Perpetuating Factors

More times than we can count, when a question comes up about why our diseases seems to be progressive, someone will answer that as long as the "perpetuating factors" are not controlled, their cascading effects will cause further worsening of our symptoms.

It seems that this phrase may be too technical because seldom does anyone question that answer. Since it's so darned important, I thought I'd try to compile some research on the FMS/CFIDS perpetuating factors.

Dr. Devin Starlanyl in "Fibromyalgia and Chronic Myofascial Pain Syndrome" identified perpetuating factors as:

Posture/Structural	Nutritional
body asymmetry, poor posture	allergies, infections, air pollution
computer, typewriter use, furniture, prolonged sitting	electrolyte imbalance, nutritional inadequacies, anemia, vitamin inadequacies, low amino acids
Morton's Neuroma, Morton's foot	chronic sleep deprivation, non-restorative sleep
FMS for MPS, MPS for FMS	Crohn's Disease, IBS
mechanical factors	constipation, hemorrhoids
fallen arches, foot deformations, intrinsic foot TrPs, FMS, MPS foot, ill-fitting shoes	depression, anxiety, smoking, obesity, reactive hypoglycemia
repetitive motion, muscle abuse	systemic viral, bacterial, yeast, or protozoal illness
immobility	low hormones

Depression	Hormones	Allergies	Yeast	Chemicals, odors, fumes
Inactivity	Osteoporosis	Anemias	Hypothyroid	Stressors

Dr. Jacob Teitelbaum, "In Search of the Missing Link: Hypothalamic Dysfunction as a Central and Treatable Cause of CFIDS/FMS," considers these to be perpetuating factors and explains them very well:

Immune dysfunction with multiple opportunistic infections. Decreased metabolic activity, specifically in the hypothalamus, limbic system, and thalamus. This (as well as low estrogen) could account for the decreases in brain blood flow seen in the fascinating research done by Jay Goldstein, M.D.

Autonomic and temperature regulation dysfunction. When given the choice, sleep deprived test animals will often choose a higher room temperature. (Isn't it wonderful what science can test for?). Higher nighttime room temperatures may further worsen sleep quality.

Marked hyperphosphatemia --Dr. St. Amand postulates that a defect of phosphate metabolism is important in FMS and has found that guaifenesin (and other uric acid excreting agents) can improve symptoms. It is possible the sleep disorder triggers the phosphate defect. (Although I have been told that a recent controlled study by Dr. Bennett did not find guaifenesin to be beneficial, Dr. St. Amand feels that the study had critical design flaws. Personally, I have heard beneficial reports from enough patients who failed other "placebos/treatments" to encourage me to study guaifenesin further despite this one negative study).

Allodynia (when normally comfortable touch causes discomfort). It is postulated that in FMS this is caused by elevated substance P secondary to low brain serotonin levels. If sleep deprivation causes allodynia, might it also cause increased substance P and decreased serotonin? Evidence suggests that low acetylcholine function can contribute to CFIDS/FMS and a recent study also found that treating this with an acetylcholinesterase inhibitor resulted in significant improvement in CFIDS symptoms (Galanthamine Hydrobromide 10 mg three times a day for two months).

The hypothalamus is the master gland controlling most other glands in the body. Autoimmune injury can also damage the glands. Effects of the hormonal dysfunctions include:

Low thyroid -- This can cause decreased metabolism with weight gain and low body temperature (which can cause poor enzyme and metabolic function).

Low vasopressin (anti-diuretic hormone) -- This causes decreased ability to hold onto fluid resulting in frequent urination and increased thirst. Dehydration then occurs despite increased water intake. As vasopressin is also a stimulus for ACTH and adrenal function, low vasopressin could also result in decreased adrenal function. Both dehydration and low cortisol can both increase the susceptibility to NMH (Neurally Mediated Hypotension).

Decreased Cortisol -- This causes immune dysfunction and hypotension and the tendency to "crash" in stressful situations.

Low ovarian and testicular functions -- Low estrogen can contribute to the decreased blood flow to specific areas in the brain that is seen in CFIDS/FMS. Low testosterone (in both males and females) can cause immune dysfunction. Although total testosterone levels are usually normal, I have found that the active (free or unbound serum) testosterone levels are usually low in the majority of men or women with CFIDS/FMS. In men, bringing free testosterone levels back to mid-to-high-normal (with testosterone injections) often dramatically improved symptoms after two months. (Caution: This, and the testosterone deficiency itself, may lower sperm counts).

Elevated Prolactin -- The hypothalamus normally suppresses prolactin production. It is not clear what role (if any) elevated prolactin plays in CFIDS. Excessive melatonin intake can also cause elevated prolactin levels.

Oxytocin is a hypothalamic neurotransmitter. Jorge Fleches, M.D. notes that many FMS/CFIDS patients improve with Oxytocin therapy. At this point, though it is not clear what causes the decreased levels of multiple neurotransmitters.

Although the causes of the immune dysfunction are not clear, hypothalamic dysfunction may play a role (as noted above). The implications are that CFIDS patients also seem to have opportunistic infections (i.e., with organisms that usually do not cause illness in most people) and recurrent other infections. These infections can cause CFIDS/FMS to persist. They include:

Bowel infections -- A major player in CFIDS/FMS parasitic, fungal, and bacterial overgrowths (including Clostridia Difficile) are common and often account for the "irritable bowel syndrome". They can cause CFIDS/FMS and can cause the nutritional deficiencies (malabsorption) and the "leaky gut" with secondary food sensitivities and liver overload (the liver may have to detoxify many large molecules that should not have been absorbed intact or would normally have been broken down before absorption). Liver overload, combined with immune overactivation (part of the immune dysfunction e.g. elevated interleukin levels) and decreased adrenal function, can contribute to the food, chemical/environmental, and medication sensitivity. This can occur when the liver is overwhelmed and more slowly metabolizes or detoxifies these substances.

Rickettsia, mycoplasma, and other unusual organisms Several organisms which are difficult to test for may both trigger and perpetuate CFIDS/FMS (e.g. post polio syndrome, and post Lyme fatigue). Doxycycline (a tetracycline antibiotic) given long term four to six weeks at a time may eradicate these, but may cause yeast overgrowth.

Viral infections -- Some viruses can cause hypothalamic suppression. Although in most people this resolves when the virus goes away, in CFIDS/FMS it may not. Because many patients get well without antiviral treatments, I suspect the virus is long gone by several months after the illness begins, or is eliminated when the immune suppression is treated and resolves.

The autonomic (sympathetic/parasympathetic) nervous system is also controlled by the hypothalamus. Its malfunction can cause:

Nasal congestion with secondary fatigue and increased risk of chronic sinusitis.

Low body temperatures cause the body's energy and enzyme systems to work inefficiently (enzyme function is very temperature-sensitive). Dr. Denis Wilson has found that if the body temperature is raised back to 98.6° (using sustained release T3 thyroid hormone -- not Synthroid) people often feel much better. He feels that stress or starvation (e.g., dieting) can trigger low T3 (a form of low thyroid with normal blood tests) and a self-sustaining low body temperature. Altered temperature regulation may also further contribute to impaired sleep.