Chronic fatigue syndrome and experience with the Lightning Process

The cause of chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) is not well understood and is disputed, and therapeutic options are limited. Many patients who attended the Lightning Process course reported positive effects. This should lead to a randomised controlled intervention trial.

Since 2008 several thousand patients with CFS/ME have attended the Lightning Process (LP) course in Norway (1). The course is a three-day intensive brain rehearsal programme with the option for follow-up. Although what triggers CFS/ME in the individual case may vary, it is assumed that symptoms maintenance and chronification can be attributed to a stress response with elevated state of alertness and persisting activation of the sympathetic nervous system, driven by classic and operant conditioning mechanisms. The Lightning Process is based on these theories of stress.

You can read the rest of this article here: http://tidsskriftet.no/en/2016/03/chronic-fatigue-syndrome-and-experience-lightning-process

 

Source: Landmark L, Lindgren RM, Sivertsen B, Magnus P, Conradi S, Thorvaldsen SN, Stanghelle JK. Chronic fatigue syndrome and experience with the Lightning Process. Tidsskr Nor Laegeforen. 2016 Mar 15;136(5):396. doi: 10.4045/tidsskr.15.1214. ECollection 2016. [Article in English, Norwegian] http://tidsskriftet.no/en/2016/03/chronic-fatigue-syndrome-and-experience-lightning-process (Full article)

 

Methods of applying the 1994 case definition of chronic fatigue syndrome – impact on classification and observed illness characteristics

Abstract:

BACKGROUND: Multiple case definitions are in use to identify chronic fatigue syndrome (CFS). Even when using the same definition, methods used to apply definitional criteria may affect results. The Centers for Disease Control and Prevention (CDC) conducted two population-based studies estimating CFS prevalence using the 1994 case definition; one relied on direct questions for criteria of fatigue, functional impairment and symptoms (1997 Wichita; Method 1), and the other used subscale score thresholds of standardized questionnaires for criteria (2004 Georgia; Method 2). Compared to previous reports the 2004 CFS prevalence estimate was higher, raising questions about whether changes in the method of operationalizing affected this and illness characteristics.

METHODS: The follow-up of the Georgia cohort allowed direct comparison of both methods of applying the 1994 case definition. Of 1961 participants (53 % of eligible) who completed the detailed telephone interview, 919 (47 %) were eligible for and 751 (81 %) underwent clinical evaluation including medical/psychiatric evaluations. Data from the 499 individuals with complete data and without exclusionary conditions was available for this analysis.

RESULTS: A total of 86 participants were classified as CFS by one or both methods; 44 cases identified by both methods, 15 only identified by Method 1, and 27 only identified by Method 2 (Kappa 0.63; 95 % confidence interval [CI]: 0.53, 0.73 and concordance 91.59 %). The CFS group identified by both methods were more fatigued, had worse functioning, and more symptoms than those identified by only one method. Moderate to severe depression was noted in only one individual who was classified as CFS by both methods. When comparing the CFS groups identified by only one method, those only identified by Method 2 were either similar to or more severely affected in fatigue, function, and symptoms than those only identified by Method 1.

CONCLUSIONS: The two methods demonstrated substantial concordance. While Method 2 classified more participants as CFS, there was no indication that they were less severely ill or more depressed. The classification differences do not fully explain the prevalence increase noted in the 2004 Georgia study. Use of standardized instruments for the major CFS domains provides advantages for disease stratification and comparing CFS patients to other illnesses.

 

Source: Unger ER, Lin JM, Tian H, Gurbaxani BM, Boneva RS, Jones JF. Methods of applying the 1994 case definition of chronic fatigue syndrome – impact on classification and observed illness characteristics. Popul Health Metr. 2016 Mar 12;14:5. doi: 10.1186/s12963-016-0077-1. eCollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788915/ (Full article)

 

MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS/ME) is a complex multisystem disease of unknown aetiology which causes debilitating symptoms in up to 1% of the global population. Although a large cohort of genes have been shown to exhibit altered expression in CFS/ME patients, it is currently unknown whether microRNA (miRNA) molecules which regulate gene translation contribute to disease pathogenesis. We hypothesized that changes in microRNA expression in patient leukocytes contribute to CFS/ME pathology, and may therefore represent useful diagnostic biomarkers that can be detected in the peripheral blood of CFS/ME patients.

