http://journal.frontiersin.org/Journal/119937/abstract
Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study
Satoshi Umeda1*, Neil A. Harrison2, Marcus Gray3, Christopher Mathias4 and Hugo Critchley2
1Psychology, Keio University, Japan
2Brighton and Sussex Medical School, University of Sussex, United Kingdom 3The University of Queensland, Australia
4National Hospital for Neurology and Neurosurgery, University College London, United Kingdom
Abstract
Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by orthostatic intolerance, and is
frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred
vision, fatigue, anxiety and depression.
Although the estimated prevalence of PoTS is approximately 5-10 times as common as the better-known condition
orthostatic hypotension, the neural substrates of the syndrome are poorly characterized.
In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the
diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure to examine variation in
regional brain structure associated with PoTS.
We recruited eleven patients with established PoTS and twenty-three age-matched normal controls. Group comparison
of grey matter volume revealed diminished grey matter volume within the left anterior insula, right middle frontal gyrus
and right cingulate gyrus in the PoTS group.
We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and postcentral gyrus, paracentral lobule and superior frontal gyrus in PoTS patients.
Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and
depression scores.
Together, these findings of structural differences, particularly within insular and cingulate components of the salience
network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic
control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients.
http://www.tandfonline.com/doi/abs/10.1080/21641846.2014.978109#.VI...
Chronic fatigue syndrome and co-morbid and consequent conditions: evidence from a multi-site clinical
epidemiology study
Lucinda Bateman, Salima Darakjy, Nancy Klimas (shown above), Daniel Peterson, Susan M. Levine, Ali Allen, Shane
A. Carlson, Elizabeth Balbin, Gunnar Gottschalk & Dana March*
Abstract
Background: Epidemiologic data that inform our understanding of the type, frequency, and burden of co-morbidities
with chronic fatigue syndrome is limited.
Purpose: To elucidate co-morbid and consequent conditions, using data from a clinical epidemiology study of long-term
CFS patients.
Methods: Some 960 adults with CFS were identified at four sites specializing in the diagnosis and treatment of CFS.
Patients reported their demographics, CFS course, other medical diagnoses, and current functioning. We determined
associations between: co-morbidities and a patient's current health relative to their health when diagnosed with CFS;
CFS symptom severity at onset and subsequent diagnosis with a co-morbid condition; and presence of a co-morbidity
and functional ability. We also modeled the change in CFS symptom severity over time as it relates to the presence of a
co-morbidity.
Results: Of the sample, 84% was diagnosed with one or more co-morbid conditions after CFS onset. Fibromyalgia,
depression, anxiety, and hypothyroidism were the most common diagnoses. Nearly 60% of the sample reported a
mental illness.
Conclusions: In general, co-morbid conditions reduced functional ability and were associated with the worsening of
CFS symptoms over time. This study provides important new information on the prevalence of co-morbid conditions and
their impact on the course of CFS.
http://www.ncbi.nlm.nih.gov/pubmed/25464926
Cytokine. 2014 Nov 15. pii: S1043-4666(14)00555-9. doi:
10.1016/j.cyto.2014.10.011. [Epub ahead of print]
The relationship between interleukin-6 in saliva, venous and capillary plasma, at rest and in response to
exercise.
Cullen T1, Thomas AW2, Webb R2, Hughes MG3, Cardiff Metropolitan University, Cardiff CF5 2YB, UK.
3Cardiff School of Sport, Cardiff Metropolitan University, Cardiff CF23 6XD, UK.
Abstract
IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical
depression and also plays a major role in inflammatory and immune responses to exercise.
The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous
plasma, saliva and capillary plasma. Five male and five females completed 2 separate exercise trials, both of which
involved standardized exercise sessions on a cycle ergometer.
Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples
were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked
immunosorbent assay (ELISA).
In Trial A venous plasma IL-6 increased significantly from 0.4±0.14pg/ml to 0.99±0.29pg/ml (P<0.01) while there was no
increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when
expressed as an exercise induced change.
In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22±0.18 to 0.74±0.28pg/ml (P⩽0.01);
capillary: 0.37±0.22 to 1.08±0.30pg/ml (P<0.01). Venous and capillary plasma responses did not correlate at rest
(r=0.59, P=0.07) but did correlate post exercise (r=0.79, P⩾0.001) and when expressed as an exercise induced change
(r=0.71, P=0.02).
Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary
plasma responses are reflective of systemic IL-6 responses to exercise.
Copyright © 2014 Elsevier Ltd. All rights reserved.
http://link.springer.com/article/10.1007/s00296-014-3172-2
Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a
potentially useful tool in differential diagnosis
Daniel J. Wallace, Igor M. Gavin, Oleksly Karpenko, Farnaz Barkhordar, Bruce S. Gillis
Abstract
Making a correct diagnosis is pivotal in the practice of clinical rheumatology. Occasionally, the consultation fails to
provide desired clarity in making labeling an individual as having fibromyalgia (FM), systemic lupus erythematosus
(SLE) or rheumatoid arthritis (RA).
A chemokine and cytokine multiplex assay was developed and tested with the goal of improving and achieving an
accurate differential diagnosis. 160 patients with FM, 98 with RA and 100 with SLE fulfilling accepted criteria were
recruited and compared to 119 controls.
Supernatant cytokine concentrations for IL-6, IL-8, MIP-1 alpha and MIP-1 beta were determined using the Luminex
multiplex immunoassay bead array technology after mitogenic stimulation of cultured peripheral blood mononuclear
cells. Each patient’s profile was scored using a logistical regression model to achieve statistically determined weighting
for each chemokine and cytokine.
Among the 477 patients evaluated, the mean scores for FM (1.7 ± 1.2; 1.52–1.89), controls (−3.56 ± 5.7; −4.59 to
−2.54), RA (−0.68 ± 2.26; −1.12 to −0.23) and SLE (−1.45 ± 3.34, −2.1 to −0.79). Ninety-three percent with FM scored
positive compared to only 11 % of healthy controls, 69 % RA or 71 % SLE patients had negative scores.
The sensitivity, specificity, positive predictive and negative predictive value for having FM compared to controls was 93,
89, 92 and 91 %, respectively (p < 2.2 × 10−16).
Evaluating cytokine and chemokine profiles in stimulated cells reveals patterns that are uniquely present in patients with
FM. This assay can be a useful tool in assisting clinicians in differentiating systemic inflammatory autoimmune
processes from FM and its related syndromes and healthy individuals.
Note: more on the proposed ASIA ME/CFS link-
fulltext-http://www.2ndchance.info/onesize4all-Perricone2013.pdf
Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and
diagnostic aspects
Carlo Perricone a,b, Serena Colafrancesco a,b, Roei D. Mazor a, Alessandra Soriano a,c, Nancy Agmon-Levin a,
Yehuda Shoenfeld a,d,*
a The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel b Reumatologia,
Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy c Department of
Clinical Medicine and Rheumatology, University Campus Bio-Medico of Rome, Italy d Incumbent of the Laura SchwarzKipp Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel
Abstract
In 2011 a new syndrome termed ‘ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants’ was defined
pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus
such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as
infectious components, that also may have an adjuvant effect.
All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in
humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with postvaccination phenomena
and macrophagic myofasciitis syndrome.
Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic
favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity
of these phenomena.
This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of
different adjuvants which lead to the autoimmune/inflammatory response.
The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the
interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance
http://www.ncbi.nlm.nih.gov/pubmed/25427994
Immunol Res. 2014 Nov 27. [Epub ahead of print]
Hepatitus B Virus
Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle
of the 'autoimmune (auto-inflammatory) syndrome induced by adjuvants' (ASIA).
Agmon-Levin N1, Zafrir Y, Kivity S, Balofsky A, Amital H, Shoenfeld Y., The Zabludowicz Center for Autoimmune
Diseases, Chaim Sheba Medical Center, 52621, Tel-Hashomer, Israel.
Abstract
The objectives of this study were to gather information regarding demographic and clinical characteristics of patients
diagnosed with either fibromyalgia (FM) or chronic fatigue (CFS) following hepatitis B vaccination (HBVv) and
furthermore to apply the recently suggested criteria of autoimmune (auto-inflammatory) syndromes induced by
adjuvants (ASIA), in the aim of identifying common characteristics that may suggest an association between
fibromyalgia, chronic fatigue and HBV vaccination.
Medical records of 19 patients with CFS and/or fibromyalgia following HBVv immunization were analyzed. All of which
were immunized during 1990-2008 in different centers in the USA. All medical records were evaluated for
demographics, medical history, the number of vaccine doses, as well as immediate and long term post-immunization
adverse events and clinical manifestations.
In addition, available blood tests, imaging results, treatments and outcomes were analyzed. ASIA criteria were applied
to all patients.
The mean age of patients was 28.6 ± 11 years, of which 68.4 % were females. 21.05 % had either personal or familial
background of autoimmune disease. The mean latency period from the last dose of HBVv to onset of symptoms was
38.6 ± 79.4 days, ranging from days to a year.
Eight (42.1 %) patients continued with the immunization program despite experiencing adverse events. Manifestations
that were commonly reported included neurological manifestations (84.2 %), musculoskeletal (78.9 %), psychiatric (63.1
%), fatigue (63.1 %), gastrointestinal complains (58 %) and mucocutaneous manifestations (36.8 %).
Autoantibodies were detected in 71 % of patients tested. All patients fulfilled the ASIA criteria. This study suggests that
in some cases CFS and FM can be temporally related to immunization, as part of ASIA syndrome.
The appearance of adverse event during immunization, the presence of autoimmune susceptibility and higher titers of
autoantibodies all can be suggested as risk factors. ASIA criteria were fulfilled in all patients eluding the plausible link
between ASIA and CFS/FM.
PMID: 25427994 [PubMed - as supplied by publisher]
Original, full article from the New York Times: http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chro...
Blood vessels in the brain
Brains of People with Chronic Fatigue Syndrome Offer Clues About Disorder
Two recent studies — one from investigators at Stanford a few weeks ago and another from a Japanese research team
published earlier this year — have found that the brains of people with chronic fatigue syndrome differ from those of
healthy people, strengthening the argument that serious physiological dysfunctions are at the root of the condition.
Both studies were small, however, and their results must be replicated before firm conclusions can be drawn. Still, other
studies presented at scientific conferences this year also have demonstrated physiological dysfunctions in these
patients.
In the most recent study, published by the journal Radiology, researchers at Stanford University compared brain images
of 15 patients with the condition to those of 14 healthy people. The scientists found differences in both the white matter,
the long, cablelike nerve structures that transmit signals between parts of the brain, and the gray matter, the regions
where these signals are processed and interpreted.
The most striking finding was that in people with the disorder, one neural tract in the white matter of the right
hemisphere appeared to be abnormally shaped, as if the cablelike nerve structures had crisscrossed or changed in
some other way. Furthermore, the most seriously ill patients exhibited the greatest levels of this abnormality.
