A System Theoretic Investigation of Cortisol Dysregulation in Fibromyalgia Patients with Chronic Fatigue

Abstract:

Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome (CFS) are complex medical conditions with similar symptoms such as anxiety, fatigue, depression, headaches, muscle aches and joint pain. The etiology of both these syndromes is unknown. The objective of this study is to characterize FMS, both in the presence and in the absence of CFS, by analyzing variations in cortisol secretion patterns, timings, amplitudes, and the number of the underlying pulses as well as infusion and clearance rates.

The comparison is performed against matched healthy control subjects. We estimate the hormonal secretory events by deconvolving cortisol data using a two-step coordinate descent approach. The first step implements a sparse recovery approach to infer the amplitudes and the timings of the cortisol secretion events from limited cortisol hormone data. The main advantage of this method is estimating the cortisol secretory events using a system theoretic approach. The second step is to estimate the physiological system parameters (i.e. infusion and clearance rates). This approach has been verified on healthy individuals previously.

Our results show that the clearance rate of cortisol by the liver is relatively lower in patients as compared to the matched healthy individuals. This suggests that there is a relatively higher accumulation of serum cortisol in patients when compared to matched healthy subjects.

Source: Pednekar DD, Amin MR, Azgomi HF, Aschbacher K, Crofford LJ, Faghih RT. A System Theoretic Investigation of Cortisol Dysregulation in Fibromyalgia Patients with Chronic Fatigue. Conf Proc IEEE Eng Med Biol Soc. 2019 Jul;2019:6896-6901. doi: 10.1109/EMBC.2019.8857427. https://www.ncbi.nlm.nih.gov/pubmed/31947425

Patients with fibromyalgia and chronic fatigue syndrome show increased hsCRP compared to healthy controls

Abstract:

Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are both chronic disorders that have a devastating effect on the lives of the affected patients and their families. Both conditions have overlapping clinical features that partly resemble those of inflammatory disorders. The etiology is still not understood, and it is suggested that the immune system might be a contributing factor. So far, the results are inconclusive. The purpose of this study was to compare the two conditions and investigate the level of the inflammatory marker high-sensitivity CRP (hsCRP) in CFS and FM patients compared to healthy controls.

Female participants aged 18-60 years were enrolled in this study. The group consisted of 49 CFS patients, 57 FM patients, and 54 healthy controls. hsCRP levels were significantly higher for both the CFS and the FM groups compared to healthy controls when adjusting for age, smoking, and BMI (p < .001).

There was no difference between the two patient groups. The level of hsCRP was affected by BMI but not by age and smoking. Patients with CFS and FM have higher concentrations of hsCRP compared to healthy controls. This remains significant even after adjusting for BMI. CFS and FM cannot be distinguished from each other on the basis of hsCRP in our study.

Copyright © 2019. Published by Elsevier Inc.

Source: Groven N, Fors EA, Klæbo Reitan S. Patients with fibromyalgia and chronic fatigue syndrome show increased hsCRP compared to healthy controls. Brain Behav Immun. 2019 Jun 6. pii: S0889-1591(19)30208-9. doi: 10.1016/j.bbi.2019.06.010. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31176728

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences

Abstract:

This commentary presents a simplified way of making the diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) using the 1994 Centers for Disease Control and Prevention case definition. The format used can easily be modified for other case definitions. The commentary then discusses whether ME/CFS is the same or a different illness from fibromyalgia.

Because overlap exists between the 2 syndromes, some investigators have posited that they are variants of the same illness. I have viewed this as an empirically testable hypothesis and have summoned considerable amounts of data that suggest that the 2 illnesses differ. Were differences to exist, that would suggest different pathophysiologic processes for each, leading to different treatments.

Copyright © 2019. Published by Elsevier Inc.

Source: Natelson BH. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences. Clin Ther .2019 Feb 19. pii: S0149-2918(19)30003-7. doi: 10.1016/j.clinthera.2018.12.016. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/30795933

Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population

Abstract:

INTRODUCTION: Silicone breast implants (SBI) may induce systemic autoimmune disease as part of autoimmune syndrome induced by adjuvants (ASIA). This syndrome bears similarities to fibromyalgia and chronic fatigue syndrome (CFS). We sought to determine whether there are any associations between SBI and depression, fibromyalgia and CFS in a rheumatology clinic population.

