Tuesday, February 28, 2012

dorsal root ganglia channelopathie associated with severe fibromyalgia


A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

Gilberto Vargas-Alarcon, Edith Alvarez-Leon, Jose-Manuel Fragoso, Angelica Vargas, Aline Martinez, Maite Vallejo and Manuel Martinez-Lavin

For all author emails, please log on.
BMC Musculoskeletal Disorders 2012, 13:23 doi:10.1186/1471-2474-13-23
Published: 20 February 2012

Abstract (provisional)


A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM); and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7) act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms.


We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP) were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637.


The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036) mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88) than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002) and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001).


In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that some patients with severe FM may have a dorsal root ganglia sodium channelopathy.

Monday, February 27, 2012

Lois Owen, another ME patient who has died because CBT psychiatrists have blocked proper research and treatment for ME

Derby Telegraph, Monday, February 27, 2012:

"SIX words and she would be exhausted."

That was how Roger Owen explained his daughter's reluctance to be visited by doctors.

"She just couldn't cope with any more information than that," he said. "Even her lunch took four hours to eat because chewing used up energy."

University graduate Lois Owen, 34, died after her weight plummeted to just 3st 2lbs (20kg), leaving her exhausted and barely able to move.

She had battled for years with chronic fatigue syndrome and medics said she also had anorexia.

Neither Mr Owen or his wife could face sitting through the inquest held into her death. Mr Owen attended only to give evidence.

He told the hearing that those involved in Lois's care were "powerless" as everything they tried – from home visits to admitting her to hospital – made her condition worse.

Even Lois's GP said the best course of action was to allow her to remain bed-bound, at home with a team of carers.

Chronic fatigue syndrome is a disorder that affects one in 250,000 people in the UK and results in extreme tiredness. The cause is not known and there is no cure

Treating Autism With Antibiotics (France 3 TV, Feb 17, 2012)

Monday, February 20, 2012

Christopher R. Snell: it is only a matter of time before biomarkers are identified, etiologies understood, and remedies devised for ME/CFS


An International Perspective on the Future of Research in Chronic Fatigue Syndrome

Edited By: Christopher R. Snell

ISBN 978-953-51-0072-0, Hard cover, 104 pages
Publisher: InTech
Publication date: February 2012
Subject: Medical Genetics, Immunology, Allergology and Rheumatology

While the chapters in this book are a long way from solving the enigma that is CFS, they do represent important attempts to understand this complex and perplexing disease. A common theme in them all is CFS as a multisystem disease with the possibility of more than one cause and influenced by a variety of interacting factors. Further, they acknowledge the reality of CFS for persons with this disease and the importance of finding causes, treatments and ultimately a cure. As advanced biomedical research techniques are increasingly applied to the study of CFS, it is surely only a matter of time before biomarkers are identified, etiologies understood, and remedies devised.

See also: Pacific Labs in California (Snell, Stevens et al): it is dangerous to put patients with M.E. through a graded exercise program

Saturday, February 18, 2012

British Journal of Cancer February 2012: involvement of XMRV in the pathogenesis of MCC and prostate carcinomas remains unclear

British Journal of Cancer , (16 February 2012) | doi:10.1038/bjc.2012.51


No evidence for the involvement of XMRV or MCV in the pathogenesis of breast cancer

G Khan, P S Philip, M Naase and K M I Al Zarouni


The aetiology of breast cancer remains elusive. A viral aetiology has been proposed, but to date no virus has been conclusively demonstrated to be involved. Recently, two new viruses, namely Merkel cell polyomavirus (MCV) and xenotropic murine leukaemia virus-related virus (XMRV) have been identified and implicated in the pathogenesis of Merkel cell carcinoma (MCC) and familial form of prostate cancer, respectively.


We examined 204 samples from 58 different cases of breast cancer for presence of MCV or XMRV by PCR. Samples consisted of both malignant and non-malignant tissues. Additionally, we included 6 cases of MCC and 12 cases of prostate cancer as potential controls for MCV and XMRV, respectively.


