ME and CFS Definitions

The case definition of chronic fatigue syndrome has been a source of great confusion and has served as a major roadblock with regard to the development of an understanding of the disease. Looking back at the history of ME and CFS is necessary to understand how things went awry.

In 1956, the term “Myalgic Encephalomyelitis” first appeared in the medical literature, to describe a perplexing series of outbreaks that had been observed over the preceding few decades in various locations throughout the world. These included Iceland, Australia, Durban, Los Angeles, upstate New York, Switzerland, England and Denmark.

Regardless of where the outbreaks were located, the illness observed was remarkably consistent. Writing in the Canadian Medical Association Journal, Rosemary Lindan gave a precise description:

The onset resembles that of poliomyelitis with headaches, lassitude, neck stiffness and sore throat accompanied by pains in the limbs and back, and possibly paraesthesiae and palsies. In contrast to poliomyelitis, however, the fever is never very high; the temperature rarely exceeds 100 degrees F and may persist for long periods. The clinical picture is dominated by the severe muscular pains, accompanied at first by spasms and exaggerated tendon reflexes. These pains are not transient; they often persist long after any local signs have subsided and may be accompanied by an exquisite tenderness, but at no time does any muscular wasting develop. A further distinguishing feature of the disease is the onset of behavioural changes, such as emotional lability, irritability and depression....Disturbances of the cranial nerves such as diplopia and nystagmus, facial weakness, deafness or, in some cases hyperacusis, are common. A high proportion of cases show evidence of involvement of the reticuloendothelial system with enlargement of the cervical lymph nodes, particularly those in the posterior triangle, and, in some patients, hepatitis and splenomegaly. (Lindan R. Benign Myalgic Encephalomyelitis. Can Med Assoc J. 1956 Oct 1;75(7):596-7. PMID: 20325349)

Over the next three decades, further reports of occasional, scattered outbreaks in various places continued to appear in the medical literature. The most famous case was

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one associated with the Royal Free Hospitals in London in 1955, with over 300 people (mostly nurses) being affected. That case was written up in various places (including the leading British medical journal The Lancet) by Donald Acheson, who went on to serve as the Britain’s Chief Medical Officer from 1983-1991.

Journal articles provided an increasingly detailed picture of the illness during this time. Although most of the cases continued to be seen as part of epidemics, scattered individual cases were found. The observations that many patients remained quite sick for years and that a few died from the illness led to the word “benign” being dropped from the name. Specific lab findings (including “normal” levels on all ordinary labs) were reported, and hypotheses about the cause of the illness were presented:

In a recent survey of clinical enzymology Wilkinson (1978) discusses the release of enzymes from cells. He concludes that intracellular energy content is important in the control of membrane permeability and instances loss of enzymes resulting from a variety of insults such as anoxia, deprivation of glucose, high potassium concentrations, high energy phosphates and metabolic inhibitors to both rat muscle and human erythrocytes. If the aetiological factor in benign 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. (Ramsay AM, Rundle A. Clinical and biochemical findings in ten patients with benign myalgic encephalomyelitis. Postgrad Med J. 1979 Dec;55(654):856-7. PMID: 548947)

By the mid 1970s, a few observers argued that the epidemics might have been due to mass hysteria. The editors of the British Medical Journal firmly dismissed that idea:

Some authors have attempted to dismiss this disease as hysterical, but the evidence now makes such a tenet unacceptable. Some purely psychiatric symptoms may well occur, particularly in patients entering the chronic phase. Nevertheless, the organic basis is clear -- from the finding that the putative agent can be transferred to monkeys; the detection of increased urinary output of creatine; the persistent finding of abnormal lymphocytes in the peripheral blood of some patients; the presence of lymphocytes and an increased protein concentration in the cerebrospinal fluid of occasional patients; and the neurological findings. Increased serum concentrations of lactic dehydrogenases and transaminases have been found in several patients

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examined during the acute attack. (Epidemic myalgic encephalomyelitis. Br Med J. 1978 Jun 3;1(6125):1436-7. PMID: 647324)

In 1984, an outbreak matching all the characteristics of the other outbreaks occurred in the Lake Tahoe area of northern Nevada. Doctors (including Byron Hyde) who had published in the medical literature on the disease eventually visited the town and confirmed that the patients there were suffering from a particularly severe outbreak of ME.

Because the disease up until that point had only occurred in scattered outbreaks and had not been featured in the prominent U.S. medical journals, the treating physicians in Lake Tahoe were not familiar with the disease. They thus reported the outbreak to the Centers for Disease Control and Prevention (CDC), which conducted an investigation.

During the next three years, a number of outbreaks of what clearly seemed the same disease were reported in various locations in the U.S., including California (Sacramento, San Francisco, Truckee), Nevada (Carson City, Yerington), upstate New York (Lyndonville) and North Carolina. Outbreaks also occurred in other countries, including New Zealand and England. Hundreds of individual cases matching the descriptions of ME in the literature also were reported.

In 1987, the CDC released a description of the illness, based in part on the group of cases in the Lake Tahoe outbreak. For reasons that remain unclear, the organization put aside both the name and the established descriptions of ME. It instead presented a much more non-specific picture of the illness, which it called “the chronic fatigue syndrome.”

The CDC’s description became even more nondescript in 1994, when it was adopted as the official definition of the disease and the number of secondary symptoms (in addition to fatigue) needed to qualify was dropped from eight to four.

The CDC’s description of Chronic Fatigue Syndrome immediately almost obliterated the concept of Myalgic Encephalomyelitis from the literature. Since 1990, ME has almost never been mentioned in the medical literature except as an alternative name in a paper focusing on CFS.

The main problem here is not that the name “Chronic Fatigue Syndrome” makes the disease that used to be called ME sound more trivial and less complicated than it

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actually is (although that is true too). The more important issue is that a disease with a very specific presentation and course has been redefined by a loose set of criteria that does not accurately distinguish it from other kinds of conditions.

For instance, neurasthenia is a condition that was commonly diagnosed throughout the first half of the 20th Century. Its symptoms (fatigue, cognitive disturbances, headache, sleep problems, muscle pains) would allow the easy diagnosis of CFS, under the CDC’s criteria. However, doctors reporting on ME during this time period did not consider neurasthenia to be an acceptable explanation for the outbreaks, since the symptoms were much more extensive and severe than were seen in neurasthenia.

Many other health problems (e.g. multiple chemical sensitivity, mold illness/sick building syndrome, Lyme disease, mononucleosis, major depression) may allow people to qualify for a diagnosis of CFS, according to the CDC’s current criteria, even though these health problems look markedly different than the ones described in the literature on ME.

Certainly, it is possible that a common etiology (such as a pathogen, a genetic defect or a toxin) may underlie a variety of disease presentations. It also is the case that many people with less specific illness presentations (such as would meet the Fukuda criteria for CFS) go on to develop illness of the sort described in the early ME literature. Conceivably, certain conditions might be determined to be “precursors” or “variants” to ME, if more were known about ME.

Unfortunately, the non-specificity of the CDC case definition has been part of the reason that more about any of the illnesses has not been learned. With a high level of heterogeneity in people who meet the CDC’s case definition, the likelihood that research will turn up anything enlightening is small. This is especially the case since people who are not very sick are easier to study than people who are bedbound -- resulting in the vast majority of the literature on CFS focusing on people who either have mild versions of ME or who would never have qualified for the illness at all.

Thus, a group of researchers and physicians knowledgeable about the illness recently published a case definition of ME (the ME International Consensus Criteria) that is much closer to the ones first presented back in the 1950s. It is hoped that this will lead to specific research of a more homogenous population of sufferers of the illness, thus bringing about the development of more specific and useful knowledge about it.

-Lisa Petrison, Ph.D.

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ME AND CFS DEFINITIONS

ME: INTERNATIONAL CONSENSUS CRITERIA (CARRUTHERS 2011)

Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AP, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S. Myalgic Encephalomyelitis: International Consensus Criteria. J Intern Med. 2011 Jul 20. PMID: 21777306

Adult and PediatricClinical and Research

Myalgic encephalomyelitis is an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport are prominent features. Although signs and symptom are dynamically interactive and causally connected, the criteria are grouped by regions of pathophysiology to provide general focus.

A patient will meet the criteria for post-exertional neuroimmune exhaustion (A), at least one symptom from three neurological impairment categories (B), at least one symptom from three immune/gastro-intestinal /genitourinary impairment categories (C), and at least one symptom from energy metabolism/transport impairments (D).

