ME/CFS Research Recap 2012

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Last Updated: 23 November 2015 23 November 2015

This is a recap of studies and relevant articles on ME/CFS published during 2012  (formerly posted on our News around the Web page).

Half of CFS patients with high HHV-6 & EBV titers improve 30% or better on Valcyte: Montoya (ProHealth) Review of a recent article, "Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers", published by Jose G Montoya, et al, in the Journal of Medical Virology, Oct 10, 2012;84(12), pp 1967-1974.

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis (BioMed Central, open access article, as PDF) Brenu et al, a research group from Australia which also included Dr. Daniel Peterson, a well-known CFS/ME specialist from Nevada, USA, studied Natural Killer (NK) cell cytotoxic activity, NK cell subsets and cytokines in patients with CFS/ME over the course of a 12 month period. Their research was published in the Journal of Translational Medicine, 2012, 10:88, and for the entire period of time, they consistently found altered regulation of immunological function, in particular reduced cytotoxic activity of innate immune cells, in CFS/ME patients.

Constellation of 5 immune markers—may be diagnostic for post-mono ME/CFS (ProHealth) ProHealth provides a summary about a study published in the Journal of Translational Medicine, Sept. 13, 2012, by a group of ME/CFS researchers at clinics in Canada and several US states that looked at broad range of cytokines in patients who had developed an infection with the same pathogen, Epstein-Barr Virus (EBV), and remained ill at 24 months post infection. The study was able differentiate these patients from recovered control subjects by identifying an atypical immune response in post-infection group. 

Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) —link to original, full text article. [International Journal of Clinical and Experimental Medicine, published June 30, 2012; Volume 5, Issue 3:208-220] The authors of this study, Norman E Booth, Sarah Myhill, and John McLaren-Howard, found measurable mitochondrial dysfunction in white blood cells in all patients tested which correlated with the severity of the illness.

ME/CFS associated with later life non-Hodgkin lymphoma: Medicare statistics (ProHealth) An article based on a study, "Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults" (Cancer, May 30, 2012) that looked at chronic immune activation or an infection in CFS which might explain this increased risk.

The NIH on ME/CFS in 2012: Pt II—the STUDIES! Cort Johnson, the creator of the Phoenix Rising website, writes about the challenges and rigorous procedures that investigators face when applying to the National Institutes of Health (NIH) for research grants. This investigative piece includes a comprehensive list of ME/CFS research and clinical trials, in progress or about to end, funded by the NIH.

A Double-Blind, Placebo-Controlled, Randomized, Clinical Trial of the TLR-3 Agonist Rintatolimod in Severe Cases of Chronic Fatigue Syndrome (PLoS ONE, Mar 14, 2012,  link to free, open access, full text article)  Research results from a 12-site clinical trial of rintatolimod (U.S. brand name,  Ampligen) show objective improvement in severe CFS. Rintatolimod has been used to treat ME/CFS in Canada and several European countries since the late 1990s, but in the U.S. it has been met by many delays and conflicts.

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis—a new potential diagnostic biomarker (Physiological Measurement, vol. 33, p. 231-241, 2012) An in-depth evaluation of pulse wave analysis in CFS patients and its potential use as illness biomarker.   

Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study (PubMed, Feb, 2012) Abstract of research published in the European Journal of Clinical Investigation that provides more evidence in how exercise impacts individuals with CFS differently from healthy controls.

Understanding the Immune System A good, basic  explanation, with illustrations, of the immune system response prepared by the National Institute of Allergy and Infectious Diseases (NIAID). Once at the NIAID site, click/select desired subtopic to view from the left side bar.


List of videos or audios released by researchers during 2012 on various topics pertaining to ME/CFS:

Now Available for Viewing A series of videos made by Dr. Kenneth Friedman for cfsKnowledgeCenter, during 2012, covering physiological aspects of ME/CFS, causes, biomarkers, and more. Once at the ME-CFSCommunity home page (part of the cfsKnowledgeCenter organization), please follow their instructions on how to sign in and access the videos and other valuable information.

