ME and
CFS References
Number
4
|
1st
October 2009
|
NEUROLOGY
Pietrangelo T, Toniolo L, Paoli A, Fulle S,
Puglielli C, Fano G, Reggiani C. Functional characterization of muscle
fibres from patients with chronic fatigue syndrome: case-control study.
International Journal of Immunopathology and Pharmacology, 2009, 22, 2,
427-436.
CFS is a disabling condition characterized by
unexplained chronic fatigue that impairs normal activities. Although
immunological and psychological aspects are present, symptoms related to
skeletal muscles, such as muscle soreness, fatigability and increased lactate
accumulation, are prominent in CFS patients. In this case-control study, the
phenotype of the same biopsy samples was analyzed by determining i) fibre-type
proportion using myosin isoforms as fibre type molecular marker and gel
electrophoresis as a tool to separate and quantify myosin isoforms, and ii)
contractile properties of manually dissected, chemically made permeable and
calcium-activated single muscle fibres. Patients were diagnosed using the CDC
criteria (n=10) and compared to ten healthy, age and sex-matched, sedentary
controls (n=9). Biopsies were taken from the vastus lateralis muscle.
The results showed that fibre-type proportion was
significantly altered in CFS samples, which showed a shift from the slow- to the
fast-twitch phenotype (2X). Cross sectional area, force, maximum shortening
velocity and calcium sensitivity were not significantly changed in single muscle
fibres from patient samples. Thus, the contractile properties of muscle
fibres were preserved but their proportion was changed, with an increase in
the more fatigue-prone, energetically expensive fast fibre type (2X MyHC).
Taken together, these results support the view
that muscle tissue is directly involved in the pathogenesis of CFS and it might
contribute to the early onset of fatigue typical of the skeletal muscles of CFS
patients.
[Ed. Note: Unpublished data in
the discussion suggests that the findings were not due to inactivity or
disuse, also supported by the absence of change in the fibre size. See also
Lane et al, 1998. The authors speculate that increased ATP consumption
during contraction may be a factor in fatigue.]
IMMUNOLOGY
Ortega-Hernandez, OD., Cuccia, M., Bozzini, S.,
Bassi, N., Moscavitch, S., Diaz-Gallo, LM., Blank, M., Agmon-Levin, N and
Shoenfeld, Y.
Autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte
antigen class II alleles in chronic fatigue syndrome. Annals of the New York
Academy of Sciences, 2009, 1173, 589-599.
This study aimed to determine the influence of
autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte
antigen (HLA) class II genes on age at CFS onset and symptoms. Eighty-one CFS
patients (CDC criteria '94 and 2005, 7% reporting myalgia, 62% with unexplained
fever, none with impaired concentration or sore throat) were enrolled, and
clinical data were recorded. Autoantibodies to different components of the
central nervous system were tested. Polymorphisms in the promoter of the
serotonin transporter gene (l/s) and a single nucleotide polymorphism in the
serotonin receptor-2A gene (A/G) as well as HLA class II alleles were
determined. Multivariate logistic-regression analyses were carried out.
The mean age at CFS onset + SD was 33.5
+ 12.5 years. An age at CFS onset (ACFSO) during the third decade of life
was associated with the serotonin receptor AA genotype and the HLA-DRB1*03
allele. An ACFSO during the fourth decade of life was associated with the
HLA-DRB1*07 allele, whereas an ACFSO > 43 years was associated with
having at least one copy of the serotonin G allele. Concerning CFS symptoms, the
serotonin AG genotype was protective against depressive symptoms. Although
having at least one copy of the serotonin A allele and being female were
associated with risk for arthralgia, the presence of antineuronal cell
antibodies was protective against this. Episodes of unexplained fever were
associated with the HLA-DRB1*11 allele. None of the genetic or
serological features was associated with myalgia. Moreover, none of the
antibodies determined correlated with any ACFSO or other symptoms.
Our results reveal that in CFS, like other
autoimmune diseases, different genetic features are related to age at CFS onset
and symptoms.
See also Ortega-Hernandez, OD and Shoenfeld, Y.
Infection, vaccination, and autoantibodies in chronic fatigue syndrome,
cause or coincidence? Ibid, 1173, 600-609.
Viewpoint article speculating about the role of
immunological variables and enterobacteria.
PHYSIOLOGY AND BIOCHEMISTRY
Blaney, GP., Albert, PJ and Proal, AD.
Vitamin D metabolites as clinical markers in autoimmune and chronic disease.
Annals of the New York Academy of Sciences, 2009, 1173, 384-390.
Recent research has implicated vitamin D
deficiency (serum levels of 25-hydroxyvitamin D <50 nmol/L) with a number of
chronic conditions, including autoimmune conditions such as multiple sclerosis,
lupus, and psoriasis, and chronic conditions such as osteoporosis, osteo-arthritis,
metabolic syndrome and CFS/fibromyalgia (FM) (n=43).
It has been assumed that low levels of
25-hydroxyvitamin D (25-D) accurately indicate vitamin D storage and vitamin D
receptor (VDR)-mediated control of calcium metabolism and innate immunity. To
evaluate this assumption, 25-D and 1,25-dihydroxyvitamin D3 (1,25-D, also known
as calcitriol, "the active form of vitamin D") levels were measured in 100
Canadian patients with these conditions. Additionally, other inflammatory
markers (CK, CRP) were measured.
Of the patients with CFS/FM, 10 had <50 nmol/L of
25-D while 38 had >110 pmol/L of 1,25-D. Eight patients had elevated levels of
C-reactive protein and only one had an elevated level of creatine kinase.