A. Post-Exertional Neuroimmune Exhaustion (PENE pen’ -e) Compulsory

This cardinal feature s a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions. Characteristics are:

1. Marked, rapid physical and/or cognitive fatiguability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause relapse.

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2. Post-exertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.

3. Post-exertional exhaustion may occur immediately after activity or be delayed by hours or days.

4. Recovery period is prolonged, usually taking 24 hours or longer. A relapse can last days, weeks or longer.

5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

Operational notes: For a diagnosis of ME, symptom severity must result in a significant reduction of the patient’s premorbid activity level. Mild (an approximate 50% reduction in pre-illness activity level), moderate (mostly housebound), severe (mostly bedridden), or very severe (totally bedridden and need help with basic functions). There may be marked fluctuation of symptom severity and hierarchy from day to day or hour to hour. Consider activity, context and interactive effects. Recovery time: e.g. Regardless of a patient’s recovery time from reading for 1/2 hour, it will take much longer to recover from grocery shopping for 1/2 hour and even longer if repeated the next day -- if able. Those who rest before an activity or have adjusted their activity level to their limited energy may have shorter recovery periods than those who do not pace their activities adequately. Impact: e.g. An outstanding athlete could have a 50% recovery in his/her pre-illness activity level and is still more active than a sedentary person.

B. Neurological Impairments

At least One Symptom from three of the following four symptom categories.

1. Neurocognitive Impairments

a. Difficulty processing information: slowed thought, impaired concentration e.g. confusion, disorientation, cognitive overload, difficulty with making decisions, slowed speech, acquired or exertional dyslexia

b. Short-term memory low: e.g. difficulty remembering what one wanted to say, what one was saying, retrieving words, recalling information, poor working memory

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2. Pain

a. Headaches: e.g. chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; migraine; tension headaches

b. Significant pain can be experienced in muscles, muscle-tendon junctions, joints, abdomen or chest. It is non-inflammatory in nature and often migrates. e.g. generalized hyperalgesia, widespread pain (may meet fibromyalgia criteria), myofascial or radiating pain

3. Sleep Disturbance

a. Disturbed sleep patterns: e.g. insomnia, prolonged sleep including naps, sleeping most of the day and being awake most of the night, frequent awakenings, awakening much earlier than before illness onset, vivid dreams/nightmares

b. Unrefreshing sleep: e.g. awaken feeling exhausted regardless of duration of sleep, day-time sleepiness

4. Neurosensory, Perceptual and Motor Disturbances

a. Neurosensory or perceptual: e.g. inability to focus vision, sensitivity to light, noise, vibration, odour, taste and touch; impaired depth perception

b. Motor: e.g. muscle weakness, twitching, poor coordination, feeling unsteady on feet, ataxia

Notes: Neurocognitive impairments, reported or observed, become more pronounced with fatigue. Overload phenomena may be evident when two tasks are performed simultaneously. Abnormal reaction to light - fluctuation or reduced accommodation responses of the pupils with retention of the reaction. Sleep disturbances are typically expressed by prolonged sleep, sometimes extreme, in the acute phase and often evolve into marked sleep reversal in the chronic stage. Motor disturbances may not be evident in mild or moderate cases but abnormal tandem gait and positive Romberg test may be observed in severe cases.

C. Immune, Gastro-Intestinal and Genitourinary Impairments

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At least One Symptom from three of the following five symptom categories.

1. Flu-like symptoms may be recurrent or chronic and typically activate or worsen with exertion. e.g. sore throat, sinusitis, cervical and/or axillary lymph nodes may enlarge or be tender on palpitation

2. Susceptibility to viral infections with prolonged recovery periods

3. Gastro-intestinal tract: e.g. nausea, abdominal pain, bloating, irritable bowel syndrome

4. Genitourinary: e.g. urinary urgency or frequency, nocturia

5. Sensitivities to food, medications, odours or chemicals

Notes: Sore throat, tender lymph nodes, and flu-like symptoms obviously are not specific to ME but their activation in reaction to exertion is abnormal. The throat may feel sore, dry and scratchy. Faucial infection and crimson crescents may be seen in the tonsillar fossae, which are an indication of immune activation.

D. Energy Production/Transportation Impairments: At least One Symptom

1. Cardiovascular: e.g. inability to tolerate an upright position - orthostatic intolerance, neurally mediated hypotension, postural orthostatic tachycardia syndrome, palpitations with or without cardiac arrhythmias, light-headedness/dizziness

2. Respiratory: e.g. air hunger, laboured breathing, fatigue of chest wall muscles

3. Loss of thermostatic ability: e.g. subnormal body temperature, marked diurnal fluctuations; sweating episodes, recurrent feelings of feverishness with or without low grade fever, cold extremities

4. Intolerance of extremes of temperature

Notes: Orthostatic intolerance may be delayed by several minutes. Patients who have orthostatic intolerance may exhibit mottling of extremities, extreme pallor or Raynaud’s Phenomenon. In the chronic phase, moons of finger nails may recede.

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Pediatric Considerations

Symptoms may progress more slowly in children than in teenagers or adults. In addition to post-exertional neuroimmune exhaustion, the most prominent symptoms tend to be neurological: headaches, cognitive impairments, and sleep disturbances.

1. Headaches: Severe or chronic headaches are often debilitating. Migraine may be accompanied by a rapid drop in temperature, shaking, vomiting, diarrhoea and severe weakness.

2. Neurocognitive impairments: Difficulty focusing eyes and reading are common. Children may become dyslexic, which may only be evident when fatigued. Slow processing of information makes it difficult to follow auditory instructions or take notes. All cognitive impairments worsen with physical or mental exertion. Young people will not be able to maintain a full school program.

3. Pain may seem erratic and migrate quickly. Joint hyper-mobility is common.

Notes: Fluctuation and severity hierarchy of numerous prominent symptoms tend to vary more rapidly and dramatically than in adults.

Classification:

___ Myalgic Encephalomyelitis

___Atypical Myalgic Encephalomyelitis: meets criteria for post-exertional neuroimmune exhaustion but has two or less than required of the remaining criterial symptoms. Pain or sleep disturbance may be absent in rare cases.

Exclusions:

As in all diagnoses, exclusion of alternate explanatory diagnoses is achieved by the patient’s history, physical examination, and laboratory/biomarker testing as indicated. It is possible to have more than one disease but it is important that each one is identified and treated. Primary psychiatric disorders, somatoform disorder and substance abuse are excluded. Paediatric: ‘primary’ school phobia.

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Co-Morbid Entities:

Fibromyalgia, Myofascial Pain Syndrome, Temporomandibular Joint Syndrome, Irritable Bowel Syndrome, Interstitial Cystitis, Raynaud’s Phenomenon, Prolapsed Mitral Valve, Migraines, Allergies, Multiple Chemical Sensitivities, Hashimoto’s Thyroiditis, Sicca Syndrome, Reactive Depression. Migraine and irritable bowel syndrome may precede ME but then become associated with it. Fibromyalgia overlaps.

http://niceguidelines.files.wordpress.com/2011/07/myalgic-encephalomyelitis-international-consensus-criteria.pdf

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ME/CFS CANADIAN CONSENSUS CRITERIA (CARRUTHERS 2003)

Carruthers BM, Jain, AK, De Meirleir KL, Peterson DL, Klimas NG, Lerner AM, Bested AC, Henry PF, Joshi P, Powles ACP, Sherkey JA, van de Sande M. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome, Vol. 11(1), 2003.

A patient with ME/CFS will meet the criteria for fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; have two or more neurological/cognitive manifestations and one or more symptoms from two or more of the categories of autonomic, neuroendocrine and immune manifestations; and adhere to item 7.

1. Fatigue. The patient must have a significant degree of new onset, unexplained, persistent or recurrent physical and mental fatigue that substantially reduces activity level.

2. Post-Exertional Malaise and/or Fatigue: There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post-exertional malaise and/or fatigue and/or pain and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. There is a pathologically slow recovery period -- usuall 24 hours or longer.

3. Sleep Dysfunction: There is unrefreshed sleep or sleep quantity or rhythm disturbances such as reversed or chronic diurnal sleep rhythms.

4. Pain. There is a significant degree of myalgia. Pain can be experienced in the muscles and/or joints, and is often widespread and migratory in nature. Often there are significant headaches of new type, pattern or severity.

