Neuroimmune Alliance is a charity run by M.E sufferers for M.E sufferers. M.E can be a complex disease that is often misunderstood by the medical profession, leaving sufferers feeling isolated and scared. This leaflet aims to answer some basic questions about M.E.

I had the flu at the same time as my friend but she recovered and I didn’t. Why?

A very common question, why? Evidence suggests that there are specific genes in people with M.E that allows a virus to become a trigger, switching off the immune system and allowing it to be invaded by host bacteria and pathogens. This in turn can lead to multiple autoimmune disorders within the illness itself. Abnormal SPECT scans have revealed viral brain injury in patients. M.E is a multi organic complex disease that is little understood by the medical profession but a few pioneering experts are making waves with research into the condition.

Some patients with M.E (PWME) have viral infections in the brain, i.e. viral encephalitides. These are difficult to knock out, but some are treatable with existing antivirals, as has been shown by Daniel Peterson, M.D. of Incline Village, NV.
Testing for these infections involves performing analyses, including PCR analyses, on spinal fluid taken from a spinal tap (lumbar puncture).
PWME who have pressure-type headaches and a variety of neurological symptoms are suspects for having encephalitides.

I have been diagnosed with M.E and am unhappy with being offered only exercise therapy and cognitive behaviour therapy, what should I do?

Some NHS services fare better than others but most are based within mental health units of hospitals and base their treatments on the psychosocial model of ME – i.e. fear of symptoms leads to de-conditioning that can be helped with exercise therapy and behaviour modification. This is a general CFS clinic service, based on the NICE Guidelines for M.E which can be found here http://www.nice.org.uk/CG053

Small amounts of exercise can be beneficial but there is a right and a wrong way of doing it.

If you believe that your local NHS service isn’t right for you, do not go there. There are links on this site to supplementation, pacing, activity management and ideas for managing your condition. We also plan on offering pathology and clinical services in the future. Also, sign up for our newsletters which will feature tips from top professionals.

Why do I feel worse when I exercise?

By Professor Art Ayers:

M.E results in increased levels of the receptors for IL-6 and TNF, but not for the corresponding cytokines, IL-6 and TNF, which trigger fatigue and wasting associated with chronic inflammatory diseases. These findings suggest that people with M.E should be very sensitive to activities or conditions that produce inflammatory cytokines

People with CFS/ME do not seem to benefit from exercise, but rather the combination of exercise-induced IL-6, together with enhanced preexisting IL-6 receptors, produces extreme fatigue.

Many doctors discourage M.E sufferers from exercising, because the exercise-based IL-6 never reaches therapeutic levels required for muscle enhancement.

These recent studies explain what people with M.E have experienced -- exercise is bad for M.E. Hopefully, therapy will follow the new insights.

In 1999 Professor Paul Cheney, one of the pioneers of CFS research, went on record as stating: “The most important thing about exercise is ****not to have [patients with CFS] do aerobic exercise*****. I believe that even progressive aerobic exercise is counter-productive.

If you have a defect in mitochondrial function and you push the mitochondria by exercise, you kill the DNA” (Lecture given in Orlando, Florida at the International Congress of Bioenergetic Medicine, 5th-7th February 1999). 

My friend/family/loved one is a severely affected sufferer and I keep being told my M.E Clinic does not cater for the severely affected, what should I do?

First of all, don’t panic. There is support and help out there; you just need to know where to look. The best thing is that you have found this site which has excellent links to some of the world’s top experts in M.E. The first thing we recommend is a supportive GP who can set up a nurse home visit service for you. If your GP isn’t supportive or does not believe in M.E it is unwise to keep asking for referrals and suchlike so we suggest finding a GP who does believe in M.E. If this is not possible then Neuroimmune Alliance would be happy to put some paperwork together to send in to your GP’s. Contact with your local nurse and hospital is paramount to managing your condition.

My child has M.E and I really need some advice, where should I go?

For help and support with educational matters please refer to the Tymes Trust. http://www.tymestrust.org/

 It is important not to let your child over do things as evidence suggests that pushing activity on young sufferers can make things worse.

I want to offer money for M.E Research, who should I donate to?

Invest in ME and its sub project ‘Let’s Do it For M.E’, raising funds for a research and treatment centre at the University of East Anglia. All linked research associations have websites with details on how you can donate to them also.

More details can be found at:

http://blog.ldifme.org/

http://www.investinme.org/IiME%20Awareness%20Events%20LDIFME.htm

How do I deal with fluctuating symptoms?

One of the most difficult things to deal with regarding M.E symptoms is that they fluctuate in severity. One day you may be in bed with a fever, feeling too exhausted to even lift your head off the pillow, the next you feel able to walk about. The never-ending cycle of this constant yo yoing of symptoms is hard to deal with as on your good days you may feel tempted to do more than your body can deal with, which is when Post Exertional Malaise kicks in – your body’s inflammatory response to exertion which is grossly exaggerated in M.E patients.