Overall, the results showed a strong positive
association between these autoimmune conditions and levels of 1,25-D >110 pmol/L.
However, there was little association with vitamin D deficiency or the other
inflammatory markers, meaning that the results challenge the assumption that
serum levels of 25-D are a sensitive measure of the autoimmune disease state.
Rather, these findings support the use of 1,25-D as a clinical marker in
autoimmune conditions.
High levels of 1,25-D may result when
dysregulation of the VDR by bacterial ligands prevents the receptor from
expressing enzymes necessary to keep 1,25-D in a normal range.
Extracts from the discussion: Vitamin D
supplementation leads to the formation of 25-D rather than 1,25-D. High levels
of 25-D do not appear to prevent inflammatory disease, as 34 out of the 100
patients tested had 25-D levels above 80 nmol/L. This is consistent with other
poor results of vitamin D supplementation in the treatment of inflammatory
disease, particularly over long periods of time... In contrast, 1,25-D appears
to be a highly sensitive clinical marker in diagnosis of autoimmune and
associated diseases. It may be fruitful to consider why levels of 1,25-D are
elevated in patients with autoimmune diagnoses. One possibility is that the
vitamin D receptor (VDR) becomes dysregulated when exposed to sufficient
quantities of substances created by bacteria that antagonize or otherwise
inhibit the VDR. One such substance is the sulfonolipid ligand capnine. The
protease caspase-3, which is up-regulated by P. aeruginosa and H.
pylori, has a similar effect on the VDR, effectively inactivating it by
cleaving it. The persistent and difficult-to-culture bacteria that create these
substances may play a role in the pathogenesis of autoimmune and related
diseases. As bacterial ligands compromise the activity of the VDR, the receptor
is prevented from expressing CYP24, an enzyme that breaks the 1,25-D down into
its inactive metabolites. This allows 1,25-D levels to rise without a feedback
system to keep them in check, resulting in the elevated levels of the hormone as
observed in our cohort.
[Ed. Note: the authors report
that a trial of a VDR agonist resulted in reduced 1,25-D levels as
inflammation decreased.]
PSYCHOLOGY AND PSYCHIATRY
Royle, GH and Pimm, JT. A pilot study of
the process of change in a group chronic fatigue syndrome management programme.
Bulletin of the IACFS/ME, 2009, 17, 2, 53-68.
Cognitive-behavioural therapy (CBT) and graded
exercise therapy are efficacious therapies in patients with CFS. There is some
evidence for the efficacy of group programmes that employ the same principles of
rehabilitation. Little is known about the process of change with these
interventions, however it is important to understand why change occurs in order
to improve outcomes.
The aims were to investigate the process of change
and related outcomes in participants in a CFS group management programme (n=17,
Oxford criteria, no co-morbid psychiatric disorders.) Measures included the
Chalder Fatigue Scale. Task analysis was used to generate a health
professionals’ model specifying the psychological shifts thought necessary for
participants to improve. Following this, data from participant interviews were
analysed to see whether they matched the shifts specified in the model.
Participants were able to identify ‘key moments’
which they thought were involved in change. One commonly cited key moment
involved participants coming to the realization that they were not unique in
their difficulties and there were others in the group who understood, and had
experienced similar problems. Four of the six shifts identified by health
professionals were also identified as key moments by participants.
This study highlights the potential benefits of
group work for people with CFS/ME including opportunities for validation from
peers, sharing and modelling, all of which are suggested to be important in the
process of change. "The findings also suggest the important role of health
professionals in validating patient experience, facilitating the development of
an adaptive conceptualisation, utilising strategies to encourage acceptance, and
facilitating confidence through experimentation and modelling."
[Ed. Note: This uncontrolled
trial used a small, broadly-defined sample. There are controversial claims
regarding the efficacy of group CBT and CBT overall, as well as pacing and
the PACE Trial (which assesses APT, not pacing as devised by Goudsmit/Jason/Friedberg)
plus the role of avoidance. There is a paucity of information of the
treatment programme, so it is not replicable. The use of the Oxford criteria
is unusual in current research; this and other issues suggest that the
results should be interpreted with caution.]
GENETICS
Gow, JW., Hagan, S., Herzyk, P., Cannon, C.,
Behan, PO and Chaudhuri, A.
A gene signature for post-infectious chronic fatigue
syndrome. BMC Medical Genomics, 2009, 2:38. doi:10.1186/1755-8794-2-38.
At present, there are no clinically reliable disease markers for CFS. DNA
chip microarray technology provides a method for examining the differential
expression of mRNA from a large number of genes. Our hypothesis was that a gene
expression signature, generated by microarray assays, could help identify genes
which are dysregulated in patients with post-infectious CFS and so help identify
biomarkers for the condition.
Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from
33,000 gene sequences) were used to compare the levels of gene expression in the
peripheral blood mononuclear cells of male patients with post-infectious chronic
fatigue (CDC criteria '94, n=8) and male healthy control subjects (n=7).
Patients and healthy subjects differed significantly in the level of
expression of 366 genes. Analysis of the differentially expressed genes
indicated functional implications in immune modulation, oxidative stress and
apoptosis. Prototype biomarkers were identified on the basis
of differential levels of gene expression and possible biological
significance
Differential expression of key genes identified in this study offer an
insight into the possible mechanism of chronic fatigue following infection. The
representative biomarkers identified in this research appear promising as
potential biomarkers for diagnosis and treatment.
http://www.biomedcentral.com/1755-8794/2/38
Lee, E., Cho, S., Kim, K and Park, T. An integrated approach to infer
causal associations among gene expression, genotype variation, and disease.