5. Neurological/Cognitive Manifestations: Two or more of the following difficulties should be present: confusion, impairment of concentration and short-term memory consolidation, disorientation, difficulty with information processing, categorizing and word retrieval, and perceptual and sensory disturbances -- e.g. spatial instability and disorientation and inability to focus vision. Ataxia, muscle weakness and fasciculations are common. There may be overload phenomena: cognitive, sensory -- e.g. photophobia and hypersensitivity to noise -- and/or emotional overload, which may lead to “crash” periods and/or anxiety.

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6. At least one symptom from two of the following categories:

a. Autonomic Manifestations: orthostatic intolerance (neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension); light-headedness; extreme pallor; nausea and irritable bowel syndrome; urinary frequency and bladder dysfunction; palpitations with or without cardiac arrrhythmias; exertional dyspnea.

b. Neuroendocrine Manifestations: loss of thermostatic stability (subnormal body temperature and marked diurnal fluctuation, sweating episodes, recurrent feelings of feverishness and cold extremities); intolerance of extremes of heat and cold; marked weight change (anorexia or abnormal appetite); loss of adaptability and worsening of symptoms with stress.

c. Immune Manifestations: tender lymph nodes; recurrent sore throat; recurrent flu-like symptoms; general malaise; new sensitivities to food, medications and/or chemicals.

7. The illness persists for at least six months. It usually has a distinct onset, although it may be gradual. Preliminary diagnosis may be possible earlier. Three months is appropriate for children.

http://www.cfids-cab.org/MESA/ccpccd.pdf

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ME AND CFS DEFINITIONS

CDC Criteria for Chronic Fatigue Syndrome (Fukuda 1994)

Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994 Dec 15;121(12):953-9.

Clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is

* of new or definite onset (has not been lifelong)* is not the result of ongoing exertion* is not substantially alleviated by rest and* results in substantial reduction in previous levels of occupational, educational, social

or personal activities

Additional requirements

The concurrent occurrence of four or more of the following symptoms, all of which must have persisted or recurred during 6 or months of illness and must have predated the fatigue:

1. Self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social or personal activities.

2. Sore throat3. Tender cervical or axillary lymph nodes4. Muscle pain5. Multi-joint pain without joint swelling or redness6. Headaches of a new type, pattern or severity7. Unrefreshing sleep8. Post-exertional malaise lasting more than 24 hours

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ME AND CFS DEFINITIONS

CDC Case Definition for The Chronic Fatigue Syndrome (Holmes 1988)

Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988 Mar;108(3):387-9. PMID: 2829679

Major Criterion:

Must have new onset of persistent or relapsing, debilitating fatigue or easy fatigability in a person who has no previous history of similar symptoms, that does not resolve with bedrest, and that is severe enough to reduce or impair average daily activity below 50% of the patient's premorbid activity level for a period of at least 6 months.

Exclusionary Criterion:

Other clinical conditions that may produce similar symptoms must be excluded by thorough evaluation. (Excluded conditions mentioned are malignancy; autoimmune disease; localized infection such as occult abscess; bacterial disease such as endocarditis, Lyme disease, or tuberculosis; fungal disease such as histoplasmosis, blastomycosis, or coccidioidomycosis; parasitic disease such as toxoplasmosis, amebiasis, giardiasis, or helminthic infestation; disease related to HIV infection; chronic psychiatric disease such as endogenous depression, hysterical personality disorder, anxiety neurosis, or schizophrenia; chronic use of major tranquilizers, lithium, or antidepressive medications; chronic inflammatory disease such as sarcoidosis, Wegener granulomatosis, or chronic hepatitis; neuromuscular disease such as multiple sclerosis or myasthenia gravis; endocrine disease such as hypothyroidism, Addison disease, Cushing syndrome, or diabetes mellitus; alcohol or drug dependency or abuse; side effects of a chronic medication or other toxic agent such as a chemical solvent, pesticide, or heavy metal; or other known or defined chronic pulmonary, cardiac, gastrointestinal, hepatic, renal, or hematologic disease.)

Minor Criterion:

For a diagnosis of CFS, the patient must fulfill 8 or more of the following criteria (including 6 or more of criteria 1-11).

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1. Mild fever (oral temperature between 37.5° C and 38.6° C) or chills. 2. Sore throat.3. Painful lymph nodes in the anterior or posterior cervical or axillary distribution.4. Unexplained generalized muscle weakness.5. Muscle discomfort or myalgia.6. Prolonged (24 hours or greater) generalized fatigue after levels of exercise that would

have been easily tolerated in the patient’s premorbid state.7. Generalized headaches (of a type, severity or pattern that is different than the patient

may have had in the premorbid state).8. Migratory arthralgia without joint swelling or redness.9. Neuropsychologic complaints (one or more of the following: photophobia, transient

visual scotomata, forgetfulness, excessive irritability, confusion, difficulty thinking, inability to concentrate, depression)

10. Sleep disturbance (hypersomnia or insomnia)11. Description of the main symptom complex as initially developing over a few hours to

a few days12. Low-grade fever (37.8 to 38.8 degrees C), documented by a physician on at least

two occasions, at least one month apart13. Nonexudative pharyngitis, documented by a physician on at least two occasions, at

least one month apart14. Palpable or tender anterior or posterior cervical or axillary lymph nodes,

documented by a physician on at least two occasions, at least one month apart

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ME AND CFS DEFINITIONS

UK Criteria for Chronic Fatigue Syndrome (Oxford)

Severe disabling fatigue of at least a 6-month duration that affects both physical and mental functioning, and that is present for more than 50% of the time.

Other symptoms -- particularly myalgia, sleep and mood disturbances -- may be present.

Exclusion criteria:

* Active, unresolved or suspected disease that is likely to cause fatigue* Psychotic, melancholic or bipolar depression (but not uncomplicated major

depression)* Psychotic disorders* Dementia* Anorexia or bulimia nervosa

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RELATED/CO-MORBID DISEASES

Fibromyalgia (FM)

A disease with many of the same symptoms as CFS and ME. However, the emphasis in FM is on widespread trigger point or tender point pain throughout the body. Although “fibromyalgia” literally means “muscle pain,” the issue in this illness seems to be more with the fascia. Other symptoms that may be experienced include cognitive dysfunction (brain fog and memory problems), tingling of the skin, muscle spasms, weakness of limbs, nerve pain, palpitations, bowel disturbances, sleep disturbances, and emotional symptoms. Fatigue, post-exertional relapse and cognitive dysfunction in FM tend to be less severe than in ME. Many patients qualify for FM, CFS and ME diagnoses.

Chronic Lyme Disease

Lyme Disease is an infection with the bacteria called borrelia, generally transmitted through a tick bite. Especially when not treated early with antibiotics, it can become a chronic condition with specific symptoms similar to those experienced in CFS and ME. These can include severe fatigue, neuropathies (shooting pains, numbness, tingling), difficulties with concentration and memory, brain inflammation, weakness in the legs, awkward gait, facial palsy, bladder problems, vertigo, arthritis and certain emotional problems (panic attack, rage, psychosis). Many doctors believe that especially in the chronic stage, the problems of Lyme Disease are mostly related to the neurotoxins made by the bacteria rather than to the bacteria themselves. Many patients qualify for Chronic Lyme, ME and CFS diagnoses.

Toxic Mold Illness

Individuals spending time in water-damaged buildings may suffer health effects from the micoorganisms growing inside. Toxic molds (such as Stachybotrys chartarum or “black mold”) create mycotoxins, which (especially in combination with specific toxic bacteria also found in bad buildings) cause neurological toxicity and a wide variety of other systemic damage. Symptoms include most of those reported in CFS, including fatigue, weakness, muscle aches, headaches, light and sound sensitivity, a wide variety of cognitive issues, mood swings, temperature and hormonal dysregulation, neuropathies and vertigo. Some patients recover slowly or incompletely after removal from the bad

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building. Many CFS and ME patients have a history of substantial toxic mold exposures.

Aquatic Biotoxin Illnesses

Ciguatera is a foodborne illness caused by eating certain reef fishes whose flesh is contaminated with toxins originally produced by dinoflagellates. About 5% of those affected go on to have chronic ciguatera, with symptoms often lasting for many years. Initial symptoms resemble the flu (with nausea, vomiting and diarrhea); long-term symptoms are more neurological and include cognitive and memory issues, headaches, muscle aches, numbness, coordination issues, and severe fatigue. It is thought that most people who acquire ciguatera do not know they have it and attribute their symptoms to something else.

Harmful Algae Blooms (HAB’s) can include a range of toxin producers, including toxic cyanobacteria and dinoflagellates. These occur in both freshwater and marine waters. Symptoms are generally considered to be most problematic when individuals swim in infested waters, but breathing in spores also has an effect on some individuals. The World Health Organization has set limits on recommended levels in drinking water, but no standards are present in the US. Symptoms vary based on the specific microorganism, but typically include drowsiness, fatigue, numbness and cognitive issues.

