Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome

Abstract:

BACKGROUND: It has been suggested that postural orthostatic tachycardia syndrome (POTS) be considered in the differential diagnosis of those with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Currently, measurement of haemodynamic response to standing is not recommended in the UK NICE CFS/ME guidelines.

OBJECTIVES: To determine prevalence of POTS in patients with CFS/ME.

DESIGN: Observational cohort study.

METHODS: Fifty-nine patients with CFS/ME (Fukuda criteria) and 52 age- and sex-matched controls underwent formal autonomic assessment in the cardiovascular laboratory with continuous heart rate and beat-to-beat blood pressure measurement (Task Force, CNSystems, Graz Austria). Haemodynamic responses to standing over 2 min were measured. POTS was defined as symptoms of orthostatic intolerance associated with an increase in heart rate from the supine to upright position of >30 beats per minute or to a heart rate of >120 beats per minute on standing.

RESULTS: Maximum heart rate on standing was significantly higher in the CFS/ME group compared with controls (106 +/- 20 vs. 98 +/- 13; P = 0.02). Of the CFS/ME group, 27% (16/59) had POTS compared with 9% (5) in the control population (P = 0.006). This difference was predominantly related to the increased proportion of those in the CFS/ME group whose heart rate increased to >120 beats per minute on standing (P = 0.0002). Increasing fatigue was associated with increase in heart rate (P = 0.04; r(2) = 0.1).

CONCLUSION: POTS is a frequent finding in patients with CFS/ME. We suggest that clinical evaluation of patients with CFS/ME should include response to standing. Studies are needed to determine the optimum intervention strategy to manage POTS in those with CFS/ME.

 

Source: Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Dec;101(12):961-5. doi: 10.1093/qjmed/hcn123. Epub 2008 Sep 19. http://qjmed.oxfordjournals.org/content/101/12/961.long (Full article)

 

Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study

Abstract:

Deficient endogenous pain inhibition, e.g. Diffuse noxious inhibitory controls (DNIC), or hormonal abnormalities like hypocortisolism, could be responsible for chronic widespread pain in Chronic Fatigue Syndrome (CFS). Thirty-one CFS-patients with chronic pain and 31 healthy controls were subjected to spatial summation of thermal noxious stimuli by gradual immersion (ascending or descending) of the arm in warm water (46 degrees C). They rated pain intensity every 15s. Every immersion took 2 min, alternated with 5 min rest. Before and after immersion, salivary cortisol was assessed.

Overall pain ratings were higher in CFS-patients, but the evolution was not different between patients and controls, during both ascending and descending immersion. Pain intensity and immersed surface were only correlated during the descending session in both patients (r=.334) and controls (r=.346). When comparing the first and the last 15s of every emersion, it was found that pain inhibition starts slower for CFS-patients in comparison to healthy subjects. Both pre- or post-values and cortisol response did not differ between controls and patients. The drop in cortisol was significantly correlated to pain intensity in CFS (r between .357 and .402).

In addition to the hyperalgesia in CFS, DNIC react slower to spatial summation of thermal noxious stimuli. We found no evidence for hypocortisolism in CFS, and the cortisol response to nociception was not different in CFS compared to healthy subjects. In conclusion, delayed pain inhibition may play a role in chronic widespread pain in CFS but further research is required.

 

Source: Meeus M, Nijs J, Van de Wauwer N, Toeback L, Truijen S. Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study. Pain. 2008 Oct 15;139(2):439-48. doi: 10.1016/j.pain.2008.05.018. Epub 2008 Jul 9. https://www.ncbi.nlm.nih.gov/pubmed/18617327

 

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia

Abstract:

INTRODUCTION: We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal.

METHODS: We compared sleep structures and subjective scores on visual analog scales for sleepiness and fatigue in CFS patients with or without coexisting fibromyalgia (n = 12 and 14, respectively) with 26 healthy subjects. None had current major depressive disorder, and all were studied at the same menstrual phase.