Dr. Peterson Says ‘Hold On, There's Hope' (Pro-Health) A video interview (approximately 11 minutes long) of leading ‘chronic fatigue syndrome' clinician Daniel Peterson, MD by ME/CFS Alert (episode 26) co-host Llewellyn King

VIDEO: ME/CFS Alert # 31— Virologist Konnie Knox (ProHealth) Llewellyn King interviews Konstance Knox, PhD, a renowned virologist from Milwaukee, who has collaborated with Dr. Dan Peterson on ME/CFS research since 1996. She has a particular interest in the neurocognitive component of this illness and reviews her theories on the role of viruses in ME/CFS as well as Fibromyalgia.

VIDEO: ME/CFS Alert #32: Staci Stevens explains post-exertion malaise testing (ProHealth) Llewellyn King features Staci Stevens, an exercise physiologist at the Pacific Fatigue Lab in Stockton, CA, who describes the testing process for post exertion malaise (PEM) and explains how it can provide objective evidence of PEM.

Fibromyalgia studies 2012

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Last Updated: 08 November 2015 08 November 2015

This is a recap of studies and relevant articles on Fibromyalgia which were published during 2012 (formerly posted on our News around the Web page).

"Working Memory Impairment in Fibromyalgia Patients Associated with Altered Frontoparietal Memory Network" (PLoS One) A study conducted by Korean researchers using functional magnetic resonance imaging (fMRI) to demonstrate differences in working memory between FM patients and healthy subjects.

“Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia”
(da Cunha Ribeiro et al, Arthritis Research & Therapy 2011, 13:R190 doi:10.1186/ar3519) Research by a team of rheumatologists at University of Sao Paulo School of Medicine, Brazil, that found some patients with FM experienced various cardiac irregularities in response to exercise.

“Autonomic dysfunction in women with fibromyalgia” — an editorial in response to the article published by Ribeiro and colleagues in Arthritis Research & Therapy, supporting the finding of autonomic dysfunction at rest in FM patients.

Research on Fibromyalgia Skin Sensitivities (Fibromyalgia Network) Researchers provide answers about what might be causing itchy or burning sensations and other skin sensitivities frequently experienced in FM.

New Device Cuts Fibromyalgia Pain in Pilot Study (Clinical Psychiatry News Digital Network) Results from a small pilot study of FM patients who were treated with an investigational transcranial stimulation device designed to target a region deep in the brain linked to chronic pain.

Developments in Fibromyalgia Treatments 2012

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Last Updated: 03 January 2016 03 January 2016

This group of articles, published in 2012 at various sources, evaluates status of commonly prescribed recommendations and treatments for Fibromyalgia.

"Fibro Doctors Chose Pfizer Over You "(Fibromyalgia Network, posted May 30, 2012) An editorial by Kristin Thorson, founder and editor of the Fibromyalgia Network, on the FibroCollaborative Roadmap for Change program. Disclaimer: This editorial is being provided as a source of information. The opinions expressed are those of the author and do not necessarily state or reflect the views of Massachusetts CFIDS/ME & FM Association.

"Fibro Out-of-Control?" (One of the free, sample articles available at Fibromyalgia Network) Dr. Charles Lapp and Dr. Carol Beals explain why FM symptoms get worse and offer ways to tackle.

"Increase in Diagnosis Rates and Penetration into New Markets Drives the Global Fibromyalgia Therapeutics Market, According to New Report by Global Industry Analysts, Inc." (PR Web) An article that takes a look at unmet medical needs for Fibromyalgia from a business standpoint.

"Low-Dose Naltrexone for Autoimmune Diseases and Fibromyalgia? The Unfinished Story" (ProHealth, Dec. 21, 2011)

“Milnacipran Beneficial for Fibromyalgia in Patients With Inadequate Response to Duloxetine” (Monthly Prescribing Reference (MPR)   Review of two FM-specific medications (i.e., milnacipran (brand name, Savella) and duloxetine (brand name, Cymbalta) that includes study observations/ recommendations made by Dr. Lucinda Bateman at The Fatigue Consultation Clinic in Salt Lake City, UT.

"Omega-3 Trial Suggests 'a Nutritional Supplement Might Actually Make a Difference in Aging'" (ProHealth) An interesting article examining some of the benefits of supplemental omega-3 fatty acids as shown in a trial, "Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial," by Kiecolt-Glaser JK, et al. Ohio State University College of Medicine and College of Public Health; University of California, San Francisco, CA, published in Brain, Behavior, and Immunity, Sept. 23, 2012.