The researchers also found in M.E./C.F.S. patients a thickening of the gray matter at the two points of the right
hemisphere connected by this particular neural tract. And the overall volume of white matter in the brains of patients
was reduced, compared with the brains of people without the disorder.
The relationship between the symptoms experienced by patients and the findings is unclear. The two parts of the brain
connected by the abnormally shaped white matter are believed to be important for language use.
Dr. Zeineh said these differences, if borne out by further studies, could eventually serve as biological and diagnostic
markers for the illness.
In the other brain study, published in March by The Journal of Nuclear Medicine, a team led by researchers from Osaka
City University compared PET scans of nine people with M.E./C.F.S. to those of 10 healthy controls. They reported
widespread cerebral inflammation in the patients, and found that those with the most severe illness had more
inflammation.
If there is widespread inflammation going on, that could explain many of the symptoms.
Many experts now believe that in people with M.E./C.F.S., a viral infection or some other physiological insult or
exposure, or perhaps a combination of exposures, has kicked the immune system into permanent overdrive, leading to
the cascade of symptoms.
Use of ultra-low-dose (≤6 mg) doxepin for treatment of
insomnia in older people
1. Carlos H. Rojas-Fernandez, BSc(Pharm), PharmD
2. Yannan Chen, BMSc, BSc(Pharm)
Contact carlos.rojas-fernandez@uwaterloo.ca.
Insomnia pharmacotherapy can be challenging in older people, and until recently there has been a lack of new
medications that might represent desirable alternatives. We therefore sought to evaluate the evidence for
ultra-low-dose doxepin in the management of insomnia, with a particular focus on its use in older patients.
La pharmacothérapie contre l’insomnie chez les personnes âgées est un défi. Jusqu’à tout récemment, peu de
nouveaux médicaments constituaient des alternatives intéressantes. Nous avons donc évaluer les données
concernant l’usage de la doxépine à dose ultra faible pour la prise en charge de l’insomnie, avec une attention
particulière aux personnes âgées.
Abstract
Background: Insomnia is one of the most frequent complaints encountered in primary care practice, one that results
in significant clinical consequences and cost burden to the public health system. It is more common in elderly adults
(≥65 years of age), with frequent complaints regarding sleep maintenance and early morning wakening. Current
treatment options have limitations. This review was conducted to evaluate the evidence behind ultra-low-dose
doxepin in insomnia and to discuss its potential advantages, its place in therapy and its implications in practice in
the treatment of older patients.
Methods: A systematic literature search was conducted of MEDLINE via Ovid, PubMed and EMBASE using the MeSH
and key terms “doxepin,” “sleep initiation and maintenance disorders,” “insomnia,” and “low dose.” Only randomized
controlled trials comparing 3 mg and/or 6 mg of doxepin to placebo and involving participants diagnosed with
primary insomnia were included. Primary outcomes for this review were objective sleep study parameters.
Results: Five studies were identified, 3 of which (n = 571) were conducted in older adults. Doxepin 3 mg and 6 mg
significantly reduced waking after sleep onset and increased total sleep time. There was no significant difference
between the 2 doses of doxepin. Latency to persistent sleep did not differ significantly compared with placebo for
any doses of doxepin. The most frequent adverse events reported were somnolence and headache. Adverse events
did not appear to be dose-related, and studies reported the incidence of adverse effects to be comparable to
placebo.
Conclusion: Doxepin 3 mg and 6 mg significantly improved and sustained sleep maintenance and sleep duration
into the last third of the night but did not significantly affect sleep onset. Sleep benefits were achieved without
next-day residual or discontinuation effects. Doxepin appears to be well suited for managing insomnia in older
people.
Irritable Bowel Syndrome and Chronic Fatigue 6 Years After
Giardia Infection: A Controlled Prospective Cohort Study
Journal of Clinical Infectious Diseases Vol 59 Issue 10
1. Kurt Hanevik, Knut-Arne Wensaas, Guri Rortveit , Geir Egil Eide , Kristine Mørch, and
2. Nina Langeland
+ Author Affiliations
1.
2.
3.
4.
5.
Department of Clinical Science, University of Bergen
2Research Unit for General Practice, Uni Research Health
3Department of Global Public Health and Primary Care, University of Bergen
4Centre for Clinical Research
5National Centre for Tropical Infectious Diseases, Department of Medicine, Haukeland University
Hospital, Bergen, Norway
1
1. Correspondence: Kurt Hanevik, PhD, University of Bergen, Department of Clinical Science, 8th floor, Labbuilding, N-5021 Bergen, Norway (kurt.hanevik@med.uib.no).
Abstract
Background. Functional gastrointestinal disorders and fatigue may follow acute infections. This study aimed to
estimate the persistence, prevalence, and risk of irritable bowel syndrome and chronic fatigue 6 years after Giardia
infection.
Methods. We performed a controlled prospective study of a cohort of 1252 individuals who had laboratoryconfirmed Giardia infection during a waterborne outbreak in 2004. In total, 748 cohort cases (exposed) and 878
matched controls responded to a postal questionnaire 6 years later (in 2010). Responses were compared to data
from the same cohort 3 years before (in 2007).
Results. The prevalences of irritable bowel syndrome (39.4%) by Rome III criteria and chronic fatigue (30.8%) in the
exposed group 6 years after giardiasis were significantly elevated compared with controls, with adjusted relative
risks (RRs) of 3.4 (95% confidence interval [CI], 2.9–3.9) and 2.9 (95% CI, 2.3–3.4), respectively. In the exposed
group, the prevalence of irritable bowel syndrome decreased by 6.7% (RR, 0.85 [95% CI, .77–.93]), whereas the
prevalence of chronic fatigue decreased by 15.3% from 3 to 6 years after Giardia infection (RR, 0.69 [95% CI, .62–
.77]). Giardia exposure was a significant risk factor for persistence of both conditions, and increasing age was a risk
factor for persisting chronic fatigue.
Conclusions. Giardia infection in a nonendemic setting is associated with an increased risk for irritable bowel
syndrome and chronic fatigue 6 years later. The prevalences of both conditions decrease over time, indicating that
this intestinal protozoan parasite may elicit very long-term, but slowly self-limiting, complications
Received March 18, 2014. Accepted July 2, 2014. © The Author 2014. Published by Oxford University Press on
behalf of the Infectious Diseases Society of America.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence
(http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium,
provided the original work is not altered or transformed in any way, and that the work properly cited. For commercial re-use, please contact
journals.permissions@oup.com.
http://hyper.ahajournals.org/content/early/2014/12/15/HYPERTENSIONA...
Oscillatory Cerebral Blood Flow Is Associated With Impaired Neurocognition and Functional Hyperemia in
Postural Tachycardia Syndrome During Graded Tilt
Julian M. Stewart, Andrew T. Del Pozzi, Akash Pandey, Zachary R.
Messer, Courtney Terilli, Marvin S. Medow; From the Departments of Pediatrics (J.M.S., A.T.D.P., A.P., Z.R.M.,
C.T., M.S.M.) and Physiology (J.M.S., M.S.M.), New York Medical College, Valhalla.
Abstract
We hypothesize that upright cognitive impairment in patients with postural tachycardia syndrome (POTS) is caused by
reduced cerebral blood flow (CBF). The CBF velocity (CBFv) measured by transcranial Doppler ultrasound decreased
excessively during 70° tilt in a minority of patients with intermittent hyperpnea/hypocapnia. Incremental tilt showed no
difference in mean CBFv. But N-back memory tasking indicated progressive compromised memory, reduced functional
hyperemia, and reduced neurovascular coupling.
Orthostasis caused slow oscillations in CBFv linked to oscillations in arterial pressure in patients with POTS. We also
hypothesize that oscillatory CBFv degrades neurovascular coupling. We performed 2-back testing when subjects were
in supine position and during incremental tilts to 15°, 30°, 45°, and 60° in 11 patients with POTS and 9 controls.
Oscillatory arterial pressure, oscillatory CBFv, and neurovascular coupling were similar in supine position. The
oscillatory arterial pressure increased by 31%, 45%, 67%, and 93% in patients with POTS during tilt and remained
unchanged in the controls.
Oscillatory CBFv increased by 61%, 82%, 161%, and 264% in patients with POTS during tilt and remained unchanged
in the controls.
Functional hyperemia decreased from 4.1% to 3.0%, 1.1%, 0.2%, and to 0.04% in patients with POTS, but it was
unchanged at 4% in the controls. Percent correct N-back responses decreased from 78% to 33% in patients with POTS,
whereas they remained at 89% in the controls.
In patients with POTS, oscillatory CBFv was linearly correlated with functional hyperemia (r2=0.76). Increased
oscillatory CBF is associated with reduced neurovascular coupling and diminished cognitive performance in patients
with POTS.
http://www.molecularpain.com/content/10/S1/O12/
This article is part of the supplement: Proceedings of the Seventh Scientific Meeting of The TMJ
Association http://www.molecularpain.com/supplements/10/S1
Small-fiber polyneuropathy (SFPN), a common underlying diagnosis in syndromes involving unexplained
chronic pain and multi-system symptoms
Anne Louise Oaklander12*, Heather Downs1, Zeva Daniela Herzog1 and Max Klein1, 1 Department of Neurology,
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; 2 Departments of Pathology
(Neuropathology), Massachusetts General Hospital, Boston, MA 02114, USA
Oral presentation
Background: Syndromes involving unexplained chronic widespread pain (CWP) and multi-system symptoms are
common, with 1-5% prevalence for fibromyalgia alone. They more often affect females and cause disability and
high costs [1-3]. Other common syndromes include chronic fatigue, seronegative Lyme, and Gulf War Illness.
Fragmentary syndromes include TMJD, POTS, CRPS, irritable bowel). Our work suggests that unrecognized
SFPN contributes to several syndromes involving CWP and multi-organ symptoms.
Materials and methods: With IRB permission, we retrospective analyzed the medical records of 41 patients with onset
of unexplained CWP and multisymptoms before age 21; most had objective testing for SFPN [9].
We also prospectively studied 27 adult patients with fibromyalgia and
30 healthy volunteers using history, examination, skin biopsies and AFT [10].
Results: Retrospective chart review identified definite (in 59%) and probable SFPN (in 17%) among the young patients
with onset before age 21 [9]. We characterized the clinical features, diagnostic, and treatment options for this new earlyonset SFPN. Studying children, who lacked the typical causes of late-onset SFPN, implicated autoimmune causality in
most.
Among patients treated with immunomodulatory therapies, pain and other symptoms improved in 2/3 [9]. Among adults
with fibromyalgia, 41% of skin biopsies from subjects with fibromyalgia vs. 3% of biopsies from controls were diagnostic
for SFPN, and symptom and examination scores were higher in fibromyalgia subjects than in controls (all P ≤ 0.001)
[10].