All of the breast cancer samples examined were negative for both MCV and XMRV. However, 4/6 MCC and 2/12 prostate cancer samples were found to be positive for MCV and XMRV, respectively. Sequence analysis of the amplified products confirmed that these sequences belonged to MCV and XMRV.


We conclude that there is no evidence for the involvement of MCV or XMRV in the pathogenesis of breast cancer. What role these viruses have in the pathogenesis of MCC and prostate carcinomas remains to be demonstrated.

Thursday, February 16, 2012

Mitochondrial myopathy presenting as fibromyalgia

Mitochondrial myopathy presenting as fibromyalgia: a case report
Mishal Abdullah, Sahana Vishwanath, Amro Elbalkhi and Julian L. Ambrus
For all author emails, please log on.

MA: mishalabdullah@hotmail.com
SV: sahana_vishwanath@yahoo.com
AE: amrbalkhi@yahoo.com
JLAJr: jambrus@buffalo.edu

Journal of Medical Case Reports 2012, 6:55 doi:10.1186/1752-1947-6-55
Published: 10 February 2012
Abstract (provisional)
To the best of our knowledge, we describe for the first time the case of a woman who met the diagnostic criteria for fibromyalgia, did not respond to therapy for that disorder, and was subsequently diagnosed by biochemical and genetic studies with a mitochondrial myopathy. Treatment of the mitochondrial myopathy resulted in resolution of symptoms. This case demonstrates that mitochondrial myopathy may present in an adult with a symptom complex consistent with fibromyalgia.

Case presentation
Our patient was a 41-year-old Caucasian woman with symptoms of fatigue, exercise intolerance, headache, and multiple trigger points. Treatment for fibromyalgia with a wide spectrum of medications including non-steroidal anti-inflammatory drugs, antidepressants, gabapentin and pregabalin had no impact on her symptoms. A six-minute walk study demonstrated an elevated lactic acid level (5mmol/L; normal <2mmol/L). Biochemical and genetic studies from a muscle biopsy revealed a mitochondrial myopathy. Our patient was started on a compound of coenzyme Q10 (ubiquinone) 200mg, creatine 1000mg, carnitine 200mg and folic acid 1mg to be taken four times a day. She gradually showed significant improvement in her symptoms over a course of several months.

This case demonstrates that adults diagnosed with fibromyalgia may have their symptom complex related to an adult onset mitochondrial myopathy. This is an important finding since treatment of mitochondrial myopathy resulted in resolution of symptoms.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.


Mitochondrial myopathies are disorders characterized by morphological abnormalities of
muscle mitochondria. Accumulating evidence suggests that mitochondrial disorders are
among the most common inherited metabolic diseases [10]. Similar to fibromyalgia,
patients may present with muscle weakness, pain, fatigue and exercise intolerance that
progressively worsens over time.
Several steps are involved in Adenosine-5'-triphosphate (ATP) generation in the
mitochondria, and defects in any part of the cycle may impair energy production leading
to symptoms [11]. These abnormalities in generation and utilization of ATP can be
assessed by specific tests, which as in our patient pointed towards problems in energy
metabolism [12].

Genetic testing with sequencing of the mitochondrial genome and
chromosomal genes affecting mitochondrial function may also be pursued, as was
performed in our patient. Mutations in POLG1 and several mitochondrial genome
polymorphisms were noted. our patient was started on a regimen of coenzyme Q10 (Co-Q10;
ubiquinone), creatine, carnitine, folic acid and α-lipoic acid. Co-Q10 transports electrons
between complex I and complex III of the mitochondrial respiratory chain and has been
shown to improve mitochondrial function in several studies [13]. Creatine generates
additional ATP through the creatine phosphate shuttle. Carnitine enhances transport of
fatty acids into the mitochondria. Folic acid is a cofactor for several mitochondrial
enzymes, while α-lipoic acid is a strong antioxidant [14]. Although this treatment
regimen was started several years after symptom onset, within the first few months our
patient showed tremendous improvement. With continued therapy, her complaints
dissipated over several months, with a gradual but sustained resolution of all symptoms.


