Cerebral Blood Flow and Heart Rate Variability in Chronic Fatigue Syndrome: A Randomized Cross-Over Study

Abstract:

BACKGROUND: Pain, fatigue, and concentration difficulties are typical features of chronic fatigue syndrome (CFS). The exact underlying mechanisms of these symptoms are still unknown, but available evidence suggests an important role for impaired pain modulation. As evidence also suggests that pain modulation is related to cardiovascular mechanisms, it seems logical to investigate whether cerebral blood flow (CBF) and heart rate variability (HRV) are altered in these patients.

OBJECTIVES: We aimed to investigate the role of the cardiovascular system in pain modulation and symptoms of CFS; the response of CBF and HRV to physical stress and their relation to the change in temporal summation (TS) of pressure pain and self-reported symptoms was evaluated.

STUDY DESIGN: A controlled, randomized cross-over trial.

SETTING: University Hospital Brussels.

METHODS: Twenty CFS patients and 20 sedentary healthy controls were included in this study. In both of the groups, the change in TS of pressure pain, CBF (using transcranial Doppler), and HRV (using finger plethysmography) was examined during physical and emotional stress (to control for potential bias), as well as their association mutually and with self-reported symptoms of pain, fatigue, and concentrations difficulties.

RESULTS: There was no significant interaction or group (F-values ranging from .100 to 1.862, P-values ranging from .754 to .181) effect in CBF or HRV parameters. HRV and CBF did change during physical exercise, but the changes did not differ between patients and controls. While pain scores during TS at the trapezius site reduced in the control group after the physical exercise protocol (P = .037), they did not change in the CFS group (P = .108), suggesting impaired pain modulation. There were no significant correlations between CBF, HRV, TS, and self-reported symptoms (all P-values of correlation analyses > .01).

LIMITATIONS: Although effect sizes were medium to large, the study sample was relatively low. Also, the mild nature of the exercise bout is discussable. Nonetheless, this mild exercise was able to provoke endogenous pain modulation in the control group, which endorsed a proper execution of the cycling exercise. Moreover, mild exercises are more applicable to daily physical activities in CFS patients than vigorous exercises.

CONCLUSION: These results seem to refute the previously suggested alterations of CBF/HRV in CFS patients. These cardiovascular parameters appear not to explain pain before, during, and following exercise.

Source: Malfliet A, Pas R, Brouns R, De Win J, Hatem SM, Meeus M, Ickmans K, van Hooff RJ, Nijs J. Cerebral Blood Flow and Heart Rate Variability in Chronic Fatigue Syndrome: A Randomized Cross-Over Study. Pain Physician. 2018 Jan;21(1):E13-E24. https://www.ncbi.nlm.nih.gov/pubmed/29357332 Full article can be viewed as a PDF here: http://www.painphysicianjournal.com/current/pdf?article=NTAwOA%3D%3D&journal=109

Chronic fatigue syndrome treated with transcutaneous electrical acupoint stimulation: a randomized controlled trial

Abstract:

OBJECTIVE: To evaluate the clinical therapeutic effects and safety of chronic fatigue syndrome treated with transcutaneous electrical acupoint stimulation (TEAS) on the conception vessel and the governor vessel.

METHODS: Eighty-nine patients of chronic fatigue syndrome were randomized into an observation group (46 cases) and a control group (43 cases). In the observation group, TEAS was applied at Dazhui (GV 14) and Mingmen (GV 4), Shenque (CV 8) and Guanyuan (CV 4) [the current intensity: (14±2) mA]. In the control group, the simulated TEAS was applied at the same acupoints as the observation group (the current intensity: 1 mA). The treatment was given for 30 min, once a day, 5 times a week and the treatment of 4 weeks was as 1 session in the two groups. One session of treatment was required. Before treatment and at the end of 1 session of treatment, the fatigue severity scale (FSS) was adopted to evaluate the fatigue symptoms and the somatic and psychological health report (SPHERE) was adopted to evaluate the potential symptoms and observe the safety of TEAS therapy.

