This text is also available as a PDF download at: http://www.meactionuk.org.uk/Organic_evidence_for_Gibson.pdf
Pages 1 - 8, and from page 128 onward are particularly recommended.
THE GROUP ON SCIENTIFIC RESEARCH INTO MYALGIC ENCEPHALOMYELITIS (THE GIBSON PARLIAMENTARY INQUIRY)
Illustrations of Clinical Observations and International Research Findings from 1955 to 2005 that demonstrate the organic aetiology of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
By Professor Malcolm Hooper, Eileen Marshall and Margaret Williams, 12th December 2005
Prepared for The Group on Scientific Research into Myalgic Encephalomyelitis (the Gibson Parliamentary Inquiry) that has been established “to assess the progress of scientific research on ME since the publication of the Chief Medical Officer’s Working Group Report into CFS/ME in 2002, (and) to increase public understanding of scientific research into ME/CFS (and) to identify research and funding requirements in establishing the cause of ME/CFS”.
This document is a compilation of illustrations taken from the published evidence-base of the organic aetiology of ME/CFS over the fifty years from 1955 to 2005.
To faciliate comparison it also includes Appendices of illustrations from the published works of psychiatrists who believe ME/CFS to be a behavioural disorder.
Malcolm Hooper
Emeritus Professor of Medicinal Chemistry
Department of Life Sciences
University of Sunderland
SR2 7EE, UK
There is a large and significant published international evidence-base that ME/CFS is a legitimate medical disorder with numerous reproducible biomarkers of organic pathology, but this evidence has been consistently buried in the UK by “Wessely School” psychiatrists (so named after its leading activist Professor Simon Wessely) who have vested interests in promulgating their own hypothesis that ME is nothing but an “aberrant illness belief” that is best managed by compulsory “behavioural rehabilitation” regimes.
Wessely School psychiatrists themselves admit that their favoured therapies have limited impact on the disorder and that any modest improvement disappears after several months
Despite this, the Medical Research Council (MRC) and the UK Government have directed substantial funding into these therapies but nil funding for biomedical research into ME/CFS
This is a human rights travesty
Patients with ME/CFS who are not mentally ill are forced to attend psychiatric clinics; a single attendance at a psychiatric unit constitutes a de facto psychiatric diagnosis in the eyes of many, including GPs, employers, insurance companies, and family members
No credible evidence exists that ME/CFS is a mental health issue, yet Wessely School psychiatrists continue to exercise a virtual monopoly on ME/CFS research in the UK
There is an urgent need to end the Wessely School stranglehold on ME/CFS research, as well as the promulgation of their retrograde belief that the scientific biomedical approach to disease is a (quote) “blind alley” that should be replaced by a “psychosocial” model of disease (in which thoughts, feelings, beliefs and behaviour in the social context are responsible for diseases), and also their potentially seriously damaging psychosocial “management” regimes that are imposed on those with ME/CFS on pain of withdrawal of State and medical insurance benefits
The Wessely School argument that syndromes like ME/CFS cause “unnecessary expenditure of medical resources” has been criticised by a leading US researcher for its pernicious public policy implications (see Lancet Correspondence, 11th December 1999:354, Number 9195)
Research funding for ME/CFS must be urgently directed towards scientific and medical disciplines other than psychiatry and the MRC must cease to reject high quality biomedical research proposals on ME/CFS (known to have been submitted)
Many GPs and most NHS Consultants (for example, cardiologists, neurologists, chest physicians, rheumatologists, immunologists) have virtually no accurate knowledge about ME/CFS and therefore underestimate both its seriousness and the multi-system dysfunction it causes, so patients are simply dismissed and abandoned without support
The malign influence of Wessely School dogma extends throughout Government Departments, throughout the NHS, and even extends to the Judiciary: one High Court litigant was told that “Judges regard ME as psychological self-indulgence”; one Local Health Board will only fund treatment for ME/CFS where the prime focus is cognitive behavioural therapy and/or graded exercise therapy; a spokesman for Grampian NHS Trust is on record in 2003 (ie. more than a year after the publication of the CMO’s Working Group report) as stating: “ME is not a condition we recognize or treat”
The damage perpetrated on those with ME/CFS by Wessely School adherents cannot be quantified
Illustrations from the international literature showing that the Wessely School hypothesis about the nature of ME/CFS is wrong begin on page 9 below
Appendices: (provided for direct comparison of the biomedical with the psychosocial models of the disorder)
Illustrations of actual quotations about patients with ME/CFS from psychiatrist Professor Simon Wessely (page 129)
Illustrations of actual quotations about patients with ME/CFS from psychiatrist Professor Michael Sharpe (page 146)
“Wessely’s Wisdom? Some more open questions for Professor Wessely” (page 162). This document asks Professor Wessely some cardinal questions about ME/CFS that he and other Wessely School adherents have consistently failed to address
“Unanswered Questions: do inconsistencies matter in medicine?” (page 171). This document looks at the irrationality of drawing conclusions across differing patient populations; at the absurdity of relying on assumptions as the basis for a compulsory management regime of behavioural modification for patients with ME/CFS; at the divergent assertions about the efficacy of cognitive behaviour therapy and at the inherent danger of applying a ‘one size fits all’ policy
This document has been compiled to acquaint Members of Parliament with the existing international evidence base on the organic nature of myalgic encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS). It should be read in conjunction with our previous submission entitled “For UK Parliamentary Inquiry into ME/CFS: Chronological List of Documents Relevant to the Inquiry” (7th November 2005).
On 28th July 2005 there was a meeting between Dr Gibson MP, Professor Malcolm Hooper and members of the Norfolk ME community, at which Dr Gibson stressed his determination to hear evidence from both sides of the medical divide (ie. from those advocating a biomedical aetiology and from those advocating a purely psychosocial aetiology), and especially from affected patients. What Dr Gibson offered at that meeting was an open-minded, comprehensive and transparent examination and evaluation of all the evidence, including and especially the failure of the insurance industry to meet legitimate claims by those with ME/CFS, the problems of those with ME/CFS in obtaining State benefits, and the lack of all support for those with ME/CFS.
We and others, including senior NHS Consultants, are concerned that Members of the Parliamentary Inquiry should understand the travesty that currently exists in the UK in relation to ME/CFS. A group of psychiatrists known to patients and researchers alike as the “Wessely School” strenuously promotes their own hypothesis that ME/CFS is a mental health disorder that is best managed by a regime of cognitive behavioural therapy (CBT) which incorporates compulsory graded exercise therapy (GET) as a form of “rehabilitation”. CBT is described in the Chief Medical Officer’s Working Group 2002 Report on CFS/ME as “a tool for constructively modifying attitudes and behaviour”.
Emanating from the Wessely School, a spurious medical consensus has emerged, namely that the syndrome is a primary psychiatric (behavioural) disorder. There is no evidence whatever that ME/CFS is a psychiatric disorder, and even adherents of the Wessely School themselves admit that CBT/GET has limited impact on the illness.
Objective evidence that such interventions are effective in ME/CFS is lacking: in 2001 a Leading Article found there was no such evidence and questioned whether the reported improvement might actually be an illusion (JAMA 2001:286:11:1360-1368).
Professor Simon Wessely himself has conceded that his therapies are “not remotely curative” and are only “modestly effective” and that “these interventions are not the answer to ME/CFS” (Trials and Tribulations: JAMA 2001:286:11).
Professor Wessely is also on record as stating: “cognitive behaviour therapy has been shown to improve functional impairment and fatigue for up to eight months after treatment. Observed gains may be transient” (Am J Psychiatry 2001:158:2038-2042).
It was as long ago as 1997 that Simon Wessely made public his own knowledge about the questionable safety of such therapies: “People involved in psychotherapy should know that it has side effects and risks. There is evidence that some intensive courses do have rates of casualties” (Guardian, 11th March 1997, page 16). This must surely raise legitimate doubts about the assertions of Wessely School psychiatrists that the regime they promote so assiduously for those with ME/CFS is “safe” and “acceptable to patients” when there is no such evidence (because evidence of the efficacy of CBT/GET in those with authentic ME does not exist).
Despite these contra-indications, the Medical Research Council (MRC) and the UK Government have directed millions of pounds sterling into these psychotherapy strategies, which are the only Government-funded provision for patients with ME/CFS. This imbalance in funding has had negative consequences for those afflicted by ME/CFS.
The evidence set out below needs to be borne in mind when considering the unproven dogma about ME/CFS that currently dominates UK Government policy, namely that “CFS/ME” is a mental health issue.
It is important to understand that the expedient term “CFS/ME” is a heterogeneous label that specficially and intentionally includes psychiatric disorders in which “fatigue” is a dominant feature and which therefore cannot be synonymous with ME/CFS, also known as Post Viral Fatigue Syndrome / PVFS, and sometimes known in the US as Chronic Fatigue and Immune Dysfunction Syndrome or CFIDS.
The view that “CFS/ME” is a mental health issue also prevails at the Medical Research Council -- see the 32 page Report of January 2005 from the MRC Neurosciences and Mental Health Board’s Strategy and Portfolio Overview Group, which clearly states: “Mental health research in this instance covers CFS/ME” (NMHB Mental Health Scoping Study Report). Given that ME/CFS is internationally classified by the World Health Organisation as a neurological disorder, the MRC was questioned about its own “classification” and in a written response dated 6th December 2005 Dr Robin Buckle stated: “This classification for the Mental Health Scoping Study was pragmatic, and related to the grants associated with the activities of one section of the office, allowing for an analysis of research trends”.
It is unacceptable that Wessely School psychiatrists continue to exert a virtual monopoly on ME/CFS research in the UK when the international evidence clearly does not support their hypothesis about the nature of it.
The Wessely School view of ME/CFS is not accepted by most of Wessely’s medical peers in the USA, nor is it shared by all psychiatrists in the UK.
However, to the detriment of UK patients, the Wessely School hypothesis is now misguidedly believed to be scientific fact by many UK doctors, as well as by the medical insurance industry with which these psychiatrists are closely involved as medical advisers, and by the commercial company that holds the contract to carry out assessments for State benefits (formerly a French company called SEMA, then from 2002 a Franco-German conglomerate called Schlumberger SEMA and currently a massive multi-national company with headquarters in Paris called Atos Origin whose UK head office is at 4, Triton Square, Regents Place, London NW1 3HG).
We draw attention to the fact that five years ago, there was an Inquiry by the House of Commons Social Security Select Committee that resulted in a major 245 page Report (“Medical Services”; HC 183, 12th April 2000): it was condemnatory about the way the SEMA Group mishandled Social Security claims and it took evidence from at least eight sources about specific difficulties experienced by those with ME/CFS. There was a long debate in the House of Commons on the Government’s response. Nothing, however, has changed since the publication of that Report: if anything, the situation has worsened considerably for many patients with ME/CFS.
We wish to place on record our concern that the Gibson Inquiry does not allow itself to be misdirected or misled into believing that post-2002 “progress” in research in ME/CFS in the UK has been significant simply by virtue of the setting up of 50 Government-funded “CFS Centres”, because these Centres offer only the same psychotherapy regimes that are promoted by the Wessely School; indeed, the situation has deteriorated so dramatically that, for example, the South & East Dorset NHS Primary Care Trust actively includes ‘somatisation’ in its GP referral protocol for “CFS/ME” patients (somatisation is the manifestation of emotional distress through constantly changing physical symptoms).
Not only are CBT and GET regimes potentially harmful for those with ME/CFS (unknown numbers of whom may be in a form of heart failure), but they continue to ignore the existing and established evidence-base of scientific knowledge that demonstrates the organic nature of the disorder, which cannot be in sufferers’ best interests, since the evidence is abundant that even moderate physical exercise is likely to induce relapse.
Should the Gibson Inquiry allow itself to be misdirected or misled, it will be seen as yet another manipulated betrayal of the ME/CFS community, particularly as the terms of reference currently make no mention of the need for effective support for both patients and their carers.
We wish to make it plain that we fully endorse the need to move forwards, but we maintain that the only way to do this is to build upon, not ignore, the existing knowledge base of biomedical research evidence.
We completely support Dr Gibson’s view as set out in his Press Release of 1st December 2005: three years on from the CMO’s Working Group Report, “the time is right to evaluate how much further we have come in understanding the causes of ME, establishing a programme of research on all aspects of the condition and securing adequate investment for this research”.
This present document is lengthy because it provides some indication of how extensive is the existing biomedical evidence-base that has been so effectively buried by those who insist that the disorder is perpetuated by the “aberrant behaviour” of both ME sufferers themselves and those medical professionals who support them in their conviction that ME is a physical, not a mental health issue.
It has been compiled because (i) we accept it is unrealistic to expect Members of Parliament on the Inquiry to visit and review the existing knowledge-base for themselves, and (ii) because we maintain that without this knowledge, their deliberations will inevitably be based on fallacious assumptions.
According to Anthony Komaroff, Professor of Medicine at Harvard and a renowned world expert on ME/CFS, there are more than 2,000 papers which demonstrate that ME/CFS is an organic, not psychiatric, disorder. The following examples are therefore merely illustrative but provide hard evidence of some of the published clinical observations as well as some of the international biomedical research findings on ME/CFS from 1955 to 2005.
Based on this evidence, it is submitted that in the light of the undisputed biomarkers of serious organic pathology, the psychiatric paradigm lacks both validity and scientific credibility, as do the numerous attempts by Wessely School adherents to re-classify ME from its current neurological classification in the World Health Organisation International Classification of Diseases to a mental (behavioural) classification.
Indeed in 1999, Leonard Jason, Professor of Psychology, DePaul University, Chicago, was outspoken, writing that it is regrettable that the disorder is portrayed in such a narrow way, and that flaws in the case definition of “CFS” have led to “inaccurate and biased characterization of ME/CFS which incorrectly favours a psychiatric view of the illness” because “the British case definition does not consider psychiatric disorders are exclusionary for (ME)CFS”.
Jason pointed out that “the erroneous inclusion of people with primary psychiatric conditions in ME/CFS samples will have detrimental consequences for the interpretation of treatment efficacy findings”.
He also stated that there has been an ignoring of “a large body of medical research demonstrating biological abnormalities in individuals with ME/CFS. For years, investigators have noted numerous biomedical abnormalities among ME/CFS patients, including over-activated immune systems, biochemical dysregulation in the 2-5A synthetase / RNASE L pathway, muscle abnormalities, cardiac dysfunction, abnormal EEG profiles, abnormalities in cerebral white matter, decreases in blood flow throughout the brain, and autonomic nervous system dysfunction. Unfortunately, some uninformed physicians continue to believe that (ME)CFS and other disorders like it are primarily psychiatric in nature. Some confuse (ME)CFS with neurasthenia. Biases such as these have been filtered through to the media, which portrays ME/CFS in an overly simplistic and stereotyped way (which) compromises patient-doctor relationships and medical care for patients” (see LISTSERV home page at LISTSERV.NODAK.EDU 18th March 1999).
We submit that the behaviour of the Wessely School in relation to ME/CFS may be considered to be perverse and may even amount to scientific misconduct because of its adverse impact on the health and well-being of sufferers.
This is because of the Wessely School’s relentless dismissal for almost two decades of the international biomedical evidence that ME/CFS is an organic (not psychiatric) disorder, particularly:
their repeated failure to distinguish between “chronic fatigue” and ME/CFS (even though the differences have been repeatedly brought to their attention and even though as long ago as 1990, the American Medical Association issued a specific notice emphasizing that chronic fatigue is not the same as chronic fatigue syndrome)
their demonstrable bias that has resulted in the deliberate suppression of the biomedical evidence on ME/CFS by UK medical journals
their selective manipulation of others’ published papers (by claiming other authors’ findings support their own view when such is not the case)
their unscrupulous determination to “eradicate” ME by asserting that it is nothing more than an “aberrant illness belief” and their tactics of denial (for referenced evidence and illustrations of such tactics of denial, see “The Mental Health Movement: Persecution of Patients” available online at http://www.meactionuk.org.uk/SELECT_CTTEE_FINAL_VERSION.htm and “Consideration of Some Issues Relating to the Published Views of Psychiatrists of the ‘Wessely School’ in relation to their belief about the nature, cause and treatment of ME” at http://www.meactionuk.org.uk/consideration.htm )
their focusing on the single symptom of chronic “fatigue” in ME/CFS and ignoring of other significant symptoms and signs, especially cardiovascular, neurological and immunological
their deliberate dilution of the case description to include any “medically unexplained” fatigue, ie. their obfuscation of the case definition so that it specifically includes somatisation disorders (which instantly greatly increases the numbers of patients with an alleged diagnosis of “CFS/ME” who can be coerced into enrolling in the Wessely School management regime); if those with ME/CFS are physically unable to continue and have no option but to withdraw from these regimes, they immediately risk losing their State benefits and their medical insurance payments)
their advice to Government that no tests should be performed on those with ME/CFS to confirm the diagnosis (other than the most basic screening, which is universally known to be normal in ME/CFS)
their advice to Government that the reported biomedical abnormalities “should not deflect the clinician from the biopsychosocial approach and should not focus attention towards a search for an ‘organic’ cause” (ref: Joint Royal Colleges’ Report on CFS, CR54, 1996)
their influence and functioning in areas of medicine in which they have no expertise: as psychiatrists, it follows that areas of complex medical science such as immunology, vascular biology and muscle pathology which underpin ME/CFS are not within their remit of expertise. In July 2005 the General Medical Council criticised and struck off Professor Sir Roy Meadow from the Medical Register for acting outside his area of expertise. The Chairman of the Disciplinary Hearing told Meadow: “Your misguided belief in the truth of your argument is both disturbing and serious. You should not have strayed into areas that were not within your remit of expertise”. During the GMC hearing, Robert Seabrook QC stated that Meadow had ignored almost three decades of relevant research and that this was not simply a case of poor research or simple error: it was a calculated move that enabled him to impress his own theses on the public mind. Many in the ME community draw a parallel with Professor Wessely in relation to ME/CFS. (For a more detailed consideration, see http://www.meactionuk.org.uk/Another_Meadow.htm ).
As Professor Jason stated in his letter of 12th May 2005 to the Editor of Psychology Today, ME/CFS is a “devastating” chronic disorder and he questioned why it is assumed that it is only sufferers themselves who believe it to be an organic disorder when many scientists, including himself, support such a view.
He noted that much of the published data asserting a psychiatric aetiology derives from tertiary centres where instruments to assess psychiatric symptoms have often been inappropriately selected, so one cannot conclude that ME/CFS is a psychiatric illness.
Jason further noted that although there is a group of investigators who feel it is the “misbeliefs” that the patient support groups “inadvertently re-inforce” which account for the illness, many other researchers hold the view that there are neurologic, neuroendocrine, autonomic and immunologic explanations for ME/CFS.
