Assessment of fibromyalgia & chronic fatigue syndrome: a new protocol designed to determine work capability–chronic pain abilities determination (CPAD)

Abstract:

The objective was to design a protocol to assess work ability in people suffering ill-defined painful and disabling disorders, the outstanding prototype of which is fibromyalgia/chronic fatigue syndrome (FM/CSF).Following an extensive literature search, the mos appropriate components of current methods of assessment of physical and cognitive abilities were incorporated into the protocol, occasionally with appropriate modification to suit the specific requirements of the individual.

The initial part of the assessment consists of a standard history taking, principally focusing on the patient’s self-reported physical and cognitive abilities and disabilities, as well as the completion of established pain and fatigue scales, and relevant disability questionnaires.

Following this, physical and cognitive abilities are objectively assessed on two separate occasions, utilizing computerized hand-held dynamometers, inclinometers, algometers, and force dynamometers. Specific work simulation tests using the industrial standards Methods-Time-Measurement testing are availed of, as is aerobic testing using the Canadian Aerobic Fitness Test (CAFT). Objective computerised neuro-cognitive testing are also utilised as an integral component of the assessment. All results are then subject to specific computerized analysis and compared to normative and standardised work-based databases.

The designed system produces reliable, consistent and reproducible results. It also proves capable of detecting any inconsistencies in patient input and results, in addition to being independent of any possible assessor bias. A new protocol has been designed to determine the working capability of individuals who suffer from various chronic disabling conditions, and represents a significant step forward in a difficult but rapidly expanding area of medical practice.

 

Source: Kelly M, Gagne R, Newman JD, Olney C, Gualtieri C, Trail D. Assessment of fibromyalgia & chronic fatigue syndrome: a new protocol designed to determine work capability–chronic pain abilities determination (CPAD). Ir Med J. 2008 Oct;101(9):277-8. https://www.ncbi.nlm.nih.gov/pubmed/19051616

 

Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls

Abstract:

PURPOSE: Since physical exertion is known to exacerbate the symptoms of chronic fatigue syndrome (CFS) and metabolic changes and including oxidative stress can modulate heat shock protein (HSP) expression responses, we sought to determine whether HSP expression is altered in CFS patients before and after exercise. Heat shock proteins (HSPs) in peripheral blood mononuclear cells (PBMC) were examined from 6 chronic fatigue syndrome (CFS) patients and 7 controls before and after a standardized treadmill exercise. Basal hsp27 was significantly higher among CFS patients compared to controls, and decreased immediately post-exercise, remaining below basal levels even at 7 days. A similar pattern was observed for HSP60, which gradually decreased in CFS patients but increased in controls post-exercise. These findings suggest an abnormal adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.

METHODS: HSP27, HSP60, HSP70 and HSP90 expression from 6 CFS patients and 7 age- and sex-matched controls were examined by western blot analysis of peripheral blood mononuclear cells immediately before, after, and at 1 day and 7 days following a standardized treadmill exercise.

RESULTS: Basal HSP27 was higher among CFS patients than in controls (0.54 +/- 0.13 vs. 0.19 +/- 0.06, mean +/- SEM; P < 0.01). In addition, these levels in CFS patients decreased immediately post-exercise (0.25 +/- 0.09; P < 0.05) and remained below basal levels at day 1 post-exercises (0.18 +/- 0.05; P < 0.05). P < 0.05). This declining expression of HSP27 during the post-exercise period among CFS patients was confirmed by one-way ANOVA analysis with repeated measures (P < 0.05). In contrast, HSP27 levels remained relatively constant following exercise among control subjects. Similar patterns of declining HSP levels in CFS patients were also observed for HSP60 (0.94 +/- 0.40 vs. 1.32 +/- 0.46; P < 0.05), and for HSP90 (0.34 +/- 0.09 vs. 0.49 +/- 0.10; P < 0.05) at day 7 post-exercise compared with basal levels, respectively. In contrast, HSP60 levels in control subjects increased at day 1 (1.09 +/- 0.27) and day 7 (1.24 +/- 0.50) post-exercise compared to corresponding levels immediately post-exercise (0.55 +/- 0.06) (P < 0.05, respectively).

CONCLUSION: These preliminary findings suggest an abnormal or defective adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.

 

Source: Thambirajah AA, Sleigh K, Stiver HG, Chow AW. Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls. Clin Invest Med. 2008 Dec 1;31(6):E319-27. https://www.ncbi.nlm.nih.gov/pubmed/19032901

 

Are patients with chronic fatigue syndrome just ‘tired’ or also ‘sleepy’?

Abstract:

It is presently unclear whether chronic fatigue syndrome (CFS) patients exhibit daytime sleepiness in addition to fatigue. Both, fatigue, such as that seen in CFS patients, and excessive daytime sleepiness, such as in sleep apnea-hypopnea syndrome (SAHS), remain poorly understood. Both daytime conditions are generally related to unrefreshing sleep and show affective symptoms. This study’s objective was to contribute to the understanding of the relationship between fatigue and sleepiness in CFS patients not co-morbid for primary sleep or psychiatric disorders.

