CFS Research Findings

We love to report on CFS research findings like many of those you’ll find below because they demonstrate that real progress is being made towards finding ways to better diagnose and treat CFS. Even when studies don’t pan out or results are not as hoped, the opportunity to learn something new about CFS strengthens the entire field.

There are more than 4,000 articles in the peer-reviewed literature that provide evidence of abnormalities in multiple body systems of CFS patients. If you’re new to your understanding of CFS, it may help to read this overview of the research literature. Many of the findings over the past 25 years represent early research or are observations or associations made in small groups of patients. Validating early stage research is crucial to it being accepted by the scientific and medical communities.

Several models have been proposed to explain how many of these research findings “fit” together. One of the many benefits of scientific conferences and workshops is the opportunity for researchers working in specific disciplines to learn how other studies in other disciplines may shed light on their own work.

Here’s some useful information about how to better understand research studies:

• PUBLICATIONS
• PRESENTATIONS & CONFERENCES

PUBLICATIONS

2012

Global Measure of Sleep Quality Inadequate: Mariman et al. at the University Hospital Ghent (Belgium) used a sleep questionnaire to assess sleep disturbances in 413 CFS patients. Subjects showed disturbances that clustered into three groups: Sleep Efficiency, Perceived Sleep Quality and Daily Disturbances. Based on this analysis, the authors conclude that global measure of sleep quality is not adequate for assessing sleep quality in CFS patients. (Journal of Psychosomatic Research, Feb. 2012)

Brain Imaging Study Points to Oxidative Stress: Dikoma Shungu et al. at Weill Cornell (NYC) compared levels of various brain chemicals in 15 subjects with CFS (1994-Fukuda), 15 subjects with major depression and 13 healthy volunteers. There were differences between the two disease groups and healthy controls, but not statistically significant differences between CFS and MDD in the main analyses. In other exploratory analyses, they found that ventricular lactate and cortical GSH were inversely correlated, suggesting a role for oxidative stress in CFS. This study was funded by the CFIDS Association. (NMR Biomedicine, Jan. 27, 2012)  

Minimum Data Elements Recommended: Members of the federal CFS Advisory Committee responded to the need for greater consistency in reported methods in CFS research as identified at the April 2011 NIH-sponsored ME/CFS State of the Knowledge Workshop. They present a consensus on minimum data elements to be collected and reported. (Brain, Behavior and Immunity, Jan. 26, 2012)

Differences in Pulse Timing and Amplitude: Dr. Julia Newton’s group in Newcastle (U.K.) reported results of testing 14 CFS (1994-Fukuda) patients and 14 healthy controls using non-invasive optical multi-site photoplethysmography to measure pulse timing and amplitude before and after a showed three-minute tilt test. Measurements were taken at ear, finger and toe sites. A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group — 26% for CFS compared to 37% for controls. With more study and comparison to other disease groups with and without orthostatic intolerance, this non-invasive test could objectively distinguish CFS from healthy controls. (Physiologic Measurement, Jan. 25, 2011)

2011

Markers Differentiate CFS from MS: A new study from the Light team at Univ. of Utah showing unique post-exercise markers in CFS compared to patients with MS and healthy controls. Postexercise increases in metabolite-detecting receptors were unique to patients with CFS, whereas both patients with MS and patients with CFS showed abnormal increases in adrenergic receptors. This study was funded in part by the CFIDS Assn. (Psychosomatic Medicine, Dec. 30, 2011)

No XMRV in Animal Lab Workers Tested: The possibility that lab workers in regular contact with mice might be especially vulnerable to XMRV infection was investigated by a group in Canada and they found no evidence of XMRV/MLV infection. (Transfusion, Dec. 30, 2011)  http://bit.ly/wmeOju

No XMRV in Spanish Patient Cohort: From Arredondo et al. in Spain and colleagues at Abbott Labs, a report of testing for XMRV in 1103 samples collected from people with CFS, FM, prostate cancer, HIV, HTLV, hepatitis B, hepatitis C, autoimmune disease and healthy blood donors. There was no evidence for XMRV in this cohort. (AIDS Research and Human Retroviruses, Dec. 29, 2011)

Pair of Retractions Issued:  On Dec. 23, Science editor-in-chief Bruce Alberts issued a rare editorial retraction of the 2009 paper by Lombardi et al. that first linked CFS to XMRV. On Monday, Dec. 26, the authors of the only other published paper supporting this association retracted their study from the Proceedings of the National Academy of Sciences.

No MLV-Related Viruses in 8 Vaccines: Researchers at the CDC, Blood Systems Research Institute and Univ. of Cal. at San Francisco report the results of their PCR and deep sequencing tests of 8 live vaccines for MLVs. All were negative for XMRV and MLVs. This is the second published report finding no presence of these viruses in vaccines. (PLoS ONE, Dec. 22, 2011)

Pacing Acceptable, Effective: Goudsmit, Nijs, Jason and Wallman report that pacing can reduce the severity of the exertion-related symptoms of ME/CFS. (Disability and Rehabilitation, Dec. 19, 2011)

Drs. Marvin Medow and Julian Stewart

Upright Posture Impairs Cognition: Marvin Medow, PhD, and colleagues at New York Medical College conducted cognitive tests during tilt table testing and made other circulatory measures of brain blood flow on 25 CFS patients with POTS and 20 healthy control subjects. “Overall, our data show that blood flow fails to increase during [cognitive] tasking for all [levels of difficulty], with clear reductions in task-dependent neuronal activated cerebral blood flow velocity as the orthostatic stress increases.” In control subjects, progressive tasking difficulty enhances blood flow. This study was funded in part by the CFIDS Association. (American Journal of Physiology – Heart and Circulatory Physiology, Dec. 16, 2011; abstract only)

Moderate Exercise Better Challenge for Detecting CFS: A new study published this week by Dane Cook, PhD, and colleagues at UW-Madison, shows that sustained submaximal exercise challenge demonstrates differences between CFS, CFS+FM and healthy controls better than a short-duration maximal exercise challenge. (Medicine & Science in Sports & Exercise, Dec. 12, 2011)

