Summary of 2011 IACFS/ME Conference by Rosamund Vallings

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Last Updated: 05 December 2015 05 December 2015

[With thanks to Dr. Vallings for giving permission to post her summary on this website. Ed.]

Summary of IACFS/ME conference, September 22-25,2011, Ottawa, Canada

by Rosamund Vallings MB BS

The conference opened with the keynote speaker, Christine Kozak (Bethesda, USA), who discussed and clarified issues relating to “Gammaretroviruses of mice and their links to Prostate cancer and CFS/ME”. She described how MLVs cause leukaemias in mice, and penetrate right into the cell nucleus, and can be transmitted genomically. There are 3 categories: ectotropic, xenotropic and polytropic. The latter two are distributed widely in house mice species.

Xenotropic viruses have a wide range of hosts, and there are 5 functional variants of receptors. XMRV can replicate in some species of mice. Various host factors restrict XMRVs in mice, such as serum factors, receptor block, receptor variation, Apobec 3 and Fv1 (both of which can block viral replication at the reverse transcriptase stage) and tetherin at the budding stage.

Humans do not have Fv1, but have TRIM5αa retrovirus restriction factor. The conclusion was that MLVs and ERVs are found in house-mice worldwide. Receptor variants have evolved in mice carrying XMRVs. XMRV has a distinct host range. XMRV contributes to induced neoplastic diseases. Multiple host restriction factors limit virus transmission. Contamination may be the reason we see this virus in humans.

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Virology research

XMRV mouse retrovirus involvement in ME/CFS controversy

G.Simmons (San Francisco, USA) discussed multi-laboratory evaluations of XMRV detection assays. He presented work investigating the prevalence of XMRV in blood donors. Published work on 22/9/11 in Science Express showed a failure to detect XMRV in any sample. Only one lab found clinical samples to be nucleic acid test (NAT) positive. These positives were not reliable among replicates. Using a number of techniques, there was very little correlation between positives from the original WPI study and other assays. The conclusion was that routine screening of blood donors for XMRV is not warranted.

K.de Meirleir (Brussels, Belgium) detected anti-XMRV antibodies in the serum of patients and healthy blood donors. Of 84 Belgian CFS patients, 21 had developed CFS after receiving a blood transfusion. Controls were 44 healthy blood donors. 57% of CFS patients and 16% of controls tested antibody positive. 10 of the 21 CFS patients who had had a blood transfusion tested positive. PCR was not used. Western blot was used to confirm the serology data. These results were statistically significant. Samples were blinded and analysed at the WPI.

M.Hansen (NY, USA) presented work looking for MLV-like gag sequences in blood and cell lines incubated with plasma from CFS patients and controls. 30 were patients from D.Bell, 24 from S.Levine and 12 controls from Ithaca, NY. No XMRV was detected in the Bell group. Cells were cultured for 30 days—some gag sequences were found but no other retroviral sequences could be found. There were no statistical differences between patients and controls. Everything possible was done to avoid contamination. The Levine samples were all negative for gag sequences. This research is ongoing.

J.Mikovits (Reno, USA) and J.Coffin (Boston, USA) discussed the case for and against human gammaretroviruses in CFS. Mikovits outlined her earlier work involving detection of XMRV. As well as identifying the virus in a significant number of patients, their lab have identified an inflammatory cytokine and chemokinesignature that distinguishes XMRV-infected patients from controls with 94% sensitivity and specificity. Further tests are being developed for detection and characterisation of XMRV. Coffin’s lab had looked hard for XMRV in mice, and did not find it in any mouse strain tested, but found an XMRV ancestor in the mouse genome. A detection assay has been developed. He pointed out that XMRV is a virus and MLV is not a virus, but fragments.

Mice are extremely widespread, and mouse DNA can be found on laboratory surfaces and can contaminate common reagents and materials. Most virologists now consider XMRV to be a consequence of a collection of artifacts originating from endogenous MLVs prevalent in the laboratory. It is likely to be an accidental laboratory creation from the 1990s. It is yet to be worked out how it has got into clinical samples from CFS patients.

ME/CFS after SARS and other immunological findings

Post-SARS Syndrome was outlined by H. Moldofsky (Toronto, Canada). SARS results from infection by a coronavirus A. It creeps into the brain via the olfactory bulb in mice, and possibly via this route in humans. 250 cases occurred in Toronto, transmitted by one person who had been in Hong Kong. There were 44 deaths and 50 cases who remained ill post-SARS. These correlated with a diagnosis of CFS. Sleep was disordered and this was similar to that seen in fibromyalgia syndrome (FMS), but there was a lower rating of the alpha EEG sleep anomaly in post-SARS as compared to FMS. The myalgia was also less severe.

J.Montoya (Stanford, USA) considered the role of the immune response in CFS. Typical pathogens in CFS are involved, and are mostly intracellular. There is initial tropism (e.g., respiratory or GI) followed by involvement of target organs (eglymphatics)). Different pathogens take similar pathways. CFS may be sustained for years, and pathogens reactivate periodically. Reactivation tends to be at low levels. This leads to an immune response, but this is not strong enough to kill the organisms, so the bugs remain latent, and then reactivate again leading to symptoms. CFS is a multi-system disease with phases of immune response.

Peripheral blood studies are useful and convenient but imperfect. Immune abnormalities have been inconsistent across labs, although some are consistent. Inconsistency may be due to host variables, multiple triggers, fluctuating nature of the disease, duration and severity. There are also other non-CFS variables such as methodological variables and statistical issues. There is a need to involve all available data, apply new technology and coordinate research.

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Treatment advances

D.Strayer (Philadelphia, USA) gave an update on the use of Rintatolimod (previously known as Ampligen). They had studied the use of the drug in XMRV/pMRV antibody positive patients. Of the patients selected, 33.7% were antibody positive. The antibody negative group had lower activity for daily living scores. Those who were antibody-positive showed a significantly greater increase in exercise treadmill tolerance when treated with the drug than those treated with placebo and those who were antibody negative. The responding patients also showed a decrease in use of other medication.

The use of Rifampicin was found to augment the effects of oxymatrine (Equilibrant) in ME/CFS patients by J.Chia (Torrance, USA). Those with chronic enterovirus infection had previously been shown to benefit from oxymatrine (Equilibrant). 46 ME/CFS patients were treated with Rifampicin 300mg bd for 7 days while taking oxymatrine and compared with patients taking just oxymatrine, and a control group. Initially flu-like symptoms occurred in those taking the rifampicin plus oxymatrine, but subsequent symptomatic improvement was observed in 60%.  Short courses of rifampicin may therefore be beneficial in oxymatrine responders. Rifampicin induces nitric oxide from human aveolar macrophages causing the initial flu-like symptoms. 2nd or longer courses of rifampicin did not appear to help.

F.Friedberg (Stonybrook, NY) tested a brief self-management protocol for unexplained chronic fatigue and ME/CFS in primary care. Two self-management sessions focussing on CBT were undertaken in 3 study conditions: 1) standard medical care alone, 2) standard medical care plus nurse-delivered attention control condition of symptom monitoring and 3) standard medical care plus nurse-delivered self-management CBT. There was modest improvement in fatigue severity and patient global impression of change (PGIC) ratings in the self-management programme. Ratings tended to reflect different attitudes to the illness and/or differential exposures to negative major life events. Improved patients reported increased awareness of behaviour and affirmative steps to pursue more healthy activities. Self-management can generate improved outcomes.