Tuesday, February 14, 2012

CDC: ME is accompanied by neurologic and muscular signs and has a case definition distinct from that of CFS

‎"The name myalgic encephalomyelitis (ME) was coined in the 1950s to clarify well-documented outbreaks of disease; however, ME is accompanied by neurologic and muscular signs and has a case definition distinct from that of CFS."


See also: The main characteristic of ME is an abnormally delayed muscle recovery after doing trivial things, if you don't have that, you don't have ME

Sunday, February 12, 2012

a deepening state of apartheid for people with disabilities

Ian Birrell 7 Feb 2012


What would you think if you heard the Home Office was colluding with newspapers to fuel hatred against gay people? Or if affable Ken Clarke at the Ministry of Justice fed propaganda to broadcasters designed to disparage ethnic minorities? There would, quite rightly, be an outcry.

This is the issue confronting another minority - and one far more ostracised in society. Ministers at the Department for Work and Pensions, desperate to force through cuts to their budgets, have demonised disabled people with smears designed to give the impression that many are cheats and scroungers.

Daily life is already tough enough for the disabled. A majority of Britons believe most people see them as being inferior. Little wonder they find it harder to get a job, are more likely to live in poverty and, increasingly, are victims of hate crime.

Typical is a case heard last week when a teenager attacked a man walking along the street, shouting: "He's disabled. He deserves everything he gets."

The charity Scope has revealed increasing antagonism towards disabled people, with two-thirds saying they have experienced recent abuse.
This dark new mood is terrifying for people who struggle to access things the rest of us take for granted: not just jobs but public transport or a meal out. It destroys confidence and makes people change behaviour; I know one man who barely left home after being targeted and others who always ensure they are back before dark.

This is shocking enough. But what is so scandalous is that a government department - run by ministers calling themselves compassionate Conservatives - has fuelled this disturbing new climate. It distorts data, manipulates facts and misuses statistics to feed a false media narrative that scapegoats the vulnerable.

So they give the impression that fraud is commonplace, conflate benefits designed to support people in jobs with those supporting people unable to work, and encourage the idea that filling in a simple form is the passport to a life of luxury at taxpayers' expense. Oh yes, with an expensive car thrown in, even if your child just has mild behavioural issues.

The facts are very different: levels of fraud for disability benefits are significantly lower than for other benefits, with more money wasted by officials making errors. Not that we hear much about maladministration, do we? Nor that taxpayers save more by disabled people not claiming than is spent on overpayments.

Instead there is a spate of drip-fed stories about "scroungers" and a decline in sympathetic articles - not just in tabloids but in broadsheets and on the BBC. Columnists talk about the "fake" disabled, or think it witty to say we should all pretend to be disabled to get lucrative handouts.

The legacy of such negative stereotyping is more hostility, more attacks, more fear and a deepening state of apartheid for people with disabilities.

Perversely, this comes as Mr Clarke extends hate crime laws to ensure tougher penalties for those attacking the disabled.

There is nothing wrong in stopping fraud or imposing cuts at a time of austerity. But it is revolting to see politicians and the media collude to target people who just want to join society. Or do we want to live in a world in which people with disabilities are driven further into the shadows?

Tuesday, February 7, 2012

Experts now generally believe that infectious agents set off a persistent, hyperactive immune response that causes chronic fatigue syndrome

By DAVID TULLER Published: February 6, 2012: An estimated one million people in the United States suffer from chronic fatigue syndrome, which is characterized by profound exhaustion, a prolonged loss of energy following minimal exertion, swollen lymph nodes, sore throat, cognitive dysfunction and other symptoms. Experts now generally believe that one or more infectious agents, or perhaps exposure to toxins, set off a persistent, hyperactive immune response — the likely cause of many of the symptoms.