CFS/ME an under-recognized cause of school absence: A study of three secondary school populations led by Crawley et al. in Bristol (U.K.) sought to identify the cause of absences in students who missed more than 20 percent of school in a six-week term. Based on previous diagnoses (5 children) and diagnoses made following referral to specialist clinics, a total of 28 children met NICE guidelines for CFS/ME. Based on this sample, they estimate 1 in 100 (1 percent) school children may fit these CFS/ME criteria, which require 3 months of persistent fatigue plus other symptoms (pain, disturbed sleep, cognitive problems, etc.). In general, the children diagnosed by the specialty clinic had fewer symptoms and less severe symptoms compared to the children with prior diagnosis of CFS/ME. The 23 newly diagnosed students were offered treatment follow-up appointments to address sleep problems and for cognitive behavioral therapy or graded exercise. Nineteen did so; 63.2 percent of them improved within the six-month follow-up period. The authors conclude, “Together with referral to specialist services, school-based clinics have the potential to improve overall school attendance.” Several U.K. and U.S. news outlets covered the study results, including HealthDay, BBC News and the Guardian. (BMJ Open, Dec. 12, 2011)

CFS and myalgic encephalomyelitis (ME) case definitions compared: Jason and colleagues at DePaul Univ. compared cases who met criteria for CFS (Fukuda, 1994), ME/CFS (Carruthers, 2003) and ME (Dowsett, 1990; Dowsett, 1994; Goudsmit, 2009). When applied to a population meeting the CFS case definition, ME/CFS and ME criteria appear to select a more severe subset of patients. Note: the latest ME criteria (Carruthers, 2011) was not evaluated in this study. (Evaluation & the Health Professions, Dec. 7, 2011)

MRI study finds grey and white matter volumetric changes: Puri et al. of Hammersmith Hospital (U.K.) evaluated 26 CFS patients and 26 matched controls and concluded, “These data support the hypothesis that significant neuroanatomical changes occur in CFS, and are consistent with the complaint of impaired memory that is common in this illness; they also suggest that subtle abnormalities in visual processing, and discrepancies between intended actions and consequent movements, may occur in CFS.” (British Journal of Radiology, Nov. 29, 2011)

Small heart with low cardiac output for orthostatic intolerance:  From Miwa and Fujita at the Miwa Naika Clinic (Japan), a report that CFS patients with orthostatic intolerance (OI) (n=26) and patients with OI (alone) (n=11) may have smaller hearts and reduced cardiac performance. A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. Agreeing with other reports, CFS with OI seems to constitute a well-defined and predominant subgroup of CFS. (Journal of Clinical Cardiology, Nov. 28, 2011; full text available) 

Acute infection and history of physical activity affect resting levels and response to exercise:: Jammes and colleagues at Aix-Marseille University (France) evaluated 43 patients with CFS (18 of whom had previous high-level sports history and 9 of whom had severe acute infection) and 23 matched sedentary healthy controls. Their data suggests “the combination of two or more stressors might be the cause in later life of a persisting depletion of heat shock protein (HSP) production resulting in an exacerbation of oxidative stress.” (Journal of Internal Medicine, Nov. 24, 2011) 

XMRV does not pose a risk to blood recipient safety: Dodd (American Red Cross) and colleagues at several other institutions tested samples collected from 17,249 blood donors or recipients for the presence of antibodies to XMRV-related recombinant antigens and/or for XMRV RNA. They conclude, “XMRV and related murine leukemia virus (MLV) markers are not present among a large population of blood donors and evidence of transfusion transmission could not be detected. Thus, these viruses do not currently pose a threat to blood recipient safety and further actions relating to XMRV and MLV are not justified.” Additional Research1st coverage here.  (Transfusion, Nov. 21, 2011)

No evidence for XMRV in Canadian CFS patients: Steffen and colleagues at several Canadian and U.S. institutions tested for XMRV and MLVs using several testing methods in blood and plasma collected from 58 CFS patients and 57 healthy controls. They found no evidence of XMRV or MLVs. (PLoS ONE, Nov. 14, 2011; full text available) 

Large and small artery endothelial dysfunction in CFS: David Newton et al, Univ. of Dundee (U.K.), studied 30 patients with CFS (Fukuda) and 27 healthy controls and found that subjects with “ME/CFS have reduced flow-mediated dilatation in the brachial artery and reduced post-occlusive reactive hyperemia in the forearm skin microcirculation. These responses are both endothelium-mediated via an increase in shear stress… and the results therefore lend further support to the hypothesis that endothelial function is impaired in ME/CFS, both in large vessels and in the microcirculation.” (International Journal of Cardiology, Nov. 10, 2011)

Social support needs for equity in health and social care: Led by de Carvalho Leite at Univ. of East Anglia, this group of U.K. researchers interviewed 35 adults with CFS/ME about needs for equity in health and social care. They conclude that, “Policy development should include shared decision-making and coordinated action across organizations working for people with CFS/ME, human rights and disadvantaged groups.” (International Journal for Equity in Health, Nov. 2, 2011)

Sleep-stage dynamics: Natelson (Beth Israel Medical Center) and colleagues in Japan looked at sleep architecture in 12 patients who had CFS (alone), 14 patients with CFS plus fibromyalgia (FM) and 26 healthy controls. They found that transition from REM sleep to waking was significantly greater in subjects with CFS and concluded that “CFS and FM may be different illnesses associated with different problems of sleep regulation.” (Sleep, Nov. 1, 2011)

Symptom fluctuations and daily physical activity: Meeus and colleagues at Vrije Universiteit Brussel (Belgium) studied 67 women with CFS for six days. They found that the more patients with CFS are sedentary and the better activity is dispersed, the fewer symptoms and variations they experience on the same and next day. Inversely, more symptoms and variability is experienced when patients were more active that day or the day before. This paper supports the common practice of pacing used by CFS patients to reduce symptom flares brought on by over-activity. (Archives of Physical Medicine and Rehabilitation, Nov. 2011)