Listen to your body. If you don’t feel able to do something, don’t do it. If you feel able to manage a small walk or sit in the garden, then go ahead. If you need to sleep, then sleep. The idea that the M.E clinics put forward, that we need to increase our activity levels, does not apply to true M.E patients. Take heed of the words of Paul Cheney above, “If you have a defect in mitochondrial function and you push the mitochondria by exercise, you kill the DNA”.

Eat sensibly. This sounds really basic but you’d be surprised how many severely ill people do not get a balanced diet. Eat lots of fruit and vegetables, complex carbohydrates to give you energy, jacket potatoes, brown rice, pulses like lentils, barley, oats, and peas. If you feel nauseous then ginger tea and tablets are beneficial.

How can I PACE and manage my energy levels?

Some patients feel better at night, others in the morning. When you feel your best, do not push yourself but allow a slot of say, two hours to do something, then rest. Then do something else, then rest. Constant resting is crucial to M.E as pushing the body can damage the cells. A good sleep pattern is essential, I find that getting up in the morning, no matter how tired I am and staying up for three hours, even if those three hours are sitting in an armchair, puts my bodyclock in the correct place. I never push beyond those three hours, if I have to then I give myself a few days to recover from it as the post exertional malaise will set in.

After those three hours, I generally sleep for a few hours then do some light activity in the evening until around nine PM where I will be so exhausted I sleep or my nervous system is so overactive I cannot sleep, then I will take sleeping medication. Sleep is a vital part of M.E but sleep problems are a major symptom and if sleep cannot be managed then professional advice is recommended.

In comparison, in May 2007 the British Polio Fellowship, in association with the Lane Fox Unit at St Thomas’ Hospital London, produced an exemplary 15 page booklet entitled “Pacing for Activity and Exercise:  Lifestyle adjustment tips for everyday life to ease symptoms and maintain independence”.  In 1995, it was shown that the mechanism of extreme fatigue of post-polio was identical to the fatigue of ME/CFS (Annals of the New York Academy of Sciences 1995: vol. 753: 1-409), so the booklet may be helpful for those with ME/CFS.  The advice includes the following:

 

        “It is thought that too much activity can lead to an increase in weakness and fatigue in people with  (post) polio.  There is a theory that over-use can lead to a further decrease in function”

 

        “The practice of resting before you become tired or exhausted is so effective that it should be your number one priority in energy conservation”

 

        “Muscle tightness may sometimes be the body’s way of compensating for muscle weakness”

 

        “Exercise for people with PPS (post-polio syndrome) should be non-fatiguing”

 

        “Never carry out aerobic exercise on two or more days in a row”

 

        “Symptoms that last longer may mean muscle over-work and possible injury”

 

        “Symptoms of over-use that may show a need to stop or decrease the amount of exercise include: muscle cramps and spasms, muscle twitching, muscle pain and extreme fatigue”

 

        “Any exercise that causes additional weakness or unusual muscle twitching should be stopped”

 

        “It is important to respect these symptoms in order to avoid doing permanent harm to your muscles”

 

        “Remember the key to achieving lifestyle balance is to avoid pushing yourself beyond your abilities”.

 What test diagnoses M.E?

M.E can be difficult to diagnose. There are currently no laboratory tests and universally agreed consensus criteria to make an official clinical diagnosis. A multidisciplinary approach is advised. Bryon Hyde recommends the following tests. Please contact us for more information.

TEST #1:  Cardio-Pulmonary Exercise Testing with measurement of VO2 max, anaerobic threshold, and maximal heart rate and respiration.

TEST #2: Brain neuro SPECT & PET scans and MRI brain scan

TEST #3: Mitochondrial Dysfunction

TEST #4:  TH1/TH2 imbalance
TEST #5:  Natural Killer Cell Function (Activity) testing

TEST #6: abnormalities of the 2-5A pathway (RNase-L ratio)

TEST #7: Virology
TEST #8: Heart Function

TEST #9: Neurocognitive testing & sleep studies
TEST #10: Endocrine testing

Commentary

Additional References & Poor man's tilt table testing description 

What are the typical symptoms of M.E?

The Canadian Expert Consensus Panel has published a medical milestone, the first clinical case definition for the disease known as myalgic encephalomyelitis/chronic fatigue syndrome. This  definition is clearly a vast improvement over the CDC's 1994 case definition for CFS, which led to misunderstanding in both research and treatment modalities by making "fatigue" a compulsory symptom but by downplaying or making optional the disease's hallmark of post-exertional sickness and other cardinal ME/CFS symptoms. In sharp contrast to the CDC's 1994 definition, this new clinical case definition makes it compulsory that in order to be diagnosed with ME/CFS, a patient must become symptomatically ill after exercise and must also have neurological, neurocognitive, neuroendocrine, dysautonomic, circulatory, and immune manifestations. In short, symptoms other than fatigue must be present for a patient to meet the criteria. The complete 109-page article "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols," was published in the Journal of Chronic Fatigue Syndrome, Vol. 11 (1) 2003, pp. 7-116.