All fibromyalgia patients diagnosed with SFPN then had blood tests for all known causes [8]. None had diabetes but
62% had test-results consistent with dysimmunity, and some had genetic causes [10]. Other laboratories have now also
linked fibromyalgia to SFPN [11-15].
Conclusions: Some patients with unexplained widespread pain and multi-system syndromes such as fibromyalgia
have objectively diagnosable SFPN. SFPN can affect children and young adults, not just older adults. Multiple lines of
evidence suggest that early-onset SFPN has novel causes that can be treated. The prevalence of SFPN among TMJD
patients is unstudied.
A Randomized, Placebo-Controlled, Double-Blind, Trial of Duloxetine in the Treatment of General Fatigue in Patients
with Chronic Fatigue Syndrome
Lesley M. Arnold, Thomas J. Blom, Jeffrey A. Welge, Elizabeth Mariutto, Alicia Heller
Published Online: December 16, 2014
DOI: http://dx.doi.org/10.1016/j.psym.2014.12.003
Abstract
Objective: To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome.
Methods: A 12-week, randomized, double-blind study was designed to compare duloxetine 60-120 mg/day (n=30) with
placebo (n=30) for efficacy and safety in the treatment of patients with chronic fatigue syndrome. The primary outcome
measure was the Multidimensional Fatigue Inventory (MFI) general fatigue subscale (range 4–20, with higher scores
indicating greater fatigue). Secondary measures were the remaining MFI subscales, Brief Pain Inventory (BPI), Medical
Outcomes Study Short Form-36 (SF-36), Hospital Anxiety and Depression Scale (HADS), CDC Symptom Inventory,
Patient Global Impression of Improvement (PGI-I), and Clinical Global Impression of Severity (CGI-S). The primary
analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample, with treatment-bytime interaction as the measure of effect.
Results: The improvement in the duloxetine group on the MFI general fatigue scores was not significantly greater than
the placebo group (P=0.23; estimated difference between groups at week 12 = −1.0 [95% confidence interval −2.8,
0.7]). The duloxetine group was significantly superior to placebo on the MFI mental fatigue score, BPI average pain
severity and interference scores, SF-36 bodily pain domain, and CGI-Severity score. Duloxetine was generally well
tolerated.
Conclusion: The primary efficacy measure of general fatigue did not significantly improve with duloxetine compared to
placebo. Significant improvement in secondary measures of mental fatigue, pain, and global measure of severity
suggests that duloxetine may be efficacious for some CFS symptom domains, but larger, controlled trials are needed to
confirm these results.
fulltext- http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652014005030081&lng=en&nrm=iso&tlng=en
An. Acad. Bras. Ciênc., ahead of print Epub Dec 09, 2014
http://dx.doi.org/10.1590/0001-3765201420130081
Soluble fractalkine in the plasma of fibromyalgia
JUAN J. GARCIA, EDUARDO ORTEGA
Immunophysiology Research Group, Department of Physiology, Faculty of Sciences, University of Extremadura,
Badajoz, 06071, Spain
ABSTRACT
Fibromyalgia is a form of non-articular rheumatism in which inflammatory cytokines seem to be involved. However,
there is still no analytical specific diagnostic criterion for this disease. The aim was to examine a possible role of
fractalkine as a biomarker in fibromyalgia. Plasma levels of soluble fractalkine were compared between women
diagnosed with fibromyalgia (n=17) and healthy women
(n=10) as controls. Fractalkine released by monocytes was also evaluated. Fibromyalgia patients showed lower plasma
fractalkine than healthy women. Since most inflammatory pathologies show elevated plasma levels of soluble
fractalkine, the results may contribute towards a differential diagnosis for fibromyalgia.
https://prevention.nih.gov/docs/programs/mecfs/ODP-MECFS-DraftRepor...
Pathways to Prevention Workshop: Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue
Syndrome
DRAFT EXECUTIVE SUMMARY
Carmen R. Green, M.D.; Penny Cowan; Ronit Elk, Ph.D.; Kathleen M. O’Neil, M.D.; Angela L. Rasmussen, Ph.D.
This National Institutes of Health (NIH) workshop is co-sponsored by the NIH Office of Disease Prevention (ODP) and
the Trans-NIH Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Research Working Group.
A multidisciplinary working group developed the workshop agenda, and an Evidence-based Practice Center prepared
an evidence report through a contract with the Agency for Healthcare Research and Quality (AHRQ) to facilitate the
workshop discussion.
During the 1½-day workshop, invited experts discussed the body of evidence, and attendees had opportunities to
provide comments during open discussion periods. After weighing evidence from the evidence report, expert
presentations, and public comments, an unbiased, independent panel prepared this draft report, which identifies
research gaps and future research priorities.
This draft report will be posted on the ODP website, and public comments will be accepted for 4 weeks. The final report
will be released several weeks later.
Link to P2P Draft Report webpage
Download the Draft Report (PDF - 3.45 MB) https://prevention.nih.gov/docs/programs/mecfs/ODP-MECFSDraftRepor...
The report has been posted for public comments, which can be submitted from Thursday, December 18, 2014
through Friday, January 16, 2015.
Watch an NIH videocast for this workshop (Day 1 – December 9, 2014)
http://videocast.nih.gov/summary.asp?Live=14723&bhcp=1
Watch an NIH videocast for this workshop (Day 2 – December 10, 2014)
http://videocast.nih.gov/summary.asp?Live=14727&bhcp=1
Download the Program Book (PDF - 921 KB) https://prevention.nih.gov/docs/programs/mecfs/ODPMECFS_ProgramBoo...
The program book provides attendees with a workshop overview and agenda, presentation summaries, speaker
biographies, and financial disclosures from planners and presenters. The program book also lists working group
and panel members, Office of Disease Prevention staff, and educational planners.
fulltext- http://journal.frontiersin.org/Journal/10.3389/fneur.2014.00230/full
Front Neurol. 2014 Nov 28;5:230. doi: 10.3389/fneur.2014.00230.
eCollection 2014.
Clinical features in patients with long-lasting macrophagic myofasciitis.
Rigolet M1, Aouizerate J2, Couette M3, Ragunathan-Thangarajah N2, Aoun-Sebaiti M3, Gherardi RK4, Cadusseau J5,
Authier FJ4., Reference Center for Neuromuscular Diseases Garches-Necker-Mondor-Hendaye , Créteil , France ;
Paris Est-Créteil University , Créteil , France.
Abstract
Macrophagic myofasciitis (MMF) is an emerging condition characterized by specific muscle lesions assessing abnormal
long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected
patients usually are middle-aged adults, mainly presenting with diffuse arthromyalgias, chronic fatigue, and marked
cognitive deficits, not related to pain, fatigue, or depression.
Clinical features usually correspond to that observed in chronic fatigue syndrome/myalgic encephalomyelitis.
Representative features of MMF-associated cognitive dysfunction include dysexecutive syndrome, visual memory
impairment, and left ear extinction at dichotic listening test.
Most patients fulfill criteria for non-amnestic/dysexecutive mild cognitive impairment, even if some cognitive deficits
appear unusually severe. Cognitive dysfunction seems stable over time despite marked fluctuations.
Evoked potentials may show abnormalities in keeping with central nervous system involvement, with a
neurophysiological pattern suggestive of demyelination. Brain perfusion SPECT shows a pattern of diffuse cortical and
subcortical abnormalities, with hypoperfusions correlating with cognitive deficiencies.
The combination of musculoskeletal pain, chronic fatigue, and cognitive disturbance generates chronic disability with
possible social exclusion. Classical therapeutic approaches are usually unsatisfactory making patient care difficult.
http://www.ncbi.nlm.nih.gov/pubmed/25506472
Ann Med Health Sci Res. 2014 Nov;4(6):829-36. doi: 10.4103/2141-9248.144870.
Hepatitis B vaccination and associated oral manifestations: a non-systematic review of literature and case
reports.
Tarakji B1, Ashok N1, Alakeel R2, Azzeghaibi S1, Umair A1, Darwish S1, Mahmoud R3, Elkhatat E3.,1Department of
Oral Maxillofacial Sciences, Alfarabi College of Dentistry and Nursing, Riyadh, Saudi Arabia. 2Department of
Clinical Laboratory Sciences, King Saud University, Alfarabi College of Medicine, Riyadh, Saudi
Arabia. 3Department of Restorative Dentistry Sciences, Alfarabi College of Dentistry and Nursing, Saudi Arabia.
Abstract
Hepatitis B vaccine has been administered in children and adults routinely to reduce the incidence of the disease.
Even though, hepatitis B vaccine is considered as highly safe, some adverse reactions have been reported. A literature
search was carried out in PubMed, accessed via the National Library of Medicine PubMed interface, searching used the
following keywords: Hepatitis B vaccine and complications from 1980 to 2014.
A total of 1147 articles were obtained out of which articles, which discuss the complications occurring orally or occurring
elsewhere in the body, which have the potential to manifest orally after hepatitis B vaccination were selected.
A total of 82 articles were identified which included 58 case series or case reports, 15 review articles, 4 cross sectional
studies, 3 prospective cohort studies, one retrospective cohort study and a case control study.
After reviewing the literature, we observed that complications seen after Hepatitis B vaccination are sudden infant death
syndrome, multiple sclerosis, chronic fatigue syndrome, idiopathic thrombocytopenic purpura, vasculititis optic neuritis,
anaphylaxis, systemic lupus erytymatosus, lichen planus and neuro-muscular disorder.
Of these complications, some are manifested orally or have the potential to manifest orally. Although, most of the
complications are self-limiting, some are very serious conditions, which require hospitalization with immediate medical
attention.
fulltext- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238837/
Neurological aspects of human parvovirus B19 infection: a systematic review.
Barah F1, Whiteside S, Batista S, Morris J., Center for Neuroscience and Cell Biology, Faculty of Medicine,
University of Coimbra, Coimbra, Portugal.
Abstract
Parvovirus B19 has been linked with various clinical syndromes including neurological manifestations. However, its role
in the latter remains not completely understood. Although the last 10 years witnessed a surge of case reports on B19associated neurological aspects, the literature data remains scattered and heterogeneous, and epidemiological
information on the incidence of B19-associated neurological aspects cannot be accurately extrapolated.
The aim of this review is to identify the characteristics of cases of B19-associated neurological manifestations. A
computerized systematic review of existing literature concerning cases of B19-related neurological aspects revealed 89
articles describing 129 patients; 79 (61.2%) were associated with CNS manifestations, 41 (31.8%) were associated with
peripheral nervous system manifestations, and 9 (7.0%) were linked with myalgic encephalomyelitis.
The majority of the cases (50/129) had encephalitis. Clinical characteristic features of these cases were analyzed, and
possible pathological mechanisms were also described.
In conclusion, B19 should be included in differential diagnosis of encephalitic syndromes of unknown etiology in all age
groups. Diagnosis should rely on investigation of anti-B19 IgM antibodies and detection of B19 DNA in serum or CSF.