Rituximab Shows Promise Treating CFS: A double-blind placebo-controlled phase II clinical trial of rituximab showed encouraging results. 67 percent of the 15 patients treated with rituximab, a monoclonal antibody, showed improvement after two infusions given two weeks apart, compared to 12 percent of the 15 patients who received placebo. Drs. Olav Mella and Øystein Fluge and their team at Haukeland Medical Center in Bergen, Norway, attracted international attention with the hopeful news. They hypothesize that CFS is an autoimmune condition and that impaired B cells play a role in the illness, based on the delayed response to therapy. More Research1st coverage here. (PLoS ONE, Oct. 19, 2011)

Role Infectious Agents & Neurologic Dysfunction Reviewed: Harvard physician-researcher Anthony Komaroff and neurologist Tracey Cho review the literature on these two critical aspects of CFS. They report the evidence on central nervous system involvement as demonstrated in neuroendocrine studies, imaging tests using MRIs, functional MRIs, MRS and SPECT, EEG studies, tests of spinal fluid samples, and of pain and cognition. They report on autonomic system involvement and how studies have shown CFS to be distinct from depression. In reviewing the literature on infections, they examined the epidemiology and immunology of CFS as well as evidence of mitochondrial dysfunction, oxidative and nitrosative stress. The specific agents included in the review are Epstein-Barr virus, HHV-6, XMRV, polytropic MLVs, enteroviruses, parvovirus and bacterial infections. They conclude, “As with other diseases without a well-defined pathologic etiology, such as M.S., there may be multiple underlying triggers of an inflammatory process, which in certain susceptible individuals leads to the clinical manifestations of CFS.” (Seminars in Neurology, e-pub. Sept. 30, 2011)

Review of Neuroendocrine Abnormalities: In this summary of the literature, the authors find that the weight of current evidence supports the presence of the following factors related to hypothalamic–pituitary–adrenal (HPA) axis dysfunction in patients with CFS: mild hypocortisolism; attenuated diurnal variation of cortisol; enhanced negative feedback to the HPA axis; and blunted HPA axis responsiveness. Furthermore, HPA axis changes seem clinically relevant, as they are associated with worse symptoms and/or disability and with poorer outcomes to standard treatments for CFS. Given what is now a fairly consistent pattern of findings for the type of HPA axis changes found in CFS, we recommend that future work focuses on improving our understanding of the cause and relevance of these observed changes. (Nature Reviews Endocrinology, Sept. 27, 2011)

Orthostatic Stress Impairs Cognition: 16 subjects who met criteria for CFS and postural orthostatic tachycardia syndrome (POTS) were compared to 20 healthy volunteers. Subjects performed cognitive testing while lying flat, then while tilted to 15, 30,45,60 and 70 degrees for 10 minutes at each angle. The test was stopped if the subject became hypotensive or requested to stop. The two groups had similar drop-out rates. At baseline, the subjects had increased heart rate and respiratory rates, but comparable intelligence and cognitive performance. However, during the tilt, compared to controls the CFS-POTS subjects cognitive performance worsened as orthostatic stress increased. The subjects had decreased accuracy and longer normalized reaction time during difficult tasks imposed on orthostatic stress. This study, performed at New York Medical College, was funded by the CFIDS Association. (Clinical Science, Sept. 15, 2011)

POTS Seen Frequently in CFS: 47 patients with postural orthostatic tachycardia syndrome (POTS) referred to the Vanderbilt University Autonomic Dysfunction Center were evaluated for CFS. 64 percent fufilled CDC criteria for CFS (CFS-POTS) and tended to have a longer disease duration than those with POTS alone. Both groups had significant deficit in red cell volume compared to normative data, but were not different from each other. Those who met CFS criteria had highers markers of sympathetic activity than those with POTS alone. There was a trend towards lower aldosterone in the CFS-POTS group. “We speculate that orthostatic intolerance in POTS may be a more important determinant of functional impairment than fatigue…CFS symptoms may arise from a common pathophysiology.” (Clinical Science, Sept. 12, 2011)

Multicenter Study of XMRV Does Not Support Link: Phase III of the Blood XMRV Scientific Research Working Group study tested samples collected from 15 individuals who were previously positive for XMRV or MLVs, 15 pedigreed negative subjects and 3 spiked positive controls. Nine participating labs used a total of 19 assays, most of which had excellent sensitivity. Only two labs found positive results in clinical samples, and the positives were as likely to be from controls as the prior-positive subjects. “Based on these findings, we conclude that currently available XMRV/P-MLV assays… cannot reproducibly detect direct virus markers or specific antibodies in blood samples from subjects previously characterized as XMRV/P-MLV positive or healthy blood donors.” This study was published with a partial retraction of data from the original report linking XMRV to CFS, as well as an 8-page news article. Find more resources here. (Science, online ahead of print on Sept. 22, 2011)

Giardia Linked to IBS, Chronic Fatigue: A three-year follow-up study of people in Bergen, Norway, who became ill with giardiasis following contamination of a local water reservoir with Giardia lamblia reports that 46.1% had IBS, compared to 14% of unaffected controls. The same percentage (although not all the same people), 46.1%, reported chronic fatigue, compared to 12% of controls. The foll0w-up survey was conducted by mail, so it is not possible in this study design to assess how many of those experiencing chronic fatigue would also meet criteria for CFS, ME/CFS or ME. However, this study adds to literature on a variety of infectious agents that trigger post-infectious illnesses that bear many similarities to CFS. More Research1st coverage here. (Gut, Sept. 12, 2011)

Case Definition Face-Off: A group of researchers led by Leonard Jason, PhD, used data mining techniques to determine which questions were most effective for accurately identifying cases using two definitions: the Canadian ME/CFS clinical definition (Carruthers, 2003) and the “empiric” definition proposed by CDC in 2005. Their findings show that the Canadian definition selects cardinal features of the illness better than the empiric and is better at discriminating cases from noncases. (Journal of Clinical Psychology, Aug. 5, 2011)