Genomics, 2009, doi:10.1016/j.ygeno.2009.06.002.
Gene expression data and genotype variation data are now capable of providing
genome-wide patterns across many different clinical conditions. However, the
separate analysis of these data has limitations in elucidating the complex
network of gene interactions underlying complex traits, such as common human
diseases. More information about the identity of key driver genes of common
diseases comes from integrating these two heterogeneous types of data. We
developed a two-step procedure to characterize complex diseases by integrating
genotype variation data and gene expression data. The first step elucidates the
causal relationship among genetic variation, gene expression level, and disease.
Based on the causal relationship determined at the first step, the second step
identifies significant gene expression
traits whose effects on disease status or whose responses to disease status
are modified by the specific genotype variation. For the selected significant
genes, a pathway enrichment analysis can be performed to identify the genetic
mechanism of a complex disease.
The proposed two-step procedure was shown to be an effective method for
integrating three different levels of data, i.e., genotype variation, gene
expression and disease status. By applying the proposed procedure to a CFS
dataset (CDC criteria '94), we identified a list of potential causal genes for
CFS, and found an evidence for difference in genetic mechanisms of the etiology
between CFS without ‘a major depressive disorder with melancholic features’
(CFS, n=46) and CFS with ‘a major depressive disorder with melancholic features’
(CFS-MDD/m, n=19). Especially, the SNPs within NR3C1 gene were shown to
differently influence the susceptibility of developing CFS and CFS-MDD/m through
integrative action with gene expression levels.
THERAPEUTICS
Fluge, Ø and Mella, O. Clinical impact of B-cell depletion with the
anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case
series. BMC Neurology 2009, 9:28. doi:10.1186/1471-2377-9-28.
CFS is a disease of unknown aetiology. A patient with CFS had unexpected,
marked recovery of CFS symptoms lasting for five months during and after
cytotoxic chemotherapy for Hodgkin’s disease. We reasoned that the transient CFS
recovery was related to methotrexate treatment which induces immunomodulation in
part through B-cell depletion.
In a case series, this patient and two additional CFS patients (fatigue
following cancer, glandular fever, the other fatigue following glandular fever
alone) were B-cell depleted by infusion of the monoclonal anti-CD20 antibody
rituximab.
All three had improvement of all CFS symptoms. Patients 1 and 2 had major
amelioration from 6 weeks after intervention, patient 3 slight improvement from
the same time, but then improved markedly from 26 weeks after intervention. The
symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse,
all were re-treated with a single (patient 1) or double rituximab infusion
(patients 2 and 3). Again, all three had marked symptom improvement, mimicking
their first response. After new symptom recurrence, patients 1 and 2 were given
weekly oral methotrexate, patient 1 having effect also from this agent. Patients
1 and 2 were again treated for a third rituximab infusion after new relapse,
again with a marked clinical benefit. No unexpected toxicity was seen.
These observations suggest that B-lymphocytes are involved in CFS
pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed
symptom relief following B-cell depletion, the kinetics of relapses, and the
effect also from methotrexate treatment, provide suggestive evidence that
B-cells play a significant role in the ongoing clinical features, and that CFS
may be amenable to therapeutic interventions aimed at modifying B-cell number
and function. More systematic investigations of this therapeutic strategy, and
of its biological basis, are now needed.
http://www.biomedcentral.com/content/pdf/1471-2377-9-28.pdf
MISCELLANEOUS
Arroll, MA and Senior, V. Symptom typology
and sub-grouping in chronic fatigue syndrome. Bulletin of the IACFS/ME,
2009, 17, 2, 39-52.
CFS is a condition of unknown aetiology with a
heterogeneous population. The variability in symptomatology produces
difficulties in studying CFS, therefore this study aimed to establish symptom
typology and sub-groups within a sample of participants by use of data reduction
techniques.
Two-hundred and forty-six participants recruited
from groups with self-reported CFS com-pleted two symptom measures (one of which
evaluated CFS-specific symptoms – PFRS - and the other a general symptom
checklist - PILL) which were subsequently combined and analysed. Symptom types
were established with factor analysis, whereas sub-groups within the sample were
determined by cluster analysis.
Five symptom types resulted from the factor
analysis which were labelled FMS-like, depression/anxiety, fatigue/post-exertional
malaise, cognitive/neurological and IBS-like symptoms, with the FMS-like
accounting for the majority of the variance in the data. Cluster analysis
illustrated that the sample could be divided into three sub-groups based upon
the symptom reports. The clusters that emerged were formed of a low
symptomatology sub-group (LSS-G), a medium symptomatology sub-group (MSS-G) and
a high symptomatology sub-group (HSS-G), which, as the names suggests, signified
symptom severity. Notably, these subgroups did not differ in respect to age,
sex, illness duration or time taken to gain a diagnosis which infers that the
groupings were not influenced by demographic concerns.
This study illustrated that symptomatology in CFS
can be divided into distinct categories that concur with the most recent
guidelines for the condition. Additionally, the illness can be separated into
discrete subgroups, although these groupings are linked to overall severity,
rather than symptom types.
[Ed. Note: The five categories
do not match those of the Canadian criteria. However, this was a
self-selected patient group and the diagnosis was not checked, e.g. using
medical examinations.]
Attree, EA., Dancey, CP and Pope, AL. An
assessment of prospective memory retrieval in women with chronic fatigue
syndrome using a virtual-reality environment: An initial study.
Cyberpsychology & Behavior, 2009, 12, 4, 379-385.