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Fibromyalgia (FM)

A lively debate followed between R.Staud (Florida, USA) and D.Clauw (Ann Arbor, USA) entitled: “Are tender points necessary?”  Staud outlined the American College of Rheumatology criteria for FM (1990) which includes widespread body pain of 3 months duration and presence of 11 out of 18 tender points.  The tenderness should be with 4kg of thumb pressure.

In trials this has not been found to be reliable and a more accurate diagnosis can be made using the 2010 provisional FM criteria: 3/12 duration of pain with a widespread pain index in 19 areas with a severity scale of at least 9. This scoring system is quite different, and additional symptoms include fatigue, unrefreshing sleep, cognitive symptoms and somatic symptoms. (There is overlap with CFS).

Many different ways have been looked at for triggering pain for measurement. Emotional “windup” could be useful, but is not reliable. Tonic heat and mechanical stimulation can be applied to painful and non-painful areas. This can be used for assessment of pain or for stimulating pain. Tenderness does correlate with pain and can be measured by quantitative measurement of pain sensation (QST). For clinical purposes, tender points provide little mechanistic information about an individual’s pain and associated symptoms.

Clauw feels that tender points in diagnosis are unnecessary, and outlined 10 reasons why:

1. Convey inappropriate message about FM
2. Excludes males
3. Practitioners do not know how to do it, and often do not want to learn
4. Very few chronic pain states have a specific examination to diagnose pain
5. Tender points are an inadequate measure to assess experimental pain threshold
6. There are better ways to assess pain threshold
7. Tender points are not normally distributed
8. Tender point count was never meant to be a “physical exam” and should not replace routine clinical examination
9. No evidence that they are necessary in diagnosis
10. Is the horse dead yet?!!

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Case definitions

B.Carruthers (Canada) outlined the New International Criteria for ME. The 2003 Canadian definition has been further refined. The 6 month period is no longer required, but left to clinical judgement at 3 months. Post-Exertional Neuro-immune Exhaustion (PENE) was kept criterial and further articulated. Modifications for paediatric cases have been included. The illness is called ME rather than CFS. The Canadian definition clearly separated out genuine cases, and this new definition can be used clinically and in research and epidemiology.

L.Jason presented work contrasting case definitions. The Fukuda definition has only 4 core symptoms, which do not include post-exertional malaise. But this definition has been used by researchers for over 15 years. He compared this definition with the 2003 ME/CFS Canadian criteria and the older Dowsett ME criteria. His study suggests that the more recent criteria and the ME criteria could be used to identify patients with more homogenous and severe symptomatology and functional impairment.

His second paper describes Data Mining as being a useful tool in aiding the diagnosis of ME/CFS. An objective computer-driven decision is combined with a physician’s medically influenced decision. The Canadian criteria (compared to the Reeves 2005 criteria) were found to have more construct validity and were more accurate, identifying 87% of cases. Post-exertional malaise, neurocognitive symptoms and sleep disorders were not identified as discriminating symptoms with the Reeves criteria.

E.Unger (CDC Atlanta, USA) continued discussions about case definitions. She explained that definitions are not specific to CFS. They are used for epidemiological studies, clinical diagnosis and to determine the biological basis of disease. She stressed the importance of standardization. She asked the question “Will refining lead to a homogenous population?”, and pointed out that heterogeneity is challenging. Phenotypes are imperfect indicators of biology. Case definitions may not be sufficient to discover pathways to pathogenesis. Standardized measures will allow stratification and subtyping.

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Exercise challenge

B.Keller (New York, USA) studied the effects of fatigue on functional capacity in patients with CFS. There is a need to quantify impairment. The cardiopulmonary exercise test (CPET) measures functional impairment and is an objective measure of energy expenditure and physical work. It is validated and reliable in health and disease, but she questioned whether it was useful in CFS. The purpose of the study was to measure the effects of post-exertional malaise in CFS. She concluded that patients’ disability went from mild to moderate on first test and from moderate to severe on second 24 hours later. Looking at maximum exercise tests, it was shown that those with CFS will exacerbate symptoms associated with post-exertional malaise simply by completing normal daily activities.

C.Snell (Stockton, USA) then covered the importance of exercise challenge, and the need for a standardised measured approach in diagnosis and management.  He described fatigue as a reduced efficiency as a result of doing “work”. Some measures can be indirect (e.g., heart rate) or direct (e.g., gas exchange). Field tests are easy to administer and require minimal equipment but are unmonitored and therefore less likely to be accurate. Motivation and pacing both play a big role in the results. He discussed the PACE trial and showed that the results actually equate to 1.94 – 2.35 mph and at 2 METS this equates to 7ml/min/Kg oxygen. The NY Heart Association would classify this as “severely disabled”. Anything greater than 3mph is the anaerobic threshold for most CFS patients. Direct assessment of aerobic capcity should be the gold standard. CPET is uniquely able to quantify efficiency with measures of workload and the metabolic cost of the work. Healthy people do better on a second test, but in CFS there is a massive drop. Post-exertional malaise (PEM) is an exacerbation of symptoms after exertion. Most healthy people will recover in 48 hours, but in the group studied, only one patient with CFS recovered in 48 hours. The respiratory exchange rate (RER) is the most reliable gauge of subject effort—it encompasses an analysis of expired gases.

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Immunology

Natural killer cell (NK) function in a prospective cohort of adolescents with CFS compared to controls following infectious mononucleosis (IM) was discussed by B.Katz (Chicago, USA). He felt the study was important because NK function has been much studied and results are not always consistent. 9 with CFS and 9 matched controls were studied. Blood was taken at 6, 12 and 24 months following IM.  NK quantification and function was measured. There was no difference in NK cell numbers at each of the 3 points of analysis compared to controls. However NK cell function was higher in cases than controls at 6 months, with less differential at 12 and 24 months. The conclusion was that there was no decrease in NK cell function in this group.

However, E.Brenu (Gold Coast, Australia) looked at cytotoxic function of NK-cells and CD8+T cells in CFS, and her findings showed significant decreases in cytotoxic activity compared to controls at baseline, at 6 and 12 months. NK CD56 bright cells remained decreased in those with CFS. The study confirmed reduced immune function in CFS, and she highlighted the possibility that NK-cell cytotoxic function could be a potential biomarker.

Her second study assessed proteins and receptors secreted and expressed by CD4+T lymphocytes over time. At baseline IL-10, TNFα and IFNγ were increased in the CFS group. At 6 months, IL-2 was increased and IL-10 and IL-!7a were significantly decreased in the  CFS group, and at 12 months only IL-2 was significantly increased in the CFS group. The results suggest that the cytokine profile in CFS changes over time during disease progression. Experimental findings need to be matched with data on clinical disease progression.