Study Estimates Rates of ME/CFS in England, Compares Case Definitions: The ME/CFS Observatory conducted a study of ME/CFS in three distinct areas of England to determine prevalence, incidence and the ability of three different definitions to detect ME/CFS (CFS) in 29 general medical practices that served a total population of 143,000. “The prevalence rate of cases meeting the CDC-1994 definition was 0.19%, of cases meeting the Canadian definition 0.11%, and of cases meeting [an Epidemiological Case Definition devised for this study] 0.03%.” Prevalence was higher in London (urban), among women and among white-British, compared to industrial or rural areas, men or non-white ethnic minorities. About half of cases that met the CDC-1994 definition also met the Canadian definition. “Comparisons between the groups conforming to the Canadian criteria and CDC-1994 criteria only (non-Canadian) have shown that all the reported symptoms were higher in the Canadian group.” The paper concludes by reinforcing the burden represented by the illness (regardless of definition) and the need to improve identification of subgroups to strengthen research. “Both groups have high levels of need for service provision, including health and social care. We suggest combining the use of both the CDC-1994 and Canadian criteria for ascertainment of ME/CFS cases, alongside careful clinical phenotyping of study participants.” (BMC Medicine, July 28, 2011)  

Magnetic Resonance Tagging Reveals Impaired Cardiac Function: Julia Newton’s group at Newcastle University used a new method of assessing the shape, structure and function of the heart in this study of 12 CFS patients and 10 healthy controls. They found that compared to controls, “CFS patients have markedly reduced cardiac mass and blood pool volumes, particularly end diastolic volume: this results in significant impairments in stroke volume and cardiac output compared to controls.” (Journal of Internal Medicine, July 27, 2011; accepted article approved for publication, yet to undergo copy-editing and proof correction.)

No XMRV Detected in Twin Pairs Discordant for CFS: Keith Jerome at University of Washington and colleagues tested a total of 85 samples from same-sex twin pairs recruited to the Chronic Fatigue Twin Registry by Dedra Buchwald, MD. Twin pairs in this cohort, one of whom has CFS (by 1994 Fukuda criteria) and the other does not, have been studied extensively. The team used four PCR assays to test banked samples for XMRV under blinded conditions. Apart from one inconclusive result on a twin who does not have CFS, XMRV was not found in any of the twins with CFS. The authors conclude, “…our results do not appear to be consistent with the original report of XMRV being present in 67 percent of patients with CFS.” Diagnostic Microbiology and Infectious Disease, (July 26, 2011)

New Criteria for Myalgic Encephalomyelitis by Independent Consensus Panel of International Experts: Led by Bruce Carruthers, who also led the development of the first Canadian consensus definition for ME/CFS, a panel of 26 physicians, researchers and teaching faculty from 13 countries, propose new criteria for myalgic encephalomyelitis (ME) and recommend use of this term and criteria as a replacement for CFS: “…it is more appropriate and correct to use the term “ME” because it indicates an underlying pathophysiology.” The criteria propose one compulsory feature — post-exertional neuroimmune exhaustion (PENE) — plus seven symptoms from three subdivided symptom clusters: neurological, immunological and energy production/transport impairments. The criteria are intended for clinical and research use and the paper states that the panel is developing Physicians’ Guidelines and an International Consensus Symptom Scale for use in these settings. The criteria are summarized here. There is sure to be more discussion about the change in both the name and criteria for both have potentially far-reaching consequences for research, policy and education. (Journal of Internal Medicine, July 20, 2011; accepted article approved for publication; published online ahead of print on Aug. 22, 2011 and published in print Oct. 2011. The final full-text version is available open access.) 

EEG Spectral Data Distinguishes CFS From Depressed and Healthy Controls: A group at Harvard analyzed spectral data from electroencephalograms (EEGs) performed on 70 CFS patients (1994 criteria), 390 healthy controls, 24 subjects with major depression and 148 patients with prolonged generalized fatigue, a total of 632 subjects. Senior author Anthony Komaroff, M.D., diagnosed the CFS patients. Ten factors were found to distinguish CFS from healthy and depressed controls, with the highest rate of differentiation among unmedicated female CFS patients and female healthy controls, without misclassifying the subjects with major depression as CFS. The model lost some statistical power when applied to subjects taking psychoactive medications; the authors suggest this may reflect a therapeutic effect on the brain function or may modify EEG measurements. ”CFS patients manifest patterns of functional brain coupling that differ from those of normal controls. Such a difference of CFS brain physiology may help explain known differences in cognition, memory, sleep, and affect that afflict CFS patients.” They report that chief among the distinguishing factors were those involved in the brain’s temporal lobe function. (BMC Neurology, July 1, 2011) 

Repeat Exercise Testing Identifies Abnormalities, Subgroups: 18 CFS patients (1994 criteria) and 12 matched sedentary controls were recruited into Professor Julia Newton’s center at Newcastle University (U.K.). Participants were tested for cardiopulmonary fitness and magnetic resonance spectroscopy to assess muscle bioenergetic function in response to three bouts of exercise. Similar to other studies, CFS patients as a group had reduced cardio-respiratory reserve and lower anaerobic threshold compared to sedentary controls. The response to maximal voluntary contraction (MVC) separated the CFS subjects into two distinct groups. ”The group of CFS patients who achieved normal levels of phosphocreatinine (PCr) depletion (>33%) had comparable MCV values to the normal controls, but exhibited markedly greater muscle acidosis. The second group had low PCr depletion and no excess acidosis, but this appeared to be entirely as a consequence of having markedly lower MVC values than either the normal PCr depletion CFS patients or the normal controls.” Eight CFS patients fell into the first group and 10 were in the second group. Both groups reported maximal perceived effort during the exercise challenge and both groups reported similar rates of pain upon exercise. In the first group, exercise induced profound and sustained acidosis. “We believe that the local and systemic sequalae of this sustained acid exposure contribute significantly to the expression of fatigue in CFS.” However, based on objective measures, the second group exhibited a reduced drive to exercise, possibly due to perceived negative consequences of exercise. (The study was not designed to determine reasons for differences between the two groups.) The authors stated, ”Our findings suggest that MR-directed stratification strategies would represent a potentially important tool in future studies of exercise and exercise therapy in CFS.” (European Journal of Clinical Investigation, June 10, 2011) 