People with CFS have increased rates of
depression, anxiety, and illness intrusiveness; they may also suffer from
cognitive problems such as retrospective memory (RM) deficits and concentration
difficulties that can stem from diminished information-processing capability. We
predicted that this diminished capacity may also lead to deficits in other
cognitive functions, such as prospective memory (ProM).
Event-, time-, and activity-based ProM was
assessed in 11 women with CFS (physician-diagnosed) and 12 healthy women using a
computer-generated virtual environment (VE). RM was assessed using a free-recall
test, and subjective assessment of both ProM and RM was assessed by
questionnaire. Groups were equivalent in age and measures of IQ.
People with CFS performed slightly worse than
healthy controls on both the event- and time-based ProM measures, although these
were not statistically significant. However, the CFS group performed
significantly worse than the healthy controls on both the free recall-task and
on subjective assessment of both RM and ProM.
Women with CFS do have some subtle decrements in
memory, particularly RM. However, it is possible that the decrements found in
the present sample would be greater in real life.
Further studies utilizing both healthy controls and illness controls are now
needed to ascertain how sensitive the VE measure is and to inform the
development of tasks in the VE that place progressively increasing demands on
working memory capacity.
Boneva, RS., Lin, JM., Maloney, EM., Jones, JF
and Reeves, WC. Use of medications among people with chronic fatigue
syndrome and healthy persons: a population-based study of fatiguing illness in
Georgia. Health and Quality of Life Outcomes, 2009 Jul 20;7:67.
doi:10.1186/1477-7525-7-67.
CFS is a debilitating condition of unknown
etiology and no definitive pharmacotherapy.
Patients are usually prescribed symptomatic treatment or self-medicate. We
evaluated prescription and non-prescription drug use among persons with CFS in
Georgia and compared it to that in non-fatigued Well controls and also to
chronically Unwell individuals not fully meeting criteria for CFS.
This was a population-based, case-control study.
To identify persons with possible CFS-like illness and controls, we conducted a
random-digit dialing telephone screening of 19,807 Georgia residents, followed
by a detailed telephone interview of 5,630 to identify subjects with CFS-like
illness, other chronically Unwell, and Well subjects. All those
with CFS-like illness (n=469), a random sample of chronically Unwell
subjects (n=505), and Well individuals (n=641) who were age-, sex-,
race-, and geographically matched to those with CFS-like illness were invited
for a clinical evaluation and 783 participated (48 % overall response rate).
Clinical evaluation identified 113 persons with CFS (CDC criteria '94 and '03),
264 Unwell subjects with insufficient symptoms for CFS (named ISF), and
124 Well controls; the remaining 280 subjects had exclusionary medical or
psychiatric conditions, and 2 subjects could not be classified. Subjects were
asked to bring all medications taken in the past 2 weeks to the clinic where a
research nurse viewed and recorded the name and the dose of each medication.
More than 90% of persons with CFS used at least
one drug or supplement within the preceding two weeks. Among users, people with
CFS used an average of 5.8 drugs or supplements, compared to 4.1 by ISF and 3.7
by Well controls. Persons with CFS were significantly more likely to use
antidepressants, sedatives, muscle relaxants, and anti-acids than either Well
controls or the ISF group. In addition, persons with CFS were significantly more
likely to use pain-relievers, anti-histamines and cold/sinus medications than
were Well controls.
Researchers and medical care providers of patients
with CFS should be aware of polypharmacy as a problem in such patients, and the
related potential iatrogenic effects and
drug interactions.
http://www.hqlo.com/content/pdf/1477-7525-7-67.pdf
Donalek, JG. When a patient is chronically
ill: chronic fatigue syndrome. Nursing Research, 2009, 58, 5, 332-339.
Chronic illness may reshape not only the life of
the ill parent but also that of the entire family, but research in this area
remains limited. More specifically, little is known about how an ill parent and
the family respond to a particularly devastating and controversial chronic
illness, CFS.
The objective of this study was to describe the
responses of the parent and the ensuing family system responses to the presence
of CFS as a chronic parental illness. Parents were interviewed individually, and
then the ill parent and as many immediate family members as possible were
interviewed collectively. After consent or assent, interviews were
audiotaped and transcribed. Thematic analyses at the individual, intrafamily,
and across-family levels were used to explore these phenomena.
Eight ill parents first described the onset of
illness, an ongoing struggle to receive diagnosis and care, and the significance
of the illness in transforming present and future roles. Multiple
members of the family together with the ill parent described how they struggled
with the reality of the illness, the shifting roles and responsibilities, the
reduced family income, and the frequent social isolation that could be
exacerbated by the controversial nature of the illness. Families described and
demonstrated their struggles to maintain normal family life and plans in the
face of continuing uncertainty.
This study is situated within current scholarship
on family responses to chronic parental illness. The value of the family
research interview is affirmed. Recommendations are made for future directions
in family nursing research exploring responses of families in which a parent is
chronically ill.
Heim, C. New perspective on chronic fatigue
syndrome: lessons from developmental neuroscience. Future Neurology,
2009, 4, 4, 377-381.
[Ed. Note: Editorial using a
broad definition of CFS and emphasising the role of emotional, psychological
and sexual abuse in childhood, with its effects on HPA regulation and immune
function. The author acknowledges the existence of subgroups, but does not
mention the epidemics and post-viral subsets e.g. ME. The suggestion is that
CFS represents a failure to adapt to stressors.]
Hokama, Y., Campora, CE., Hara,
C., Kuribayashi, T., Le Huynh, D and Yabusaki, K. Anti-cardiolipin
antibodies in the sera of patients with diagnosed chronic fatigue syndrome.