¶ The events of the past couple of years, though disheartening to chronic fatigue syndrome patients, may have a silver lining: Research into the disease, much of it privately financed, is ratcheting up.

¶ A new research and treatment center has been created at Mount Sinai Hospital in New York. The Hutchins Family Foundation is investing $10 million in the Chronic Fatigue Initiative, an effort to find causes and treatments that has recruited top researchers from Columbia, Harvard, Duke and other institutions.

¶ “The disease had languished in the background at N.I.H. and C.D.C., and other scientists had not been paying much attention to it,” said John Coffin, a professor of molecular biology at Tufts University. “This has brought it back into attention.”

¶ Dr. Coffin, who at first supported the mouse retrovirus theory but later disputed it, noted that the illness “does seem to have characteristics that would suggest infectious origins” and that other retroviruses could be involved.

¶ Despite the personal and professional setbacks for Dr. Mikovits, many patients, like Ms. Solomon, continue to believe that a retrovirus is causing their illness.

¶ “But even if the retroviral research does not pan out, her work, and the publicity it has brought to our illness, has forever changed the landscape,” said Ms. Solomon.

Read more>>

Sunday, February 5, 2012

Denial to the point of being delusional

Margaret Williams 4th February 2012:

Questions for Professors Frank J M van Kuppeveld and Jos W M van der Meer

Margaret Williams   4th February 2012


Professors Frank J M van Kuppeveld and Jos W M van der Meer have recently stated in plain terms that “In the past, several infectious agents have been associated with CFS but none of these could be confirmed in subsequent studies….” (Lancet 4th February 2012: 379: 9814, e27 – e28 doi:10.1016/S0140-6736(11)60899).

Where is their evidence for the assertion that no infectious agent “could be confirmed in subsequent studies” in (ME)CFS patients?
Is their assertion correct?  Did The Lancet’s editorial team check the authenticity of that assertion before publishing it?
Here is some evidence that Professors van Kuppeveld and van der Meer (and The Lancet’s editors) seem to have overlooked:

“Virological studies revealed that 76% of the patients with suspected myalgic encephalomyelitis had elevated Coxsackie B neutralising titres (and symptoms included) malaise, exhaustion on physical or mental effort, chest pain, palpitations, tachycardia, polyarthralgia, muscle pains, back pain, true vertigo, dizziness, tinnitus, nausea, diarrhoea, abdominal cramps, epigastric pain, headaches, paraesthesiae, dysuria)….The group described here are patients who have had this miserable illness” (BD Keighley, EJ Bell. JRCP 1983:33:339-341).

“Recently associations have been found between Coxsackie B infection and a more chronic multisystem illness….referred to as…myalgic encephalomyelitis…140 patients presenting with symptoms suggesting a postviral syndrome were entered into the study…Coxsackie B antibody levels were estimated in 100 control patients…All the Coxsackie B virus antibody tests were performed blind…Of the 140 ill patients, 46% were found to be Coxsackie B virus antibody positiveThis study has confirmed our earlier finding that there is a group of symptoms with evidence of Coxsackie B infection.  We have also shown that clinical improvement is slow and recovery does not correlate with a fall in Coxsackie B virus antibody titre” (BD Calder et al. JRCGP 1987:37:11-14).

“These results show that chronic infection with enteroviruses occurs in many PVFS (post-viral fatigue syndrome, a classified synonym for ME/CFS) patients and that detection of enterovirus antigen in the serum is a sensitive and satisfactory method for investigating infection in these patients….Several studies have suggested that infection with enteroviruses is causally related to PVFS…The association of detectable IgM complexes and VP1 antigen in the serum of PVFS patients in our study was high…This suggests that enterovirus infection plays an important role in the aetiology of PVFS” (GE Yousef, EJ Bell, JF Mowbray et al. Lancet  January 23rd 1988:146-150).