 

The Canadian Clinical Case Definition is summarized as follows: http://www.cfids-cab.org/MESA/ccpc.html

1.        POST-EXERTIONAL MALAISE AND FATIGUE: There is a loss of physical and mental stamina, rapid muscular and cognitive fatigability, post-exertional fatigue, malaise and/or pain, and a tendency for other symptoms to worsen.  A pathologically slow recovery period (it takes more than 24 hours to recover).  Symptoms exacerbated by stress of any kind.  Patient must have a marked degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level. [Editor’s note: The M.E. Society prefers to use “delayed recovery of muscle function,” weakness, and faintness rather than “fatigue.” Further, we disagree that the muscle dysfunction and post-exertional sickness is “unexplained.”  See our Cardiac Insufficiency Hypothesis page and our Research-Based Subsets page for researchers’ medical explanations on this website.]

2.       SLEEP DISORDER: Unrefreshing sleep or poor sleep quality; rhythm disturbance.

3.       PAIN:  Arthralgia and/or myalgia without clinical evidence of inflammatory responses of joint swelling or redness.  Pain can be experienced in the muscles, joints, or neck and is sometimes migratory in nature.  Often, there are significant headaches of new type, pattern, or severity.  [Editor’s note: neuropathic pain is a common symptom and should be added here as well.]

4.        NEUROLOGICAL/COGNITIVE MANIFESTATIONS:  Two or more of the following difficulties should be present: confusion, impairment of concentration and short-term memory consolidation, difficulty with information processing, categorizing, and word retrieval, intermittent dyslexia, perceptual/sensory disturbances, disorientation, and ataxia.  There may be overload phenomena: informational, cognitive, and sensory overload -- e.g., photophobia and hypersensitivity to noise -- and/or emotional overload which may lead to relapses and/or anxiety.

5.        AT LEAST ONE SYMPTOM OUT OF TWO OF THE FOLLOWING CATEGORIES:

AUTONOMIC MANIFESTATIONS: Orthostatic Intolerance: e.g., neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension, vertigo, light-headedness, extreme pallor, intestinal or bladder disturbances with or without irritable bowel syndrome (IBS) or bladder dysfunction, palpitations with or without cardiac arrhythmia, vasomotor instability, and respiratory irregularities. [Editor’s note: low plasma and/or erythrocyte volume should be added as another explanation for orthostatic intolerance in this disease. More cardiac symptoms should be listed such as left-side chest aches and resting tachycardias, which, in addition to low blood volume, have also been documented in the research. The full text of the case definition does suggest 24-hour Holter monitoring, and when tachycardias with T-wave inversions or flattenings are present that they not be labeled as nonspecific since they aid in the diagnosis of ME/CFS. The frequent tachycardias seen in ME/CFS have been shown by Dr. Paul Cheney to be a compensatory mechanism that serves to increase cardiac output in the presence of low stroke volume due to diastolic dysfunction in the heart. Orthostatic problems may also be related to diastolic dysfunction as recently shown by Dr. Paul Cheney.  See our Cardiac Insufficiency Hypothesis page.]

NEUROENDOCRINE MANIFESTATIONS: loss of thermostatic stability, heat/cold intolerance, anorexia or abnormal appetite, marked weight change, hypoglycemia, loss of adaptability and tolerance for stress, worsening of symptoms with stress and slow recovery, and emotional lability.

IMMUNE MANIFESTATIONS: tender lymph nodes, sore throat, flu-like symptoms, general malaise, development of new allergies or changes in status of old ones, and hypersensitivity to medications and/or chemicals.

The illness persists for at least 6 months.  It usually has an acute onset, but onset also may be gradual.  Preliminary diagnosis may be possible earlier.  The disturbances generally form symptom clusters that are often unique to a particular patient.  The manifestations may fluctuate and change over time.  Symptoms exacerbate with exertion or stress.

Unexplained Symptoms

 “Evidence for the superiority of new ways of thinking about and managing such patients is growing.  These new treatments, often referred to as cognitive behavioural therapies, take a new approach (which) is in keeping with the evidence that the perpetuation of unexplained somatic symptoms is best understood in terms of psychological factors (such as) misinterpretation of bodily sensations and unhelpful coping behaviour.” Treating medically unexplained symptoms.  EDITORIAL (Editor’s Choice).Richard Mayou and Michael Sharpe.  BMJ 1997:3:15:561-562

We want to start by reassuring you that no symptom of M.E is either a product of your imagination nor ‘medically unexplained’. M.E is a complex neuro-immune disease of which there are many layers that affect the immune, endocrine and nervous systems. There are biomedical explanations for M.E symptoms, some of which are explored on this site. I reiterate the point that I am not a doctor but I closely monitor all aspects of M.E research to keep patients up to date with the latest developments in the M.E biomedical world.