Amnesic Shellfish Poisoning (ASP) is a human illness first discovered in 1987 and caused by consumption of a marine biotoxin called domoic acid. This substance can bioaccumulate in seafood and then be consumed by humans. Symptoms are similar to those experienced in severely ill ME patients (such as those in the Lake Tahoe outbreak) and include gastrointestinal distress, headache, dizziness, disorientation, vision disturbances, loss of short-term memory, motor weakness, seizures, profuse respiratory secretions, hiccoughs, unstable blood pressure, neuropathies, cardiac arrhythmias, coma and death.

Although these toxin-induced conditions appear to have a good deal in common with CFS and ME, their specific connection -- if any -- is unclear.

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Multiple Chemical Sensitivity (MCS)

This is a chronic medical condition characterized by symptoms attributed to exposures to low levels of various chemicals. Commonly suspected substances may include smoke, pesticides, plastics, synthetic fabrics, scented products, petroleum products and paints. Symptoms may include feeling tired, cognitive issues (brain fog, short-term memory problems, difficulty concentrating), muscle pain, difficulty breathing, skin irritation, numbness, trembling, anxiety, sleep disturbance, digestive issues and many others. Usually they qualify for a CFS diagnosis. Most medical professionals familiar with ME agree that MCS is something different, but many patients qualify for both of these diagnoses.

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ME AND CFS DEFINITIONS

SOME MYALGIC ENCEPHALOMYELITIS OUTBREAKS

1934! Los Angeles County Hospital - Atypical Poliomyelitis1936! Fond Du Lac, Wisconsin - St. Agnes Convent - Encephalitis1937! Erstfeld, Switzerland -  Abortive Poliomyelitis1937! St. Gallen, Switzerland  - Frohburg Hospital – Abortive Poliomyelitis1939! Middlesex, England - Harefield Sanatorium -  persistent Myalgia following sore ! throat1939! Degersheim, Switzerland - Abortive Poliomyelitis1945! Hospital of the University of Pennsylvania - epidemic Pleurodynia with prominent ! neurological symptoms and no demonstrable cause1946! Iceland –  disease resembling Poliomyelitis with the character of Akureyri disease1948! Iceland, North Coast towns - epidemic simulating Poliomyelitis1949! Adelaide, South Australia - a disease resembling Poliomyelitis1950! Louisville, Kentucky -- St. Joseph’s Infirmary - outbreak in nurses’ training school ! described as “epidemic Neuromyasthenia”1950! Upper State New York -- outbreak resembling the   Iceland disease, simulating ! acute Anterior Poliomyelitis1952! London, England - Middlesex Hospital Nurses’ Home - Encephalomyelitis ! associated with Poliomyelitis virus1952! Copenhagen, Denmark - epidemic Myositis1952! Lakeland, Florida - epidemic Neuromyasthenia1953! Coventry and District, England - an illness resembling Poliomyelitis observed in ! nurses1953! Rockville, Maryland - Chestnut Lodge Hospital - Poliomyelitis-like epidemic ! Neuromyasthenia1953! Jutland, Denmark - epidemic Encephalitis with vertigo1954! Seward, Alaska - benign Myalgic Encephalomyelitis (Iceland Disease)1954! Berlin, Germany - British army - further outbreak of a disease resembling ! Poliomyelitis1954! Liverpool, England - outbreak among medical and nursing staff in a local         ! hospital1955! Dalston, Cumbria, England – epidemic and sporadic outbreak of an unusual ! disease1955! London, England - Royal Free Hospital - outbreak in staff and patients of Benign ! Myalgic Encephalomyelitis

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1955! Perth, Australia - virus epidemic in waves1955! Gilfac Goch, Wales - outbreak of benign Myalgic Encephalomyelitis1955! Durban City, South Africa - Addington Hospital - outbreak among nurses of ! “Durban Mystery Disease”1955! Segbwema, Sierra Leone - outbreak of Encephalomyelitis1955! Patreksfjorour and Porshofn, Iceland - unusual response to polio vaccine1955! Northwest London, England - nurses’ residential home - acute Infective ! Encephalomyelitis simulating poliomyelitis1956! Ridgefield, Connecticut - epidemic Neuromyasthenia1956! Punta Gorda Florida - outbreak of epidemic Neuromyasthenia1956! Newton-le-Willows, Lancashire, England - Lymphocytic Meningoencephalitis with ! myalgia and rash1956! Pittsfield and Williamstown, Massachusetts - benign Myalgic Encephalomyelitis1956! Coventry, England - epidemic malaise, benign Myalgic Encephalomyelitis1957! Brighton, South Australia - Cocksakie Echo virus Meningitis, epidemic Myalgic ! Encephalomyelitis1958! Athens, Greece - nurses’ school - outbreak of benign Myalgic Encephalomyelitis ! with periostitis and arthopathy noted.1958! Southwest London, England - reports of sporadic cases of Myalgic ! Encephalomyelitis1959! Newcastle Upon Tyne, England - outbreak of benign Myalgic Encephalomyelitis1961! Basel, Switzerland - sporadic cases of benign Myalgic Encephalomyelitis1961! New York State - outbreak of epidemic Neuromyasthenia in a convent1964! Northwest London, England - epidemic malaise, epidemic Neuromyasthenia1964! Franklin, Kentucky - outbreak of Neuromyasthenia in a factory1967! Edinburgh, Scotland - sporadic cases resembling benign Myalgic ! Encephalomyelitis1968! Fraidek, Lebanon - benign Myalgic Encephalomyelitis1969! Brooklyn, New York - State University of New York Downstate Medical Center - ! epidemic Neuromyasthenia, unidentified symptom complex1970! Lackland Air Force Base, Texas - epidemic Neuromyasthenia1970! London, England - Great Ormond Street Hospital for Children - outbreak of ! Neuromyasthenia among nurses1975! Sacramento, California - Mercy San Juan Hospital - Infectious Venulitis, epidemic ! Phelobodynia1976! Southwest Ireland - epidemic Neuromyasthenia, benign Myalgic ! Encephalomyelitis1977! Dallas – Fort Worth, Texas - epidemic Neuromyasthenia1979! Southampton, England - Myalgic Encephalomyelitis

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1980! West Kilbridge, Ayrshire, Scotland - epidemic Myalgic Encephalomyelitis1980! San Francisco, California – epidemic persistent flu-like illness1981! Stirlingshire, Scotland  - sporadic Myalgic Encephalomyelitis1982! West Otago, Dunedin and Hamilton, New Zealand - Myalgic Encephalomyelitis1983! Los Angeles, California - initial cases of an unknown, chronic symptom complex ! involving profound “fatigue”1984! Lake Tahoe Area of California/Nevada - start of a yearlong epidemic involving ! over 160 cases of chronic illness eventually characterized as Chronic Fatigue ! Syndrome

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ME AND CFS DEFINITIONS

MEDICAL LITERATURE

Illness Name, Definition and Subtypes:

Maes M, Anderson G, Morris G, Berk M. Diagnosis of myalgic encephalomyelitis: where are we now? Expert Opin Med Diagn. 2013 May;7(3):221-5. PMID: 23480562

Pattern recognition methods showed the existence of three qualitatively different categories related to CFS: (a) chronic fatigue not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS.

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Johnston S, Brenu EW, Staines DR, Marshall-Gradisnik S. The adoption of chronic fatigue syndrome/myalgic encephalomyelitis case definitions to assess prevalence: a systematic review. Ann Epidemiol. 2013 Jun;23(6):371-6. PMID: 23683713

A systematic review of primary studies reporting the prevalence of CFS since 1990 was conducted. The authors suggest that future assessments of prevalence should consider adopting more recent developments, such as the newly available International Consensus Criteria.

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Morris G, Maes M. Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions. Neuro Endocrinol Lett. 2013 May 20;34(3):185-199. PMID: 23685416

Both ME and CFS are complex disorders that share neuro-immune disturbances, which are more severe in ME than in CFS.

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Jason LA, Brown A, Clyne E, Bartgis L, Evans M, Brown M. Contrasting case definitions for chronic fatigue syndrome, Myalgic Encephalomyelitis/chronic fatigue syndrome and myalgic encephalomyelitis. Eval Health Prof. 2012 Sep;35(3):280-304. PMID: 22158691

When applied to a population meeting the 1994 CFS Fukuda/CDC case definition, both the ME/CFS Canadian case definition and ME International Consensus criteria appear to select a more severe subset of patients.

