Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial
Emily Y. Chew, MD1; Traci E. Clemons, PhD2; Elvira Agrón, MA1; Lenore J. Launer, PhD3; Francine Grodstein, ScD4,5; Paul S. Bernstein, MD, PhD6 ; for the Age-Related Eye Disease Study 2 (AREDS2) Research Group
[+-] Author Affiliations
1Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute/National Institutes of Health, Bethesda, Maryland
2The EMMES Corporation, Rockville, Maryland
3Neuroepidemiology Section, National Institute on Aging/National Institutes of Health, Bethesda, Maryland
4Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
5Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
6Moran Eye Center, University of Utah, Salt Lake City
JAMA. 2015;314(8):791-801. doi:10.1001/jama.2015.9677.
ABSTRACT
Importance Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease.
Objective To test the effects of oral supplementation with nutrients on cognitive function.
Design, Setting, and Participants In a double-masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study.
Interventions Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc.
Main Outcomes and Measures The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from −22 to 17, with higher scores representing better function.
Results A total of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not. The yearly change in the composite cognitive function score was −0.19 (99% CI, −0.25 to −0.13) for participants randomized to receive LCPUFAs vs −0.18 (99% CI, −0.24 to −0.12) for those randomized to no LCPUFAs (difference in yearly change, −0.03 [99% CI, −0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite cognitive function score was −0.18 (99% CI, −0.24 to −0.11) for participants randomized to receive lutein/zeaxanthin vs −0.19 (99% CI, −0.25 to −0.13) for those randomized to not receive lutein/zeaxanthin (difference in yearly change, 0.03 [99% CI, −0.14 to 0.19]; P = .66). Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant.
Conclusions and Relevance Among older persons with AMD, oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function.
CYTOKINE
Vol 78 Feb 2016
Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome
Lyme disease: time for a new approach?
Valerie Obsomer, ecological and environmental risk expert6
<>[email protected]
Many more questions than answers
Lyme disease is the most common vector borne disease in North America and Europe, with 300 000 new cases in the United States1 and an estimated 100 000 new cases in Europe each year.2 These numbers are likely to be underestimates because case reporting is inconsistent3 and many infections go undiagnosed.4 Climate change may have contributed to a rapid increase in tick borne diseases, with migratory birds disseminating infected ticks.5
Our common understanding of Lyme disease is that a tick bite is followed by the development of a classic rash pattern (erythema migrans). When treated early with a relatively short course of antibiotics, most patients have good outcomes.6 But the standard two tier testing for Lyme disease is inaccurate in the early stages.
http://www.ncbi.nlm.nih.gov/pubmed/26623235
Borderline Intracranial Hypertension Manifesting as Chronic Fatigue Syndrome Treated by Venous Sinus Stenting.
Higgins N, Pickard J, Lever A.
Abstract
Chronic fatigue syndrome and cases of idiopathic intracranial hypertension without signs of raised intracranial pressure can be impossible to distinguish without direct measurement of intracranial pressure. Moreover, lumbar puncture, the usual method of measuring intracranial pressure, can produce a similar respite from symptoms in patients with chronic fatigue as it does in idiopathic intracranial hypertension.
This suggests a connection between them, with chronic fatigue syndrome representing a forme fruste variant of idiopathic intracranial hypertension. If this were the case, then treatments available for idiopathic intracranial hypertension might be appropriate for chronic fatigue.
We describe a 49-year-old woman with a long and debilitating history of chronic fatigue syndrome who was targeted for investigation of intracranial pressure because of headache, then diagnosed with borderline idiopathic intracranial hypertension after lumbar puncture and cerebrospinal fluid drainage.
Further investigation showed narrowings at the anterior ends of the transverse sinuses, typical of those seen in idiopathic intracranial hypertension and associated with pressure gradients.
Stenting of both transverse sinuses brought about a life-changing remission of symptoms with no regression in 2 years of follow-up. This result invites study of an alternative approach to the investigation and management of chronic fatigue.
http://www.researchgate.net/publication/283476227_Psychogenic_expla...
Psychogenic Explanations of Physical Illness: Time to Examine the Evidence
Carolyn E. Wilshire and Tony Ward, Victoria University of Wellington, Wellington, New Zealand
In some patients with chronic physical complaints, detailed examination fails to identify a well-recognized underlying disease process. In this situation, the physician may suspect a psychological cause. This review critically evaluates the evidence for this causal claim, focusing on complaints presenting as neurological disorders.
There were four main conclusions.
First, patients with these complaints frequently exhibit psychopathology, but not consistently more often than patients with a comparable “organic” diagnosis, so a causal role cannot be inferred.
Second, these patients report a high incidence of adverse life experiences, but again, this evidence is insufficient to infer causation:A psychogenic diagnosis is likely to prompt careful reexamination of negative past experiences, thereby introducing a recall bias.
Third, although psychogenic illnesses are believed to be more responsive to psychological interventions than comparable “organic” illnesses, there is currently no evidence to support this claim.
Finally, recent evidence suggests that biological and physical factors play a much greater causal role in these illnesses than previously believed. We conclude that there is currently little evidential support for psychogenic theories of illness in the neurological domain. Future research needs to take a wider view concerning the etiology of these illnesses.
http://www.ncbi.nlm.nih.gov/pubmed/26615570
Cytokine. 2015 Nov 23;78:27-36. doi: 10.1016/j.cyto.2015.11.018. [Epub ahead of print]
Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome.
Landi A, Broadhurst D, Vernon SD, Tyrrell DL, Houghton M.
Abstract
Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3years. In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls.
We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients. All three biomarkers were significantly correlated in a multivariate cluster analysis.
In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-γ (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients.
Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced. Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients. To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients. In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease.
This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes. Further studies of other ME/CFS and overlapping disease cohorts are warranted in future.
Copyright © 2015 Elsevier Ltd. All rights reserved.
fulltext- http://www.biomedcentral.com/1472-6955/14/64
Fatigue in adults with post-infectious fatigue syndrome: a qualitative content analysis
Eva Stormorken, Leonard A. Jason and Marit Kirkevold
Abstract
Background: Fatigue is a major problem among individuals with post-infectious fatigue syndrome (PIFS), also known as chronic fatigue syndrome or myalgic encephalomyelitis. It is a complex phenomenon that varies across illnesses. From a nursing perspective, knowledge and understanding of fatigue in this illness is limited. Nurses lack confidence in caring for these patients and devalue their professional role. The aim of this study was to explore in-depth the experiences of fatigue among individuals with PIFS. A detailed description of the phenomenon of fatigue is presented. Increased knowledge would likely contribute to more confident nurses and improved nursing care.
Methods: A qualitative study with open interviews was employed.
In-depth interviews with patients were fully transcribed and underwent a qualitative content analysis. A maximum variation sample of 26 affected adults between 26–59 years old was recruited from a population diagnosed at a fatigue outpatient clinic.
Results: The fatigue was a post-exertional, multidimensional, fluctuating phenomenon with varying degrees of severity and several distinct characteristics and was accompanied by concomitant symptoms.
Fatigue was perceived to be an all-pervasive complex experience that substantially reduced the ability to function personally or professionally. A range of trigger mechanisms evoked or worsened the fatigue, but the affected were not always aware of what triggered it.
There was an excessive increase in fatigue in response to even minor activities. An increase in fatigue resulted in the exacerbation of other concomitant symptoms. The term fatigue does not capture the participants’ experiences, which are accompanied by a considerable symptom burden that contributes to the illness experience and the severe disability.
Conclusions: Although some aspects of the fatigue experience have been reported previously, more were added in our study, such as the dimension of awakening fatigue and the characteristic beyond time, when time passes unnoticed. We also identified trigger mechanisms such as emotional, neurological, social, financial, and pressure on oneself or from others. This in-depth exploration of fatigue in PIFS provides an overview of the dimensions, characteristics, and trigger mechanisms of fatigue, thus making better clinical observations, early recognition, improved communication with patients and more appropriate nursing interventions possible.
http://www.ncbi.nlm.nih.gov/pubmed/26613325
Rev Environ Health. 2015 Dec 1;30(4):223-249. doi: 10.1515/reveh-2015-0026.
Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians.
Bested AC, Marshall LM.
Abstract
This review was written from the viewpoint of the treating clinician to educate health care professionals and the public about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). It includes: the clinical definition of ME/CFS with emphasis on how to diagnose ME/CFS; the etiology, pathophysiology, management approach, long-term prognosis and economic cost of ME/CFS.After reading this review, you will be better able to diagnose and treat your patients with ME/CFS using the tools and information provided. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic medical condition characterized by symptom clusters that include: pathological fatigue and malaise that is worse after exertion, cognitive dysfunction, immune dysfunction, unrefreshing sleep, pain, autonomic dysfunction, neuroendocrine and immune symptoms.
ME/CFS is common, often severely disabling and costly. The Institute of Medicine (IOM) reviewed the ME/CFS literature and estimates that between 836,000 and 2.5 million Americans have ME/CFS at a cost of between 17 and 24 billion dollars annually in the US. The IOM suggested a new name for ME/CFS and called it Systemic Exertion Intolerance Disease (SEID). SEID's diagnostic criteria are less specific and do not exclude psychiatric disorders in the criteria.
The 2010 Canadian Community Health Survey discovered that 29% of patients with ME/CFS had unmet health care needs and 20% had food insecurity - lack of access to sufficient healthy foods. ME/CFS can be severely disabling and cause patients to be bedridden.