It is the tragedy of our age that an illness which requires a multi disciplinary approach to treatment and care is pushed aside and merged with somatoform disorders so that primary care and welfare costs can be kept down; mass cognitive behaviour therapy is cheaper than research, drug trials and treatment.

M.E is not rare; the number of patients in Europe is estimated to be two million. This figure is assumed to be merely the tip of the iceberg, as the illness often goes unrecognized and is therefore not diagnosed. There are - in any case - more patients with ME/CFS than with AIDS, multiple sclerosis, lupus or lung cancer. ME/CFS occurs in all races and age groups and in all levels of society. At least 10% of the ME/CFS population is younger than 15, including children under the age of 4. British research has shown that half of all children with a long-term illness have ME/CFS, thus accounting for the largest school absenteeism of all existing illnesses.

The illness has a very negative impact on the patient and quality of life is alarmingly low. Approximately one quarter of ME/CFS patients are entirely house-, bed- or wheelchair bound. One in ten dies prematurely due to major organ failure, cancer, heart disease or suicide.

Less than 4% of patients are reported to recover spontaneously, and a number of these are believed to have originally been misdiagnosed with ME/CFS. Without effective treatment, any degree of recovery is almost non-existent. This illustrates the need to fund research that will lead to the development of effective treatment protocols.  

http://esme-eu.com/me-facts-and-figures/socio-economic-impact-of-me-cfs-on-patients-and-society-article30-124.html

Symptom 1: Nervous System Disruption and Sensory Overload

Spacial Disorientation is usually associative with pilots and aircraft. To quote Wiki:

“it is an inability to correctly interpret aircraft attitude, altitude or airspeed, in relation to the Earth or point of reference. Spatial disorientation is a condition in which an aircraftpilot's perception of direction (proprioception) does not agree with reality. While it can be brought on by disturbances or disease within the vestibular system, it is more typically a temporary condition resulting from flight into poor weather conditions with low or no visibility. Under these conditions the pilot may be deprived of an external visual horizon, which is critical to maintaining a correct sense of up and down while flying.”

One thing most of us take for granted is our sense of where we are at any given moment. Our ability to stand in a crowd of people and focus, walk around shops, let our eyes absorb colour and our ears multiple contrasting layers of sound is controlled by the peripheral nervous system, which is made up of sensory receptors, sensory neurons and motor neurons. Sensory receptors are activated by a stimulus (change in the internal or external environment). The stimulus is converted to an electronic signal and transmitted to a sensory neuron. Sensory neurons connect sensory receptors to the CNS. The CNS processes the signal, and transmits a message back to an effector organ (an organ that responds to a nerve impulse from the CNS) through a motor neuron.

The Peripheral Nervous System comprises of two parts: the somatic nervous system and the autonomic nervous system. The somatic nervous system, or voluntary nervous system, enables humans to react consciously to environmental changes. It includes 31 pairs of spinal nerves and 12 pairs of cranial nerves. This system controls movements of skeletal (voluntary) muscles.

Research has found that patients with M.E have abnormalities and inflammation in the dorsal root, thus this part of the peripheral nervous system in M.E patients appears to be broken. Many patients have reported experiencing symptoms of ‘spacial disorientation’. Some doctors attribute the symptoms to panic attacks but these very unique symptoms are down to central nervous system failure.

The patient can have a sense that everything around them is heightened – all nerves and responses are on edge – the body is effectively in ‘fight or flight mode’.

A room can often feel like the walls are distorted, or ‘caving in’ around the patient, or a sense of spinning can be felt. Distance can feel exaggerated, like everything appears stretched and a road will be forever on the horizon. Each noise is heard abruptly and reverberates, like an echo, the brain unable to process multiple sounds and will make the patient feel confused and muggy headed. The same goes for excessive visual stimuli, too much movement or bright light can render a patient feeling overwhelmed and confused. One might forget where they are and become completely detached from their surroundings even though it may be a familiar place. The person may freeze on the spot, their heart rate increasing and become increasingly confused as to where they are. They also may forget that they need to move – some patients have reported experiencing this in the middle of a busy road and have endangered themselves by trying to cross alone. This can often be seen in Alzheimer’s patients.

Postural Orthostatic Tachycardia Syndrome/Dysautonomia

Postural orthostatic tachycardia syndrome (POTS) is one of a group of disorders which has orthostatic intolerance (OI) as their primary symptom. OI describes a condition in which an excessively reduced volume of blood returns to the heart after an individual stands up from a lying down position. The primary symptom of OI is lightheadedness or fainting. In POTS, the lightheadedness or fainting is also accompanied by a rapid increase in heartbeat of more than 30 beats per minute, or a heart rate that exceeds 120 beats per minute, within 10 minutes of rising. The faintness or lightheadedness of POTS are relieved by lying down again. Anyone at any age can develop POTS, but the majority of individuals affected (between 75 and 80 percent) are women between the ages of 15 to 50 years of age. Some women report an increase in episodes of POTS right before their menstrual periods. POTS often begins after a pregnancy, major surgery, trauma, or a viral illness. It may make individuals unable to exercise because the activity brings on fainting spells or dizziness.