The objectives of a study presented by V.Falkenberg (Atlanta, USA) were to determine the pattern of perforin gene methylation in conjunction with gene expression, and whether these features were altered in CFS. Increased promoter DNA methylation correlated with reduced perforin expression in the non-fatigued group, the relationship was not seen in CFS. Small but significant differences in methylation were detected over the day and there were differences between both groups. Further studies are needed to help explain and understand these differences.

N.Klimas (chairing this session) pointed out the importance of these papers in helping us understand the nature of the immune response and the variations over time.

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Paediatrics

G.Broderick (Edmonton, Canada) looked at the links between lymphocyte metabolites and the clinical course of post-infectious fatigue in a group of adolescents following infectious mononucleosis (IM). They were followed over 2 years and 3 clinical courses were distinguished. 1) sustained increase in fatigue after early partial remission 2) a monotonic decrease in fatigue and 3) slow decrease in fatigue after a peak at 12 months. They surveyed lymphocyte gene expression. 107 genes were differentially expressed. 40% were linked to immune metabolism and 20% to immune signalling and cell functioning. Gene expression supports directed functional interaction. Processes are linked to the biochemistry of the stress response. Phenylalanine metabolic activity supported the separation of the fatigue sub-groups. High activity was linked to a more favourable prognosis. Results correlated with the clinical course over 2 years.

T.Miike (Hyogo, Japan) presented a fascinating overview of the daily life of children in Japan, with emphasis on their vulnerability for developing CFS. These children are subject to sleep deprivation as a result of modern daily life in Japan, and developed abnormal sleep rhythms. He discussed the importance of reducing risk of developing CFS by attention to children’s daily life and lifestyle in Japan.

S.Tajema (Kobe, Japan) confirmed the relationship in Japan between the abnormal biological clock system and childhood chronic fatigue. At their newly-formed centre, they are now treating this disorder. In the study, the treatment of children with CFS with bright light therapy, thermal therapy (20 minutes of 60̊C to the head), medication (melatonin, clonidine and sedative psychotropics), CBT and lifestyle training over 8 weeks was presented. Circadian rhythm and sleep disorders were much improved, but other symptoms of CFS were not significantly improved at this time. Recovery from the sleep disturbances is looked on as the first stage of improvement for these patients.

K.Rowe (Melbourne, Australia) had seen 788 paediatric patients (aged 6-18) between 1991 and 2009, and she presented follow-up to look at the natural history of the illness. The average duration of the illness was 5 years, with a range of 1-15 years. By 5 years, 60% reported recovery. By 12 years 88% reported recovery, but in approximately 1/3 of these they reported conscious monitoring of their workload. Less than 5% were not working or studying, often due to factors other than CFS, such as marrying or having children. 90% completed or intended to complete post-secondary training. Treatments used were studied and the only alternative practitioners who were deemed helpful were those providing relief of muscle pain with massage or who provided good dietary advice. Restrictive diets and supplements did not reach placebo levels of response. The important issues were balancing life to include social contact, physical activity, educational input and a commitment to attend at least one activity each week. Ability to engage in education was the best predictor of functional outcome. She concluded that the outcomes for young people in Australia with this illness are generally positive although prolonged.

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Epidemiology

L.Jason (Chicago, USA) had looked at the natural history of the illness over 10 years. His study’s major finding was that rates of CFS appear to have been relatively stable over the past decade. 67% of those with CFS continued to have CFS over time. Some of those initially diagnosed with Idiopathic Chronic Fatigue (ICF) had progressed to CFS, suggesting that ICF is a group at higher risk of developing CFS. Of those in remission, 50% went from a diagnosis of CFS to ICF, indicating that while they no longer fitted the CFS criteria, they did still suffer from fatigue. Post-exertional malaise is the cardinal symptom. Of interest 29.4% of the CFS patients had had a blood transfusion.

CFS knowledge and illness management among US healthcare providers was reviewed by E.Unger (Atlanta,USA). When looking at results for health practitioners, 94% of doctors had heard of CFS, 71% believed it was a medical and psychological illness, 14% believed it was a psychiatric illness, 37% had made a diagnosis. Studies of public knowledge indicated that 57% had heard of CFS, 27% considered it a medical condition and 2% believed it was a psychological illness. Nearly 10% of the public knew of someone with CFS. The top 3 ways in which health care providers manage CFS were: referral to a medical specialist (35%), medication (29%), and referral to a psychologist/prescribing graded exercise therapy (26%). The public sought information by talking to family doctor (72%), searching the internet (54%) and talking to a medical specialist (25%). Only 7% would join a support group.

J.Allegre (Barcelona, Spain) presented results of a study to determine the sociodemographic, clinical and therapeutic characteristics of CFS patients in Spain. The condition was found to affect mainly middle-aged, educated women. Onset most often occurs following an identifiable trigger, such as infection, delivery or stress, and was sudden in 20%. At the time of diagnosis 62.5% were not working. Treatments were: symptomatic medication (analgesics, antidepressants, anxiolytics) in 78.3%, alternative treatments in 3% and physical exercise and/or CBT in 5%.

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Genomics and genetics

Expression patterns of genes relevant to immune function were discussed by E. Brenu (Gold Coast, Australia). Her study confirmed changes in microRNA expression in cytotoxic cells that may be related to the poor function of these cells in CFS patients.

M.Rajeevan (Atlanta, USA) had looked at the immune and inflammatory alterations in CFS to determine if genetic variants in inflammation and immune pathways could be linked to CFS, as well as to quantitative measures of functional impairment, fatigue and symptom inventory. Compared to controls, CFS was associated with 34 functionally relevant single nucleotide polymorphisms (SNPs). 12 of these are in pathways related to complement cascade, chemokines and cytokines/cytokine signalling and Toll-like receptor signalling. Differences in these associations found for subjects with exclusionary conditions otherwise meeting criteria for CFS, suggests important differences between these groups.

L.Bateman (Salt Lake City, USA) presented work to determine whether baseline and/or post-exercise expression of genes involved in signalling and modulating sensory fatigue and muscle pain are potential biomarkers for distinguishing those with CFS and FM from healthy controls. At least 2 sub-groups of patients were identified by gene expression following exercise. The larger subgroup showed increases in mRNA for sensory ion channels and adrenergic receptors and a cytokine. Symptom severity was associated with greater post-exercise increases in these genes. The smaller subgroup were mainly patients with orthostatic intolerance and there was no post-exercise increase in any gene, and was defined by decreases in mRNA for α2A adrenergic receptor. The FM only patients were identified by baseline increases in 3 genes. Post-exercise increase in 4 genes distinguished CFS from controls, and could be an objective biomarker for CFS. Diagnosis based on gene expression may eventually be possible.

Following work with Gulf War veterans, L.Steele (Waco, USA) investigated, with a small sample whether exposure to neurotoxicants are risk factors for developing Gulf War Illness (GWI). Some troops who were exposed however did not develop illness, so genetic differences may have been implicated.  Findings are supportive that GWI may be associated with the PON1 genotype. PON1 is a detoxifying enzyme. GW veterans whose PON1 genotype is known to provide slower hydrolysis of some organophosphate pesticides are at greater risk of GWI in relation to reported use of pesticides and prolonged use of pyridostigmine. And GW veterans who carry the R allele PON1192, which is known to provide inefficient hydrolysis of sarin were at increased risk of GWI if they had heard chemical alarms, which indicated potential exposure.