METHODS: miRNA expression in peripheral blood mononuclear cells (PBMC) from CFS/ME patients and healthy controls was analysed using the Ambion Bioarray V1. miRNA demonstrating differential expression were validated by qRT-PCR and then replicated in fractionated blood leukocyte subsets from an independent patient cohort. The CFS/ME associated miRNA identified by these experiments were then transfected into primary NK cells and gene expression analyses conducted to identify their gene targets.

RESULTS: Microarray analysis identified differential expression of 34 miRNA, all of which were up-regulated. Four of the 34 miRNA had confirmed expression changes by qRT-PCR. Fractionating PBMC samples by cell type from an independent patient cohort identified changes in miRNA expression in NK-cells, B-cells and monocytes with the most significant abnormalities occurring in NK cells. Transfecting primary NK cells with hsa-miR-99b or hsa-miR-330-3p, resulted in gene expression changes consistent with NK cell activation but diminished cytotoxicity, suggesting that defective NK cell function contributes to CFS/ME pathology.

CONCLUSION: This study demonstrates altered microRNA expression in the peripheral blood mononuclear cells of CFS/ME patients, which are potential diagnostic biomarkers. The greatest degree of miRNA deregulation was identified in NK cells with targets consistent with cellular activation and altered effector function.

 

Source: Petty RD, McCarthy NE, Le Dieu R, Kerr JR. MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME). PLoS One. 2016 Mar 11;11(3):e0150904. doi: 10.1371/journal.pone.0150904. ECollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788442/ (Full article)

 

Illness progression in chronic fatigue syndrome: a shifting immune baseline

Abstract:

BACKGROUND: Validation of biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) across data sets has proven disappointing. As immune signature may be affected by many factors, our objective was to explore the shift in discriminatory cytokines across ME/CFS subjects separated by duration of illness.

METHODS: Cytokine expression collected at rest across multiple studies for female ME/CFS subjects (i) 18 years or younger, ill for 2 years or less (n = 18), (ii) 18-50 years of age, ill for 7 years (n = 22), and (iii) age 50 years or older (n = 28), ill for 11 years on average. Control subjects were matched for age and body mass index (BMI). Data describing the levels of 16 cytokines using a chemiluminescent assay was used to support the identification of separate linear classification models for each subgroup. In order to isolate the effects of duration of illness alone, cytokines that changed significantly with age in the healthy control subjects were excluded a priori.

RESULTS: Optimal selection of cytokines in each group resulted in subsets of IL-1α, 6, 8, 15 and TNFα. Common to any 2 of 3 groups were IL-1α, 6 and 8. Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration sub-groups produced ME/CFS classification accuracies of 75-88 %. The contribution of IL-1α, higher in recently ill adolescent ME/CFS subjects was progressively less important with duration. While high levels of IL-8 screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years. Similarly, while low levels of IL-6 suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years.

CONCLUSIONS: These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.

 

Source: Russell L, Broderick G, Taylor R, Fernandes H, Harvey J, Barnes Z, Smylie A, Collado F, Balbin EG, Katz BZ, Klimas NG, Fletcher MA. Illness progression in chronic fatigue syndrome: a shifting immune baseline. BMC Immunol. 2016 Mar 10;17:3. doi: 10.1186/s12865-016-0142-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785654/ (Full article)

 

Moxibustion at Gaohuang (BL 43) for chronic fatigue syndrome: a randomized controlled trial

Abstract:

OBJECTIVE: To observe the clinical effect of chronic fatigue syndrome (CFS) treated with moxibustion at Gaohuang (BL 43).