Doctors aren't sure yet what causes the reduced return of blood to the heart that occurs in OI, or why the heart begins to beat so rapidly in POTS.  Current thinking is that there are a number of mechanisms.  Some patients have peripheral denervation (neuropathic POTS); some have symptoms that are due to sustained or parosyxmal overactivity of the sympathetic nervous system (hyperadrenergic POTS); and some individuals have PTOS dominated by features of deconditioning. 

OI is the development of a set of characteristic symptoms while standing or sitting upright. It has been associated with CFS in both adults and children.

The 1986 definition of myalgic encephalomyelitis (M.E.) by Melvin A. Ramsey, M.D., includes “orthostatic tachycardia” as one of the accompanying features. The first research study connecting OI and CFS was published in the Lancet in 1995, by Peter Rowe, MD, and associates at Johns Hopkins University, who identified a type of OI called neurally mediated hypotension (NMH) in CFS patients. Since 1995, scientists have learned much more about the broader problem of OI in CFS. It is now thought that many CFS patients (up to 97 percent in some studies) have some form of OI and it seems to be a particular problem in young people with CFS

NMH is a precipitous drop (at least 20-25 mm Hg) in systolic blood pressure when standing. The blood pressure drop is accompanied or preceded by an increase in symptoms.

POTS is a rapid increase in heart rate (pulse) of more than 30 beats per minute (bpm) from baseline, or to more than 120 bpm total, during the first 10 minutes of standing. It is also known as chronic orthostatic intolerance, or COI.

Taking supplemental tyrosine at a dosage of up to 1,500 mg per day is another thing to consider to counteract blood pooling, because tyrosine is the substrate for making norepinephrine, the
neurotransmitter used by the sympathetic nervous system to contract the muscles around the veins in the lower body.

There is evidence of low tyrosine in some PWCs and of a deficit in norepinephrine production in some with othostatic intolerance.

Fludrocortisone has been prescribed by some clinicians as a treatment for orthostatic intolerance in PWCs, but its efficacy is not clear.
Midodrine has also received some testing, and has been helpful for some with orthostatic hypotension.
It is an alpha-1 adrenoceptor agonist, and thus acts in place of norepinephrine to constrict blood vessels. Clinicians should be alert, however, to possible excessive elevation of supine blood pressure by this agent.

LINKS http://www.dinet.org/

http://www.stars.org.uk/

Endocrine Abnormalities

Bashetti has published a number of studies on cortisol and CFS. He writes in the Journal of Endocrinology and Metabolism, “Hydrocortisone, the glucocorticoid that is routinely prescribed to correct the chronic cortisol deficiency of patients with Addison’s disease, has recently been confirmed to be significantly effective also in the treatment of chronic fatigue syndrome (CFS). This comes as no surprise if we consider that CFS and Addison’s disease share 26 features.” . Riccardo Baschetti, M.D. Investigations of Hydrocortisone and Fludrocortisone in the Treatment of Chronic Fatigue Syndrome The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 6 2263-2264

Hypothalamus / Pituitary / Pineal Dysfunction: Overview


The Endocrine system is an intricate "feedback" system, in which hormones release or suppress other hormones, controlling the way the body works. Balance is crucial, because an unhealthy component (gland) could cause repercussions to cascade down into all parts of the body.  

For example, an unhealthy pituitary can produce too much growth hormone (leading possibly to giantism) or too little, which can lead to premature aging and wasting of tissue.

The hypothalamus gland produces a releasing factor known as thyroid stimulation hormone releasing factor, or TSH-RF. It is a secretion of the brain that controls the pituitary gland. It regulates survival processes, such as reproduction, nourishment, and self-defense, by initiating the appropriate physical response through nerve impulses and chemical messengers.

The pituitary, which is controlled by the hypothalamus, has two distinct parts, the anterior and posterior lobes. Each one releases different hormones. The hypothalamus is and essential link between the brain and the pituitary. For example, the hypothalamus releases hormones stored in the posterior pituitary, including: oxytocin, vital in childbirth and nursing, and vasopressin, the water-regulating hormone; it also releases "turn on" hormones form the anterior pituitary, which stimulates secretions by other endocrine glands.

The pineal gland works in harmony with the hypothalamus gland, directing the body's thirst, hunger, sexual desire and the biological clock that determines our aging process. It is the "third eye" of the brain, responsible for telling the brain when it is day or night. It also controls the body's hormonal systems, sleep-wake cycle, and other so-called "circadian" (24-hour) body rhythms. It is in essence, the body's internal clock.

The pineal gland produces a hormone called melatonin, levels of which are what directly influence the function of various brain centers (appetite, sleep, the hypothalamus and pituitary gland).