L.Garcia (Miami, USA) compared gene expression patterns in CFS and GWI. Study was based on Jonathan Kerr’s work which had identified 79 genes associated with CFS with defined subgroups. Her group used gene activation patterns in CFS and GWI during and after exercise challenge to better understand the mediators of persistence and relapse. Kerr’s earlier findings were confirmed in the CFS group. There were significant differences when compared to controls. There were important overlaps with GWI. EB12 (an EBV induced gene) was 6-fold higher in CFS than in controls, and 2-fold higher in GWI. ETS1 was upregulated in both groups. Transcription factor 3 was markedly elevated in GWI and less so in CFS, though was significant. Apoptosis genes were markedly elevated in both groups though 400 fold higher in GWI. The overall trend however was that most of the gene regulation activities associated with CFS were not significantly different between GWI and controls. Additional genes specific to GWI have however been identified by the group. With exercise challenge, there were changes in genes at peak of exercise which were unique to CFS. This was accompanied by altered immune signalling pathways.

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Brain and neuro-endocrine functioning

I.Treasaden (London, UK) looked at volumetric changes in regional grey and white matter in CFS using Voxel 3D MRI techniques. He compared 26 CFS patients with controls. In the CFS patients there was reduced grey matter in the occipital lobes (associated with visual processing), in the right angular gyrus (involved in perceptual sequence learning, conscious awareness of actions) and in the posterior division of the left parahippocampalgyrus (associated with memory function and retrieval). There was also reduction of white matter in the left occipital lobe. This data helps to confirm a neurological diagnosis, and needs to be correlated with biochemical changes.

That there is evidence for reduced aldosterone in those with CFS was presented by R.Boneva (Atlanta, USA). Many of the symptoms in some CFS patients do overlap with those of Addison’s disease. These include orthostatic intolerance, orthostatic tachycardia and heat/cold intolerance. Maintenance of blood volume may be poor and this is dependent on regulation by aldosterone and mineralocorticoid receptors in the brain. In this study of 70 CFS patients and 212 controls, those with CFS had comparatively lower aldosterone levels. A previous study (Wichita) had reported higher plasma renin levels. Further studies should measure aldosterone response to salt restriction and postural changes.

A.Miller (Atlanta, USA) presented 2 papers. The first was on behalf of J.Jones (Atlanta, USA) using functional MRI (fMRI). It has been suggested that CFS symptoms may be linked to altered cognitive or pre-cognitive processing in the CNS. This study investigated the sense of “self” and “illness-related semantic information”. The focus was on the right anterior insula, an area associated with awareness and self-related processing. Conclusions were that there is a real alteration of body physiology in CFS. The interoceptive landscape is acquired cognitively and precognitively in an altered way, enhancing the prominence of symptoms related to fatigue.

The second paper demonstrated decreased basal ganglia activity in CFS associated with fatigue by fMRI. Results compared to controls, showed decreased activation in the right caudate and right globuspallidus. The decreased activation in the right globuspallidus was significantly correlated with increased mental fatigue, general fatigue and reduced activity. Dopamine has a central role in basal ganglia regulation, so alterations in dopamine metabolism may be involved. Dopamine transmission and metabolism in these areas may be due to activated immune pathways. Pharmacologic strategies targeting dopamine and the basal ganglia may be therapeutic possibilities.

J.Dyke (New York, USA) discussed a new brain imaging technique known as arterial spin labelling MRI was used to compare regional cerebral blood flow (rCBF) in CFS, patients with major depression (MDD) and healthy controls. The 2 patient groups were psychotropic-medication free for 1 week prior to scanning. rCBF was significantly decreased in CFS in the left anterior cingulate cortex and the right lingual region compared to controls, while those with MDD had a trend towards significantly lower rCBF in the left anterior cingulate cortex.  rCBF for CFS and MDD did not differ significantly. It is unclear whether the hypoperfusion in rCBF in CFS would account for previous observation of increased ventricular lactate. This increase could be due to oxidative stress, mitochondrial dysfunction or decreased rCBF.

Conference summary

The conference ended with an excellent over view by Anthony Komaroff (Boston, USA). He mentioned an informal meeting which had taken place to discuss multicentre research initiatives. He stressed the importance of a variety of initiatives pulling clinicians and researchers together. Forms, laboratory tests etc. need to be standardised. He pointed out that “Research Needs Money”.

IACFS/ME 2011 International Conference Summary by Dr. Charles Lapp

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Last Updated: 05 December 2015 05 December 2015

This article is reprinted with the permission of the author, Dr. Charles Lapp. Editorial notes are the author's.

By Charles W. Lapp, M.D. Director
Hunter-Hopkins Center, P.A., Charlotte, North Carolina
October 7, 2011

The biennial meeting of the IACFS [International Association for CFS/ME] was held in Ottawa, Ontario, this year. Those who expected Fall leaves and falling temperatures were greeted instead with temperatures in the high 70’s and sticky humidity. The theme of the conference could have been “Not What You Expected,” instead of “Translating Evidence Into Practice”!

While well attended, there was a notable absence of the “Old Guard” such as David Bell, Jacob Teitelbaum, Ritchie Shoemaker, Suzanne Vernon, Rich Podell, Pat Fennell, and many others. The large support groups (AFSA, NFA, CFIDS Association, CFS Knowledge) were not represented. We missed you all, but I have to say that this meeting attracted a large number of new and active participants. Overall about 200 patients and 200 providers attended, representing over 20 different countries.

Although the theme was “Translating Evidence Into Practice,” there was a dearth of papers on treatment. Nevertheless, there were a lot of new researchers and no dearth of new ideas!

This conference was kindly hosted by Lydia Nelson and the ME/CFS Action Network of Canada.

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XMRV Wars

Everybody was braced for the Point-Counterpoint between Dr. Mikovits and Dr. Coffin. However, the heat was extinguished by the introductory presentation of Dr. Graham Simmons who eloquently summarized the results of XMRV testing in 7 laboratories, all of whom were provided blinded specimens (negative controls, spiked (known) positives, and patient samples). Overall, XMRV/MLV was not confirmed in Persons with CFS (PWCs). Only Dr. Mikovits and her colleague Dr. Ruscetti found positive controls, and even these showed disagreement with replicate samples. Thus the work of Mikovits and Ruscetti seemed tainted right from the start.

Nevertheless, Dr. Mikovits (of the Whittemore-Peterson Institute, Reno NV) made a very nice presentation of her own work, explaining that she had double checked all specimens from the original article and found only 6 that were possibly contaminated, and sticking firmly to her hypothesis that XMRV is associated with ME/CFS.

Dr. Coffin (Tufts University, Department of Molecular Biology and Microbiology, Boston MA) countered with a very complicated explanation of how XMRV is most likely the consequence of artifacts originating from leukemia viruses prevalent in both wild and laboratory mice. He explained that such contaminants are widely found in labs and on work surfaces, and that many cell lines that are used to propagate viruses have been contaminated over the years.

