Tag: review

Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review

Abstract:

BACKGROUND: The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel question to explore possible overlapping aetiology in two distinct conditions. Similar neurocognitive symptoms and evidence of D-lactate producing bacteria in ME/CFS raise questions about shared mechanisms with the acute condition of D-lactic acidosis (D-la).

METHODS: D-la case reports published between 1965 and March 2016 were reviewed for episodes describing both neurological symptoms and high D-lactate levels. Fifty-nine D-la episodes were included in the qualitative synthesis comparing D-la symptoms with ME/CFS diagnostic criteria. A narrative review of D-la mechanisms and relevance for ME/CFS was provided.

RESULTS: The majority of neurological disturbances reported in D-la episodes overlapped with ME/CFS symptoms. Of these, the most frequently reported D-la symptoms were motor disturbances that appear more prominent during severe presentations of ME/CFS. Both patient groups shared a history of gastrointestinal abnormalities and evidence of bacterial dysbiosis, although only preliminary evidence supported the role of lactate-producing bacteria in ME/CFS.

LIMITATIONS: Interpretation of results are constrained by both the breadth of symptoms included in ME/CFS diagnostic criteria and the conservative methodology used for D-la symptom classification. Several pathophysiological mechanisms in ME/CFS were not examined.

CONCLUSIONS: Shared symptomatology and underlying microbiota-gut-brain interactions raise the possibility of a continuum of acute (D-la) versus chronic (ME/CFS) presentations related to D-lactate absorption. Measurement of D-lactate in ME/CFS is needed to effectively evaluate whether subclinical D-lactate levels affect neurological symptoms in this clinical population.

Source: Wallis A, Ball M, McKechnie S, Butt H, Lewis DP, Bruck D. Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review. J Transl Med. 2017 Jun 7;15(1):129. doi: 10.1186/s12967-017-1229-1. https://www.ncbi.nlm.nih.gov/pubmed/28592308

Chronic fatigue syndrome and the immune system: Where are we now?

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterised by multiple symptoms including fatigue, headaches and cognitive impairment, which have a significantly adverse effect on the normal functioning and well-being of the individual. These symptoms are often triggered or worsened following physical or mental exertion. ME/CFS has long been thought of as having a significant immunological component, but reports describing changes in immune function are often inconsistent between study groups.

Although the wide range of physical, neurocognitive and autonomic symptoms reported have seriously hampered attempts to understand pathophysiological pathways, investment in biomedical research in ME/CFS is finally increasing with a number of novel and promising investigations being published. The onset of ME/CFS may often be linked to (viral) infections which would be consistent with a variety of alterations in natural killer (NK) cell function as described by a number of different groups. Consistency in cytokine data has been lacking so far, although recently more sophisticated approaches have led to more robust data from large patient cohorts.

New hope has also been given to sufferers with the possibility that therapies that deplete B cells can result in clinical improvement. To understand the pathogenic mechanism in this complex condition, it is important to consider repeated analysis in different cohorts. In this review, we will discuss the potential of different components of the immune system to be involved in the pathogenesis of ME/CFS.

Copyright © 2017 Elsevier Masson SAS. All rights reserved

 

Source: Mensah FKF, Bansal AS, Ford B, Cambridge G. Chronic fatigue syndrome and the immune system: Where are we now? Neurophysiol Clin. 2017 Apr 11. pii: S0987-7053(17)30006-0. doi: 10.1016/j.neucli.2017.02.002. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28410877

 

CNS findings in chronic fatigue syndrome and a neuropathological case report

Abstract:

Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain, depression, weakness, mood disturbances, and neuropsychological impairment. In this mini review and case report, we address central nervous system (CNS) involvement of CFS and present neuropathological autopsy findings from a patient who died with a prior diagnosis of CFS.