Jason admonished those who improperly insist that psychiatric interventions be imposed on those with ME/CFS: “To suggest that efforts to help people cope with a chronic illness is the primary and only way to cure them does a disservice to all individuals with this condition” (see Co-Cure, 12th May 2005).
Professor Jason is a leading American psychologist who is author of one of the largest US epidemiological studies on ME/CFS, the recipient of numerous National Institutes of Health grants and the originator of a research portfolio that is widely considered to be scientifically superior in construct to that of Professor Simon Wessely.
As John Lalor noted on 4th December 2005 in the Irish Independent: “Psychiatrist and author Thomas Szasz claimed that the misuse of psychiatry was ‘linked to the political power intrinsic to the social role of the psychiatrist in totalitarian and democratic societies alike’. Szasz’ concept of power and psychiatry relates directly to the present state of health services as a whole”.
No-where is this more apposite than in relation to ME/CFS politics in the UK: it was at the Second World Congress on (ME)CFS held in Brussels in September 1999 that ME/CFS expert Professor Daniel Peterson from the US went on record saying that ten years ago (ie. in 1989) he believed that (ME)CFS would be resolved by science; he had since changed his mind and believed that it could only be resolved by politics.
The evidence below speaks for itself, from which the assertions of the Wessely School that ME/CFS is a behavioural disorder can readily be seen to be entirely without foundation, especially their assertions that it is perpetuated by “aberrant illness belief” and by “the misattribution of normal bodily sensations” and that patients “seek and obtain secondary gain by adopting the sick role”.
Indeed, the unsubstantiated and unproven beliefs of the Wessely School about the nature of ME/CFS have already been shown to be as erroneous as the equally dogmatic assertions of their psychiatrist predecessors who in the 1940s decreed that the intention tremor that characterizes Parkinsons Disease (PD, which used to be known as the shaking palsy) was caused by an inner conflict resulting from the wish to masturbate (Psychodynamcis in Parkinsonism. Booth G. Psychosomatic Medicine 1948:10:1-14). It was not until the discovery of the neurotransmitters, especially dopamine, in the late 1950s that psychosocial studies on PD were replaced by biomedical research studies.
Psychiatrists have a long track record in mis-attribution of medical disorders: the literature is replete with examples of psychiatrists having claimed – with certainty – “unexplained” symptoms as psychiatric disorder: many common conditions, including diabetes (which in the 1930s was said to represent “the last stand of neurosis” caused by sexual repression), epilepsy, multiple sclerosis, pernicious anaemia, myasthenia gravis, gastric ulcer, glaucoma, asthma and Dupuytren’s contracture have all been claimed as psychiatric disorders until medical research proved otherwise.
Such is the “certainty” of psychiatry, yet it is such “certainty”about ME/CFS that the present New Labour Government and its departments so enthusiastically espouse at incalculable cost to many severely sick people.
It is surely simplistic to think that UK government agencies can be so intellectually inferior to their international counterparts as to be unaware of the convincing science that supports an organic aetiology for ME/CFS, so why do these bodies continue to ignore this evidence?
The answer would seem to be a bizarre scandal of such magnitude that people who are unaffected by it regard it as risible and therefore dismiss it as fictional conspiracy.
ILLUSTRATIONS FROM THE LITERATURE
1955
Outbreak at the Royal Free ED Acheson (who later became Sir Donald Acheson, UK Chief Medical Officer)
Lancet 1955:394-395
“All outbreaks have been remarkable for the relatively long active course of the disease and for marked muscular pain and spasm. Sensory symptoms and signs are additional features”.
1956
A new clinical entity? Editorial (although at the time this Editorial was anonymous, it was later conceded by Sir Donald Acheson that he had written it)
Lancet 1956 (May 26);789-790
“In spite of perplexing variations in the clinical picture from case to case it soon became clear that a new clinical entity had appeared”
“Relapses are frequent”
“Among the more characteristic features are the severe muscular pains, often accompanied by exquisite tenderness. Most commonly they affect the neck, back or limbs but there may also be Bornholm-like chest and abdominal pains”
“In nearly every patient there are symptoms or signs of disease of the central nervous system”
“Hepatitis and splenomegaly may also turn out to be part of the picture”
“The term ‘benign myalgic encephalomyelitis’ does describe some of the striking features by (1) symptoms and signs of damage to the brain and spinal cord; (2) protracted muscle pain with paresis and cramp; (3) emotional disturbances in convalescence; (4) normal cerebrospinal fluid; (5) involvement of the reticulo-endothelial system; (6) a protracted course with relapses in severe cases”
“We believe that its characteristics are now sufficiently clear to differentiate it from, need it be said, hysteria”.
1959
The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland Disease and Epidemic Neuromyasthenia ED Acheson
Am J Med 1959:26:569-595
“Pain in the muscles was an almost constant feature. In severe cases it was agonizing and unresponsive even to opiates”
“Definite parasthesia occurred. Diplopia (was noted)”
“It would be manifestly erroneous to consider as hysteria the emotional instability associated with this illness. The disorder is not a manifestation of hysteria”
“Other sensory disturbances consisted of loss of memory and difficulty in concentration”
“It is concluded that the disease is recognizable in its epidemic form on clinical and epidemiological grounds and therefore may properly be considered a clinical entity”.
1969
Letter to the Editor Joyce R Adamson
New England Journal of Medicine 1969:281:798
“This entity is in danger of becoming a ‘wastebasket’ diagnosis because of its variable signs and symptoms. Almost every conceivable neurologic sign has been described under the heading of epidemic neuromyasthenia”.
1970
Encephalomyelitis resembling benign myalgic encephalomyelitis SGB Innes
Lancet 1970: (May 9):969
“Motor weakness may not be confirmed on formal testing since it appears to take the form of an incapacity for sustained muscular effort”.
1977
Iceland Disease (benign myalgic encephalomyelitis or Royal Free disease) AM Ramsay, EG Dowsett et al BMJ 1977: (May 21):1350
“Physical findings may include hepatitis”
“Objective manifestations of the disease can still be present over thirty years after the initial illness”.
1978
Epidemic myalgic encephalomyelitis Editorial
BMJ 1978: (3 June):1436-1437
“The features common to every epidemic include headache, unusual muscular pains (which may be severe), lymphadenopathy and low grade fever. In a minority of cases frank neurological signs can be detected by careful clinical examination: there may be nystagmus, diplopia, myoclonus, bulbar weakness, motor weakness, increased or decreased tendon reflexes, disturbances of the sphincters and extensor plantar responses”
“Fasciculations, cranial nerve lesions and extrapyramidal signs have also been reported”
“One characteristic feature of the disease is exhaustion, any effort producing generalised fatigue. Often there (is) emotional instability and lack of concentration. The clinical outcome may take any of three courses: some patients recover completely, some follow a relapsing course and some are permanently incapacitated”
“At a symposium held recently at the Royal Society of Medicine to discuss the disease and plan research there was clear agreement that myalgic encephalomyelitis is a distinct nosological entity”
“Other terms that have been used to describe the disease were rejected as unsatisfactory for various reasons: the cardinal clinical features show that the disorder is an encephalomyelitis…indeed, the exhaustion and tiredness are similar to that described by patients with multiple sclerosis”
“From the patient’s point of view the designation ‘benign’ is misleading, since the illness may be devastating”
“Some authors have attempted to dismiss this disease as hysterical, but the evidence now makes such a tenet unacceptable. The organic basis is clear --- from the detection of an increased urinary output of creatine, the persistent findings of abnormal lymphocytes in the peripheral blood of some patients, the presence of lymphocytes and an increased protein concentration in the cerebrospinal fluid and the neurological findings. Immunological studies showed a high incidence of serum anticomplementary activity and the presence of ill-defined aggregates on electron microscopy of acute-phase sera”. (This Editorial was fully referenced).
1978
An outbreak of encephalomyelitis in the Royal Free Hospital Group, London, in 1955
Nigel Dean Compston
Postgraduate Medical Journal 1978:54:722-724
“It became clear early on that there was organic involvement of the central nervous system. There was objective evidence of involvement (of the CNS)”
“The most characteristic symptom was the prolonged painful muscle spasms”
“Bladder dysfunction occurred in more than 25% of all the patients”
“Objective evidence of brain stem and spinal cord involvement was observed”
“McEvedy and Beard’s (psychiatric) conclusions ignore the objective findings”.
1979
Clinical and biochemical findings in ten patients with benign myalgic encephalomyelitis
AM Ramsay A Rundle
Postgraduate Medical Journal 1979:55:856-857
“Ten patients were investigated for blood levels of myoglobin and various enzymes. The biochemical pattern bears a close similarity to that found in Duchenne muscular dystrophy (DMD). These findings are discussed with particular reference to the recent suggestion that the permeability of cell membranes may be impaired by changes in intracellular energy mechanisms”
“The dominant clinical features could be classified as follows: (1) abnormal muscle fatigability (with severe pain, particularly in the legs and back) (2) circulatory impairment was a feature of all cases, suggestive of hypothalamic damage and (3) impairment of memory and inability to concentrate was common in all patients”
“The duration of illness in the ten cases was 35 years, 9 years, 6 years, 3 years, 2 years, 23 years, 17 years, 2 years, 5 years and 17 years respectively. A tendency to severe relapse was a feature of (four) cases”
“If the aetiological factor in benign myalgic encephalomyelitis impairs the permeability of the muscle cell membrane as a result of changes in the intracellular energy content, this could be followed by a differential loss of intracellular proteins”.
1981
Was it Benign Myalgic Encephalomyelitis? CS Goodwin
Lancet 1981:January 3: 37
“In 1969 it was suggested that ME should only be diagnosed if neurological and muscle signs were found. Parish has described the neurological signs and the symptoms of involvement of the autonomic nervous system”
“It is important that the title ‘myalgic encephalomyelitis’ should be restricted to patients who show some of each of the three major features of the disease: Firstly, symptoms and signs in relation to muscles, such as recurrent episodes of profound weakness and exhaustion, easy fatiguability, and marked muscle tenderness. Secondly, neurological symptoms or signs, especially affecting the eyes, or weakness of peripheral muscles, as demonstrated by the voluntary muscle test; or some loss of peripheral sensation; or involvement of the autonomic nervous system (orthostatic tachycardia, abnormal coldness of the extremities, episodes of sweating or pallor, [and] bladder disturbances). Thirdly, biochemical abnormalities, such as a raised urinary creatine, or an abnormal electrophoresis pattern with raised IgM”.
1983
Sporadic myalgic encephalomyelitis in a rural practice BD Keighley EJ Bell
JRCGP June 1983:339-341
“ME (is) a distressing and often prolonged illness. Many of the patients included in the study had been dismissed by hospital clinicians with the implication that there was no organic basis for their problems. As the study progressed, a pattern to the complexity of the symptoms developed (which 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 and dysuria”
“The group described here are patients who have had miserable illnesses. There is a large number of ill and unhappy patients in the community”.
1984
Myalgic encephalomyelitis and the general pracitioner JC Murdoch
New Zealand Family Physician 1984:11:127-128
“Recent reports have shown an association with infection with the Coxsackie (sic) and two authoritative editorials have pointed to an entirely physical basis for the disorder”
“Most sufferers had monumental problems with work, family and personal life and with their doctors. They should be warned to expect a long illness charaterised by relapses. They should be certified as unfit for work”
“In the long-term sufferer, patients are often anxious to identify food and chemical allergies”.
1984
New Zealand Medical Journal 1984: 14th November:782
“It has been my consistent observation that activity requiring physical exercise or mental concetration exacerbates the condition”
“Many ME patients also experience food and chemical intolerances, and are often therefore unusually sensitive to the side effects of drugs”.
1984
ibid
“An attempt to recover normal fitness and activity levels can exacerbate the condition and bring about a relapse”.
1985
ANZMES, 10th October 1985
“The following features are commonly represented: atopy, history of food reactions and allergies”
“ME can be indistinguishable from multi-allergy syndrome”
“(There is) a tendency to a relapsing course”
“(In addition to the classic features), other features include (a) plethora of symptoms – usually involving multi-organ systems. The person may have a moist chest, headaches with sore muscles of the shoulders, neck and back. They may have frequency of urine or an irritable bowel. There is often oesophageal reflux with oesophageal tenderness and intermittent oesophegeal spasm. Chest pain may be intermittently prominent, and may be severe enough for hospital admission (and there may be) palpitations and a tight chest. Vision (is) often blurred, (with) stinging -- often burning -- pain behind the eyes (and) sensitivity to light. (There may be) sore joints”
“The commonest mistake doctors make is failing to take a wide enough view (with) an adequate systems review when encountering apparently unconnected complaints”
1985
Persisting Illness and Fatigue in Adults with Evidence of Epstein Barr Virus Infection
Stephen E Straus et al
Annals of Internal Medicine 1985:102:7-16
(Note that in the US, the condition was at that time thought to be associated with the Epstein Barr (glandular fever) virus and so was known as chronic EBV disease)
“By all regards, including formal evaluations, many of these patients appeared to be neurotic. However, our detailed studies have uncovered a series of subtle, yet objective, organic abnormalities in these patients”
“This disorder is not rare”
“It is of immeasurable benefit to patients with this disorder to document an organic basis for their complaints”.
1985
The postviral fatigue syndrome – an analysis of the findings in 50 cases PO Behan, WMH Behan, E J Bell Journal of Infection 1985:10:211-222
“Our data confirm the organic basis of the illness (and) suggest that it is associated with disordered regulation of the immune system and persistent viral infection”
“The illness was severe, with a high morbidity and a disastrous effect on their lives”.
1985
Electrophysiological studies in the post-viral fatigue syndrome Goran A Jamal Stig Hansen
JNNP 1985:48:691-694
“The post-viral fatigue syndrome, also known as ME, has been recognised recently as a distinct neurological entity with increasing evidence of the organic nature of the disease”
“The most important findings were type II fibre predominance, subtle and scattered fibre necrosis and bizarre tubular structures and mitochondrial abnormalities”
“About 75% of the patients had definitely abnormal single fibre electromyography results. This was regarded as evidence of abnormality in the peripheral part of the motor unit”
“We conclude that we have shown clear electrophysiological evidence of an abnormality in the peripheral part of the motor end unit in patients with post-viral fatigue syndrome”.
1986
Correlation between allergy and persistent Epstein-Barr virus infection in chronic active EBV infected patients George B Olsen James F Jones et al
(Note that in the 1980s (ME)CFS was known as Chronic EBV Disease)
“Eighty percent of patients demonstrate clinically significant IgE mediated allergic disease, including food and drug reactions”
“The data indicate that patients have a high association with hypersensitivity states”
“Percent positive responsiveness to allergens is consistent with the high degree of allergy observed in these patients”.
1987
The postviral fatigue syndrome: a review MI Archer
JRCGP 1987:37:212-216
“Relapses are precipitated by undue physical or mental stress”
“However compelling the evidence for an hysterical basis may be, there is further, equally compelling, evidence of organic disease”
“Some patients do have frank neurological signs”
“Muscle biopsies showd necrosis and type II fibre predominance”.
1987
J Campbell Murdoch
The New Zealand Family Physician 1987:14:51-54
“Two hundred patients fitting the criteria were seen between January 1985 and December 1986”
“All had other symptoms, the most common of which were irritability, lack of concentration, short-term memory problems, vertigo, visual upset, recurrent sore throat, difficulty with breathing, palpitations, abdominal distension and diarrhoea”
“On examination there were two important common findings – the presence of acute tenderness in the muscle bulk and a positive Romberg’s sign, indicating vestibular upset”
“17% of patients had a positive smooth muscle antibody and a further 11% had a weakly positive SMA. 4% had anti-nuclear antibody and two patients had weakly positive thyroid autoantibody”
“This syndrome has about the same prevalence as Parkinson’s disease and is more prevalent than multiple sclerosis”
“The clinical findings strongly suggest that the musculature and the central nervous system are the main sites of disorder in these patients”
“In addition, nuclear magnetic resonance revealed abnormal muscle metabolism”
“Such patients become immunocompromised. That ME patients are immunocompromised is beyond question”
“Surely the underlying message is that patients with this syndrome need not await the solving of this puzzle
before they are accorded the sick role (and) in the interim, it is our duty to care for them as sick”.
1987
Phenotypic and functional deficiency of natural killer cells in patients with Chronic Fatigue Syndrome Michael Caliguri, Dedra Buchwald, Paul Cheney, Daniel Peterson, Anthony L Komaroff et al
J Immunol 1987:139:3306-3313
“These studies show that a majority of patients with (ME)CFS have low numbers of NKH1 T3- lymphocytes”
“When tested for cytotoxicity against a variety of different target cells, patients with CFS consistently demonstrated low levels of killing”
“In this study we demonstrate that a majority of patients with (ME)CFS have abnormally low numbers of NKH1+T3- cells that result in a distinct NK subset abnormality, as well as a deficiency of cytotoxicty against both standard and viral-infected targets”
“(This study) will hopefully improve our understanding of the immunopathogenesis of this illness”.
1987
“Drug therapy is not recommended in general, and there are some drugs, particulary anaesthetics, that can have disastrous effects”.
1987
“Certain factors are almost guaranteed to worsen ME. Surgery and general anaesthetics may cause relapse”.
1988
A Consultant Anaesthetist (Dr F.L.M of the McNeil Centre for Research in Anaesthesia, Philadelphia)
“When there may be neural involvement by a disease, spinal or epidural anaesthesia is not recommended because of the risk of worsening symptoms”
“Normally, a depolarizing muscle relaxant is used, (but) in persons with neuromuscular disease such as demyelination, which has been decribed for (ME/CFS), this drug has a known risk of causing potassium release from muscle, which can lead to cardiac arrest”
“Because of chronic muscle weakness, breathing may be impaired (and) muscle weakness increases the risk of respiratory failure”
“More care than usual is appropriate in the case of (ME/CFS)”.
1988
Postviral fatigue syndrome PO Behan WMH Behan
Crit Rev Neurobiol 1988:4:2:157-178
“Any kind of muscle exercise can cause the patient to be almost incapacitated for some days afterward. In severe cases, the patient is usually confined to bed”
“Psychiatric diagnoses abound: many patients will already have been labelled as neurotic, neurasthenic, or depressed”
“What is certain is that when one reviews PFS with its clinical features and laboratory results, it becomes plain that this is an organic illness in which muscle metabolism is severely affected”.
1988
Human Enteroviral Infection EG Dowsett
J Hosp Inf 1988:11:103-115
“Enteroviral syndromes range from trivial to severe and many are unrecognised or underinvestigated”
“Myalgic encephalomyelitis has been the cause of more than 50 epidemics. Serious (neurological) sequelae are common. Enteroviral infections in humans, as in animals, may be persistent”
“The main features (of ME) are prolonged fatigue following muscular exercise, an extended relapsing course which, unlike other postviral fatigue, lasts for months or years”
“An association with neurological, cardiac and other characteristic enteroviral complications (including) pancreatitis has long been recognised as part of severe generalised enteroviral infection”.