XMRV/pMLV multi-center study disproves hypothesis 2012

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Last Updated: 24 November 2015 24 November 2015

The recent multi-center study published on September 18, 2012 in mBio® (the online open-access journal of the American Society for Microbiology) concludes that no evidence of XMRV (xenotropic murine leukemia virus-related virus) and pMLV (polytropic murine leukemia virus) was found in patients with Chronic Fatigue Syndrome, disproving previous findings and hypothesis.

W. Ian Lipkin of Columbia University, a co-author on the study, reported "The bottom line is we found no evidence of infection with XMRV and pMLV. These results refute any correlation between these agents and disease." (Source: Neuroscience News, September 18, 2012).

Follow the instructions below to obtain access (free) to the full-text study.  

A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus (American Society for Microbiology, doi:10.1128/mBio.00266-12) Link provides access to multi-center study on XMRV and ME/CFS co-authored by Harvey J. Alter, Judy A. Mikovits, William M. Switzer, Francis W. Ruscetti, Shyh-Ching Lo, Nancy Klimas, Anthony L. Komaroff, Jose G. Montoya, Lucinda Bateman, Susan Levine, Daniel Peterson, Bruce Levin, Maureen R. Hanson, Afia Genfi, Meera Bhat, HaoQiang Zheng, Richard Wang, Bingjie Li, Guo-Chiuan Hung, Li Ling Lee, Stephen Sameroff, Walid Heneine, John Coffin, Mady Hornig and W. Ian Lipkin.

Once at the mBio® site, click on the right side bar for full text display or PDF of this study. This is an open-access (OA) article released on 09/18/2012 (under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Dr. Gudrun Lange Reviews Neuropsychological Testing for CFS and FM

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Last Updated: 20 November 2015 20 November 2015

Dr. Gudrun Lange reviewed the process of neuropsychological testing for Chronic Fatigue Syndrome (CFS) and FM at the April 28, 2012 Educational Forum co-sponsored by the Massachusetts CFIDS/ME & FM Association (MassCFIDS) and the Massachusetts Department of Public Health.

Dr. Lange said that in the absence of objective biomarkers neuropsychological testing is "the silver bullet" when it comes to qualifying for disability. Cognitive testing is accepted as an objective measure of impairment in function by the Social Security Administration.

[Note: For some long-term disability policies, a finding of impaired cognitive function could lead to a limitation of benefits to two years. Read your policy!—Editor]

Gudrun Lange, Ph.D., is a Clinical Neuropsychologist with sixteen years of experience in the assessment and study of the cognitive and behavioral aspects of chronic pain and persistent fatigue. She has received federal grants for her work and most recently, received National Institutes of Health (NIH) funds for a pilot study to assess the tolerability and efficacy of vagus nerve stimulation (VNS) therapy in patients with severe Fibromyalgia (FM) pain.

Dr. Lange's approach

Dr. Lange uses a quantitative, individualized approach to neuropsychological testing that allows for detailed interpretation of the test data within the context of an individual's overall profile of cognitive strengths and weaknesses.

While individuals with Chronic Fatigue Syndrome (CFS) generally report that the cognitive problems they experience are of great impact on their lives and everyday function, quantitative, objective neuropsychological testing often reveals very subtle cognitive problems.

Many times the deficits found on objective testing do not rise to the level of an absolute impairment.

Dr. Lange argued that any deficits observed need to be interpreted relative to the individuals other strengths and weaknesses, otherwise it may lead to misleading findings.

Difference between focal or diffuse brain injury

Dr. Lange provided a brief overview of the developmental history of clinical neuropsychology. She mentioned that neuropsychological testing evolved to assess individuals with focal acquired brain injuries for diagnosis and management. She distinguished acquired brain injuries that occur after birth from those that an individual is born with, congenital or genetic brain conditions. Before the advances made in neuroimaging technology such as CAT and MRI scans, neuropsychology was used to pinpoint the area of dysfunction in the brain. However, damage to the brain is not always focal, but can be diffuse in nature. Dr. Lange explained that neuropsychological assessment of diffuse brain injuries, affecting many interconnecting areas of the brain, is difficult as the measures were developed to reveal dysfunction in specific brain regions. These conditions include Multiple Sclerosis, Parkinson's disease and Chronic Fatigue Syndrome.