Yet most patients (80%) struggle to get a diagnosis because doctors have not been taught how to diagnose or treat ME/CFS in medical schools or in their post-graduate educational training. Consequently, the patients with ME/CFS suffer. They are not diagnosed with ME/CFS and are not treated accordingly. Instead of compassionate care from their doctors, they are often ridiculed by the very people from whom they seek help.
The precise etiology of ME/CFS remains unknown, but recent advances and research discoveries are beginning to shed light on the enigma of this disease including the following contributors: infectious, genetic, immune, cognitive including sleep, metabolic and biochemical abnormalities. Management of patients with ME/CFS is supportive symptomatic treatment with a patient centered care approach that begins with the symptoms that are most troublesome for the patient.
Pacing of activities with strategic rest periods is, in our opinion, the most important coping strategy patients can learn to better manage their illness and stop their post-exertional fatigue and malaise.
Pacing allows patients to regain the ability to plan activities and begin to make slow incremental improvements in functionality.
PMID: 26613325 [PubMed - as supplied by publisher]
SLEEP MEDICINE
December 2015Volume 24, Pages 1–12
Herbal medicine for insomnia: A systematic review and meta-analysis
Matthew J. Leach
Amy T. Page
Affiliations
Publication History
Published Online: December 17, 2014Accepted: December 9, 2014; Received in revised form: December 9, 2014; Received: April 6, 2014;
.Summary
Insomnia is a prevalent sleep disorder that can profoundly impact a person's health and wellbeing. Herbal medicine represents one of the most frequently used complementary and alternative treatments of insomnia. However, the safety and efficacy of herbal medicine for the treatment of this disorder is currently uncertain. In order to ascertain the evidence base for herbal medicine for insomnia, we systematically searched seventeen electronic databases and the reference lists of included studies for relevant randomised controlled trials (RCTs). Fourteen RCTs, involving a total of 1602 participants with insomnia, met the inclusion criteria. Four distinct orally administered herbal monopreparations were identified (i.e., valerian, chamomile, kava and wuling). There was no statistically significant difference between any herbal medicine and placebo, or any herbal medicine and active control, for any of the thirteen measures of clinical efficacy. As for safety, a similar or smaller number of adverse events per person were reported with kava, chamomile and wuling when compared with placebo. By contrast, a greater number of events per person were reported with valerian. While there is insufficient evidence to support the use of herbal medicine for insomnia, there is a clear need for further research in this area.
Keywords:
Chamomile, Complementary and alternative medicine, Herbal medicine, Insomnia, Sleep disorders, Kava, Systematic review, Valerian, Wuling
Journal of Clin Pathol doi:10.1136/jclinpath-2015-203455
The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease
Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein.
Current Neuropharmacology, 2015, 13, 701-734 701
Myalgic Encephalomyelitis: Symptoms and Biomarkers
Leonard A. Jasona,*, Marcie L. Zinn1 and Mark A. Zinn2
Department of Psychology, Center for Community Research, DePaul University, Chicago, Illinois,
United States
Abstract: Myalgic Encephalomyelitis (ME) continues to cause significant morbidity worldwide with
an estimated one million cases in the United States. Hurdles to establishing consensus to achieve
accurate evaluation of patients with ME continue, fueled by poor agreement about case definitions,
slow progress in development of standardized diagnostic approaches, and issues surrounding research
priorities. Because there are other medical problems, such as early MS and Parkinson’s Disease,
which have some similar clinical presentations, it is critical to accurately diagnose ME to make a
differential diagnosis. In this article, we explore and summarize advances in the physiological and
neurological approaches to understanding, diagnosing, and treating ME. We identify key areas and approaches to
elucidate the core and secondary symptom clusters in ME so as to provide some practical suggestions in evaluation of ME
for clinicians and researchers. This review, therefore, represents a synthesis of key discussions in the literature, and has
important implications for a better understanding of ME, its biological markers, and diagnostic criteria. There is a clear
need for more longitudinal studies in this area with larger data sets, which correct for multiple testing.
Vaccine
Volume 33, Issue 46, 17 November 2015, Pages 6173–6177
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine
Abstract
Background
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination.
Methods
Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression.
Results
The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91–1.04), while it was 2.04 (95% CI: 1.78–2.33) after being diagnosed with influenza infection during the peak pandemic period.
Conclusions
Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.
Corresponding author. Tel.: +47 92683119.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Reuters Health Information
Ticks Carrying Lyme Disease in Almost Half of U.S. CountiesBy Lisa Rapaport
| January 19, 2016
(Reuters Health) - Ticks that can spread Lyme disease now live in almost half of U.S. counties, according to a new study from the Centers for Disease Control and Prevention.
Varieties of the blacklegged tick that may carry Borrelia burgdorferi responsible for Lyme disease are present in 45% of counties nationwide, compared with just 30% in 1998, researchers found.
"It's important for people to be aware that there may be ticks in areas where they haven't seen them previously so that they can take steps to help protect themselves and their families," lead study author Rebecca Eisen, a research biologist at the CDC, said by email.
Since the late 1990s, the number of reported Lyme disease cases in the U.S. has more than tripled, Eisen and colleagues report online January 18 in the Journal of Medical Entomology.
Lyme disease is spread by the blacklegged tick, Ixodes scapularis, also known as deer ticks, and the western blacklegged tick, Ixodes pacificus. These ticks are typically found in wooded and grassy areas.
Common symptoms of Lyme disease can include fever, headache, and fatigue, all of which can be easily confused with the flu. Some patients, but not all, develop a characteristic bull's eye rash soon after the tick bite.
If caught early, Lyme disease can be treated with antibiotics. But untreated Lyme disease can lead to lasting cognitive problems, joint and muscle pain and mood disorders.
To assess changes in the tick population, researchers analyzed data reported by counties using the same surveillance methods from 1998.
They found deer ticks in 1,420 out of 3,110 counties in the continental U.S., or about 46% of counties, and found western blacklegged ticks in 111 counties, or about 4%. Combined, this is a 45% increase from 1998 when ticks were reported in 1,058 counties.
Deer ticks are now established in 842 counties across 35 states, compared with 396 counties in 32 states in 1998. These ticks used to be concentrated in northeastern states but have moved west and south.
Western blacklegged ticks are now established in 95 counties across six states, up from 90 counties in 1998. These ticks remain concentrated in Pacific coast states.
Outside of the U.S., ticks carry the disease in forested areas of Asia, northwestern, central and eastern Europe, according to the World Health Organization.
Even though the tick population is spreading, the risk of catching Lyme disease isn't the same everywhere the ticks live, because the number of ticks infected with Lyme bacteria varies, as do the odds that infected ticks may bite people, Eisen noted.
To minimize the risk of catching Lyme disease from ticks, people can spray skin and clothing with insect repellants such as DEET or lemon permethrin, said Dr. Keith Berndtson of the Center for Research on Biotoxin Associated Illness in Pocomoke, Maryland. Long sleeves and pants legs tucked into socks can also keep ticks away, and light-colored fabrics can make the ticks easier to spot.
After a day outdoors, tossing all clothes in the dryer for about 20 minutes can kill most ticks. People should also have a friend or family member check their body for ticks, and check any pets. Saving ticks for testing can also help assess whether the bugs carried bacteria that can lead to Lyme disease, Berndtson, who wasn't involve in the study, added by email.
Environmental and climate changes may be helping ticks to expand their territory in the U.S., noted Dr. Bobbi Pritt, director of clinical parasitology at the Mayo Clinic in Rochester, Minnesota.
"Warmer temperatures, increases in rainfall, and milder winters can favor tick survival," Pritt, who wasn't involved in the study, said by email. "These factors can also favor survival and expansion of the mammals and birds that the ticks feed on."
SOURCE: http://bit.ly/1OslYEC
J Med Entomol 2016.
fulltext- http://downloads.hindawi.com/journals/jar/aip/328971.pdf
Understanding muscle dysfunction in Chronic Fatigue Syndrome
Gina Rutherford1 MSc, Philip Manning1 PhD, Julia L Newton MD, PhD 1,2
1Institute of cellular medicine, Newcastle University, Newcastle UK.
2 Newcastle hospitals NHS foundation trust, UK NIHR biomedical research centre in ageing and age related disease, Newcastle University, Newcastle UK
Abstract
Introduction: Chronic fatigue syndrome/ Myalgic Encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology and is characterised by severe disabling fatigue in the absence of an alternative diagnosis.
Historically, there has been a tendency to draw psychological explanations for the origin of fatigue, however this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial and neuronal pathways.
For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examines the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level.
Methods: This narrative review examines literature following searches of PUB MED, MEDLINE and Google scholar, using key words such as (e.g.
CFS,ME, Immune, autoimmune, mitochondria, muscle, acidosis).
Results: Studies show evidence for skeletal muscle bio-chemical abnormality in CFS/ME patients. Following a low-level repeat exercise protocol CFS/ME patients exhibited a significantly greater muscular acidosis in addition to a slowed time to recovery from acidosis. There is also evidence for impaired AMPK activation following electrical pulse stimulation in CFS/ME patient myotube samples.
Discussion: Bio-energetic peripheral muscle dysfunction is evident in CFS/ME, with a tendency towards an over-utilisation of the lactate dehydrogenase pathway during low-level exercise, in addition to delayed acid clearance post-exercise. AMPK activation is impaired in CFS/ME myotube samples following electrical pulse stimulation.