1988
Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase
LC Archard, NE Bowles et al
JRSM 1988:81:325-331
“These data show that enterovirus RNA is present in skeletal muscle of some patients with postviral fatigue syndrome up to 20 years after onset of disease and suggest that persistent viral infection has an aetiological role”
“These results provide further evidence that Coxsackie B virus plays a major role in ME, either directly or by triggering immunological responses which result in abnormal muscle metabolism”.
1988
Transmissible disease and psychiatry RP Yonge
JRSM 1988:81:322-325
“This was the first time that it was possible to show unequivocally that there was an organic basis for the fatigue experienced by a patient diagnosed as having postviral syndrome”
“Nuclear magnetic resonance (imaging) has shown a metabolic basis for the fatigue experienced by some patients diagnosed as suffering from postviral fatigue syndrome”
“We have shown that muscle fatigue and weakness for which there has previously been no explanation is indeed in the muscle rather than in the mind”.
1988
Chronic fatigue syndromes: relationship to chronic viral infections Anthony L Komaroff
“The fatigue and associated symptoms are debilitating in all patients and can be fully disabling in some”
“There are a group of conditions which go by different names but which may share a final common pathogenic pathway. (These include) true chronic mononucelosis; another, much less frequent group have apparent severe chronic active EBV infection; another chronic, fatiguing illness is called myalgic encephalomyelitis; another illness characterized by chronic fatigue is fibromyalgia (and) finally, there are patients with what we now call chronic fatigue syndrome”
“One simple piece of evidence that these (“CFS”) patients are suffering from an ‘organic’ illness is the sudden onset of the illness in 85% of the patients”
“A few of the individuals in our group had acute neurologic events: primary seizures (7%); acute, profound ataxia (6%); focal weakness (5%); transient blindness (4%) and unilateral parasthesias not in a dermatomal distribution”
“On past medical history, the only clearly striking finding is a high frequency of atopic or allergic illness in approximately 50%”
“On physical examination, unusual and abnormal findings are observed in up to 50% of patients, (including) hepatosplenomegaly”
“Because of the neurologic and cognitive symptoms, (some) patients have had lumbar punctures. In 45% of the patients, there was pleocytosis (the presence of an abnormally large number of lymphocytes in the cerebrospinal fluid). In several patients, the lymphocytes were described as ‘atypical’ ”
“It is the judgment of the neuropsychologists that the pattern of test performance suggests an ‘organic’ deficit, rather than cognitive dysfunction secondary to mood disorder”.
1988
Allergy and the chronic fatigue syndrome Stephen E Straus et al
J Allergy Clin Immunol 1988:81:791-795
“Many patients report inhalant, food or drug allergies (and) this article emphasizes our assessment of one of (the syndrome’s) more common manifestations, allergy”
“Allergies are a common feature of patients with the chronic fatigue syndrome”
“Attempts to avoid all the allergens further isolate the victims of ‘total allergy’ ”
“A variety of immunologic abnormalities can be detected in patients with the chronic fatigue syndrome, abnormalities that suggest that the immune system may participate in the pathogenesis of this disease”
“It is possible that individuals with a heightened reactivity to allergens also respond more vigorously to certain infectious antigens. Inherent hyper-responsiveness would be the initiation by certain infectious agents of a level and duration of lymphokines and interleukin release that would in themselves perpetuate the reactive symptoms of the syndrome”
“Among the features of this syndrome is a high prevalence of allergy, an allergy that appears to be substantial”.
1988
FHN Spracklen
“The frequency of this condition is demonstrated by the increasing number of ME associations being founded around the world”
“The strength of the ME lobby in the UK is illustrated by the fact that the Member of Parliament for Clydesdale, Jimmy Hood, drew attention to ME with the first reading of a Bill on 23rd February 1988 and the second reading on 15th April 1988. This was used to attract public attention and counter the suffering and injustice caused by this terrible illness”
“Hood requested an annual report on progress made in investigating the causes, effects anmd treatment of ME”
“A promise was given by the Parliamentary Under-Secretary of State for the Department of Health and Social Services, Mrs Edwina Curry, that ME was recognized under the NHS and would be treated correctly in all NHS hospitals”
“The difficulty in understanding (ME)CFS is that one is probably dealing with several different entities, all of which can result in the Ramsay triad of (i) muscle fatiguability, where even after a minor degree of physical effort, three or more days may elapse before muscle power is restored; (ii) an extraordinary variability or fluctuation of symptoms even over 24 hours; and (iii) an alarming chroncity”
“In Mowbray’s opinion, 62% of cases are due to persistent infection with enteroviruses, especially when muscle fatigue occurs only on exertion”
“Mowbray stresses that pericraditis is found in 10% of patients”
“Reflecting British thinking, Dowsett has stated that the evidence for persistent enteroviral infection is so strong that the use of the term CFS as opposed to ME is to be deplored”
“There is no question that fatigue is worsened by exercise”
“It seems unlikely that the neuropsychiatric symptoms described in this syndrome are causative”
“Attempts to invoke concepts like mass hysteria (and) psychosomatic illness seem unwarranted”
“Two-thirds of patients report respiratory or gastro-intestinal symptoms”
“While the onset in 20% of cases may be insidious, the remainder follow acute vertigo, Bornholm’s disease, pericarditis, herpangina, thyroiditis, parotitis, viral meningitis or acute visual disturbances”
“Electron microscopy has shown increased mitochondria and ‘bizarre tubular structures’ ”
“Periods of physical stress should be avoided”
“Since exertion and physiotherapy are known to aggravate symptoms, rest is probably the most important treatment”.
1989
The Chronic Fatigue Syndrome Anthony L Komaroff, Stephen E Straus, Nelson M Gantz, James F Jones
Ann Int Med 1989:110:5:407
“We agree that primary psychiatric disease is common in patients with fatigue and that only an occasional patient seeking medical care for chronic fatigue has a well-recognised organic illness”
“We believe there is another disorder, the chronic fatigue syndrome, that is likely to be an organic disorder”
“A critical question has not been addressed: are patients fatigued because they have a primary mood disorder, or has a mood disorder developed as a secondary component of a chronic organic illness?”
“We are concerned about the interpretation of data: many of the instruments base the diagnosis of psychiatric disease on the presence of symptoms that could well reflect an underlying organic illness”
“It would be inappropriate to conclude that patients with chronic fatigue had only a primary psychiatric disorder”.
1989
Statement to the (USA) House Appropriations Subcommittee, 25th April 1989
James F Jones, National Jewish Center for Immunology, Denver
CFIDS Chronicle: Spring 1989:28-30
“For the patients, there is no question that the illness exists. For the physicians who see these patients, the similarities among them allow ready identification of a distinct clinical illness. For those who scoff at this
concept, one can only query as to what happened to their curiosity and their ability to listen to patients”.
Nancy Eby, Seymour Grufferman et al
In: Natural Killer Cells and Host Defense. Ed: Ades EW and Lopez C. 5th International Natural Killer Cell Workshop. Pub: Karger, Basel, 1989:141-145
1989
Stephen E Straus, National Institutes for Allergy and Infectious Diseases
CFIDS Chronicle: Spring 1989:77-78
“Many of the immunological and physical features of ME/CFS cannot be explained by mental illness”.
John Esdale, Rheumatologist, Montreal General Hospital.
CFIDS Chronicle: Spring 1989:79
“It is a real organic problem and people who have it don’t need the additional stress of hearing doctors tell them they are crazy”.
1989
CFIDS in Children David S Bell, Instructor in Paediatrics, Harvard Medical School
CFIDS Chronicle: Spring 1989:34-37
“The most obvious factor is of course the severity of CFIDS”.
1989
Chronic Fatigue Syndrome Gerald H Ross et al
Canadian Medical Association Journal 1989:140:361
“We have found that many people with this clinical picture have concomitant food and chemical sensitivities”
“We were therefore greatly surprised to learn from Dr Holland (ibid: 706) that ‘it would be non-therapeutic to offer such a patient empathy’ and that we must not condone a belief in a ‘non-existent disease’ ”
“These statements are difficult to reconcile with the immunologic abnormalities, disorders of muscle metabolism and abnormal results of muscle biopsies found in such patients”.
1989
Chronic Fatigue Syndrome Gerald H Ross, William Rea et al
“Being unable to find physical diagnoses for (ME)CFS does not necessarily mean that psychologic illness is the cause. It may simply be that our understanding of the factors precipitating the illness is far from complete”
“Medical history teaches us that once physical causes for ‘psychologic’ symptoms are discovered, the condition moves as if by magic from the psychiatic to the medical realm”
“It is our experience that a substantial percentage of (ME)CFS cases may arise or be worsened by adverse reactions to components of the environment, such as food, inhalants and chemicals”.
Carolyn L Warner
(also in Neurology, March 1989:39:3:Suppl 1:420)
“The abnormalities we found provide evidence for central nervous system and neuromuscular involvement”.
1989
Chronic Fatigue J Cuozzo
JAMA 1989:261:5:697
“The disabling weakness and exhaustion a patient with ME/CFS experiences is so profound that ‘fatigue’ is probably an insult”.
1989
Immunological abnormalities in the chronic fatigue syndrome Andrew R Lloyd, Denis Wakeford, Clement R Broughton and John M Dwyer
Med J Australia 1989:151:122-124
“A concurrent immunological disturbance is likely to be associated with the persistence of viral antigen”
“The finding of significantly increased numbers of peripheral blood mononuclear cells that express class II histocompatibility antigens (HLA-DR) in our patients implies immunological activation of these cells”
“These cell-surface antigens may have been induced by interferons or other cytokines. Once activated, these cells may continue to produce the cytokines which may mediate the symptoms of CFS”.
1989
Myalgic encephalomyelitis: postviral fatigue syndrome and the heart Norman Grist
BMJ 1989:299:1219
“Similar immunological and metabolic disturbances in myalgic encephalomyelitis may also result from chronic infection, usually with enteroviruses, providing the organic basis of the postviral fatigue syndrome”
“This condition is characterised by severe fatiguability and recuperation through rest. The myocardium, however, cannot rest --- except terminally”.
1989
Postviral fatigue syndrome DO Ho-Yen
British Journal of Hospital Medicine 1989:42:250
“I believe that postviral fatigue syndrome is a distinct entity with a precise definition. In only a few patients is there confusion with psychiatric illness”
“As I understand the article (referring to an article by Wessely), graded exercise has been suggested but has not ‘led to improvement in patients’. This article’s suggestion of exercise until symptoms cease is the reason why a patient may be hospitalised”.
1989
Neuropsychological Deficits in Chronic Fatigue Syndrome Sheila Bastien
Paper presented at the International Conference ‘Epstein-Barr Virus: The First 25 Years”, Oxford University, UK, April 1989; also published in CFIDS Chronicle, Summer / Autumn 1989: 24-26
“A population of (ME)CFS patients was tested neuropsychologically over a period of three years. The age range was 16 to 65. All patients had multiple physical symptom complaints that are typical of this condition”
“(Patients) reported problems with memory, concentration, sequencing, spatial relations, calculation, word-finding, comprehension, visual discrimination, and motor ability”
“Many of these individuals were observed to have significant motor and balance problems”
“Verbal memory was 68% below the mean T score on the immediate condition and 68% below the mean T score on the delayed condition”
“The pattern of focal and lateralised impairments in these patients is consistent with an atypical organic brain syndrome”.
1989
In addition to the commonly known symptoms such as profound fatigue, low grade fever, sore throat, painful lymph nodes, muscle weakness, myalgia, sleep disturbance, headaches, migratory arthralgia, photophobia, transient visual scotoma, forgetfulness, confusion and cognitive difficulties, the following form part of the clinical picture: “spacial disorientation, blurring of vision, sensitivity to light, eye pain, frequent (spectacle) prescription changes, emotional lability, chills and night sweats, shortness of breath, dizziness and balance problems, sensitivity to heat and cold, irregular heartbeat, abdominal pain, dirrahoea, numbness of face or extremities, burning in hands or feet, hearing sensitivity, menstrual problems, hypersensitivity of the skin, chest pain, rashes, allergies and sensitivities to odours and chemicals, weight changes without changes in diet, feeling ‘in a fog’, fainting, muscle twitching, seizures, and hair loss”.
1990
“The number of patients having (ME)CFS has increased. Research has demonstrated that cognitive (and) affective symptoms are prominent (and) psychiatrists are being asked to participate in the assessment and management of patients with this syndrome”
“Two patterns of illness have been recognized: relapsing and remitting, and continuous”
“It is not yet certain whether psychoneurosis can fully explain some of the physical and immunological aberrations noted in such patients”
“All of the findings regarding psychopathology are descriptive and do not allow for conclusions about the direction of the relationship --- ie. whether the psychopathology is secondary to (ME)CFS) or is the cause of (it)”
“Findings related to psychopathology may be artifactual”
“The pathophysiology of fatigue attributable to psychiatric disease remains unclear (and) it is premature to make aetiological assumptions”.
1990
Clinical and General Research Findings in CFIDS Paul Cheney
“I believe this is a disease that affects the central nervous system and I’ll show you some slides to help convince you of that. We are going to explore what evidence there is for neurologic disease.”
“This is a study done by Dr Carolyn Warner from the Dent Neurologic Institutue in Buffalo, New York, which specializes in multiple sclerosis. Some people think that (ME)CFS can look like MS and there are clinical features that are overlapping”
“I think this study is important because this is an MS specialist looking at (ME)CFS and seeing they are not MS, and then looking at them neurologically”
“Here are a number of symptoms. You can see that the great majority of these (ME)CFS cases have neurologic symptoms”
“The most specific neurologic symptoms that I find in (ME)CFS is dysequilibrium”
“These patients have a balance disturbance and on certain simple neurologic tests they fall over”
“On more sophisticated tests of vestibular fuinction they are often grossly abnormal”
“Nearly every patient had something abnormal within the central nervous system”
“Our evidence of central nervous system involvement can be demonstrated by tests looking directly at the CNS”
“These inflammatory and/or demyelinating plaques can be seen in the white matter, in the cerebellum and white matter tracks throughout the high cerebral convexities and in the frontal lobes”
“These lesions are not specific, they could be inflammation, they could be demyelination, there could be an element of destruction. What it says is that there is something going on in the brain”.
1990
The diagnosis of postviral syndrome DJD Perrins
JRSM 1990:83:413
“The clinical pattern of myalgic encephalomyelitis has much in common with multiple sclerosis”.
1990
The chronic fatigue syndrome: a return to common sense AM Denman
Postgraduate Medical Journal 1990:66:499-501
“It is salutary to reflect how many sufferers from infectious mononucleosis (glandular fever) may in the past have been maligned for their allegedly ‘functional’ illness before appropriate laboratory tests became available. Similar considerations apply to chronic fatigue following enteroviral infection, particularly by Coxsackie B virus”
“In some patients, muscle pain and easy fatiguability may be so prominent as to suggest a separate diagnostic category ‘myalgic encephalomyelitis’. This is also a point of practical importance if a form of the syndrome existed in which active physical rehabilitation were contra-indicated”
“Progress will only be achieved if the different categories of chronic fatigue are dissected with scientific objectivity and therapeutic reason”.
1990
Patient management of the postviral fatigue syndrome DO Ho-Yen
JRCGP 1990:40:37-39
“The subgroup of patients with immunological abnormalities may have a prolonged illness”
“It has been suggested that a new approach to the treatment of patients with postviral fatigue syndrome would be the adoption of a cognitive behavioural model (Wessely S, David A, Butler S, Chalder T: Management of chronic (postviral) fatigue syndrome. JRCGP 1989:39:26-29). Those who are chronically ill have recognised the folly of the approach and, far from being maladaptive, their behaviour shows that they have insight into their illness”.
1990
Objective measurement of personality variables in epidemic neuromyasthenis patients
A. Sricklin et al
South African Medical Journal 1990:77:31-34
“Too often only one aspect of the illness is treated, with little attention to other symptoms”.
1990
The psychiatric status of patients with the chronic fatigue syndrome Ian Hickie et al
Br J Psychiat 1990:156:534-540
“We conclude that psychological disturbance is likely to be a consequence of rather than an antecedent risk factor to the syndrome. Our results suggest that patients are no more psychologically disturbed before the onset of their illness than members of the general population”
“There is no evidence from our well-defined sample to support the hypothesis that CFS is a somatic presentation of an underlying psychological disorder. In particular, there is no evidence that CFS is a variant or expression of a depressive disorder”.
1990
Myalgic encephalomyelitis: an alternative theory CWM Wilson
JRSM 1990:83:481-483
“In his discussion paper on myalgic encephalomyelitis (April 1989 JRSM), Wessely suggested that a new term should be used to describe the observed symptoms. In his definition of CFS, he did not refer to any of the somatic symptoms which are always present”
“Evidence of biochemical and neurological changes have been reported in the brain. These symptoms are resistant to tranquillisers and antidepressant therapy in ME. Indeed, patients are often allergically sensitive to these drugs”
“The identification of viral antibodies in the tissues confirms the existence of a previous viral challenge”.
1990
CD8 Deficiency in patients with muscle fatigue following suspected enteroviral infection (myalgia encephalitica) JR Hobbs, JA Mowbray, JE Monro et al
In: Protides of the Biological Fluids 1990:36:391-398
“Postviral states have been shown to be associated with acquired (secondary) T-cell deficiencies, particularly with CD8 dysfunction, and even immune paresis”
“It is also clear that the acquisition of T-cell deficiency, particularly the CD8 subset, can itself impair immune regulation and predispose to atopy not previously experienced by the patient”
“It is known that psychological disturbance can influence immunity. We, ourselves, have undertaken extensive T-cell subset measurements in normal subjects subjected to psychological stress, and would point out that in none of these did we see CD8 levels as low as in some 40% of our ME patients”
“It seems unlikely that the severe CD8 deficiency found could be due to psychological disturbance”.
1990
Immunologic Abnormalities in Chronic Fatigue Syndrome Nancy Klimas et al (Nancy Klimas is Professor of Medicine, University of Miami School of Medicine; she is also Director of Immunology, Director of AIDS research and Director of the Allergy Clinic at Miami)
J Clin Microbiol 1990:28:6:1403-1410
“(ME)CFS is a clinical state of some complexity. In order to characterize in a comprehensive manner the status of laboratory markers associated with cellular dysfunction in patients with this syndrome, 30 patients were studied”
“All the subjects were found to have multiple abnormalities in these markers”
“The most consistent immunological abnormality detected was low natural killer (NK) cell cytotoxicity”
Lymphocyte phenotypic marker analysis of peripheral blood lymphocytes showed that there were significant differences between patients with (ME)CFS and controls”
“The pattern of immune marker abnormalities observed was compatible with a chronic viral reactivation syndrome”
“Depression of cell-mediated immunity was noted in our study population, with over 80% of patients having values below the normal mean”
“The values obtained were closely similar to those we observed in a group of human immunodeficiency virus type I-seropositive (HIV) intravenous drug users”
“Result from the present study indicate that there is an elevation in activated T-cells”
“A strikingly similar elevation in CD2+ CDw26+ cells has been reported in patients with multiple sclerosis”
“Functionally, the CD45RA+ CD4 cells, also termed Tinf, for inflammatory CD4 cells, can transfer delayed-type hypersensitivity”
“Selective depletion of CD4+ CD45RA+ cells was noted during the active phases of multiple sclerosis, but not in patients in remission or with inactive multiple sclerosis or other neurological diseases. Deficiencies quantitatively similar to those observed in patients with (ME)CFS were also reported in patients with other autoimmune diseases”
“The results of the present study suggest that (ME)CFS is a form of acquired immunodeficiency”.