She noted that appropriate interpretation of test data from individuals with these conditions requires a significant degree of interpretation and knowledge by the practitioner. If a neuropsychologist has not had the opportunity to deal with patients with an illness that affects the brain in a diffuse and subtle manner, such as CFS, they might not be sensitive to the type of cognitive dysfunctions seen in these patients. Patients need to find neuropsychologists who are sensitive and knowledgeable about these issues. When a patient is looking for a neuropsychologist, he or she must find someone who is knowledgeable about CFS and FM. Patients must interview neuropsychologists to determine the best candidate, because neuropsychological testing is expensive. CFS patients have deficits. A knowledgeable neuropsychologist must look at the numbers across the different cognitive domains for an appropriate reflection of the cognitive profile with its strengths and weaknesses.

Not less smart, just less fast

The brain is organized in a fashion where basic motor and sensory functions are well represented, allowing for a significant degree of redundancy. Therefore, if a problem occurs in one of these regions, the brain can adjust for it.

This is less true for cognitive functions that are considered "higher" functions, such as executive function, attention, working memory and information processing. Symptoms in CFS such as brain fog and memory impairments fall under these higher levels of brain function. Although many patients find ways to compensate and may not notice their full impairments all at once, it gets more exhaustive for the patient as they have to exert increased amounts of energy to do the same mental tasks.

Specific to CFS patients

It is not the case that patients with CFS become less intelligent. Many patients are concerned that they are "dementing." Dr. Lange stated that she has not seen a CFS patient with dementia. CFS is not a degenerative neurological disorder. I.Q. tests are divided between steady state functions, well-entrenched information firmly planted in the brain, and more transient functions. The steady state information does generally not decay in patients with CFS.

In Dr. Lange's experience, the major problem with CFS patients is the slowing down of information processing. It affects working memory, the ability to keep pieces of information in mind for immediate use. For instance, hearing a phone number and then being able to recall it five minutes later to make the call. For most CFS patients, that is impossible. The resulting frustration then makes the cognitive problem worse.

Dr. Denise Park has called this the "premature aging of the brain," meaning that the brain in a thirty-five-year-old fibromyalgia patient in Park's study (Park Dl et al, "Cognitive Function in Fibromyalgia Patients," Arthritis & Rheumatism 44, No. 9 (2001): 2125-2133) reflected the neuropsychological testing performance of a person 20 years older.

Neuropsychological testing for CFS

Dr. Lange described how she conducts neuropsychological testing. First, she conducts a thorough clinical interview, which lasts about two hours. After the clinical interview, patients receive a full I.Q. assessment.

After the I.Q. testing, she tests for memory, attention, visual, language, and motor function, and executive function including multi-tasking and decision-making. Language, visual and motor function are almost never affected, but attention and executive function are usually abnormal and often relatively impaired.

Overall, she spends a total of 20-25 hours on a case, first reviewing the medical records, then spending time with the patient in the initial interview, then hours of testing and scoring with several more hours for writing up the report.

If a patient is required to redo the testing for Social Security, Dr. Lange uses a screening tool and taps into the specific issues previously identified to keep the time and costs down. That usually takes 3-4 hours.

To test or not

If a patient is trying for Social Security disability, neuropsychological testing is the only objective test to show a dysfunction in the brain. MRI and SPECT scans are not standardized for CFS. Again, Dr. Lange pointed out that there are no focal injuries in CFS. It is a diffuse assault of the central nervous system in the brain, so static MRI scans are generally normal.

Dr. Lange urged patients to carefully think about undergoing neuropsychological testing before paying the expense of the testing procedures. She recommended discussing it with a patient's physician before moving forward to identify a clinical neuropsychologist with knowledge about cognitive function in CFS.

Dr. Lange also recommended patients proceed with integrative medicine because a CFS patient must approach the chronic condition in an integrative fashion. That includes pharmacological approaches, but also complementary alternative methods such as low impact physical modalities—tai chi and Qi Gong are two techniques that patients can do at their own pace. Dr. Lange underscored the importance of "coaching," an intervention that can help patients learn ways to gain a modicum of control back over their lives and ultimately, feel better.