Among the most remarkable pathological features of the case are focal areas of white matter loss, neurite beading, and neuritic pathology of axons in the white matter with axonal spheroids. Atypical neurons displaying aberrant sprouting processes in response to injury are observed throughout cortical gray and white matter. Abundant amyloid deposits identical to AD plaques with accompanying intracellular granular structures are observed as well. Neurofibrillary tangles are also present in the white matter of the frontal cortex, thalamus and basal ganglia.

Taken together, these neuropathological findings warrant further studies into CNS disease associated with CFS.

 

Source: Kimberly Ferrero, Mitchell Silver, Alan Cocchetto, Eliezer Masliah, Dianne Langford. CNS findings in chronic fatigue syndrome and a neuropathological case report. Journal of Investigative Medicine. DOI: 10.1136/jim-2016-000390 Published 6 April 2017. http://jim.bmj.com/content/early/2017/04/06/jim-2016-000390

 

Acupuncture and moxibustion for chronic fatigue syndrome in traditional Chinese medicine: a systematic review and meta-analysis

Abstract:

BACKGROUND: As the etiology of chronic fatigue syndrome (CFS) is unclear and the treatment is still a big issue. There exists a wide range of literature about acupuncture and moxibustion (AM) for CFS in traditional Chinese medicine (TCM). But there are certain doubts as well in the effectiveness of its treatment due to the lack of a comprehensive and evidence-based medical proof to dispel the misgivings. Current study evaluated systematically the effectiveness of acupuncture and moxibustion treatments on CFS, and clarified the difference among them and Chinese herbal medicine, western medicine and sham-acupuncture.

METHODS: We comprehensively reviewed literature including PubMed, EMBASE, Cochrane library, CBM (Chinese Biomedical Literature Database) and CNKI (China National Knowledge Infrastructure) up to May 2016, for RCT clinical research on CFS treated by acupuncture and moxibustion. Traditional direct meta-analysis was adopted to analyze the difference between AM and other treatments. Analysis was performed based on the treatment in experiment and control groups. Network meta-analysis was adopted to make comprehensive comparisons between any two kinds of treatments. The primary outcome was total effective rate, while relative risks (RR) and 95% confidence intervals (CI) were used as the final pooled statistics.

RESULTS: A total of 31 randomized controlled trials (RCTs) were enrolled in analyses. In traditional direct meta-analysis, we found that in comparison to Chinese herbal medicine, CbAM (combined acupuncture and moxibustion, which meant two or more types of acupuncture and moxibustion were adopted) had a higher total effective rate (RR (95% CI), 1.17 (1.09 ~ 1.25)). Compared with Chinese herbal medicine, western medicine and sham-acupuncture, SAM (single acupuncture or single moxibustion) had a higher total effective rate, with RR (95% CI) of 1.22 (1.14 ~ 1.30), 1.51 (1.31-1.74), 5.90 (3.64-9.56). In addition, compared with SAM, CbAM had a higher total effective rate (RR (95% CI), 1.23 (1.12 ~ 1.36)). In network meta-analyses, similar results were recorded. Subsequently, we ranked all treatments from high to low effective rate and the order was CbAM, SAM, Chinese herbal medicine, western medicine and sham-acupuncture.

CONCLUSIONS: In the treatment of CFS, CbAM and SAM may have better effect than other treatments. However, the included trials have relatively poor quality, hence high quality studies are needed to confirm our finding.

 

Source: Wang T, Xu C, Pan K, Xiong H. Acupuncture and moxibustion for chronic fatigue syndrome in traditional Chinese medicine: a systematic review and meta-analysis. BMC Complement Altern Med. 2017 Mar 23;17(1):163. doi: 10.1186/s12906-017-1647-x. https://www.ncbi.nlm.nih.gov/pubmed/28335756

 