Treatment of severe cases might benefit from a combined regime of intravenous immunoglobulins and steroids.
To confirm these outcomes, goal-targeted studies are recommended to exactly identify epidemiological scenarios and
explore potential pathogenic mechanisms of these complications.
Performing retrospective and prospective and multicenter studies concerning B19 and neurological aspects in general,
and B19 and encephalitic syndromes in particular, are required.
http://www.sciencedirect.com/science/article/pii/S1043466614006024
Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis
Svetlana F. Khaiboullina, Kenny L. DeMeirleir, Shanti Rawat, Grady S.
Berk, Rory S. Gaynor-Berk, Tatjana Mijatovic, Natalia Blatt, Albert A.
Rizvanov, Sheila G. Young, Vincent C. Lombardi
Highlights
• Gulf War illness (GWI) is characterized by a Th1/Th17 shift.
• Th1, Th2 and inflammatory cytokines characterize myalgic encephalomyelitis (ME).
• Cytokine importance by Random Forest were IL-7, IL-4, TNF-α, IL-13, and IL-17F.
• GWI and ME have distinct cytokine profiles despite similar symptomology.
Abstract
Gulf War illness (GWI) is a chronic disease of unknown etiology characterized by persistent symptoms such as
cognitive impairment, unexplained fatigue, pervasive pain, headaches, and gastrointestinal abnormalities. Current
reports suggest that as many as 200,000 veterans who served in the 1990–1991 Persian Gulf War were afflicted.
Several potential triggers of GWI have been proposed including chemical exposure, toxins, vaccines, and unknown
infectious agents. However, a definitive cause of GWI has not been identified and a specific biological marker that can
consistently delineate the disease has not been defined.
Myalgic encephalomyelitis (ME) is a disease with similar and overlapping symptomology, and subjects diagnosed with
GWI typically fit the diagnostic criteria for ME. For these reasons, GWI is often considered a subgroup of ME.
To explore this possibility and identify immune parameters that may help to understand GWI pathophysiology, we
measured 77 serum cytokines in subjects with GWI and compared these data to that of subjects with ME as well as
healthy controls. Our analysis identified a group of cytokines that identified ME and GWI cases with sensitivities of
92.5% and 64.9%, respectively.
The five most significant cytokines in decreasing order of importance were IL-7, IL-4, TNF-α, IL-13, and IL-17F. When
delineating GWI and ME cases from healthy controls, the observed specificity was only 33.3%, suggesting that with
respect to cytokine expression, GWI cases resemble control subjects to a greater extent than ME cases across a
number of parameters.
These results imply that serum cytokines are representative of ME pathology to a greater extent than GWI and further
suggest that the two diseases have distinct immune profiles despite their overlapping symptomology
Two age peaks in the incidence of chronic fatigue
syndrome/myalgic encephalomyelitis: a population-based
registry study from Norway 2008–2012
Inger Johanne Bakken1*, Kari Tveito2, Nina Gunnes1, Sara Ghaderi1, Camilla Stoltenberg13, Lill Trogstad1, Siri
Eldevik Håberg1 and Per Magnus1 * Corresponding author: Inger J Bakken inger.johanne.bakken@fhi.no
Author Affiliations
1
Norwegian Institute of Public Health, Nydalen, Oslo, N-0403, Norway
Norway
3
2
The Norwegian Medical Association, Oslo,
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
BMC Medicine 2014, 12:167 doi:10.1186/s12916-014-0167-5
The electronic version of this article is the complete one and can be found online at:
http://www.biomedcentral.com/1741-7015/12/167Published:
1 October
2014
© 2014 Bakken et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise
stated.
Abstract
Background
The aim of the current study was to estimate sex- and age-specific incidence rates of chronic fatigue syndrome/myalgic
encephalomyelitis (CFS/ME) using population-based registry data. CFS/ME is a debilitating condition with large impact on
patients and their families. The etiology is unknown, and the distribution of the disease in the general population has not
been well described.
Methods
Cases of CFS/ME were identified in the Norwegian Patient Register (NPR) for the years 2008 to 2012. The NPR is nationwide
and contains diagnoses assigned by specialist health care services (hospitals and outpatient clinics). We estimated sex- and
age-specific incidence rates by dividing the number of new cases of CFS/ME in each category by the number of person years
at risk. Incidence rate ratios were estimated by Poisson regression with sex, age categories, and year of diagnosis as
covariates.
Results
A total of 5,809 patients were registered with CFS/ME during 2008 to 2012. The overall incidence rate was 25.8 per 100,000
person years (95% confidence interval (CI): 25.2 to 26.5). The female to male incidence rate ratio of CFS/ME was 3.2 (95%
CI: 3.0 to 3.4). The incidence rate varied strongly with age for both sexes, with a first peak in the age group 10 to 19 years
and a second peak in the age group 30 to 39 years.
Conclusions
Early etiological clues can sometimes be gained from examination of disease patterns. The strong female preponderance and
the two age peaks suggest that sex- and age-specific factors may modulate the risk of CFS/ME.
Keywords:
Chronic fatigue syndrome; Myalgic encephalomyelitis; Incidence rate; Sex; Age
PUBLIC RELEASE: 4-FEB-2015
Study finds link between early menopause
and CFS
THE NORTH AMERICAN MENOPAUSE SOCIETY (NAMS)
CLEVELAND, Ohio (February 4, 2015)--A newfound link between chronic fatigue syndrome (CFS) and early menopause
was reported online today in Menopause, the journal of The North American Menopause Society (NAMS). This link, as
well as links with other gynecologic problems and with pelvic pain, may help explain why CFS is two to four times more
common in women than in men and is most prevalent in women in their 40s. Staying alert to these problems may also
help healthcare providers take better care of women who may be at risk for CFS, say the authors of this population-based,
case-control study.
Based on a long-term study of CFS and fatiguing illnesses in Georgia, this analysis from Centers for Disease Control
scientists included 84 women with CFS and 73 healthy control women who completed detailed gynecologic history
questionnaires. Striking differences emerged from the comparison between those groups.
The women with CFS were some 12 times more likely to have pelvic pain that wasn't related to menstruation (such as
pelvic floor dysfunction, interstitial cystitis/painful bladder syndrome or IC/PBS, and irritable bowel syndrome) than the
control women. The women with CFS also reported excessive bleeding (74% vs 42%) much more often as well as
significantly more bleeding between periods (49% vs 23%) and missing periods (38% vs 22%). In addition, they used
hormones for purposes other than contraception (such as to treat irregular periods, menopausal symptoms or bone loss)
much more often (57% vs 26%).
Also striking, most women with CFS--66%--had undergone at least one gynecologic surgery, compared with only 32% of
controls, most commonly hysterectomy (55% versus 19%). Women with CFS underwent menopause early (at or before
age 45) because of hysterectomy much more often (62% vs 33%). (Surgical menopause occurs immediately when both
ovaries are removed at hysterectomy and often prematurely even when ovaries are preserved.) Bleeding as the reason
for hysterectomy was significantly more common in the women with CFS. They also underwent natural menopause
earlier, but the numbers were too small to show a significant difference.
Although CFS has previously been linked with pelvic pain and gynecologic conditions such as endometriosis, IC/PBS,
polycystic ovaries, and menstrual abnormalities, this is the first study to show a link with early menopause. Sex hormone
abnormalities or their early decrease or disappearance may underlie these links, and the authors called for more research
to find out whether they do play a role in causing or perpetuating CFS in some women. But meanwhile, they emphasized,
women's healthcare providers need to stay alert for symptoms of CFS, such as sleep or memory problems, muscle and
joint pain, and worse symptoms after exertion, developing in women who have these gynecologic or pelvic pain problems.
"CFS can take a tremendous toll on women's lives at midlife and on our society and healthcare system. Being aware of
the association of CFS and earlier menopause can help providers assist women in sorting out symptoms of CFS from
symptoms of menopause," says NAMS Executive Director Margery Gass, MD, NCMP. This paper also raises the chicken
and egg question: Is early menopause the cause of later health problems or simply the result of earlier health problems
not recognized as the cause of early menopause?
The article, "Early menopause and other gynecologic risk indicators for chronic fatigue syndrome in women," will be
published in the August print edition of Menopause.
Founded in 1989, The North American Menopause Society (NAMS) is North America's leading nonprofit organization
dedicated to promoting the health and quality of life of all women during midlife and beyond through an understanding of
menopause and healthy aging. Its multidisciplinary membership of 2,000 leaders in the field--including clinical and basic
science experts from medicine, nursing, sociology, psychology, nutrition, anthropology, epidemiology, pharmacy, and
education--makes NAMS uniquely qualified to serve as the definitive resource for health professionals and the public for
accurate, unbiased information about menopause and healthy aging. To learn more about NAMS, visit
http://www.menopause.org.
The North American Menopause Society
Eileen Petridis
Phone: (216) 696-0229
epetridis@fallscommunications.com
Soy Spells Fewer Hot Flashes for Certain Women The key is their bodies’ ability to produce equol
from soy
CLEVELAND, Ohio (November 17, 2014)—Does soy in the diet help with hot flashes? It does, but only for women
whose bodies can produce the soy metabolite equol, reports a study of American women just published online in
Menopause, the journal of The North American Menopause Society. About 20% to 50% of North American and European
women have this ability.
The researchers surveyed women from age 45 to 55 in a Seattle, Washington-area healthcare system to find study
participants who weren’t using hormone therapy and ate soy foods at least three times a week. The participants recorded
how many and how severe and bothersome their hot flashes and night sweats were and also had their hot flashes measured
with a skin monitor. Urine tests showed which women produced equol, which is metabolized from the soy isoflavone
diazden by bacteria in the gut.
Of the 357 participants, 34% were equol producers. And among the equol producers, those who had the most soy in their
diet were 76% less likely to report a higher than average number of hot flashes and night sweats than those who had the
least soy in their diet. But for the women who did not produce equol, soy made no difference. Soy intake didn’t affect how
severe or bothersome the hot flashes and night sweats were for either group.
Measuring equol in urine is a test that’s only done in research centers, so it’s not realistic for women who are not
participating in studies to be tested. And the effect of soy for women who do produce equol needs to be confirmed in
controlled, randomized studies, so making a definite recommendation to women on soy and hot flashes is premature, said
the authors.
“Women who are interested in trying dietary soy for their hot flashes can do their own experiment by incorporating it as a
healthy food in their diet. If it doesn’t help in four to six weeks, they can assume it probably won’t and can try other
lifestyle or medical therapies for their hot flashes,” says NAMS Executive Director Margery Gass, MD, NCMP.
That may be what some women in this study did. The clue is that about the same proportion of Caucasian and Asian
women in this study were equol producers (36% and 38%, respectively), although it’s known that a much higher
proportion of Asian women can produce equol. So it may be that the Caucasian women who found soy foods helped
regularly included these foods in their diet.
