Good Article - In the beginning of

[briarrose]

Cut and paste from http://home.tampabay.rr.com/lymecfs/hypovolemia.htm

A large piece of the puzzle has been discovered about the elusive and complex illness called CFIDS/FMS. It evolved in a strange but fortuitous way.

David Bell, M.D., the renowned CFIDS expert, had a young child in his practice who was severely ill and getting worse. He found he was missing an important hormone in his body. Desperate to help the child, Dr. Bell contacted Dr. Peter Rowe, the John Hopkins expert who discovered NMH (neurally mediated hypotension) in a sub-set of PWCs (persons with CFIDS). Dr. Rowe hadn't progressed into the area needed by Dr. Bell and suggested that he contact Dr. Ronald Schoendorf of Montreal, a physician who also has been working on NMH, but uses Mitodrine and pressure pants to help this condition instead of Florinef. Dr. Schoendorf suggested that Dr. Bell contact Dr. H.P. Streeten. Dr. Bell had never heard of him nor had Dr. Streeten heard of Dr. Bell. Dr. Bell wrote to Dr. Streeten and a small miracle began to unfold.

David H. P Streeten, M.B., B.CH., D.Phi., FR.C.P, F.A.A.P, is a soft-spoken, brilliant Englishman who was a Professor of Medicine and Chief of the Endocrine Section of New York Health Science Center in Syracuse. He had retired a few years ago after publishing many medical articles as well as a book on his specialty for medical professionals. He knew nothing about the illness that Dr. Bell contacted him about except that it was called "The Yuppie FIu," yet he had been treating patients with the exact same symptoms before his retirement, and he had cured some of them The patients were referred to him with a diverse array of complaints. Dr. Streeten discovered what was going wrong in their bodies (the mechanism) and set about trying to reverse it. He called these problems "orthostatic disorders of the circulation" and even had published a book by the same title (1987, Plenum Publishing Corporation, NY) which told of the mechanism, manifestations, and treatments he had used. The text is now out of print, but can be ordered from the publisher. Without knowing it, Dr. Streeten had published a book about the mechanism of CFIDS!

To put it very simply, Dr. Streeten found that there were two groups of patients (actually PWCs). The first group had an abnormally low volume of red blood cells circulating in the body. They seemed to be milder cases. The second group had this same problem along with an abnormally low plasma volume. (see illustration)

When Dr. Streeten corrected the problem, the patient returned to good health. He assumed that this dysregulation was due to a brain injury. What caused this brain injury was not in his field, but he also assumed that the patients had a genetic predisposition about which Dr. Robert Suhadolnik has recently published. (See Medical Journal Summaries in this issue.)

In other words, having too little blood circulating in the body is like someone having a stroke. In many ways, PWCs have been feeling the same effects as if they were living in shock. Dr. Bell convinced Dr. Streeten that "CFS" was, indeed, a very serious illness that appeared to be what the retired doctor had been having success with before his retirement. When told of the multitudes who suffered from this illness world-wide, Dr. Streeten agreed to come out of retirement to test some of Dr. Bell's patients to see if, indeed, the same mechanism was responsible. Seventeen severely ill patients began a clinical trial. The trial failed to help the patients but future trials may prove this to be a nearly total therapy for less acute PWCs. Every PWC in the trial had an abnormal test result! Will this be the answer for all PWCs? It doesn't appear to be right now, but it definitely helps a small percentage who fall into the first category and may, in the future, be a help to every PWC. There's still much more research to be done in this area, but discovering this mechanism is a huge leap for CFIDS research. Seventeen is not a large number, but Dr. Bell has had more patients tested for this abnormality since then and found all of them to be positive. Encouraged, he then asked Dr. Charles Lapp and Dr. Nancy Klimas to test some of their patients to find if the low volume was a part of every PWC's problem. The results are not available yet, but a paper has been submitted for publication. Dr. Streeten first submitted a paper to the New England Journal of Medicine, but it was returned to him with a cryptic note saying they did not publish in this area. The NEJM has never published on CFIDS! It is one of the most highly respected medical journals in the world. The refusal speaks volumes of their own belief in CFIDS! Dr. Streeten then submitted the paper to The Journal of the American Medical Association (JAMA), another highly regarded journal where he is a reviewer for the staff. In fact, he had reviewed the Johns Hopkins paper and vigorously supported its publication, saying it was "brilliant"! They, too, turned it down! Dr. Streeten was astonished He had never been rejected for publication and has had dozens of papers published during his esteemed career. But he had never tried to publish a paper on CFIDS before. The bias against this illness had hit him!

Wanting to publish quickly so that other researchers could use this knowledge to build upon it, Dr. Streeten turned to the small but growing Journal of Chronic Fatigue Syndrome (JCFS). The article will be published in the January issue. [Editor's Note: Call 1800-3-HAWORTH to subscribe.] The 90s are OUR decade and big things are happening with this illness that most still refuse to take seriously. In spite of the government calling cognitive behavioral therapy the only way to treat CFIDS, dedicated researchers have not given up and continue to unravel the mysteries of this illness.