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Maes M, Twisk FN, Johnson C. Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data. Psychiatry Res. 2012 Dec 30;200(2-3):754-60. PMID: 22521895

Using fatigue, a subjective feeling of infection and PEM, the researchers found that ME, CFS, and chronic fatigue were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. They conclude that Fukuda's criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM).

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Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AP, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S. Myalgic Encephalomyelitis: International Consensus Criteria. J Intern Med. 2011 Jul 20. PMID: 21777306

In view of recent research and clinical experience with CFS that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term "myalgic encephalomyelitis"(ME), because it indicates an underlying pathophysiology. Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other health care providers, improve consistency of diagnoses in adult

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and paediatric patients internationally, and facilitate clearer identification of patients for research studies.

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Jason LA, Skendrovic B, Furst J, Brown A, Weng A, Bronikowski C. Data mining: comparing the empiric CFS to the Canadian ME/CFS case definition. J Clin Psychol. 2011 Aug 5. PMID: 21823124

Two different definitions of CFS are compared with data mining.

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Ruiz E, Alegre J, García Quintana AM, Aliste L, Blázquez A, Fernández de Sevilla T. Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units. Rev Clin Esp. 2011 Jul 25. PMID: 21794854

The authors found that using the Canadian Consensus Criteria for ME/CFS as a diagnosis tool results in a homogenous patient population.

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Jason LA, Boulton A, Porter NS, Jessen T, Njoku MG, Friedberg F. Classification of myalgic encephalomyelitis/chronic fatigue syndrome by types of fatigue. Behav Med. 2010 Jan-Mar;36(1):24-31. PMID: 20185398

CFS patients may be appropriately classified into subgroups depending on the type of fatigue they experience.

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Christley Y, Duffy T, Martin CR. A review of the definitional criteria for chronic fatigue syndrome. J Eval Clin Pract. 2010 Oct 4. PMID: 21029269

The variety of case definitions for CFS and the problems that this has caused for the pursuit of CFS research are discussed.

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Hickie I, Davenport T, Vernon SD, Nisenbaum R, Reeves WC, Hadzi-Pavlovic D, Lloyd A; International Chronic Fatigue Syndrome Study Group. Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings? Aust N Z J Psychiatry. 2009 Jan;43(1):25-35. PMID: 19085525

Researchers determined a five-factor model of the key symptom domains in CFS: 'musculoskeletal pain/fatigue', 'neurocognitive difficulties', 'inflammation', 'sleep disturbance/fatigue' and 'mood disturbance.’

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Jason L, Porter N, Shelleby E, Till L, Bell DS, Lapp CW, Rowe K, De Meirleir K. Severe versus Moderate criteria for the new pediatric case definition for ME/CFS. Child Psychiatry Hum Dev. 2009 Dec;40(4):609-20. PMID: 19513826

The Pediatric Case Definition for ME/CFS can distinguish between those with this illness and controls, and between those with Severe versus Moderate manifestations of the illness.

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Aslakson E, Vollmer-Conna U, Reeves WC, White PD. Replication of an empirical approach to delineate the heterogeneity of chronic unexplained fatigue. Popul Health Metr. 2009 Oct 5;7:17. PMID: 19804639

This analysis evaluated 386 women identified in a population-based survey of chronic fatigue and unwellness in metropolitan, urban, and rural populations of the state of Georgia, USA. and used statistical analysis to subtype them. Participants in Class 1 (25%) were polysymptomatic, with sleep problems and depressed mood. Class 2 (24%) was also polysymptomatic, with insomnia and depression, but participants were also obese with associated metabolic strain. Class 3 (20%) had more selective symptoms but was equally obese with metabolic strain. Class 4 (20%) and Class 5 (11%) consisted of nonfatigued, less symptomatic individuals, Class 4 being older and Class 5 younger. People with CFS fell equally into Classes 1 and 2.

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Hashimoto N. History of chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):975-82. PMID: 17561685

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The history of CFS and the need for new diagnostic guidelines is discussed.

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Vernon SD, Reeves WC. The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome. Pharmacogenomics. 2006 Apr;7(3):345-54. PMID: 16610945

Data was collected during a 2-day in-hospital study of persons with CFS, other medically and psychiatrically unexplained fatiguing illnesses and nonfatigued controls identified from the general population of Wichita, KS, USA. While in the hospital, the participants' psychiatric status, sleep characteristics and cognitive functioning was evaluated, and biological samples were collected to measure neuroendocrine status, autonomic nervous system function, systemic cytokines and peripheral blood gene expression.

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Jason LA, Corradi K, Torres-Harding S, Taylor RR, King C. Chronic fatigue syndrome: the need for subtypes. Neuropsychol Rev. 2005 Mar;15(1):29-58. PMID: 15929497

Subtyping individuals with CFS on sociodemographic, functional disability, viral, immune, neuroendocrine, neurology, autonomic, and genetic biomarkers can provide clarification for researchers and clinicians who encounter CFS's characteristically confusing heterogeneous symptom profiles.

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Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome--a clinically empirical approach to its definition and study. BMC Med. 2005 Dec 15;3:19. PMID: 16356178

The objective of this study was to apply the 1994 CFS criteria by standardized reproducible criteria. This population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS; (2) non-fatigued controls; (3) persons with medically unexplained fatigue not CFS (ISF); (4) CFS accompanied by melancholic depression; and (5) ISF plus melancholic depression. Subjects empirically

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classified as CFS had significantly worse impairment, more severe fatigue, more frequent and severe accompanying symptoms than those with ISF, who in turn had significantly worse scores than the not ill.

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King C, Jason LA. Improving the diagnostic criteria and procedures for chronic fatigue syndrome. Biol Psychol. 2005 Feb;68(2):87-106. PMID: 15450690

Using statistical procedures, three methods for improving the diagnostic criteria found to have potential: identification of new diagnostic symptoms, the use of severity ratings for symptomatology, and the identification of standardized measures that differentiate cases of CFS from other conditions.

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Nisenbaum R, Reyes M, Unger ER, Reeves WC. Factor analysis of symptoms among subjects with unexplained chronic fatigue: what can we learn about chronic fatigue syndrome? J Psychosom Res. 2004 Feb;56(2):171-8. PMID: 15016574

A population of CFS patients in Wichita, Kansas, was studied. The authors confirmed three factors: musculoskeletal, infection and cognition-mood-sleep.

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Kennedy G, Abbot NC, Spence V, Underwood C, Belch JJ. The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfill the criteria. Ann Epidemiol. 2004 Feb;14(2):95-100. PMID: 15018881

Three groups of patients meeting the CDC CFS criteria but self-reporting different etiologies (Gulf War Syndrome, pesticide exposure, other) had different sorts of symptoms. This suggests that the CDC criteria needs to be more specific.

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Jason LA, Helgerson J, Torres-Harding SR, Carrico AW, Taylor RR. Variability in diagnostic criteria for chronic fatigue syndrome may result in substantial differences in

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patterns of symptoms and disability. Eval Health Prof. 2003 Mar;26(1):3-22. PMID:12629919

Significant variance with regard to a number of symptoms (neurologic, neuropsychiatric, fatigue/weakness, rheumatological) occurs depending on which definition is used (ME, CDC CFS, chronic fatigue), and it thus may be inappropriate to merge the definitions together.

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Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER; International Chronic Fatigue Syndrome Study Group Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.BMC Health Serv Res. 2003 Dec 31;3(1):25. PMID: 14702202

This paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.

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Jason LA, Eisele H, Taylor RR. Assessing attitudes toward new names for chronic fatigue syndrome. Eval Health Prof. 2001 Dec;24(4):424-35. PMID: 11817200

A questionnaire was distributed at the American Association of Chronic Fatigue Syndrome's biannual convention in Washington in January 2001 as well as through various Internet Web sites and listserves during early February and March of 2001. Most respondents (86%) indicated they wanted a name change, although more patients than scientists were in favor of this change.

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Jason LA, Taylor RR, Kennedy CL, Song S, Johnson D, Torres S. Chronic fatigue syndrome: occupation, medical utilization, and subtypes in a community-based sample. J Nerv Ment Dis. 2000 Sep;188(9):568-76. PMID: 11009329

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Those diagnosed with CFS were subclassified based on a variety of categories, including duration of illness, mode of illness onset, and presence or absence of a stressful life event directly preceding onset.