1990
Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA L Cunningham NE Bowles
RJM Lane V Dubowitz LC Archard
J Gen Virol 1990:71:1399-1402
“This suggests that enteroviral persistence in muscle is due to a defect in control of viral RNA synthesis”
“These data are the first demonstration of persistence of defective virus in clinical samples from patients
with (ME)CFS”.
1990
Myalgic encephalomyelitis --- a persistent enteroviral infection? EG Dowsett AM Ramsay et al
Postgraduate Medical Journal 1990:66:526-530
“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 of characteristic enteroviral infection”
“Advice to avoid over-exertion is mandatory”
“In our opinion, two major errors are responsible for the present confusion surrounding the case definition, aetiology and diagnosis of ME. First, there has been a failure to distinguish the syndrome from postviral debility following Epstein Barr mononucleosis, influenza and other common fevers. Second, there has been a failure to recognise the unique epidemiological pattern of ME”.
1990
Aerobic work capacity in patients with chronic fatigue syndrome MS Riley DR McClusky et al
“Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects”
“We found that patients with the chronic fatigue syndrome have a lower exercise tolerance than either normal subjects or patients with the irritable bowel syndrome. The main reason for the impaired exercise performance seems not to be diminished motivation”
“Previous studies have shown biochemical and structural abnormalities of muscle in patients with the chronic fatigue syndrome”
“Patients with (ME)CFS invariably indicated an aspiration to return to (their) previous level of activity”.
1991
Immunological Markers in ME/CFS Presentation at the AACFS Research Conference, November 1990. Professor Nancy Klimas
(reported in CFIDS Chronicle: Spring 1991:47-50)
“The most compelling finding was that the NK (natural killer) cell cytotoxicity in (ME)CFS was as low as we have ever seen in any disease. This is very significant data. (ME)CFS patients represent the lowest cytotoxicty of all populations, including HIV AIDS, we have ever studied”.
1991
The Disease of a Thousand Names David S Bell
Pollard Publications, New York, 1991
In addition to the standard symptoms such as exhaustion, headache, malaise, short term memory loss, muscle pain and abdominal pain, included in his list of 50 commonly presented symptoms in ME/CFS are the following: double vision, balance disturbance, dizziness, palpitations, shortness of breath, easy bruising, swelling of extremities and eyelids, incontinence, and hair loss”.
1991
Chronic fatigue syndrome and depression Ian Hickie et al
Lancet 1991: (April 13):337
“Kendell seeks to draw together similarities between (ME)CFS and depression but ignores important differences. Patients with typical depression are characterised by clinical features such as anhedonia, weight loss, suicidal ideation, psychomotor retardation or agitation that are notably absent in (ME)CFS”
“Patients with (ME)CFS lack many essential characteristics of patients with primary depression; their symptoms more closely resemble those seen with depression complicating primary medical disorders”.
1991
Chronic fatigue syndrome: clinical condition associated with immune activation
Alan L Landay, Carol Jessop, Evelyne Lennette, Jay A Levy
Lancet 1991: (21 September):338:707-712
“Despite (the) clinical findings, some physicians question whether there is such a syndrome”
“Immunological disorders such as those seen in viral infections have been described in (ME)CFS – eg. decreased function of NK cells and macrophages, reduced mitogenic response of lymphocytes, B-cell subset changes, and activation of CD8 cells”
“These findings further support the notion that (ME)CFS involves immune disorders due most likely to an infectious agent”
“Depression developed in many patents after two years of illness”
“We found that patients could be placed into three groups according to their symptoms. Group A consisted of patients whose illness was so severe that they had less than 25% of their normal daily activity and also had multiple symptoms; group B had reduced physical activity and group C initially had many symptoms but had substantially improved”
“Three cell surface markers gave noteworthy results. These data point to a high probability (90%) of having active (ME)CFS if an individual has two or more of the CD8 cell subset alterations”
“Evaluation of CD8 cell subsets in control subjects with a diagnosis of depression showed no significant differences compared with healthy controls”
“Laboratory findings have shown low level autoantibodies which may reflect an underlying autoimmune disease”
“When all (ME)CFS patients were considered, we found a state of immune activation specifically among the CD8 lymphocyte population. Moreover, the suppressor subset of CD8 (CD11b) was reduced in many patients, significantly so in patients with multiple symptoms and severe incapacitating illness (group A)”
“Our findings suggest that the CD8 CD11b population is reduced, and the CD38 and HLA-DR markers remain persistently raised”
“The immune disorder in CFS does not seem to reflect depression”.
1991
Mitochondrial abnormalities in the post-viral fatigue syndrome WMH Behan et al
Acta Neuropathol 1991:83:61-65
“The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection”
“The pleomorphism of the mitochondria in the patients’ muscle biopsies was in clear contrast to the findings in the normal control biopsies”
“Diffuse or focal atrophy of type II fibres has been reported, and this does indicate muscle damage and not just muscle disuse”.
1991
Evidence for Impaired Activation of the Hypothalamic Pituitary Adrenal Axis in Patients with Chronic Fatigue Syndrome Mark A Demitrack, Stephen E Straus et al
J Clin Endocrinology & Metabolism 1991:73:1224-1234
“Several lines of evidence suggest that the various components of the hypothalamic pituitary adrenal axis (the HPA axis) merit further study in these patients, for instance, debilitating fatigue, and abrupt onset precipitated by a stressor, arthralgias, myalgias, post-exertional fatigue, exacerbation of allergic responses and disturbances of mood and sleep are all characteristic of glucocorticoid insufficiency”
“A deficiency of CRH (cortico-releasing hormone) could theoretically contribute to the lethargy and fatigue that are the cardinal symptoms of (ME)CFS”
“Identification of psychological illness by standard diagnostic criteria includes many symptoms that are an inherent part of the definition of (ME)CFS”
1991
Biopsychosocial aspects of Chronic Fatigue Syndrome JDL Yeomans SP Conway
J Inf 1991:23:263-269
“(ME)CFS is associated with physical, psychological and social distress. The illness cannot be defined using just one of these dimensions. Such a unilateral approach has resulted in unnecessary controversy over the nature of the ‘real’ core of (ME)CFS”
“Psychiatric case definition is central to a psychiatrist’s work and deserves careful attention in discussions of (ME)CFS with medical colleagues”
“It was hoped (that our present study) would avoid selection biases favouring the presence of psychiatric illness as might occur with selection by specialised fatigue clinics”
“A single item on the HAD depression scale refers to ‘feeling slowed down’. Not surprisingly, this was cited by all patients. When this single item was removed from analysis, no patient retained a rating of depression. This emphasised the importance of possible false positive diagnosis of depression on the basis of somatic symptoms”
“Wessely and Powell (JNNP 1989:52:940-948) found the total psychiatric morbidity in (ME)CFS was 72% ---other studies have found it to be 21%. (Our) study finds a variable prevalence depending on the criteria used. This emphasised the ease with which psychiatric rating scales may lead to false positive diagnoses in patients with physical symptoms”
“It is possible that studies of (ME)CFS have had a tendency to over-estimate the prevalence of depression”
“The absence of (biological markers) has been interpreted as support for a psychogenic aetiology for (ME)CFS. It is important to diagnose such syndromes correctly, and (our) study suggests that questionnaires alone may over-emphasise psychiatric syndromes”
“It is unnecessary and indeed unproductive to force patients into unsuitable diagnostic categories as a condition of treatment”.
1991
Postviral fatigue: current neurobiological perspective PGE Kennedy
In: Postviral Fatigue Syndrome. British Medical Bulletin 1991:47:4:809-814 Ed: PO Behan, DP Goldberg and JF Mowbray pub: Churchill Livingstone
“It is clear that there is now a widespread consensus that postviral fatigue syndrome (PVFS) is a definite disease entity. Recent intense research has made it no longer acceptable to dismiss PVFS as non-organic”
“Molecular viral studies have proved to be extremely useful. They have confirmed the likely important role of enteroviral infections, particularly with Coxsackie B virus”
“The PVFS has now come of age as a definite organic entity”.
1991
The management of Post Viral fatigue Syndrome in General Practice David G Smith
ibid:265-279
“In the absence of any coherent move in Britain to develop criteria for the disease, the medical profession has had to fall back on the American Working Case definition of chronic fatigue syndrome, Holmes et al 1988, although this is not synonymous with ME”.
1991
Assessment and Diagnosis of ME in the Psychiatric Clinic Rachel Jenkins
ibid 241-246
“Once one is familiar with the concept of post-viral fatigue syndrome, such patients are in practice not too difficult to differentiate from those with true psychiatric illnesses such as depressive illnesses, anxiety, hypochondriasis or hysteria”
“The classic diurnal variation of mood in severe depressive illnesses is not seen: the patient with ME will relate their depression to the frustration felt at not being able to do the active things they enjoy doing”
“The depressed patient feels fatigued and will be unmotivated to exercise, but can do most activities if required and sustain them, including climbing a hillside, standing upright for two hours or carrying a heavy object. The sufferer with ME, on the other hand, cannot do more than a fraction of these activities”
“There are also subtle difference between the impairment of concentration in depression and that in ME; in ME, the impairment of concentration tends to be associated with the timing and severity of the fatigue”
“In addition, specific cognitive abnormalities are present in ME, including difficulty in marshalling material, difficulty in finding the correct words in a sentence, and in appropriate syntax; speech is sometimes slurred, and the patient appears more clumsy than usual. They tend to bump into doorways and furniture more frequently, may display old bruises, and may complain of a feeling of dysequilibrium
“The physical symptoms should be an aid to diagnosis, although they may be wrongly attributed to primary psychological illness unless care is taken in eliciting them”
“Under a regime of pushing beyond physical limits, severe relapses occur and physical limits decrease. This is the exact opposite of what happens in a depressed person who is otherwise physically well, where steady pushing beyond physical limits will extend those limits and increase physical fitness”
“People with this illness do not tolerate antidepressants well”
“Patients with postviral fatigue syndrome are often very scared and in considerable pain”.
1991
History of Chronic Fatigue Syndrome Stephen E Straus
Review of Infectious Diseases 1991:13: Suppl 1: S2-S7
“It is my goal to review briefly the history of (ME)CFS. In so doing, it becomes apparent that (ME)CFS is not of recent origin”
“Despite the broad divergence of opinion in the medical community, there is little doubt that classic allergy and atopy are inexplicably prevalent in (ME)CFS. In a recent study, a high proportion (50%) of patients were found to be reactive to a variety of inhalant or food allergens when innoculated epicutaneously in the classic manner”
“Because neurologic symptoms have dominated in certain of the case clusters (and even in some sporadic ones), the syndrome has been called benign myalgic encephalitis (sic)”
“Certainly patients with (ME)CFS differ immunologically from their healthy counterparts and it is this observation, more than any other today, that is evoked in support of the organic hypothesis of disease causation”.
1991
Defining the Chronic Fatigue Syndrome Gary P Holmes
ibid S53-S55
“Preferably, patients with (ME)CFS who have such immune abnormalities might be considered a subset of the larger group: ie. persons with (ME)CFS who have immune dysfunction”.
1991
Review of Laboratory Findings for Patients with Chronic Fatigue Syndrome
Dedra Buchwald Anthony L Komaroff
ibid S12-S18
“Those most consistently reported include depressed natural killer cell function and reduced numbers of natural killer cells; low levels of circulating immune complexes; low levels of autoantibodies, particularly antinuclear antibodies and antithyroid antibodies; altered levels of immunoglobulins; abnormalities in number and function of lymphocytes”
1991
Chronic Fatigue Syndrome in Northern Nevada Sandra A Daugherty, Daniel Peterson, Sheila Bastien et al ibid S39 - S44
“Enlargement of the spleen and liver is not unusual”
“The striking distortion of cognitive function along with the abnormal results of the MRI scans observed in these patients suggests a pathologic process in the brain”
“The pattern of focal and lateral impairments in these patients is more consistent with that of an atypical organic brain syndrome”
“This is not the pattern seen in depression, psychosis, anxiety or situational stress”.
1991
Jordan Grafman et al
ibid: S45- S52
“The potential for confusing fatigue induced by virus with fatigue associated with mood is great”
“(Kennedy states that in (ME)CFS the) ‘fatigue is the decline in performance that occurs in any prolonged or repeated task’ ”
“We remain cautious in attributing the cause of (ME)CFS in the vast majority of cases to an underlying psychiatric conflict. The tendency towards such an attribution is currently popular”.
1991
Laboratory Abnormalities in Chronic Fatigue Syndrome Dedra Buchwald
“Allergies are a common feature of patients with (ME)CFS”.
1991
Postviral Fatigue Syndrome and the Cardiologist RG Gold
ibid: 227-231
“The patient suffering from PVFS (ME) is referred to a cardiologist almost always because of chest pain. The usual cause of the chest pain in these patients is chronic benign pericarditis. When we reviewed this condition in 1967, we felt then that the pericarditis was the final common pathway in an abnormal immunological response”
“The pain of pericarditis has some highly characteristic features which suggest the diagnosis to the clinician who is aware of these”
“(The) chest pain is variable in character. It is sometimes severe, sharp and stabbing, or it may be dull and aching. The pain may last for several hours or even days. It frequently occurs centrally but even in the same patient may recur on a different occasion in the right or left chest or back. It is commonly aggravated by sudden movement, change of posture, respiration, or swallowing”
“The patient may complain of shortness of breath”
“Palpitations are frequent, with sinus tachycardia being a common and at times distressing symptom”
“The presence of the pericardial rub is independent of the intensity of pain”
“The diagnosis of the cause of chest pain as a complication of ME rests almost entirely on careful clinical evaluation. Chronic benign pericarditis may continue or recur for many years and, like ME, be a distressing and debilitating illness. There is, alas, no way of predicting how long the condition will persist, and no reliably successful means of treating it”
“The main role of the clinician is to provide symptomatic relief and sympathetic support”.
1991
USA: Multiple chemical sensitivity JB Sibbison
“Exposure to trace amounts of chemicals in indoor air or common foods has been said to produce symptoms such as headaches, memory loss, dizziness (etc)”
“There is no specfic treatment for MCS, whose existence is widely acknowledged”
“Treatment usually consists of avoidance of the offending substance (by special diets, for example)”
“Some governments will not wait for questions to be answered through research. The Bush administration is already requiring special accommodation for the chemically sensitivie in its housing policy”
“The Chemical Manufacturers Association’s senior officials are concerned about the mounting litigation”.
1991
Peter O Behan
“Many different neurological and psychiatric syndromes follow viral infections. Recently, attention has been focused on (a) common postviral neurological syndrome, ie. the postviral fatigue syndrome, termed myalgic encephalomyelitis”
“Guidelines from the Medical Research Council may be unhelpful, since they suggest that “CFS” is a better term”
“The chief organ affected is skeletal muscle and severe fatigue, with or without myalgia, is the main symptom. The fatigue appears clinically to be of central origin in most patients but a peripheral component, ie. muscle involvement, has also been demonstrated by biochemical, electrophysiological, pathological and virological studies”
“Muscle metabolism is undoubtedly disturbed, but other organs, particularly the brain, heart, endocrine system and immune system are also affected”.
“The idea that mass hysteria might account for these outbreaks was fashionable at one time, but like the majority of illnesses for which a psychiatric aetiology has been put forward, this hypothesis lacked all scientific merit and with the emergence of hard data, can be totally rejected”
“Some patients never exhibit any psychiatric manifestations whatsoever”
“It is quite clear to anyone who has experience in dealing with these patients that their symptoms differ considerably to those (with) endogenous depression”
“Gastro-intestinal symptoms are often made worse by certain foods and antibiotics”
“Patients who present with labyrinthitis often have a dysequilibrium syndrome, so that they are uncertain of their balance when walking”
“The recent attempt by Oxford psychiatrists to formulate (another case definition) has not taken us any further”
“It should be pointed out that there are definite subgroups who will have signs and symptoms of myocarditis”
“We have seen a large number of patients who presented with classical postviral fatigue syndrome and who continue to have intermittent but definite abnormalities in liver enzymes”
“Some patients exhibit all the symptoms of irritable bowel syndrome in addition to PVFS”
“We have demonstrated mitochondrial abnormalities on electronmicroscopy”
“75% of patients were found, using single fibre EMG, to have prolonged jitter values”
“Our experience with patients who have had the illness for one year or more and in whom there continues to be fluctuation in symptoms intensity but no remission, is that the prognosis is poor for recovery”.
1992
US Department of Health and Human Services
“Many patients have a history of allergies years before the onset of (ME)CFS, and allergic symptoms may worsen after these patients become ill. Allergies are so prevalent in (ME)CFS patients that it is important to differentiate those symptoms that are allergy-related”
“(ME)CFS symptoms overlap with those of many well-recognised illnesses, for example, lupus erythematosus (SLE) and multiple sclerosis”
“Psychiatric evaluations fail to identify any psychiatric disorders in some patients”
“Many people with (ME)CFS have neurologic symptoms, including parasthesias, dysequilibrium and visual blurring. A few patients have more dramatic neurologic events such as seizures, periods of severe visual impairment, and periods of paresis”
“Many investigators believe that the illness involves a constant antigenic challenge to the immune system and, as a consquence, a constant immunologic response to that challenge”
“Evidence suggests that several latent viruses may be actively replicating more often in (ME)CFS patients that in healthy control subjects”
“Most investigators believe that reactivation of these viruses is probably secondary to some immunologic challenge”
“For many patients, it is important to avoid situations that are physically stressful”
“A balanced diet and rest enhance well-being”
“For now, physicians do not have all the answers, but in treating people with (ME)CFS, they can offer guidance with compassion”.
1992
Ocular manifestations of Chronic Fatigue and Immune Dysfunction Syndrome
Walter Potaznick, Neil Kozol
“Whatever name is used, the syndrome most often consists of neurological symptoms, immunological abnormalities, cognitive impairments (and) disabling fatigue in a variety of other symptoms reflecting involvement in some if not all body systems”
“(We looked at) over 200 patients and over 200 controls and evaluated the data for each of 25 (ocular) symptoms”
“Statistical analysis shows that the increased rate at which patients with CFIDS report ocular symptoms is not explained by chance alone”
“Many CFIDS patients experience very troubling and disabling symptoms”
“It appears that the ocular symptoms of CFIDS are genuine”.