An approach that could help more women reduce hot flashes—whether they can produce equol or not—is to use
supplemental equol. A supplement of equol for hot flashes and other menopausal symptoms is being studied now in the
United States by Otsuka Pharmaceutical Company, Ltd, which sponsored this study, and its subsidiary Pharmavite LLC,
the supplement manufacturer.
The article, “A cross-sectional study of equol producer status and self-reported vasomotor symptoms,” will be published
in the May 2015 print edition of Menopause.
Arthritis Rheumatol. 2015 Feb;67(2):568-75. doi: 10.1002/art.38905.
The prevalence of fibromyalgia in the general population: a comparison of the american college of
rheumatology 1990, 2010, and modified 2010 classification criteria.
Jones GT1, Atzeni F, Beasley M, Flüß E, Sarzi-Puttini P, Macfarlane GJ.
Abstract
OBJECTIVE: The American College of Rheumatology (ACR) 1990 fibromyalgia classification criteria are based on the
presence of widespread pain and tenderness. In 2010, new criteria were proposed that focused more on multiple
symptoms, and these criteria were later modified to require only self report of symptoms. The current study aimed to
determine the population prevalence of fibromyalgia and to compare differences in prevalence using the alternative
criteria.
METHODS: A cross-sectional survey was conducted. Questionnaires, including items on pain, symptoms, and
rheumatologic diagnoses, were mailed to
4,600 adults in northeast Scotland. Participants who had chronic widespread pain or those who met the modified 2010
criteria, plus a subsample of other participants, were invited to attend a research clinic. Attendees completed an
additional questionnaire and underwent a rheumatologic examination, and their signs and symptoms were classified
according to the ACR 1990, 2010, and modified 2010 criteria. The prevalence of fibromyalgia according to each set of
criteria was calculated, weighting back to the target population by age, sex, and area of residence.
RESULTS: Of 1,604 questionnaire participants, 269 were invited to attend the research clinic, and 104 (39%) attended;
32 of these subjects (31%) met ≥1 set of fibromyalgia criteria. The prevalence of fibromyalgia according to the 1990,
2010, and modified 2010 criteria was 1.7% (95% confidence interval [95% CI] 0.7-2.8), 1.2% (95% CI 0.3-2.1), and
5.4% (95% CI 4.7-6.1), respectively. The ratio of females to males was 13.7:1, 4.8:1, and 2.3:1 of those meeting the
respective criteria sets.
CONCLUSION: Fibromyalgia prevalence varies with the different sets of classification criteria applied. In particular,
prevalence is higher and a greater proportion of men are identified with the modified 2010 criteria as compared to the
criteria sets requiring clinician input.
This has important implications for the use of the new criteria, both in research and in clinical practice.
Copyright © 2015 by the American College of Rheumatology.
PMID: 25323744 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/25647777
Menopause. 2015 Feb 2. [Epub ahead of print]
Early menopause and other gynecologic risk indicators for chronic fatigue syndrome in women.
Boneva RS1, Lin JM, Unger ER.
Abstract
OBJECTIVE: This study aims to examine whether gynecologic conditions are associated with chronic fatigue syndrome
(CFS).
METHODS: This study includes a subset of 157 women from a population-based case-control study in Georgia, United
States, conducted in 2004-2009. Gynecologic history was collected using a self-administered questionnaire. Crude
odds ratios (ORs) with 95% CIs and ORs adjusted for body mass index and other covariates, where relevant, were
estimated for gynecologic conditions between 84 CFS cases and 73 healthy controls.
RESULTS: Cases and controls were of similar age. Women with CFS reported significantly more gynecologic
conditions and surgical operations than controls: menopause status (61.9% vs 37.0%; OR, 2.37; 95% CI, 1.21-4.66),
earlier mean age at menopause onset (37.6 vs 48.6 y; adjusted OR, 1.22; 95% CI, 1.09-1.36), excessive menstrual
bleeding (73.8% vs 42.5%; adjusted OR, 3.33; 95% CI, 1.66-6.70), bleeding between periods (48.8% vs 23.3%;
adjusted OR, 3.31; 95% CI, 1.60-6.86), endometriosis (29.8% vs 12.3%; adjusted OR, 3.67; 95% CI, 1.53-8.84), use of
noncontraceptive hormonal preparations (57.1% vs 26.0%; adjusted OR, 2.95; 95% CI, 1.36-6.38), nonmenstrual pelvic
pain (26.2% vs 2.7%; adjusted OR, 11.98; 95% CI, 2.57-55.81), and gynecologic surgical operation (65.5% vs 31.5%;
adjusted OR, 3.33; 95% CI, 1.66-6.67), especially hysterectomy (54.8% vs 19.2%; adjusted OR, 3.23; 95% CI, 1.467.17). Hysterectomy and oophorectomy occurred at a significantly younger mean age in the CFS group than in controls
and occurred before CFS onset in 71% of women with records of date of surgical operation and date of CFS onset.
CONCLUSIONS: Menstrual abnormalities, endometriosis, pelvic pain, hysterectomy, and early/surgical menopause are
all associated with CFS. Clinicians should be aware of the association between common gynecologic problems and
CFS in women. Further work is warranted to determine whether these conditions contribute to the development and/or
perpetuation of CFS in some women.
PMID: 25647777 [PubMed - as supplied by publisher]
http://1.usa.gov/18sLsl9
PubMedhttp://1.usa.gov/18sLsl9
Slow wave sleep in the chronically fatigued: Power spectra distribution patterns in chronic fatigue syndrome
and primary insomnia.
Neu D1, Mairesse O2, Verbanck P3,
Le Bon O4.
Abstract
OBJECTIVES: To investigate slow wave sleep (SWS) spectral power proportions in distinct clinical conditions sharing
non-restorative sleep and fatigue complaints without excessive daytime sleepiness (EDS), namely the chronic fatigue
syndrome (CFS) and primary insomnia (PI).
Impaired sleep homeostasis has been suspected in both CFS and PI.
METHODS: We compared perceived sleep quality, fatigue and sleepiness symptom-intensities, polysomnography
(PSG) and SWS spectral power distributions of drug-free CFS and PI patients without comorbid sleep or mental
disorders, with a good sleeper control group.
RESULTS: Higher fatigue without EDS and impaired perceived sleep quality were confirmed in both patient groups.
PSG mainly differed in sleep fragmentation and SWS durations. Spectral analysis revealed a similar decrease in central
ultra slow power (0.3-0.79Hz) proportion during SWS for both CFS and PI and an increase in frontal power proportions
of faster frequencies during SWS in PI only.
The latter was correlated to affective symptoms whereas lower central ultra slow power proportions were related to
fatigue severity and sleep quality impairment.
CONCLUSIONS: In combination with normal (PI) or even increased SWS durations (CFS), we found consistent
evidence for lower proportions of slow oscillations during SWS in PI and CFS.
SIGNIFICANCE: Observing normal or increased SWS durations but lower proportions of ultra slow power, our findings
suggest a possible quantitative compensation of altered homeostatic regulation.
Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd.
All rights reserved.
PMID: 25620040 [PubMed - as supplied by publisher]
http://1.usa.gov/1K17kiZ
Neuro Endocrinol Lett. 2014 Dec 24;35(7):577-585
Attenuation of autoimmune responses to oxidative specific epitopes, but not nitroso-adducts, is associated
with a better clinical outcome in Myalgic Encephalomyelitis/chronic fatigue syndrome.
Maes M1, Leunis JC2.
Abstract
OBJECTIVES: There is evidence that inflammatory, oxidative and nitrosative stress (IO&NS) pathways participate in
the pathophysiology of a subgroup of patients with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Increased IgM-related autoimmune responses to oxidative specific epitopes (OSEs), including malondialdehyde (MDA),
oleic acid and phosphatidyl inositol (Pi), and nitroso-(NO)-adducts, including NO-tryptophan (NOW), NO-arginine and
NO-cysteinyl, are frequently observed in ME/CFS.
Autoimmune responses in ME/CFS may be driven by increased bacterial translocation as measured by IgM and IgA
responses to LPS of gram negative bacteria.
METHODS: The aim of this study is to examine whether IgM responses to OSEs and NO-adducts are related to a better
outcome as measured by the Fibromyalgia and Fatigue Rating Scale (FF).
76 ME/CFS patients with initially abnormal autoimmune responses were treated with care-as-usual, including
nutraceuticals with anti-IO&NS effects (NAIOS), such as L-carnitine, coenzyme Q10, taurine + lipoic acid, with or
without curcumine + quercitine or N-acetyl-cysteine, zinc + glutamine.
RESULTS: We found that use of these NAIOS was associated with highly significant reductions in initially increased
IgM-mediated autoimmune responses to OSEs and NO-adducts.
A greater reduction in autoimmune responses to OSEs during intake of these NAIOS was associated with a lower FF
score.
Reductions in IgM responses to oleic acid, MDA and Pi, but not in any of the NO-adducts, were associated with
reductions in severity of illness.
These associations remained significant after adjusting for possible effects of increased bacterial translocation (leaky
gut).
CONCLUSIONS: Our results show that autoimmune responses to OSEs are involved in the pathophysiology of
ME/CFS and that these pathways are a new drug target in a subgroup of ME/CFS patients.
Although hypernitrosylation and nitrosative stress play a role in ME/CFS, reductions in these pathways are not
associated with lowered severity of illness.
Randomized controlled trials with NAIOS should be carried out in the subgroup of ME/CFS patients with initially
increased autoimmune responses to OSEs.
PMID: 25617880 [PubMed - as supplied by publisher]
Fulltexthttp://www.ehjournal.net/content/14/1/4
http://www.ehjournal.net/content/pdf/1476-069X-14-4.pdf
Butyrylcholinesterase genotype and enzyme activity in relation to Gulf War illness: preliminary evidence of
gene-exposure interaction from a case–control study of 1991 Gulf War veterans
Lea Steele, Oksana Lockridge, Mary M Gerkovich, Mary R Cook and Antonio Sastre
Environmental Health 2015, 14:4 doi:10.1186/1476-069X-14-4
Abstract
Background: Epidemiologic studies have implicated wartime exposures to acetylcholinesterase (AChE)-inhibiting
chemicals as etiologic factors in Gulf War illness (GWI), the multisymptom condition linked to military service in the
1991 Gulf War. It is unclear, however, why some veterans developed GWI while others with similar exposures did not.
Genetic variants of the enzyme butyrylcholinesterase (BChE) differ in their capacity for metabolizing AChE-inhibiting
chemicals, and may confer differences in biological responses to these compounds. The current study assessed BChE
enzyme activity and BChE genotype in
1991 Gulf War veterans to evaluate possible association of this enzyme with GWI.
Methods: This case–control study evaluated a population-based sample of 304 Gulf War veterans (144 GWI cases,
meeting Kansas GWI criteria, and 160 controls). BChE enzyme activity levels and genotype were compared, overall, in
GWI cases and controls. Potential differences in risk associated with cholinergic-related exposures in theater were
explored using stratified analyses to compare associations between GWI and exposures in BChE genetic and enzyme
activity subgroups.