Coffin cited the inability of other labs to duplicate Mikovits’s efforts; but Dr. Mikovits pointed out that other labs used techniques different from hers and that it took years for labs to find the HIV virus and corroborate findings. In Dr. Mikovits’s eyes, the issue is not dead (but perhaps on life support).

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Diagnosis of FM

A second debate considered whether tenderpoints are necessary or not to diagnose Fibromyalgia. This debate stems from the release of new clinical criteria that require no physical examination. These were published by the American College of Rheumatology in 2010. The physician need only check off the patient’s symptoms and record the number of painful areas on a patient in order to confirm or reject the diagnosis of FM.

Dr. Roland Staud (University of Florida) argued the superior value of tenderpoints compared to dolorimetry (a mechanical device for measuring the severity of tender points), as well as the correlation of tenderpoints with fatigue, anxiety, depression and sleep. He pointed out that tenderpoints reflect the amount of distress more than pain. He was especially negative about the new clinical criteria because it is self-reported and ‘too easy to check off boxes’ and therefore meet criteria for FM.

Dr. Dan Clauw (University of Michigan) used David Letterman’s Top Ten List format to argue against tenderpoints. He argued that tenderpoints convey an incorrect message that FM is about pain alone; that many practitioners don’t know how to test for tenderpoints; tenderpoints are not a good measure of pain threshold; and there is no evidence they are necessary to make a diagnosis.

[Ed. note:  Both debaters made excellent points but I think they missed two big ones. First, finding more than 11 tenderpoints on a patient confirms the clinical impression for the doctor, and second, tenderpoints represent a physical sign of “something wrong.” They validate for the patient and doctor alike that the pain is real and meets some internationally accepted standard. Besides, I firmly agree that patients need to be examined and touched. Just providing another checklist (like the new clinical criteria) just doesn’t do it!]

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Diagnosis of ME/CFS debate

Speaking of criteria, Dr. Bruce Carruthers (medical advisor to the National ME/FM Network, and lead author of the 2003 Canadian Clinical Criteria for ME/CFS) introduced new recommendations for the Canadian criteria. His committee has recommended abandoning the 6 month waiting period, and suggested calling ME/CFS Post-Exertional-Neuroimmune-Exhaustion (or PENE). The committee clarified some of the symptoms required in the prior criteria, and modifications were added for pediatric cases.

[Ed. note:  Enough is enough! The 2003 criteria are satisfactory and widely used. The new “changes” are really quite trivial, and the new name is ridiculous.  ME/CFS was gaining popularity with doctors and patients alike, so introducing a new name just confuses everybody.]

Lenny Jason, PhD (DePaul University, Chicago) next compared and contrasted the original Ramsey definition of Myalgic Encephalomyelitis, the 1994 CDC (Fukuda or research) criteria, and the 2003 Canadian clinical criteria. The Ramsey criteria are quite succinct, requiring only (1) acute onset of symptoms following a viral-like episode, (2) post-exertional malaise, (3) cognitive difficulties, and (4) autonomic issues. He pointed out that the 1994 Fukuda criteria emphasize fatigue over post-exertional malaise as the key symptom. Also, only 4 of 8 symptom criteria are required by the Fukuda definition, but the diagnosis would be strengthened if 7 of the 8 were required. Finally, the Canadian criteria identified more severe functional and cognitive symptoms, thereby selecting fewer psychiatric cases and more severely ill patients.

[Ed. note. We continue to use primarily the 1994 CDC criteria because they have been accepted for over 15 years and used in the majority of scientific papers, However, we also record the 2003 Canadian criteria. Clinicians should be familiar with both.]

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Various physical findings

Betsy Keller (Ithaca College, NY) described Cardio-Pulmonary Exercise Testing, pointing out that it is the most reliable and repeatable measure of functional ability in ME/CFS. She also pointed out that results do not change significantly in normal individuals who are tested and then re-tested 24 hours later. However, in PWCs the aerobic capacity  (VO₂ max), work load, heart rate, and other measures fall more than 8%, confirming the clinical impression post-exertional malaise. She pointed out that many PWCs function at very low levels (say 2-3 METS at their Anaerobic Threshold) and that it takes 1.3 METS to just sit, 1.8 METS to sit and read or write, and 3 METS to just stroll leisurely at the mall. Most activities of daily living require at least 3-5 METS, which explains why patients struggle to keep up at home.

Chris Snell (University of the Pacific, Stockton) and his group have done much to promote Cardio-Pulmonary Exercise Testing as a measure of impairment and post-exertional malaise. Today the Stevens Test-Retest Protocol is widely used for disability purposes, and was named after one member of the team, Staci Stevens. Snell pointed out that regression equations are used to estimate the aerobic work capacity and anaerobic threshold following indirect estimations of work ability (treadmill test, 6-minute walk, 1.5 miles-for-time), but are notoriously inaccurate due to assumptions made. Only exercise testing with expired gas testing is accurate. Snell also pointed out that the notorious British PACE Trial used the 6-minute walk test as a measure of improvement. At baseline, subjects walked an average of 312 meters in 6 minutes, and after 52 weeks of training they could walk 379 meters, a 21% improvement. This sounds wonderful until you realize that this is the equivalent of walking 2.35 mph (instead of 1.94 mph) for 6 minutes, or about 2 METS—still in the severely disabled category after a year of work!

Ian Treaseden (Imperial College, London) used voxel-based MRI studies to show that white and gray brain matter was decreased in PWCs in their occipital lobes (which control balance), left angular gyrus (affects perceptual sequence learning, action awareness, movement consequences), and the left hippocampal gyrus (which encodes and retrieves memory). These changes can explain many of the balance and cognitive difficulties seen in PWCs, and argue strongly for an organic basis in ME/CFS. Treaseden reassured us, however, that these changes are not permanent.

Many symptoms of CFS and can be attributed to autonomic system dysregulation, poor sympathetic nervous system control, and/or low blood volume. The latter would reduce stroke volume or cardiac output from the heart. Roumiana Boneva (CDC, Atlanta GA) investigated the possibility that low aldosterone levels lead to low blood volume in ME/CFS. Studying 69 PWCs and 212 controls, Boneva showed that the mean aldosterone was 4.46 in ME/CFS and 6.05 in controls. Neither of these is terribly low, but significantly different (OR = 1.65). The cause is unknown.

[Ed. note: this study confirms the similar study by Bell and Streeten many years ago. Also, the CDC Witchita Study showed that renin is elevated as a regulatory response to low aldosterone.]

Changing gears, Ekua Brenu, a young PhD candidate and very active researcher from Queensland AU, studied cytotoxic function and markers in PWCs at 6 month intervals to determine the stability of these observations over time. She confirmed that suppression of NK-cells (CD56) was the most reliable finding, and could be a potential biomarker for ME/CFS. On the other hand, a number of other markers (TH-1, TH-2, TH-17 cytokines, IL-1α, IL-1β, and TGF-β) varied over time.