1992
Chronic Fatigue Syndrome N Phillips
Australia and New Zealand Journal of Psychiatry 1992:26:329-330
“ It is important for psychiatrists to familiarise themselves with the complexities of this syndrome and to be aware of the rapidly expanding body of new literature on this illness”
“Wessely’s work on depression and (ME)CFS is methodologically flawed; (his patients) were not diagnosed using the full diagnostic criteria and therefore included many ‘non-pure’ (ME)CFS cases”
“Psychiatrists need to utilise such terminologies as ‘the sick role’ and ‘abnormal illness behaviour’ with great caution when discussing chronic illness. Not only will they alienate their medical colleagues, but, more importantly, the patients they are trying to help”
1992
CFIDS Chronicle Special Bulletin Walter Gunn (Principal Investigator of CFS studies at the Centres for Disease Control (CDC), USA February 1992
“Our surveillance study does not support the notion that CFS is a psychiatric disease and, in fact, suggests that it has an organic basis”.
1992
Cell-mediated immunity in patents with chronic fatigue syndrome, healthy controls and patients with major depression A Lloyd I Hickie J Dwyer et al
Clin Exp Immunol 1992:87:76-79
“Evaluation of the psychiatric status of patients with (ME)CFS does not support the contention that (ME)CFS is simply a depressive equivalent”
“Although depression is common in patients with (ME)CFS, the disturbance in cell-mediated immunity in this disorder differs in prevalence and magnitude from those associated with major depression”
“It is likely therefore that this disorder is generated and maintained by an immunopathological process within the central nervous system”.
1992
A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpes Type 6 infection
Dedra Buchwald, Paul Cheney, Robert Gallo (co-discoverer of the HIV virus), Anthony L Komaroff et al
Ann Intern Med 1992:116:2:103-113
“57% of patients were bed-ridden, shut in or unable to work”
“Immunologic (lymphocyte phenotying) studies revealed a significantly increased CD4 / CD8 ratio. Taken together, the controlled studies cited above and many others, seem to indicate an immune system chronically responding to a ‘perceived’ antigenic challenge”
“Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with oedema or demyelination in 78% of patients”
“Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically-mediated inflammatory process of the central nervous system”.
1992
Possible up-regulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome AMO Bakeit, PO Behan, TG Dinan et al
BMJ 1992:304:1010-1012
“”In the past few years evidence which shows the organic nature of this condition has accumulated”
“The results suggest upregulation of the hypothalamic 5-hydroxytryptamine (5-HT) receptors in patients with PVFS but not in those with primary depression”
“Most of these patients had objective evidence of muscle damage, as shown by mitochondrial changes and the persistence of enteroviral RNA sequenced in muscle”
1992
Postviral fatigue syndrome Costa DC, Brostoff J, Douli V, Ell PJ
BMJ 1992:304:1567
“ (SPECT scans have demonstrated) significant deficits in brain perfusion, particularly in the hypothalamus and pons”.
1992
The postviral fatigue syndrome WRC Weir
Current Medical Literature (Royal Society of Medicine) 1992:6:1
“In more acutely affected individuals the advice to ‘exercise back to fitness’ is a recipe for disaster”.
1992
Neuro-opthalmological Manifestations of Chronic Fatigue Syndrome Alfredo A Sadun and Pravin U Dugel In: The Clinical and Scientific Basis of Myalgic Encephalomyelitis Chronic Fatigue Syndrome Ed: Byron M Hyde, Jay Goldstein and Paul Levine Pub: The Nightingale Research Foundation, Ottawa, Canada 1992
“The neuro-opthalmological manifestations of (ME)CFS are myriad and common. Two thirds of the patients complained of blurred vision; one patient (complained of) binocular diplopia. The most obvious objective sign was nystagmus; it was even more astonishing that approximately one quarter of the patients had a primary nystagmus, since such nystagmus is always pathological”.
1992
How do I diagnose a patients with Chronic Fatigue Syndrome? J Goldstein
In: The Clinical and Scientific Basis of ME CFS. Ed: BM Hyde, J Goldstein, P Levine. Pub: the Nightingale Research Foundation, Ottawa, Canada, pp247-252
“Other disease associations such as irritable bowel syndrome, polycystic ovarian disease, thyroiditis and endometriosis are probably part of (ME)CFS. It is a rare woman with (ME)CFS who has not had hair loss, usually diffuse”.
1992
Jay A Levy, Alan L Landay et al
“Since about 1986, clinicians in the San Francisco area have seen an upsurge of (ME)CFS in their practice”
“In the majority of cases, the onset of depression occurred six months after the onset of the illness”
“Three (immune) markers were found to be highly significant: the data indicate a high (90%) probability that an individual with two or more of the CD8+ cell subset changes will have active (ME)CFS”
“We expect that when the clinical data on these individuals are tabulated, severe illness will again correlate with signficiantly abnormal lymphocyte phenotypic findings”
“Our observations strongly suggest that a large population of (ME)CFS patients have immunologic disorders and that their symptoms could be explained by a chronic immune activiation state”
“We speculate that (ME)CFS represents a type of autoimmune disease. Because of the known higher prevalence of (ME)CFS in women, the 3:1 female/male ratio would not be unexpected: autoimmune syndromes are more common in women”
“Because of the autoreactive nature of this condition, it might also lead to other immune disorders, such as well recognized autoimmune diseases and multiple sclerosis”.
1992
Massimo Riccio, Ariel F Lant et al
“At the present time, the term ME is viewed as probably the most satisfactory in encompassing all the features of this distressing illness”
“The acute presentation in all patients followed a similar pattern”
“Muscle pain was common after even trivial attempts at exercise”
“All patients reported difficulty in concentration which was often profound”
“All reported an inability to socialize because of exhaustion”
“Few controversies in modern medicine have raged so fiercely as that over the syndrome which has been called ME”
“(This) study offers an insight into the nature of the central nervous system component of the disorder. The results presented here may point to the presence of an organic aetiology for the neuropsychiatric abnormalities which have bee noted clinically in some patients”
“The neurpsychological abnormalities we have shown are not accountable wholly in terms of depression”
“In the presence of evidence of organic memory impairement, it seems reasonable that the patients should consider themselves to be ill”
“In conclusion, the present study provides evidence that, in some patients with operationally defined ME, cognitive abnormalities which may be compatible with an organic cause can be detected”
1993
Clinical presentation of chronic fatigue syndrome Anthony L Komaroff
“Many diseases that today are well-established -- for example, multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis – were at one time controversial until definitive objective abnormalities were identified”
“(ME)CFS can last for years and is associated with marked impairment”
“(ME)CFS is) a terribly destructive illness”
“The tenacity and ferocity of the fatigue can be extraordinary”
“On past medical history, the only clearly striking finding is a high frequency of atopic or allergic illness in approximately 50-80%, in contrast to a background prevalence of about 10% in the population at large”
“As for the symptoms that accompany the fatigue, it is striking that these symptoms are experienced not just occasionally but are present virtually all the time”
“In our experience, 80% of patients with (ME)CFS have an exceptional post-exertional malaise”
“(Physical examination findings) include abnormal Romberg test (and) hepatomegaly (and) splenomegaly”
“Anyone who has cared for patients with (ME)CFS will recognize that (the) description of the patient with lupus eloquently describes many patients with (ME)CFS as well”.
1993
John DeLuca Susan Johnson Benjamin Natelson
The objective of this study was to compare the cognitive performance of subjects with (ME)CFS, MS, and healthy controls.
“The MS group was added so that the performance of the (ME)CFS group could be compared with a population presenting with a symptoms cluster similar to that of patients with (ME)CFS, but of known organic cause”
“The results of this study clearly demonstrate that subjects with (ME)CFS and MS exhibit difficulties in information processing efficiency compared with matched controls”
“These results indicate that subjects with (ME)CFS and subjects with MS show signficiant impairment when compared with appropriate controls”
“The results of our study indicate that depression alone cannot account for the deficits observed in the (ME)CFS and MS groups”.
1993
Biochemical and muscle studies in patients with acute onset postviral fatigue syndrome
VR Preedy et al
J Clin Pathol 1993:46:722-725
“Patients with acute onset PVFS lose muscle protein synthesis potential, but not muscle bulk. Histopathology is consistent with these observations. These peturbations may contribute to the apparent feature of perceived muscle weakness associated with the persistent viral infection in the muscles themselves”.
1993
Persistence of enterovirus RNA in muscle biopsy samples suggest that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy
NE Bowles, LC Archard et al
Journal of Medicine 1993:24:2:145-160
“The term PVFS has been widely misused to describe all forms of chronic fatigue”
“Investigation with strand-specific riboprobes demonstrated that in each of the PFS cases found positive for virus RNA, enterovirus persisted in these non-inflammatory muscle biopsies as a replication defective mutant"
“Our data confirm that enterovirus infection of muscle is not a general feature of the population”
“This association of enterovirus infection is compatible with what is often considered an autoimmune disease”
“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”
1993
Testimony before the US FDA Scientific Advisory Committee, 18th February 1993
Paul Cheney, Professor of Medicine, Capital University, USA; Medical Director of the Cheney Clinic, North Carolina, USA (one of the world’s leading exponents on ME/CFS)
“I have evaluated over 2,500 cases. At best, it is a prolonged post-viral syndrome with slow recovery. At worst, it is a nightmare of increasing disability with both physical and neurocognitive components. The worst cases have both an MS-like and an AIDS-like clinical appearance. We have lost five cases in the last six months. The most difficult thing to treat is the severe pain. Half have abnormal MRI scans. 80% have abnormal SPECT scans. 95% have abnormal cognitive-evoked EEG brain maps. Most have abnormal neurological examination. 40% have impaired cutaneous skin test responses to multiple antigens. Most have evidence of T cell activation. 80% have evidence of an up-regulated 2-5A antiviral pathway. 80% of cases are unable to work or attend school. We admit regularly to hospital with an inability to care for self”.
1993
Memory deficits associated with chronic fatigue immune dysfunction syndrome
Curt Sandman (Professor of Psychiatry and Human Behaviour, University of California School of Medicine)
Biol Psych 1993:618-623
“The performance of the CFIDS patients was sevenfold times worse than either the control or the depressed group. These results indicated the memory deficit in CFIDS patients was more severe than assumed by CDC criteria. A pattern emerged supporting neurological compromise in CFIDS”.
1994
Summary and Perspective: Epidemiology of Chronic Fatigue Syndrome Paul H Levine
Clin Inf Dis 1994:18: (Suppl 1):S57-S60
“Epidemiologists play a number of roles in the study of diseases; the functions of these specialists include case definitions, descriptions of disease patterns, identification of risk factors, and analysis of clinical trials. In the study of a complex illness such as (ME)CFS, for which no definitive diagnostic test exists, the most important aspect is case definition – all other areas of investigation depend on this standard for appropriate interpretation of results”
Most patients affected in a cluster of ‘epidemic neuromyasthneia’ do not fit the 1988 case definition of (ME)CFS”
“It has been noted for a number of years that a history of allergies appears to be an important risk factor for (ME)CFS”
“The spectrum of illnesses associated with a dysregulated immune system must now include (ME)CFS”
“The precipitating factors leading to (ME)CFS were also an important focus of this symposium. In addition to a history of allergy, other factors such as exposure to chemicals and noxious agents were noted to be possible triggers”
“It is likely that host response, due to genetic predisposition, contributes to the development of (ME)CFS as an outcome of the exposure”.
1994
Association between HLA Class II Antigens and the Chronic Fatigue Immune Dysfunction Syndrome
RH Keller, MA Fletcher, N Klimas et al
ibid S154-S159
“The chronic fatigue immune dysfunction syndrome (CFIDS) is a major subgroup of the chronic fatigue syndrome (ME/CFS). We and other investigators have reported a strong association between immune dysfunction and a serological viral reactivation pattern among patients in this group. This finding appeared similar to that for a variety of conditions such as chronic active hepatitis, juvenile rheumatoid arthritis and systemic lupus erythematosus (SLE or lupus), in which a definite association between a particular HLA-DR/DQ haplotype and increased disease frequency has been reported”
“It is possible that DR4 (relative risk for CFIDS 1.6) and DR5 (relative risk for CFIDS 1.8) are also associated with an increased risk of developing CFIDS”
“The data presented herein suggest that CFIDS, together with a variety of immune-mediated diseases, may share similar sequences of pathogenic mechanisms”
“It may be speculated that in a particular sub-population, a genetic predisposition may be triggered immunologically by any of a number of potential stimuli, resulting in a state of chronic immune dysequilibrium”
“This model could easily explain the recent findings with regard to acute viral infection, allergies or other mechanisms that are obscured by the process of chronic immune activation”.
1994
Decreased Natural Killer Cell Activity is Associated with Severity of Chronic Fatigue Immune Dysfunction Syndrome EJ Ojo-Amaize et al
ibid S157-S159
“Our results confirm and extend previous reports that low NK cell cytotoxicity is a pronounced immunologic abnormality found in some patients with CFIDS”
“The fact that NK cell activity decreases with the increased severity and duration (of the disorder) suggests that measurement of NK cell function could be useful for stratification of patients and for monitoring the progression of CFIDS”.
1994
Immunologic studies of CFS Andrew R Lloyd
“Circumstantial evidence suggests that (ME)CFS may result from a disordered immune response to a precipitating infection or antigenic challenge”
“Findings from several case reports and one controlled study have suggested that serum levels of IgG subclasses (especially IgG1 and IgG3) may be reduced in patients with (ME)CFS”
“The three most prominent and reproducible findings are (1) impaired lymphocyte proliferation in response to stimulation by mitogens has been repeatedly documented and has also been shown to be dissociated from the potential effect of concurrent mood disturbance on this response; (2) investigators have reported increased number of peripheral blood lymphocytes bearing activation markers such as HLA-DR and interleukin-2R in these patients; (3) impaired cell-mediated immune function”
“It is likely that conflicting data may arise because of the heterogeneity of the sample populations studied”.
1994
Upregulation of the 2-5A Synthetase/ Rnase L Antiviral Pathway Associated with Chronic Fatigue Syndrome Robert J Suhadolnick Daniel L Peterson Dharam Ablashi et al
“The object of this study was to measure key parameters of the 2-5A synthetase/Rnase L antiviral pathway in order to evaluate possible viral involvement in (ME)CFS”
“The data presented suggest that the pathway is an important indictaor of the antiviral state in (ME)CFS”
“Evidence that this pathway is activated in (ME)CFS was identified in the subset of severely disabled patients as related to virological and immunological status”.
1994
Closing Remarks of the Symposium Anthony L Komaroff and Nancy Klimas
ibid S166-167
“Few studies by psychiatrists are presented in this symposium. Many investigators who have argued that (ME)CFS is primarily a psychiatric disorder chose not to present their work”.
1994
Simultaneous Measurement of Antibodies to Epstein Barr Virus, Human Herpes Virus 6, Herpes Simplex Virus Types 1 and 2, and 14 Enteroviruses in Chronic Fatigue Syndrome: Is there evidence of Activation of a Nonspecific Polyclonal Immune Response? FA Manian
Clin Inf Dis 1994:19:44-53
“Of the 14 enteroviruses tested for, (only) those to Coxsackie B1 and B4 were present at significant titres in cases versus controls at a percentage significantly higher than that of controls”.
1994
David S Bell (Instructor in Paediatrics, Harvard Medical School)
Postgraduate Medicine 1994:98:73-81
“Abnormalities of immune function, hypothalamic and pituitary function, neurotransmitter regulation and cerebral perfusion have been found in patients with (ME)CFS. Recent research has yielded remarkable data. The symptoms of (ME)CFS have long been viewed as a neurologic pattern, as confirmed by names such as myalgic encephalomyelitis. A link is being forged between the symptoms of (ME)CFS and objective evidence of central nervous system dysfunction. The view that (ME)CFS is a primary emotional illness has been undermined by recent research”.
1994
The ocular signs and symptoms of chronic fatigue syndrome Caffery BE et al
“(ME)CFS affects the ocular system in many ways”
“Every patient seen with (ME)CFS presented with at least one ocular symptom”
“There were three major prevalent ocular findings in patients with (ME)CFS: all patients presented with ocular symptoms; (some) patients had reduced accommodation (and some) patients had objective abnormalities of preocular tear film and ocular surface”
“In the past, the ocular signs and symptoms of (ME)CFS have not been considered to be a major component of the disease process. However, it appears that the ocular system may be very much affected by this systemic disease”
“The objective findings of the anterior segment suggests an organic aetiology”
“The number of patients presenting with tear film and ocular surface abnormalities was remarkable”
“There are histological studies that demonstrate lacrimal gland invasion by inflammatory cells in Sjogrens syndrome. One could speculate that there may be similar histological findings in patients with (ME)CFS”
“The ocular neurological symptoms that presented in such a large number of (ME)CFS patients suggests a neurological basis of the disease. The visual symptoms combined with the reduced motor skills of these patients might lead some clinicians to entertain the diagnosis of multiple sclerosis”.
1994
Detection of Intracranial Abnormalities in Patients with Chronic Fatigue Syndrome: Comparison of MR Imaging and SPECT
RB Schwartz AL Komaroff et al
AJR (American Roentgen Ray Society) 1994:935-941
“SPECT scans showed more abnormalities than MR scans did in patients with (ME)CFS”
“The complaints of afflicted patients, particularly those involving the central nervous system, can be misdiagnosed or even considered by some to be factitious. The finding of abnormal neuroimaging studies in the vast majority (94%) of patients with (ME)CFS indicates that this condition is associated with physiologic changes that can be observed objectively”
“As with any chronic inflammatory condition affecting the central nervous system, the T2-bright foci on MR in (ME)CFS may represent a perivascular cellular infiltrate and / or reactive demyelination of the surrounding white matter. Alternatively, these abnormalities may reflect the results of a vasculopathy involving the small vessels of the cerebral white matter; indeed, the distribution of lesions on MR in ME/CFS is similar to that observed in occlusive arteriolar disease of any origin”
“The cortical defects measured with SPECT likewise may result from direct infection of neurological elements, from cellular dysfunction due to circulating cytokines, or from decreased flow through cortical arterioles owing to vasculitis”
“Specifically, on the basis of our observations, the white matter abnormalities seen on MR images may represent foci of chronic demyelination which appear to be irreversible”.
