Tag: 2018

The international collaborative on fatigue following infection (COFFI)

Abstract:

Background: The purpose of the Collaborative on Fatigue Following Infection (COFFI) is for investigators of post-infection fatigue (PIF) and other syndromes to collaborate on these enigmatic and poorly understood conditions by studying relatively homogeneous populations with known infectious triggers. Utilising COFFI, pooled data and stored biosamples will support both epidemiological and laboratory research to better understand the etiology and risk factors for development and progression of PIF.

Methods: COFFI consists of prospective cohorts from the UK, Netherlands, Norway, USA, New Zealand and Australia, with some cohorts closed and some open to recruitment. The 9 cohorts closed to recruitment total over 3000 participants, including nearly 1000 with infectious mononucleosis (IM), > 500 with Q fever, > 800 with giardiasis, > 600 with campylobacter gastroenteritis (CG), 190 with Legionnaires disease and 60 with Ross River virus. Follow-ups have been at least 6 months and up to 10 years. All studies use the Fukuda criteria for defining chronic fatigue syndrome (CFS).

Results: Preliminary analyses indicated that risk factors for non-recovery from PIF included lower physical fitness, female gender, severity of the acute sickness response, and autonomic dysfunction.

Conclusions: COFFI (https://internationalcoffi.wordpress.com/) is an international collaboration which should be able to answer questions based on pooled data that are not answerable in the individual cohorts. Possible questions may include the following: Do different infections trigger different PIF syndromes (e.g. CFS vs. irritable bowel syndrome)?; What are longitudinal predictors of PIF and its severity?

Source: Ben Z Katz, Simon M Collin, Gabrielle Murphy, Rona Moss-Morris, Vegard Bruun Wyller, Knut-Arne Wensaas, Jeannine L.A. Hautvast, Chantal P Bleeker-Rovers, Ute Vollmer-Conna, Dedra Buchwald, Renée Taylor, Paul Little, Esther Crawley, Peter D White & Andrew Lloyd. The international collaborative on fatigue following infection (COFFI). Fatigue: Biomedicine, Health & Behavior Vol. 0, Iss. 0, 2018. http://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1426086?journalCode=rftg20

A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications

Abstract:

Currently, a psychologically based model is widely held to be the basis for the aetiology and treatment of chronic fatigue syndrome(CFS)/myalgic encephalomyelitis (ME)/systemic exertion intolerance disease (SEID). However, an alternative, molecular neurobiological approach is possible and in this paper evidence demonstrating a biological aetiology for CFS/ME/SEID is adduced from a study of the history of the disease and a consideration of the role of the following in this disease: nitric oxide and peroxynitrite, oxidative and nitrosative stress, the blood-brain barrier and intestinal permeability, cytokines and infections, metabolism, structural and chemical brain changes, neurophysiological changes and calcium ion mobilisation. Evidence is also detailed for biologically based potential therapeutic options, including: nutritional supplementation, for example in order to downregulate the nitric oxide-peroxynitrite cycle to prevent its perpetuation; antiviral therapy; and monoclonal antibody treatment. It is concluded that there is strong evidence of a molecular neurobiological aetiology, and so it is suggested that biologically based therapeutic interventions should constitute a focus for future research into CFS/ME/SEID.

Source: Monro JA, Puri BK. A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications. Mol Neurobiol. 2018 Feb 6. doi: 10.1007/s12035-018-0928-9. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29411266

Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons

Abstract:

BACKGROUND: Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of D-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS.

METHODS: An open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons. Participants included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 105 cfu/g (wet weight of faeces) and with a count greater than 5% of the total count of aerobic microorganisms. The 4-week treatment protocol included alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily and probiotic (D-lactate free multistrain probiotic, 5 × 1010 cfu twice daily). 2 × 2 repeated measures ANOVAs were used to assess sex-time interactions and effects across pre- and post-intervention for microbial, lactate and clinical outcomes. Ancillary non-parametric correlations were conducted to examine interactions between change in microbiota and clinical outcomes.