Various functions and rhythms of the human body are controlled by hormones which might be defined as chemical messengers. Most of these hormones are produced by these and the other major endocrine glands, but several other organs also manufacture hormones - the stomach, liver, intestines, kidneys, and heart all contain groups of hormone-secreting cells.

In patients with M.E the HPA Axis is faulty, whether this cause is genetic or viral, research has yet to discover.

The broken HPA axis causes the body to produce hormones at a lower than normal level, sleep dysfunction, temperature regulation and thyroid function.

There is clear evidence that adrenal axis dysfunction is present in patients with chronic fatigue syndrome (CFS) and fibromyalgia (FM) 1-21,23-28 and that treatment with low physiologic doses of cortisol have been shown to be safe, appropriate and effective.8,9,10,23,30 It should be considered the standard of care to treat patients with CFS and FM who have baseline cortisol levels under 12 ug/ml.8,9,10,31,32,33

Evidence for significant HPA axis dysfunction with resultant adrenocortical dysfunction:

A study published in the Annals New York Academy of Sciences entitled Evidence for and Pathophysiologic Implications of Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Fibromyalgia and Chronic Fatigue Syndrome discussed the evidence for HPA axis insufficiency in CFS and FM. They conclude, “Our group has established the impaired activation of the hypothalamic-pituitary-adrenal axis is an essential neuroendocrine feature of this condition.”

Demitrack MA, Crofford LJ. Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann N Y Acad Sci 1998 May 1;840:684-69

IGF1 Deficiency

Consider and treat as necessary any Thryoid problems, low to borderline adrenal function and sex hormone deficiencies. DHEA and 7-KETO DHEA may be useful; routine endocrine tests can come back normal but current research is focusing on growth hormone irregularities. Insulin growth hormone (IGF1) is secreted mainly in the liver in response to growth hormone release. Growth hormone deficiency in adults has been associated with low energy, poor general health, reduced exercise capacity, muscle weakness, cold intolerance, impaired cognitive, dysthymia and decreased lean body mass. A few studies done so far have found symptomatic improvement of ME symptoms with growth hormone injections. [Eduardo S. Pavia, Atul Deodhar, Kim D Jones, Robert Bennett; Oregon Health Sciences University, Portland.

Gut Infections and M.E – below is a helpful article detailing how the gut is affected in M.E patients and supplements that can help.

ME/CFS & Chronic Infections – Notes on Dr. Kenny De Meirleir’s Presentation in Perth

ProHealth.com
by Blake Graham, BSc, AACNEM*
November 11, 2007

In a recent presentation at the University of Western Australia, Dr. Kenny De Meirleir, MD, PhD, explored evidence suggesting that the gut of 80% to 90% of ME/CFS patients may be compromised by bacterial and/or viral pathogen infections, discussed how these may contribute to immune activation, and outlined a range of therapies that may support significant improvements in various ME/CFS symptoms. Dr. De Meirleir is Professor of Physiology, Pathophysiology, Internal Medicine and Sports Medicine at Vrije Universiteit, Brussels, and Clinical Professor, University of Nevada Medical School, USA.

Following is a summary of Dr. De Meirleir’s presentation by Clinical Nutritionist Blake Graham, director of the Nutritional Healing clinic in Perth. It is reproduced with permission from Blake’s November 8 posting on the Co-Cure Listserv.

* * * * *

Dr. Kenny De Meirleir's Lecture on ME/CFS - November 3, 2007

Dr. Kenny De Meirleir, MD, PhD, spoke in Perth, Western Australia on November 3, 2007 at a seminar sponsored by the ME/CFS Society (WA). Kenny has seen over 12,000 CFS patients and first became interested in CFS in 1989. His research team has performed over 4,000 in vitro experiments and published many peer reviewed articles on CFS. I attended both his talks to the general public and to health professionals, plus got the opportunity to ask a large number of questions after the professionals talk. The following is based on written notes and from memory, not directly quoting Kenny.

Gastrointestinal Problems

More than 80% to 90% of patients have gastrointestinal symptoms. Gastrointestinal abnormalities range from one end of the gastrointestinal tract to the other.

Saliva pH is low (below 7 - acidic) which leads to both dental problems and disturbed oral flora.

Patients display delayed gastric emptying. Biopsies of gastric mucosa on patients show all patients have atrophic gastritis [chronic inflammation of the stomach mucosa, or lining]. When biopsy of the cecum is performed infiltration of lymphocytes is also found in all patients. [Lymphocytes are white blood cells with specialized immune functions. The cecum is a pouch where the small intestine transitions to the large intestine. Branching off from it is the small worm-like appendix.]

In Kenny's last 100 patients, a point [at] 2 cm right then 2 cm down from the umbilicus is tender after mild pressure. This is the point just above the cecum. Tenderness is a sign of imbalanced intestinal bacteria.

Intestinal Mucosal Health

Patients have a compromised gastrointestinal mucosal integrity which contributes to immune activation and is a major factor in CFS. The cause of intestinal barrier damage is multifactorial and complex. One factor is likely viruses (Epstein-Barr Virus and HHV-6). EBV attacks the immune system of the gut. Kenny has observed that a significant proportion of patients with CFS have relatives with Crohn's Disease. A genetic predisposition to gastrointestinal problems likely exists.