Journal of Clinical Laboratory Analysis, 2009, 23, 210-213.
Examination of anticardiolipin antibodies (ACAs)
in the 40 sera of patients clinically diagnosed with CFS (based on the CDC
criteria '94, some also had diagnoses such as diabetes, leukaemia) using an
enzyme-linked immunoassay procedure demonstrated the presence of immunoglobulin
M isotypes in 95% of CFS serum samples tested. The presence of immunoglobulin G
and immunoglobulin A isotypes were also detected in a subset of the samples.
Future studies will focus on elucidating whether
alterations to mitochondrial inner membranes and/or metabolic functions play a
possible role in the expression of ACAs.
Huang, L-C., Hsu, S-J and Lin, E.
A comparison of classification methods for predicting
chronic fatigue syndrome based on genetic data. Journal of Translational
Medicine, 2009, 7:81. doi:10.1186/1479-5876-7-81.
A paper describing "
a
promising method to assess the associations between CFS and SNPs" (single
nucleotide polymorphisms).
Jason, LA., Jessen, T., Porter, N., Boulton,
A., Gloria-Njoku, M and Friedberg, F. Examining types of fatigue among
individuals with ME/CFS. Disability Studies Quarterly, 2009, 29, 3. Epub.
Severe, persisting fatigue is a prominent symptom
of Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS), but individuals
with this illness frequently report the occurrence of unique fatigue states that
might be different from conventional symptoms of fatigue.
The present study attempted to assess a
comprehensive set of fatigue symptoms that have been commonly reported among
patients with ME/CFS. A 22-item fatigue questionnaire was developed and
administered to 130 persons diagnosed with ME/CFS (recruited from groups,
newspapers etc) and 251 controls.
Adequate scale reliability was found. Factor
analyses revealed a five-factor structure for participants with ME/CFS but only
a one-factor solution for the control group. The new scale was also contrasted
with other more traditional scales developed to measure fatigue.
Findings suggest that individuals with ME/CFS
experience different types of fatigue than what are reported in the general
populations
.
http://www.dsq-sds.org/article/view/938/1113
Katz, BZ., Shiraishi, Y., Mears, CJ., Binns, HJ
and Taylor, R. Chronic fatigue syndrome after infectious mononucleosis in
adolescents. Pediatrics, 2009,124, 1, 189-193.
The goal was to characterize prospectively the
course and outcome of CFS in adolescents during a 2-year period after infectious
mononucleosis (IM).
A total of 301 adolescents (12-18 years of age)
with IM were identified and screened for nonrecovery 6 months after IM by using
a telephone screening interview. Nonrecovered adolescents underwent a medical
evaluation, with follow-up screening 12 and 24 months after IM. After blind
review, final diagnoses of CFS at 6, 12, and 24 months were made by using
established pediatric criteria.
Six, 12, and 24 months after IM, 13%, 7%, and 4%
of adolescents, respectively, met the criteria for CFS. Most individuals
recovered with time; only 2 adolescents with CFS at 24 months seemed to have
recovered or had an explanation for chronic fatigue at 12 months but then were
reclassified as having CFS at 24 months. All 13 adolescents with CFS 24 months
after IM were female and, on average, they reported greater fatigue severity at
12 months. Reported use of steroid therapy during the acute phase of IM did not
increase the risk of developing CFS.
IM may be a risk factor for CFS in adolescents.
Female gender and greater fatigue severity, but not reported steroid use during
the acute illness, were associated with the development of CFS in adolescents.
Additional research is needed to determine other predictors of persistent
fatigue after infectious mononucleosis.
Li, H., Meng, S., Levine, SM., Stratton, CW and
Tang, YW. Sensitive, qualitative detection of human herpesvirus-6 and
simultaneous differentiation of variants A and B. Journal of Clinical
Virology, 2009, 46, 1, 20-23.
The current limitations of laboratory testing for
the detection of human herpesvirus virus 6 (HHV-6) in clinical specimens with
low HHV-6 viral loads make this area a priority for further research and
development.
The objectives were to develop and validate a
sensitive qualitative assay for simultaneous HHV-6 detection and variant
differentiation. We developed a diagnostic procedure, which combines a magnetic
bead-based nucleic acid extraction, PCR amplification, and colorimetric
microtiter plate identification (MAG-PCR-EIA), for the sensitive detection of
HHV-6 and the simultaneous differentiation of HHV-6A and HHV-6B.
Analytic sensitivities of the MAG-PCR-EIA assay
were 10 copies per reaction for both HHV-6A and HHV-6B variants, which is
equivalent to 20 copies/ml when 1ml of clinical specimen was processed. A
proficiency panel containing 11 blinded specimens covering HHV-6A viral loads
from 0 to 100,000 copies was tested, and the MAG-PCR-EIA was able to detect the
lowest concentration at one copy in 200 μl. A panel of 27 urine specimens, which
were collected from patients with and without CFS, was tested by the MAG-PCR-EIA.
HHV-6 was detected in two (HHV-6A) patients who
have chromosomally integrated HHV-6A and in one (HHV-6B) patient who was a
healthy control and diagnosed as having cervical cancer later on. The HHV-6
results did not correlate with results previously deter-mined by HHV-6
antigenemia in urine.
With large specimen volumes processed and an
additional signal amplification incorporated, the MAG-PCR-EIA provides a
sensitive and qualitative system for HHV-6 detection and simultaneous variant
differentiation. Clinical relevance of the assay awaits further investigation.
Light, AR., White, AT., Hughen, RW and Light,
KC. Moderate exercise increases expression for sensory, adrenergic, and
immune genes in chronic fatigue syndrome patients but not in normal subjects.