Mast Cells Implicated: Mast cells play important roles in allergy and anaphalaxis, as well as protection from infection and wound healing. They also play a role in the inflammatory process. This group at Tufts University observed that antidepressants are used to treat several conditions characterized by pain (CFS, fibromyalgia and interstitial cystitis), but that there was no known mechanism to explain the benefit they provide to some patients. To test whether these drugs might affect mast cells, they incubated human mast cells with several different classes of antidepressants and then stimulated the cells with substance P, a neuropeptide involved with pain processing. Only amitriptyline (brand name Elavil and other names) and prochloperazine (brand name Compazine and other names) inhibited mast cells. The authors suggest this finding may implicate mast cells in the pathogenesis of CFS. (Journal of Clinical Psychopharmacology, June 2011)

Study Fails to Confirm XMRV Test Results: Konstance Knox et al. tested newly collected samples from 61 CFS patients of which 43 had received positive test results for XMRV from either the Whittemore Peterson Institute or its commercial laboratory, VIP Diagnostics. This team used a variety of methods to detect XMRV and did not detect XMRV in any of the freshly collected samples. Following on reports from other laboratories, they tested a variety of reagents used to perform polymerase chain reaction and found 9 of 17 to be contaminated with mouse DNA similar to sequences reported by Lo et al. in the Proceedings of the National Academy of Sciences.  They conclude, “We believe that the detection of MLV in human blood in previous studies reflects contamination of reagents used to assess their presence and/or contamination of human samples during laboratory manipulation of the infectious XMRV clone, VP62.” This study attracted high profile media coverage from hundreds of outlets, in part due to the simultaneous publication of a study reporting the origin of XMRV to be a laboratory recombination of two endogenous mouse viruses and an editorial Expression of Concern by Science’s editor-in-chief about the original publication from Lombardi et al. published in Science in Oct. 2009. A more detailed analysis of this study and its conclusion is provided here on Research1st. (Science, May 31, 2011)

Immune Markers Distinguish CFS/ME Patients from Healthy Controls: Researchers at Bond University in Australia teamed with long-time CFS researcher and immunologist Nancy Klimas of the University of Miami to study the immune profiles of 95 CFS/ME patients compared to 50 healthy controls. Subjects were recruited from practices in Queensland and New South Wales. Blood samples were collected at one point in time, at rest. Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4+CD25+ T cells, FoxP3 and VPACR2 expression. The cell-killing activity of specific immune cells was significantly decreased in patients compared to controls. Expression of two proteins that cells used to control viruses, granzymes A and K, were reduced, while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. Perforin is released by immune cells to kill other cells. The authors state that, “These results illustrate a severely compromised immunomodulation mechanism in CFS/ME where attempts to regulate or restore immune homeostasis appear to be impaired.” (Journal of Translational Medicine, May 28, 2011)

Heritable Predisposition of CFS Found: Utilizing the Utah Population Database, researchers at the University of Utah, Fatigue Consultation Clinic and Veterans Administration Medical Center in Salt Lake City searched linked medical records for the diagnostic code for CFS (780.71). They identified 941 persons with a CFS diagnosis for whom there was available geneology data; 811 cases were included in the assessment. The analysis ”shows clear evidence of significant excess familial clustering and significantly elevated risks for CFS among first, second, and third degree relatives of CFS cases. The results strongly support a genetic contribution to predisposition to CFS.” The authors report that this is the first population-based analysis to comprehensively support this claim. (BMC Neurology, May 27, 2011) 

Exercise Challenge Reveals Potential Biomarkers: Following up on earlier work, this University of Utah team has reported that a sustained moderate exercise challenge of 25 minutes provoked gene expression changes that meet published criteria for a “Very Good” to “Excellent” diagnostic tool for a subgroup of CFS patients studied. Forty-eight CFS patients were studied and two distinct subgroups were identified on the basis of changes to the α-2A receptor, a key regulator of neurotransmitters in the central nervous system. The larger group of CFS subjects (71%) could be identified with a combination of four biomarkers (P2XR, α-2A, β-2 and IL10) at any time point within 48 hours following the exercise challenge with high specificity and sensitivity. The smaller group showed a large decrease in α-2A, opposite of the larger group. Most of the members of this subgroup had a clinical history of orthostatic intolerance. 18 subjects with fibromyalgia were also evaluated and a baseline marker combining 3 genes was identified. All subjects in the study (CFS and FM) exhibited post-exertional relapse of symptoms for at least 48 hours following the exercise task, but 49 healthy controls did not. We have provided a more detailed summary of this study funded by the CFIDS Association, the NIH and AFSA. (Journal of Internal Medicine, May 26, 2011)

Inflammatory response of cytokines

Inflammatory Cytokine and Chemokine Signature: Blood samples collected from 118 CFS patients who had tested positive for XMRV were compared to samples obtained from 138 controls subjects. Concentrations of 26 plasma markers belonging to different immune classes were evaluated by xMAP technology from Luminex. Of the 26 cytokines and chemokines tested, 19 were different between patients and controls. The greatest difference was between interleukin-8, a major mediator of the inflammatory response, which was upregulated in cases compared to controls. The authors from the Whittemore Peterson Institute and University of Reno suggest that this data supports the description of XMRV-related CFS as an inflammatory disease and propose that multiplex cytokine and chemokine analysis in conjunction with XMRV testing “may serve as a useful diagnostic for CFS.” (IN VIVO, May 16, 2011)