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Etiology (causes) and biomarkers

The possibility of an enteroviral infection as a trigger for ME/CFS in some patients remains intriguing. Enteroviral infections mostly cause flu-like gastrointestinal symptoms (nausea, diarrhea) during the Summer months. John Chia MD (a pathologist and infectious disease specialist in Torrance, California) has long maintained that he and his son contracted ME/CFS from an enterovirus. Using paraffin-embedded biopsies from 132 PWCs, enteroviral protein VP1 was detected in 82% and and dsDNA in 64% of cases. He and his son both recovered by using an herbal antiviral (Equilibrant, see “Treatments” below).

Dr. Martin Lerner, an infectious disease specialist at Wayne State University (Michigan) presented an interesting poster concerning EB virus and ME/CFS. He treated 6 PWCs with valacyclovir (Valtrex, 14.3 mg/kg every 6 hours) for more than 12 months. Checking periodically for the continued presence of EBV, he found no evidence of EBV replication, but instead found “latent abortive reactive replication.” That is, the whole virus was not being manufactured in the body, but various parts of the virus were. These fragments were not infective.

Harvey Moldofsky is a sleep specialist in Toronto, and one of the first doctors to study Fibromyalgia, or fibrositis as it was known in 1975. Moldofsky reported an outbreak of SARS (Severe Acute Respiratory Distress Syndrome, a frequently fatal disease caused by the coronavirus) in Toronto. Of thousands infected, he studied 22 subjects, 21 of whom were first responder / healthcare workers, who developed chronic symptoms after infection. The symptoms included persistent fatigue, chronic widespread pain, disordered sleep, and depression. Thus, severe viral infections may be counted as one of the many triggers for CFS/ME/FM.

Adverse childhood experiences were evaluated by Jose Alegre (Hospital Vall d’Hebron, Barcelona SP) in 133 adult PWCs. Using personal interviews, childhood adverse experiences were reported by 40%. These included physical abuse (10.4%), sexual abuse (10.4%), emotional neglect (13.7%), and bullying (14.8%).

[Ed. note:  some have suggested childhood emotional traumas as one of the major risk factors for ME/CFS, while others conclude that childhood trauma may cause chronic fatigue but not ME/CFS. This paper suggests that the majority of PWCs are not traumatized, and does not prove any causal relationship between trauma and ME/CFS.]

Our old friend, Byron Hyde (Nightingale Foundation, Ottawa) was on hand to warn about a high incidence of thyroid cancer in Canadian patients. One hundred consecutive patients underwent “total body investigation” including thyroid ultrasound and/or scanning. The incidence of thyroid malignancy in this group exceeded 6000 per 100,000, whereas the natural incidence is only 30 per 100,000. Malignant nodules were usually solitary, hypervascular, and > 1cm in diameter.

[Ed note:  I have seen only an occasional thyroid malignancy in our population of patients, no more than expected. Hyde’s findings are not alarming, therefore, but will cause me to investigate thyroid nodules more aggressively.]

Mary Ann Fletcher and Nancy Klimas (University of Miami) performed prospective cytokine studies in PWCs to determine which biomarkers were most abnormal compared to controls. They found that Lymphotoxin A (or LT, increased 257%), IL4 (240%), IL6 (100%), IL 12 (120%) IL5 (95%), and Neuropeptide Y were most increased above controls, while NK cell numbers were decreased. Lymphocyte Proliferation to mitogen stimulation was decreased, and lymphocyte activation markers (CD26, CD38) were increased. They found little difference in IL13, IL10, IL2, TNFα, IFN, IL15, and IL8. These findings may lead to markers for ME/CFS, and suggest that T cells are metabolically limited in performing their helper function.

[Ed. note:  Cytokines are notoriously difficult to measure and vary over time (see Ekua Brenu’s work above). The other findings are not new. Of interest, Neuropeptide Y is frequently increased in ME/CFS and correlates best with perceived stress, anger, depression, negative thoughts, and maladaptive coping.]

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Treatments

John Chia MD ( Torrance, California) has long maintained that he and his son contracted ME/CFS from an enterovirus infection. Enteroviruses (which include the coxsackie and polio viruses) usually cause flu-like symptoms in the Summer months (atypical for influenza, which occurs in the late Fall and Winter). At the last conference in 2009 Chia reported success treating himself, his son, as well as numerous patients who had stomach biopsies positive for enteroviral protein VP1. Treated subjects were given up to 600mg per day of oxymatrine for 3 to 6 months. 52% of the treated subjects improved on a 7-point scale (much better to unchanged to much worse), while only 6% of controls improved. In this year’s account, Chia reports an enhanced response when the antibiotic rifampin (300mg twice daily for 7 days) is given concurrently with oxymatrine. Of 48 subjects treated, 32 (67%) responded to such therapy. Two-thirds had a febrile response and transient worsening of symptoms, however, when rifampin was added. Oxymatrine (with or without rifampin) appears to be an effective therapy in a subset of PWCs with evidence of enteroviral infection in the gut.

[Ed. note:  Oxymatrine is a traditional herbal Chinese medication used for the treatment of viral hepatitis, viral myocarditis, some skin disorders, and even cancer. It is thought to inhibit the pro-inflammatory cytokines TNF-alpha and IL-6. It may also inhibit Substance P (a neurotransmitter partly responsible for fibropain) and antagonizes opioid receptors. Chia currently uses the Equilibrant brand, starting at 1 pill twice daily, then 2 twice daily, then 3 twice daily (available from equilibranthealth.com). The maintenance dose is 1 pill twice daily. Adverse effects include hyperkalemia or hypertension in 1% of cases, and 10% of subjects discontinued the herb due to intolerable side effects. Chia follows patient response by measuring coxsackie B3 antibody titers, TNF-α, and the IL-12/IL-10 ratio.]

An Ampligen update was provided by Dr. David Strayer (Hemispherx Biopharma Inc, Philadelphia), who reminded us that in previous studies 40 weeks of  Ampligen therapy improved exercise tolerance by 16.6% (compared to 4.8% on placebo) and reduced concurrent medication use by 72% (56% on placebo). In the current study, 208 Ampligen subjects were analyzed for antibody against XMRV. 33.7% of subjects were positive for XMRV. These subjects were sicker (as measured by activities of daily living and actigraphy). On treatment with Ampligen these same subjects demonstrated a 14% greater exercise response and 24% more reduction in medication use, compared to XMRV-negative subjects.

[Ed. note:  The generic name for Ampligen has now been designated as “rintatolimod” by the World Health Organization. Rintatolimod is considered a toll-like receptor agonist (TLR3 agonist). Although XMRV has been discredited by many, this study suggests that persons with antibody to XMRV are sicker than non-positive subjects, but respond better to rintatolimid treatment. Ampligen remains an experimental treatment for ME/CFS, and is available on a cost-recovery basis only at 4 centers in the USA, including the Hunter-Hopkins Center. Potential subjects must meet specific criteria and be approved.]

Fred Friedberg (University of NY/Stony Brook) exposed 68 persons with CFS (40%) or unexplained chronic fatigue (60%) to a Fatigue Self Management Course (n=21), usual medical care plus symptom monitoring (n=26), or usual medical care (n=21). The course involved two sessions with a nurse educator who discussed relaxation, pacing, cognitive coping strategies, walking, pleasant activities, and social support with the subjects. To make a long story short, the Fisk Fatigue Score and Patient Global Impression of Change both improved for those who received the self management course, which was attributed to education, better awareness, and behavioral or lifestyle changes in those who took the course. Those who did not improve generally experienced negative external stressors during the study, such as divorce or financial distress.