Potentially, these bio-chemical abnormalities may lead to the perception of severe muscular fatigue in CFS/ME
http://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1124520?jo...
Case definitions integrating empiric and consensus perspectives for myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS)
Leonard A. Jason, Stephanie McManimen, Madison Sunnquist, Abigail Brown, Jacob Furst, Julia L. Newton & Elin Bolle Strand
Abstract
Background: There has been considerable controversy regarding how to name and define the illnesses known as myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS).
The Institute of Medicine (IOM) report has proposed new clinical criteria and a new name for this illness, but aspects of these recommendations have been scrutinized by patients and scientists.
Purpose: It is possible that both empiric and consensus approaches could be used to help settle some of these diagnostic challenges.
Using patient samples collected in the USA, Great Britain, and Norway (N = 556), the current study attempted to categorize patients using more general as well as more restricted case definitions.
Results: Overall, the outcomes suggest that there might be four groupings of patients, with the broadest category involving those with chronic fatigue (N = 62), defined by six or more months of fatigue which cannot be explained by medical or psychiatric conditions.
A second category involves those patients who have chronic fatigue that can be explained by a medical or psychiatric condition (N = 47). A third category involves more specific criteria that have been posited both by the IOM report, Canadian Clinical Case criteria, ME-ICC criteria and a more empiric approach.
These efforts have specified domains of substantial reductions of activity, post-exertional malaise, neurocognitive impairment, and sleep dysfunction (N = 346). Patients with these characteristics were more functionally impaired than those meeting just chronic fatigue criteria, p < .05.
Finally, those meeting even more restrictive ME criteria proposed by Ramsay, identified a smaller and even more impaired group, p < .05.
Conclusion: It is important that scientists world-wide develop consensus on how to identify and classify patients using clinical and research criteria, and ultimately develop subtypes within such categories.
http://jpet.aspetjournals.org/content/early/2016/01/13/jpet.115.230...
Substance P, Hemokinin-1, CRH, TNF and IL-6 are increased in serum of patients with Fibromyalgia Syndrome and may serve both as biomarkers and targets for treatment
Irene Tsilioni, Irwin J Russell, Julia M Stewart, Rae M Gleason, and Theoharis C Theoharides
1 Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiol;
2 Fibromyalgia Research and Consulting, Arthritis and Osteoporosis Center of South Texas, San Antonio,;
3 National Fibromyalgia and Chronic Pain Association, Logan, UT, USA
Abstract
Fibromyalgia Syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting more women than men. Even though clinical and laboratory studies have provided evidence of altered central pain pathways, the lack of definitive pathogenesis or objective diagnostic markers has hampered development of effective treatments.
Here we report for the first time that the neuropeptides corticotropin-releasing hormone (CRH), substance P (SP) and its structurally related Hemokinin-1 (HK-1) were significantly (p=0.026, p<0.0001 and p=0.002, respectively) elevated (0.82±0.57 ng/mL, 0.39±0.18 ng/mL and 7.98±3.12 ng/mL, respectively) in the serum of patients with FMS as compared to healthy controls (0.49±0.26 ng/mL, 0.12±0.1 ng/mL and 5.71±1.08 ng/mL, respectively).
Moreover, SP and HK-1 levels were positively correlated (Pearson’s r=0.45, p=0.002).
The serum concentrations of the inflammatory cytokines IL-6 and TNF were also significantly (p=0.029 and p=0.006, respectively) higher (2.97±2.35 pg/mL and 0.92±0.31 pg/mL, respectively) in the FMS group as compared to healthy subjects (1.79±0.62 pg/mL and 0.69±0.16 pg/mL, respectively).
In contrast, serum IL-31 and IL-33 levels were significantly lower (p=0.0001 and p=0.044, respectively) in the FMS patients (849.5±1005 pg/mL and 923.2±1284 pg/mL, respectively) in comparison to healthy controls (1281±806.4 pg/mL and 3149±4073 pg/mL, respectively).
Our results indicate that neuro-inflammation may contribute to the symptoms of FMS patients, especially since we had previously shown that CRH and SP are known to stimulate IL-6 and TNF release from mast cells. Treatment directed at preventing the secretion on antagonizing these elevated neuroimmune markers may be useful in the management of FMS patients.
The American Society for Pharmacology and Experimental Therapeutics
http://www.ncbi.nlm.nih.gov/pubmed/26745400
J Rehabil Res Dev. 2015;52(7):805-814. doi: 10.1682/JRRD.2014.11.0293.
Reduced gait automaticity in female patients with chronic fatigue syndrome: Case-control study.
Eyskens JB1, Nijs J, Wouters K, Moorkens G.
Abstract
Patients with chronic fatigue syndrome (CFS) report difficulties walking for a prolonged period of time. This study compares gait automaticity between women with CFS and nondisabled controls.
The "stops walking with eyes closed with secondary cognitive task" test is based on the classic "stops walking while talking" test but compares walking with eyes closed while performing a secondary cognitive task in a female CFS population (n = 34) and in female nondisabled controls (n = 38).
When initiating gate, 23.5% of patients with CFS looked toward the ground compared with only 2.6% of nondisabled controls.
After 7 m, subjects were asked to close their eyes, and after another 7 m, they were asked, "How much is 100 minus 7?" Of the patients with CFS, 55.9% stopped walking compared with 5.3% of nondisabled controls.
Less automated walking was observed in patients with CFS than in nondisabled controls (p < 0.001). The test-retest reliability is moderate for global stopping.
This simple test observed reduced gait automaticity in patients with CFS for the first time. Dual tasking could be helpful to address the functional limitations found in this particular study.
http://www.ncbi.nlm.nih.gov/pubmed/26717948
Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature.
Walitt B1, Ceko M, Gracely J, Gracely RH.
Abstract
Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes.
We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes.
Evoked sensory paradigms reveal sensory augmentation to both painful and non-painful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin.
However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature.
Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes.
A defining neuroimaging "signature" cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes.
At this time, the existence of "central sensitivity syndromes" is based more soundly on clinical and epidemiological evidence. A coherent picture of a "central sensitization" mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence.
PMID:26717948 [PubMed - as supplied by publisher]
fulltext- http://journals.plos.org/plosone/article?id=10.1371/journal.pone.01...
PLoS One. 2015 Dec 22;10(12):e0143970. doi:
10.1371/journal.pone.0143970. eCollection 2015.
A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren's Syndrome.
James K, Al-Ali S, Tarn J, Cockell SJ, Gillespie CS, Hindmarsh V, Locke J, Mitchell S, Lendrem D, Bowman S, Price E, Pease CT, Emery P, Lanyon P, Hunter JA, Gupta M, Bombardieri M, Sutcliffe N, Pitzalis C, McLaren J, Cooper A, Regan M, Giles I, Isenberg D, Saravanan V, Coady D, Dasgupta B, McHugh N, Young-Min S, Moots R, Gendi N, Akil M, Griffiths B; UK Primary Sjögren’s Syndrome registry, Wipat A, Newton J, Jones DE, Isaacs J, Hallinan J, Ng WF.
Abstract
BACKGROUND: Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms.
METHODS: Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray.
The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W).
RESULTS: Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525
(SE(W) 0.006), respectively.
CONCLUSIONS: Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.
http://www.sciencedirect.com/science/article/pii/S0730725X15003033
Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: An arterial spin-labeling fMRI study
Jeff Boissoneault, Janelle Letzen, Song Lai, Andrew O'Shea, Jason Craggs, Mike Robinson, Roland Staud
Abstract
Background: Myalgic encephalomyelitis/chronic fatigue syndrome
(ME/CFS) is a debilitating disorder characterized by severe fatigue and neurocognitive dysfunction. Recent work from our laboratory and others utilizing arterial spin labeling functional magnetic resonance imaging (ASL) indicated that ME/CFS patients have lower resting state regional cerebral blood flow (rCBF) in several brain areas associated with memory, cognitive, affective, and motor function. This hypoperfusion may underlie ME/CFS pathogenesis and may result in alterations of functional relationships between brain regions. The current report used ASL to compare functional connectivity of regions implicated in ME/CFS between patients and healthy controls (HC).
Methods: Participants were 17 ME/CFS patients (Mage = 48.88 years, SD = 12) fulfilling the 1994 CDC criteria and 17 age/sex matched HC (Mage = 49.82 years, SD = 11.32). All participants underwent T1-weighted structural MRI as well as a 6-min pseudo-continuous arterial spin labeling (pCASL) sequence, which quantifies CBF by magnetically labeling blood as it enters the brain. Imaging data were preprocessed using SPM 12 and ASL tbx, and seed-to-voxel functional connectivity analysis was conducted using the CONN toolbox. All effects noted below are significant at p < 0.05 with cluster-wise FDR correction for multiple comparisons.
Results: ME/CFS patients demonstrated greater functional connectivity relative to HC in bilateral superior frontal gyrus, ACC, precuneus, and right angular gyrus to regions including precuneus, right postcentral gyrus, supplementary motor area, posterior cingulate gyrus, and thalamus. In contrast, HC patients had greater functional connectivity than ME/CFS in ACC, left parahippocampal gyrus, and bilateral pallidum to regions including right insula, right precentral gyrus, and hippocampus. Connectivity of the left parahippocampal gyrus correlated strongly with overall clinical fatigue of ME/CFS patients.