Journal of Pain, 2009 Aug 3. [Epub ahead of print].
doi:10.1016/j.jpain.2009.06.003
CFS is characterized by debilitating fatigue,
often accompanied by widespread muscle pain that meets criteria for FM syndrome.
Symptoms become markedly worse after exercise. Previous studies implicated
dysregulation of the sympathetic nervous system (SNS), and immune system (IS) in
CFS and FMS. We recently demonstrated that acid sensing ion channel (probably
ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the transient
receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse
sensory neurons detecting metabolites that cause acute muscle pain and possibly
muscle fatigue. These molecular receptors are found on human leukocytes along
with SNS and IS genes.
Real-time, quantitative PCR showed that 19 CFS
patients (CDC criteria '94, 42% previously diagnosed with depression, 68% also
met criteria for FM) had lower expression of β-2 adrenergic receptors but
otherwise did not differ from 16 control subjects before exercise.
After a sustained moderate exercise test, CFS patients showed greater increases
than control subjects in gene expression for metabolite detecting receptors
ASIC3, P2X4, and P2X5, for SNS receptors α-2A, β-1, β-2, and COMT and IS genes
for IL10 and TLR4 lasting from 0.5 to 48 hours (p<.05). These increases were
also seen in the CFS subgroup with comorbid FM and were highly correlated with
symptoms of physical fatigue, mental fatigue, and pain.
These new findings suggest dysregulation of
metabolite detecting receptors as well as SNS and IS in CFS and CFS-FM. Muscle
fatigue and pain are major symptoms of CFS. After moderate exercise, CFS and
CFS-FMS patients show enhanced gene expression for receptors detecting muscle
metabolites and for SNS and IS, which correlate with these symptoms. These
findings suggest possible new causes, points for intervention, and objective
biomarkers for these disorders.
Lyle, N., Gomes, A., Sur, T., Munshi, S., Paul,
S., Chatterjee, S and Bhattacharyya D. The role of antioxidant properties of
Nardostachys jatamansi in alleviation of the symptoms of the chronic fatigue
syndrome. Behavioural Brain Research, 2009, 202, 2, 285-290.
[ED. Note: Study using animal
model.]
Reynolds, NJ., Brown, MM and Jason, LA. The
relationship of Fennell phases to symptoms among patients with chronic fatigue
syndrome. Evaluation of the Health Professions, 2009, 32, 3, 264-280.
The Fennell Phase Inventory (FPI) is an instrument
designed to measure phases of the illnesses known as Myalgic
Encephalomyelitis/chronic fatigue syndrome (ME/CFS). The current study explored
how the FPI was related to physical and psychological functioning as well as
coping style.
Based on FPI scores, 111 adults with ME/CFS were
placed in one of three groups: crisis, stabilization, or resolution. Results
showed that the crisis group demonstrated significantly worse functioning than
at least one other group for depression, quality of life, mental functioning,
anxiety, and self efficacy; and utilized less adaptive coping styles. These
results indicate that patients with ME/CFS who are in the crisis phase tend to
experience more severe psychological and physical symptoms and utilize poorer
coping strategies. Those in the resolution phase maintain the most adaptive
coping strategies. Implications for these findings are discussed.
Sheedy, JR., Wettenhall, REH., Scanlon, D.,
Gooley, PR., Lewis, DP., McGregor, N., Stapleton, DI., Butt, HL and De Meirleir,
KL. Increased D-lactic acid intestinal bacteria in patients with chronic
fatigue syndrome. In Vivo, 2009, 23, 4, 621-628.
Patients with CFS are affected by symptoms of
cognitive dysfunction and neurological impairment, the cause of which has yet to
be elucidated. However, these symptoms are strikingly similar to those of
patients presented with D-lactic acidosis. First morning bowel samples were
assessed.
A significant increase of Gram positive
facultative anaerobic faecal microorganisms in 108 patients with CFS (CDC '88,
'94 and Canadian) as compared to 177 control subjects (p<0.01) is presented in
this report. Symptoms were assessed with a questionnaire.
The viable count of D-lactic acid producing
Enterococcus and Streptococcus spp. in the faecal samples from the CFS group
(3.5×107 cfu/L and 9.8×107 cfu/L respectively) were significantly higher than
those for the control group (5.0×106 cfu/L and 8.9×104 cfu/L respectively).
Analysis of exometabolic profiles of Enterococcus
faecalis and Streptococcus sanguinis, rep-resentatives of Enterococcus and
Streptococcus spp. respectively, by NMR and HPLC showed that these organisms
produced significantly more lactic acid (p<0.01) from
13C-labeled glucose, than the Gram negative Escherichia coli. Further, both E.
faecalis and S. sanguinis secrete more D-lactic acid than E. coli.
This study suggests a probable link between
intestinal colonization of Gram positive facultative anaerobic D-lactic acid
bacteria and symptom expressions in a subgroup of patients with CFS. Given the
fact that this might explain not only neurocognitive dysfunction in CFS patients
but also mitochondrial dysfunction, these findings may have important clinical
implications.
Staines, DR., Brenu, EW and Marshall-Gradisnik,
S.
Postulated vasoactive
neuropeptide immunopathology affecting the blood–brain/blood–spinal barrier in
certain neuropsychiatric fatigue-related conditions: A role for
phosphodiesterase inhibitors in treatment? Neuropsychiatric Disease and
Treatment, 2009, 5, 81–89.