Intestinal Flora

Kenny routinely does a blood test for immunoglobulin A (IgA) and immunoglobulin M (IgM) [antibodies] for a range of intestinal bacteria - called the Immunobilan test.

He generally starts treatment with antibiotics to lower levels of problematic bacteria, then adds in probiotics. Kenny did a small study using the antibiotic ciprofloxacin and high quality probiotics. Patients reported a 58% improvement and elastase dropped 74%.

Kenny most commonly uses a high potency multi-strain probiotic called VSL#3 (http://www.vsl3.com), which contains 450 billion bacteria per serve. Normal probiotics contain 25 billion or less. It mimics the bacteria normally present in the bowel. He also uses MutaflorR, which is a supplement of healthy intestinal Escherichia coli (E. coli) bacteria. At present this product is only available directly from Germany where it is it produced (http://www.metpharmacy.de).

Fructose Malabsorption and Lactose Intolerance

In a study of 143 patients, fructose malabsorption was found in 45.8% of patients. Lactose intolerance was found in 20.3%. Both can be measured via a simple hydrogen breath test:

25 grams of fructose or lactose is administered to a fasting patient.

Breath hydrogen levels are measured before administration and at 30 minute intervals for 3.5 hours.

Sugar malabsorption contributes to intestinal dysbiosis (bacterial imbalance), among other issues. Fructose malabsorption is treated with a fructose poor diet, while lactose intolerance is treated with a lactose free diet. A high baseline hydrogen breath measurement indicates intestinal bacterial overgrowth.

Clinicians can buy the equipment to do the fructose and lactose breath testing in their offices. Kenny believes these intolerances were present before the illness onset, acting as a predisposing factor and may also get worse after illness onset. He observes these issues are often present in family members. Common associations with fructose malabsorption are:

Fatty liver. Most patients with fatty liver have fructose malabsorption.

Steatorrhea (fat in the stool/fat malabsorption).

Constipation. Whereas those with lactose intolerance are more likely to have diarrhea.

Hypoglycemia. Most patients with significant hypoglycemia have fructose malabsorption. [Hypoglycemia occurs when blood sugar drops too low to provide enough energy for the body’s activities.]

Sensitivity to tyramine. [A compound that is produced as the amino acid tyrosine breaks down and is found in many foods, especially aged cheese, all nuts, and dried, fermented, salted, smoked or pickled foods.]

Bloating.

Gluten Intolerance

Gluten intolerance is also found in a subset of patients. He uses immunoglobulin G (IgG) blood testing for testing gluten sensitivity. Sensitivity to gluten is a spectrum with celiac disease at one end and normal tolerance at the other, rather than tolerance being an all or nothing issue. A range of different levels of sensitivity exist.

Diet

Kenny's patients consult with his dietitian. A diet is created based on tolerance to fructose, lactose and gluten. He recommends patients drink 3 to 4 liters of water a day. [Slightly more than 3 to 4 quarts.]

Heavy Metals

Kenny uses the MelisaR metal reactivity test (http://www.melisa.org) to assess sensitivity to heavy metals. He also uses provoked urine testing using IV DMPS and EDTA [chelating drugs that bind to certain metals and “pull them out of the body” via the urine]. The two heavy metals most significant are mercury and nickel. Nickel is found in soil and enters our food supply.

Amalgam fillings are one source of mercury and Kenny suggests careful removal when patients are sensitive to mercury. Kenny presented in vitro evidence supporting greatly increased sensitivity to the toxic effects of mercury in CFS patients.

He has found palladium in some patients, and based on this elevation is able to predict where in Belgium patients live with a high degree of accuracy. Increased levels of heavy metals are likely due to increased intestinal uptake and genetic abnormalities in certain detoxification proteins, including multidrug-resistance protein 1 (MRP1).

The two options for treatment include pharmaceutical chelators (DMPS or DMSA) or combination products of herbs/nutrients (dose = 2x1/day) designed for detoxification. The names of the Belgium herbal/nutritional formulas are:

TMD (Toxic Metal Detox – http://www.labosp.com/lib/compendium_an/INT_165.pdf).

HMP (Heavy Metal Protect – http://www.labosp.com/lib/compendium_an/BE_165.pdf).

These products contain [as discussed in the pdfs]:

  GSH (reduced glutathione)

  Lipoic acid (tiotic)

  SOD

  Selenomethionine

  Vitamin E (DL-alpha-tocopherol)

  Pycnogenol (OPC extract of grape seed)

  Vitamin B2 (Riboflavin)

  Mycelium shitake (atomized)

  Willow extract

Glutathione

Glutathione is low in patients. It can be treated via taking LipoceuticalTM Glutathione made by ReadisorbTM (http://www.readisorb.com). Normal oral glutathione is ineffective as it is broken down in the gut, and transdermal glutathione has variable metabolism. The benefit of IV glutathione is relatively short lived.