Conclusion: This is the first ASL based connectivity analysis of patients with ME/CFS. Our results demonstrate altered functional connectivity of several regions associated with cognitive, affective, memory, and higher cognitive function in ME/CFS patients. Connectivity to memory related brain areas (para-hippocampal gyrus) was correlated with clinical fatigue ratings, providing supporting evidence that brain network abnormalities may contribute to ME/CFS pathogenesis.
http://onlinelibrary.wiley.com/doi/10.1111/nmo.12741/abstract
Genome-wide DNA methylation profiling of peripheral blood mononuclear cells in irritable bowel syndrome
S. Mahurkar, C. Polytarchou, D. Iliopoulos, C. Pothoulakis, E.A. Mayer and L. Chang
Abstract
Background: Irritable bowel syndrome (IBS) is a stress-sensitive disorder. Environmental factors including stress can trigger epigenetic changes, which have not been well-studied in IBS. We performed a pilot study investigating genome-wide DNA methylation of IBS patients and healthy controls (HCs) to identify potential epigenetic markers and associated pathways. Additionally, we investigated relationships of epigenetic changes in selected genes with clinical traits.
Methods: Twenty-seven IBS patients (59% women; 10 IBS-diarrhea, 8 IBS-constipation, 9 IBS-mixed) and 23 age- and sex-matched HCs were examined. DNA methylation from peripheral blood mononuclear cells
(PBMCs) was measured using HM450 BeadChip, and representative methylation differences were confirmed by bisulphite sequencing. Gene expression was measured using quantitative PCR. Gastrointestinal (GI) and non-GI symptoms were measured using validated questionnaires.
Associations were tested using non-parametric methods.
Key Results: Genome-wide DNA methylation profiling of IBS patients compared with HCs identified 133 differentially methylated positions
(DMPs) (mean difference ≥10%; p < 0.05). These genes were associated with gene ontology terms including glutathione metabolism related to oxidative stress and neuropeptide hormone activity. Validation by sequencing confirmed differential methylation of subcommissural organ (SCO)-Spondin (SSPO), glutathione-S-transferases mu 5 (GSTM5), and tubulin polymerization promoting protein genes. Methylation of two promoter CpGs in GSTM5 was associated with epigenetic silencing.
Epigenetic changes in SSPO gene were positively correlated with hospital anxiety and depression scores in IBS patients (r > 0.4 and false discovery rate <0.05).
Conclusions & Inferences: This study is the first to comprehensively explore the methylome of IBS patients. We identified DMPs in novel candidate genes which could provide new insights into disease mechanisms; however, these preliminary findings warrant confirmation in larger, independent studies.
http://solvecfs.org/wp-content/uploads/2015/12/Chronicle_Winter2015...
The SolveCFSChronical, Winter 2015
Breaking News: The $5.4 million in Centers for Disease Control funding for ME/CFS has been restored in its entirety! This is a huge win for the entire ME/CFS community and one that has taken many months of dedicated effort to achieve.
Had the funding not been restored, the CDC’s multi-year multi-site study on ME/CFS would not have been completed. Given the state of the budget discussions, this was a very real possibility that fortunately did not come to pass.
Additionally, a potentially very significant development has occurred with the National Institutes of Health, which received a $2 billion increase in funding in the new budget. The entire budget package will be formally voted on by Congress this Friday and is expected to pass. This additional NIH funding bodes well for ME/CFS, given that we have heard from our contacts in the past that they are unable to take research funds already dedicated to diseases and reappropriate them to ME/CFS. This substantial additional funding opens a wealth of possibilities for funding our disease.
Significant Breakthrough for ME/CFS at the NIH
On Oct. 29, the National Institutes of Health announced that it is taking several major steps to advance research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. NIH is launching a research project at the NIH Clinical Center to intensely study individuals with ME/CFS and will also be funding external research on the disease to a degree that will be “substantially greater” than our disease has received in the past, according to NIH Director Dr. Francis S. Collins.
Additionally, NIH announced that the leadership role for ME/CFS research, which was assigned to the Office of Research on Women’s Health, has now been assigned to the National Institute of Neurological Disorders and Stroke (NINDS). NINDS will lead a multi-institute ME/CFS research effort and a re-invigorated Trans-NIH ME/CFS Research Working Group. This move marks a very positive elevation of the status of our disease within NIH. NINDS Director Dr.
Walter Koroshetz will chair the Working Group, along with Vicky Holets Whittemore, PhD, the NIH representative to the U.S. Department of Health and Human Services’ Chronic Fatigue Syndrome Advisory Committee (CFSAC), on which Solve ME/CFS Initiative President Carol Head serves.
fulltext- http://journals.plos.org/plosone/article?id=10.1371/journal.pone.01...
Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Sanjay K. Shukla, Dane Cook, Jacob Meyer, Suzanne D. Vernon, Thao Le, Derek Clevidence, Charles E. Robertson, Steven J. Schrodi, Steven Yale, Daniel N. Frank
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain.
In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance.
Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation.
To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined.Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla.
Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005).
There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls.
These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise.
These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.
http://onlinelibrary.wiley.com/doi/10.1111/cei.12749/abstract
Clin Exp Immunol. 2015 Dec 8. doi: 10.1111/cei.12749. [Epub ahead of print]
Extended B-cell phenotype in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A cross-sectional study.
Mensah F, Bansal A, Berkovitz S, Sharma A, Reddy V, Leandro MJ, Cambridge G.
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous condition of unknown etiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months.
Recently, two clinical trials of B-cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B-cells has therefore been proposed. Studies of the relative percentages of B-cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC).
In order to explore whether more subtle alterations in B-cell subsets related to B-cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19+ B-cells. The panel utilized IgD, CD27 and CD38 (classical B-cell subsets) together with additional markers.
A total of 38 patients fulfilling Canadian, Centre for Disease Control, and Fukuda ME/CFS criteria and 32 age/sex-matched HC were included.
We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (p<0.01) and expression (MFI; p=0.03) of CD24 on total B-cells, confined to IgD+ subsets.
Within memory subsets, a higher frequency of CD21+ CD38- B-cells (>20%) was associated with the presence of ME/CFS (Odds ratio: 3.47 (1.15-10.46); p=0.03) compared with HC and there was a negative correlation with disease duration.
In conclusion, we identified possible changes in B-cell phenotype in patients with ME/CFS. These may reflect altered B-cell function and if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab-therapy.
This article is protected by copyright. All rights reserved. © 2015 British Society for Immunology.
fulltext: http://www.jneuro.com/neurology-neuroscience/evaluation-of-antivira...
Evaluation of Antiviral Antibodies against Epstein-Barr Virus and Neurotransmitters in Patients with Fibromyalgia
Reshkova V, Kalinova D and Milanov I
Abstract
Fibromyalgia (FM) is characterized by chronic widespread pain lasting for a minimum of three months, and pain at mechanical pressure in at least 11 of the 18 tender points. The cause of fibromyalgia is unknown. Several hypotheses have been developed including "central sensitization".
This theory proposes that fibromyalgia patients have a lower threshold for pain because of increased reactivity of painsensitive neurons in the spinal cord or brain. Some researchers supposed that different neurotransmitters (serotonin, catecholamine) could be involved in the pathophysiology of fibromyalgia-associated symptoms.
The connection of FM to different viral infections has been proposed. Epstein Barr Virus (EBV) has been considered a possible cause of FM because of similarity of symptoms, but so far, the connection has not been proven.
The objective of this study was to determine the prevalence of antibodies (Abs) IgM and IgG against EBV, and respectively the presence of a viral infection in a group of patients with FM. We also analysed the association between the titter of the antiviral antibodies, some neurotransmitters (serotonin, noradrenaline and adrenaline) and different clinical symptoms.
The obtained results revealed that high EBV IgG concentrations in the serum of patients with FM correlated with pain intensity and associated clinical symptoms. This is consistent with the fact that FM is connected to the immune response to certain infectious agents (e.g. EBV, CMV).
Mol Neurobiol
DOI 10.1007/s12035-015-9262-7
The Putative Role of Viruses, Bacteria, and Chronic Fungal
Biotoxin Exposure in the Genesis of Intractable Fatigue
Accompanied by Cognitive and Physical Disability
Gerwyn Morris1 & Michael Berk2,3 & Ken Walder4 & Michael Maes2,5
Received: 24 December 2014 /Accepted: 28 May 2015
# Springer Science+Business Media New York 2015
Abstract Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited,with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls.Similarly, exercise regimes either produce significant,but practically unimportant, benefit or provoke symptom exacerbation.
Many such patients are afforded the exclusionary,non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms.More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure.
Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed,how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased.The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients,and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles,
genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.
Keywords Immune . Inflammation . Oxidative stress .Toll-like receptor . Cognition . Depression . Chronic fatigue syndrome . Neurology . Psychiatry
Emily Y. Chew, MD1; Traci E. Clemons, PhD2; Elvira Agrón, MA1; Lenore J. Launer, PhD3; Francine Grodstein, ScD4,5; Paul S. Bernstein, MD, PhD6 ; for the Age-Related Eye Disease Study 2 (AREDS2) Research Group
[+-] Author Affiliations
1Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute/National Institutes of Health, Bethesda, Maryland
2The EMMES Corporation, Rockville, Maryland
3Neuroepidemiology Section, National Institute on Aging/National Institutes of Health, Bethesda, Maryland
4Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
5Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
6Moran Eye Center, University of Utah, Salt Lake City
JAMA. 2015;314(8):791-801. doi:10.1001/jama.2015.9677.