[Ed. note:  Education and understanding of the condition are stressed at the Hunter-Hopkins Center for just these reasons – patients do better when they are better informed. For those who seek more self help, I suggest taking the online course with Dr. Bruce Campbell (cfsselfhelp.org) or tackling the self-guided course produced by Drs. Lapp and Campbell at treatCFSFM.org.]

Two old friends, Richard Van Konynenburg and Norman Booth, presented posters again this year supporting their hypotheses.

Rich Van Konynenburg posits that gluthathione depletion causes a partial blockage of the metabolic methylation cycle, which in turn can explain many ME/CFS symptoms.  In 2009 he presented a treatment protocol, which he recommends again this year. Details can be found at aboutmecfs.org/Trt/TrtMethylStudy09.pdf, but in brief summary he recommends gently unblocking the methylation cycle by using 200 mcg of folate, 200 mcg of folate as folic acid and methyl-folate (Actifolate™, Metagenics Labs), a small amount of multivitamin, phosphatidyl serine 500mg, and hydroxycobalamin (oral B12) 2000 mcg. Konynenburg warns about using excessive amounts of these supplements.

Norman Booth once again presented Dr. Sarah Myhill’s hypothesis that mitochondrial function is blocked or failed in ME/CFS. An excellent summary of her work and recommendations can be found at drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure. In 2009 Dr. Booth explained a test of mitochondrial function that demonstrated decreased mitochondrial function in 70 of 71 PWCs, compared to a control group of 53 normal healthy subjects. The poster presentation this year focused on a therapeutic protocol consisting of pacing (rest periods and limit setting), a nutritious diet, nutritional supplements, and detoxification. All patients on the protocol moved up at least one point on the Bell Activity Scale (see drlapp.com/more-hhc/forms-and-patient-information, then click on “Adult Forms”), and some as much a 6 units. Booth and Myhill conclude that “whatever the cause of CFS/ME, mitochondrial dysfunction which can affect every cell in the body is a major factor.”

[Ed. note:  the diet mostly avoided dairy and gluten, but also limited sugar, caffeine, alcohol, aspartame, and MSG. Detoxification was accomplished by infrared sauna therapy. The supplements simply included a multivitamin, B12, vitamin D, CoQ10, and glutathione.]

GcMAF (pronounced “gee-see- MAFF”) is the newest fad in ME/CFS treatment. This compound is thought to activate macrophages that are not responding properly, whereby it is also known as Macrophage Activating Factor (MAF) derived from Vitamin D Binding Protein. GcMAF starts as an amino acid attached to three different sugars. B-lymphocytes cleave one sugar, and T-lymphocytes cleave the other, leaving just an amino acid – sugar complex. This complex (GcMAF) binds to dormant macrophages and activates them.

Macrophages are the “police” or “first responders” in our immune systems. When they contact “foreigners” such as viruses or bacteria, macrophages signal lymphocytes of the invasion, then gobble up the invader. Drs. Kenny DeMeirleir (Vrije University, Brussels BE) and Paul Cheney (Asheville NC) presented treatment papers featuring this compound, which has also been tried as an immune modulator in HIV and cancer.

DeMeirleir injected 0.25 to 1 ml weekly (subcu or intravenously) into adult subjects for up to 40 weeks. All were XMRV/MLV positive. He reported that 68/108 (63%) reported “noticeable improvement” in fatigue, sleep quality, pain, neurocognitive function, recovery time, orthostatic intolerance and digestive problems. Side effects occurred in 18%, mostly headache or sleep disturbance, and 7% dropped out due to these symptoms.

Cheney treated 21 patients for at least 2 months with sublingual GcMAF. 10/21 showed improvement in symptoms, and 5/21 failed to respond or got worse. Most subjects experienced exacerbation of their CFS symptoms, and two developed Vitamin D toxicity.

[Ed. note:  We are all seeking new treatments for ME/CFS but I don’t think this is it. These posters only described very modest improvement, numbers were small, and side effects were legion. I have now seen several patients who were involved in these studies and they report utter failure. At one time there was a voluntary website where subjects could report their results. When I checked the site, none reported any significant response, but the website has since been shut down.]

Tomohiro Sugino (Soiken Pharmaceuticals, Japan) offered that oxidative stress is very high in PWCs, so anti-oxidants are likely candidates for therapy. He treated 207 fatigued individuals (not ME/CFS) with imidazole dipeptides (carnosine and anserine derived from chicken breast), using 200mg or 400mg daily, compared to placebo. Fatigue (measured by Visual Analog Scale) was reportedly much improved at both doses, especially 400 mg daily. [Ed. note:  is this the next “5-Hour Energy” treatment?!]

EECP, or Enhanced External CounterPulsation, is a technique typically applied to persons with angina or congestive heart failure. Balloon-like leggings expand rapidly during the diastolic (relaxation) phase of the heart, pumping blood from the lower extremities to the heart. This increases cardiac output and improves coronary artery perfusion. Because stroke volume and cardiac output have been reported reduced in PWCs, Derek Enlander (NY, NY) treated 20 ME/CFS subjects without coronary artery disease with EECP for 7 weeks. There were no adverse events. There was a modest improvement in the patients’ overall well-being ( KPS from 56.2 + 8.3 to 62.1 + 9.6), while stroke volume and cardiac output did improve significantly.

[Ed. note:  I have had two patients who underwent EECP. One had cardiac disease, the other did not but did not meet criteria for ME/CFS either. Both reported remarkable improvement of their fatigue and other symptoms. Except that this technique is costly and time consuming, there might be benefit for selected patients.]

I have included one study in the treatment section that might fit as well into epidemiology. Irma Pinxterhuis (Oslo University Hospital, NO) entitled her poster, “What Can Be Done To Prevent Deterioration and Promote Occupational Performance.” Studying 15 severely affected women over time, Pinxterhuis aptly defined what helped and did not help. Improvement was affected negatively by lack of support and understanding, expectations or demands from themselves and others, and financial insecurity. What helped is worth emphasizing:

• Support of health care providers and others
• Social support
• Stress management
• Lowered expectations for themselves and from others
• Balanced nutrition and healthy or whole foods

Pinxterhuis wrote, “they needed above all peace of mind and a feeling that they and their family were taken care of, so that they could use all their energy on getting better.”

[Ed. note:  Who has worked with severely ill persons and not wondered, “What can be done?” I would add to the guidelines above:  Limited mental activity (reading, writing, computing, concentrating); very low activity levels, proceeding slowly (supine range of motion > range of motion with light resistance > very light aerobic activity); minimizing medications and supplements; and prescribing low doses of medication and increasing slowly.]