METHODS: The electronic files of rheumatology clinic patients at the Royal Adelaide Hospital between 2000 and 2017 were searched for patients who had received SBI prior to rheumatological diagnosis. Demographics, diagnosis, implant history and whether the patient had depression, fibromyalgia or CFS were recorded. Controls were rheumatology clinic patients, half of whom had systemic sclerosis (SSc) and the other half had systemic lupus erythematosus (SLE). They were matched to cases 3:1 for age (within 2 years) and gender.

RESULTS: Thirty patients had received SBI (mean age 47.9, 100% female). Twelve had a diagnosis of depression, 6 of fibromyalgia and 3 of CFS. Implant rupture was not associated with any of these (p = 1). There was no difference in the incidence of depression (p = 1), fibromyalgia (p = 0.76) or CFS (p = 0.3) between cases and SLE controls. When compared with SSc controls, there were significantly more patients with fibromyalgia and/or CFS in the case group (20.0% of cases vs 2.2% of SSc controls, p = 0.01) but no difference in depression (p = 0.12).

CONCLUSION: Fibromyalgia and CFS are more common in patients with silicone implants than SSc controls but not SLE controls. Prospective study of development of depression, fibromyalgia and CFS in recipients of SBI is required.

Source: Khoo T, Proudman S, Limaye V. Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population. Clin Rheumatol. 2019 Jan 31. doi: 10.1007/s10067-019-04447-y. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30706290

Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia

Abstract:

OBJECTIVE: Chronic Fatigue Syndrome (CFS) is a disorder of unknown etiology associated with debilitating fatigue. One symptom commonly reported is disequilibrium. The goal of this study was to determine if CFS patients demonstrated verified balance deficits and if this was effected by comorbid fibromyalgia (FM).

METHODS: Twenty-seven patients with CFS (12 with comorbid FM) and 22 age and gender matched controls performed posturography.

RESULTS: Balance scores were significantly correlated with physical functional status in the CFS group (R2 = 0.43, P < 0.001), which was not found for mental functional status (R2 = 0.06, P > 0.5). CFS patients (regardless of FM) had significantly higher anxiety subscale of the vertigo symptom scale scores. CFS patients, regardless of FM status, demonstrated significantly lower overall composite balance scores (Controls – 78.8±1.5; CFS – 69.0±1.4, P < 0.005) even when controlling for anxiety and also had worse preference scores, indicating they relied on visual information preferentially even when visual information was incorrect. Interestingly, the CFS+FM group, not CFS only, demonstrated significantly worse vestibular scores (Controls – 70.2±2.4; CFS only – 67.9±3.8; CFS with FM – 55.4±4.6, P = 0.013).

INTERPRETATION: The major findings are that poor balance may be associated with poorer self-reported physical health. In addition, CFS patients seemed to rely preferentially on visual inputs, regardless of whether it was correct. The finding that vestibular function may be impaired in patients with CFS+FM but not in those with CFS alone suggests that the pathophysiology of CFS+FM may differ as has been suggested by some.

Source: Serrador JM, Quigley K, Zhao C, Findley T, Natelson BH. Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia. NeuroRehabilitation. 2018;42(2):235-246. doi: 10.3233/NRE-172245.

Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: Dyspnea perception is distorted in patients with medically unexplained dyspnea. The goals of this study were 1) to replicate these results in patients with fibromyalgia and/or chronic fatigue syndrome (CFS), and 2) to investigate predictors of distorted symptom perception within the patient group, with a focus on negative affectivity (NA), psychiatric comorbidity and somatic symptom severity.

METHODS: Seventy-three patients diagnosed with fibromyalgia and/or CFS and 38 healthy controls (HC) completed a rebreathing paradigm, consisting of a baseline (60s of room air), a rebreathing phase (150s, gradually increasing ventilation, partial pressure of CO2 in the blood, and self-reported dyspnea), and a recovery phase (150s of room air). Dyspnea, respiratory flow and FetCO2 levels were measured continuously.