Neuropsychiatric symptoms occur in a number of
neurological fatigue-related conditions including multiple sclerosis (MS),
Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and CFS. These
conditions have been attributed variably to neuroinflammatory and
neurodegenerative processes. While autoimmune pathology, at least in part, has
long been suspected in these conditions, proof has been elusive. Autoimmune
pathomechanisms affecting the blood–brain barrier (BBB) or blood–spinal barrier
(BSB) may predispose the BBB/BSB to ‘leakiness’ and be a precursor to additional
autoimmune events resulting in neuroinflammatory or neurodegenerative processes.
The aim of the paper is to postulate
immunopathology of the cerebrospinal perivascular compartment involving certain
vasoactive neuropeptides, specifically pituitary adenylate cyclase-activating
polypeptide (PACAP) and vasoactive intestinal peptide (VIP), in the etiology of
certain neuropsychiatric fatigue-related conditions such as MS, ALS, PD, and
CFS. Vasoactive neuropeptides (VNs) such as PACAP and VIP have critical roles as
neurotransmitters, vasodilators including perfusion and hypoxia regulators, and
immune and nociception modulators. PACAP and VIP are widely distributed in the
central nervous system (CNS) and have key roles in CNS blood vessels including
maintaining functional integrity of the BBB and BSB.
Autoimmunity affecting these VNs would likely have
a detrimental effect on BBB and BSB functioning arguably predisposing to further
pathological processes. Virchow–Robin spaces (VRS) are perivascular compartments
surrounding small vessels within the CNS which contribute to the BBB and BSB
integrity and contain PACAP and VIP receptors.
Autoimmunity of these receptors would likely
affect BBB and VRS function and therefore may contribute to the etiology of
these conditions by affecting CNS and immunological homeostasis, including
promoting neuropsychological symptomatology. PACAP and VIP, as potent activators
of adenylate cyclase (AC), have a key role in cyclic adenosine monophosphate (cAMP)
production affecting regulatory T cell (Treg) and other immune functions.
Phosphodiesterase enzymes (PDEs) catalyze cAMP and PDE inhibitors (PDEIs)
maintain cAMP levels and have proven and well known therapeutic benefit in
animal models such as experimental allergic encephalomyelitis (EAE). Therefore
PDEIs may have a role in therapy for certain neuropsychiatric fatigue-related
conditions.
Van Houdenhove, B and Luyten, P. Treatment
of chronic fatigue syndrome: how to find a 'new equilibrium'? Patient
Education and Counseling, 2009, Sep 20, [Epub ahead of print].
doi:10.1016/j.pec.2009.09.001.
Commentary on the findings by
Goudsmit et al and Jason et al, published in the journal.
Walker, K., Lindner, H and Noonan, M. The
role of coping in the relationship between depression and illness severity in
chronic fatigue syndrome. Journal of Allied Health, 2009, 38, 2, 91-99.
The self-regulatory model (SRM) proposes that both
cognitive and emotional illness representations influence the coping processes
adopted in response to an illness. This study used the SRM to explore the role
of coping in the relationship between depression and self-appraisals of illness
severity in a population of patients with CFS.
The sample comprised 156 participants, 34 men and
121 women, aged between 18 and 78 yrs, recruited through groups and the media,
who had been medically diagnosed with CFS. Participants were asked to complete
three questionnaires: the Cardiac Depression Scale, Ways of Coping Questionnaire
(WOCQ), and Severity Subscale of the Illness Perceptions Questionnaire-Revised.
Analyses revealed that almost 70% of the
participants were moderately or severely depressed. Additionally, two particular
subscales, social support seeking and positive reappraisals, emerged as
positively contributing to self-appraisals of illness severity (β = 0.20 [p <
0.05] and β= 0.21 [p < 0.05], respectively), thereby supporting the SRM.
Furthermore, results indicated that a combination of depression and coping was a
better predictor of illness severity than depression alone, accounting for 22%
of the variance compared with 8%, respectively.
The findings suggest that focusing on depression,
and particularly coping styles, during treatment interventions could have
important implications for therapeutic interventions. This could lead to better
treatment strategies for health professionals who work with patients with CFS.
[Ed. Note: There was no
significant relationship between escape-avoidant coping and severity. The
authors suggest that treatments might encourage patients to obtain
information, and use social support.]
Weinstein, AA., Drinkard, BM., Diao, G., Furst,
G., Dale, JK., Straus, SE and Gerber, LH. Exploratory analysis of the
relationships between aerobic capacity and self-reported fatigue in patients
with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome.
PM & R,
2009, 1, 7, 620-628.
The objective of this study was to determine if
self-reported levels of physical activity and fatigue are related to peak oxygen
uptake (VO2peak) and whether these relationships differ among the patient groups
(rheumatoid arthritis [RA], polymyositis [PM], and CFS). This was a
correlational investigation set in 2 ambulatory research clinics at the National
Institutes of Health, Clinical Center, Bethesda, MD. There were 9 patients with
PM, 10 with RA, and 10 with CFS (CDC criteria '94).
Measures included VO2peak during bicycle ergometry
and self-reported fatigability, fatigue, and physical activity. VO2peak was used
as the criterion measurement of physiological fatigue with which the
self-reported variables were compared.
For the CFS group, the Pearson r revealed that
self-reported physical activity correlated with VO2peak (r = .61, p=.06) and
with the self-reported fatigability scales (r=.61, p=.05). However in the PM and
RA groups, the association between self-reported activity and VO2peak was
significant although fatigability and fatigue did not correlate with VO2peak.
Linear regression analysis was performed to assess the effects of diagnosis
group, self-reported activity level or fatigue, and their interaction. A trend
in the data showed a distinctive relationship between fatigue/fatigability
within the 3 groups. In addition, when controlling for group status,
self-reported activity predicted aerobic capacity as measured by VO2peak.