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Nisenbaum R, Reyes M, Mawle AC, Reeves WC. Factor analysis of unexplained severe fatigue and interrelated symptoms: overlap with criteria for chronic fatigue syndrome. Am J Epidemiol. 1998 Jul 1;148(1):72-7. PMID: 9663406

The objective of this study was to identify factors explaining the correlations among unexplained severe fatigue of different durations and symptoms reported as being significant health problems during a preceding 4-week period amongst CFS patients in San Francisco, California. Common factor analyses identified three correlated factors, defined as "fatigue-mood-cognition" symptoms, "flu-type" symptoms, and "visual impairment."

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Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994 Dec 15;121(12):953-9.

The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. The authors propose a conceptual framework and a set of guidelines, including recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.

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Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988 Mar;108(3):387-9. PMID: 2829679

Although the syndrome has received recent attention, and has been diagnosed in many patients, the chronic Epstein-Barr virus syndrome has not been defined consistently.

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The authors propose a new name for the chronic Epstein-Barr virus syndrome--the chronic fatigue syndrome--that more accurately describes this symptom complex as a syndrome of unknown cause characterized primarily by chronic fatigue. We also present a working definition for the chronic fatigue syndrome designed to improve the comparability and reproducibility of clinical research and epidemiologic studies.

Myalgic Encephalomyelitis:

Wessely S. Myalgic encephalomyelitis. J R Soc Med. 1991 Mar;84(3):182-3. PMID: 2013912

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293160/pdf/jrsocmed00126-0074c.pdf

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Hyde BM. Myalgic encephalomyelitis (chronic fatigue syndrome): an historic perspective. Can Dis Wkly Rep. 1991 Jan;17 Suppl 1E:5-8. PMID: 1669354

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Brodrick J. Myalgic encephalomyelitis: yuppie 'flu--a real illness. Interview by Charlotte Alderman. Nurs Stand. 1990 Aug 29-Sep 4;4(49):18. PMID: 2119747

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Wilson CW. Myalgic encephalomyelitis: an alternative theory. J R Soc Med. 1990 Aug;83(8):481-3. PMID: 2231572

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292769/pdf/jrsocmed00133-0005b.pdf

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Dowsett EG, Ramsay AM, McCartney RA, Bell EJ. Myalgic encephalomyelitis--a persistent enteroviral infection? Postgrad Med J. 1990 Jul;66(777):526-30.PMID: 2170962

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429637/pdf/postmedj00163-0031.pdf

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Lynch S, Seth R. Depression and myalgic encephalomyelitis. J R Soc Med. 1990 May;83(5):341. PMID: 2380955

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292666/pdf/jrsocmed00136-0073a.pdf

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Shepherd C. How I treat myalgic encephalomyelitis: forum. Practitioner. 1990 Apr 8;234(1486):326. PMID: 2371218

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Powell S. Myalgic encephalomyelitis. Br J Gen Pract. 1990 Apr;40(333):170. No abstract available. PMID: 2115368

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1371257/pdf/brjgenprac00081-0042a.pdf

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Hodson AD. Myalgic encephalomyelitis. J R Soc Med. 1990 Mar;83(3):199-200. PMID: 20894766

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292588/pdf/jrsocmed00138-0079c.pdf

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-----. Myalgic encephalomyelitis. J R Soc Med. 1990 Mar;83(3):199-200. No abstract available. PMID: 2325071

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292587/pdf/jrsocmed00138-0079b.pdf

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Prasher D, Smith A, Findley L. Sensory and cognitive event-related potentials in myalgic encephalomyelitis. J Neurol Neurosurg Psychiatry. 1990 Mar;53(3):247-53. PMID: 2324756

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1014138/pdf/jnnpsyc00513-0063.pdf

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Wessely S. Old wine in new bottles: neurasthenia and 'ME'. Psychol Med. 1990 Feb;20(1):35-53. PMID: 2181519

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Grist NR. Myalgic encephalomyelitis: postviral fatigue and the heart. BMJ. 1989 Nov 11;299(6709):1219. PMID: 2513065

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838100/pdf/bmj00258-0049b.pdf

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Lev M. Myalgic encephalomyelitis. J R Soc Med. 1989 Nov;82(11):693-4. PMID: 2593126

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292388/pdf/jrsocmed00144-0069.pdf

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-----. Myalgic encephalomyelitis by proxy. BMJ. 1989 Oct 21;299(6706):1030-1. PMID: 2511950

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1837896/pdf/bmj00255-0046c.pdf

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Snow P. Myalgic encephalomyelitis. N Z Med J. 1989 Aug 23;102(874):449. PMID: 2761898

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Murdoch JC. The myalgic encephalomyelitis syndrome. N Z Med J. 1989 Jul 26;102(872):372-3. PMID: 2797553

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Coakley JH. Myalgic encephalomyelitis and muscle fatigue. BMJ. 1989 Jun 24;298(6689):1711-2. PMID: 2503189

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Zala J. Diagnosing myalgic encephalomyelitis. Practitioner. 1989 Jun 22;233(1471):916-9. PMID: 2594656

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1836756/pdf/bmj00237-0063d.pdf

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-----. Myalgic encephalomyelitis. BMJ. 1989 Jun 10;298(6687):1577-8. PMID: 2503125

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1836797/pdf/bmj00235-0051b.pdf

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Richmond C. Myalgic encephalomyelitis, Princess Aurora, and the wandering womb.BMJ. 1989 May 13;298(6683):1295-6. PMID: 2500204

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1836497/pdf/bmj00231-0039.pdf

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Welch JC. Abnormal erythrocytes in myalgic encephalomyelitis. N Z Med J. 1989 Apr 26;102(866):202. PMID: 2710458

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Wessely S. Myalgic encephalomyelitis-a warning: discussion paper. J R Soc Med. 1989 Apr;82(4):215-7. PMID: 2716018

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292087/pdf/jrsocmed00151-0033.pdf

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Simpson LO. Nondiscocytic erythrocytes in myalgic encephalomyelitis. N Z Med J. 1989 Mar 22;102(864):126-7. PMID: 2927808

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Cant BR. Myalgic encephalomyelitis. N Z Med J. 1989 Feb 8;102(861):52. PMID: 2739970

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Willoughby E. Myalgic encephalomyelitis. N Z Med J. 1989 Jan 25;102(860):19-20. PMID: 2913521

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Shepherd C. Myalgic encephalomyelitis--is it a real disease? Practitioner. 1989 Jan;233(1461):41-2, 44, 46. PMID: 2798285

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Murdoch JC. The myalgic encephalomyelitis syndrome. Fam Pract. 1988 Dec;5(4):302-6. Review. PMID: 2852613

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-----. Myalgic encephalomyelitis. N Z Med J. 1988 Nov 23;101(858):800-1. PMID: 3194079

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Hyde B, Bergmann S. Akureyri disease (myalgic encephalomyelitis), forty years later. Lancet. 1988 Nov 19;2(8621):1191-2. PMID: 2903396

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Willoughby EW. Myalgic encephalomyelitis. N Z Med J. 1988 Nov 9;101(857):773. PMID: 3186037

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Spracklen FH. The chronic fatigue syndrome (myalgic encephalomyelitis)--myth or mystery? S Afr Med J. 1988 Nov 5;74(9):448-52. Review. PMID: 3055363

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-----. Myalgic encephalomyelitis. N Z Med J. 1988 Oct 26;101(856 Pt 1):672. No abstract available. PMID: 3186016

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Gordon N. Myalgic encephalomyelitis. Dev Med Child Neurol. 1988 Oct;30(5):677-82. Review. PMID: 3068084

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Murdoch JC. Cell-mediated immunity in patients with myalgic encephalomyelitis syndrome.N Z Med J. 1988 Aug 10;101(851):511-2. PMID: 3261407

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-----. Myalgic encephalomyelitis, or what? Lancet. 1988 Jul 9;2(8602):100-1. PMID: 2898668

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Holborow PL. Pathophysiology of myalgic encephalomyelitis. Med J Aust. 1988 Jun 6;148(11):598, 600. PMID: 3374430

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Lloyd AR, Wakefield D, Boughton C, Dwyer J. What is myalgic encephalomyelitis? Lancet. 1988 Jun 4;1(8597):1286-7. PMID: 2897549

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Archard LC, Bowles NE, Behan PO, Bell EJ, Doyle D. Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase. J R Soc Med. 1988 Jun;81(6):326-9. PMID: 3404526

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291623/pdf/jrsocmed00161-0020.pdf

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Bell EJ, McCartney RA, Riding MH. Coxsackie B viruses and myalgic encephalomyelitis. J R Soc Med. 1988 Jun;81(6):329-31. PMID: 2841461