Results: Overall, GWI cases and controls did not differ by mean BChE enzyme activity level or by BChE genotype.
However, for the subgroup of Gulf War veterans with less common, generally less active, BChE genotypes (K/K, U/AK,
U/A, A/F, AK/F), the association of wartime use of pyridostigmine bromide (PB) with GWI (OR = 40.00, p = 0.0005) was
significantly greater than for veterans with the more common U/U and U/K genotypes (OR = 2.68, p = 0.0001).
Conclusions: Study results provide preliminary evidence that military personnel with certain BChE genotypes who
used PB during the 1991 Gulf War may have been at particularly high risk for developing GWI.
Genetic differences in response to wartime exposures are potentially important factors in GWI etiology and should be
further evaluated in conjunction with exposure effects.
http://www.ncbi.nlm.nih.gov/pubmed/25591540
Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(10 Vypusk 2 Rasseiannyi skleroz):99-104.
Asthenia, chronic fatigue syndrome, emotional disorders and quality of life of patients with multiple sclerosis.
[Article in Russian] Lebedeva AV1, Shchukin IA1, Soldatov MA1, Boĭko OV2, Petrov SV3, Khozova AA3, Ismailov AM3,
Shikhkerimov RK3, Boĭko AN4.
Abstract
Objective. The evaluation of the dynamics of asthenia, chronic fatigue syndrome, emotional disorders and quality of life
of patients with multiple sclerosis (MS) and to explore the possibility of using idebenon (noben) in treatment of these
impairments.
Material and methods. We studied 35 patients, 18 men and 17 women, with MS (mean age 36.4±8.86 years, mean
disease duration 10.33±6.07 years); 83% of patients had remitting type and others - secondary progressive type.Along
with neurological examination, we used the Modified Fatigue Impact Scale (MFIS 21), the Hospital Anxiety and
Depression Scale and a quality of life questionnaire (EQ5D). Patients had marked asthenia and chronic fatigue at
baseline. The old age of the patients and duration of MS and its severity according to EDSS predicted the higher levels
of asthenia, chronic fatigue and anxiety with depression and lower quality of life on EQ5D. All patients received noben in
dosage 90 mg daily (30 mg 3 times a day) during 6 months.
Results and conclusion. Idebenon (noben) reduced the severity of chronic fatigue syndrome, asthenia and depression
in MS patients. The dose used in the study may be regarded as the optimal dose that provides best efficacy with
minimal side-effects.
PMID: 25591540 [PubMed - as supplied by publisher]
http://journals.cambridge.org/action/displayAbstract?fromPage=onlin...
Epidemiol Infect. 2015 Jan 13:1-8. [Epub ahead of print]
Severely impaired health status of non-notified Q fever patients leads to an underestimation of the true burden
of disease.
VAN Loenhout JA1, Wielders CC2, Morroy G1, Cox MJ1, VAN DER Hoek W3, Hautvast JL1, Paget WJ1, VAN DER
Velden J1.
Author information
1Academic Collaborative Centre AMPHI,Department of Primary and Community Care,Radboud university medical
center,Nijmegen,The Netherlands. 2Department of Medical Microbiology and Infection Control,Jeroen Bosch Hospital,
's-Hertogenbosch,The Netherlands. 3Centre for Infectious Disease Control,National Institute for Public Health and the
Environment (RIVM),Bilthoven,The Netherlands.
Abstract
SUMMARY Q fever patients are often reported to experience a long-term impaired health status, including fatigue,
which can persist for many years. During the large Q fever epidemic in The Netherlands, many patients with a
laboratory-confirmed Coxiella burnetii infection were not notified as acute Q fever because they did not fulfil the clinical
criteria of the acute Q fever case definition (fever, pneumonia and/or hepatitis).
Our study assessed and compared the long-term health status of notified and non-notified Q fever patients at 4 years
after onset of illness, using the Nijmegen Clinical Screening Instrument (NCSI). The study included 448 notified and 193
non-notified Q fever patients.
The most severely affected subdomain in both patient groups was 'Fatigue' (50•5% of the notified and 54•6% of the
non-notified patients had severe fatigue). Long-term health status did not differ significantly between the notified and
non-notified patient groups, and patients scored worse on all subdomains compared to a healthy reference group.
Our findings suggest that the magnitude of the 2007-2009 Q fever outbreak in The Netherlands was underestimated
when only notified patients according to the European Union case definition are considered.
The Gut Microbiome and the Brain
To cite this article:
Galland Leo. Journal of Medicinal Food. December 2014, 17(12): 1261-1272. doi:10.1089/jmf.2014.7000.
Published in Volume: 17 Issue 12: December 5, 2014
Online Ahead of Print: November 17, 2014
Author information
Leo Galland
Foundation for Integrated Medicine, New York, New York, USA.
Address correspondence to: Leo Galland, MD, Foundation for Integrated Medicine, New York, NY, 10011, USA, E-mail:
Lgallandmd@aol.com.
Manuscript received 9 September 2014
Revision accepted 9 October 2014
ABSTRACT
The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as
lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial
dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central
nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional
responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid
and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can
produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these
hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric
nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the
architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and
cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue
syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of
celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet,
probiotics, and prebiotics.
Science Advances: 27.2.2015
Vol 1 no:1 e1400121
Distinct plasma immune signatures in ME/CFS are
present early in the course of illness
Mady Hornig,1,2* José G. Montoya,3 Nancy G. Klimas,4 Susan Levine,5 Donna Felsenstein,6
Lucinda Bateman,7 Daniel L. Peterson,8 C. Gunnar Gottschalk,8 Andrew F. Schultz,1
Xiaoyu Che,1 Meredith L. Eddy,1 Anthony L. Komaroff,9 W. Ian Lipkin1,2,10
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may
affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or
management despite global efforts to find biomarkers of disease. We considered the possibility that inability to
identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing
of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies
of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables.
Controls were frequency-matched on key variables known to affect immune status, including season of
sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune
signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in
subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases
had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine
regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures
of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical
implications for discovery of interventional strategies and early diagnosis of ME/CFS.
fulltext- http://downloads.hindawi.com/journals/mi/aip/929720.pdf
Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.
Peterson D. 2, Brenu E.W.1, Gottschalk G. 2, Ramos S. 1, Ngyuen T. 1, Staines D. 1, Marshall-Gradisnik S1.
1.Griffith Health Institute, School of Medial Sciences, National Centre forNeuroimmunology and Emerging Diseases,
Griffith University, Parklands,Queensland, Australia. 2.Simmaron Research, Incline Village, 948 Incline Way, Nevada,
USA.
Abstract
Objectives: Previous research has provided evidence for dysregulation in peripheral cytokines in patients with Chronic
Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To date only one study has examined cytokines in
cerebrospinal fluid (CSF) samples of CFS/ME patients. The purpose of this pilot study was to examine the role of
cytokines in CSF of CFS/ME patients.
Methods: CSF was collected from 18 CFS/ME patients and 5 healthy controls. The CSF samples were examined for
the expression of 27 cytokines [interleukin (IL)-1β, IL-1ra, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15,
IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, PDGF-BB, RANTES, TNFα and VEGF] using the bio-plex human cytokine 27-plex assay.
Results: Of the 27 cytokines examined, only IL-10 was significantly reduced in the CFS/ME patients in comparison to
the controls.
Conclusions: This preliminary investigation suggests that perturbations in inflammatory cytokines in the CSF of
CFS/ME patients may contribute to the neurological discrepancies observed in CFS/ME.
fulltext- http://omicsonline.org/open-access/characterisation-of-b-cell-subse...
Characterisation of B cell Subsets and Receptors in Chronic Fatigue Syndrome Patients
Ramos S1, Brenu E1, Nuyen T1, Ng J2, Staines D1 and Marshall-Gradisnik S1, 1National Centre of Neuroimmunology
and Emerging Diseases – NCNED, Griffith University, Queensland, Australia 2Paradise Rheumatoid Clinic, Southport,
Queensland, Australia
Abstract
Limited immunological changes have been previously reported in B cell phenotype in Chronic Fatigue Syndrome (CFS)
patients, so there is no clear established role of B cells in the pathophysiology of CFS patients.
The aim of this study was to evaluate B cells subsets including naive, memory naive, memory switched, memory nonswitched, double negative, transitional, plasmablasts, HLA-DR+, plasma and regulatory B cells (Breg) in CFS patients
compared with non-fatigued controls. B cell activation markers (CD81, CD21) and surface receptors (CD79a/b, IgM,
IgD, IgA, IgE) were also examined in CFS patients compared with non-fatigued controls. 46 CFS patients (age=50.00 ±
2.00 years) and 34 non-fatigued controls (age=49.00 ± 2.16 years) participated in the study.
The percentage of BCR IgM+ B cells was significantly increased in the CFS group compared with non-fatigued controls
(p=0.037). Similarly, there was a significant decrease in the CD1d+ B cells in the CFS group compared with nonfatigued
controls (p=0.046).
No additional differences in B cell phenotypes, activation markers and surface receptors were found in the CFS patients
compared with the non-fatigued control group.
The differences observed in the B cell phenotype of CFS patients compared with non-fatigued controls may explain
some of the disturbances in the immune homeostasis, however whether this is causal or the consequence of
immunological imbalances previously reported in CFS patients requires further investigation.
Copyright: © 2015 Ramos S, et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original
author and source are credited.
http://on.wsj.com/17EjVwo
More Evidence Found of Biological Basis to Chronic Fatigue Syndrome Discovery
In what is perhaps the most significant evidence yet that chronic fatigue syndrome has a biological basis, researchers
said they found an immune system signature that is present in newly diagnosed patients but not in healthy people.
The pattern, published on Friday in a paper in Science Advances, wasn't seen in people who had been ill for more than
three years, but the discovery may help identify and treat patients earlier.
The researchers, led by Columbia University's Mailman School of Public Health, looked at 51 proteins, also known as
cytokines, released by cells involved in the immune system.
Among 646 patients studied, including CFS patients and healthy controls, people who were ill for three years or less
had higher protein levels than the others, the researchers found.
The immune signature must be replicated by other labs, but "I think it is convincing," Said Benjamin Natelson, director of
the Pain and Fatigue Study Center at Mount Sinai Beth Israel in Manhattan.
The Science Advances study, funded by the private Chronic Fatigue Initiative of the Hutchins Family Foundation and
the National Institutes of Health, comes as new attention is focused on the condition, also known as myalgic
encephalomyelitis/chronic fatigue syndrome (http://on.wsj.com/1ASuKFg).
The Institute of Medicinerecently studied the biological evidence for the disease, which they estimate affects up to 2.5
million Americans.