METHODS: With stratified block randomization, 72 patients accorded with inclusive criteria were divided into a moxibustion at Gaohuang (BL 43) group (moxibustion group) and an acupuncture group, 36 cases in each one. In the moxibustion group, Gaohuang (BL 43) was treated with big moxa cones as the main acupoint, 10 cones a time; Qihai (CV 6) and Zusanli (ST 36) were added with big moxa cones, 7 cones a time. In the acupuncture group, acupoints were the same as those in the moxibustion group, and twirling reinforcing method was used after qi arriving, 60 times one minute and 360° with range. In the two groups, 10-day treatment was made into one course and there were two days between courses. The treatment was given once a day for 3 courses. Changes of fatigue assessment index (FAI) before and after treatment and clinical effects were observed.

RESULTS: The total effective rate was 88.9% (32/36) in the moxibustion group, which was better than 72.2% (26/36) in the acupuncture group apparently (P < 0.05). After treatment in the two groups, FAI scores were obviously declined compared with those before treatment (both P < 0.01) and FAI score in the moxibustion group was apparently lower than that in the acupuncture group (P < 0.05).

CONCLUSION: Moxibustion at Gaohuang (BL 43) can improve the FAI score of patients with CFS and the clinical efficacy is definite.

 

Source: Tian L, Wang J, Luo C, Sun R, Zhang X, Yuan B, Du XZ. Moxibustion at Gaohuang (BL 43) for chronic fatigue syndrome: a randomized controlled trial. Zhongguo Zhen Jiu. 2015 Nov;35(11):1127-30. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/26939325

 

Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study

Abstract:

Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial.

A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the fatigue severity scale (FSS), visual analog scale (VAS) and multidimensional fatigue inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup.

The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p=0.0242), VAS (p=0.0009) and MFI (p=0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS.

 

Source: Park SB, Kim KN, Sung E, Lee SY, Shin HC. Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study. Biol Pharm Bull. 2016 May 1;39(5):674-9. doi: 10.1248/bpb.b15-00623. Epub 2016 Feb 25. https://www.jstage.jst.go.jp/article/bpb/39/5/39_b15-00623/_html (Full article)

 

Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome

Abstract:

Introduction. Symptoms of mitochondrial diseases and chronic fatigue syndrome (CFS) frequently overlap and can easily be mistaken.

Methods. We report the case of a patient diagnosed with CFS and during follow-up was finally diagnosed with mitochondrial myopathy by histochemical study of muscle biopsy, spectrophotometric analysis of the complexes of the mitochondrial respiratory chain, and genetic studies.

Results. The results revealed 3% fiber-ragged blue and a severe deficiency of complexes I and IV and several mtDNA variants. Mother, sisters, and nephews showed similar symptoms, which strongly suggests a possible maternal inheritance. The patient and his family responded to treatment with high doses of riboflavin and thiamine with a remarkable and sustained fatigue and muscle symptoms improvement.

Conclusions. This case illustrates that initial symptoms of mitochondrial disease in adults can easily be mistaken with CFS, and in these patients a regular reassessment and monitoring of symptoms is recommended to reconfirm or change the diagnosis.

 

Source: Galán F, de Lavera I, Cotán D, Sánchez-Alcázar JA. Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome. J Investig Med High Impact Case Rep. 2015 Sep 24;3(3):2324709615607908. doi: 10.1177/2324709615607908. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748504/ (Full article)

 

A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

Abstract:

Background. CD8+ T cells have putative roles in the regulation of adaptive immune responses during infection. The purpose of this paper is to compare the status of CD8+ T cells in Multiple Sclerosis (MS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

Methods. This preliminary investigation comprised 23 CFS/ME patients, 11 untreated MS patients, and 30 nonfatigued controls. Whole blood samples were collected from participants, stained with monoclonal antibodies, and analysed on the flow cytometer. Using the following CD markers, CD27 and CD45RA (CD45 exon isoform 4), CD8+ T cells were divided into naïve, central memory (CM), effector memory CD45RA- (EM), and effector memory CD45RA+ (EMRA) cells.

Results. Surface expressions of BTLA, CD127, and CD49/CD29 were increased on subsets of CD8+ T cells from MS patients. In the CFS/ME patients CD127 was significantly decreased on all subsets of CD8+ T cells in comparison to the nonfatigued controls. PSGL-1 was significantly reduced in the CFS/ME patients in comparison to the nonfatigued controls.