“The main features (of ME) are: prolonged fatigue following muscular exercise or mental strain, an extended relapsing course; an association with neurological, cardiac, and other characteristic enteroviral complications. Coxsackie B neutralisation tests show high titres in 41% of cases compared with 4% of normal adults…These (chronic enteroviral syndromes) affect a young, economically important age group and merit a major investment in research” (EG Dowsett. Journal of Hospital Infection 1988:11:103-115).

“Skeletal samples were obtained by needle biopsy from patients diagnosed clinically as having CFS (and) most patients fulfilled the criteria of the Centres for Disease Control for the diagnosis of CFS (Holmes et al 1988)…These data are the first demonstration of persistence of defective virus in clinical samples from patients with CFS…We are currently investigating the effects of persistence of enteroviral RNA on cellular gene expression leading to muscle dysfunction” (L Cunningham, RJM Lane, LC Archard et al. Journal of General Virology 1990:71:6:1399-1402).

“Myalgic encephalomyelitis is a common disability but frequently misinterpreted…This illness is distinguished from a variety of other post-viral states by a unique clinical and epidemiological pattern characteristic of enteroviral infection33% had titres indicative and 17% suggestive of recent CBV infection…Subsequently…31% had evidence of recent active enteroviral infectionThere has been a failure to recognise the unique epidemiological pattern of ME…Coxsackie viruses are characteristically myotropic and enteroviral genomic sequences have been detected in muscle biopsies from patients with ME. Exercise related abnormalities of function have been demonstrated by nuclear magnetic resonance and single-fibre electromyography including a failure to coordinate oxidative metabolism with anaerobic glycolysis causing abnormal early intracellular acidosis, consistent with the early fatiguability and the slow recovery from exercise in ME.  Coxsackie viruses can initiate non-cytolytic persistent infection in human cells. Animal models demonstrate similar enteroviral persistence in neurological disease… and the deleterious effect of forced exercise on persistently infected muscles.  These studies elucidate the exercise-related morbidity and the chronic relapsing nature of ME” (EG Dowsett, AM Ramsay et al. Postgraduate Medical Journal 1990:66:526-530).

“Persistent enteroviral infection of muscle may occur in some patients with postviral fatigue syndrome and may have an aetiological role….The features of this disorder suggest that the fatigue is caused by involvement of both muscle and the central nervous system…We used the polymerase chain reaction to search for the presence of enteroviral RNA sequences in a well-characterised group of patients with the postviral fatigue syndrome…53% were positive for enteroviral RNA sequences in muscle…Statistical analysis shows that these results are highly significant…On the basis of this study…there is persistent enteroviral infection in the muscle of some patients with the postviral fatigue syndrome and this interferes with cell metabolism and is causally related to the fatigue” (JW Gow et al. BMJ 1991:302:696-696).

A major publication (Postviral Fatigue Syndrome. British Medical Bulletin 1991:47:4: 793-907, published by Churchill Livingstone for The British Council) contains the following:

Molecular viral studies have recently proved to be extremely useful.  They have confirmed the likely important role of enteroviral infections, particularly with Coxsackie B virus” (Postviral fatigue syndrome: Current neurobiological perspective. PGE Kennedy. BMB 1991:47:4:809-814)

We conclude that persistent enteroviral infection plays a role in the pathogenesis of PVFS…The strongest evidence implicates Coxsackie viruses…Patients with PVFS were 6.7 times more likely to have enteroviral persistence in their muscles (JW Gow and WMH Behan. BMB 1991:47:4:872-885).

“We will report at the First International Research Conference on Chronic Fatigue Syndrome to be held at Albany, New York, 2-4 October 1992, our new findings relating particularly to enteroviral infection…We have isolated RNA from patients and probed this with large enterovirus probes…detailed studies...showed that the material was true virus…Furthermore, this virus was shown to be replicating normally at the level of transcription. Sequence analysis of this isolated material showed that it had 80% homology with Coxsackie B viruses and 76% homology with poliomyelitis virus, demonstrating beyond any doubt that the material was enterovirus (Press Release for the Albany Conference, Professor Peter O Behan, University of Glasgow, October 1992).