One of the strengths of the Science Advances study is that researchers identified 52 people who had the illness less
than three years.
Previous studies have looked at fewer patients, making it harder to detect patterns or differences between various
groups.
Mady Hornig, the study's lead author and director of translational research at the Center for Infection and Immunity at
Columbia's Mailman School, said that in the early phase of the disease, there is evidence of proteins that are usually
found in blood when someone is fighting an infection.
Those proteins should return to normal levels after the acute illness has faded.
But in the newly diagnosed ME/CFS patients, "The immune system doesn't quiet down,"
She said. This finding fits in with reports by many, but not all, patients, that they were sick with an infection and never
completely recovered.
Dr. Hornig said the reason why the same immune signature cannot be found after patients have been ill for more than
three years is: "The immune system shows evidence of exhaustion."
There are existing monoclonal antibodies that target some of the elevated proteins and might eventually be tested with
newly diagnosed ME/CFS patients, Dr. Hornig said.
The hope is that immune-modifying drugs used early enough might help stave off the decline experienced by patients
who have been ill for longer.
fulltext- http://advances.sciencemag.org/content/1/1/e1400121
Distinct plasma immune signatures in ME/CFS are present early in the course of illness
Mady Hornig, José G. Montoya, Nancy G. Klimas, Susan Levine, Donna Felsenstein, Lucinda Bateman, Daniel L.
Peterson, C. Gunnar Gottschalk, Andrew F. Schultz, Xiaoyu Che, Meredith L. Eddy, Anthony L. Komaroff, W. Ian Lipkin
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect
up to 4 million people in the United States alone.
There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of
disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria
and laboratory methods as well as the timing of sample collection during the course of the illness.
Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune
signatures with diagnosis, illness duration, and other clinical variables.
Controls were frequency-matched on key variables known to affect immune status, including season of sampling and
geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the
course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of
illness (n = 246).
Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and
anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks.
We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity,
suggesting that the immunopathology of ME/CFS is not static.
These findings have critical implications for discovery of interventional strategies and early diagnosis of
ME/CFS.
http://www.ncbi.nlm.nih.gov/pubmed/25711200
J Urol. 2015 Feb 21. pii: S0022-5347(15)00392-4. doi:
10.1016/j.juro.2015.02.082. [Epub ahead of print]
Brain white matter abnormalities in female interstitial cystitis/bladder pain syndrome: A MAPP Network
neuroimaging study.
Farmer MA, Huang L, Martucci K, Yang CC, Maravilla KR, Harris RE, Clauw DJ, Mackey S, Ellingson BM, Mayer EA,
Schaeffer AJ, Apkarian AV; MAPP Research Network.
Abstract
PURPOSE: Several chronic pain conditions may be distinguished by condition-specific brain anatomical and functional
abnormalities observed by imaging suggestive of underlying disease processes. Here we present the first
characterization of IC/BPS-associated white matter (axonal) abnormalities based on multi-center neuroimaging from the
Multidisciplinary Approach to the Study of Chronic Pelvic Pain
(MAPP) Research Network.
MATERIALS AND METHODS: Women with IC/BPS (n=34) and healthy controls
(n=32) were assessed with questionnaires on pain, mood, and daily function. White matter microstructure was
evaluated with diffusion tensor imaging (DTI) to model directional water flow along axons, or fractional anisotropy (FA).
Regions that correlated with clinical parameters were further examined for sex and syndrome dependence.
RESULTS: Women with IC/BPS exhibited numerous white matter abnormalities that correlated with severity of pain,
urinary symptoms, and impaired quality of life. IC/BPS was characterized by decreased FA in aspects of the right
anterior thalamic radiation, left forceps major, and right longitudinal fasciculus. Increased FA was detected in the right
superior and bilateral inferior longitudinal fasciculi.
CONCLUSIONS: The first characterization of brain white matter abnormalities in women with IC/BPS reveals that
regional decreases and increases in white matter integrity, across multiple axonal tracts, are associated with symptom
severity in IC/BPS. Given that white matter abnormalities closely correlate with hallmark symptoms of IC/BPS, including
bladder pain and urinary symptoms, brain anatomical alterations suggest neuropathological contributions to chronic
urological pelvic pain.
Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights
reserved.
PMID: 25711200 [PubMed - as supplied by publisher]
fulltext- http://onlinelibrary.wiley.com/doi/10.1002/nbm.3261/full
NMR Biomed. 2015 Mar;28(3):404-13. doi: 10.1002/nbm.3261
Evidence in chronic fatigue syndrome for severity-dependent upregulation of prefrontal myelination that is
independent of anxiety and depression.
Barnden LR1, Crouch B, Kwiatek R, Burnet R, Del Fante P. 1Department of Nuclear Medicine, The Queen Elizabeth
Hospital, Woodville, SA, Australia; School of Chemistry and Physics, University of Adelaide, Adelaide, SA, Australia;
National Centre for NeuroImmunology and Emerging Diseases, Griffith University, Gold Coast, Qld, Australia.
Abstract
White matter (WM) involvement in chronic fatigue syndrome (CFS) was assessed using voxel-based regressions of
brain MRI against CFS severity scores and CFS duration in 25 subjects with CFS and 25 normal controls (NCs). As well
as voxel-based morphometry, a novel voxel-based quantitative analysis of T1 - and T2 -weighted spin-echo (T1w and
T2w) MRI signal level was performed.
Severity scores included the Bell CFS disability scale and scores based on the 10 most common CFS symptoms.
Hospital Anxiety and Depression Scale (HADS) depression and anxiety scores were included as nuisance covariates.
By relaxing the threshold for cluster formation, we showed that the T1w signal is elevated with increasing CFS severity
in the ventrolateral thalamus, internal capsule and prefrontal WM. Earlier reports of WM volume losses and
neuroinflammation in the midbrain, together with the upregulated prefrontal myelination suggested here, are consistent
with the midbrain changes being associated with impaired nerve conduction which stimulates a plastic response on the
cortical side of the thalamic relay in the same circuits.
The T2w signal versus CFS duration and comparison of T2w signal in the CFS group with the NC group revealed
changes in the right middle temporal lobe WM, where impaired communication can affect cognitive function.
Adjustment for depression markedly strengthened cluster statistics and increased cluster size in both T1w severity
regressions, but adjustment for anxiety less so. Thus, depression and anxiety are statistical confounders here, meaning
that they contribute variance to the T1w signal in prefrontal WM but this does not correlate with the co-located variance
from CFS severity.MRI regressions with depression itself only detected associations with WM volume, also located in
prefrontal WM.
We propose that impaired reciprocal brain-body and brain-brain communication through the midbrain provokes
peripheral and central responses which contribute to CFS symptoms. Although anxiety, depression and CFS may share
biological features, the present evidence indicates that CFS is a distinct disorder.
© 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.
PMID: 25702943
Fatigue in Child Chronic Health
Conditions: A Systematic Review of
Assessment Instruments
Alison Crichton, DPsycha,b,c, Sarah Knight, PhDa,b,d, Ed Oakley, PhDb,d,e, Franz E. Babl, MDb,d,e, Vicki Anderson, PhDb,c,e
abstract
BACKGROUND AND OBJECTIVE: Fatigue
is common in chronic health conditions in childhood, associated
with decreased quality of life and functioning, yet there are limited data to compare
assessment instruments across conditions and childhood development. Our objective was to
describe fatigue assessment instruments used in children with chronic health conditions and
critically appraise the evidence for the measurement properties of identified instruments.
METHODS: Data sources included Medline, Cumulative Index to Nursing and Allied Health
Literature, and PsycINFO (using the EBSCOhost platform). Study selection included
quantitative assessment of fatigue in children with health conditions. Data extraction was as
follows: (1) study design, participant and fatigue instruments, (2) measurement properties of
fatigue instruments, (3) methodological quality of included studies, and (4) synthesis of the
quality of evidence across studies for the measurement properties of fatigue instruments.
RESULTS: Twenty fatigue assessment instruments were identified (12 child reports, 7 parent
reports, 1 staff report), used in 89 studies. Fatigue was assessed in over 14 health conditions,
most commonly in children with cancer and chronic fatigue syndrome. Evidence for the
measurement properties of instruments varied, and overall quality was low. Two fatigue
instruments demonstrated strong measurement properties for use in children with diverse
health conditions and children with cancer.
CONCLUSIONS: The review is limited to children younger than 18 years and results are specific to
health conditions described, limiting generalizability of findings to other populations. Evidence
for the measurement properties of fatigue instruments varied according to the population in
which instruments were used and informant. Further evidence is required for assessment of
fatigue in younger children, and children with particular health conditions.
Victorian Pediatric Rehabilitation Service, Monash Children’s, Melbourne, Australia; Murdoch Childrens Research Institute,
Melbourne, Australia; School of Psychological Sciences and Department of Pediatrics, University of Melbourne, Melbourne,
Australia; and Royal Children’s Hospital, Melbourne, Australia
Dr Crichton conceptualized and designed the study, carried out the literature searches, completed the initial analysis, drafted the
initial manuscript, and revised the manuscript; Dr Knight assisted with the data collection instrument, screened articles for inclusion,
reviewed analysis, and reviewed the manuscript; Dr Anderson supervised data collection and critically reviewed the manuscript; Drs
Oakley and Babl cosupervised data collection and reviewed the manuscript; and all authors approved the final manuscript as
submitted.
www.pediatrics.org/cgi/doi/10.1542/peds.2014-2440
DOI: 10.1542/
Original Article
Molecular Psychiatry , (31 March 2015) | doi:10.1038/mp.2015.29
Cytokine network analysis of cerebrospinal fluid in myalgic
encephalomyelitis/chronic fatigue syndrome
M Hornig, G Gottschalk, D L Peterson, K K Knox, A F Schultz, M L Eddy, X Che and W I Lipkin
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is
frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32
cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex
using a 51-plex cytokine assay. Group-specific differences were found for the majority of analytes with an
increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis
revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor
1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1α or interleukin 1β,
suggesting a disturbance in interleukin 1 signaling. Our results indicate a markedly disturbed immune
signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central
nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity.
ORIGINAL ARTICLE
Two Clusters of Ciguatera Fish Poisoning in Paris,
France, Related to Tropical Fish Imported From the
French Caribbean by Travelers
1.
2.
3.
4.
5.
6.
Loïc Epelboin MD1,2,
Alice Pérignon MD1,
Virginie Hossen MSc3,
Renaud Vincent MD4,
Sophie Krys PhD3 and
Eric Caumes MD, PhD1,2
Article first published online: 27 OCT 2014
© 2014 International Society of Travel Medicine
Journal of Travel Medicine
Volume 21, Issue 6, pages 397–402, November/December 2014
Abstract
Background
Ciguatera fish poisoning (CFP) is a food-borne illness due to the consumption of reef fish containing pathogenic toxins. CFP is endemic to tropical
areas and may be described in travelers in non-endemic areas.