We compared 16 untreated CFS patients (mean age 32.8, all females) with 13 untreated SAHS (mean age 47.7, all females) patients and 12 healthy controls (mean age 32.2, all females). Objective sleepiness was measured using multiple sleep latency tests (MSLT). Subjective sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Fatigue Severity Scale, respectively. Mean Sleep Latency (SL) on the MSLT was significantly shorter in SAHS patients than in CFS patients and CFS patients showed significantly shorter mean SL than matched controls but within normal range.

Subjective sleepiness was greatest in SAHS patients and subjective fatigue was highest in CFS patients. Affective symptoms showed highest intensities in CFS patients. While higher than the control group on all measures, compared to SAHS, the CFS group had higher subjective fatigue and lower subjective and objective sleepiness. Despite possible overlap in symptoms and signs of both daytime conditions, our data indirectly support the clinical distinction between fatigue and sleepiness.

 

Source: Neu D, Hoffmann G, Moutrier R, Verbanck P, Linkowski P, Le Bon O. Are patients with chronic fatigue syndrome just ‘tired’ or also ‘sleepy’? J Sleep Res. 2008 Dec;17(4):427-31. doi: 10.1111/j.1365-2869.2008.00679.x. Epub 2008 Oct 17. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2869.2008.00679.x/full (Full article)

 

Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome

Abstract:

Complement activation resulting in significant increases of C4a split product may be a marker of postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on identification of the transcriptional control that may contribute to the increased C4a in CFS subjects after exercise.

We used quantitative reverse-transcription polymerase chain reaction to evaluate differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear cells (PBMCs). Calibrated expression values were normalized to the internal reference gene peptidylpropyl isomerase B (PPIB), the external reference gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs.

At 1 hour postexercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher levels (> or = 2-fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045). This result may be due to the significant but transient downregulation of MASP2 in control subjects (PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both groups.

In conclusion, lectin pathway responded to exercise differentially in CFS than in control subjects. MASP2 down-regulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.

 

Source: Sorensen B, Jones JF, Vernon SD, Rajeevan MS. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Mol Med. 2009 Jan-Feb;15(1-2):34-42. doi: 10.2119/molmed.2008.00098. Epub 2008 Nov 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/ (Full article)

 

Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. Following two microarray studies, we reported the differential expression of 88 human genes in patients with CFS; 85 of these genes were upregulated and 3 were downregulated.

The top functional categories of these 88 genes were hematologic disease and function, immunologic disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from CFS/ME patients revealed seven subtypes with distinct differences in Short Form (SF)-36 scores, clinical phenotypes, and severity. Gene signatures in each subtype implicate five human genes as possible targets for specific therapy.

Development of a diagnostic test for subtype status is now a priority. The possibility that these subtypes represent individual host responses to particular microbial infections is being investigated and may provide another route to specific therapies for CFS patients.

 

Source: Kerr JR. Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis. Curr Rheumatol Rep. 2008 Dec;10(6):482-91. https://www.ncbi.nlm.nih.gov/pubmed/19007540

 

A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome.

Abstract:

Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.

 

Source: Exley C, Swarbrick L, Gherardi RK, Authier FJ. A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome. Med Hypotheses. 2009 Feb;72(2):135-9. doi: 10.1016/j.mehy.2008.09.040. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19004564

 

Memory and attention problems in children with chronic fatigue syndrome or myalgic encephalopathy

Abstract:

OBJECTIVE: To understand more about the problems children with chronic fatigue syndrome (CFS) or myalgic encephalopathy (ME) experience with memory and attention, and to test the feasibility of quantitative measurement of both memory and attention.

DESIGN: Four-item semistructured questionnaire and neuropsychological test battery with 10 psychometric subtests.

SETTING: Family home of the child taking part.

PATIENTS: 20 children with a diagnosis of CFS/ME experiencing memory and/or concentration problems were recruited between April and October 2007 from a regional CFS/ME clinical service (female 13; average age 13.5 years; range 8-16).

METHODS: Each child, parent and teacher was asked to describe the child’s memory and attention problems. Responses were subject to thematic analysis by two independent researchers. In addition, each child completed a battery of 10 tests to measure: processing speed; attention; immediate and delayed memory; working memory; executive function. Raw scores were converted into age-scaled scores and the children’s psychometric scores on the 10 tests taken were compared with normative data using t tests.

RESULTS: Children with CFS/ME, their parents and teachers described problems with focussed attention, sustained attention, recall and stress. Scores for sustained attention (mean 8.1, 95% CI 6.3 to 9.9), switching attention (7.5, 5.5 to 9.4), divided attention (6.9, 5.5 to 8.2), auditory learning (8.2, 6.8 to 9.6) and immediate recall (8.7, 7.3 to 10.0) appeared lower than the normative mean of 10.

CONCLUSIONS: Children with CFS/ME appear to experience problems with attention, which may have adverse implications for verbal memory. These cognitive problems may explain some of the educational difficulties associated with CFS.