ABSTRACT
Importance Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease.
Objective To test the effects of oral supplementation with nutrients on cognitive function.
Design, Setting, and Participants In a double-masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study.
Interventions Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc.
Main Outcomes and Measures The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from −22 to 17, with higher scores representing better function.
Results A total of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not. The yearly change in the composite cognitive function score was −0.19 (99% CI, −0.25 to −0.13) for participants randomized to receive LCPUFAs vs −0.18 (99% CI, −0.24 to −0.12) for those randomized to no LCPUFAs (difference in yearly change, −0.03 [99% CI, −0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite cognitive function score was −0.18 (99% CI, −0.24 to −0.11) for participants randomized to receive lutein/zeaxanthin vs −0.19 (99% CI, −0.25 to −0.13) for those randomized to not receive lutein/zeaxanthin (difference in yearly change, 0.03 [99% CI, −0.14 to 0.19]; P = .66). Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant.
Conclusions and Relevance Among older persons with AMD, oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function.
CYTOKINE
Vol 78 Feb 2016
Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome
- Abdolamir Landia, , , David Broadhurstb, Suzanne D. Vernonc, D. Lorne J. Tyrrella, Michael Houghtona, ,
- Abstract
- Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3 years. In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls. We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients. All three biomarkers were significantly correlated in a multivariate cluster analysis. In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-γ (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients. Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced. Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients. To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients. In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease. This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes. Further studies of other ME/CFS and overlapping disease cohorts are warranted in future.
Lyme disease: time for a new approach?
- BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h6520 (Published 03 December 2015) Cite this as: BMJ 2015;351:h6520
Valerie Obsomer, ecological and environmental risk expert6
<>[email protected]
Many more questions than answers
Lyme disease is the most common vector borne disease in North America and Europe, with 300 000 new cases in the United States1 and an estimated 100 000 new cases in Europe each year.2 These numbers are likely to be underestimates because case reporting is inconsistent3 and many infections go undiagnosed.4 Climate change may have contributed to a rapid increase in tick borne diseases, with migratory birds disseminating infected ticks.5
Our common understanding of Lyme disease is that a tick bite is followed by the development of a classic rash pattern (erythema migrans). When treated early with a relatively short course of antibiotics, most patients have good outcomes.6 But the standard two tier testing for Lyme disease is inaccurate in the early stages.
http://www.ncbi.nlm.nih.gov/pubmed/26623235
Borderline Intracranial Hypertension Manifesting as Chronic Fatigue Syndrome Treated by Venous Sinus Stenting.
Higgins N, Pickard J, Lever A.
Abstract
Chronic fatigue syndrome and cases of idiopathic intracranial hypertension without signs of raised intracranial pressure can be impossible to distinguish without direct measurement of intracranial pressure. Moreover, lumbar puncture, the usual method of measuring intracranial pressure, can produce a similar respite from symptoms in patients with chronic fatigue as it does in idiopathic intracranial hypertension.
This suggests a connection between them, with chronic fatigue syndrome representing a forme fruste variant of idiopathic intracranial hypertension. If this were the case, then treatments available for idiopathic intracranial hypertension might be appropriate for chronic fatigue.
We describe a 49-year-old woman with a long and debilitating history of chronic fatigue syndrome who was targeted for investigation of intracranial pressure because of headache, then diagnosed with borderline idiopathic intracranial hypertension after lumbar puncture and cerebrospinal fluid drainage.
Further investigation showed narrowings at the anterior ends of the transverse sinuses, typical of those seen in idiopathic intracranial hypertension and associated with pressure gradients.
Stenting of both transverse sinuses brought about a life-changing remission of symptoms with no regression in 2 years of follow-up. This result invites study of an alternative approach to the investigation and management of chronic fatigue.
http://www.researchgate.net/publication/283476227_Psychogenic_expla...
Psychogenic Explanations of Physical Illness: Time to Examine the Evidence
Carolyn E. Wilshire and Tony Ward, Victoria University of Wellington, Wellington, New Zealand
In some patients with chronic physical complaints, detailed examination fails to identify a well-recognized underlying disease process. In this situation, the physician may suspect a psychological cause. This review critically evaluates the evidence for this causal claim, focusing on complaints presenting as neurological disorders.
There were four main conclusions.
First, patients with these complaints frequently exhibit psychopathology, but not consistently more often than patients with a comparable “organic” diagnosis, so a causal role cannot be inferred.
Second, these patients report a high incidence of adverse life experiences, but again, this evidence is insufficient to infer causation:A psychogenic diagnosis is likely to prompt careful reexamination of negative past experiences, thereby introducing a recall bias.
Third, although psychogenic illnesses are believed to be more responsive to psychological interventions than comparable “organic” illnesses, there is currently no evidence to support this claim.
Finally, recent evidence suggests that biological and physical factors play a much greater causal role in these illnesses than previously believed. We conclude that there is currently little evidential support for psychogenic theories of illness in the neurological domain. Future research needs to take a wider view concerning the etiology of these illnesses.
http://www.ncbi.nlm.nih.gov/pubmed/26615570
Cytokine. 2015 Nov 23;78:27-36. doi: 10.1016/j.cyto.2015.11.018. [Epub ahead of print]
Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome.
Landi A, Broadhurst D, Vernon SD, Tyrrell DL, Houghton M.
Abstract
Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3years. In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls.
We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients. All three biomarkers were significantly correlated in a multivariate cluster analysis.
In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-γ (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients.
Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced. Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients. To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients. In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease.
This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes. Further studies of other ME/CFS and overlapping disease cohorts are warranted in future.
Copyright © 2015 Elsevier Ltd. All rights reserved.
fulltext- http://www.biomedcentral.com/1472-6955/14/64
Fatigue in adults with post-infectious fatigue syndrome: a qualitative content analysis
Eva Stormorken, Leonard A. Jason and Marit Kirkevold
Abstract
Background: Fatigue is a major problem among individuals with post-infectious fatigue syndrome (PIFS), also known as chronic fatigue syndrome or myalgic encephalomyelitis. It is a complex phenomenon that varies across illnesses. From a nursing perspective, knowledge and understanding of fatigue in this illness is limited. Nurses lack confidence in caring for these patients and devalue their professional role. The aim of this study was to explore in-depth the experiences of fatigue among individuals with PIFS. A detailed description of the phenomenon of fatigue is presented. Increased knowledge would likely contribute to more confident nurses and improved nursing care.
Methods: A qualitative study with open interviews was employed.
In-depth interviews with patients were fully transcribed and underwent a qualitative content analysis. A maximum variation sample of 26 affected adults between 26–59 years old was recruited from a population diagnosed at a fatigue outpatient clinic.
Results: The fatigue was a post-exertional, multidimensional, fluctuating phenomenon with varying degrees of severity and several distinct characteristics and was accompanied by concomitant symptoms.
Fatigue was perceived to be an all-pervasive complex experience that substantially reduced the ability to function personally or professionally. A range of trigger mechanisms evoked or worsened the fatigue, but the affected were not always aware of what triggered it.
There was an excessive increase in fatigue in response to even minor activities. An increase in fatigue resulted in the exacerbation of other concomitant symptoms. The term fatigue does not capture the participants’ experiences, which are accompanied by a considerable symptom burden that contributes to the illness experience and the severe disability.
Conclusions: Although some aspects of the fatigue experience have been reported previously, more were added in our study, such as the dimension of awakening fatigue and the characteristic beyond time, when time passes unnoticed. We also identified trigger mechanisms such as emotional, neurological, social, financial, and pressure on oneself or from others. This in-depth exploration of fatigue in PIFS provides an overview of the dimensions, characteristics, and trigger mechanisms of fatigue, thus making better clinical observations, early recognition, improved communication with patients and more appropriate nursing interventions possible.
http://www.ncbi.nlm.nih.gov/pubmed/26613325
Rev Environ Health. 2015 Dec 1;30(4):223-249. doi: 10.1515/reveh-2015-0026.
Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians.
Bested AC, Marshall LM.
Abstract
This review was written from the viewpoint of the treating clinician to educate health care professionals and the public about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). It includes: the clinical definition of ME/CFS with emphasis on how to diagnose ME/CFS; the etiology, pathophysiology, management approach, long-term prognosis and economic cost of ME/CFS.After reading this review, you will be better able to diagnose and treat your patients with ME/CFS using the tools and information provided. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic medical condition characterized by symptom clusters that include: pathological fatigue and malaise that is worse after exertion, cognitive dysfunction, immune dysfunction, unrefreshing sleep, pain, autonomic dysfunction, neuroendocrine and immune symptoms.
ME/CFS is common, often severely disabling and costly. The Institute of Medicine (IOM) reviewed the ME/CFS literature and estimates that between 836,000 and 2.5 million Americans have ME/CFS at a cost of between 17 and 24 billion dollars annually in the US. The IOM suggested a new name for ME/CFS and called it Systemic Exertion Intolerance Disease (SEID). SEID's diagnostic criteria are less specific and do not exclude psychiatric disorders in the criteria.
The 2010 Canadian Community Health Survey discovered that 29% of patients with ME/CFS had unmet health care needs and 20% had food insecurity - lack of access to sufficient healthy foods. ME/CFS can be severely disabling and cause patients to be bedridden.
