cardiotoxic chemotherapeutic agents.

The prevalence of abnormal cardiac wall motion (ACWM) at rest in CFS patients was 10 out of 87 patients (11.5%). With stress exercise, 21 patients (24.1%) demonstrated ACWM. Cardiac biopsies in 3 of these CFS patients with ACWM showed a cardiomyopathy. Among the controls, ACWM at rest was present in 4 out of 191 patients (2%) (p=0.0018). A progressive cardiomyopathy caused by incomplete virus multiplication of EBV and/or HCMV in CFS patients is present.

 

Source: Lerner AM, Dworkin HJ, Sayyed T, Chang CH, Fitzgerald JT, Beqaj S, Deeter RG, Goldstein J, Gottipolu P, O’Neill W. Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of Epstein-barr Virus and/or cytomegalovirus in patients with chronic fatigue syndrome. In Vivo. 2004 Jul-Aug;18(4):417-24. http://iv.iiarjournals.org/content/18/4/417.long (Full article)

 

Development of the chronic fatigue syndrome in severely fatigued employees: predictors of outcome in the Maastricht cohort study

Abstract:

STUDY OBJECTIVE: To identify risk factors of the development of the chronic fatigue syndrome (CFS), the persistence or recurrence of fatigue, or recovery from fatigue in a large sample of fatigued employees.

DESIGN: Analyses were based on the Maastricht cohort study (MCS), a prospective population based cohort study among more than 12 000 employees. Multiple regression models were used to identify predictors of CFS-like caseness (meeting research criteria for CFS), non-CFS fatigue caseness, or no fatigue caseness.

SETTING: The working population in the Netherlands.

PARTICIPANTS: 1143 employees with medically unexplained fatigue were followed up prospectively for 44 months.

MAIN RESULTS: At 44 month follow up, 8% of the employees were CFS-like cases (none of who reported to have received a CFS diagnosis), 40% were non-CFS fatigue cases, and 52% were no longer fatigue cases. Factors that predicted CFS-like caseness compared with non-CFS fatigue caseness were high age, exhaustion, female sex, low education, and visits to the general practitioner. Factors that predicted CFS-like caseness compared with no fatigue caseness were fatigue, exhaustion, low education, visits to the GP and occupational physician, and bad self rated health. Factors that predicted non-CFS fatigue caseness compared with no fatigue caseness were fatigue, low self perceived activity, exhaustion, anxious mood, and bad self rated health.

CONCLUSIONS: Unexplained fatigue among employees in some instances is a precursor of the development of CFS. The prognostic role of self rated health suggests that prevention and treatment of chronic fatigue should be aimed at changing the perception of health or illness. Less clear is the role of health care seeking or receiving a CFS diagnosis.

 

Source: Huibers MJ, Kant IJ, Knottnerus JA, Bleijenberg G, Swaen GM, Kasl SV. Development of the chronic fatigue syndrome in severely fatigued employees: predictors of outcome in the Maastricht cohort study. J Epidemiol Community Health. 2004 Oct;58(10):877-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1763327/