RESULTS: At the end of treatment, FSS score and SPHERE score in the control group were not different significantly as compared with those before treatment (both P>0.05). FSS score and SPHERE score in the observation group were reduced significantly as compared with those before treatment (both P<0.01). FSS score and SPHERE score in the observation group were reduced apparently as compared with those in the control group (both P<0.001). In the entire process of treatment with TEAS, no any adverse reaction occurred.

CONCLUSION: TEAS on the conception vessel and the governor vessel relieves fatigue symptoms and the potential symptoms in the patients of chronic fatigue syndrome. It is a safe therapy.

Source: Li J, Xie J, Pan Z, Guo X, Li Y, Fu R. Chronic fatigue syndrome treated with transcutaneous electrical acupoint stimulation: a randomized controlled trial. Zhongguo Zhen Jiu. 2017 Dec 12;37(12):1276-9. doi: 10.13703/j.0255-2930.2017.12.006. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/29354991

Chaihu Longgu Muli decoction combined with acupuncture at back-shu points for chronic fatigue syndrome

Abstract:

OBJECTIVE: To observe the effect difference between Chaihu Longgu Muli decoction combined with acupuncture at back-shu points and simple Chaihu Longgu Muli decoction for chronic fatigue syndrome.

METHODS: Sixty patients were randomly assigned into an herbal group and a combination group, 30 cases in each one. Simple Chaihu Longgu Muli decoction was used in the herbal group for continuous one month, one decoction a day. Based on that in the herbal group, 30 min acupuncture was used in the combination group at bilateral Xinshu (BL 15), Feishu (BL 13), Pishu (BL 20), Ganshu (BL 18) and Shenshu (BL 23), with acupoints according to syndrome differentiation. Acupuncture was given for 3 courses, 10 times as a course with 3 days between two courses, once a day. Fatigue status was evaluated before and after treatment by fatigue scale 14 (FS-14) and self-rating anxiety scale (SAS).

RESULTS: The FS-14 scores, including body fatigue scores, mental fatigue scores and total scores, and SAS scores after treatment were lower than those before treatment in the two groups (all P<0.01), with better improvements in the combination group (all P<0.01).

CONCLUSION: Chaihu Longgu Muli decoction combined with acupuncture at back-shu points can improve chronic fatigue syndrome, which are better than simple Chaihu Longgu Muli decoction.

Source: Qi Y, Song S, Dou Z, Chen J, He G, Zhang L, Yao J. Chaihu Longgu Muli decoction combined with acupuncture at back-shu points for chronic fatigue syndrome. Zhongguo Zhen Jiu. 2017 Nov 12;37(11):1187-90. doi: 10.13703/j.0255-2930.2017.11.013. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/29354956

Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by fatigue lasting for at least six months, post-exertional malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance. ME/CFS has been a controversial illness because it is defined exclusively by subjective complaints. However, recent studies of neuroimaging as well as analysis of blood markers, energy metabolism and mitochondrial function have revealed many objective biological abnormalities. Specifically, it is suspected that the symptoms of ME/CFS may be triggered by immune activation – either inside or outside the brain – through release of inflammatory cytokines. In this review, we summarize potentially important recent findings on ME/CFS, focusing on objective evidence.

Source: Komaroff AL, Takahashi R, Yamamura T, Sawamura M. Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review. Brain Nerve. 2018 Jan;70(1):41-54. doi: 10.11477/mf.1416200948. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/29348374

Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years after Giardia Infection

Abstract:

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a complication that can follow gastrointestinal infection, but it is not clear if patients also develop chronic fatigue. We investigated the prevalence and odds ratio of IBS and chronic fatigue 10 years after an outbreak of Giardia lamblia, compared with a control cohort, and changes in prevalence over time.