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291624/pdf/jrsocmed00161-0023.pdf

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Jennekens FG, van Gijn J. [Postviral fatigue syndrome or myalgic encephalomyelitis]. Ned Tijdschr Geneeskd. 1988 May 28;132(22):999-1001. Dutch. PMID: 3380192

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Wakefield D, Lloyd A, Dwyer J, Salahuddin SZ, Ablashi DV. Human herpesvirus 6 and myalgic encephalomyelitis. Lancet. 1988 May 7;1(8593):1059. PMID: 2896906

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Maros K. Myalgic encephalomyelitis? Med J Aust. 1988 Apr 18;148(8):424. PMID: 3357477

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David AS, Wessely S, Pelosi AJ. Postviral fatigue syndrome: time for a new approach.Br Med J (Clin Res Ed). 1988 Mar 5;296(6623):696-9. Review. PMID: 3128374

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2545306/pdf/bmj00275-0042.pdf

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Lloyd A, Hanna DA, Wakefield D. Interferon and myalgic encephalomyelitis.Lancet. 1988 Feb 27;1(8583):471. PMID: 2893889

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Byrne E. Idiopathic chronic fatigue and myalgia syndrome (myalgic encephalomyelitis): some thoughts on nomenclature and aetiology. Med J Aust. 1988 Jan 18;148(2):80-2. PMID: 3336341

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Ho-Yen DO, Carrington D, Armstrong AA. Myalgic encephalomyelitis and alpha-interferon. Lancet. 1988 Jan 16;1(8577):125. PMID: 2891971

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Behan PO, Behan WM. Postviral fatigue syndrome. Crit Rev Neurobiol. 1988;4(2):157-78. Review. PMID: 3063394

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Matthew C. Myalgic encephalomyelitis and the doctor. N Z Med J. 1987 Sep 9;100(831):569. PMID: 3451147

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Mukherjee TM, Smith K, Maros K. Abnormal red-blood-cell morphology in myalgic encephalomyelitis. Lancet. 1987 Aug 8;2(8554):328-9. PMID: 2886780

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Archer MI. The post-viral syndrome: a review. J R Coll Gen Pract. 1987 May;37(298):212-4. Review. PMID: 3320358

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1710789/pdf/jroyalcgprac00029-0021.pdf

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Taerk GS, Toner BB, Salit IE, Garfinkel PE, Ozersky S. Depression in patients with neuromyasthenia (benign myalgic encephalomyelitis). Int J Psychiatry Med. 1987;17(1):49-56. PMID: 3583562

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Matthew C. Myalgic encephalomyelitis. N Z Med J. 1986 Sep 10;99(809):678. PMID: 3463904

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Blackmore RJ. Myalgic encephalomyelitis and Immunovir. N Z Med J. 1986 Jul 9;99(805):513. PMID: 3461389

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McCartney RA, Banatvala JE, Bell EJ. Routine use of mu-antibody-capture ELISA for the serological diagnosis of Coxsackie B virus infections. J Med Virol. 1986 Jul;19(3):205-12. PMID: 3016163

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Simpson LO, Shand BI, Olds RJ. Blood rheology and myalgic encephalomyelitis: a pilot study. Pathology. 1986 Apr;18(2):190-2. PMID: 3093959

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Rowlandson PH, Stephens JA. Cutaneous reflex responses recorded in children with various neurological disorders. Dev Med Child Neurol. 1985 Aug;27(4):434-47.PMID: 2993087

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Staines D. Myalgic encephalomyelitis hypothesis. Med J Aust. 1985 Jul 22;143(2):91. PMID: 4021881

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Byrne E, Trounce I, Dennett X. Chronic relapsing myalgia (Post viral): clinical, histological, and biochemical studies. Aust N Z J Med. 1985 Jun;15(3):305-8. PMID: 3864422

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Maurizi CP. Raphe nucleus encephalopathy (myalgic encephalomyelitis, epidemic neuromyasthenia). Med Hypotheses. 1985 Apr;16(4):351-4. PMID: 4010573

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-----. Myalgic encephalomyelitis. N Z Med J. 1985 Jan 23;98(771):20-1. PMID: 3855509

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Gow PJ. Myalgic encephalomyelitis. N Z Med J. 1984 Dec 12;97(769):868. PMID: 6595571

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-----. Myalgic encephalomyelitis. N Z Med J. 1984 Nov 14;97(767):782. PMID: 6593632

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-----. Myalgic encephalomyelitis. N Z Med J. 1984 Oct 10;97(765):698-9. PMID: 6592485

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Bell EJ, McCartney RA. A study of Coxsackie B virus infections, 1972-1983. J Hyg (Lond). 1984 Oct;93(2):197-203. PMID: 6094660

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2129449/pdf/jhyg00014-0036.pdf

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Gow PJ. Myalgic encephalomyelitis. N Z Med J. 1984 Sep 12;97(763):620. PMID: 6591048

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Calder BD, Warnock PJ. Coxsackie B infection in a Scottish general practice. J R Coll Gen Pract. 1984 Jan;34(258):15-9. PMID: 6319691

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1959663/pdf/jroyalcgprac00169-0017.pdf

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Keighley BD, Bell EJ. Sporadic myalgic encephalomyelitis in a rural practice. J R Coll Gen Pract. 1983 Jun;33(251):339-41. PMID: 6310105

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1972871/pdf/jroyalcgprac00078-0021.pdf

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Fegan KG, Behan PO, Bell EJ. Myalgic encephalomyelitis--report of an epidemic. J R Coll Gen Pract. 1983 Jun;33(251):335-7. PMID: 6310104

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------. Know your organizations: the Myalgic Encephalomyelitis Association. Health Visit. 1982 Jul;55(7):350. PMID: 6921182

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Parish G. Myalgic encephalomyelitis: faulty fibres? Nurs Mirror. 1981 Oct 7;153(15):41-2. PMID: 6913031

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Ramsay M. Myalgic encephalomyelitis: a baffling syndrome. Nurs Mirror. 1981 Oct 7;153(15):40-1. PMID: 6913030

*Parish JG. Myalgic encephalomyelitis. Lancet. 1981 Apr 25;1(8226):950-1. PMID: 6112360

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Layzer RB. Myoglobinaemia in benign myalgic encephalomyelitis. Lancet. 1981 Mar 21;1(8221):670. PMID: 6110899

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Goodwin CS. Was it benign myalgic encephalomyelitis? Lancet. 1981 Jan 3;1(8210):37-8. PMID: 6109065

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May PG, Donnan SP, Ashton JR, Ogilvie MM, Rolles CJ. Personality and medical perception in benign myalgic encephalomyelitis. Lancet. 1980 Nov 22;2(8204):1122-4.PMID: 6107734

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Church AJ. Myalgic encephalomyelitis. Med J Aust. 1980 Aug 23;2(4):224. PMID: 7432298

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Behan PO. Epidemic myalgic encephalomyelitis. Practitioner. 1980 Aug;224(1346):805-7. PMID: 7433399

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Bishop J. Epidemic myalgic encephalomyelitis. Med J Aust. 1980 Jun 14;1(12):585-6, 609. PMID: 7402153

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Church AJ. Myalgic encephalomyelitis "an obscene cosmic joke"? Med J Aust. 1980 Apr 5;1(7):307-8. PMID: 7393056

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Ramsay AM, Rundle A. Clinical and biochemical findings in ten patients with benign myalgic encephalomyelitis. Postgrad Med J. 1979 Dec;55(654):856-7. PMID: 548947

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425703/?tool=pubmed

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Pampiglione G, Harris R, Kennedy J. Electro-encephalographic investigations in myalgic encephalomyelitis. Postgrad Med J. 1978 Nov;54(637):752-4. PMID: 746023

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1606252/pdf/brmedj00135-0058a.pdf

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Behan PO. Post-infectious encephalomyelitis: some aetiological mechanisms. Postgrad Med J. 1978 Nov;54(637):755-9. PMID: 34143

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1606252/pdf/brmedj00135-0058a.pdf

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Wookey C. Epidemic myalgic encephalomyelitis. Br Med J. 1978 Jul 15;2(6131):202. PMID: 678851

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-----. Epidemic myalgic encephalomyelitis. Br Med J. 1978 Jun 3;1(6125):1436-7. PMID: 647324

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1604957/pdf/brmedj00128-0006b.pdf

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Ramsay AM, Dowsett EG, Dadswell JV, Lyle WH, Parish JG. Icelandic disease (benign myalgic encephalomyelitis or Royal Free disease) Br Med J. 1977 May 21;1(6072):1350. PMID: 861618