1994
“There is a group of commonly-used anaesthetic agents which are known histamine-releasers and are best avoided by CFIDS patients”
“Since so many of these histamine-releasing agents are commonly used during emergency surgery, it would be advisable (for patients with (ME)CFS) to wear a medical alert bracelet”
1995
SPECT Imaging of the Brain: Comparison of Findings in Patients with Chronic Fatigue Syndrome, AIDS Dementia Complex and Major Unipolar Depression
RB Scwartz, AL Komaroff et al
AJR (American Roentgen Ray Society)1994:162:943-951
“This study demonstrates that (ME)CFS shares some similarities on SPECT imaging with AIDS Dementia Complex (ADC). By this objective standard, the pathophysiologic processes in the central nervous system of patients with (ME)CFS would seem more similar to that in patients with ADC than in patients with unipolar depression”
“The similarity in MCUI data between patients with ADC and (ME)CFS suggests a similar origin for the neurologic dysfunction in these conditions (and) the similarity in appearance on SPECT suggests the possibility of similar underlying abnormalities in ADC and (ME)CFS”.
1995
Daniel L Peterson
JCFS 1995:1:3-4:123-125
“In my experience, ME/CFS is one of the most disabling diseases that I care for, far exceeding HIV disease except for the terminal stages”.
1995
Immunology Roberto Patarca
ibid: 195-202
“Several groups have been working on defining immune status variables of relevance to the nosology and follow-up of (ME)CFS patients”
“One rationale for the immunological approach stems from the experience accumulated with similar syndromes of heterogeneous presentations such as autoimmune and environmentally-triggered diseases”
“The hypothesis was entertained that (ME)CFS may be associated with certain HLA class II antigens, as are some forms of environmental disease”
“Viruses are frequently reactivated in association with immune system dysregulation in (ME)CFS and may contribute indirectly to the symptomatology”
“These observations underscore the distinction between (ME)CFS and psychiatric maladies”
1995
‘Abnormal’ Illness Behaviour in Chronic Fatigue Syndrome and Multiple Sclerosis
Peter Trigwell Simon Hatcher
BMJ 1995:311:15-18
“Those who see (ME)CFS as primarily a psychiatric disorder regard it as a variety of somatisation. The concept of somatisation overlaps with that of ‘abnormal illness behaviour’. There is an explicit judgment to be made in concluding that a patient is exhibiting abnormal illness behaviour: it is that the doctor does not think that the patient’s objective pathology entitles him to be placed in the sick role he expects”
“If (ME)CFS is a variety of somatisation, then we should expect to find evidence of abnormal illness behaviour with the syndrome”
“We wanted to confirm whether patients with (ME)CFS have abnormally high levels of disease conviction and if so, whether it is associated with other elements of abnormal illness behaviour or is, indeed, merely a corollary of chronic disease”
“We draw two conclusions from our study. Firstly, the illness behaviour questionnaire seems to be unsatisfactory as a measure of abnormal illness behaviour in (ME)CFS. Secondly, we have confirmed that disease conviction is common in (ME)CFS”
“Scores on illness behaviour questionnaires cannot be taken as evidence that (ME)CFS is a variety of abnormal illness behaviour because the same profile occurs in multiple sclerosis”.
1995
Exercise response and psychiatric disorder in chronic fatigue syndrome
Russell JM Lane Leonard C Archard et al
BMJ 1995:311:544-545
“In previous studies patients with (ME)CFS showed exercise intolerance in incremental exercise tests, which seemed to be related to an increased perception of effort. We examined venous blood lactate responses to exercise at a work rate below the anaerobic threshold in relation to psychiatric disorder”
“Our results suggest that some patients with (ME)CFS have impaired muscle metabolism that is not readily explained by physical inactivity or psychiatric disorder”.
1995
Brainstem perfusion in chronic fatigue syndrome DC Costa C Tannock J Brostoff
Quarterly Journal of Medicine 1995:88:767-773
“Patients with (ME)CFS have a generalised reduction of brain perfusion, with a particular pattern of hypoperfusion of the brain stem”.
1995
Detection of Enterovirus-specific RNA in Serum: the Relationship to Chronic Fatigue
Geoffrey B Clements et al
J Med Virol 1995:45:156-161
“In the study described here, enteroviral sequences were found in significantly more (ME)CF patients than in the two comparison groups. The presence of the enteroviral sequences in a significant number of patients points to some role in (ME)CF”
“A variety of immunological disturbances have been reported for (ME)CF patients which may relate in some way to the enteroviral persistence”
“This study provides evidence for the involvement of enteroviruses in just under half of the patients presenting with (ME)CF and it confirms and extends previous studies using muscle biopsies”
“We provide evidence for the presence of viral sequences in serum in over 40% of (ME)CF patients and also in some buffy coat cells and stool samples”.
1995
Pathophysiology of a Central Cause of Post Polio Fatigue Richard L Bruno et al
In: Ann NY Acad Sci 1995:753:257-275
“These relationships and recent empirical comparisons between post polio and chronic fatigue will be described”
“Beginning in Los Angeles in 1934 and continuing for more than 20 years, a dozen outbreaks occurred of a disease that was at first diagnosed as poliomyelitis, then as ‘atypical’ poliomyelitis and finally named myalgic encephalomyelitis (ME)”
“Most patients were left with a marked exhaustion and fatiguability that were always made worse by exercise and emotional stress”
“A more direct association between the polio virus and ME was seen in 1948”
“More recent support for a relationship between poliovirus and ME came in 1989 when a dangerously rising titre to type III poliovirus was documented in a patient who did not have polio but who had been diagnosed with ME”
“A constellation of symptoms resembling ME was termed ‘chronic fatigue syndrome’ (CFS) --- like ME and post-polio fatigue, CFS is characterized by complaints of chronic fatigue and impaired concentration that are triggered or exacerbated by physical exertion and emotional stress”
“Hyperintense signal imaged along white matter tracts may have resulted from damage to the brain parenchyma by a local, tissue-toxic effect of the poliovirus”
“Notably, periventricular and deep white (but not grey) matter HS have been imaged in between 40 and 100% of (ME)CFS patients and have been suggested to represent either enlarged, fluid-filled spaces around arterioles, or demyelination”
“Neuroradiologic and neuroendocrine data have indicated damage to brain areas responsible for cortical activation and attention in polio survivors and others with chronic fatigue”
“Word-finding difficulties are reported by 82% of polio survivors with fatigue, and appear similar to word-finding problems reported by (ME)CFS patients”.
1996
Prognosis in chronic fatigue syndrome: a prospective study on the natural course
JM Vercoulen et al
JNNP 1996:60:489-494
“Comprehensive assessment of (ME)CFS entails measurement on all dimensions simultaneously”
“The finding that on three out of seven outcome measures these patients did not show improvement underlines the importance of multidimensional assessment in studies on prognosis”
“Psychological well-being (including depression) did not predict improvement in this study, although others (Wessely et al) have suggested that this factor plays a part in the perpetuation of complaints”
“Avoidance of physical activity is also thought to play a part in the perpetuation of complaints (Wessely et al) but the present study is not conclusive on this issue”
“The improvement rate in patients with a relatively long duration of complaints is small”.
1996
Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome.
Jan H M M Vercoulen, Caroline Swanink et al
Lancet, 1996:347:858-861
“Antidepressant therapy is commonly used (in (ME)CFS). However, there has been no randomised, placebo-controlled double-blind studies showing the effectiveness of antidepressant therapy in (ME)CFS. We have carried out such a study to assess the effect of fluoxetine (Prozac) in depressed and non-depressed (ME)CFS patients”
“There have been anecdotal reports that fluoxetine is poorly tolerated by patients with (ME)CFS. In our trial, 15% of fluoxetine-treated patients withdrew because of side effects, a higher withdrawal rate than in fluoxetine trials in depressed patients on the same regime”.
“In our study, fluoxetine was no better than placebo in treating depression”.
“Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS”.
“We conclude that prescription of 20mg fluoxetine in CFS is unwarranted, irrespective of whether depressive symptoms are present; it does not lead to improvement in any area of the patient’s functioning”.
1996
Chronic Fatigue Syndrome: is total body potassium important? Burnet RB et al
Medical Journal of Australia, 1996:164:6:384
The authors found that total body potassium (TBK) was lower in patients with (ME)CFS and they suggest that abnormal potassium handling by muscle in the context of low overall body potassium may contribute to fatigue in (ME)CFS.
1996
Lung function test findings in patients with chronic fatigue syndrome.
De Lorenzo et al
Australia and New Zealand Journal of Medicine, 1996:26:4:563-564.
The authors found that compared with controls, patients with (ME)CFS showed a significant reduction in all lung function parameters tested.
1996
Abnormality of adrenal function in the patients with chronic fatigue syndrome.
(Abstract of presentation at the Proceedings of the First World Congress on CFS, Brussels, November 9-11,1995) Yamaguti K et al
JCFS, 1996:2:2/3
“The level of DHEA decreases in some patients and the level of DHEA - S decreases in most patients with (ME)CFS. These abnormalities found in (ME)CFS are quite different from those found in patients with mental and physical diseases reported previously”.
1996
Eosiniphil cationic protein serum levels and allergy in chronic fatigue syndrome.
Conti F et al
Allergy: 1996:51:124-127
“ECP serum levels were significantly higher in (ME)CFS patients than in controls. In (ME)CFS patients, the prevalence of radio-allergosorbent (RAST) positive responses to one or more allergens was 77%, while no control showed positive RAST”.
1996
Chronic Fatigue Syndrome: evaluation of a 30-criteria score and correlation with immune activation. Hilgers A and Frank J.
Journal of Chronic Fatigue Syndrome,1996:2:4:35-47.
The aim of this study was to develop a score to evaluate the severity of (ME)CFS and to correlate the degree of severity with parameters of immune activation; five hundred and five patients were studied using a 45-criteria score and basic laboratory programmes, together with immunological profiles. In most of the patients, further tests of complement system, immune activation markers, hormones and viral serology were evaluated.
385 patients fulfilling the 1994 CDC criteria showed significant differences to healthy controls in 40 of the 45 symptoms assessed. Thirteen symptoms corresponding to CDC criteria were all significant, but 17 further significant criteria were added to improve precision:
respiratory infections; palpitations; dizziness; dyspepsia; dryness of mouth / eyes; allergies; nausea; paraesthesia; loss of hair; skin alterations; eczema; dys-coordination (sic); chest pain; personality changes; general infections; urogenital infections; twitches.
A correlation between the 30-criteria score and immunological parameters could be evaluated in 472 of the 505 patients.
Significant positive correlation was found in numbers of CD8+ T lymphocytes, HLA DR+ lymphocytes, gamma globulins, 1gM, lgG, and for the numbers of types of autoantibodies (mainly ANA, ACA, antithyroid and antiparietal cell antibodies).
Significant negative correlation was found in albumin-globulin ratio, eosinophils and lgE.
Most of these parameters also correlated with one another.
“In increasingly larger groups of patients with (ME)CFS and related constellations we often see clinical signs and longer anamnesis of other symptoms beside the classical criteria of (ME)CFS, especially a high prevalence of local and general infections and hints to prolonged inflammation processes…A reduced or unstable immune control can lead to a chronic neuro-immune activation state and autoimmune disorders. Hypersensitivity symptoms of the patients might not be mediated by classical allergies alone but also result from a type IV hypersensitivity”.
1996
The neuroendocrinology of chronic fatigue syndrome Scott LV Dinan TG
JCFS: 1996:2:4:49-59
The authors note that there is an increasing volume of evidence to support the view that patients with (ME)CFS have unique neuroendocrinology patterns.
Central to this endocrine dysfunction is altered hypothalamic-pituitary-adrenal axis (HPA) activity.
The cardinal findings include attenuated adrenocorticotrophic hormone (ACTH) responses to corticotrophin-releasing hormone (CRH) and low 24 hour urinary cortisol. These are compatible with a mild central adrenal insufficiency.
Adrenal steroids have widespread impact in the brain, and of particular importance is their dense concentration on serotonergic and noradrenergic neurotransmitter pathways.
The authors propose that the disruption of the HPA axis (which may be triggered by a number of stressors) may represent a primary phenomenon, and that neurotransmitter abnormalities (serotonin and noradrenalin) are in fact secondarily heralded by prolonged HPA dysregulation.
1996
Evidence that abnormalities of central neurohormonal systems are key to understanding Fibromyalgia and Chronic Fatigue Syndrome Leslie J.Crofford Mark A.Demitrack
Rheum Dis Clin North America:1996:22:2:267-284
The concept that disorders such as fibromyalgia (FM) and chronic fatigue syndrome (ME/CFS) are associated with subtle and undetectable disturbances in the central nervous system was introduced in 1869 by Beard. Great strides have been made in recent years towards defining neurochemical abnormalities in FM and (ME)CFS, and both FM and (ME)CFS fall into the spectrum of what might be termed stress-related illnesses by virtue of the clinical observation that the onset of both is coincident with physical or emotional stress. The article focuses on abnormalities of the HPA axis and sympathetic nervous system (SNS), ie. the major stress response systems, and the authors point out that it is important to keep in mind that activity of stress response systems is determined by genetic and environmental factors.
The authors present data which supports the view that FM and (ME)CFS could represent different forms of insufficient stimulation of the HPA axis, with both syndromes expressing low hypothalamic CRH but with FM being characterised by increased exposure of the corticotrophs to AVP, while (ME)CFS patients have decreased AVP levels. Patients with a longer duration of disease tend to have more severe basal abnormalities in cortisol levels.
When oestrogenic stimulation diminishes, relative hypo-function of the HPA axis could follow, contributing to the development or maintenance of FM / (ME)CFS.
Further research into the nature of the neurohormonal peturbations in FM and (ME)CFS may elucidate treatment strategies for these disorders.
1996
Neuroimmune mechanisms in health and disease. Part 2: Disease Anisman H et al.
Can Med Assoc.J: 1996:155(8) 1075-1082
In the second part of their article on the emerging field of neuroimmunology, the authors present an overview of the role of neuroimmune mechanisms in defence against infectious disease and in immune disorders. Profound neuroendocrine and metabolic changes take place: acute phase proteins are produced in the liver; bone marrow function and the metabolic activity of leukocytes are greatly increased, and specific immune reactivity is suppressed. Defects in regulatory processes (which are fundamental to immune disorders and inflammatory diseases) may lie in the immune system, the neurendocrine system or both.
Defects in the HPA axis have been observed in autoimmune disease, chronic inflammatory disease, (ME) chronic fatigue syndrome and fibromyalgia.
Defective neural regulation of inflammation is likely to play a pathogenic role in allergy and in gastrointestinal inflammatory disease.
A better understanding of neuroimmunoregulation holds the promise of new approaches to the treatment of immune and inflammatory disease with the use of hormones, neurotransmitters and neuropeptides and drugs which modulate these newly recognised immune regulators.
1996
Prevalence of irritable bowel syndrome in chronic fatigue Gomborone JE et al
JRCP Lond 1996:30:6:512-513
The purpose of this study was to determine the prevalence of irritable bowel syndrome in chronic fatigue sufferers.
A questionnaire about bowel symptoms was sent to 4,000 members of Action for ME self help group, and was returned by 1,797 (45%).
The people with chronic fatigue reported more bowel symptoms including the Manning criteria than the general population.
Seventy three per cent qualified for the diagnosis of IBS, which greatly exceeds estimates of lBS prevalence of up to 22% in the general population.
1996
Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome
Cordero DL Natelson BH et al.
Clin Auton Res: 1996:6:(6):329-333
The purpose of this study was to determine if patients with (ME)CFS have less vagal power during walking and during rest periods following walking.
Patients had significantly less vagal power than the control subjects, despite there being no significant group-wise differences in mean heart rate, tidal volume, minute volume, respiratory rate, oxygen consumption or total spectrum power.
Notably, patients with (ME)CFS had a significant decline in resting vagal power after periods of walking.
These results suggest a subtle abnormality in vagal activity to the heart in patients with (ME)CFS.
1996
Autoantibodies to Nuclear Envelope Antigens in Chronic Fatigue Syndrome
K.Konstantinov D.Buchwald J.Jones et al
J.Clin Invest 1996:98:8:1888-1896
The authors identified and partially characterised the autoantibodies in sera of 60 patients with (ME)CFS.
The autoantibodies were of the lgG isotype.
The occurrence of autoantibodies to a conserved intracellular protein like lamin BI provides new laboratory evidence for an autoimmune component in (ME)CFS.
The immunological abnormalities described are in accordance with a growing body of evidence suggesting chronic, low-level activation of the immune system in (ME)CFS.
The authors found that 52% of patients with (ME)CFS develop autoantibodies to components of the nuclear envelope (NE), mainly nuclear lamins. Their findings suggest that in addition to the other disturbances of the immune system, humoral autoimmunity against polypeptides of the NE is a prominent immune derangement in (ME)CFS.
67% of (ME)CFS patients were positive for NE reactivity, compared with 10% of normal subjects in control groups I and II. In addition, none of the patients with chronic depression or atopy showed reactivity to NE proteins.
These results confirm that the NE reactivity of some (ME)CFS sera is against lamin B. Autoantibodies to NE proteins are relatively infrequent in routine ANA serology, and most of these fall into the broad category of an unusual connective tissue disease subset characterised by brain or skin vasculitis.
The authors state that future work should be directed at a better understanding of the autoimmune response of (ME)CFS patients to other NE proteins.
1996
Randomized, double-blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome Benjamin H.Natelson et al
Psychopharmacology 1996:124: 226-230
The authors investigated the possibility that (ME)CFS was a disorder of reduced central sympathetic drive; their study allowed the authors to evaluate patients for a placebo effect: no evidence for this was found, suggesting that (ME)CFS is not an illness due to patients being overly suggestible, and negating the proposal by some investigators that (ME)CFS is not a disease at all but simply a form of aberrant illness behaviour related to the suggestibility of the patient.
The authors conclude that their results are certainly not consistent with what might be expected in suggestible patients with psychogenic illness.
The authors state that “no clear effect of any commercially available treatment has ever been demonstrated in this devastating illness”.
1996
Barbara Marcel Anthony L Komaroff et al
“Subjects with (ME)CFS and healthy controls were administered a lengthy neuropsychological battery”
“The results indicate that (ME)CFS patients have a statistically signficiant impairment in learning and memory”
“It is also significant that impairments in memory, category fluency and word monitoring persisted even after test scores were covaried for psychiatric symptomatology in subjects”
“This suggests that cognitive dysfunction in (ME)CFS is likely to be related to mechanisms independent of any psychiatric symptoms”.
Evidence for enteroviral persistence in humans
Daniel N.Galbraith Carron Nairn Geoffrey B.Clements
Journal of General Virology 1997: 78:307-312
The authors present for the first time evidence for enteroviral persistence in humans based on sequence comparison of serial PCR products from the 5’ non-translated region (NTR).
A group of (ME)CFS patients was being followed prospectively, and showed closely related enteroviral sequences containing a unique shared pattern detectable in sera of individual patients for up to 24 months, providing good evidence for viral persistence.
The sequences from the (ME)CFS patients form a group demonstrating a close genetic relationship with each other, and fall into a subgroup that is related to Coxsackie B viruses.