METHODS: We performed a prospective follow-up study of 1252 laboratory-confirmed cases of giardiasis (exposed), which developed in Bergen, Norway in 2004. Statistics Norway provided us with information from 2504 unexposed individuals from Bergen, matched by age and sex (controls). Questionnaires were mailed to participants 3, 6, and 10 years after the outbreak. Results from the 3- and 6-year follow-up analyses have been published previously. We report the 10-year data and changes in prevalence among time points, determined by logistic regression using generalized estimating equations.

RESULTS: The prevalence of IBS 10 years after the outbreak was 43% (n=248) among 576 exposed individuals and 14% (n=94) among 685 controls (adjusted odds ratio for development of IBS in exposed individuals, 4.74; 95% CI, 3.61-6.23). At this time point, the prevalence of chronic fatigue was 26% (n=153) among 587 exposed individuals and 11% (n=73) among 692 controls (adjusted odds ratio, 3.01; 95% CI, 2.22-4.08). The prevalence of IBS among exposed persons did not change significantly from 6 years after infection (40%) to 10 years after infection (43%; adjusted odds ratio for the change 1.03; 95% CI, 0.87-1.22). However, the prevalence of chronic fatigue decreased from 31% at 6 years after infection to 26% at 10 years after infection (adjusted odds ratio for the change 0.74; 95% CI, 0.61-0.90).

CONCLUSION: The prevalence of IBS did not change significantly from 6 years after an outbreak of Giardia lamblia infection in Norway to 10 years after. However, the prevalence of chronic fatigue decreased significantly from 6 to 10 years afterward. IBS and chronic fatigue were still associated with giardiasis 10 years after the outbreak.

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Source: Litleskare S, Rortveit G, Eide GE, Hanevik K, Langeland N, Wensaas KA. Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years after Giardia Infection. Clin Gastroenterol Hepatol. 2018 Jan 25. pii: S1542-3565(18)30088-0. doi: 10.1016/j.cgh.2018.01.022. [Epub ahead of print]

An analysis of Dutch hallmark studies confirms the outcome of the PACE trial: cognitive behaviour therapy with a graded activity protocol is not effective for chronic fatigue syndrome and Myalgic Encephalomyelitis

Abstract:

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are considered to be enigmatic diseases. Several studies propose that the combination of cognitive behaviour therapy with a graded activity protocol (CBT+), justified by a so-called (bio)psychosocial (explanatory) model, is an effective treatment option for CFS (ME).

Objective :A critical review of five Dutch hallmark studies that allegedly support this claim.

Methods: An analysis of the five CBT+ studies with special attention to the patients studied, the criteria (subjective and objective measures and cut-off scores) used to select participants and to define improvement and recovery, the consistency of the definitions of caseness (being diagnosed as a CFS patient at entry) versus the definitions of improvement and recovery after CBT+, and the objective effects.

Results: The studies investigated suffer from various methodological flaws. Apart from these methodological shortcomings, the claim that CBT+ is an effective treatment option for CFS is not substantiated by the data reported. Some studies investigated CFS patients, other studies investigated CF patients, labelled as CFS patients, or combinations of CFS and CF patients. No study investigated the effect of CBT+ in a group of patients meeting the (original) diagnostic criteria for ME. The effects of CBT+ on subjective measures, for example fatigue and disability, if present, are insufficient to achieve normal values. Impressive recovery and improvement rates are based on very loose criteria for subjective measures. Cut-off scores for subjective measures used to define improvement and recovery in studies show overlap with cut-off scores for CFS caseness in one or more of the other studies. More importantly, looking at the objective measures, the proof of clinical improvement after CBT+ is lacking.

Conclusion: Solid evidence of effectiveness of CBT+ for CFS, let alone ME, is lacking in the five hallmark studies. The lack of objective improvement indicates CBT+ is ineffective. This finding confirms the outcome of the large-scale PACE-trial in the UK.