Will this same mechanism be found in Gulf War Illness or Multiple Chemical Sensitivity? Only time will tell. However, at least one participant of the trial, and a non-responder thus far, found that her hypersensitivities were gone after just weeks on one of the medications. This patient was able to tolerate foods that she was unable to eat for over 7 years and smells of chemicals did not bother her. Although her success did not last, we now know that these problems can be reversed She also experienced huge cognitive improvement during this time. We're very hopeful that this information will lead to better treatment and, perhaps, even a cure for many! We'll keep you updated on the progress.

TESTING FOR A CIRCULATORY PROBLEM

Just recently, medical students have been advised to take blood pressure readings and heart rate tests while the patient is in an upright position. Orthostatic hypotension was described as early as 1925, but Dr. David Streeten published the first book for medical professionals that was devoted to problems that the body had trying to adjust to different postures.

While it is known that changes in the body's posture from lying down to sitting and standing involve neurological, endocrine, and cardiovascular adjustments to maintain normal circulation in the body, there are several orthostatic disorders that have gotten little attention because they are not felt to be life threatening. Using grants from the U.S. Public Health Service, Dr. Streeten described many of these resulting problems in previous publications. He had no idea, however, that while he was writing his book, an entity inappropriately named Chronic Epstein-Barr Virus by The National Institutes of Health was actually the same mechanism he had been studying. To detect the low volume, Dr. Streeten ran several tests. Only the final blood volume test, done correctly and using the right radioactive isotope, will be needed to prove this in all PWCs. A clinical trial, however, needs more data for proof.

First the patient was in a reclining position with an automatic blood pressure mechanism attached to their arm. Every two minutes, the pressure would automatically print out results. The patient was then asked to sit and stand. As in the tilt-table test, this Emeritus Professor of Medicine was looking for a plunge in blood pressure, but was also taking careful notes on all reactions by the patient. Why not use a tilt table test for this? "People don't tilt!" exclaimed Dr. Streeten, "They sit, they lie down, they stand, but they don't tilt." Further testing is done with a MAST suit which is also called "shock pants This is like a giant blood pressure cuff that envelopes the lower body and looks like a huge pair of rubber pants. The blood in the body, instead of going to the heart when a person stands, pools in the extremities, especially the legs. When this "suit" is inflated, most patients feel enormous relief from the pain they were experiencing when they had to stand in one place without shifting their feet or weight. A physical examination follows this test.

The final phase of testing in this clinical trial involved a blood volume test. Three total volumes are sought: red blood cell (RBC) volume, plasma volume, and total volume. This is the only test necessary for most PWCs to prove that low circulating volume is the problem. A radioactive dye using Chromium 1 is injected. It is about the same amount of radiation one would get if having a lung x-ray. The blood is then drawn at intervals to read the volumes. (See diagram on p. 6) [Not provided here.]

Treatment for the volume reduction depends on the outcome of the tests. Some patients have found Florinef effective while others have found Mitodrine works best for them. Both enhance volume . Florinef is a corticosteroid while Mitodrine is an alpha adrenergic agonist that was approved by the FDA (Federal Food and Drug Administration) in 1996, although it was used in other countries for many years.

Unfortunately, a mechanism for totally reversing this abnormality has not yet been found, although one is being tried now in a clinical trial. More information will be included in the January issue of The Journal of Chronic Fatigue Syndrome. There is still another piece of the puzzle that still is elusive. However, low circulating blood volume disorders can account for the many diverse symptoms seen in CFIDS/ FMS including menstrual problems, intracranial symptoms, cardiovascular problems, fluid accumulation, fatigue, musculoskeletal pain, severe thirst, glucose intolerance, tachycardia, etc. At least two symptoms were new to Dr. Streeten: hyperreflexia and thermal control. It is possible that the patients he treated earlier were not as severe because they were not sick as long.

PWCs with severe hypertension cannot be treated by the methods now being tested, although borderline hypertension could be "predominantly or exclusively orthostatic," according to Dr. Streeten. Nearly all the symptoms of CFIDS can be attributed to reduced cerebral blood flow caused by the lowered volume and the inadequate autoregulation in the brain. Dull chest pain, mitral valve prolapse, even impotence and incontinence can be attributed to this disorder. Other common symptoms are syncope (faintness), dull chest pain, flushing, excessive sweating, nausea, and impaired cognition are explainable. Indeed, even the exercise debate that is raging throughout the CFIDS community can be answered by this enormous step forward: walking will help mild patients, but NOT severe patients. In 1941, Stead and Ebert wrote that strenuous activity aggravates the symptoms to a great degree! In 1925, Bradbury and Eggleston noted that seizures can occur with orthostasis, although they are NOT grand mal! There are even orthostatic disorders that explain the weight gain seen in CFIDS. Although this mechanism needs much more study, merely discovering it brings us closer to a day when treatment will be possible. Indeed, if nothing else is gained, the clinical trial proved that no damage is permanent with this illness. When the right treatment is found, CFIDS can be totally reversible!

(With special thanks to "downeast" for pointing us all to this significant research!!)

Index of CFS/FMS/MCS/Lyme Info Pages

[briarrose]

http://www.anapsid.org/cnd/diagnosis/oi.html

Tests of orthostatic intolerance shed light on cuase and severity of symptoms

Joan S. Livingston, The Update, Mass. CFIDS Association, Summer 2000, 13(2)

When Dr. David S. Bell last addressed members of the Mass. CFIDS Association, he reported on a fairly astonishing finding: his discovery, along with Syracuse endocrinologist Dr. David Streeten, that a majority of Bell's chronic fatigue syndrome patients had "extraordinarily" low circulating blood volume (a combination of plasma and the red blood cells via which the plasma delivers oxygen throughout the body). While his average patients ran about 70 percent of normal, several PWCs had only half the blood volume of a healthy person, an amount so low that it would ordinarily cause shock and prove fatal in a car accident. (See Winter 1997-98 Update for details on that study.)

