Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are poorly understood disorders that share similar demographic and clinical characteristics. The etiology and pathophysiology of these diseases remain unclear. Because of the similarities between both disorders it was suggested that they share a common pathophysiological mechanisms, namely, central nervous system (CNS) dysfunction. Current hypotheses center on atypical sensory processing in the CNS and dysfunction of skeletal muscle nociception and the hypothalamic-pituitary-adrenal (HPA) axis.

Researches suggest that the (CNS) is primarily involved in both disorders in regard to the pain, fatigue and sleep disturbances. Many patients experience difficulty with concentration and memory and many others have mood disturbance, including depression and anxiety. Although fibromyalgia is common and associated with substantial morbidity and disability, there are no US Food and Drug Administration (FDA)-approved treatments except pregabalin.

Recent pharmacological treatment studies about fibromyalgia have focused on selective serotonin and norepinephrine (NE) reuptake inhibitors, which enhance serotonin and NE neurotransmission in the descending pain pathways and lack many of the adverse side effects associated with tricyclic medications. CFS is a descriptive term used to define a recognisable pattern of symptoms that cannot be attributed to any alternative condition. The symptoms are currently believed to be the result of disturbed brain function.

To date, no pharmacological agent has been reliably shown to be effective treatment for CFS. Management strategies are therefore primarily directed at relief of symptoms and minimising impediments to recovery. This chapter presents data demonstrating CFS, abnormal pain processing and autonomic nervous system (ANS) dysfunction in FM and CFS and concludes by reviewing the new concepts in treatments in CFS and FM.

 

Source: Gur A, Oktayoglu P. Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment. Curr Pharm Des. 2008;14(13):1274-94. https://www.ncbi.nlm.nih.gov/pubmed/18537652

 

A systematic review of chronic fatigue syndrome: don’t assume it’s depression

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is characterized by profound, debilitating fatigue and a combination of several other symptoms resulting in substantial reduction in occupational, personal, social, and educational status. CFS is often misdiagnosed as depression. The objective of this study was to evaluate and discuss different etiologies, approaches, and management strategies of CFS and to present ways to differentiate it from the fatigue symptom of depression.

DATA SOURCES: A MEDLINE search was conducted to identify existing information about CFS and depression using the headings chronic fatigue syndrome AND depression. The alternative terms major depressive disorder and mood disorder were also searched in conjunction with the term chronic fatigue syndrome. Additionally, MEDLINE was searched using the term chronic fatigue. All searches were limited to articles published within the last 10 years, in English. A total of 302 articles were identified by these searches. Also, the term chronic fatigue syndrome was searched by itself. This search was limited to articles published within the last 5 years, in English, and resulted in an additional 460 articles. Additional publications were identified by manually searching the reference lists of the articles from both searches.

STUDY SELECTION AND DATA EXTRACTION: CFS definitions, etiologies, differential diagnoses (especially depression) and management strategies were extracted, reviewed, and summarized to meet the objectives of this article.

DATA SYNTHESIS: CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression. Genetic, immunologic, infectious, metabolic, and neurologic etiologies were suggested to explain CFS. A biopsychosocial model was suggested for evaluating, managing, and differentiating CFS from depression.

CONCLUSIONS: Evaluating and managing chronic fatigue is a challenging situation for physicians, as it is a challenging and difficult condition for patients. A biopsychosocial approach in the evaluation and management is recommended. More studies about CFS manifestations, evaluation, and management are needed.

 

Source: Griffith JP, Zarrouf FA. A systematic review of chronic fatigue syndrome: don’t assume it’s depression. Prim Care Companion J Clin Psychiatry. 2008;10(2):120-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292451/ (Full article)

 

Possible role for early-life immune insult including developmental immunotoxicity in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME)

Abstract:

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME) in some countries, is a debilitating disease with a constellation of multi-system dysfunctions primarily involving the neurological, endocrine and immune systems. While substantial information is available concerning the complex dysfunction-associated symptoms of CFS, environmental origins of the disease have yet to be determined.

Part of the dilemma in identifying the cause(s) has been the focus on biomarkers (hormones, neurotransmitters, cytokines, infectious agents) that are contemporary with later-life CFS episodes. Yet, recent investigations on the origins of environmental diseases of the neurological, endocrine, reproductive, respiratory and immune systems suggest that early life toxicologic and other insults are pivotal in producing later-life onset of symptoms. As with autism and childhood asthma, CFS can also occur in children where the causes are certainly early-life events.