RESULTS: Patients reported more dyspnea than HC in the recovery phase (p=0.039), but no differences between patients and HC were found in the baseline (p=0.07) or rebreathing phase (p=0.17). No significant differences between patients and HC were found in physiological reactivity. Within the patient group, the effect in the recovery phase was predicted by somatic symptom severity (p=0.046), but not by negative affectivity or by the number of psychiatric comorbidities.

CONCLUSION: This study extended earlier findings in patients with medically unexplained dyspnea to patients with fibromyalgia and CFS. This suggests that altered symptom perception is a non-symptom-specific mechanism underlying functional somatic syndromes in general, particularly in patients with high levels of somatic symptom severity. The results are discussed in a predictive coding framework of symptom perception.

Source: Van Den Houte M, Bogaerts K, Van Diest I, De Bie J, Persoons P, Van Oudenhove L, Van den Bergh O. Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome. J Psychosom Res. 2018 Mar;106:49-55. doi: 10.1016/j.jpsychores.2018.01.007. Epub 2018 Jan 11. https://www.ncbi.nlm.nih.gov/pubmed/29455899

Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia

Abstract:

Background: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) frequently have overlapping symptoms, leading to the suggestion that the same disease processes may underpin the two disorders – the unitary hypothesis. However, studies investigating the two disorders have reported substantial clinical and/or biological differences them, suggesting distinct pathophysiological underpinnings.

Purpose: The purpose of this study was to further add to the body of evidence favoring different disease processes in CFS and FM by comparing ventricular cerebrospinal fluid lactate levels among patients with CFS alone, FM alone, overlapping CFS and FM symptoms, and healthy control subjects.

Methods: Ventricular lactate was assessed in vivo with proton magnetic resonance spectroscopic imaging (1H MRSI) with the results normed across the 2 studies in which the data were collected.

Results: Mean CSF lactate levels in CFS, FM and CFS+FM did not differ among the three groups, but were all significantly higher than the mean values for control subjects.

Conclusion: While patients with CFS, FM and comorbid CFS and FM can be differentiated from healthy subjects based on measures of CFS lactate, this neuroimaging outcome measure is not a viable biomarker for differentiating CFS from FM or from patients in whom symptoms of the two disorders overlap.

Source: Natelson BH, Vu D, Coplan JD, Mao X, Blate M, Kang G, Soto E, Kapusuz T, Shungu DC. Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia. Fatigue. 2017;5(1):15-20. doi: 10.1080/21641846.2017.1280114. Epub 2017 Feb 20.  https://www.ncbi.nlm.nih.gov/pubmed/29308330 

 

Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients

Abstract:

BACKGROUND: Myalgic encephalomyelitis chronic fatigue syndrome (ME/CFS) is a common debilitating disorder associated with an intense fatigue, a reduced physical activity, and an impaired quality of life. There are no established biological markerof the syndrome. The etiology is unknown and its pathogenesis appears to be multifactorial. Various stressors, including intense physical activity, severe infection, and emotional stress are reported in the medical history of ME/CFS patients which raises the question whether any physiological and biological abnormalities usually found in these patients could be indicative of the etiology and/or the quality-of-life impairment.

METHODS: Thirty-six patients and 11 age-matched healthy controls were recruited. The following variables that appear to address common symptoms of ME/CFS were studied here: (1) muscle fatigue during exercise has been investigated by monitoring the compound muscle action potential (M-wave); (2) the excessive oxidative stress response to exercise was measured via two plasma markers (thiobarbituric acid reactive substances: TBARS; reduced ascorbic-acid: RAA); (3) a potential inflammatory component was addressed via expression of CD26 on peripheral blood mononuclear cells; (4) quality-of-life impairment was assessed using the London Handicap Scale (LHS) and the Medical Outcome Study Short Form-36 (SF-36). The medical history of each patient, including the presence of stressors such as intense sports practice, severe acute infection and/or severe emotional stress was documented.

RESULTS: We observed that: (1) there were striking differences between cases and controls with regard to three biological variables: post-exercise M-wave, TBARS variations and CD26-expression at rest; (2) each of these three variables correlated with the other two; (3) abnormalities in the biomarkers associated with health-related quality of life: the LHS score was negatively correlated with the exercise-induced TBARS increase and positively correlated with CD26-expression while the pain component of SF-36 was negatively correlated with CD26-expression; (4) the TBARS increase and the M-wave decrease were the highest, and the CD26-expression level the lowest in patients who had been submitted to infectious stressors.