“Samples from 25.9% of the PFS (postviral fatigue syndrome) were positive for the presence of enteroviral RNA, compared with only 1.3% of the controls…We propose that in PFS patients, a mutation affecting control of viral RNA synthesis occurs during the initial phase of active virus infection and allows persistence of replication defective virus which no longer attracts a cellular immune response (NE Bowles, RJM Lane, L Cunningham and LC Archard. Journal of Medicine 1993:24:2&3:145-180).

“These data support the view that while there may commonly be asymptomatic enterovirus infections of peripheral blood, it is the presence of persistent virus in muscle which is abnormal and this is associated with postviral fatigue syndrome…Evidence derived from epidemiological, serological, immunological, virological, molecular hybridisation and animal experiments suggests that persistent enteroviral infection may be involved in… PFS” (PO Behan et al. CFS: CIBA Foundation Symposium 173, 1993:146-159).

“Individuals with CFS have characteristic clinical and laboratory findings including…evidence of viral reactivation…The object of this study was to evaluate the status of key parameters of the 2-5A synthetase/RNase L antiviral pathway in individuals with CFS who participated in a placebo-controlled, double-blind, multi-centre trial…The present work confirms the finding of elevated bioactive 2-5A and RNase L activity in CFS…RNase L, a 2-5A-dependent enzyme, is the terminal effector of an enzymatic pathway that is stimulated by either virus infection or exposure to exogenous lymphokines.  Almost two-thirds of the subjects…displayed baseline RNase L activity that was elevated above the control mean”  (Robert J Suhadolnik, Daniel L Peterson, Paul Cheney et al. In Vivo 1994:8:599-604).

In his Summary of the Viral Studies of CFS, Dr Dharam V Ablashi concluded: “The presentations and discussions at this meeting strongly supported the hypothesis that CFS may be triggered by more than one viral agent…Komaroff suggests that, once reactivated, these viruses contribute directly to the morbidity of CFS by damaging certain tissues and indirectly by eliciting an on-going immune response” (Clin Inf Dis 1994:18 (Suppl 1):S130-133). 

“These results suggest there is persistence of enterovirus infection in some CFS patients and indicate the presence of distinct novel enterovirus sequencesSeveral studies have shown that a significant proportion of patients complaining of CFS have markers for enterovirus infection….It is worth noting that the enteroviral sequences obtained from patients without CFS were dissimilar to the sequences obtained from the CFS patients…This may provide corroborating evidence for the presence of a novel type of enterovirus associated with CFS”  (DN Galbraith, C Nairn and GB Clements. Journal of General Virology 1995:76:1701-1707).

“In the CFS study group, 42% of patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group…Enteroviral PCR does, however, if positive, provide evidence for circulating viral sequences, and has been used to show that enteroviral specific sequences are present in a significantly greater proportion of CFS patients than other comparison groups (C Nairn et al. Journal of Medical Virology 1995:46:310-313).

“To prove formally that persistence rather than re-infection is occurring, it is necessary to identify a unique feature retained by serial viral isolates from one individual.  We present here for the first time evidence for enteroviral persistence (in humans with CFS)…” (DN Galbraith et al.  Journal of General Virology 1997:78:307-312).

“Over the last decade a wide variety of infectious agents has been associated with CFS by researchers from all over the world.  Many of these agents are neurotrophic and have been linked to other diseases involving the central nervous system (CNS)…Because patients with CFS manifest a wide range of symptoms involving the CNS as shown by abnormalities on brain MRIs, SPECT scans of the brain and results of tilt-table testing, we sought to determine the prevalence of HHV-6, HHV-8, EBV, CMV, Mycoplasma species, Chlamydia species and Coxsackie virus in the spinal fluid of a group of patients with CFS. Although we intended to search mainly for evidence of actively replicating HHV-6, a virus that has been associated by several researchers with this disorder, we found evidence of HHV-8, Chlamydia species, CMV and Coxsackie virus in (50% of patient) samples…It was also surprising to obtain such a relatively high yield of infectious agents on cell free specimens of spinal fluid that had not been centrifuged” (Susan Levine. JCFS 2002:9:1/2:41-51).