Immune dysfunction is recognized as part of the CFS phenotype but has received comparatively less attention than aberrant neurological or endocrine function. However, recent research results suggest that early life immune insults (ELII) including developmental immunotoxicity (DIT), which is induced by xenobiotics, may offer an important clue to the origin(s) of CFS.

The developing immune system is a sensitive and novel target for environmental insult (xenobiotic, infectious agents, stress) with major ramifications for postnatal health risks. Additionally, many prenatal and early postnatal neurological lesions associated with postnatal neurobehavioral diseases are now recognized as linked to prenatal immune insult and inflammatory dysregulation. This review considers the potential role of ELII including DIT as an early-life component of later-life CFS.

 

Source: Dietert RR, Dietert JM. Possible role for early-life immune insult including developmental immunotoxicity in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME). Toxicology. 2008 May 2;247(1):61-72. doi: 10.1016/j.tox.2008.01.022. Epub 2008 Feb 8. https://www.ncbi.nlm.nih.gov/pubmed/18336982

 

A systematic review of acupuncture and moxibustion treatment for chronic fatigue syndrome in China

Abstract:

Studies on the treatment of chronic fatigue syndrome (CFS) with acupuncture and moxibustion in China were reviewed. All studies concluded the treatments were effective, with response rates ranging from 78.95% to 100%. However, the qualities of the studies were generally poor, and none of them used a RCT design. The common acupoints/sites used in the treatment of CFS, which may reflect the collective experience of acupuncturists in China based on Traditional Chinese Medicine theories can be used to evaluate the effectiveness of acupuncture for the treatment of CFS in future studies using more scientifically rigorous study designs.

 

Source: Wang T, Zhang Q, Xue X, Yeung A. A systematic review of acupuncture and moxibustion treatment for chronic fatigue syndrome in China. Am J Chin Med. 2008;36(1):1-24. https://www.ncbi.nlm.nih.gov/pubmed/18306446

 

Chronic fatigue syndrome: characteristics and possible causes for its pathogenesis

Abstract:

Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by disabling fatigue, difficulty in concentration and memory, and concomitant skeletal and muscular pain. Several mechanisms have been suggested to play a role in CFS, such as excessive oxidative stress following exertion, immune imbalance characterized by decreased natural killer cell and macrophage activity, immunoglobulin G subclass deficiencies (IgG1, IgG3) and decreased serum concentrations of complement component. Autoantibodies were also suggested as a possible factor in the pathogenesis of CFS. Recent studies indicate that anti-serotonin, anti-microtubule-associated protein 2 and anti-muscarinic cholinergic receptor 1 may play a role in the pathogenesis of CFS. It has been demonstrated that impairment in vasoactive neuropeptide metabolism may explain the symptoms of CFS.

 

Source: Bassi N, Amital D, Amital H, Doria A, Shoenfeld Y. Chronic fatigue syndrome: characteristics and possible causes for its pathogenesis. Isr Med Assoc J. 2008 Jan;10(1):79-82. http://www.ima.org.il/IMAJ/ViewArticle.aspx?year=2008&month=01&page=79 (Full article)

 

Intracellular immune dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: state of the art and therapeutic implications

Abstract:

BACKGROUND: Evidence in support of intracellular immune dysfunctions in people with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is accumulating, but few studies have addressed intracellular immunity as a potential therapeutic target.

OBJECTIVE: To provide an overview of our present understanding of intracellular immunity in ME/CFS, to relate the intracellular immune dysfunctions to other aspects of the illness like decreased natural killer cell function, the presence of infections and poor exercise performance, and to point to potential therapeutic targets.

METHODS: An in-depth review of the scientific literature of intracellular immunity in people with ME/CFS was performed.

RESULTS/CONCLUSION: From the scientific literature it is concluded that proteolytic cleavage of the native RNase L enzyme is characteristic of the dysregulation of intracellular immunity in people with ME/CFS, but the origin of the dysregulation is speculative. There is increasing evidence for immune cell apoptosis and upregulation of various aspects of the 2′-5′ oligoadenylate (2-5A) synthetase/RNase L pathway in ME/CFS. This review provides the theoretical rationale for conducting studies examining the effectiveness of direct or indirect drug targeting of the 2-5A synthetase/RNase L pathway in ME/CFS patients.