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1607215/pdf/brmedj00463-0058b.pdf

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Parish JG. Benign myalgic encephalomyelitis. Br J Psychiatry. 1973 Jun;122(571):735. PMID: 4716076

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Ramsay AM. Benign myalgic encephalomyelitis. Br J Psychiatry. 1973 May;122(570):618-9. PMID: 4717041

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Walther H. [Epidemic myalgic encephalomyelitis]. Schweiz Rundsch Med Prax. 1972 Apr 11;61(15):469-80. German. PMID: 5022278

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-----. Benign myalgic encephalomyelitis. Med J Aust. 1970 Jul 4;2(1):3. PMID: 5447847

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Lyle WH. Encephalomyelitis resembling benign myalgic encephalomyelitis. Lancet. 1970 May 23;1(7656):1118-9. PMID: 4191997

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Innes SG. Encephalomyelitis resembling benign myalgic encephalomyelitis. Lancet. 1970 May 9;1(7654):969-71. PMID: 4191935

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McEvedy CP, Beard AW. Concept of benign myalgic encephalomyelitis.Br Med J. 1970 Jan 3;1(5687):11-5. PMID: 5411596

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700895/pdf/brmedj02268-0023.pdf

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Mourad S, Chidiac J. Benign myalgic encephalomyelitis in Lebanon. J Med Liban. 1969;22(6):735-40. PMID: 5370523

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Kendell RE. The psychiatric sequelae of benign myalgic encephalomyelitis. Br J Psychiatry. 1967 Aug;113(501):833-40. PMID: 6048369

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Gsell O. [Benign myalgic encephalomyelitis, epidemic pseudoneurasthenia]. Schweiz Med Wochenschr. 1963 Feb 2;93:197-200. German. PMID: 13950994

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Price JL. Myalgic encephalomyelitis. Lancet. 1961 Apr 8;1(7180):737-8. PMID: 13737972

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Pool JH, Walton JN, Brewis EG, Uldall PR, Wright AE, Gardner PS. Benign myalgic encephalomyelitis in Newcastle upon Tyne. Lancet. 1961 Apr 8;1(7180):733-7. PMID: 13737057

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Klajman A, Pinkhas B, Rannon L. [An outbreak of an epidemic of benign myalgic encephalomyelitis]. Harefuah. 1960 May 15;58:314-5. Hebrew. PMID: 14409571

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Bornstein B, Bechar M, Lass H. Benign myalgic encephalomyelitis. (Report of five cases). Psychiatr Neurol (Basel). 1960 Mar;139:132-40. PMID: 13802904

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Daikos GK, Garzonis S, Paleologue A, Bousvaros GA, Papadoyannakis N. Benign myalgic encephalomyelitis: an outbreak in a nurses' school in Athens. Lancet. 1959 Apr 4;1(7075):693-6. PMID: 13642848

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Acheson ED. The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia. Am J Med. 1959 Apr;26(4):569-95. PMID: 13637100

http://www.meresearch.org.uk/information/keypubs/Acheson_AmJMed.pdf

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Bhatia BB, Chandra S, Bhushan C. Benign myalgic encephalomyelitis. J Indiana State Med Assoc. 1958 Oct;31(8):327-8. PMID: 13611265

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Gsell O. [Encephalitis myalgica epidemica, a poliomyelitis-like disease; epidemic neuromyasthenia, benign myalgic encephalomyelitis]. Schweiz Med Wochenschr. 1958 May 17;88(20):488-91. German. PMID: 13568694

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Greene IM. Benign myalgic encephalomyelitis; syndrome mimicking anterior poliomyelitis. J Fla Med Assoc. 1958 Apr;44(10):1105-6. PMID: 13525606

*Galpin JF. Benign myalgic encephalomyelitis. Br J Clin Pract. 1958 Mar;12(3):186-8 passim. PMID: 13510534

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Deisher JB. Benign myalgic encephalomyelitis (Iceland disease) in Alaska. Northwest Med. 1957 Dec;56(12):1451-6. PMID: 13484090

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-----. [Benign epidemic myalgic encephalomyelitis]. Recenti Prog Med. 1957 Nov;23(5):525-31. Italian. PMID: 13518620

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-----. EPIDEMIC myalgic encephalomyelitis. Br Med J. 1957 Oct 19;2(5050):927-8. PMID: 13472011

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962482/pdf/brmedj03125-0047.pdf

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Acheson ED. Benign myalgic encephalomyelitis. Lancet. 1957 Apr 20;272(6973):834-5. PMID: 13417614

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Galpine JF, Brady C. Benign myalgic encephalomyelitis. Lancet. 1957 Apr 13;272(6972):757-8. PMID: 13417586

*Lindan R. Benign Myalgic Encephalomyelitis. Can Med Assoc J. 1956 Oct 1;75(7):596-7. PMID: 20325349

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1824640/pdf/canmedaj00742-0051.pdf

*Blattner RJ. Benign myalgic encephalomyelitis (Akureyri disease, Iceland disease). J Pediatr. 1956 Oct;49(4):504-6. PMID: 13358047

Chronic Epstein-Barr

Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985 Jan;102(1):1-7.

Forty-four patients, including 26 adults and 18 children under 15 years of age, were referred for evaluation of recurrent or persistent illnesses, with symptoms including pharyngitis, lymphadenopathy, fever, headaches, arthralgia, fatigue, depression, dyslogia, and myalgia. Thirty-nine patients were positive for Epstein-Barr virus antibody with antibody levels compatible with active infection for at least 1 year. PMID: 2578266

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Straus SE, Tosato G, Armstrong G, Lawley T, Preble OT, Henle W, Davey R, Pearson G, Epstein J, Brus I, et al. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985 Jan;102(1):7-16.

Clinical, serologic, virologic, and immunologic evaluations for 31 adults with chronic illness and fatigue suggested that 23 had persisting Epstein-Barr virus infection. Among these 23 patients, cellular immune mechanisms were generally normal, but 4 had mild immunoglobulin deficiencies. The authors believe that the Epstein-Barr virus may be associated with chronic illness in adults.

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DuBois RE, Seeley JK, Brus I, Sakamoto K, Ballow M, Harada S, Bechtold TA, Pearson G, Purtilo DT. Chronic mononucleosis syndrome. South Med J. 1984 Nov;77(11):1376-82. PMID: 6093268

The authors present data on 14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection.

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Tobi M, Morag A, Ravid Z, Chowers I, Feldman-Weiss V, Michaeli Y, Ben-Chetrit E, Shalit M, Knobler H. Prolonged atypical illness associated with serological evidence of persistent Epstein-Barr virus infection. Lancet. 1982 Jan 9;1(8263):61-4. PMID: 6119490

Seven patients with prolonged atypical illness were followed up for more than a year. Sera taken during that period showed significantly increased titres of IgM antibodies against the viral capsid antigen (VCA) of Epstein-Barr virus (EBV). In four of the patients antibodies to the R component of the early antigen (EA) complex of EBV were clearly detectable. Only one of these seven patients had presented with symptoms of classic infectious mononucleosis. Serological and clinical observations in these patients suggest that the prolonged atypical illness was probably the result of persistent EBV infection.

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Neurasthenia

Lillestøl K, Bondevik H. Neurasthenia in Norway 1880-1920. Tidsskr Nor Laegeforen. 2013 Mar 19;133(6):661-5. PMID: 23552163

On the basis of Norwegian medical journals from the period 1880-1920, the authors sought to study the introduction, understanding and application of the concept of neurasthenia in Norwegian medical practice.

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ME AND CFS DEFINITIONS

MEDIA COVERAGE

December 14, 2011MSN Her (UK)Are You Permanently Tired Or Is It ME?By Zoe Zahra

http://style.uk.msn.com/health/are-you-permanently-tired-or-is-it-me

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March 5, 2011Wall Street JournalAn Illness That’s Hard to Live With -- Or DefineBy Leonard A. Jason

http://online.wsj.com/article/SB10001424052748704507404576179031979295592.html?mod=wsj_share_facebook

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March 4, 2011The New York TimesDefining an Illness is Fodder for DebateBy David Tuller

http://www.nytimes.com/2011/03/08/health/research/08fatigue.html?src=ISMR_AP_LI_LST_FB

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Copyright 2013, Paradigm Change/Lisa Petrison, Ph.D.

This document may be distributed freely in its entirety. Quotations may be used without restriction insofar as attribution is provided.

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For more information, visit Paradigm Change at www.paradigmchange.me.

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