Yet most patients (80%) struggle to get a diagnosis because doctors have not been taught how to diagnose or treat ME/CFS in medical schools or in their post-graduate educational training. Consequently, the patients with ME/CFS suffer. They are not diagnosed with ME/CFS and are not treated accordingly. Instead of compassionate care from their doctors, they are often ridiculed by the very people from whom they seek help.
The precise etiology of ME/CFS remains unknown, but recent advances and research discoveries are beginning to shed light on the enigma of this disease including the following contributors: infectious, genetic, immune, cognitive including sleep, metabolic and biochemical abnormalities. Management of patients with ME/CFS is supportive symptomatic treatment with a patient centered care approach that begins with the symptoms that are most troublesome for the patient.
Pacing of activities with strategic rest periods is, in our opinion, the most important coping strategy patients can learn to better manage their illness and stop their post-exertional fatigue and malaise.
Pacing allows patients to regain the ability to plan activities and begin to make slow incremental improvements in functionality.
PMID: 26613325 [PubMed - as supplied by publisher]
SLEEP MEDICINE
December 2015Volume 24, Pages 1–12
Herbal medicine for insomnia: A systematic review and meta-analysis
Matthew J. Leach
Amy T. Page
Affiliations
- Western Australian Centre for Rural Health, University of Western Australia, Australia
Publication History
Published Online: December 17, 2014Accepted: December 9, 2014; Received in revised form: December 9, 2014; Received: April 6, 2014;
.Summary
Insomnia is a prevalent sleep disorder that can profoundly impact a person's health and wellbeing. Herbal medicine represents one of the most frequently used complementary and alternative treatments of insomnia. However, the safety and efficacy of herbal medicine for the treatment of this disorder is currently uncertain. In order to ascertain the evidence base for herbal medicine for insomnia, we systematically searched seventeen electronic databases and the reference lists of included studies for relevant randomised controlled trials (RCTs). Fourteen RCTs, involving a total of 1602 participants with insomnia, met the inclusion criteria. Four distinct orally administered herbal monopreparations were identified (i.e., valerian, chamomile, kava and wuling). There was no statistically significant difference between any herbal medicine and placebo, or any herbal medicine and active control, for any of the thirteen measures of clinical efficacy. As for safety, a similar or smaller number of adverse events per person were reported with kava, chamomile and wuling when compared with placebo. By contrast, a greater number of events per person were reported with valerian. While there is insufficient evidence to support the use of herbal medicine for insomnia, there is a clear need for further research in this area.
Keywords:
Chamomile, Complementary and alternative medicine, Herbal medicine, Insomnia, Sleep disorders, Kava, Systematic review, Valerian, Wuling
Journal of Clin Pathol doi:10.1136/jclinpath-2015-203455
The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease
- Correspondence to Professor Jonathan R Kerr, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Quinta de Mutis, Bogotá 111221, Colombia; [email protected]
- Received 13 October 2015
- Accepted 6 November 2015
- Published Online First 7 December 2015
Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein.
Current Neuropharmacology, 2015, 13, 701-734 701
Myalgic Encephalomyelitis: Symptoms and Biomarkers
Leonard A. Jasona,*, Marcie L. Zinn1 and Mark A. Zinn2
Department of Psychology, Center for Community Research, DePaul University, Chicago, Illinois,
United States
Abstract: Myalgic Encephalomyelitis (ME) continues to cause significant morbidity worldwide with
an estimated one million cases in the United States. Hurdles to establishing consensus to achieve
accurate evaluation of patients with ME continue, fueled by poor agreement about case definitions,
slow progress in development of standardized diagnostic approaches, and issues surrounding research
priorities. Because there are other medical problems, such as early MS and Parkinson’s Disease,
which have some similar clinical presentations, it is critical to accurately diagnose ME to make a
differential diagnosis. In this article, we explore and summarize advances in the physiological and
neurological approaches to understanding, diagnosing, and treating ME. We identify key areas and approaches to
elucidate the core and secondary symptom clusters in ME so as to provide some practical suggestions in evaluation of ME
for clinicians and researchers. This review, therefore, represents a synthesis of key discussions in the literature, and has
important implications for a better understanding of ME, its biological markers, and diagnostic criteria. There is a clear
need for more longitudinal studies in this area with larger data sets, which correct for multiple testing.
Vaccine
Volume 33, Issue 46, 17 November 2015, Pages 6173–6177
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine
- Per Magnusa, , , Nina Gunnesa, Kari Tveitob, Inger Johanne Bakkena, Sara Ghaderia, Camilla Stoltenberga, Mady Hornigc, W. Ian Lipkinc, Lill Trogstada, Siri E. Håberga
- a Norwegian Institute of Public Health, 4404 Nydalen, 0403 Oslo, Norway
- b Journal of the Norwegian Medical Association, Oslo, Norway
- c Center for Infection and Immunity, Columbia University, NY, NY, USA
Abstract
Background
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination.
Methods
Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression.
Results
The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91–1.04), while it was 2.04 (95% CI: 1.78–2.33) after being diagnosed with influenza infection during the peak pandemic period.
Conclusions
Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.
Corresponding author. Tel.: +47 92683119.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Reuters Health Information
Ticks Carrying Lyme Disease in Almost Half of U.S. CountiesBy Lisa Rapaport
| January 19, 2016
(Reuters Health) - Ticks that can spread Lyme disease now live in almost half of U.S. counties, according to a new study from the Centers for Disease Control and Prevention.
Varieties of the blacklegged tick that may carry Borrelia burgdorferi responsible for Lyme disease are present in 45% of counties nationwide, compared with just 30% in 1998, researchers found.
"It's important for people to be aware that there may be ticks in areas where they haven't seen them previously so that they can take steps to help protect themselves and their families," lead study author Rebecca Eisen, a research biologist at the CDC, said by email.
Since the late 1990s, the number of reported Lyme disease cases in the U.S. has more than tripled, Eisen and colleagues report online January 18 in the Journal of Medical Entomology.
Lyme disease is spread by the blacklegged tick, Ixodes scapularis, also known as deer ticks, and the western blacklegged tick, Ixodes pacificus. These ticks are typically found in wooded and grassy areas.
Common symptoms of Lyme disease can include fever, headache, and fatigue, all of which can be easily confused with the flu. Some patients, but not all, develop a characteristic bull's eye rash soon after the tick bite.
If caught early, Lyme disease can be treated with antibiotics. But untreated Lyme disease can lead to lasting cognitive problems, joint and muscle pain and mood disorders.
To assess changes in the tick population, researchers analyzed data reported by counties using the same surveillance methods from 1998.
They found deer ticks in 1,420 out of 3,110 counties in the continental U.S., or about 46% of counties, and found western blacklegged ticks in 111 counties, or about 4%. Combined, this is a 45% increase from 1998 when ticks were reported in 1,058 counties.
Deer ticks are now established in 842 counties across 35 states, compared with 396 counties in 32 states in 1998. These ticks used to be concentrated in northeastern states but have moved west and south.
Western blacklegged ticks are now established in 95 counties across six states, up from 90 counties in 1998. These ticks remain concentrated in Pacific coast states.
Outside of the U.S., ticks carry the disease in forested areas of Asia, northwestern, central and eastern Europe, according to the World Health Organization.
Even though the tick population is spreading, the risk of catching Lyme disease isn't the same everywhere the ticks live, because the number of ticks infected with Lyme bacteria varies, as do the odds that infected ticks may bite people, Eisen noted.
To minimize the risk of catching Lyme disease from ticks, people can spray skin and clothing with insect repellants such as DEET or lemon permethrin, said Dr. Keith Berndtson of the Center for Research on Biotoxin Associated Illness in Pocomoke, Maryland. Long sleeves and pants legs tucked into socks can also keep ticks away, and light-colored fabrics can make the ticks easier to spot.
After a day outdoors, tossing all clothes in the dryer for about 20 minutes can kill most ticks. People should also have a friend or family member check their body for ticks, and check any pets. Saving ticks for testing can also help assess whether the bugs carried bacteria that can lead to Lyme disease, Berndtson, who wasn't involve in the study, added by email.
Environmental and climate changes may be helping ticks to expand their territory in the U.S., noted Dr. Bobbi Pritt, director of clinical parasitology at the Mayo Clinic in Rochester, Minnesota.
"Warmer temperatures, increases in rainfall, and milder winters can favor tick survival," Pritt, who wasn't involved in the study, said by email. "These factors can also favor survival and expansion of the mammals and birds that the ticks feed on."
SOURCE: http://bit.ly/1OslYEC
J Med Entomol 2016.
fulltext- http://downloads.hindawi.com/journals/jar/aip/328971.pdf
Understanding muscle dysfunction in Chronic Fatigue Syndrome
Gina Rutherford1 MSc, Philip Manning1 PhD, Julia L Newton MD, PhD 1,2
1Institute of cellular medicine, Newcastle University, Newcastle UK.
2 Newcastle hospitals NHS foundation trust, UK NIHR biomedical research centre in ageing and age related disease, Newcastle University, Newcastle UK
Abstract
Introduction: Chronic fatigue syndrome/ Myalgic Encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology and is characterised by severe disabling fatigue in the absence of an alternative diagnosis.
Historically, there has been a tendency to draw psychological explanations for the origin of fatigue, however this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial and neuronal pathways.
For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examines the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level.
Methods: This narrative review examines literature following searches of PUB MED, MEDLINE and Google scholar, using key words such as (e.g.
CFS,ME, Immune, autoimmune, mitochondria, muscle, acidosis).