The authors point out that co-existence of populations of different enteroviral sequences has been shown in poliovirus where reversion of attenuated vaccine strains to a neurotropic type can occur in an individual.
1997
Biochemical Evidence for a Novel Low Molecular Weight 2-5A-Dependent RNase L in Chronic Fatigue Syndrome
Robert J.Suhadolnik Daniel L.Peterson Paul R.Cheney Kenny de Meirleir et al
Journal of Interferon and Cytokine Research 1997:17:377-385
Previous studies from this laboratory have demonstrated a statistically significant dysregulation in several key components of the 2’ 5’A synthetase / RNase L and PKR antiviral pathways in (ME)CFS. The 2-5A synthetase I RNase L pathway is part of the antiviral defence mechanism in mammalian cells.
An accumulating body of evidence suggests that (ME)CFS is associated with dysregulation of both humoral and cellular immunity, including mitogen response, reactivation of viruses, abnormal cytokine production, diminished natural killer (NK) cell function and changes in intermediary metabolites.
Marked and striking differences have been observed in the molecular mass and RNase L enzyme activity of 2-5A binding proteins in extracts of PBMC from individuals with (ME)CFS compared with healthy controls.
The authors present biochemical evidence for an RNase L enzyme dysfunction in (ME)CFS, in particular for an upregulated RNase L activity associated with (ME)CFS.
The biochemical and immunological data presented in this paper have identified a potential subgroup of individuals with (ME)CFS with an RNase L enzyme dysfunction that is more profound than previously observed in (ME)CFS, and which the authors believe is related to the severity of (ME)CFS symptoms.
1997
Elevation of Bioactive Transforming Growth Factor-ß in Serum from Patients with Chronic Fatigue Syndrome
Adrienne L.Bennett Dedra Buchwald Anthony L.Komaroff et al.
Journal of Clinical Immunology: 1997:17:2:160-166
The authors provide evidence that patients with (ME)CFS had significantly higher levels of bioactive TGF-ß levels compared to the healthy controls, to patients with major depression, patients with SLE, patients with relapsing/remitting multiple sclerosis and patients with CP (chronic progressive) MS, ie. that in patients with (ME)CFS, the levels were significantly higher compared to patients with various diseases known to be associated with immunologic abnormalities and / or pathologic fatigue.
The authors state that perhaps of greatest relevance to CFS are the effects of TGB- on cells of the immune and central nervous systems, and the evidence that it may play a role in autoimmune and inflammatory disease.
1997
Paul S Marshall et al
A battery of cogntivie function tests was given to (ME)CFS patients and controls.
“(ME)CFS patients did not qualify as having affectve disorder by several diagnostic criteria”
“These cognitive changes (might) have significant adverse consequences for effectiveness and productivity in many daily and work-related activities”
“These (ME)CFS patients had no history of major depression by extensive structured (DIS) interviews, psychometric evlaution, or medical history”
“(ME)CFS patients’ pattern of ratings is much more like that of medically ill patients who experience a reactive depression”.
1997
Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein kinase RNA A Vojdani CW Lapp et al
Journal of Internal Medicine 1997:242:465-478
The authors state that a prominent feature of (ME)CFS is a disordered immune system and recent evidence indicates that induction of apoptosis (programmed cell death) might be mediated in a dysregulated immune system by the upregulation of growth inhibitory cytokines.
The authors’ results are in agreement with previous reports on abnormal cytokine production in (ME)CFS patients.
Quantitative analysis of apoptotic cell population in (ME)CFS patients has shown a statistically significant and marked increase compared with healthy controls. Such an abnormality in cell cycle progression is an indication of abnormal mitotic cell division.
Activation of PKR can result in inhibition of protein synthesis and induction of apoptosis, and activation of the PKR pathway could result from a dysregulated immune system or from chronic viral infection
“PKR-mediated apoptosis in (ME)CFS individuals may contribute to the pathogenesis and the fatigue symptomatology associated with (ME)CFS”.
1997
Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome Timothy G.Dinan Tahir Majeed Peter Behan et al
Psychoneuroendocrinology 1997:22:4:261-267
The authors state that (ME)CFS is a clinically defined syndrome in which serotonergic activation of the HPA axis is defective, with the release of ACTH (but not cortisol) in response to ipsapirone challenge being significantly blunted, and that patients with (ME)CFS show disturbances of HPA function which differ markedly from those seen in melancholic depression.
The authors note that an increase in peripheral turnover of the major metabolite of 5HT might explain the heightened allergic responsiveness, as well as the musculoskeletal pain seen in CFS patients.
1997
Politics, Science, and the Emergence of a New Disease Leonard A.Jason Karen M.Jordan et al
American Psychologist:1997:52:9:973-983
This significant paper states that many physicians minimised the seriousness of (ME)CFS and interpreted the symptoms as being equivalent to a psychiatric disorder and the authors state that these attitudes have had negative consequences for the treatment of (ME)CFS
They point out that use of the original case definition of (ME)CFS and the type and scoring of psychiatric tests appear to have produced erroneous estimates of the extent of (ME)CFS comorbidity with psychiatric disorders.
The authors specifically mention the work of Wessely, pointing out that he was “influential”, and also pointing out that Wessely’s findings have led some to conclude that (ME)CFS is solely a psychiatric disorder.
The authors comment on “unfortunate biases” having been introduced, and they point out that the DIS (a structured psychiatric instrument designed for use in community surveys) has frequently been used to assess psychiatric comorbidity in (ME)CFS, when that instrument was not designed for use with medically ill populations.
The authors point out that high or low psychiatric rates in (ME)CFS samples may relate to whether symptoms are attributed by physicians to psychiatric or non-psychiatric cause.
The authors consider methodological problems with the “broadened” case definition (as advocated by Wessely et al to include all cases of unexplained “fatigue” lasting for at least one month), and point out that by broadening the (ME)CFS definition, it is important to ensure that those patients with solely a psychiatric disorder are not erroneously included within the (ME)CFS rubric, as to do so could seriously complicate the interpretation of epidemiological and treatment studies.
Professor Jason points out that some (ME)CFS investigators would not see this as a confounding problem because they believe that high rates of psychiatric comorbidity indicate that (ME)CFS is mainly a psychiatric disorder.
The authors urge caution with graded exercise regimes in (ME)CFS, saying that for those (ME)CFS individuals who do not have psychologically mediated reductions in activity, such a directed approach would be inappropriate and could even be counterproductive.
The authors point out that differences observed by investigators (named as Sharpe et al, a UK psychiatrist and close collaborator of Wessely) could well be due to Sharpe’s focus on illness beliefs, so Sharpe’s sample of CFS patients might have been less impaired than a severely ill group.
The authors re-iterate that biases in the scoring and selection of psychiatric tests contributed to high levels of psychiatric comorbidity in (ME)CFS claimed by this group of psychiatrists, and that these findings were possibly due to the psychiatrists’ belief that (ME)CFS was predominantly a psychiatric rather than a medical disorder, and that the findings were influenced by “flawed epidemiological research”.
The papers states “Other investigators, such as Wessely et al, believe that (ME)CFS represents an arbitrarily defined end point and that there are no clear cutoff points separating those with severe fatigue from (ME)CFS”.
“Psychiatrists and physicians have also regarded fatigue as one of the least important of presenting symptoms (Lewis and Wessely, 1992). These biases have been filtered to the media, which has portrayed (ME)CFS in simplistic and stereotypic ways”.
The authors comment on the disregard of the severity of (ME)CFS symptoms; they conclude by commenting “We believe that it is crucial for (ME)CFS research to move beyond fuzzy recapitulations of the neurasthenia concept and clearly delineate precise criteria for diagnosing pure (ME)CFS”.
1997
Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease John de Luca Benjamin H.Natelson et al
JNNP 1997:62:151-155
The authors conclude that impaired cognition in (ME)CFS cannot be explained solely by the presence of a psychiatric condition and is contrary to expectations based on a model of “depression - induced” cognitive impairment in (ME)CFS.
“The results of the present study suggest that at least in a subgroup of patients, (ME)CFS is not simply a manifestation of a primary psychiatric disorder”.
1997
Neuroendocrine correlates of chronic fatigue syndrome: a brief review Mark A Demitrack.
J Psychiat Res 1997:31:1:69-82
The author begins his review by stating “Over time, it has not escaped the view of clinical authors that (ME)CFS and its historical antecedents shares many characteristics with endocrine disease states. Contemporary clinical research efforts have clearly documented that neuroendocrine disturbances are evident in patients with (ME)CFS”.
“In almost all studies, at least 25% of subjects show no evidence, either past or current, for formally diagnosable psychiatric illness”.
“Indeed, the accumulating body of evidence is contributing to a view of (ME)CFS as a disorder which is, in part, characterised by a novel dysregulation of the stress response”.
The author surveys the published literature of neuroendocrine abnormalities in patients with (ME)CFS; he provides confirmatory support for an impairment of the HPA axis (consistent with the view that adrenocortical function is impaired); he notes the overall observation of reduced adrenocortical activation is a common feature to both fibromyalgia and (ME)CFS; he underlines the role of stress in the onset and course of (ME)CFS, and provides concluding remarks on the implications of this work.
1997
Epidemiological Advances in Chronic Fatigue Syndrome Paul H Levine
J Psychiat Res 1997:31:1:7-18
“Epidemiologic studies of (ME)CFS have been hampered by the absence of a specific diagnostic test. Working case definitions have not always been utilized precisely by various investigators. The separation of those patients with and without pre-existing depression and other psychologic diagnoses that are not exclusive to (ME)CFS continues to be of major importance”.
The author comments specifically on the fact that all physical findings were dropped from the CDC 1994 case definition of CFS (note that UK psychiatrist Michael Sharpe is a named co-author of this revised definition and that Simon Wessely is listed as being a member of the International Chronic Fatigue Syndrome Study Group who produced the CDC 1994 definition)
Levine states: “Not surprisingly, the differences among these and earlier studies persist due to the different populations evaluated”.
This author (as others) notes that “The effect of stress on the neuroendocrine and immune function is being increasingly well characterised”.
He states: “The data suggest a poorer prognosis in those with more severe debilitation for a prolonged period of time”.
This author is another to comment specifically that “The importance of the definition of subgroups is apparent. The heterogeneity of the disorder clearly highlights their existence”.
Professor Levine points out that “The most important risk factors for (ME)CFS continue to be gender and a recent history of severe stress”.
1997
Precipitating Factors for the Chronic Fatigue Syndrome Irving E Salit.
J psychiat Res 1997:31:1:59-65
This author also points out that “Stressful events were very common in the year preceding the onset of (ME)CFS”. He concludes by stating “Even more compelling is the evidence that (ME)CFS can and does occur after physically traumatic events such as motor vehicle accidents”.
1997
Visual Dysfunction in Chronic Fatigue Syndrome Lesley Vedelago
“There are few references in the literature to visual and/or ocular disturbances in (ME)CFS, even though visual problems are common. It becomes very obvious when working with these patients that the ocular system is very much affected by, and turn affects, this systemic condition”
“The visual symptoms typically encountered with (ME)CFS include: blurred or foggy vision (distance or near); difficulty focusing from distance to near or near to distance; inability to focus on objects, particularly near; difficulty tracking lines of print; diplopia or ghosting of images; problems with peripheral vision; misjudging distances; inability to tolerate looking at moving objects; spots, flashes of light, floaters and halos; intolerance to light (glare); gritiness, burning, dryness or itchiness; eyes becoming sore as the day wears on”
“Objective ocular findings: upon examination, findings may include poor oculomotor control; saccades (rapid intermittent eye movements made as the attention switches from one point to another) -- these normally quick eye movements are very slow, with marked jerkiness; conscious effort goes into changing visual fixation; pursuits (tracking an object) are not smooth and cannot be done quickly; exophoria (the tendency for one eye to diverge when the other eye is covered); remote near-point convergence (this may be quite painful in ME/CFS); poor convergence at near; constricted peripheral fields; slow and incomplete blinking; small pupils; tear film and ocular surface abnormalities; visual mid-line shift (a neurological event interferes with vision processing from only one side of the body, and patients tend to have poor balance and tend to lean to one side or the other; nystagmus”
“Because (ME)CFS is an illness of increasing prevalence, it is important that eye specialists are not only fully informed about the condition itself, but also cognizant of the ocular/visual disturbances”.
1997
The Quality of Life of Persons with Chronic Fatigue Syndrome JS Anderson CE Ferrans
The Journal of Nervous and Mental Disease l997:185:5:359-367
The purpose of this study was to explore the quality of life (QOL) of persons with (ME)CFS.
Over all scores on the quality of life index, people with (ME)CFS were significantly lower than for other chronic illness groups.
The authors conclude that “The findings suggest that quality of life is particularly and uniquely disrupted in (ME)CFS”.
The authors note that there has been little research into this aspect, and their study revealed that 90% of their sample group experienced frequent feelings of isolation, alienation and inadequacy due to (ME)CFS.
They warn that what may be considered a disability for one person may be merely a nuisance for another, and they point out that the quality of life index (QLI) is one of the few available instruments which takes account of this phenomenon, and that the reliability and consistency of the QLI is well established.
All participants stated that (ME)CFS had had a profound impact on every aspect of their lives in ways they had never imagined possible.
All participants related profound and multiple losses, including the loss of jobs, relationships, financial security, future plans, daily routines, hobbies, stamina and spontaneity, and even their sense of self because of (ME)CFS. Activity was reduced to basic survival needs in some subjects.
These profound losses significantly affected the participants’ mental health and outlook for the future.
Participants had difficulty in describing their illness because of the marked variability in symptoms.
Symptoms were reported to be multiple, diverse, variable and pervasive. Participants reported that symptom variability tended to impede diagnosis and credibility and made it difficult for them to adjust and cope with the illness.
Symptom variability also made it impossible for those with (ME)CFS to predict their level of functioning, which interfered with efforts to plan activities. For this reason, symptom variability was regarded as an especially frustrating aspect of (ME)CFS, and the uncertainty was one of the most difficult aspects of CFS to deal with.
Patients reported that they were exhausted and could not function, and that “it never goes away”.
All participants (100%) felt that (ME)CFS had devastated social relationships and activities: “Friends of 15 years stopped returning my calls and quietly disappeared”. A third reported that they had lost most, if not all, of their previous friendships; 18% currently had no friends whatsoever. Several participants reported that they had no family.
The authors conclude that the extent of the losses experienced in (ME)CFS was devastating, both in number and in intensity.
Participants described a sense of hopelessness that was integral to the illness due to symptom variability, length of illness and repeated relapses. Over time, those who were initially optimistic became emotionally exhausted.
Patients were particularly concerned about their long-term financial needs.
The authors note that such fatigued patients may lack the energy to seek out social support, and they may lack the energy to maintain existing relationships.
The authors found that the impact of (ME)CFS on patients’ life was so total and so devastating that participants had difficulty in accepting their illness and its consequences.
The authors conclude by stating “(ME)CFS is a poorly understood and often trivialized illness, which in reality causes marked disruption and devastation”.
1997
A 56 year old woman with Chronic Fatigue Syndrome: Clinical Crossroads:
Conference Report. Anthony L Komaroff
JAMA, 1997: 278:14:1179 -1185
(This conference took place at the Medicine Grand Rounds of the Beth Israel Deaconess Medical Center, West Campus, Boston, Mass. on June 11th 1997.Dr Komaroff is Professor of Medicine, Division of General Medicine, Brigham & Women’s Hospital, Harvard Medical School, Boston, Mass. He is a world
acclaimed expert on ME/CFS)
Dr Komaroff told the Conference that two themes emerge: (i) the enormous frustration of suffering from an illness that is poorly understood and (ii) the loss of legitimacy that a patient with (ME)CFS feels.
He explained that (ME)CFS is not just a state of chronic fatigue (such as many people experience), but a truly debilitating state, associated with impaired memory / concentration, sore throat, adenopathy, myalgias, arthalgias, new headache, unrefreshing sleep, postexertional malaise, anorexia, nausea, drenching night sweats, intolerance of alcohol and pharmaceuticals that affect the central nervous system, and dizziness.
He reminded those present that objective, biological abnormalities can be found in patients with (ME)CFS, and that the medical literature of the past decade indicates that there are indeed such abnormalities.
Komaroff made the point that it is now evident that this illness is not simply an imaginary one, nor the result of anxiously amplifying normal bodily sensations. Komaroff dealt with the evidence of central nervous system (CNS) involvement in (ME)CFS: in his experience, a majority of (ME)CFS patients have symptoms which could reflect an underlying CNS process, for example, difficulty with memory, concentration and balance; photophobia and paraesthesias; in addition, substantial objective evidence of abnormalities in the CNS is now available: MRI scans have revealed areas which may represent inflammation and / or demyelination.
Komaroff told the Conference that the signal abnormalities in (ME)CFS patients “most closely resemble those seen in AIDS encephalopathy”.
Autonomic nervous system testing “frequently reveals abnormalities of the sympathetic and parasympathetic systems”.
Komaroff then dealt with the evidence of chronic immune activation in (ME)CFS: he discussed this evidence, and concluded that a state of chronic immune activation could lead to the production of cytokines that disrupt neurotransmitter function, resulting in the symptoms of (ME)CFS.
He made the point that the state of chronic immune activation in (ME)CFS suggests the possibility of a chronic infectious process, saying that some physicians (including himself) believe that infectious agents may trigger and even perpetuate the symptoms of (ME)CFS; he referred to the evidence for a chronic viral infection as demonstrated by Suhadolnick, which showed an abnormality in an antiviral lymphocyte enzyme system (2-5A pathway), which is found to be chronically activated in patients with (ME)CFS.
Komaroff referred to the findings that many (ME)CFS patients have experienced atopic symptoms from childhood, and that the atopic symptoms often flare up in (ME)CFS.
Komaroff stated that perhaps the most important nonpharmacologic intervention was to encourage patients to avoid physical or emotional stress, and to pace themselves.
He stated that it is antitherapeutic for the clinician to dismiss any patient’s symptoms out of hand, especially in (ME)CFS, which is a “de-legitimating illness”, as “patients often experience rejection by family, friends and physicians. The illness is hardly ‘imaginary’”.
1997
Chronic Fatigue Syndrome: A Challenge to the Clinical Professions
Derek Pheby (Director, Unit of Applied Epidemiology, University of the West of England, Bristol, UK)
Physiotherapy: 1997:83:2:53-56
“No-one who has experienced this illness, or who has had the responsibility of caring for a family member who has had the misfortune to suffer from it, can have any doubt not only about the extent of the real pain, suffering and distress that it can cause, but also as to the disastrous effect it can have on social relationships and life in the community”.
“The most seriously affected individuals may be bed-ridden most or all of the time and can do little or nothing for themselves”.
“In this illness, ‘recovery’ is very much a relative term: in follow-up studies, after 48 years (sic), eight out of ten patients continued to have some form of disability (Hyde & Bergman 1991). This is in line with Ramsay (1986) who wrote that complete recovery is confined to one third of cases”.