Review of Qualitative Studies Yields Information for Clinicians: Researchers at DePaul University systematically reviewed and analyzed 34 qualitative studies on ME/CFS. Three themes focused on: (1) experiences of people with ME/CFS, (2) experiences of physicians and (3) themes that intersect both of these groups. For patients, illness development influenced identity, reductions in functioning and coping. Physician-specific themes described lack of awareness about ME/CFS and recommended improvement in educational resources. Intersecting themes expressed issues with diagnosis creating tensions and fueling the stigmatization of ME/CFS. The researchers suggest that future qualitative studies recognize the various facets of the ME/CFS experience, the network members of people with ME/CFS, and the sociocultural environment through which the illness is understood. This review shows that health care professionals can gain unique insight from patient experiences, allowing for more accurate diagnoses and treatment recommendations. (Patient Education and Counseling, May 13, 2011)

Evidence of Brainstem Dysfunction and Altered Homeostasis: Researchers in Australia explored brain involvement in CFS. They used statistical parametric mapping of brain MR images and compared against clinical scores for 25 CFS subjects and 25 normal controls. Clinical scores included CFS fatigue duration, a score based on the 10 most common CFS symptoms, the Bell score, the hospital anxiety and depression scale (HADS) anxiety and depression and hemodynamic parameters from 24-h blood pressure monitoring. Midbrain white matter volume was observed to decrease with increasing fatigue duration. A strong correlation in CFS between brainstem grey matter volume and pulse pressure suggested impaired cerebrovascular autoregulation. It can be argued that at least some of these changes could arise from astrocyte dysfunction. These results are consistent with an insult to the midbrain at fatigue onset that affects multiple feedback control loops to suppress cerebral motor and cognitive activity and disrupt local CNS homeostasis, including resetting of some elements of the autonomic nervous system. (NMR in BioMedicine, May 11, 2011)

XMRV Link Not Confirmed: A comprehensive follow-up study of XMRV using multiple testing methods on freshly collected samples from 100 well-characterized clinic patients, 200 healthy volunteers from the same geographic area and 14 patients who had previously tested positive for XMRV by investigators at the Whittemore Peterson Institute (WPI). The team, led by senior author Ila Singh, PhD, processed, tested and analyzed all samples in an identical fashion. In spite of these measures and every hope of obtaining a positive result, they could not detect XMRV or polytropic MLVs in any of the samples and therefore could not confirm the link between this family of retroviruses and CFS. Of note is that the study followed a template published in the Nov. 3, 2010, issue of Viruses by Dr. Singh that suggests a definitive study of retroviral sequences in CFS. (Journal of Virology, e-published ahead of print on May 4, 2011; print edition July 15, 2011) This study attracted coverage by the Wall StreetJournal, ScienceInsider (Science magazine), Nature NewsBlog (Nature magazine), Los Angeles Times, Chicago Tribune, US News & World Report and other outlets. “The Iteration of X,” an analysis prepared by the CFIDS Association’s scientific director and CEO, describes the study design and authors’ conclusions.

Cognition: A group in Belgium evaluated 25 subjects with CFS, 25 subjects with major depressive disorder (MDD) and 25 healthy subjects using standardized tests of attention, working memory and verbaland visual episodic memory. They were also tested for effects related to lack of effort/simulation, suggestibility and fatigue. Patients with CFS had slower phasic alertness; they also had impaired working, visual and verbal episodic memory compared to controls. This study confirmed the presence of an objective impairment in attention and memory in patients with CFS. (Clinical Neurology and Neurosurgery, Jan. 19, 2011 [e-pub], May 2011 [print])

Psychomotor Slowing: Researchers in the Netherlands and Belgium studied 35 women with CFS with no history of depression and 25 healthy female control subjects. They tested cognitive and fine motor processing of visual-spatial information, measured by recording reaction time (RT) and movement time (MT), respectively. CFS was significantly associated with longer RT and MT in the pooled and in the task-specific analyses. These performance data on the figure-copying tasks provide confirmatory evidence for psychomotor slowing in CFS, but not for a disturbed inhibition of automatic responses. The authors conclude that computerised figure-copying tasks may be promising tools for use in neurobiological research and clinical trials in CFS. (Journal of Psychiatry Research, Apr. 30, 2011)

Disturbed Sleep: An Australian study that looked at circadian patterns of activity, sleep and cortisol secretion in CFS patients and healthy controls found that “ratings of symptoms, disability, sleep disturbance and pain sensitivity were greater in patients with CFS.” (Sleep,  Apr. 29, 2011)

Prevalence & Morbidity of Pediatric CFS: Researchers in the Netherlands collected data from general practitioners and pediatric hospitals about children with CFS ages 1o years to 18 years. They found 111 cases of CFS per 100,000 adolescents. CFS in adolescents was accepted as a distinct diagnosis by 51 percent of all responding GPs. Nijhof et al concluded: “These data strongly suggest that adolescent CFS should be regarded as a serious illness with corresponding consequences such as delay in educationaland social development.” TIME magazine’s “Healthland” blog covered this study. (Pediatrics, Apr. 2011; open access)

Similarities to Lyme Disease: The Institute of Medicine published a comprehensive report on Lyme disease. CFS was addressed throughout the report. According to several studies, 11.6 percent of patients with Lyme disease have symptoms consistent with CFS six months after the tick bite. The report provided a comprehensive summary of the literature on Lyme disease and revealed many similarities to CFS in the observed immune, endocrine and neurological abnormalities. (Institute of Medicine, Apr. 20, 2011; available online)

Post-Transplant Risks Not Found: UK researchers reported the results of a small retrospective study of 10 deceased solid organ donors who had been diagnosed with CFS and the health of the recipients of their organs. None of the organ recipients had developed CFS in the post-transplant follow-up period. They concluded with the suggestion that there is no justification for excluding those with CFS from organ donation, due to the shortage of organs and significant mortality of those awaiting transplants. The authors acknowledged the conflicting evidence for XMRV infection in CFS and indicated that transmission of viruses by solid-organ transplantation is well-recognized in cases of hepatitis B and C and HIV. This study was aimed at whether organ transplants could transmit CFS; the report did not reflect testing either donors or recipients for XMRV. (Transplantation, Apr. 15, 2011)