CONCLUSION: In ME/CFS patients, severe alterations of the muscle excitability, the redox status, as well as the CD26-expression level are correlated with a marked impairment of the quality-of-life. They are particularly significant when infectious stressors are reported in the medical history.

 

Source: Fenouillet E, Vigouroux A, Steinberg JG, Chagvardieff A, Retornaz F, Guieu R, Jammes Y. Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients. J Transl Med. 2016 Aug 31;14:251. doi: 10.1186/s12967-016-1010-x. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006431/ (Full article)

 

Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia

Abstract:

PURPOSE: The purpose of this study was to conduct a longitudinal examination of cognitive complaints and functional status in patients with chronic fatigue syndrome (CFS) alone and those who also had fibromyalgia (CFS/FM).

METHODS: A total of 93 patients from a tertiary care fatigue clinic were evaluated on four occasions, each 6 months apart. Each evaluation included a tender point assessment, and self-reported functional status and cognitive complaints.

RESULTS: Patients with CFS/FM reported significantly worse physical functioning, more bodily pain, and more cognitive difficulties (visuo-perceptual ability and verbal memory) than patients with CFS alone. Over time, bodily pain decreased only for participants with CFS alone. Verbal memory problems were associated with more bodily pain for both patient groups, whereas visuo-perceptual problems were associated with worse functional status for patients with CFS alone.

CONCLUSIONS: This study adds to the literature on functional status, longitudinal course, and cognitive difficulties among patients with CFS and those with CFS and FM. The results suggest that patients with CFS/FM are more disabled, have more cognitive complaints, and improve more slowly over time than patients with CFS alone. Specific cognitive difficulties are related to worse functional status, which supports the addition of cognitive difficulties to the FM case criteria.

 

Source: Schmaling KB, Betterton KL. Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia. Qual Life Res. 2016 May;25(5):1257-63. doi: 10.1007/s11136-015-1160-y. Epub 2015 Oct 15. https://www.ncbi.nlm.nih.gov/pubmed/26471263

 

Chronic fatigue syndrome and fibromyalgia in diagnosed sleep disorders: a further test of the ‘unitary’ hypothesis

Abstract:

BACKGROUND: Since chronic fatigue syndrome (CFS) and fibromyalgia (FM) often co-exist, some believe they reflect the same process, somatization. Against that hypothesis are data suggesting FM but not CFS was common in patients with sleep-disordered breathing (SDB). The presence of discrete case definitions for CFS and FM allowed us to explore rates of CFS alone, CFS with FM, and FM alone in SDB patients compared to those with sleep complaints that fulfilled criteria for insomnia.

METHODS: Participants were 175 sequential patients with sleep-related symptoms (122 had SDB and 21 had insomnia) and 39 healthy controls. Diagnoses were made by questionnaires, tender point count, and rule out labs; sleepiness was assessed with Epworth Sleepiness Scale and mood with Beck Depression Inventory.

RESULTS: Rates of CFS, FM or CFS + FM were high: 13% in SDB and 48% in insomnia. CFS occurred frequently in SDB and insomnia, but FM occurred frequently only in insomnia. SDB patients with CFS and/or FM had higher daytime sleepiness than those without these disorders.

CONCLUSION: CFS patients should complete Epworth scales, and sleep evaluation should be considered for those with scores ≥ 16 before receiving the diagnosis of CFS; the coexistence of depressed mood in these patients suggests some may be helped by treatment of their depression. That FM was underrepresented in SDB suggests FM and CFS may have different underlying pathophysiological causes.

 

Source: Pejovic S, Natelson BH, Basta M, Fernandez-Mendoza J, Mahr F, Vgontzas AN. Chronic fatigue syndrome and fibromyalgia in diagnosed sleep disorders: a further test of the ‘unitary’ hypothesis. BMC Neurol. 2015 Apr 12;15:53. doi: 10.1186/s12883-015-0308-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405866/ (Full article)