“Recent research has made it clear that the view that there were no specific changes demonstrable in patients with (ME)CFS has become untenable”.
“The disturbances to the HPA axis in (ME)CFS differ markedly from those found in depression, as do brain vascular perfusion patterns”.
“The overall costs associated with the syndrome are likely to be around £90 million per year (National Task Force Report, 1994, page 21). Given the tendency to chronicity, much of this cost is due to the need for long - term supportive care of patients”.
“CFS/ME is a major challenge to all health care professionals”.
1997
Chronic Fatigue Syndrome —aetiological aspects Dickinson CJ
Eur J Clin Invest: 1997:27:4:257-267
“There is some evidence both for active viral infection and for an immunological disorder in (ME)CFS. Many observations suggest that the syndrome could derive from residual damage to the reticular activating system (RAS) of the upper brain stem and / or to its cortical projections”
“Regional blood flow studies by SPECT have been more consistent (and) have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis —in both of which conditions fatigue is characteristically present”.
1997
Cardiac Involvement in Patients with Chronic Fatigue Syndrome as Documented with Holter and Biopsy Data in Birmingham, Michigan, 1991 - 1993 A. Martin Lerner et al
Infectious Diseases in Clinical Practice 1997:6:327-333
This study reports the prevalence of abnormal oscillating T-waves on Holter 24 hour monitoring in a consecutive case series of 67 (ME)CFS patients.
Resting 12 lead ECGs were normal, with the presence of labile T-wave abnormalities coming to light only with 24 hour Holter monitoring.
Repetitive T-wave flattening was a sensitive indicator of the presence of (ME)CFS, as every (ME)CFS patient (but only 22.4% of the controls) showed abnormal flattening or inversion on Holter monitoring.
Abnormal cardiac wall motion (at rest and on stress), dilatation of the left ventricle and segmental wall motion abnormalities were present. (Normal left ventricular resting ejection fraction is 50%, but in (ME)CFS, the left ventricular ejection fraction — at rest and with exercise — of as low as 30% was seen).
Abnormal T-wave oscillations (T-wave flattening or inversion) of at least 25 normally conducted beats were necessary to be considered abnormal; they frequently appeared only with the advent of sinus tachycardia.
Two cardiologists unaware of the position of the patients reviewed the Holter tracings.
“This study confirms our earlier report (see following item) that (ME)CFS patients uniformly have abnormal oscillating T-wave flattenings and T-wave inversions by Holter monitoring”
“As described here, abnormal Holter monitoring is important to the explicit diagnosis of patients with (ME)CFS (and) are a characteristic of (ME)CFS (and) appear to be an essential element to the pathologic physiology of the cardiomyopathy of (ME)CFS”.
1997
New Cardiomyopathv: pilot study of intravenous gangiclovir in a subset of the chronic fatigue syndrome. Lerner AM et al
Infectious Diseases in Clinical Practice 1997:6:2:110-117
This study involved a subset of (ME)CFS patients with oscillating repetitively abnormal aberrant T waves on Holter 24-hour electrocardiogram (ECG) recording.
None of these patients could work or manage a household.
The type of abnormalities documented in the cardiac study “are not seen in normal persons leading a sedentary life”.
1997
Does the chronic fatigue syndrome involve the autonomic nervous system?
Freeman R and Komaroff AL
American Journal of Medicine 1997:102:4:357-364
The aim of this study was to investigate the role of the ANS (autonomic nervous system) in the symptoms of (ME)CFS patients (selected if they had one of three criteria indicating ANS dysfunction).
The (ME)CFS subjects had significant increase in baseline and maximum heart-rate on standing and tilting.
Tests of the parasympathetic nervous system function were significantly less in the (ME)CFS group, as were measures of sympathetic nervous system function.
Deconditioning alone did not fully explain the documented ANS abnormalities.
89% of patients reported that an infectious illness had preceded the onset of (ME)CFS, and in 46%, the ANS symptoms occurred within four weeks of the infection. The authors described “a temporal pattern that is consistent with a postviral, idiopathic autonomic neuropathy”.
Symptoms of ANS dysfunction are not related to psychiatric disorder.
1997
A population-based incidence study of chronic fatigue
Lawrie SM, Pelosi AJ et al
Longitudinal studies using appropriate measures have shown that physical attributions do not affect outcome.
1997
Exercise limits in chronic fatigue syndrome Lapp C. (Charles Lapp is Professor of Community Medicine at Duke University, Charlotte, North Carolina, USA)
American Journal of Medicine 1997:103:83-84
This reports a trial involving 31 consecutive new (ME)CFS patients, which allowed them to reach their maximum oxygen consumption within 8 - 10 minutes of exercise.
The results showed that 74% of patients experienced worsening fatigue. None improved.
The average relapse lasted 8.82 days, although 22% were still in relapse at 12 days (when the study ended).
These findings suggest that, pushed to maximal exertion, patients with (ME)CFS may relapse.
1997
A Chaudhuri T Dinan et al
JCFS 1997:3(1):3-16
“Chronic Fatigue Syndrome is a clinical disorder that is increasingly recognized in most countries as a major health hazard. Its classical clinical feature is fatigue associated with sleep abnormalities, difficulties concentrating, memory impairment and myalgia”
“To this may be added a constellation of other symptoms, including atypical chest pain, gastrointestinal motility disorders, unexplained attacks of sweating and light headedness. The fatigue is clinically identical to that found in multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, post-polio syndrome and the fatigue that may follow posterior head injury”
“The sleep abnormality is similar to that described in patients with acquired autoimmune myasthenia gravis.
“Abnormalities in muscle, neuromuscular transmission, heart and resting energy expenditure have been found in patients with (ME)CFS”
“These abnormalities may well be secondary to a primary abnormality of central cholinergic transmssion”
“We tested this hypothesis using a neuroendocrine challenge paradigm (and) have shown that the pathogenesis involves up-regulation of post-synaptic cholinergic receptors”.
1997
Abhijit Chaudhuri et al
In: Chronic Fatigue Syndrome, Ed: Yehuda and Mostofsky; Plenum Press, New York, 1997
“Chronic fatigue syndrome is a disorder that is now receiving world-wide attention from the scientific and medical communities”
“All (study participants) had several features which should be stressed, namely, the illness was fluctuating and made worse by exercise”
“Myocarditis, with or without Bornholm-type was a common symptom in an analysis of 1,000 patients of (ME)CFS who were seen in Glasgow over the past 20 years. Several of our patients were referred by cardiologists. Various aetiologies for non-cardiac chest pain have been proposed, including oesophageal reflux and spasm, chest wall pain and microvascular coronary artery disease. We were struck by the often occurring association of patients who develop (ME)CFS with acute chest pain resembling coronary thrombosis. Nuclear magnetic resonance spectroscopy studies of skeletal muscle in patients with syndrome X are identical to those found in patients with (ME)CFS. Waldenstrom et al have suggested that there are abnormal ionophores in the skeletal muscle and cardiac cells of patients with syndrome X.
“There has been anecdotal evidence that some patients with (ME)CFS who presented to cardiologists with chest pain have abnormal thallium-201 SPECT scans (and this) prompted us to carry out cardiac thallium-201 scans on a small group of ME/CFS patients.
“Image analysis revealed moderate defects in the left ventricle of 7 of the 10 patients. This was shown to be significantly different from the expected incidence of abnormal results (and) here again we have similar results in (ME)CFS and syndrome X.
“Additionally, the TBK (total body potassium) results for the (ME)CFS patients were significantly lower than those for controls (which) fits with the hypothesis of abnormal ionophore formation (and) evidence is now accruing that patients with (ME)CFS might have a reduced TBK (which) would probably be a result of an abnormality of membrane permeability consequent to abnormal ionophores”
“These fit well with the other metabolic abnormalities of (ME)CFS patients”
“It is plausible that the defect in (ME)CFS lies at the cellular level in view of the widespread symptomatology so commonly found in this condition”
“There is compelling data to show that a number of different noxae can precipitate (ME)CFS. These include viruses, exposure to organophosphates, and incapacitating stress. It may also occur as a result of exposure to other toxins”
“We propose that ion channels, eg. potassium, sodium or even calcium channels are affected in patients with ME/CFS following exposure to viruses and organophosphates”
“It may not be in the too distant future when (ME)CFS would be considered as an example of channelopathy like many other neurological diseases”.
1997
Honor Anthony, Sybil Birtwhistle, Keith Eaton, Jonathan Maberly
“Patients with Type B allergies, especially those with chemical sensitivity, commonly give a history of slow recovery after an anaesthetic, (with) prolonged severe malaise, nausea, vomiting, pain and other symptoms”
“The risk of reactions is higher in patients who have other evidence of chemical sensitivity, and thiopentone and suxamethonium are best avoided”
“Of the intravenous induction drugs, thiopentone should eb avoided because it can cause anaphylaxis”
“Propofol is an emulsion made up in egg and soya and should be avoided in patients known to be sensitive to these foods”
“Of the inhalation anaesthetics, halothane and enflurane cause more trouble”
“Morphine and pethidine should normally be avoided as they tend to release histamine”.
Cardiovascular responses during a cognitive stressor before and after exercise in chronic fatigue syndrome versus sedentary healthy subiects SA Sisto B Natelson et al
Presented at the Fourth International AACFS Research & Clinical Conference on CFIDS. Mass. USA 1998: Abstract:page 48
Patients with (ME)CFS complain of cognitive difficulties that worsen after exercise.
The purpose of this study was to determine if patients with (ME)CFS have similar cardiovascular responses (compared with sedentary controls) during a cognitive test battery, both before and after exercise.
The (ME)CFS group demonstrated a significantly lower change in systolic blood pressure compared with the sedentary controls.
Exercise produces the expected attenuation of the cardiovascular responses in the healthy group, but not so for the (ME)CFS patients.
This hypo-responsiveness may, in part, be responsible for (ME)CFS patients reporting detrimental effects of periods of psychological stressors or excess physical exertion.
1998
CFS severity is related to reduced stroke volume and diminished blood pressure responses to mental stress Arnold Peckerman Bejamin Natelson et al
Presented at the Fourth International AACFS Research & Clinical Conference on CFIDS, Mass. USA 1998: Abstract page 47
One plausible hypothesis of the pathophysiology of (ME)CFS is a disorder of circulation.
The present study examined whether cardiovascular homeostasis at rest and centrally-mediated haemodynamic responses to behavioural challenges are altered in (ME)CFS.
The results showed that in (ME)CFS patients, a lower stroke volume was highly predictive of illness severity: across three different postures, the most severely affected (ME)CFS patients were found to have a lower stroke volume and cardiac output compared with those with more moderate illness.
These findings suggest a low flow circulatory rate in the most severe cases of (ME)CFS; this may indicate a defect in the higher cortical modulation of cardiovascular autonomic control.
In the most severely affected, situations may arise where a demand for blood flow to the brain may exceed the supply, with a possibility of ischaemia and a decrement of function.
1998
Respiratory symptoms and lung function testing in CFS patients P de Becker, K de Meirleir et al Presented at the Fourth International AACFS Research & Clinical Conference on CFIDS. Mass. USA 1998: Abstract page 104
The purpose of this study was to report the prevalence of respiratory symptoms in a cohort of (ME)CFS patients.
The following respiratory symptoms were observed: cough, chest tightness, medical history of allergy, new onset of allergy; the major respiratory complaint was found to be a pronounced exercise-induced dyspnoea.
In 60% of (ME)CFS patients, a marked bronchial hyper-responsiveness was present. (Bronchial hyper-responsiveness was defined as PD 20 his < 2 mg histamine).
(ME)CFS patients show a significant decrease in vital capacity (VC), possibly due to a significant increase of residual volume (RV).
The incidence of bronchial hyper-responsiveness in this group is remarkably high.
These observations can, at least partially, explain the respiratory symptoms in these patients.
1998
Chronic Fatigue Syndrome: An Update A.L.Komaroff D.S.Buchwald
Annu Rev Med 1998:49:1-13
Studies indicate that the illness is not simply a manifestation of an underlying psychiatric disorder, but rather is an illness characterised by activation of the immune system, various abnormalities of several hypothalamic pituitary axes and reactivation of certain infectious agents.
The most robust findings are increased numbers of CD8+ cytotoxic T cells that bear antigenic markers of immune activation on their cell surface, and depressed function of natural killer lymphocytes.
Other reported findings of immune activation are elevated levels of circulating immune complexes and immunoglobulin G, and higher frequencies of various autoantibodies.
More circumstantial evidence of a chronic viral infection in many (ME)CFS patients comes from reports of an abnormality in an antiviral lymphocyte enzyme system (the 2-5A pathway) which appears to be chronically activated in patients with (ME)CFS.
These reports provide strong evidence that (ME)CFS can be triggered by an acute infection that has the capacity to produce a chronic infection.
This paper concludes by affirming that “there is growing evidence that abnormal, objective biologic processes are present in many patients with (ME)CFS -- in particular, subtle abnormalities of the central nervous system, chronic activation of the immune system, and reactivation of several latent viruses”.
1998
Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome
Russell JM Lane Leonard C Archard et al
JNNP 1998:64:362-367
The object of this study was to examine the proportions of types I and II muscle fibres and the degree of muscle fibre atrophy and hypertrophy in patients with (ME)CFS in relation to lactate responses to exercise, and to determine to what extent any abnormalities found might be due to inactivity.
Muscle fibre histometry in patients with (ME)CFS did not show changes expected as a result of inactivity.
The authors note that one of these patients had an inflammatory infiltrate, and it would seem that inflammation and class I MHC expression may occur in biopsies from patients with (ME)CFS.
The authors note that this is of some interest, as they have argued previously that some forms of (ME)CFS may follow a previous virally-mediated inflammatory myopathy.
1998
On symptoms and life events surrounding the onset of chronic fatigue syndrome
Evengard B et al
Presented at the Fourth International AACFS Research & Clinical Conference on CFIDS, Mass. USA: 1998: Abstract page 32
This study was aimed at describing the sequence of psychosocial events and infections preceding the onset of (ME)CFS (related to the temporal development of crucial symptoms).
Sixty seven percent of the (ME)CFS patients had a clearly negative life event preceding infection, which preceded (ME)CFS onset.
1998
Gastrointestinal Manifestations of Chronic Fatigue Syndrome: Symptom Perceptions and Quality of Life Herbert Hyman Thomas E Wasser
JCFS 1998:4(1):43-52
The authors conclude that the classification of irritable bowel syndrome (IBS) should be modified to include a subset of patients who have a combination of (ME)CFS and lBS.
They enumerate not only functional gastrointestinal (GI) complaints, but also other abdominal complaints, particularly neurologic.
They point out that in (ME)CFS, immunologic abnormalities are regularly found, and that there are more lymphocytes associated with the Gl tract than any other site in the human body.
Since the gut mucosa contains immunologically active lymphoid tissue, the authors believe that a pattern of immune dysfunction exists in (ME)CFS in which immune products are transmitted to the gut via the lymphatic system, reacting on both the lumenal contents and intestinal motor system, and that the GI lymphatic system not only has an effector function, but also transmits characteristic (ME)CFS immune dysfunction to other organs.
The authors also suggest that oral antigens could be similarly effective in (ME)CFS patients by way of the immunological activity of the gut mucosa.
Some (ME)CFS patients had abdominal wall pain due to unilateral segmental neuropathy.
In summary, this study demonstrated three primary findings: (i) (ME)CFS patients showed significantly more symptom dysfunction than those in the functional bowel disease (FBD) group; (ii) (ME)CFS patients had significantly lower Quality of Life scores than the FBD group and (iii) since differences occur between (ME)CFS and FBD patients, the classification of lBS should be modified to include a subset of patients who have a combination of (ME)CFS and lBS.
1998
Chronic Fatigue Syndrome in Children and Adolescents: A Review
Karen M Jordan Leonard A Jason et al
Journal of Adolescent Health 1998:22:4-18
The majority of studies concerning (ME)CFS have concentrated on adults, but the illness does strike younger individuals, and the case definitions do not address the appropriateness for the paediatric population. The lack of specificity to the unique characteristics of children and adolescents is pervasive in much of the research literature.
Several authors reported a preponderance of acute onset with viral-type illness in children and adolescents.
Many previous epidemiological studies (one of Wessely’s studies is cited) have relied on physician referral, when (those) physicians are sceptical of the validity of (ME)CFS as a true illness.
Repetitive treatment-seeking is often necessary before a diagnosis of (ME)CFS is made: children may be less able to seek care persistently, so the prevalence rate in those under 18 years has undoubtedly been minimised.
The authors describe the Cheney proposition (Cheney PR. Proposed pathophysiological mechanism of CFIDS. CFIDS Chronicle: 1994:7: 1-3) that the common symptoms of (ME)CFS (eg. hyperreflexia, abnormalities of vestibular function, palpable and slightly enlarged discoid shaped lymph nodes, predominantly left-sided tender posterior and cervical lymph nodes) suggest a connection between immune activation and central nervous system injury: as alpha-interferon can be neurotoxic, particularly to the limbic structure and the serotonergic pathways (via opioid receptors), this may account for the abnormalities in corticotrophin-releasing hormone (CRH), and these deficiencies then contribute to a positive feed-back loop which maintains immune activation.
In addition, the decrease in TRH production could lead to reduced cellular metabolism, including impaired oxygen consumption during exercise, which is consistent with mitochondrial dysfunction.
The authors note that there has been minimal controlled study of psychiatric status for children and adolescents with (ME)CFS. However in one study, adolescents with (ME)CFS received higher scores of psychiatric comorbidity, but on further examination of the somatic complaint items, it was found that this scale was confounded by the presence of many items related to (ME)CFS symptoms (eg. headaches, pain and feeling sick).
The authors state that the overlap of (ME)CFS symptoms with those of psychiatric disorders has been found to lead to an overdiagnosis of psychiatric disorder in adult (ME)CFS populations.
The authors note that a list first supplied by Komaroff provides four discriminating characteristics of fatigue and symptoms which should assist the clinician in distinguishing between (ME)CFS and malingering or somatoform disorders, and these include symptoms which are rarely found in paediatric general practice.
The authors note that the perceived causal role of depression in (ME)CFS may have been inflated in some studies owing to frequent errors.
They note that the Diagnostic and Statistical Manual (DSM) IV criteria for depression do not include any of the primary complaints of patients who present with (ME)CFS.
Further, the DSM IV criteria for somatisation do not mention fatigue symptoms.
The DSM IV states that individuals with somatisation disorder describe their complaints in a colourful, sensational and emotional manner, with specific factual information missing.
On the contrary, people with (ME)CFS describe their symptoms clearly and concisely.
Minimal work has been done in the formal assessment of coping with illness, level of disability or quality of life issues in children and adolescents with (ME)CFS.
Paediatric patients may require assistance obtaining special services or accommodations from their school.