Results: Studies show evidence for skeletal muscle bio-chemical abnormality in CFS/ME patients. Following a low-level repeat exercise protocol CFS/ME patients exhibited a significantly greater muscular acidosis in addition to a slowed time to recovery from acidosis. There is also evidence for impaired AMPK activation following electrical pulse stimulation in CFS/ME patient myotube samples.
Discussion: Bio-energetic peripheral muscle dysfunction is evident in CFS/ME, with a tendency towards an over-utilisation of the lactate dehydrogenase pathway during low-level exercise, in addition to delayed acid clearance post-exercise. AMPK activation is impaired in CFS/ME myotube samples following electrical pulse stimulation.
Potentially, these bio-chemical abnormalities may lead to the perception of severe muscular fatigue in CFS/ME
http://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1124520?jo...
Case definitions integrating empiric and consensus perspectives for myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS)
Leonard A. Jason, Stephanie McManimen, Madison Sunnquist, Abigail Brown, Jacob Furst, Julia L. Newton & Elin Bolle Strand
Abstract
Background: There has been considerable controversy regarding how to name and define the illnesses known as myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS).
The Institute of Medicine (IOM) report has proposed new clinical criteria and a new name for this illness, but aspects of these recommendations have been scrutinized by patients and scientists.
Purpose: It is possible that both empiric and consensus approaches could be used to help settle some of these diagnostic challenges.
Using patient samples collected in the USA, Great Britain, and Norway (N = 556), the current study attempted to categorize patients using more general as well as more restricted case definitions.
Results: Overall, the outcomes suggest that there might be four groupings of patients, with the broadest category involving those with chronic fatigue (N = 62), defined by six or more months of fatigue which cannot be explained by medical or psychiatric conditions.
A second category involves those patients who have chronic fatigue that can be explained by a medical or psychiatric condition (N = 47). A third category involves more specific criteria that have been posited both by the IOM report, Canadian Clinical Case criteria, ME-ICC criteria and a more empiric approach.
These efforts have specified domains of substantial reductions of activity, post-exertional malaise, neurocognitive impairment, and sleep dysfunction (N = 346). Patients with these characteristics were more functionally impaired than those meeting just chronic fatigue criteria, p < .05.
Finally, those meeting even more restrictive ME criteria proposed by Ramsay, identified a smaller and even more impaired group, p < .05.
Conclusion: It is important that scientists world-wide develop consensus on how to identify and classify patients using clinical and research criteria, and ultimately develop subtypes within such categories.
http://jpet.aspetjournals.org/content/early/2016/01/13/jpet.115.230...
Substance P, Hemokinin-1, CRH, TNF and IL-6 are increased in serum of patients with Fibromyalgia Syndrome and may serve both as biomarkers and targets for treatment
Irene Tsilioni, Irwin J Russell, Julia M Stewart, Rae M Gleason, and Theoharis C Theoharides
1 Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiol;
2 Fibromyalgia Research and Consulting, Arthritis and Osteoporosis Center of South Texas, San Antonio,;
3 National Fibromyalgia and Chronic Pain Association, Logan, UT, USA
Abstract
Fibromyalgia Syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting more women than men. Even though clinical and laboratory studies have provided evidence of altered central pain pathways, the lack of definitive pathogenesis or objective diagnostic markers has hampered development of effective treatments.
Here we report for the first time that the neuropeptides corticotropin-releasing hormone (CRH), substance P (SP) and its structurally related Hemokinin-1 (HK-1) were significantly (p=0.026, p<0.0001 and p=0.002, respectively) elevated (0.82±0.57 ng/mL, 0.39±0.18 ng/mL and 7.98±3.12 ng/mL, respectively) in the serum of patients with FMS as compared to healthy controls (0.49±0.26 ng/mL, 0.12±0.1 ng/mL and 5.71±1.08 ng/mL, respectively).
Moreover, SP and HK-1 levels were positively correlated (Pearson’s r=0.45, p=0.002).
The serum concentrations of the inflammatory cytokines IL-6 and TNF were also significantly (p=0.029 and p=0.006, respectively) higher (2.97±2.35 pg/mL and 0.92±0.31 pg/mL, respectively) in the FMS group as compared to healthy subjects (1.79±0.62 pg/mL and 0.69±0.16 pg/mL, respectively).
In contrast, serum IL-31 and IL-33 levels were significantly lower (p=0.0001 and p=0.044, respectively) in the FMS patients (849.5±1005 pg/mL and 923.2±1284 pg/mL, respectively) in comparison to healthy controls (1281±806.4 pg/mL and 3149±4073 pg/mL, respectively).
Our results indicate that neuro-inflammation may contribute to the symptoms of FMS patients, especially since we had previously shown that CRH and SP are known to stimulate IL-6 and TNF release from mast cells. Treatment directed at preventing the secretion on antagonizing these elevated neuroimmune markers may be useful in the management of FMS patients.
The American Society for Pharmacology and Experimental Therapeutics
http://www.ncbi.nlm.nih.gov/pubmed/26745400
J Rehabil Res Dev. 2015;52(7):805-814. doi: 10.1682/JRRD.2014.11.0293.
Reduced gait automaticity in female patients with chronic fatigue syndrome: Case-control study.
Eyskens JB1, Nijs J, Wouters K, Moorkens G.
Abstract
Patients with chronic fatigue syndrome (CFS) report difficulties walking for a prolonged period of time. This study compares gait automaticity between women with CFS and nondisabled controls.
The "stops walking with eyes closed with secondary cognitive task" test is based on the classic "stops walking while talking" test but compares walking with eyes closed while performing a secondary cognitive task in a female CFS population (n = 34) and in female nondisabled controls (n = 38).
When initiating gate, 23.5% of patients with CFS looked toward the ground compared with only 2.6% of nondisabled controls.
After 7 m, subjects were asked to close their eyes, and after another 7 m, they were asked, "How much is 100 minus 7?" Of the patients with CFS, 55.9% stopped walking compared with 5.3% of nondisabled controls.
Less automated walking was observed in patients with CFS than in nondisabled controls (p < 0.001). The test-retest reliability is moderate for global stopping.
This simple test observed reduced gait automaticity in patients with CFS for the first time. Dual tasking could be helpful to address the functional limitations found in this particular study.
http://www.ncbi.nlm.nih.gov/pubmed/26717948
Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature.
Walitt B1, Ceko M, Gracely J, Gracely RH.
Abstract
Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes.
We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes.
Evoked sensory paradigms reveal sensory augmentation to both painful and non-painful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin.
However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature.
Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes.
A defining neuroimaging "signature" cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes.
At this time, the existence of "central sensitivity syndromes" is based more soundly on clinical and epidemiological evidence. A coherent picture of a "central sensitization" mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence.
PMID:26717948 [PubMed - as supplied by publisher]
fulltext- http://journals.plos.org/plosone/article?id=10.1371/journal.pone.01...
PLoS One. 2015 Dec 22;10(12):e0143970. doi:
10.1371/journal.pone.0143970. eCollection 2015.
A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren's Syndrome.
James K, Al-Ali S, Tarn J, Cockell SJ, Gillespie CS, Hindmarsh V, Locke J, Mitchell S, Lendrem D, Bowman S, Price E, Pease CT, Emery P, Lanyon P, Hunter JA, Gupta M, Bombardieri M, Sutcliffe N, Pitzalis C, McLaren J, Cooper A, Regan M, Giles I, Isenberg D, Saravanan V, Coady D, Dasgupta B, McHugh N, Young-Min S, Moots R, Gendi N, Akil M, Griffiths B; UK Primary Sjögren’s Syndrome registry, Wipat A, Newton J, Jones DE, Isaacs J, Hallinan J, Ng WF.
Abstract
BACKGROUND: Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms.
METHODS: Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray.
The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W).
RESULTS: Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525
(SE(W) 0.006), respectively.
CONCLUSIONS: Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.
http://www.sciencedirect.com/science/article/pii/S0730725X15003033
Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: An arterial spin-labeling fMRI study
Jeff Boissoneault, Janelle Letzen, Song Lai, Andrew O'Shea, Jason Craggs, Mike Robinson, Roland Staud
Abstract
Background: Myalgic encephalomyelitis/chronic fatigue syndrome
(ME/CFS) is a debilitating disorder characterized by severe fatigue and neurocognitive dysfunction. Recent work from our laboratory and others utilizing arterial spin labeling functional magnetic resonance imaging (ASL) indicated that ME/CFS patients have lower resting state regional cerebral blood flow (rCBF) in several brain areas associated with memory, cognitive, affective, and motor function. This hypoperfusion may underlie ME/CFS pathogenesis and may result in alterations of functional relationships between brain regions. The current report used ASL to compare functional connectivity of regions implicated in ME/CFS between patients and healthy controls (HC).
Methods: Participants were 17 ME/CFS patients (Mage = 48.88 years, SD = 12) fulfilling the 1994 CDC criteria and 17 age/sex matched HC (Mage = 49.82 years, SD = 11.32). All participants underwent T1-weighted structural MRI as well as a 6-min pseudo-continuous arterial spin labeling (pCASL) sequence, which quantifies CBF by magnetically labeling blood as it enters the brain. Imaging data were preprocessed using SPM 12 and ASL tbx, and seed-to-voxel functional connectivity analysis was conducted using the CONN toolbox. All effects noted below are significant at p < 0.05 with cluster-wise FDR correction for multiple comparisons.