From pain to brain fog

Bell hypothesized at that time that the low blood volume could help account for the prevalence of "orthostatic intolerance" - worsened symptoms, from pain to "brain fog" - among PWCs, because the limited amount of blood would tend to pool in the legs and feet, that common feeling of unbearable gravity and of wearing lead boots, with a corresponding drop in the amount of blood available to the brain. Other researchers' work has added to the evidence that this is a core problem in CFIDS, including reduced cerebral blood flow on SPECT scans, while some, like the Johns Hopkins group, have demonstrated neurally mediated hypotension on tilt-table testing (changes in posture).

Dr. Bell's Definition of "Fatigue"

Bell defines CFIDS symptoms as falling into four major clusters: so-called fatigue; neurological problems (balance, cognition, paresthesias, etc.); pain ("which can be anywhere-a lot of patients have skin pain, for example, and their doctor already thinks they're a fruitcake, so it's one of those symptoms the patient won't even mention to the doctor"); and multiple sensitivities.

In a disease whose formal name is (still) chronic fatigue syndrome, it's thought-provoking that Bell disdains the word "fatigue" as a "very inappropriate term for what patients experience. It's not really fatigue at all, which is defined as a normal recovery state from exertion, and that is precisely what does NOT happen in this illness. It's the limiting of activity that defines this illness. Anybody who works a 20-hour day will be fatigued, but they'll recover from it-it's not the same thing. A typical CFS patient might function on a minimal level (housework, minor errands) for a total of 3 or 4 hours a day. They may say they're fatigued, but what's really restricting their activity may be pain, like headache, tremulousness, or weakness-a sense that they are on the verge of collapse. That is not "fatigue" as we commonly think of it."

When the renowned Lyndonville, NY, clinician and researcher returned to the Boston area this May, he had further research results to disclose regarding the implications of low circulating blood volume (but no answers yet-sorry-on how to fix the problems identified). Streeten and he had conducted tests of orthostatic intolerance (hypotension, tachycardia, and other inappropriate physiological responses to standing) in 20 of Bell's patients, simply by tracking their blood pressure and pulse while lying and then standing. Like the test in which they measured blood volume, the protocol for this one was simple, requiring no special equipment like tilt tables (except time: at 40 minutes per patient, you may have trouble selling your doctor - especially HMOs - on doing this test. But, since it may document a disabling condition for Social Security, it's worth fighting for.)

Who You Calling a Wimp?

Bell and other clinicians, including Dr. Nancy Klimas, have long commented on their patients' (reported and observed) intolerance to being in an upright position, while they may feel "pretty good" while lying down. "When they get up," Bell said, "suddenly they have a lot of symptoms, so I suspected that what we call "fatigue" in chronic fatigue syndrome is really orthostatic intolerance. A patient might lie down for three hours and feel pretty okay, then get up for just 10 or 15 minutes before they're forced to lie down again to restore some blood flow to the brain."

Considering their blood volume and orthostatic intolerance, Bell's patients would be expected to have trouble during the 30-minute standing portion of his most recent testing. ["Fortunately, the nurse in our office, Paula, is very good about predicting when someone's about to go down-and obviously it's better to terminate the test than have patients hit the floor."] In addition, Bell stated, patients with CFIDS are widely assumed "to be 'wimps' - they're lazy, they're malingerers, right? But they'd say, 'I will push myself through this test, I can do it.' They might be swaying in absolute agony, but they'd finish. The normal controls, by contrast, were the wimps! After 20 minutes or so they'd say, 'I'm exhausted. Can you bring me a chair?'" Bell noted that his patients were presumably so used to "pushing to get something done that they often pushed themselves close to the point of passing out", that the sensations they experienced during the test were nothing new to them.

Hard Data

Consistent with Bell's long-held assumptions, virtually all of his patients (18 or 19 of 20) showed abnormalities when standing, hard data that could be helpful in diagnosis, that generally correlated with disease severity, and that could prove a powerful new tool in fighting for disability benefits. Quantifiable and reproducible, not subjective, not "of exclusion".

The new findings are particularly meaningful in bucking conventional notions of CFIDS as a disease of self-reported, possibly overstated symptoms. And no one, physician or Social Security judge, can reasonably provide an "AIYH" (all in your head) explanation to a patient with some of the specific physiological abnormalities itemized below, like a "pulse pressure" so low that no doctor can even read your pulse or dub as "within normal limits" a standing blood pressure so low it indicates circulatory shock.

Physical Anomalies

As an introduction to his most recent findings, Bell shared his observations about the wealth of already existing data on physical anomalies in CFIDS for those clinicians who have been willing to <look> and do more than a rote physical exam and standard blood test. "The abnormalities in this illness are numerous and striking," Dr. Bell observed. Even before the last few years' research began pinpointing increasingly more aberrations in virtually every body system, he says, "I was always quite annoyed when doctors would say you can't find anything wrong on laboratory evaluations or physical exam. <It's just not true.> Among other things, findings are very, very interesting." Findings include increased CD8+ activated T-cells (generally a sigh of active viral infection), low natural killer cell (NKC) function, and elevated circulating immune complexes. Unfortunately, few doctors other than researchers are inclined to order up such esoterica as immune system tests even when faced with a patient whose symptoms are as severe as those found in CFIDS.