RESULTS: Large treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). Mood, fatigue and urine D:L lactate ratio remained similar across time. Ancillary results infer that shifts in microbiota were associated with more of the variance in clinical changes for males compared with females.

CONCLUSIONS: Results support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population. Streptococcus spp. are not the primary or sole producers of D-lactate. Further investigation of lactate concentrations are needed to elucidate any role of D-lactate in this population. Concurrent microbial shifts that may be associated with clinical improvement (i.e., increased Bacteroides and Bifidobacterium or decreased Clostridium in males) invite enquiry into alternative strategies for individualised treatment.

Trial Registration Australian and New Zealand Clinical Trial Registry (ACTRN12614001077651) 9th October 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366933&isReview=true.

Source: Wallis A, Ball M, Butt H, Lewis DP, McKechnie S, Paull P, Jaa-Kwee A, Bruck D. Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons. J Transl Med. 2018 Feb 6;16(1):24. doi: 10.1186/s12967-018-1392-z. https://www.ncbi.nlm.nih.gov/pubmed/29409505

Cardiovascular characteristics of chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) commonly exhibit orthostatic intolerance. Abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli was previously described in numerous studies. The aim of the current study was to describe cardiological and clinical characteristics of Italian patients with CFS. All of the patients were of Caucasian ethnicity and had been referred to our center, the Cardiology Department of the University Hospital of Pavia (Pavia, Italy) with suspected CFS. A total of 44 patients with suspected CFS were included in the present study and the diagnosis was confirmed in 19 patients according to recent clinical guidelines.

The characteristics at baseline of the population confirm findings from various previous reports regarding the prevalence in females with a female to male ratio of 4:1, the age of onset of the pathology and the presence of previous infection by the Epstein-Barr virus, cytomegalovirus and other human herpesviruses. Despite the current data indicating that the majority of the cardiological parameters investigated are not significantly different in patients with and without CFS, a significant association between the disease and low levels of blood pressure was identified. Other pilot studies revealed a higher prevalence of hypotension and orthostatic intolerance in patients with CFS. Furthermore, many of the CFS symptoms, including fatigue, vertigo, decreased concentration, tremors and nausea, may be explained by hypotension.

Source: Bozzini S, Albergati A, Capelli E, Lorusso L, Gazzaruso C, Pelissero G, Falcone C. Cardiovascular characteristics of chronic fatigue syndrome. Biomed Rep. 2018 Jan;8(1):26-30. doi: 10.3892/br.2017.1024. Epub 2017 Nov 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772628/ (Full article)

Chronic fatigue syndrome in Chinese middle-school students

Abstract:

The objective of the present study was to determine the prevalence of chronic fatigue syndrome (CFS) and its associated factors in middle-school students in Suzhou, China. From September 2010 to January 2011, across-sectional study was conducted in junior- and senior middle-school students aged 10 to 18 years using a battery of confidential questionnaires. Our results indicate that 18,139 completed the questionnaires effectively, of whom 163 (0.9%) met the definition of CFS, with senior high-school students and male students predominating. The prevalence of CFS in the middle-school students increased steadily with age. The main symptoms of CFS in these students included being afraid of going to school, despondency, and irritability in addition to those specified in the Centers for Disease Control and Prevention (CDC). Our study shows that CFS is prevalent among Chinese teenagers, and requiring proper intervention and treatment.

Source: Shi J, Shen J, Xie J, Zhi J, Xu Y. Chronic fatigue syndrome in Chinese middle-school students. Medicine (Baltimore). 2018 Jan;97(4):e9716. doi: 10.1097/MD.0000000000009716. https://journals.lww.com/md-journal/fulltext/2018/01260/Chronic_fatigue_syndrome_in_Chinese_middle_school.37.aspx (Full article)

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

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