Methods
We describe two clusters of autochthonous cases of CFP in Paris, France. They were related to two fish caught in Guadeloupe (French West Indies)
and consumed in Paris after being air-transported in a cooler. In both cases, fish flesh was analyzed and the presence of ciguatoxins by mouse
bioassay (MBA) was confirmed.
Results
The first cluster involved eight individuals among whom five presented gastrointestinal symptoms and four presented neurological symptoms after
consuming barracuda flesh (Sphyraena barracuda). The second cluster involved a couple who consumed a grey snapper (Lutjanus griseus). Most of
them consulted at different emergency departments in the region of Paris.
Conclusions
CFP may be seen in non-traveler patients outside endemic countries resulting from imported species of fish. Thus, CFP may be undiagnosed as
physicians are not aware of this tropical disease outside endemic countries. The detection of ciguatoxins by MBA in the French National Reference
Laboratory is useful in the confirmation of the diagnosis.
Study Shows Why Exercise Magnifies Exhaustion for Chronic Fatigue Syndrome Patients
Released: 12-Mar-2015 2:05 PM EDT
Source Newsroom: University of Florida
Newswise — The mechanism that causes high-performance athletes to “feel the burn” turns out to be the culprit
in what makes people with chronic fatigue syndrome feel exhausted by the most common daily activities, new
University of Florida Health research shows.
Published in the February issue of the journal Pain, the study shows that the neural pathways that transmit
feelings of fatigue to the brain might be to blame. In those with chronic fatigue syndrome, the pathways do their
job too well.
The findings also provide evidence for the first time that peripheral tissues such as muscles contribute to
feelings of fatigue. Determining the origins of fatigue could help researchers develop therapies or identify
targets for those therapies.
Researchers focused on the role of muscle metabolites, including lactic acid and adenosine triphosphate, or
ATP, in the disease. The study has demonstrated for the first time that these substances, released when a person
exercises his or her muscles, seem to activate these neural pathways. Also, UF Health researchers have shown
that these pathways seem to be much more sensitive in patients with chronic fatigue syndrome than in patients
without the disease, something that hasn’t been studied before.
Chronic fatigue syndrome, which the Institute of Medicine recently renamed systemic exertion intolerance
disease, or SEID, is characterized by extreme chronic fatigue. Because its chief symptom -- fatigue -- is often
associated with many other diseases, it can be difficult to diagnose SEID for the more than 1 million people
who actually have the disease, according to the Centers for Disease Control and Prevention. The disease has no
root medical cause, and researchers don’t know what triggers it. But they are studying aspects of the disease to
figure out ways to treat it.
“What we have shown now, that has never been shown before in humans, is that muscle metabolites can induce
fatigue in healthy people as well as patients who already have fatigue,” said Dr. Roland Staud, a professor of
rheumatology and clinical immunology in the UF College of Medicine and the paper’s lead author.
During exercise, muscles produce metabolites, which are sensed by metaboreceptors that transmit information
via fatigue pathways to the brain, according to the researchers. But in patients with SEID, these fatigue
pathways have become highly sensitive to metabolites and can trigger excessive feelings of fatigue.
“For most of us, at the end of strenuous exertion we feel exhausted and need to stop — but we will recover
rapidly,” Staud said. “However, these individuals tire much more rapidly and sometimes just after moving
across a room, they are fully exhausted. This takes a toll on their lives.”
Staud and co-author Michael E. Robinson, a professor in the department of clinical and health psychology in the
UF College of Public Health and Health Professions, recruited a group of 39 patients with SEID and 29
participants without the disease. The researchers asked the participants to don a blood pressure cuff just above
their elbows on their dominant side, pick up a spring-loaded device and squeeze it to 100 percent of their
maximum capacity, which was measured by a dial.
With research assistants encouraging them, the study participants then squeezed the device so that the dial
showed they were gripping at 50 percent of their maximum capacity for as long as they could.
At the end of the hand-grip exercise, the blood pressure cuff on the participant’s arm
was inflated, almost instantly trapping the metabolites generated by the exercise within the forearm muscles.
This allowed the metabolites to collect in the forearm tissue without being cleared by the circulatory system.
There, the metabolites continued to activate fatigue pathways, sending messages of fatigue to the brain and
allowing researchers to measure how much fatigue and pain may occur because of the trapped metabolites.
With the blood pressure cuff still inflated, the participants rated fatigue and then pain in their forearms every 30
seconds. Both patients with SEID and patients without the disease reported increasing fatigue, but patients with
the disease recorded much higher levels of fatigue and pain.
“We found that the fatigued individuals reported more fatigue than the non-fatigued individuals during the
exercise, and also found that they had more pain compared to the non-fatigued individuals,” Staud said.
On the Fatigue Visual Analog Scale used to measure participants’ fatigue, patients with SEID rated their fatigue
at approximately 5.5 on a scale of 0 to 10 after the hand-grip exercise while wearing the inflated blood pressure
cuff, whereas participants without the disease rated their fatigue at approximately 1.5.
After 30 minutes, the participants repeated the exercise, but with the opposite arm and without the cinching
blood pressure cuff so the metabolites could be cleared from the arm. Both sets of participants experienced
fatigue, but the feeling of fatigue in those with the disease was much lower than when the metabolites were
trapped with the blood pressure cuff.
“This suggests that hypersensitive fatigue pathways play an important role for the often pronounced exerciserelated fatigue of patients with the disease,” Staud said.
Next, Staud plans to explore treatment interventions and to conduct brain-imaging studies of patients with
SEID.
“The take-home message here is, like many of the pain studies we have conducted, there are both peripheral and
central nervous system factors at play in these complex syndromes,” said Robinson, who is also the director of
the UF Center for Pain Research and Behavioral Health. “Our study seems to highlight the important role of
these peripheral tissues.”
Chronic Fatigue Syndrome: Wrong Name, Real Illness
Miriam E. Tucker
(Medscape Medical news)
Disclosures January 08, 2015
Introduction
Sufferers of what has been called chronic fatigue syndrome (CFS) are challenging patients, presenting with complaints of postexertional malaise,
persistent flulike symptoms, unrefreshing sleep, "brain fog," and often a long list of other symptoms that don't seem to fit any recognizable pattern.
Some appear ill, but many don't. And the routine laboratory tests often come back negative.
For that reason, those with CFS are often labelled as malingerers, depressed, or at least partially psychosomatic. But for the scientists and clinicians
in the field, the phenomenon is as real as diabetes or atherosclerosis. Despite the stigma and a severe dearth of research funding, new efforts from the
federal government and the private sector could move the field forward.
The name itself is one of the many controversies surrounding the condition. The CFS moniker has been used in the United States since 1988; in the
United Kingdom, Canada, and elsewhere it is called myalgic encephalomyelitis (ME).
Many patients abhor the term "chronic fatigue syndrome" because they feel that it trivializes the condition, which can render individuals severely
debilitated, housebound, or bedridden.
Moreover, an emerging consensus in the field is that "chronic fatigue syndrome" as defined in 1994 by the Centers for Disease Control and
Prevention (CDC) represents a more heterogeneous and less severely affected population than does "myalgic encephalomyelitis," captured by the
2003 Canadian Clinical Case Definition. Both definitions require multiple symptoms in addition to 6 months of unexplained fatigue to make the
diagnosis, but the ME criteria also require the hallmark symptom of postexertional malaise. [1]
For now, the compromise term "ME/CFS" has been adopted by the research community and officially by the various agencies within the US
Department of Health and Human Services (HHS). In early 2015, the Institute of Medicine, commissioned by HHS, will release recommendations for
new clinical diagnostic criteria and possibly will propose a name change as well.
The Microbiome and Brain Health: What's the
Connection?
Sarah R. Dash
March 24, 2015
Gut Microbiome and Diet in Psychiatry: Focus on Depression
from Medscape Psychiatry
Introduction
Researchers are now beginning to understand the ways in which bacteria living in the human gut—the gut microbiota—communicate with and
influence brain health. The concept of a faulty "gut/brain axis" has been associated with various neurologic and psychiatric outcomes and is thought
to be explained, at least in part, by immune dysfunction and inflammation triggered by poor gut health. [1]
The gut microbiota has emerged as an important focus in the understanding of noncommunicable diseases, including type 2 diabetes and
cardiovascular disease, as well as disorders of the brain. Brain-related conditions place a great burden on society, and the limitations of current
interventions reflects the need for ongoing investigations into understanding and treating brain disorders, in part by exploring the close relationship
between our biome and our brain.
Biome and Brain Overview
The human intestinal microbiome is seeded at birth; it is influenced initially by delivery and feeding mode, and reaches an adult-like state within the
first few years of life.[2] Alterations in the composition, diversity, and stability of gut microbiota have been linked to a broad range of diseases,
including autoimmune, metabolic, gastrointestinal, and brain disorders. [3,4]
Although the composition of the gut microbiota remains relatively stable during our middle years, it continues to be influenced by such factors as
geography, antibiotics, exercise, and diet. This is particularly important when considering possible prevention and intervention in brain disorders.
It is well known that bidirectional gut/brain communication may occur directly and indirectly via the central and enteric nervous systems, the vagus
nerve, and the endocrine and immunoinflammatory systems and through the modulation of neurotransmitters. [1] Diet could also utilize these
pathways, because the gut microbiota supports optimal nutritional bioavailability—for example, by maintaining normal plasma tryptophan levels, an
important building block for making serotonin, a key central nervous system neurotransmitter.[1] Advances in this field have come from the
development of DNA sequencing technology, which allows researchers to conduct large-scale screening of the bacteria in the gut and their associated
physiologic functions. This has helped researchers to link disruption of the gut microbiota with biological markers of the communication pathways
mentioned above.
It is important to note that there is so far no "gold standard" healthy intestinal microbial profile. Genetic and environmental factors mean that there
may be significant variability in gut composition from person to person. In general, a "healthy," diverse gut microbiota promotes gut health and
maintains essential structural, metabolic and signaling functions. The human gut can be "unhealthy" for a variety of reasons. Typically, a shift away
from normal gut microbiota diversity and stability—termed "dysbiosis"—means it is unable to sustain one or more of the functions of a healthy gut,
and this may contribute to metabolic, autoimmune, and brain disorders.
Increased intestinal permeability, often called "leaky gut," occurs when the mucosal gut barrier fails to prevent potentially harmful molecules from
entering the bloodstream; these molecules include lipopolysaccharides, which are found on the outer membrane of gram-negative bacteria and may
elicit inflammatory responses in the body.[5] Increased intestinal permeability is a common feature of an unhealthy gut.
Keeping in mind that each gut microbiome looks different, the terms "healthy" and "unhealthy" used here refer to instances in which gut microbiota
functioning, composition, or ratio may deviate from a person's individual-specific "normal" state.
http://www.medscape.com/viewarticle/841748_4