Results: ME/CFS patients demonstrated greater functional connectivity relative to HC in bilateral superior frontal gyrus, ACC, precuneus, and right angular gyrus to regions including precuneus, right postcentral gyrus, supplementary motor area, posterior cingulate gyrus, and thalamus. In contrast, HC patients had greater functional connectivity than ME/CFS in ACC, left parahippocampal gyrus, and bilateral pallidum to regions including right insula, right precentral gyrus, and hippocampus. Connectivity of the left parahippocampal gyrus correlated strongly with overall clinical fatigue of ME/CFS patients.
Conclusion: This is the first ASL based connectivity analysis of patients with ME/CFS. Our results demonstrate altered functional connectivity of several regions associated with cognitive, affective, memory, and higher cognitive function in ME/CFS patients. Connectivity to memory related brain areas (para-hippocampal gyrus) was correlated with clinical fatigue ratings, providing supporting evidence that brain network abnormalities may contribute to ME/CFS pathogenesis.
http://onlinelibrary.wiley.com/doi/10.1111/nmo.12741/abstract
Genome-wide DNA methylation profiling of peripheral blood mononuclear cells in irritable bowel syndrome
S. Mahurkar, C. Polytarchou, D. Iliopoulos, C. Pothoulakis, E.A. Mayer and L. Chang
Abstract
Background: Irritable bowel syndrome (IBS) is a stress-sensitive disorder. Environmental factors including stress can trigger epigenetic changes, which have not been well-studied in IBS. We performed a pilot study investigating genome-wide DNA methylation of IBS patients and healthy controls (HCs) to identify potential epigenetic markers and associated pathways. Additionally, we investigated relationships of epigenetic changes in selected genes with clinical traits.
Methods: Twenty-seven IBS patients (59% women; 10 IBS-diarrhea, 8 IBS-constipation, 9 IBS-mixed) and 23 age- and sex-matched HCs were examined. DNA methylation from peripheral blood mononuclear cells
(PBMCs) was measured using HM450 BeadChip, and representative methylation differences were confirmed by bisulphite sequencing. Gene expression was measured using quantitative PCR. Gastrointestinal (GI) and non-GI symptoms were measured using validated questionnaires.
Associations were tested using non-parametric methods.
Key Results: Genome-wide DNA methylation profiling of IBS patients compared with HCs identified 133 differentially methylated positions
(DMPs) (mean difference ≥10%; p < 0.05). These genes were associated with gene ontology terms including glutathione metabolism related to oxidative stress and neuropeptide hormone activity. Validation by sequencing confirmed differential methylation of subcommissural organ (SCO)-Spondin (SSPO), glutathione-S-transferases mu 5 (GSTM5), and tubulin polymerization promoting protein genes. Methylation of two promoter CpGs in GSTM5 was associated with epigenetic silencing.
Epigenetic changes in SSPO gene were positively correlated with hospital anxiety and depression scores in IBS patients (r > 0.4 and false discovery rate <0.05).
Conclusions & Inferences: This study is the first to comprehensively explore the methylome of IBS patients. We identified DMPs in novel candidate genes which could provide new insights into disease mechanisms; however, these preliminary findings warrant confirmation in larger, independent studies.
http://solvecfs.org/wp-content/uploads/2015/12/Chronicle_Winter2015...
The SolveCFSChronical, Winter 2015
Breaking News: The $5.4 million in Centers for Disease Control funding for ME/CFS has been restored in its entirety! This is a huge win for the entire ME/CFS community and one that has taken many months of dedicated effort to achieve.
Had the funding not been restored, the CDC’s multi-year multi-site study on ME/CFS would not have been completed. Given the state of the budget discussions, this was a very real possibility that fortunately did not come to pass.
Additionally, a potentially very significant development has occurred with the National Institutes of Health, which received a $2 billion increase in funding in the new budget. The entire budget package will be formally voted on by Congress this Friday and is expected to pass. This additional NIH funding bodes well for ME/CFS, given that we have heard from our contacts in the past that they are unable to take research funds already dedicated to diseases and reappropriate them to ME/CFS. This substantial additional funding opens a wealth of possibilities for funding our disease.
Significant Breakthrough for ME/CFS at the NIH
On Oct. 29, the National Institutes of Health announced that it is taking several major steps to advance research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. NIH is launching a research project at the NIH Clinical Center to intensely study individuals with ME/CFS and will also be funding external research on the disease to a degree that will be “substantially greater” than our disease has received in the past, according to NIH Director Dr. Francis S. Collins.
Additionally, NIH announced that the leadership role for ME/CFS research, which was assigned to the Office of Research on Women’s Health, has now been assigned to the National Institute of Neurological Disorders and Stroke (NINDS). NINDS will lead a multi-institute ME/CFS research effort and a re-invigorated Trans-NIH ME/CFS Research Working Group. This move marks a very positive elevation of the status of our disease within NIH. NINDS Director Dr.
Walter Koroshetz will chair the Working Group, along with Vicky Holets Whittemore, PhD, the NIH representative to the U.S. Department of Health and Human Services’ Chronic Fatigue Syndrome Advisory Committee (CFSAC), on which Solve ME/CFS Initiative President Carol Head serves.
fulltext- http://journals.plos.org/plosone/article?id=10.1371/journal.pone.01...
Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Sanjay K. Shukla, Dane Cook, Jacob Meyer, Suzanne D. Vernon, Thao Le, Derek Clevidence, Charles E. Robertson, Steven J. Schrodi, Steven Yale, Daniel N. Frank
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain.
In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance.
Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation.
To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined.Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla.
Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005).
There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls.
These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise.
These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.
http://onlinelibrary.wiley.com/doi/10.1111/cei.12749/abstract
Clin Exp Immunol. 2015 Dec 8. doi: 10.1111/cei.12749. [Epub ahead of print]
Extended B-cell phenotype in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A cross-sectional study.
Mensah F, Bansal A, Berkovitz S, Sharma A, Reddy V, Leandro MJ, Cambridge G.
Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous condition of unknown etiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months.
Recently, two clinical trials of B-cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B-cells has therefore been proposed. Studies of the relative percentages of B-cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC).
In order to explore whether more subtle alterations in B-cell subsets related to B-cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19+ B-cells. The panel utilized IgD, CD27 and CD38 (classical B-cell subsets) together with additional markers.
A total of 38 patients fulfilling Canadian, Centre for Disease Control, and Fukuda ME/CFS criteria and 32 age/sex-matched HC were included.
We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (p<0.01) and expression (MFI; p=0.03) of CD24 on total B-cells, confined to IgD+ subsets.
Within memory subsets, a higher frequency of CD21+ CD38- B-cells (>20%) was associated with the presence of ME/CFS (Odds ratio: 3.47 (1.15-10.46); p=0.03) compared with HC and there was a negative correlation with disease duration.
In conclusion, we identified possible changes in B-cell phenotype in patients with ME/CFS. These may reflect altered B-cell function and if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab-therapy.
This article is protected by copyright. All rights reserved. © 2015 British Society for Immunology.
fulltext: http://www.jneuro.com/neurology-neuroscience/evaluation-of-antivira...
Evaluation of Antiviral Antibodies against Epstein-Barr Virus and Neurotransmitters in Patients with Fibromyalgia
Reshkova V, Kalinova D and Milanov I
Abstract
Fibromyalgia (FM) is characterized by chronic widespread pain lasting for a minimum of three months, and pain at mechanical pressure in at least 11 of the 18 tender points. The cause of fibromyalgia is unknown. Several hypotheses have been developed including "central sensitization".
This theory proposes that fibromyalgia patients have a lower threshold for pain because of increased reactivity of painsensitive neurons in the spinal cord or brain. Some researchers supposed that different neurotransmitters (serotonin, catecholamine) could be involved in the pathophysiology of fibromyalgia-associated symptoms.
The connection of FM to different viral infections has been proposed. Epstein Barr Virus (EBV) has been considered a possible cause of FM because of similarity of symptoms, but so far, the connection has not been proven.
The objective of this study was to determine the prevalence of antibodies (Abs) IgM and IgG against EBV, and respectively the presence of a viral infection in a group of patients with FM. We also analysed the association between the titter of the antiviral antibodies, some neurotransmitters (serotonin, noradrenaline and adrenaline) and different clinical symptoms.
The obtained results revealed that high EBV IgG concentrations in the serum of patients with FM correlated with pain intensity and associated clinical symptoms. This is consistent with the fact that FM is connected to the immune response to certain infectious agents (e.g. EBV, CMV).
Mol Neurobiol
DOI 10.1007/s12035-015-9262-7
The Putative Role of Viruses, Bacteria, and Chronic Fungal
Biotoxin Exposure in the Genesis of Intractable Fatigue
Accompanied by Cognitive and Physical Disability
Gerwyn Morris1 & Michael Berk2,3 & Ken Walder4 & Michael Maes2,5
Received: 24 December 2014 /Accepted: 28 May 2015
# Springer Science+Business Media New York 2015
Abstract Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited,with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls.Similarly, exercise regimes either produce significant,but practically unimportant, benefit or provoke symptom exacerbation.
Many such patients are afforded the exclusionary,non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms.More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure.
Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed,how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased.The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients,and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles,
genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.
Keywords Immune . Inflammation . Oxidative stress .Toll-like receptor . Cognition . Depression . Chronic fatigue syndrome . Neurology . Psychiatry
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