Differences in bacterial and/or viral infections in (ME)CFS patients compared to controls were significant…The results indicate that a large subset of (ME)CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients” (Nicolson GL et al. APMIS 2003:111(5):557-566).

 Seeking to detect and characterise enterovirus RNA in skeletal muscle from patients with (ME)CFS and to compare efficiency of muscle metabolism in enterovirus positive and negative (ME)CFS patients, Lane et al obtained quadriceps biopsy samples from 48 patients with (ME)CFS. Muscle biopsy samples from 20.8% of patients were positive, while 100% of the controls were negative for enterovirus sequences.  Lane et al concluded: “There is an association between abnormal lactate response to exercise, reflecting impaired muscle energy metabolism, and the presence of enterovirus sequences in muscle in a proportion of (ME)CFS patients (RJM Lane, LC Archard et al. JNNP 2003:74:1382-1386).

In a review of the role of enteroviruses in (ME)CFS, Chia noted that initial reports of chronic enteroviral infections causing debilitating symptoms in (ME)CFS patients were met with scepticism and largely forgotten, but observations from in vitro experiments and from animal models clearly established a state of chronic persistence through the formation of double stranded RNA, similar to findings reported in muscle biopsies of patients with (ME)CFS.  Recent evidence not only confirmed the earlier studies, but also clarified the pathogenic role of viral RNA (JKS Chia. Journal of Clinical Pathology 2005:58:1126-1132).

“Early beliefs that (ME)CFS may be triggered or caused by a single virus have been shown to be unsubstantiated (and) it is likely that different viruses affect different individuals differently, dependent upon the …immune competence of the individual…Infections are known to trigger and perpetuate the disease in many cases.  Therefore, one valuable approach that has not been widely adopted in the management of (ME)CFS patients is to exhaustively investigate such patients in the hope of identifying evidence for a specific persistent infection (but in the UK, NICE specifically does not permit such investigations)….Enteroviruses have been reported to trigger approximately 20% of cases of (ME)CFS…Antibodies to Coxsackie B virus are frequently detected in (ME)CFS patients, and enterovirus protein and RNA occur in the muscle and blood of (ME)CFS patients and their presence has been associated with altered metabolism in the muscle upon exercise in the context of (ME)CFS (LD Devanur,  JR Kerr. Journal of Clinical Virology 2006: 37(3):139-150).

“(ME)CFS is associated with objective underlying biological abnormalities, particularly involving the nervous and immune system. Most studies have found that active infection with HHV-6 – a neurotropic, gliotropic and immunotropic virus – is present more often in patients with (ME)CFS than in healthy control subjects…Moreover, HHV-6 has been associated with many of the neurological and immunological findings in patients with (ME)CFS Anthony L Komaroff.  Journal of Clinical Virology 2006:37:S1:S39-S46.

Research studies have identified various features relevant to the pathogenesis of CFS/ME such as viral infection, immune abnormalities and immune activation, exposure to toxins, chemicals and pesticides, stress, hypotension…and neuroendocrine dysfunction….Various viruses have been shown to play a triggering or perpetuating role, or both, in this complex disease….The role of enterovirus infection as a trigger and perpetuating factor in CFS/ME has been recognised for decades” (Jonathan R Kerr.  Editorial. J Clin Pathol 14th September 2007. Epub ahead of print).