"It's always been said that this is an illness of exclusion, that everything must be ruled out before the diagnosis of chronic fatigue syndrome can be made," Bell noted. "<That> is not true. The pattern of symptoms is unique: <there is no other illness in general medical practice that looks like this one.>" At first, he observed, the fluctuating symptoms may be baffling to the patient and doctor alike: "Not only do they fluctuate over the course of a single day, but also over the longer term. One week your sore throat is so bad you're about to have your tonsils out, then the next week your worst symptom is irritable bowel and you're off to see the gastroenterologist. It's only over a period of time that the characteristic pattern emerges and the diagnosis becomes evident."

Sleep dysfunction

Another near-universal symptom is sleep dysfunction. "Sleep-lab studies in fibromyalgia and chronic fatigue syndrome show an amazing array if abnormal findings. Virtually everyone with these conditions has significant deviations from normal stages although different laboratories interpret the sleep data differently. I had one patient who didn't sleep for three days, and the lab report came back reading 'NORMAL STUDY; patient did not sleep for three days."

Another notable irregularity to test for is "brain fog," though that can be problematic (because most doctors don't have pre- and post-illness IQ scores to compare): "If you give patients a basic cognitive test, they usually do pretty well," Dr. Bell said. "More sophisticated tests will identify the cognitive problems specific to this illness. But on a simpler level, you can also give one cognitive test while the patient is lying down [enjoying maximum blood flow to the brain], and one while the patient is standing. The difference between the two scores is often extraordinary.

"When doctors say that the physical exam is normal, that's also inaccurate," Bell continued. "Virtually all patients will have abnormalities on physical exam [such as lymph-node tenderness or swelling, flushing rash, abdominal pain, etc.], but on average the patient will look pretty healthy. What the doctor is thinking is that the physical exam is not abnormal enough to explain why someone says they can be up only two hours a day. The degree of reported activity restriction is so dramatic physicians frequently just don't believe it's possible."

But an understanding of low blood volume and severe orthostatic intolerance makes the degree of activity restriction more than "possible": it makes it hard to believe patients function as well as they do, because, as the data now suggest, many PWCs may function in a continuous state of hypotension, tachycardia, and/or other posture-related abnormalities.

The Five Basic Working Theories

Dr Bell noted that five basic theories of the illness have been set forth over time and remain current subjects of research:

Persistent infection (by a single agent)

"This theory is beginning to slip because it's just not felt by most researchers to be the most promising candidate; the problem is that we haven't found a single agent in this illness but in fact many pathogens." Just the same, the search is still on, as the recent interest in HHV-6 demonstrates.

Agent-induced immune dysregulation (i.e., a pathogen creates an initial infection that causes the immune system to malfunction even after the infection may have cleared); "This has been the best candidate over the past five years because the disease so often begins with a sudden onset, theoretically leading to an upregulation of the immune system and other long-term immune abnormalities."

Primary sleep disorder

While common in CFIDS, it doesn't account for enough of the symptomatology.

Mitochondrial abnormality

Like sleep disorders, this is probably also just one piece of the puzzle, despite ongoing research in this area.

Autonomic nervous system injury or dysfunction (e.g., orthostatic hypotension)

Consisting of the parasympathetic and sympathetic nervous systems, the autonomic nervous system (ANS) is responsible for controlling dozens of functions, such as the functioning of the adrenals and other glands, and involuntary bodily functions like breathing, pulse, and blood pressure. The ANS is the reason you keep breathing while asleep and your heart keeps pumping, as well as why your system goes into overdrive and why you sweat more when you're nervous.

The ANS is the root of orthostatic problems, and the inappropriate release of many chemicals; its dysfunction may explain a range of CFIDS symptoms. (For a full description of the parasympathetic and sympathetic nervous systems, see a good medical dictionary, like Taber's.)

Feigning irritation with this kaleidoscope of changing theories, Bell said, "As a clinician, you don't usually have to read much to keep up with what's going on." (His was a pediatric practice in a rural community before a CFIDS cluster epidemic struck young and old there in the 1980s.) "Sore throats haven't changed in 20 years. You give baby shots, that kind of thing."

With the Lyndonville outbreak, he suddenly had more on his mind than baby shots. "With the first two theories, I had to lean about all the intricacies of the immune system, about cytokines, about natural killer cells, the workings of one pathogen after the next. As soon as I had the immune system pretty well mastered, no one seemed to be talking about it anymore; people were talking about mitochondrial function [energy production at the cellular level]. So I read up on all that, and now we're not talking about mitochondria much anymore.

"Most recently the emphasis has been on the autonomic nervous system, which absolutely <nobody> understands." In this Bell is being a little disingenuous, as he has been one of the pioneers in researching the role of ANS dysfunction in this illness.

A Word About Depression

"There is one piece of good news in this list of five theories, and that's the fact that you don't see psychiatric disease there. That theory has largely fallen out of favor. Psychiatric illness is serious and devastating, but there'' very effective treatment for it; by contrast, there is still no good treatment for chronic fatigue syndrome.