This study confirms that patients with chronic but
stable RA, PM, or CFS are fatigued and have significantly decreased aerobic
capacity. Self-reports of physical activity predicted VO2peak and may be used as
an indicator of activity-based aerobic capacity. Self-reports of fatigue,
however, did not correlate with VO2peak and hence are assessing something other
than an index of aerobic capacity, and provide additional information about
patients' perceptions, which will require further investigation.
[Ed.
Note: This is a pilot study and the samples were small. The findings should
therefore be interpreted with caution.]
ARTICLES ON FATIGUE AND RELATED SUBJECTS
Skovbjerg, S., Duus Johansen, J., Rasmussen, A., Thorsen, H and Elberling,
J. General practitioners' experiences with provision of healthcare to
patients with self-reported multiple chemical sensitivity. Scandinavian
Journal of Primary Health Care, 2009, 27, 3, 148-152.
The aim was to describe general practitioners' (GPs') evaluation of and
management strategies in relation to patients who seek medical advice because of
multiple chemical sensitivity (MCS). This was a nationwide cross-sectional
postal questionnaire survey, including a sample of 1000 Danish GPs randomly
drawn from the membership list of GPs in the Danish Medical Association.
Completed questionnaires were obtained from 691 GPs (69%). Within the last 12
months 62.4% (n=431) of the GPs had been consulted by at least one patient with
MCS. Of these, 55.2% of the GPs evaluated the patients' complaints as chronic
and 46.2% stated that they were rarely able to meet the patients' expectations
for healthcare. The majority, 73.5%, had referred patients to other medical
specialties. The cause of MCS was perceived as multi-factorial by 64.3% of the
GPs, as somatic/biologic by 27.6%, and as psychological by 7.2%. Partial or
complete avoidance of chemical exposures was recommended by 86.3%. Clinical
guidelines, diagnostic tools, or more insight in the pathophysiology were
requested by 84.5% of the GPs.
Despite the lack of formal diagnostic labelling the patient with MCS is well
known by GPs. The majority of the GPs believed that MCS primarily has a
multi-factorial explanation. However, perceptions of the course of the condition
and management strategies differed, and many GPs found it difficult to meet the
patients' expectations for healthcare. The majority of the GPs requested more
knowledge and clinical guidelines for the management of this group of patients.
Skovbjerg, S., Brorson S., Rasmussen, A., Duus Johansen, J and Elberling,
J. Impact of self-reported multiple chemical sensitivity on everyday life: A
qualitative study. Scandinavian Journal of Public Health, 2009.
doi:10.1177/1403494809105430. Online May 1st.
Multiple chemical sensitivity (MCS) is a descriptive term covering symptoms
attributed to exposure to common airborne chemicals. There are no
internationally accepted criteria, but it has been suggested that MCS is a
chronic and disabling condition. However, details of the impact of MCS on
everyday life are limited. We describe the impact of MCS on everyday life,
strategies for managing the condition, and experiences with healthcare
management.
A focus group study was conducted, including two interviews with a sample of
six women and six men between 27 and 78 years of age, a duration of MCS of at
least 1 year, and with different occupational conditions.
MCS may severely influence different aspects of everyday life, including
lifestyle, social relations, and occupational conditions. Avoiding common
airborne chemicals was the most prevalent coping strategy, which implied
creating a chemical-free living space and limiting social activities.
Experiences with healthcare management were overall reported as negative in
terms of not receiving acknowledgement of the reported symptoms.
MCS may have serious implications for daily functioning. Further research on
individual consequences and the social and psychological factors that may be
associated with MCS is needed in order to add to our understanding of this
condition and to the provision of more satisfactory healthcare.
Van 't Leven, M., Zielhuis, GA., van der Meer, JW., Verbeek, AL and
Bleijenberg, G. Fatigue and chronic fatigue syndrome-like complaints in the
general population. European Journal of Public Health, 2009, Aug 18 [epub].
doi:10.1093/eurpub/ckp113.
Study of 22500 residents of Nijmegen revealed that about 1% met the criteria
for a CFS-like illness.
http://eurpub.oxfordjournals.org/cgi/content/abstract/ckp113
COMPLETE REFERENCES FOR
SIGNIFICANT E-PUBS
Dickson, A., Toft, A and O'Carroll, RE.
Neuropsychological functioning, illness perception, mood and quality of life in
chronic fatigue syndrome, autoimmune thyroid disease and healthy participants.
Psychological Medicine, 2009, 39, 9, 1567-1576.
Jammes, Y, Steinberg, JG., Delliaux, S and
Brégeon, F. Chronic fatigue syndrome combines increased exercise-induced
oxidative stress and reduced cytokine and Hsp responses. Journal of Internal
Medicine, 2009, 266, 2, 196-206.
Jason, LA., Najar, N., Porter, N and Reh, C.
Evaluating the Centers for Disease Control's empirical chronic fatigue
syndrome case definition. Journal of Disability Policy Studies, 2009, 20,
79-92. http://dps.sagepub.com/cgi/content/abstract/20/2/93.
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Given the large number of publications on ME and CFS, we will only include summaries of the most interesting or significant findings. Sources used include Co-Cure and Medline. Editors: EM Goudsmit PhD and S. Howes. With thanks to Ray Colliton.
-
This
update is for personal use only. Not all abstracts were checked with the original
document and there may be errors due to conversion between programs. For
reliable information, please refer to the original articles.
-
Copyright EM Goudsmit
2009 ©
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rights reserved. Not
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