“Since most (ME)CFS patients have persistent or intermittent gastrointestinal (GI) symptoms, the presence of viral capsid protein 1 (VP1), enterovirus RNA and culturable virus in the stomach biopsy specimens of patients with (ME)CFS was evaluated…Our recent analysis of 200 patients suggests that… enteroviruses may be the causative agents in more than half of the patients…At the time of oesophagogastroduodenoscopy, the majority of patients had mild, focal inflammation in the antrum…95% of biopsy specimens had microscopic evidence of mild chronic inflammation…82%  of biopsy specimens stained positive for VP1 within parietal cells, whereas 20% of the controls stained positive…An estimated 80-90% of our 1,400 (ME)CFS patients have recurring gastrointestinal symptoms of varying severity, and epigastric and/or lower quadrant tenderness by examination…Finding enterovirus protein in 82% of stomach biopsy samples seems to correlate with the high percentage of (ME)CFS patients with GI complaints…Interestingly, the intensity of VP1 staining of the stomach biopsy correlated inversely with functional capacity…A significant subset of (ME)CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection which can lead to diffuse symptomatology without true organ damage” (Chia JK, Chia AY. J Clin Pathol  13th  September 2007 Epub ahead of print).

Dr John Chia, an infectious diseases specialist from Torrance, California, who specialises in ME/CFS, is on record: “I believe that the main reason (ME)CFS patients are symptomatic is due to continuing inflammatory response toward viruses living within the cells, enteroviruses in most of the cases I see We have clearly documented certain enterovirus infections triggering autoimmune responses in some patients” (http://aboutmecfs.org/blog/?p=865).

These few illustrations from the many available serve to illustrate that Professors van Kuppeveld and van der Meer’s assertion that: “In the past, several infectious agents have been associated with CFS but none of these could be confirmed in subsequent studies….” is demonstrably incorrect.

The ignoring of the evidence-base of infection in ME/CFS is all the more disturbing given that Frank van Kuppeveld is Associate Professor (Infection and Inflammation) in the Department of Medical Microbiology, Radboud University Nijmegen Medical Centre and his research focuses on enteroviruses, and Jos van der Meer is Professor of Internal Medicine and Chairman of the Division of General Internal Medicine at Radboud University Nijmegen Medical Centre who also works in the Nijmegen Institute for Infection, Inflammation and Immunity.

Do Professors van Kuppeveld and van der Meer have no concern for accuracy?

Another article in which Professor van der Meer was a co-author appeared to show a similar lack of attention to the existing biomedical evidence-base: (A controversial consensus – comment on article by Broderick et al”: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02468.x/pdf).  Professor van der Meer accuses the International Consensus Panel of bias towards the biomedical construct: “the authors seek to discard the findings in published studies that have applied the existing international criteria, if the result do not fit with their notions of causation….In a 21st century consensus document, accounting in a balanced fashion for the strength of the evidence is an essential element”, yet he does exactly the same by ignoring the biomedical evidence in his own articles.

From his two latest articles, one must question whether Professor van der Meer contributes to scientific progress in what everyone agrees is a controversial condition.

Equally, do editors of medical journals no longer see the need to adhere to elementary rules of procedure by assuring themselves that what they publish represents a potentially useful and original development of knowledge, and that any contribution is squarely built on the foundations of existing knowledge?

By publishing items that disregard the pre-existing body of knowledge, authors and editors fail in their duty to provide readers with information that can be relied upon and which can serve as a dependable basis for future work.

Investigators are not free to declare established knowledge disproven simply by ignoring the data on which that knowledge is predicated.

Merely ignoring and/or denying the existing knowledge-base, as Professors van Kuppeveld and van der Meer appear to have done, serves no scientific purpose but may actively delay the advancement of science and thus prolong the incalculable suffering of people with ME/CFS.

See also: PACE trial results are out: ME is caused by an oncogenic virus

See also: The putative agent of ME/CFS can be transferred to monkeys 

See also: Almost 5% of ME/CFS patients contracted ME/CFS from a blood transfusion


Related Posts with Thumbnails