The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multi-systemic chronic illness of unknown etiology, classified as a neurological disorder by the World Health Organization (WHO). The symptomatology of the condition appears to emanate from a variety of sources of chronic neurological disturbance and associated distortions, and chronicity, in noxious sensory signaling and neuroimmune activation. This article incorporates a summary review and discussion of biomedical research considered relevant to this essential conception perspective. It is intended to provide stakeholders with a concise, integrated outline disease model in order to help demystify this major public health problem. The primary etiopathological factors presented are:

(A) Postural/biomechanical pain signaling, affecting adverse neuroexcitation, in the context of compression, constriction, strain, or damage of vertebral-regional bone and neuromuscular tissues;

(B) Immune mediated inflammatory sequelae, in the context of prolonged immunotropic neurotrophic infection-with lymphotropic/gliotropic/glio-toxic varieties implicated in particular;

(C) A combination of factors A and B. Sustained glial activation under such conditions is associated with oxidative and nitrosative stress, neuroinflammation, and neural sensitivity. These processes collectively enhance the potential for multi-systemic disarray involving endocrine pathway aberration, immune and mitochondrial dysfunction, and neurodegeneration, and tend toward still more intractable synergistic neuro-glial dysfunction (gliopathy), autoimmunity, and central neuronal sensitization.

 

Source: Glassford JA. The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Physiol. 2017 Feb 17;8:88. doi: 10.3389/fphys.2017.00088. eCollection 2017. http://journal.frontiersin.org/article/10.3389/fphys.2017.00088/full (Full article)

 

Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome

Abstract:

This review explores the current evidence on benefits and harms of therapeutic interventions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and makes recommendations. CFS/ME is a complex, multi-system, chronic medical condition whose pathophysiology remains unknown. No established diagnostic tests exist nor are any FDA-approved drugs available for treatment. Because of the range of symptoms of CFS/ME, treatment approaches vary widely.

Studies undertaken have heterogeneous designs and are limited by sample size, length of follow-up, applicability and methodological quality. The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. Similarly, adaptive pacing appears to offer some benefits, but the results are debatable: so is the use of nutritional supplements, which may be of value to CFS/ME patients with biochemically proven deficiencies.

To summarize, the recommended treatment strategies should include proper administration of nutritional supplements in CFS/ME patients with demonstrated deficiencies and personalized pacing programs to relieve symptoms and improve performance of daily activities, but a larger randomized controlled trial (RCT) evaluation is required to confirm these preliminary observations.

At present, no firm conclusions can be drawn because the few RCTs undertaken to date have been small-scale, with a high risk of bias, and have used different case definitions. Further, RCTs are now urgently needed with rigorous experimental designs and appropriate data analysis, focusing particularly on the comparison of outcomes measures according to clinical presentation, patient characteristics, case criteria and degree of disability (i.e. severely ill ME cases or bedridden).

© 2017 The British Pharmacological Society.

 

Source: Castro-Marrero J, Sáez-Francàs N, Santillo D, Alegre J. Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome. Br J Pharmacol. 2017 Mar;174(5):345-369. doi: 10.1111/bph.13702. Epub 2017 Feb 1. https://www.ncbi.nlm.nih.gov/pubmed/28052319

 

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways

Abstract:

There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels.

This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis hypoactivity in ME/CFS, considering two possibilities: (a) Activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms, or (b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPA axis hypoactivity.

Electronic databases, i.e., PUBMED, Scopus, and Google Scholar, were used as sources for this narrative review by using keywords CFS, ME, cortisol, ACTH, CRH, HPA axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, and O&NS.

Findings show that activation of immune-inflammatory and O&NS pathways in ME/CFS are probably not secondary to HPA axis hypoactivity and that activation of these pathways may underpin HPA axis hypofunction in ME/CFS. Mechanistic explanations comprise increased levels of tumor necrosis factor-α, T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-β, elevated levels of nitric oxide, and viral/bacterial-mediated mechanisms.

HPA axis hypoactivity in ME/CFS is most likely a consequence and not a cause of a wide variety of activated immune-inflammatory and O&NS pathways in that illness.