CFS as Neuro-Inflammatory State: Arnett and colleagues at the Australian National University reviewed the evidence supporting a neuroimmunological basis for CFS, providing a strong case for inflammatory and infectious precipitants on the background of neurological changes associated with CFS. They addressed the shortcomings of behavioral therapies and suggested carefully constructed trials of centrally acting anti-inflammatory agents that might quiet the cytokine storm seen in many CFS patients. They concluded, “CFS and related conditions are debilitating and intractable conditions that often strike patients at a time of their life when they would otherwise be at their most economically and socially productive.” (Medical Hypotheses, available online Apr. 5, 2011; print publication July 2011)

Oxidative Stress: Michael Maes et al provided evidence from a study of 56 patients with ME/CFS and 37 healthy controls that plasma peroxide concentrations in the blood were higher in patients than controls. There was also a trend toward higher levels of a lipoprotein called oxLDL in patients compared to controls. Using both measures, the investigators could distinguish cases from controls and hypothesized that ME/CFS is characterized by increased oxidative stress based on these measurements and other published studies. (Medical Science Monitor, Apr. 1, 2011)

Post-SARS CFS-Like Syndrome: In 2003, Severe Acute Respiratory Syndrome (SARS) spread from southeast Asia to North America, causing a public health panic and many deaths. Fever, cough, muscle pain and air hunger were the primary presenting symptoms, and many people who did not die from the acute infection failed to recover. There has been little long-term follow-up of post-SARS cases. Moldofsky and Patcai compared 21 health care workers who had documented SARS and were not well enough to return to work one year to three years later to seven healthy females and 21 females who met fibromyalgia (FM) criteria. They found that the chronic post-SARS syndrome shares clinical and sleep features with CFS and FM. A longer term, large scale study is needed to establish the contribution of epidemic and pandemic viral disease to the disordered sleep, chronic fatigue and other symptoms of CFS/FM. (BMC Neurology, Mar. 24, 2011)

No XMRV in Japanese Study: A research group in Japan led by Rika Furata of the Japanese Red Cross published its results of multiple testing methods for XMRV/PMLVs in CFS, prostate cancer and healthy controls which found no association between these retroviruses and the population studied. (Retrovirology, Mar. 17, 2011)

Migraine Overlap: Headaches of a new type or severity is one of eight case-defining CFS symptoms. Two cohorts of Georgetown University CFS patients were evaluated using standard criteria for headache subtypes. 60 percent of CFS subjects had migraine without aura; 24 percent had migraine with aura; 12 percent had tension headaches only; only four percent had no headaches. Co-occurring tension and migraine headaches were found in 67 percent of CFS subjects. Sumatriptan (Imitrex) was beneficial for 13 out of 14 newly diagnosed CFS migraine subjects. The authors conclude, “Appropriate diagnosis and treatment with triptansmay be beneficial for CFS subjects and their complex headaches.” (BMC Neurology, Mar. 5, 2011)

Energy Envelope Can Guide Therapy: This group at DePaul University led by Leonard Jason, PhD, has several publications describing the assessment of available and expended energy in ME/CFS patients and recommending that activity be guided by an ongoing assessment of both. They have termed this approach the “energy envelope.” The latest paper reports on a study of 44 ME/CFS patients. Available and expended energy was rated before beginning a nonpharmacological treatment program. Those who started the program ”within” their energy envelope had more improvement in physicial functioning and fatigue levels compared to those who started the program in an energy deficit. The authors suggest this assessment can help guide individualized approaches to therapy. A blog post about this study and the energy envelope was posted on May 29, 2011. (Journal of Clinical Psychology, Mar. 2011)

XMRV Updates from Two Interorganizational Groups: The AABB Interorganizational XMRV Task Force published “XMRV and blood transfusion: report of the AABB interorganizational XMRV task force,” describing the current state of understanding of XMRV and disease associations. The Blood XMRV Scientific Research Working Group published a report on its four-phase study of blood safety, “The Blood XMRV Scientific Research Working Group: Mission, Progress, and Plans,” in the same issue. (Transfusion, Mar. 2011)

Kindling Model for Etiology: Dr. Leonard Jason’s group at DePaul University built on earlier publications that propose kindling as a model for ME/CFS. Kindling occurs when an organism is exposed repeatedly to an initially sub-threshold stimulus resulting in hypersensitivity and spontaneous seizure-like activity. The authors proposed that seizure activity spreads to nearby areas in the brain, leading to the varied symptoms that occur among patients with ME/CFS. Kindling may also be responsible for high levels of oxidative stress, which has been found in patients with ME/CFS. (Neuroscience & Medicine, March 2011; open access.)

Spinal Fluid Proteins: Researchers at six institutions led by the University of Medicine and Dentistry of New Jersey and Pacific Northwest National Laboratory reported finding 738 unique protein markers in spinal fluid samples collected from 43 CFS patients and compared to samples from 25 neurologic post-treatment Lyme disease patients and 11 healthy control subjects. They were able to distinguish CFS from Lyme disease. Proteins identified in CFS patients only have been linked to Parkinson’s disease and Alzheimer’s. The authors have published the library of proteins identified to facilitate deeper explorations for diagnostic tools and potential therapies. (PLoSONE, Feb. 23, 2011) The Association provided analysis of this study, which garnered attention from “The CBS Evening News” and other news agencies. BioTechniques and Expert Review of Proteomics recently covered this study.

Behavioral Therapies Compared: This large study compared four treatment approaches in 641 patients using Oxford, CDC and London criteria for CFS and ME. The study reported modest benefits following a six-month course of cognitive behavioral therapy (CBT) or graded exercise therapy (GET) compared to specialized medical care alone or adaptive pacing therapy, based on improvement in self-reported symptom scores. There were no biological measures taken during the study to correlate with the results and media reports greatly exaggerated the small gains made by some participants in self-report measures. (Lancet, Feb. 18, 2011) The Association published an analysis of and commentary on the study and submitted a letter to the editor of Lancet.