Source: Twisk FNM (2017) An analysis of Dutch hallmark studies confirms the outcome of the PACE trial: cognitive behaviour therapy with a graded activity protocol is not effective for chronic fatigue syndrome and Myalgic Encephalomyelitis. Gen Med Open, 2017 doi: 10.15761/GMO.1000117 (Full article)

Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a potentially disabling disorder. Little is known about the contributors to severe forms of the illness. We describe three consecutive patients with severe ME/CFS whose symptoms improved after recognition and surgical management of their cervical spinal stenosis.

Methods: All patients satisfied clinical criteria for ME/CFS and orthostatic intolerance, and were later found to have cervical spinal stenosis. Overall function was assessed before and after surgery using the Karnofsky score and the SF-36 physical function subscale score.

Results: Neurological findings included > 3+ deep tendon reflexes in 2 of 3, a positive Hoffman sign in 2 of 3, tremor in 2 of 3, and absent gag reflex in 1 of 3. The cervical spine canal diameter in the three patients ranged from 6 to 8.5 mm. One had congenital cervical stenosis with superimposed spondylosis, and two had single- or two-level spondylosis. Anterior cervical disc replacement surgery in two patients and a hybrid anterior cervical disc fusion and disc replacement in the third was associated with a marked improvement in myelopathic symptoms, resolution of lightheadedness and hemodynamic dysfunction, improvement in activity levels, and improvement in global ME/CFS symptoms.

Conclusions: The prompt post-surgical restoration of more normal function suggests that cervical spine stenosis contributed to the pathogenesis of refractory ME/CFS and orthostatic symptoms. The improvements following surgery emphasize the importance of a careful search for myelopathic examination findings in those with ME/CFS, especially when individuals with severe impairment are not responding to treatment.

Source: Rowe, P.C., Marden, C.L., Heinlein, S. et al. J Transl Med (2018) 16: 21. https://doi.org/10.1186/s12967-018-1397-7

Eukaryotes in the gut microbiota in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often suffer from gastrointestinal symptoms and many are diagnosed with irritable bowel syndrome (IBS). Previous studies, including from our laboratory, have demonstrated that the ME/CFS gut bacterial composition is altered and less diverse when compared to healthy individuals. Patients have increased biomarkers of inflammation and leaky gut syndrome. To further investigate dysbiosis in the ME/CFS gut microbiome, we sought to characterize the eukaryotes present in the gut of 49 individuals with ME/CFS and 39 healthy controls. Using 18S rRNA sequencing, we have identified eukaryotes in stool samples of 17 healthy individuals and 17 ME/CFS patients. Our analysis demonstrates a small, nonsignificant decrease in eukaryotic diversity in ME/CFS patients compared to healthy individuals. In addition, ME/CFS patients show a nonsignificant increase in the ratio of fungal phyla Basidiomycota to Ascomycota, which is consistent with ongoing inflammation in ME/CFS. We did not identify specific eukaryotic taxa that are associated with ME/CFS disease status.

Source: Alexandra H. Mandarano, Ludovic Giloteaux, Betsy A. Keller, Susan M. Levine, Maureen R. Hanson. Eukaryotes in the gut microbiota in myalgic encephalomyelitis/chronic fatigue syndrome. Peer J. January 22, 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784577/https://peerj.com/articles/4282/ (Full article)

Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

A recent study on the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has revealed an elevation of inflammatory and anti-inflammatory cytokines in the sera and cerebrospinal fluids of the patients and presence of autoantibodies in subgroups of ME/CFS patients. Furthermore, investigator-initiated clinical trials have proved the efficacy of anti-CD20 antibody (rituximab), that eliminate B cells, in the treatment of ME/CFS. Based on these findings, we hypothesize that immune abnormalities, such as enhanced autoimmune responses, may play an essential role in the neuroinflammatory pathogenesis of ME/CFS.

Source: Yamamura T, Ono H, Sato W. Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Brain Nerve. 2018 Jan;70(1):35-40. doi: 10.11477/mf.1416200947 [Article in Japanese]   https://www.ncbi.nlm.nih.gov/pubmed/29348373