"Having said that, I want to emphasize that, at some point in their disease, many CFIDS patients <will> become depressed. At least 60 percent of my patients have had periods of severe depression. This can take the form of despair that is truly life-threatening, and there may come a time for any individual patient when there is a role for counseling in their lives. I would hope everyone would be open to this when feelings of despair become overwhelming, and recognize that seeking help does not mean their disease is primarily psychological, but instead that counseling can play a valuable role in coping with any chronic physical illness."

Decrease In Circulating Blood Volume

Eighty percent, or the vast majority, of the patients in Bell and Streeten's first study (of 19 patients, versus the 20 in the more recent study), had a "marked, striking" decrease in circulating blood volume. "One nice thing about that finding," Bell said wryly, "is that it is a discrete physiological abnormality that cannot possibly be explained as psychosomatic."

How severe were the abnormalities? As mentioned before, the average was 70 percent of normal blood volume; still, "we have six people with only 50 percent of normal blood volume and yet they are still walking around. It seems to be a different mechanism than what happens to a healthy person [who loses that much blood] in a car accident."

In fact, the blood vessels in CFIDS seem to be constricted dramatically, and yet attempts to restore normal blood volume (through use of Florinef, salt, saline injections, transfusions) have met with only limited success so far. "All of the body's normal mechanisms to restore blood [when it is lost in other ways] seem to be turned off." It is as if the CFIDS body <wants> to have low blood volume and that its blood vessels want to stay constricted. Bell likens the blood vessels to water pipes that are only half the proper diameter - you simply cannot make a metal pipe hold any more fluid than the pipe is built to carry.

"When you tell people about these findings, their immediate question is, 'What happened to the blood? Where did it go?' The answer is we don't know. It's not like the patients bled out or are dehydrated - although they do experience a lot of thirst." Turning to the audience, Dr. Bell noted that his patients carry "buckets of fluid" with them at all times - an observation made by other clinicians. "How many people here also have excessive thirst? Whoa - look at all those hands!" It's as though some rudimentary alert system is crying out for more fluid, but because of the vasoconstriction, it just gets flushed away.

Straight Off The Presses: The Latest Findings

Bell and Streeten obtained their most recent and detailed findings about ANS dysfunction in Bell's patients through a "very simple test, one that can be performed anywhere, using only a blood pressure cuff" - much like the 'poor man's tilt-table test' - but I would argue it is more accurate because it reproduces exactly what happens to a patient waiting in the checkout line at the supermarket."

The patient lies down quietly for 10 minutes while a nurse takes his or her pulse and blood pressure (BP) several times. The patient is then asked to stand quietly for 30 minutes while the same measurements are taken.

The following <objective> abnormalities - and the number of patients who actually passed out while standing - are compelling evidence for a disability case, Bell noted. "Bank tellers will stand on their feet for 8 hours a day without much discomfort, and this test will show definitively why a CFS patient may not be able to do that for 30 minutes. You can hand this data to a disability judge and say, "Obviously, this person can't work as a bank teller."

The Context

To put the study's findings in context, here is a quick review of the normal pulse and blood pressure, drawn from Dr. Streeten's book on orthstatic hypotension.

Normal Systolic Blood Pressure (sBP; the higher number in a blood pressure measurement):

Recumbent: 100-142

Standing (after 4 minutes): 94-141

Orthostatic change, if any: -19 to +11

Normal Diastolic Blood Pressure (dBP; the lower number in a blood pressure measurement):

Recumbent: 55-90

Standing (after 4 minutes): 61-97

Orthostatic change, if any: -6 to +22

Normal Pulse Pressure (the difference between the systolic and diastolic pressures):

No known norms

Orthostatic change, if any: Difference narrows to 18 mmHg (millimeters of mercury) or lower

Normal Pulse

Recumbent: 54-96

Standing (after 4 minutes): 62-108

Orthostatic change, if any: -6 to +27

Bell noted that when a normal person stands up, the pulse may or may not rise slightly; the blood pressure usually remains stable (a graph of the systolic and diastolic numbers is notable for its constancy - a "band" that stays the same size); and the pulse pressure (the difference between the sBP and dBP) remains constant, not surprising since the systolic and diastolic remain steady.

Findings And Five Subgroups

The normal baselines just outlined proved to be significantly different from the five basic patterns or subgroups Bell found in his study, despite the fact that his patient's pulses and BPs were generally "pretty normal" while laying down.

Abnormalities in ANS function documented in virtually all of Bell's patients - some of whom had multiple severe abnormalities - were as follows:

1. Orthostatic systolic hypotension:

A fall in the sBP of 20 mmHg or more. As with the other abnormalities, this presumably reflects a desperate attempt by the body to boost blood circulation to the brain. This phenomenon, like all five of the abnormalities, is probably most obvious to the laymen with subgroup 4, Orthostatic postural tachycardia.

2. Orthostatic diastolic hypotension:

A fall in the dBP of 10 mmHg or more. "This seems to be the least common abnormality in the CFS patients I have tested. The body will put out adrenaline and other chemicals as a result of decreased blood circulation, which narrows the blood vessels still further."

3. Orthostatic diastolic hypertension:

A rise in dBP to 98 mmHg or more. "The diastolic BP often reflects systemic resistance, and while standing many CFS patients seem to 'raise' this lower number up in an attempt to push blood to the brain."