RESULTS: CFS patients had significant differences in polysomnograpic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. CFS patients as a group had less total sleep time, lower sleep efficiency, and less rapid eye movement sleep than controls. A possible explanation for the unrefreshing quality of sleep in CFS patients was revealed by stratification of patients into those who reported more or less sleepiness after a night’s sleep (a.m. sleepier or a.m. less sleepy, respectively). Those in the sleepier group reported that sleep did not improve their symptoms and had poorer sleep efficiencies and shorter runs of sleep than both controls and patients in the less sleepy group; patients in the less sleepy group reported reduced fatigue and pain after sleep and had relatively normal sleep structures. This difference in sleep effects was due primarily to a decrease in the length of periods of uninterrupted sleep in the a.m. sleepier group.

CONCLUSION: CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. This difference was due neither to diagnosable sleep disorders nor to coexisting fibromyalgia but primarily to a decrease in the length of periods of uninterrupted sleep in the patients with more sleepiness in the morning than on the night before. This sleep disruption may explain the overwhelming fatigue, report of unrefreshing sleep, and pain in this subgroup of patients.

Comment in: How much sleep apnea is too much? [Arthritis Res Ther. 2009]

 

Source: Togo F, Natelson BH, Cherniack NS, FitzGibbons J, Garcon C, Rapoport DM. Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia. Arthritis Res Ther. 2008;10(3):R56. doi: 10.1186/ar2425. Epub 2008 May 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483445/ (Full article)

 

Breathing retraining in patients with chronic fatigue syndrome: a pilot study

Abstract:

The study aimed to 1) examine the point prevalence of asynchronous breathing in chronic fatigue syndrome (CFS) patients; 2) examine whether CFS patients with an asynchronous breathing pattern present with diminished lung function in comparison with CFS patients with a synchronous breathing pattern; and 3) examine whether one session of breathing retraining in CFS patients with an asynchronous breathing pattern is able to improve lung function.

Twenty patients fulfilling the diagnostic criteria for CFS were recruited for participation in a pilot controlled clinical trial with repeated measures. Patients presenting with an asynchronous breathing pattern were given 20-30 minutes of breathing retraining. Patients presenting with a synchronous breathing pattern entered the control group and received no intervention. Of the 20 enrolled patients with CFS, 15 presented with a synchronous breathing pattern and the remaining 5 patients (25%) with an asynchronous breathing pattern. Baseline comparison revealed no group differences in demographic features, symptom severity, respiratory muscle strength, or pulmonary function testing data (spirometry). In comparison to no treatment, the session of breathing retraining resulted in an acute (immediately postintervention) decrease in respiratory rate (p < 0.001) and an increase in tidal volume (p < 0.001). No other respiratory variables responded to the session of breathing retraining.

In conclusion, the present study provides preliminary evidence supportive of an asynchronous breathing pattern in a subgroup of CFS patients, and breathing retraining might be useful for improving tidal volume and respiratory rate in CFS patients presenting with an asynchronous breathing motion.

 

Source: Nijs J, Adriaens J, Schuermans D, Buyl R, Vincken W. Breathing retraining in patients with chronic fatigue syndrome: a pilot study. Physiother Theory Pract. 2008 Mar-Apr;24(2):83-94. Doi: 10.1080/09593980701429406. https://www.ncbi.nlm.nih.gov/pubmed/18432511

 

Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome

Abstract:

Physiological and/or pathological implications of the dynamics of sleep stage transitions have not, to date, been investigated. We report detailed duration and transition statistics between sleep stages in healthy subjects and in others with chronic fatigue syndrome (CFS); in addition, we also compare our data with previously published results for rats.

Twenty-two healthy females and 22 female patients with CFS, characterized by complaints of unrefreshing sleep, underwent one night of polysomnographic recording. We find that duration of deep sleep (stages III and IV) follows a power-law probability distribution function; in contrast, stage II sleep durations follow a stretched exponential and stage I, and REM sleep durations follow an exponential function. These stage duration distributions show a gradually increasing departure from the exponential form with increasing depth of sleep toward a power-law type distribution for deep sleep, suggesting increasing complexity of regulation of deeper sleep stages. We also find a substantial number of REM to non-REM sleep transitions in humans, while this transition is reported to be virtually nonexistent in rats.