N-acetyl-cysteine (NAC) can also boost glutathione, but large doses are needed (1.8 grams).

Nutritional Supplements

The basic nutritional supplements Kenny recommends commonly to patients are:

Lipoceutical Glutathione

Vitamin C

Lipoic acid

Coenzyme Q10

Alkalizing agents (e.g., potassium bicarbonate).

Acetyl-L-carnitine.

Nexavir and Vitamin B12

Nexavir (KutapressinR) is used effectively in combination with subcutaneous vitamin B12. In one study of a general group of CFS patients, 63% of patients in the treatment group responded while only 17% of the placebo group responded.

In Kenny's experience around half of patients are pain free in 2 to 3 months and sleep often normalizes within a period of 3 days. Nexavir is a liver extract from pigs. It cuts immune activation and lowers elastase. 10 mg of vitamin B12 are used twice weekly in the form of methyl or hydroxy B12. (Most B12 shots contain 1 mg.) B12 scavenges nitric oxide (NO), often clearing up brain fog and helping with cold extremities. Nexavir can be ordered from countries other than the U.S. via a Texas pharmacy called Nexco Pharma (http://www.nexcopharma.com).

Isoprinosine and Inosine

When asked about the immune modulating medication Isoprinosine (which boosts natural killer cells), he mentioned that the basic amino acid version of inosine is as effective.

HHV-6

The role of HHV-6 is being actively debated. A subgroup of patients have a mild HHV-6 related encephalitis. HHV-6 can be treated with antivirals (e.g., ValcyteTM) and immune modulators. HHV-6 is associated with neurological symptoms with extreme fatigue and no pain. Patients with active HHV-6 are usually in the 15 to 35 age group. He doesn't think herpes viruses are the cause of CFS but rather become reactivated.

Mycoplasma

Mycoplasma (a genus of bacteria lacking cell walls) is active in the presence of low NK and T cell function. Mycoplasma releases antigens which further disrupt immune function. Antibiotics (e.g., doxycycline) for mycoplasma-positive patients have shown success, although it is unclear if this is due to antibiotics treating mycoplasma, Rickettsia (intracellular parasites contracted via bites of ticks or other arthropods) or intestinal bacteria.

Chlamydia Pneumoniae

Chlamydia pneumoniae is present in a subgroup of patients. It stimulates heat shock proteins leading to immune activation. It can be treated with azithromycin.

Rickettsia, Bartonella and Coxiella

8% to 10% of Kenny's patients have an active Rickettsia, Bartonella or Coxiella infection. Only 17% remember having a tick bite. These infections can come from ticks, dogs and cats. Ticks can carry many viruses and other infections. Australian research has found Rickettsia in a significant amount of Australian patients.

Candida

Candida (yeast) infection is found in some patients and is tested for via IgG. This is treated via diet and antifungals. Yeast is typically resistant to nystatin, so other antifungals are used. A recent study found 20% of patients have elevated bowel Candida levels.

Mycotoxins

Some patients are affected by mycotoxins - toxins produced by environmental mold. Kenny suspects mycotoxins when two people in the same house have CFS, or when symptoms significantly reduce when leaving your home for a period of days. It is more likely to be an issue in poorly ventilated houses and is known to act as an immune suppressor. Aspergillus Niger has been cultured in some homes of CFS patients. Mycotoxic patients have very low glutathione levels and glutathione helps the removal of mycotoxins from cells.

Thyroid Function

Thyroid dysfunction is present despite normal blood tests. There is both poor conversion of T4 to T3 and peripheral resistance to T3.

Peripheral resistance is present in all dys-immune diseases. An immune activation protein has a 98% homology with the T3 receptor, binding to it and competing with T3.

Kenny recommends treating with pure T3. He recommends starting low and titrating up. Patients appear to have destruction of T3 receptors over time - and after a long duration of CFS (e.g., 20 to 25 years) often do not lose weight on extremely low calorie diets (e.g., 800 calories) due to thyroid insensitivity.

Sleep

When asked about treating insomnia, Kenny said to take away the source of the problem. He stated that with NexavirR his patients often sleep normally after 3 days. If sleep cycle shift is present he treats with melatonin (6 mg) or an old anti-epileptic. (I did not catch the name.) He does sleep studies for sleep apnea and restless leg syndrome when indicated.

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* Blake Graham, BSc, AACNEM, is a clinical nutritionist specializing in nutritional and environmental treatments for patients with ME/CFS, FM, and other chronic conditions. He is an Associate of the Australasian College of Nutritional and Environmental Medicine, directs the Nutritional Healing clinic in Perth (WA) http://www.nutritional-healing.com.au, and publishes a free Nutritional Healing e-Newsletter.

Note: This information has not been evaluated by the FDA. It is generic and is not meant to prevent, diagnose, mitigate, or cure any illness, condition, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.