Conclusions. The results suggest significant deficits in the expression of receptors and adhesion molecules on subsets of CD8+ T cells in both MS and CFS/ME patients. These deficits reported may contribute to the pathogenesis of these diseases. However, larger sample size is warranted to confirm and support these encouraging preliminary findings.

 

Source: Brenu EW, Broadley S, Nguyen T, Johnston S, Ramos S, Staines D, Marshall-Gradisnik S. A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis. J Immunol Res. 2016;2016:9064529. doi: 10.1155/2016/9064529. Epub 2016 Jan 4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736227/ (Full article)

 

Chronic fatigue syndrome and sleep disorders: clinical associations and diagnostic difficulties.

Abstract:

INTRODUCTION: Chronic fatigue syndrome (CFS) is characterised by the presence of intractable fatigue and non-restorative sleep, symptoms which are also very prevalent in multiple diseases and appear as side effects of different drugs. Numerous studies have shown a high prevalence of sleep disorders in patients with CFS. However, non-restorative sleep and fatigue are frequently symptoms of the sleep disorders themselves, so primary sleep disorders have to be ruled out in many cases of CFS.

DEVELOPMENT: This review was performed using a structured search of the MeSH terms ([Sleep]+[Chronic fatigue syndrome]) in the PubMed database.

CONCLUSION: Identifying primary sleep disorders in patients meeting diagnostic criteria for CFS will allow for a more comprehensive treatment approach involving new diagnostic and therapeutic strategies that may improve quality of life for these patients.

Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

 

Source: Ferré A. Chronic fatigue syndrome and sleep disorders: clinical associations and diagnostic difficulties. Neurologia. 2016 Feb 11. pii: S0213-4853(16)00010-4. doi: 10.1016/j.nrl.2015.11.019. [Epub ahead of print] [Article in English, Spanish] https://www.ncbi.nlm.nih.gov/pubmed/26877195 (Full text available as PDF)

 

Suicide risk in people with chronic fatigue syndrome

The risk of dying is increased in many illnesses, but the mortality associated with chronic fatigue syndrome is relatively unexplored. In The Lancet, Emmert Roberts and colleagues1 report results from a case register study that linked the clinical details of more than 2000 people with chronic fatigue syndrome presenting to a specialist clinic (in London and the south of England) with mortality outcomes over 7 years. This is the largest study of its type so far, and used a robust case definition. The researchers noted that the overall risk of death in patients with chronic fatigue syndrome seemed no different from the risk in the general population. Cancer mortality was also similar. However, the findings for suicide deaths were striking—five people died during the 7-year period. Based on the suicide rate in the general population of England and Wales, the expected number would have been less than one death by suicide. In other words, suicide risk was increased almost seven-fold. A previous US study2 reported an increase in suicide mortality in people with fatigue symptoms, but was too small to show an increased suicide risk in those who met the criteria for chronic fatigue syndrome.

The results of the current study are potentially very important but need to be interpreted with caution. The study was quite small for an investigation of mortality (n=2147 patients of whom 17 died). This small sample meant that the stratified analyses in particular (investigation of the risk of death in sex, age, diagnostic, and deprivation subgroups) lacked statistical power. The increased suicide mortality (sex-standardised mortality ratio 6·85, 95% CI 2·22–15·98; p=0·002) was based on just a few deaths and the confidence intervals were wide. Two fewer suicide deaths would have meant that the findings were no longer significant.

The cohort itself was well defined but consisted of people who attended a national specialist centre run jointly by general medical and mental health service providers. This could mean that participants were representative of people with more severe or complex chronic fatigue syndrome, and the mortality findings might not be applicable to people with the disorder in primary care.

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Source: Kapur N, Webb R. Suicide risk in people with chronic fatigue syndrome. Lancet. 2016 Apr 16;387(10028):1596-7. doi: 10.1016/S0140-6736(16)00270-1. Epub 2016 Feb 10. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00270-1/fulltext (Full article)