 

Source: Morris G, Anderson G, Maes M. Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways. Mol Neurobiol. 2016 Oct 20. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27766535

 

Cognitive behavioural therapy in the treatment of chronic fatigue syndrome: A narrative review on efficacy and informed consent

Abstract:

Cognitive behavioural therapy is increasingly promoted as a treatment for chronic fatigue syndrome. There is limited research on informed consent using cognitive behavioural therapy in chronic fatigue syndrome. We undertook a narrative review to explore efficacy and to identify the salient information that should be disclosed to patients.

We found a complex theoretical model underlying the rationale for psychotherapy in chronic fatigue syndrome. Cognitive behavioural therapy may bring about changes in self-reported fatigue for some patients in the short term, however there is a lack of evidence for long-term benefit or for improving physical function and cognitive behavioural therapy may cause distress if inappropriately prescribed. Therapist effects and placebo effects are important outcome factors.

© The Author(s) 2016.

 

Source: Geraghty KJ, Blease C. Cognitive behavioural therapy in the treatment of chronic fatigue syndrome: A narrative review on efficacy and informed consent. J Health Psychol. 2016 Sep 15. pii: 1359105316667798. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27634687

 

Do evidence based interventions for chronic fatigue syndrome improve sleep? A systematic review and narrative synthesis

Abstract:

Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are recommended evidence based treatments for chronic fatigue syndrome (CFS), with research supporting their effectiveness in reducing fatigue and functional impairment. However, little research has focussed on the effect of these treatments on sleep, despite high reported sleep disturbance in CFS.

Using a narrative synthesis approach, we aimed to 1) systematically identify and summarise the current evidence for the effectiveness of CBT and GET in improving sleep; 2) consider factors influencing treatment effectiveness, including incorporation of sleep management techniques; and 3) consider the appropriateness of sleep outcome measures used within evaluations. Studies evaluating CBT and/or GET for CFS, and including a sleep outcome were eligible for inclusion. Eight studies were identified.

We found that GET interventions can improve sleep but this effect is inconsistent across studies. For CBT the evidence is limited with only one of two evaluations demonstrating sleep-related improvements.

We conclude from existing research that we know little about the effects of including sleep management components within CBT and GET interventions. We suggest that future research should explore the effectiveness of sleep components within interventions, and sleep specific interventions, using comprehensive outcome measures that fully capture the range of sleep difficulties experienced in CFS.

Copyright © 2016 Elsevier Ltd. All rights reserved.

 

Source: Russell C, Kyle SD, Wearden AJ. Do evidence based interventions for chronic fatigue syndrome improve sleep? A systematic review and narrative synthesis. Sleep Med Rev. 2016 May 13. pii: S1087-0792(16)30012-0. doi: 10.1016/j.smrv.2016.05.001. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27524207

 

A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)?

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous disorder of significant societal impact that is proposed to involve both host and environmentally derived aetiologies that may be autoimmune in nature. Immune-related symptoms of at least moderate severity persisting for prolonged periods of time are common in ME/CFS patients and B cell depletion therapy is of significant therapeutic benefit. The origin of these symptoms and whether it is infectious or inflammatory in nature is not clear, with seeking evidence of acute or chronic virus infections contributing to the induction of autoimmune processes in ME/CFS being an area of recent interest.

This article provides a comprehensive review of the current evidence supporting an infectious aetiology for ME/CFS leading us to propose the novel concept that the intestinal microbiota and in particular members of the virome are a source of the “infectious” trigger of the disease. Such an approach has the potential to identify disease biomarkers and influence therapeutics, providing much-needed approaches in preventing and managing a disease desperately in need of confronting.

 

Source: Navaneetharaja N, Griffiths V, Wileman T, Carding SR. A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)? J Clin Med. 2016 Jun 6;5(6). pii: E55. doi: 10.3390/jcm5060055. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929410/ (Full article)