The relative frequency of this REM to non-REM sleep transition is significantly lower in CFS patients than in controls, resulting in a significantly greater relative transition frequency of moving from both REM and stage I sleep to awake. Such an alteration in the transition pattern suggests that the normal continuation of sleep in light or REM sleep is disrupted in CFS. We conclude that dynamic transition analysis of sleep stages is useful for elucidating yet-to-be-determined human sleep regulation mechanisms with pathophysiological implications.

 

Source: Kishi A, Struzik ZR, Natelson BH, Togo F, Yamamoto Y. Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome. Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1980-7. doi: 10.1152/ajpregu.00925.2007. Epub 2008 Apr 16. http://ajpregu.physiology.org/content/294/6/R1980.long

 

Sexual dysfunction as related to severity of fatigue in women with CFS

Abstract:

To assess sexual function in women with chronic fatigue syndrome. The study included 27 women, aged 20 to 45 years, with chronic fatigue syndrome (CFS) and 15 healthy female controls. Sexual function was measured with the Golombok Rust Inventory of Sexual Satisfaction (GRISS) questionnaire and five clinical questions. In the patient group, total fatigue impact scale (FIS) score correlated with the GRISS satisfaction (r:-0.471, P < .005), avoidance (r: 0.632, P < .001) and sensuality (r: -0.445, P = .008) subscales. The GRISS satisfaction, avoidance, and sensuality subscale results and the fact of seeing the sexual act as a negative experience correlated with the intensity of fatigue in women with CFS.

 

Source: Blazquez A, Ruiz E, Vazquez A, de Sevilla TF, Garcia-Quintana A, Garcia-Quintana J, Alegre J. Sexual dysfunction as related to severity of fatigue in women with CFS. J Sex Marital Ther. 2008;34(3):240-7. doi: 10.1080/00926230701866232. https://www.ncbi.nlm.nih.gov/pubmed/18398762

 

Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine diurnal salivary cortisol rhythms and plasma IL-6 concentrations in persons with chronic fatigue syndrome (CFS), persons not fulfilling a diagnosis of CFS (we term them cases with insufficient symptoms or fatigue, ISF) and nonfatigued controls (NF). Previous studies of CFS patients have implicated the hypothalamic-pituitary-adrenal axis and the immune system in the pathophysiology of CFS, although results have been equivocal.

METHODS: Twenty-eight people with CFS, 35 persons with ISF, and 39 NF identified from the general population of Wichita, Kansas, were admitted to a research ward for 2 days. Saliva was collected immediately on awakening (6:30 AM), at 08:00 AM, 12 noon, 4:00 PM, 8:00 PM and at bedtime (10:00 PM) and plasma was obtained at 7:30 AM. Salivary cortisol concentrations were assessed using radioimmunoassay, and plasma IL-6 was measured using sandwich enzyme-linked immunosorbent assay.

RESULTS: People with CFS demonstrated lower salivary cortisol concentrations in the morning and higher salivary cortisol concentrations in the evening compared with both ISF and NF groups indicating a flattening of the diurnal cortisol profile. Mean plasma IL-6 concentrations were highest in CFS compared with the other groups, although these differences were no longer significant after controlling for BMI. Attenuated decline of salivary cortisol concentrations across the day and IL-6 concentration were associated with fatigue symptoms in CFS.

CONCLUSIONS: These results suggest an altered diurnal cortisol rhythm and IL-6 concentrations in CFS cases identified from a population-based sample.

 

Source: Nater UM, Youngblood LS, Jones JF, Unger ER, Miller AH, Reeves WC, Heim C. Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome. Psychosom Med. 2008 Apr;70(3):298-305. doi: 10.1097/PSY.0b013e3181651025. Epub 2008 Mar 31. https://www.ncbi.nlm.nih.gov/pubmed/18378875

 

The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome

Abstract:

Hypocortisolism has been reported in chronic fatigue syndrome (CFS), with the significance of this finding to disease etiology unclear. This study examined cortisol levels and their relationships with symptoms in a group of 108 individuals with CFS. CFS symptoms examined included fatigue, pain, sleep difficulties, neurocognitive functioning, and psychiatric status. Alterations in cortisol levels were examined by calculation of mean daily cortisol, while temporal variation in cortisol function was examined by means of a regression slope. Additionally, deviation from expected cortisol diurnal pattern was determined via clinical judgment. Results indicated that fatigue and pain were associated with salivary cortisol levels. In particular, variance from the expected pattern of cortisol was associated with increased levels of fatigue. The implications of these findings are discussed.