 

Source: Nijs J, Frémont M. Intracellular immune dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome: state of the art and therapeutic implications. Expert Opin Ther Targets. 2008 Mar;12(3):281-9. doi: 10.1517/14728222.12.3.281.https://www.ncbi.nlm.nih.gov/pubmed/18269338

 

Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions

Abstract:

Investigations into the underlying cause of chronic fatigue syndrome have advanced the field considerably in the past year. Gene microarray data have led to a better understanding of pathogenesis. Recent research has evaluated genetic signatures, described biologic subgroups, and suggested potential targeted treatments. Acute viral infection studies found that initial infection severity was the single best predictor of persistent fatigue. Genomic studies showed that persistent cases express Epstein Barr virus-specific genes and demonstrate abnormalities of mitochondrial function. Studies of immune dysfunction extended observations of natural killer cytotoxic cell dysfunction of the cytotoxic T cell through quantitative evaluation of intracellular perforins and granzymes. Other research has focused on a subgroup of patients with reactivated viral infection. These advances should result in targeted therapies that impact immune function, hypothalamic-pituitary-adrenal axis regulation, and persistent viral reactivation.

 

Source: Klimas NG, Koneru AO. Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions. Curr Rheumatol Rep. 2007 Dec;9(6):482-7. https://www.ncbi.nlm.nih.gov/pubmed/18177602

 

Chronic fatigue syndrome

Abstract:

INTRODUCTION: Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men.

METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS: We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.

 

Source: Reid SF, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue syndrome. BMJ Clin Evid. 2008 Aug 28;2008. pii: 1101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907931/ (Full article)

 

Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies

Abstract:

BACKGROUND: The aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is still unknown. The identification of risk factors for CFS/ME is of great importance to practitioners.

METHOD: A systematic scoping review was conducted to locate studies that analysed risk factors for CFS/ME using multiple predictors. We searched for published and unpublished literature in 11 electronic databases, reference lists of retrieved articles and guideline stakeholder submissions in conjunction with the development of a forthcoming national UK guideline. Risk factors and findings were extracted in a concise tabular overview and studies synthesized narratively.

RESULTS: Eleven studies were identified that met inclusion criteria: two case-control studies, four cohort studies, three studies combining a cohort with a case-control study design, one case-control and twin study and one cross-sectional survey. The studies looked at a variety of demographic, medical, psychological, social and environmental factors to predict the development of CFS/ME. The existing body of evidence is characterized by factors that were analysed in several studies but without replication of a significant association in more than two studies, and by studies demonstrating significant associations of specific factors that were not assessed in other studies. None of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice.

CONCLUSIONS: Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.

 

Source: Hempel S, Chambers D, Bagnall AM, Forbes C. Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies. Psychol Med. 2008 Jul;38(7):915-26. Epub 2007 Sep 25. https://www.ncbi.nlm.nih.gov/pubmed/17892624

 

Neuroaetiology of chronic fatigue syndrome: an overview

Abstract:

Chronic fatigue syndrome (CFS) is now recognized as a medial disorder. In contrast to recent related reports, the present review focuses primarily on aetiological aspects of CFS. Four major hypotheses are reviewed. (1) Although CFS is often associated with viral infection, the presence of viruses has as yet not consistently been detected. (2) It is not clear whether anomalies of the HPA axis often observed in CFS, are cause or the consequences of the disorder. (3) Immune dysfunction as the cause of CFS is thus far the weakest hypothesis. (4) The psychiatric and psychosocial hypothesis denies the existence of CFS as a disease entity. Accordingly, the fatigue symptoms are assumed to be the consequence of other (somatic) diseases. Other possible causes of CFS are oxidative stress and genetic predisposition. In CFS cognitive behavioural therapy is most commonly used. This therapy, however, appears to be ineffective in many patients. The suggested causes of CFS and the divergent reactions to therapy may be explained by the lack of recognition of subgroups. Identification of subtypes may lead to more effective therapeutic interventions.

 

Source: Sanders P, Korf J. Neuroaetiology of chronic fatigue syndrome: an overview. World J Biol Psychiatry. 2008;9(3):165-71. https://www.ncbi.nlm.nih.gov/pubmed/17853290