4. Orthostatic postural tachycardia:

An increase in heart rate of 28 beats per minute (bpm) OR a pulse of more than 110-120 bpm. "A healthy person's pulse will not change even if they stand up for an hour. You need a steady pulse to circulate the blood."

5. Orthostatic narrowing of pulse pressure:

A fall in the pulse pressure to 18 mmHg or lower. "Usually, when the pulse pressure falls much below 20, you can't even read the person's pulse. When it falls this low, the patient is in a state of circulatory shock.

Case Study

In his Mass. CFIDS lecture, Dr. Bell presented case examples, with details and supporting slides, for each of the five abnormalities listed above. In one of the examples, he presented a patient who actually had several of the five abnormalities, falling into more than one subgroup, and was one of Bell's patients with only 50 percent of normal circulating blood volume. Her resting BP was actually a little higher than normal, at 160/100. As soon as she stood up, however, it dropped to 90/0 (!), before flattening out at 70/60, the 10-point pulse pressure that signifies "it's basically impossible to read a pulse." Even without her other anomalies, at that pulse pressure and that BP, she was in a shock state and could no longer remain standing. In the meanwhile, her resting pulse had jumped from 80 to 120 as her ANS attempted to get blood to her brain.

Her physiological abnormalities included systolic hypotension (sBP=70), a drop to zero in her diastolic (dBP=0) immediately upon standing, and a narrowing of her pulse pressure to 10 (70/60) from her resting BP of 160/100 (pulse pressure=60). With her rise in pulse to the tachycardia figure of 120, she had a BP too low and a pulse too high to circulate her blood.

Another Drop To Zero

In the most recent edition of his publication, the Lyndonville News (CFS-DSB@juno.com) Bell wrote briefly about another woman with systolic hypertension. "One patient I follow had a normal BP while laying down (100/60) but it fell to 60/0 on standing. No wonder she was unable to stand up - a blood pressure that low is really unable to circulate blood. In any ICU they would panic seeing a patient like that, and yet she was turned down for disability because she was considered a "hypochondriac."

These two examples are certainly sensational. Of the five slides Dr. Bell showed as examples of the five disparate patterns he and Streeten identified, he mentioned that three of his patients whose data he used to illustrate three other disorders also had tachycardia, so clearly some patients suffered from more than one form of orthostatic intolerance (OI). Unfortunately, he did not enumerate precisely how many patients fit into each of the five subgroups or several, or whether the slides he showed were representative of the whole study sample or were chose because they illustrated the most severe abnormalities. Nonetheless, this was an initial study and we can probably expect more results and more details down the line.

Some Chemicals Behind BP, P, And OI: An Area For Future Research

Among the chemicals released by the ANS are cortisol, dopamine, epinephrine (adrenaline), and norepinephrine (chemically very similar to epinephrine but with somewhat less direct effect on the heart). Dr. Bell concluded his lecture by noting that these chemicals probably play a role in CFIDS, especially when released inappropriately, causing further vasoconstriction in those furnace pipes.

He favorably cited a recent article regarding norepinephrine, released by the adrenal gland. Many PWCs have long felt that the adrenal gland plays some central role in their illness, whether from underactvity, from long-term overuse, or from releasing too much adrenaline, leaving them with that frazzled, running- on-empty feeling.

In the study Bell cited, researchers performed measurements of norepinephrine on a twin subjects who have orthostatic intolerance as the result of a rare genetic defect, both while the subjects were recumbent and while standing. The subjects, who suffered from symptoms like rapid pulse, difficulty breathing, cognitive difficulties, and fainting spells, had excessive blood levels of norepinephrine while standing-but their symptoms were suggestive both of too much norepinephrine and of too little.

"It could be," Bell said, "that a physiological mishandling of norepinephrine ('norepinephrine transport'), for different reasons in CFIDS than in this exceedingly rare genetic condition, plays a role in both conditions."

Testing for "hyperadrenergic" (norepinephrine-related) orthostatic problems is likely to prove a useful tool in the future, Bell predicted. "Norepinephrine is the best method the body has for getting blood to the brain, to get that mental clarity of the fight-or-flight response," he noted. "But in CFIDS it seems to get kicked in inappropriately. Half the patients I've tested have an abnormality on testing. I think we'll soon see testing of such things as plasma norepinephnne when patients are experiencing orthostatic symptoms. It's good for getting blood to the brain but it's counterproductive in CFIDS as it probably causes further vasoconstriction and raises the pulse. It causes panicky symptoms and makes you feel tremulous, it causes exhaustion and forgetfulness, and it can cause poor sleep later."

Speaking of chemicals, Bell added, in regard to CFIDS pain, that PWCs might suffer from an inadequate supply of endorphins, the body's natural opiates. "Though there's no good research on this, there's a fellow in our area who's a superb acupuncturist, and what he's been doing with my patients has been knocking my socks off," Bell related. "I think that somehow acupuncture may have a relationship to the autonomic nervous system and centrally mediated pain."

While Bell and Streeten appear to have provided further insights into many of the body's different responses to low circulating blood volume, especially blood to the brain, there are no answers yet about how best to treat the five subgroups (and members of multiple subgroups) they identified. Perhaps one will turn out to comprise the "Florinef responders." In the past Bell has seemed bedeviled by the fact that the drug works so well for some PWCs but not others (relatively few of his own patients have shown improvement on it).