Cerebral Blood Flow: Using an MRI technique called arterial spin labeling, this New Jersey group compared blood flow in the brains of 11 subjects with CFS and 10 age-matched healthy controls. The CFS patients as a group had significantly lower global cerebral blood flow (CBF) compared to controls. The reduction in CBF occurred across nearly every region assessed. Nine of the 11 patients showed these reductions compared to the average control data, while two patients showed actual increases relative to the controls. (Journal of the Neurological Sciences, Feb. 15, 2011)

Autonomic Function: Forty-four CFS patients and 52 healthy adolescents aged 12 years to 18 years were recruited from a pediatric outpatient clinic in Norway. Twenty-four-hour ambulatory blood pressure and heart rate were recorded using a portable device. During night-time sleep, heart rate and mean blood pressure were significantly higher in CFS patients as compared with controls. During daytime, heart rate was significantly higher among CFS patients, whereas blood pressures were equal between the two groups. The findings supported other evidence of sympathetic predominance of cardiovascular control in adolescent CFS patients and suggested a possible target for therapeutic intervention. (Acta pediatrica, Feb. 2011)

Vitamin D Supplementation: Martin Pall of Washington State University has proposed increased nitric oxide synthesis as a mechanism for CFS and other conditions. In this paper, he and collaborator AD Hoeck explore the possibility that an observed deficiency of vitamin D may chronically activate a pro-inflammatory response in illnesses characterized by inflammation and fatigue and they suggest randomized clinical trials of calcium and vitamin D(3) supplementation to test the theory. (Medical Hypotheses, Feb. 2011)

Novel Pathogens: Researchers in the U.S. and Sweden reported that they examined 45 pairs of twins discordant for CFS or idiopathic chronic fatigue (one twin had CFS or ICF and the other did not) for evidence of novel pathogens. A weak association with hepatitis G virus was found in nine percent of the cases and zero percent of the controls. (BMC Microbiology, Jan. 2, 2011)

Gynecologic Problems Common: Gynecological histories of 36 women with CFS were compared to 48 nonfatigued controls. Women with CFS had more gynecological conditions, including non-menstrual pelvic pain, endometriosis and amenorrhea. CFS patients had a higher mean number of pregnancies. Seventy-six percent of the women with CFS reported hysterectomy compared to 55 percent of the healthy women. Fifty-six percent of the women with CFS had one or both ovaries removed, while only 34 percent of healthy controls had this surgery. The CDC authors concluded that more research is needed to clarify the chronological and pathophysiologic relationships between these conditions and CFS. (Journal of Women’s Health, Jan. 2011)

PRESENTATIONS & CONFERENCES:

Dr. Ian Lipkin, director of Columbia University’s Center for Infection and Immunity, gave a presentation on June 24, 2011 at the Whittemore Peterson Institute titled, “Microbe Hunting.”  Dr. Lipkin briefly describes the multicenter study he is coordinating on behalf of the National Institutes of Health to look for evidence of XMRV in CFS patients and matched healthy controls.

At the 15th International Conference on Human Retrovirology, HTLV and Related Viruses held June 6-8, 2011, eight presentations and 15 posters provided some new data and a forum for discussion of the conflicting findings in the field of XMRV.

The National Institutes of Health (NIH) hosted the ME/CFS State of the Knowledge Workshop on April 7-8, 2011. The workshop brought together subject matter experts to discuss multiple aspects of ME/CFS, including epidemiology, etiology, pathophysiology, diagnosis and treatment. The workshop panelists helped identify gaps in knowledge and opportunities for advancing biomedical research. NIH Director Francis Collins addressed the meeting and several other top Department of Health and Human Services and NIH staff attended all or part of the workshop. Secretary Kathleen Sebelius expressed her support in a letter sent to workshop participants.

The NY Academy of Sciences hosted a Mar. 29, 2011, webcast titled, “Pathogens in the Blood Supply,” featuring Ian Lipkin of Columbia University, who updated attendees and viewers about the XMRV/CFS study he is coordinating for the National Institute of Allergy and Infectious Diseases; and Judy Mikovits of the Whittemore Peterson Institute, who described that organization’s XMRV studies.

Dr. Jose Montoya of Stanford University has recently launched the Stanford Chronic Fatigue Initiative. In this presentation recorded at Stanford Hospital on Mar. 3, 2011, he discussed CFS and his research interest in infections and CFS.

More than 120 researchers and clinicians from 18 countries gathered in Reston, Virginia from Feb. 28 through Mar. 2, 2011, to attend the 7th International Conference on HHV-6 & 7. At this gathering, work was presented on the most recent implications and findings of HHV-6 in a broad spectrum of research and clinical settings. There were several presentations about the role and potential treatment of HHV-6 infection in CFS.

The 18th Conference on Retroviruses & Opportunistic Infections (CROI), held Feb. 27-Mar. 2, 2011, included one session on XMRV studies. Abstracts of the presentations and a recording of the session are available. The Association’s summary, “On the Origins of XMRV,” explains the presentations made at this meeting.

The National Institutes of Health hosted a seminar about CFS as part of its “Demystifying Medicine” series for professionals. Drs. Shyh-Ching Lo (FDA), Harvey Alter (NIH) and Fred Gill (NIH) discussed “CFS: Is There A Virus?” on Feb. 22, 2011.

On Jan. 12, 2011, Steven Kleinman, BSc, MD, presented “XMRV and Related Retroviruses: Are These A Threat to Blood Safety?” to Canada’s Centre for Blood Research.

The Food and Drug Administration’s Blood Products Advisory Committee met on Dec. 14, 2010, and heard nine presentations about MLVs/XMRV and additional statements during the public session.

If you have questions, we’ll do our best to answer them via our blog, FAQs, CFIDSLink (our free monthly e-newsletter) and other information posted on this site.

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