 

Source: Torres-Harding S, Sorenson M, Jason L, Maher K, Fletcher MA, Reynolds N, Brown M. The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome. J Appl Biobehav Res. 2008 Jan 1;13:157-180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/ (Full article)

 

Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes

Abstract:

AIM: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. The authors have recently reported a study of gene expression that identified differential expression of 88 human genes in patients with CFS/ME. Clustering of quantitative PCR (qPCR) data from patients with CFS/ME revealed seven distinct subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes and severity.

METHODS: In this study, for each CFS/ME subtype, those genes whose expression differed significantly from that of normal blood donors were identified, and then gene interactions, disease associations and molecular and cellular functions of those gene sets were determined. Genomic analysis was then related to clinical data for each CFS/ME subtype.

RESULTS: Genomic analysis revealed some common (neurological, haematological, cancer) and some distinct (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease associations among the subtypes. Subtypes 1, 2 and 7 were the most severe, and subtype 3 was the mildest. Clinical features of each subtype were as follows: subtype 1 (cognitive, musculoskeletal, sleep, anxiety/depression); subtype 2 (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4 (cognitive); subtype 5 (musculoskeletal, gastrointestinal); subtype 6 (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep, neurological, gastrointestinal, neurocognitive, anxiety/depression).

CONCLUSION: It was particularly interesting that in the seven genomically derived subtypes there were distinct clinical syndromes, and that those which were most severe were also those with anxiety/depression, as would be expected in a disease with a biological basis.

 

Source: Kerr JR, Burke B, Petty R, Gough J, Fear D, Mattey DL, Axford JS, Dalgleish AG, Nutt DJ. Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes. J Clin Pathol. 2008 Jun;61(6):730-9. Epub 2007 Dec 5. https://www.ncbi.nlm.nih.gov/pubmed/18057078

 

Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study

Abstract:

BACKGROUND: Complaints of unrefreshing sleep are a prominent component of chronic fatigue syndrome (CFS); yet, polysomnographic studies have not consistently documented sleep abnormalities in CFS patients. We conducted this study to determine whether alterations in objective sleep characteristics are associated with subjective measures of poor sleep quality in persons with CFS.

METHODS: We examined the relationship between perceived sleep quality and polysomnographic measures of nighttime and daytime sleep in 35 people with CFS and 40 non-fatigued control subjects, identified from the general population of Wichita, Kansas and defined by empiric criteria. Perceived sleep quality and daytime sleepiness were assessed using clinical sleep questionnaires. Objective sleep characteristics were assessed by nocturnal polysomnography and daytime multiple sleep latency testing.

RESULTS: Participants with CFS reported unrefreshing sleep and problems sleeping during the preceding month significantly more often than did non-fatigued controls. Participants with CFS also rated their quality of sleep during the overnight sleep study as significantly worse than did control subjects. Control subjects reported significantly longer sleep onset latency than latency to fall asleep as measured by PSG and MSLT. There were no significant differences in sleep pathology or architecture between subjects with CFS and control subjects.

CONCLUSION: People with CFS reported sleep problems significantly more often than control subjects. Yet, when measured these parameters and sleep architecture did not differ between the two subject groups. A unique finding requiring further study is that control, but not CFS subjects, significantly over reported sleep latency suggesting CFS subjects may have an increased appreciation of sleep behaviour that may contribute to their perception of sleep problems.

 

Source: Majer M, Jones JF, Unger ER, Youngblood LS, Decker MJ, Gurbaxani B, Heim C, Reeves WC. Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study. BMC Neurol. 2007 Dec 5;7:40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231384/ (Full article)