While there is still nothing as simple as a swab strep-throat culture for diagnosing CFIDS, the subgrouping may be a step in that direction, as well as toward determining the optimum treatment for each subgroup. "The reason I'm excited about this [most recent] study is that it provides a method to subgroup patients and perhaps to find the different mechanisms behind each abnormality," Bell said. With these mechanisms more fully understood, there should be advances in which therapies to use and which really work over time. And the simple orthostatic testing should provide more reliable data on treatment and responses than patients' comments on how they feel, since symptoms remit and relapse over time.

--------------------------------------------------------------------------------

The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome.

Streeten DH; Thomas D; Bell DS, Department of Medicine, State University of New York Health Science Center, Syracuse 13210, USA.

Am J Med Sci 2000 Jul;320(1):1-8

CITATION IDS: PMID: 10910366 UI: 20365736

BACKGROUND: Orthostatic hypotension during upright tilt is an important physical disorder in patients with chronic fatigue syndrome. We have tested its occurrence during prolonged standing, whether it is correctable, and whether reduced circulating erythrocyte volume is present.

METHODS: Fifteen patients were randomly selected from a large population of patients with chronic fatigue syndrome, studied, and observed for several years (by DSB). Blood pressure (BP) and heart rate (HR) measured with Dinamap every minute for 30 minutes supine and 60 minutes standing were compared with these findings in 15 healthy age- and gender-matched control subjects and later during lower body compression with military antishock trousers (MAST). Plasma catecholamines and circulating erythrocyte and plasma volumes were also measured by isotopic dilution methods.

RESULTS: Abnormal findings in the patients included excessive orthostatic reductions in systolic (P < 0.001) and diastolic BP (P < 0.001) and excessive orthostatic tachycardia (P < 0.01), together with presyncopal symptoms in 11 of the 15 patients and in none of the control subjects after standing for 60 min. Lower body compression with the MAST restored all orthostatic measurements to normal and overcame presyncopal symptoms within 10 min. Circulating erythrocyte but not plasma volumes were subnormal in the 12 women (P < 0.01) and plasma norepinephrine concentration rose excessively after standing for 10 min.

CONCLUSION: Delayed orthostatic hypotension and/or tachycardia caused by excessive gravitational venous pooling, which is correctable with external lower-body compression, together with subnormal circulating erythrocyte volume, are very frequent, although not invariably demonstrable, findings in moderate to severe chronic fatigue syndrome. When present, they may be involved in its pathogenesis.

[Guest tearose]

Thanks briar, that's a lot for me to process right now but what I read was really interesting. I'll have to print and read a bit at a time. tearose

[briarrose]

Tearose

I am sorry for so much. I know I hate reading that much too but when you just put a link out there many people have difficulties opening them and with all the hypovolemia type questions I thought I should just do a cut and paste job.

I know it is a lot of reading. I would have to print and mark off over hours or days to get through that much. I'm sorry to overwhelm anyone, really.

I know as a POTS patient I have read many articles by many doctors and I have to say that only a few have really impressed me. Dr. Grubb of course, but also the respect from all the Dysautonomia doctors towards Dr. Streeten and the steps he made in this field are very admirable.

steph

[opus88]

BriarRose,

WOW - BIIIIIG THANKS for posting this! I've done much reading and researching (not as much recently) but haven't come across anything that excited me this much in a very long time.

It seems to have hit the nail on the head for so many of the symptoms that I rarely see mentioned or described as well as what was in here: the admission (by a doctor!) of patients being looked at as hypochondriacs, the brain fog/change in IQ (a huge issue for me right now), the painful skin that we don't want to mention because we fear it will give more ammunition to the hypochondriac theory, the waxing and waning of symptoms, etc. . . . This is me, to a T!

I read everything, but will print it out, reread (probably multiple times) and keep it in my files. THANK YOU for sharing these articles!!!

[Ernie]

Hi,

Thank you for the article. I read it all and it is very informative. I really appreciate that you printed it on the forum and I enjoy reading technical stuff because it teaches me a lot. For me, the more technical the better.

Ernie

[briarrose]

Thx guys for your appreciative responses.

Sometimes I think that I inundate people with articles, statistics and facts but I really just want to share some of (what I think is the better stuff out there.) I know that many people have already found these websites but there are a lot of new people to the forum that probably haven't done the extensive searches that we have over the years.

thx

Steph

[Ernie]

Hi Steph,

I really enjoy reading these kind of articles because it explains in details what we have. This is one of the thing that I miss from going to University. I don't get to read many in-depth material anymore and I miss it. I guess I am like a runner who stops running. I miss studying and learning so when you offer some medical information, I am delighted.

Ernie

[briarrose]

Thank you Ernie hugs

steph

[Guest Julia59]

Hi Steph,

I'm glad you posted this information. There is never enough reading for me on this subject---or subjects related.

Sometimes everything kind of runs together-----you know what I mean. Dysautonomia affects so many systems------that we don't know if the chicken or egg came first.

In a way I can understand why some Docs don't want to go there. But that doesn't excuse their rude behaviour with some patients.

Very interesting information....

I like the other articles on chronic fatigue---HIV also.

Take Care.