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Epidemiology/general

Lenny Jason (DePaul University, Chicago) discussed the Natural History of chronic fatigue (not Chronic Fatigue Syndrome) based on two studies performed—about 15 years apart—in an ethnically and socioeconomically diverse community population. In 1995-1997 his team examined 213 PWCs medically and psychologically. The prevalence of ME/CFS in 1995 was 0.42%. Sixty-seven percent of these individuals still had ME/CFS 15 years later. Interestingly, of the new cases of ME/CFS, 75% came from the earlier group with Chronic Fatigue, suggesting that this group is at higher risk for developing ME/CFS. On the other hand, 50% of the ME/CFS remitters still had severe Chronic Fatigue but no longer met case definition criteria. Of all variables studied, “post-exertional malaise” best distinguished PWCs from those with chronic fatigue alone.

“CFS Knowledge Among U.S. Healthcare Providers” was discussed by Elizabeth Unger MD PhD, the new head of ME/CFS at the CDC. Unger’s group used a web-based survey of primary care providers and a consumer mail survey to ask questions about CFS knowledge and management. Remarkably, 94% of providers had heard about CFS compared to only 57% of the public. When asked if CFS was both medical and psychiatric, 71% of providers agreed compared to 30% of the public. Fourteen percent of providers considered CFS purely psychiatric. Only 37% of providers had ever made the diagnosis of ME/CFS, and these were more likely to consider ME/CFS a medical condition. The top methods for management were listed as:  refer to a medical specialist (35%), prescribe drugs (29%), refer to a psychologist (26%), or prescribe graded exercise therapy (26%). Consumers would seek information about ME/CFS by talking to a family doctor (72%), searching the internet (54%) and talking to a medical specialist (25%). Only 7% would join a support group.

[Ed.note:  It is remarkable to me that over one-third of providers had diagnosed ME/CFS, but about 80% of persons with ME/CFS still have not been diagnosed. Providing internet tools and information to family doctors would seem to be the best method of educating both providers and consumers.]

The natural course of ME/CFS was described by Dr. Katherine Rowe, a pediatrician from Melbourne AU. She followed 788 children (ages 6-18, mean 15, male:female::1:3). She obtained a history and exam from 398 of them, who were then queried every 2 years, and 390 who provided history only were contacted in 2010-2011. Follow-up data was obtained on 86% and 78%, respectively. Bottom line: within 5 years 60% reported recovery and at 12 years 88% reported recovery, although one-third were consciously monitoring their activity. More than 95% were working or studying part or full time. What helped them most to recover were symptom management, continuing social contact, physical activity, and engagement in education (the best predictor of outcome). Massage and diet advice was helpful, but restrictive diets and supplements were not.

[Ed. note: To my recollection, Dr. David Bell reported an 80% recovery rate over 15 years in his Lyndonville population of children. This is in keeping with Rowe’s findings, which suggests that the prognosis for children is far better than for adults. Bell and Rowe have both pointed out, however, that “recovery” is relative, and many children must continue to pace, set limits, and monitoring activity well into adult life. Note that continuing engagement in education was the best predictor of outcome.]

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Genomics

Researchers continue to look at the genomics of ME/CFS. Ekua Brenu (PhD candidate from Bond University AU) examined microRNAs (miRNAs) that modulate gene expression in PWCs, particularly those that modulate CD8 cells and Natural Killer cells. Both of these subsets are reduced in ME/CFS. She studied 30 PWCs and compared results from 30 healthy controls. Of the 15 miRNAs studied, six were down-regulated in ME/CFS compared to controls, substantiating that miRNAs may be responsible for poor function of these cells in ME/CFS.

One of the most enlightening studies of the meeting was performed by Drs. Alan and Kathleen Light, and presented by Dr. Cindy Bateman. The Lights compared the gene expression response to exercise in 48 PWCS (15 had CFS only, 33 had CFS+FM) to 49 controls, 20 persons with Multiple Sclerosis, and 18 persons with FM only. Subjects rode an Airdyne bicycle for 25 minutes at 70% of their maximum predicted heart rate, and mRNA was measured at 30 minutes, 8, 24, and 48 hours after exertion.

Patterns of gene expression were remarkably different in each group. Of patients with CFS only there was a subset of 5 / 15 who showed a notable reduction in Ad2A, or α-adrenergic receptors. Of these, 71% had orthostatic intolerance such as Neurally Mediated Hypotension or Postural Orthostatic Tachycardia Syndrome. In addition, gene expression patterns were able to distinguish:
o    likelihood of orthostatic intolerance
o    FM versus ME/CFS
o    FM only from Major Depressive Disorder, and
o    the severity of ME/CFS
[Ed. note:  This technology shows real promise as a marker for persons with ME/CFS or FM. ]

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Primer

There is no good source of up-to-date accurate information on the diagnosis and treatment of ME/CFS. The IACFS has stepped in to resolve this problem. A committee of 11 members has developed a brief (less than 30 pages) Primer of ME/CFS. The booklet is currently in its final draft stages and will be made available in the near future. Members of the Primer committee include Ken Friedman, Alison Bested, Ros Vallings, Fred Friedberg, Rosemary Underhill, Alan Gurwitt, Lenny Jason, Staci Stevens, Nancy Klimas, Cindy Bateman, and Chuck Lapp.

Coalition 4 ME/CFS

Many of you may be aware that over the next two years the manner in which illness is defined will be changing radically. Not only is the World Health Organization revamping its disease codes, but by January 2013 the National Center for Health Statistics will unveil the new International Classification of Diseases (ICD-10 CM). The latter is a totally new system of categorizing illness. How a disease gets categorized makes profound differences with respect to validity and understanding as well as reimbursement amounts and insurance issues.

To this end, the Coalition will be sending letters and ‘lobbying’ all agencies involved in the categorization process.

Currently CFS is classified under “Symptoms and Signs, Malaise and Fatigue,” and the Coalition proposes moving CFS to “Diseases of the Nervous System.” Post Viral Fatigue Syndrome is currently classified as “Other Disorders of the Brain,” and the Coalition proposes moving PVFS to “Diseases of the Nervous System” also. ME is currently referred to as “Benign Myalgic Encephalomyelitis” and the Coalition proposes to redefine ME as “Myalgic Encephalomyelitis (benign).” The major point here is that ME is anything but benign to one who suffers with it, but the WHO and the NCHS insist on keeping the word “benign” because “ME does not lead to imminent death.” [Ed. note:  perhaps “non-fatal” would be a better descriptor than “benign”!]

The proposals take CFS and PVFS out of the “just fatigued” category and separate them from psychological disorders that also cause fatigue; they would bring the USA into alignment with the WHO classifications already in effect in Canada and Germany; and they support the recommendation of our CFS Advisory Committee to the Department of Health and Human Services.

If asked to support the Coalition 4 ME/CFS, please give their proposals careful consideration!
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I have chosen to limit this review to the presentations that I believe would be most informative and most appreciated by clinicians and patients. This is not meant to be an exhaustive review. Presentations are summarized to the best of my ability, recognizing that errors, omissions, and misinterpretation are all possible. I apologize for any misinterpretations, and welcome your comments or corrections.

Charles W. Lapp, MD, Director
Hunter-Hopkins Center, P.A., Charlotte, North Carolina
October 7, 2011

This material is copyrighted, but may be reprinted with permission of the author and with appropriate credit.
Contact drlapp at drlapp.net.  (© 2011)