2011 JOURNAL HIGHLIGHTS

Here we briefly recap recently published studies that bolster evidence of the biological nature of CFS and/or suggest possible therapies. Also visit our XMRV resources page where you can find an overview of research about the link being intensively explored between CFS and a family of murine leukemia-virus like viruses.

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)

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, MD, 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)

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 led by Theoharis Theoharides, MD, PhD, 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)

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. Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-y, TNF-a, CD4+CD25+ T cells, FoxP3 and VPACR2 expression. 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). 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)

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 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: Thirty-four qualitative studies on ME/CFS were systematically reviewed and analyzed by researchers at DePaul University. 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)

BRAIN MRI STUDY: New study by rsearchers in Australia finds evidence of brainstem dysfunction in 25 CFS patients compared to healthy controls. A strong correlation in CFS between brainstem GM 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 (ANS). (NMR in Biomedicine May 11, 2011)

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 verbal and 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, (e-pub) May 2011 (print))

PREVALENCE & MORBIDITY OF PEDIATRIC CFS: Researchers in the Netherlands collected data from general practitioners and pediatric hospitals about children with CFS age 10-18 years of age. 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 conclude: "These data strongly suggest that adolescent CFS should be regarded as a serious illness with corresponding consequences such as delay in educational and 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 is 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 provides a comprehensive summary of the literature on Lyme disease and reveals many similarities to CFS in the observed immune, endocrine and neurological abnormalities. (Institute of Medicine, Apr. 20, 2011; available online)

CFS AS NEURO-INFLAMMATORY STATE: Arnett and colleagues at the Australian National University review 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 address the shortcomings of behavioral therapies and suggest carefully constructed trials of centrally acting anti-inflammatory agents that might quiet the cytokine storm seen in many CFS patients. They conclude: “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, Apr. 5, 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 normals. 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 they hypothesize that ME/CFS is characterized by increased oxidative stress based on these measurements and other published studies. (Medical Science Monitor, April 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 1-3 years later to 7 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, March 24, 2011)

MODEL FOR ETIOLOGY: Dr. Leonard Jason's group at DePaul University builds 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 propose 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.)

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% of CFS subjects had migraine without aura; 24% had migraine with aura; 12% had tension headaches only; only 4% had no headaches. Co-occurring tension and migraine headaches were found in 67% 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 triptans may 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. (Journal of Clinical Psychology, Mar. 2011)

SPINAL FLUID PROTEINS: Researchers at six institutions led by UMDNJ 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. (PLoS ONE, Feb. 23, 2011) The Association provided analysis of this study; the study garnered attention from “The CBS Evening News” and other news agencies. BioTechniques and Expert Review of Proteomics recently covered this study.

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: 44 CFS patients and 52 healthy adolescents aged 12-18 years were recruited from a pediatric outpatient clinic in Norway. 24-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 support other evidence of sympathetic predominance of cardiovascular control in adolescent CFS patients and suggest 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 inflammationg and fatigue and they suggest randomized clinical trials of calcium and vitamin D(3) supplemenation to test the theory. (Medical Hypotheses, Feb. 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. 76% of the women with CFS reported hysterectomy compared to 55% of the healthy women. 56% of the women with CFS had one or both ovaries removed, while only 34% of healthy controls had this surgery. The CDC authors conclude that more research is needed to clarify the chronological and pathophysiologic relationships between these conditions and CFS. (Journal of Women’s Health, Jan. 2011)

Updated most recently on August 29, 2011