Julie :0)

[briarrose]

Julia

I've been waiting for someone to say something about the correlation between CFS - Non-HIV AIDS. I've been hoping for other peoples opinions and if anyone else has heard any of this before. It actually frightened me when I first read it and I wondered about it's authenticity in medical findings.

I thought more people would respond to the article that has a statement about -Health Care Workers May Be At Increased Risk For CFS. It's the first paper that I've ever read that actually gives health care workers acknowledgement for possibly contracting CFS. I didn't realize they had attempted to do a study on it.

Thank You Julia

[Guest Julia59]

WEll in my opinion it is not discussed enough----CSF/NON HIV AIDS

I will be re-reading the article more------as it takes things a while to sink in due to my ADD. It is quite disturbing to say the least. I don't know why more is not known about all of this. Perhaps more studies need to be done before they open up THAT can of worms. Quite a lot to think about.

You know----that is how research begins, so i'm sure we will hear much more about this in the future. If the health care workers are at risk---how about the patients under their care?

I think it's a very good medical artical/journal. I have gone over to the Medical College of Ohio to pull journals for the support group. I find that I am a medical artical/journal nerd--I actually like to read them...........LOL---

Julie :0)

[blackwolf]

Thank you very much. It took a while to read but i got alot out of it.

I too was in the ICU once for the 60/0 bp!!! it really got my attention. I printed it out.

I had a hiv test at the begining to rule it out.

I also was a CNA/Med aid, but I had Fibro/CFS before I got into it. You know, now that I think about it, I was a CNA back just after I left college. I was there for about 3 months before a move.

Thank you, I will keep an eye out for these guys.

Blackwolf

[JLB]

THANK you!

Seems there may be hope for the future... God bless these doctors, and the patients who are part of the research.

Thanks again for taking the time to put these up here.

[Nicole's Mom]

Hi Steph,

I wanted to thank you for passing along this wonderful, long, excellent article. I finally was able to print it up and read it today. Although I had previously read a small bit of it from another source- MOST of it I had NEVER SEEN before. What a superb detective you are to have come across such a useful, helpful article! It is very informative yet easy to read. I really like easy. It is just so validating and so much more. I love the part where Dr. Bell (or was it Dr. Streeten?) speaks to the hypovolemia and that hypovolemia is something that nobody should dare refer to as a psychosomatic symptom.

Anyway I plan to read it again. I appreciate anything helpful like this because this illness is so complex and I want to learn about it as best I can. As the saying goes- "Knowledge is power."

Best Wishes,

Beverly

[Dizzysillyak]

Thanks ... These are some great articles ... I particularly liked this part on how our pipes are too small.

http://www.anapsid.org/cnd/diagnosis/oi.html

In fact, the blood vessels in CFIDS seem to be constricted dramatically, and yet attempts to restore normal blood volume (through use of Florinef, salt, saline injections, transfusions) have met with only limited success so far. "All of the body's normal mechanisms to restore blood [when it is lost in other ways] seem to be turned off." It is as if the CFIDS body <wants> to have low blood volume and that its blood vessels want to stay constricted. Bell likens the blood vessels to water pipes that are only half the proper diameter - you simply cannot make a metal pipe hold any more fluid than the pipe is built to carry.

"When you tell people about these findings, their immediate question is, ' What happened to the blood? Where did it go?' The answer is we don't know. It's not like the patients bled out or are dehydrated - although they do experience a lot of thirst." Turning to the audience, Dr. Bell noted that his patients carry "buckets of fluid" with them at all times - an observation made by other clinicians. "How many people here also have excessive thirst? Whoa - look at all those hands!" It's as though some rudimentary alert system is crying out for more fluid, but because of the vasoconstriction, it just gets flushed away.

Anyone besides me always have trace amounts of blood in their urine and stools ?

[Desperate Mom]

After just reading this article I was really impressed at how detailed the findings were and how closely they resemble the symptoms of CFS and OI. It amazes me when I think about so many doctors telling me these symptoms were'nt related to any illness other than depression. I was really impressed when I read about patients having excessive thirst and excessive sweating. Those are two of the many other symptoms my daughter has had and none of her doctors had an answer for. I never knew one could be tested for low blood volume, I always thought it was just assumed because of the blood pooling. Very interesting article. Thank you for putting it here. It gives me hope to know that these studies are being done.

[Dizzysillyak]

After just reading this article I was really impressed at how detailed the findings were and how closely they resemble the symptoms of CFS and OI. It amazes me when I think about so many doctors telling me these symptoms were'nt related to any illness other than depression. I was really impressed when I read about patients having excessive thirst and excessive sweating. Those are two of the many other symptoms my daughter has had and none of her doctors had an answer for. I never knew one could be tested for low blood volume, I always thought it was just assumed because of the blood pooling. Very interesting article. Thank you for putting it here. It gives me hope to know that these studies are being done.

I'm confused here ... I thought CFS and POTS / OI were known to be related. I see OI stuff in my CFS research all the time ... granted it is just one symptom of CFS though. The others being sleep disorder, neuro problems, IBS, chronic fatigue, swollen lymph nodes ..

BTW. I'm glad you saw this article and you were able to see your daughters symptoms here. It has certainly made a difference in my life being to see all this info on the internet ... Take Care ... Marcia

PS. Not to be pushy cause I hate that, but have you had your daughter tested for gluten intolerance ? She and I have so much in common ...