 

Source: Haig-Ferguson A, Tucker P, Eaton N, Hunt L, Crawley E. Memory and attention problems in children with chronic fatigue syndrome or myalgic encephalopathy. Arch Dis Child. 2009 Oct;94(10):757-62. doi: 10.1136/adc.2008.143032. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19001478

 

Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy

Abstract:

OBJECTIVE: To investigate factors associated with school attendance and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).

DESIGN: Cross-sectional study.

SETTING: Regional specialist CFS/ME service.

PATIENTS: Children and young people aged under 18 years.

OUTCOME MEASURES: Self-reported school attendance and physical function measured using the physical function subscale of the Short Form 36.

METHODS: Linear and logistic regression analysis of data from self-completed assessment forms on children attending a regional specialist service between 2004 and 2007. Analyses were done in two groups of children: with a completed Spence Children’s Anxiety Scale (SCAS) and with a completed Hospital Anxiety and Depression Scale (HADS).

RESULTS: Of 211 children with CFS/ME, 62% attended 40% of school or less. In children with completed SCAS, those with better physical function were more likely to attend school (adjusted odds ratio (OR) 1.70; 95% CI 1.36 to 2.13). This was also true for those with completed HADS (adjusted OR 2.05; 95% CI 1.4 to 3.01). Increasing fatigue and pain and low mood were associated with worse physical function. There was no evidence that anxiety, gender, age at assessment, family history of CFS/ME or time from onset of symptoms to assessment in clinic were associated with school attendance or physical function.

IMPLICATIONS: Paediatricians should recognise that reduced school attendance is associated with reduced physical function rather than anxiety. Improving school attendance in children with CFS/ME should focus on evidence-based interventions to improve physical function, particularly concentrating on interventions that are likely to reduce pain and fatigue.

 

Source: Crawley E, Sterne JA. Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy. Arch Dis Child. 2009 Oct;94(10):752-6. doi: 10.1136/adc.2008.143537. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19001477

 

Integrated weighted gene co-expression network analysis with an application to chronic fatigue syndrome

Abstract:

BACKGROUND: Systems biologic approaches such as Weighted Gene Co-expression Network Analysis (WGCNA) can effectively integrate gene expression and trait data to identify pathways and candidate biomarkers. Here we show that the additional inclusion of genetic marker data allows one to characterize network relationships as causal or reactive in a chronic fatigue syndrome (CFS) data set.

RESULTS: We combine WGCNA with genetic marker data to identify a disease-related pathway and its causal drivers, an analysis which we refer to as “Integrated WGCNA” or IWGCNA. Specifically, we present the following IWGCNA approach: 1) construct a co-expression network, 2) identify trait-related modules within the network, 3) use a trait-related genetic marker to prioritize genes within the module, 4) apply an integrated gene screening strategy to identify candidate genes and 5) carry out causality testing to verify and/or prioritize results. By applying this strategy to a CFS data set consisting of microarray, SNP and clinical trait data, we identify a module of 299 highly correlated genes that is associated with CFS severity. Our integrated gene screening strategy results in 20 candidate genes. We show that our approach yields biologically interesting genes that function in the same pathway and are causal drivers for their parent module. We use a separate data set to replicate findings and use Ingenuity Pathways Analysis software to functionally annotate the candidate gene pathways.

CONCLUSION: We show how WGCNA can be combined with genetic marker data to identify disease-related pathways and the causal drivers within them. The systems genetics approach described here can easily be used to generate testable genetic hypotheses in other complex disease studies.

 

Source: Presson AP, Sobel EM, Papp JC, Suarez CJ, Whistler T, Rajeevan MS, Vernon SD, Horvath S. Integrated weighted gene co-expression network analysis with an application to chronic fatigue syndrome.BMC Syst Biol. 2008 Nov 6;2:95. doi: 10.1186/1752-0509-2-95. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625353/ (Full article)

 

Vaccination as teenagers against meningococcal disease and the risk of the chronic fatigue syndrome

Abstract:

The etiology of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is unknown. In Norway, a vaccine against Neisseria meningitides group B was administered to teenagers in 1988–1989 in a protection trial. In order to estimate the relative risk of CFS/ME according to vaccine history, we conducted a case-control study in 2007, with 201 cases diagnosed at one of two hospitals and 389 controls. The adjusted odds ratio for CFS/ME was 1.06 (95% CI: 0.67-1.66) for subjects who received the active vaccine contrasted to subjects who did not. Using this design, no statistically significant association between vaccination against meningococcal disease in teenagers and occurrence of CFS/ME could be observed.

 

Source: Magnus P, Brubakk O, Nyland H, Wold BH, Gjessing HK, Brandt I, Eidem T, Nøkleby H, Stene-Larsen G. Vaccination as teenagers against meningococcal disease and the risk of the chronic fatigue syndrome. Vaccine. 2009 Jan 1;27(1):23-7. doi: 10.1016/j.vaccine.2008.10.043. Epub 2008 Nov 5. https://www.ncbi.nlm.nih.gov/pubmed/18984023