Tag: review

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

 

Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome

Abstract:

OBJECTIVE: We reviewed previous studies that have described an association between abnormal functioning of the hypothalamic-pituitary-adrenal axis and depression. In addition to melancholic depression, a spectrum of conditions may be associated with increased and prolonged activation of the hypothalamic-pituitary-adrenal axis. In contrast another group of states is characterized by hypoactivation of the stress system, rather than sustained activation, in which chronically reduced secretion of corticotropin releasing factor may result in pathological hypoarousal and an enhanced hypothalamic-pituitary-adrenal negative feedback. Patients with atypical depression, seasonal affective disorder and chronic fatigue syndrome fall in this category.

METHOD: The literature data on the overlap between the key-words were reviewed, summarized and discussed.

RESULTS: Many studies suggest that these conditions themselves overlap biologically, showing hypofunction of central corticotropin releasing factor neuronal systems.

CONCLUSIONS: Therefore, in the real world of clinical practice, patients often present in a grey area between classical idiopathic fatigue and early chronic atypical depression and/or seasonal depression. This underscores the potential common biological links underpinning common symptom clusters not only between depression (atypical and seasonal) and chronic fatigue syndrome, but also other conditions characterized by the hypothalamic-pituitary-adrenal axis mainly diminished the corticotropin releasing factor activity.

 

Source: Juruena MF, Cleare AJ. Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome. Rev Bras Psiquiatr. 2007 May;29 Suppl 1:S19-26. [Article in Portuguese] http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462007000500005&lng=en&nrm=iso&tlng=en (Full article)

 

Lymphatic drainage of the neuraxis in chronic fatigue syndrome: a hypothetical model for the cranial rhythmic impulse

Abstract:

The cranial rhythmic impulse is a palpable, rhythmic fluctuation believed to be synchronous with the primary respiratory mechanism. The precise physiologic mechanism of the cranial rhythmic impulse is not fully understood. Based on traditional and current views of the cranial rhythmic impulse, animal studies, and clinical findings in patients with chronic fatigue syndrome, the author argues that the cranial rhythmic impulse is the rhythm produced by a combination of cerebrospinal fluid drainage from the neuraxis (brain and spinal cord) and pulsations of central lymphatic drainage induced by the sympathetic nervous system. In addition, evidence is provided to demonstrate that a disturbed, palpable, and visible neurolymphatic process leads to chronic fatigue syndrome. This process may also explain the pathophysiologic mechanisms leading to other disease states. Finally, the author’s proposed manual treatment protocol for patients with chronic fatigue syndrome is described.

 

Source: Perrin RN. Lymphatic drainage of the neuraxis in chronic fatigue syndrome: a hypothetical model for the cranial rhythmic impulse. J Am Osteopath Assoc. 2007 Jun;107(6):218-24. https://www.ncbi.nlm.nih.gov/pubmed/17635902

 

Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome

Abstract:

There is evidence for a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (CFS), despite the negative studies and methodological difficulties. In this review, we focus on challenge studies and on the role of the HPA axis in the pathogenesis of CFS. Mild hypocortisolism, blunted adrenocorticotropin response to stressors and enhanced negative feedback sensitivity to glucocorticoids are the main findings. Several underlying mechanisms have been proposed. Currently, it is a matter of debate whether these disturbances have a primary role in the pathogenesis of CFS. However, even if the HPA axis dysfunctions are secondary to other factors, they are probably a relevant factor in symptom propagation in CFS.

 

Source: Van Den Eede F, Moorkens G, Van Houdenhove B, Cosyns P, Claes SJ. Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. Neuropsychobiology. 2007;55(2):112-20. Epub 2007 Jun 27. http://www.karger.com/Article/FullText/104468 (Full article)

 

School phobia and childhood chronic fatigue syndrome (CCFS)

Abstract:

Chronic fatigue occurring in previously healthy children and adolescents is a vexing problem encountered by pediatric practitioners and the impact of fatigue in youngsters should not be underestimated. In its severe form, it is often associated with mood disorders. Findings in children and adolescent cases suggest that severe unexplained fatigue might precede the development of fatigue-related illness, such as childhood chronic fatigue syndrome (CCFS). This is a disabling condition characterized by severe disabling fatigue and a combination of symptoms, the prominent features being self-reported impairments in concentration and short-term memory, sleep disturbances and autonomic symptoms that cannot be explained by medical or psychiatric illness. We have encountered such patients with these complaints; their major symptoms include: general fatigue, fever, headache (not migraine), and memory disturbance. From our clinical experience, we have inferred that patients with CCFS might experience changes in brain function levels, which induce an autonomic imbalance and engender symptoms such as general fatigue, higher-order level cognitive dysfunction, and memory disturbance.

 

Source: Tomoda A. School phobia and childhood chronic fatigue syndrome (CCFS). Nihon Rinsho. 2007 Jun;65(6):1121-33. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561707

 

Autonomic function and child chronic fatigue syndrome

Abstract:

It is postulated that child chronic fatigue syndrome (CFS) involves the autonomic nervous system, although the precise mechanism has not been clearly indicated. This paper reviews recent reports focusing the role of the autonomic nervous system which plays in CFS. Many of the method for measuring autonomic function have appeared in the clinical setting in parallel with advancing computer technology, but these are limited when applied in children. In these blood pressure and heart rate changes during orthostatic stress and these variability are favorably used. As a result, one third of children with CFS showed abnormal cardiovascular adjustment during posture change (orthostatic dysregulation: OD) which is characterized by instantaneous orhthostatic hypotension, postural tachycardia or neurally-mediated syncope. Most of the studies using power spectral analysis of heart rate variability showed sympathetic activation, however no consistent finding has been obtained. In conclusion, autonomic function might be partly involved in CFS such as OD, but its priority in causing CFS is unclear.

 

Source: Tanaka H. Autonomic function and child chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1105-12. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561705