Phoenix Rising – An ME/CFS/FM Newsletter by Cort Johnson (Jan 2006)
Phoenix Rising – An ME/CFS/FM Newsletter by Cort Johnson (Jan 2006)
Phoenix Rising is a monthly newsletter committed to elucidating current CFS research, describing important events, telling patient stories, suggesting alternate treatments for CFS patients, etc. Please contribute to Phoenix Rising.
NEWS -A Goodbye To Jason Breckenridge/New Ampligen Trial / New U.K. CFS Website and Newsletter / AACFS Changes Name and Message From the President / Dr. Puri Talks /Dr. Natelson Talks / Diagnosing CFS/ME clarified / Patient Stories From RemedyFind / Maximize Your Contributions
MEDIA DESK - Ignoring ME in Britain – the Cost
RESEARCH - Immune Cells ‘Burned Out’ in CFS patients / No Orthostatic Intolerance in CFS? (But Perhaps Something Else)?
EDITORIAL - Slowly We Go; How it Took Fifteen Years to Accomplish What Should Have Been Done in Five.
SPECIAL REPORT - The Neuroimmune NIH Grant For CFS: ‘Making the Difference’ or More of the Same? Part II: Reading the Grant
A Goodbye to Jason Breckenridge - Jason, a much loved member of CFSMExperimental, died suddenly on Dec 16th, 2005. You can read some of the many tributes given to Jason as well as a selection of posts from his last months by clicking here.
Registration for Ampligen CFS Trial Open - Hemishperx Biopharma is recruiting patients for an Open Label Phase III study of Ampligen in CFS. It’s not going to be cheap, patients will have to pay for buying the drugs, having them administered, laboratory costs, etc. but it does give those with the means a chance to try a drug that has been very valuable for some. Some longtime CFS researchers (Peterson, Lapp) are involved. You have to be over 18 and you can get more information at
Dr. Cheney Talks - Check out this short interview with Dr. Cheney regarding his latest cardiac findings (click here) as well as a short statement by Atrium Biotechnologies regarding a recent visit by the always very proactive doctor to challenge them to produce NatCell products focusing on the heart (click here). Thanks to Margaret Simmons for providing these.
Dr. Kerr Talks- “Invest in ME is pleased to announce that Dr. Jonathan Kerr (Hon. Consultantin Microbiology, Dept of Cellular & Molecular Medicine, St. George’s University of London) has agreed to present at the CFS/ME Conference 2006 (An Update on Clinical Diagnosis, Research Trends and Educational Support) in London on 12th May 2006″.
Dr. Kerr will be presenting on his work around Viral and Human Gene _Expression in CFS, diagnostic testing and imminent clinical trials. For more information and an application form for this conference please contact firstname.lastname@example.org or see
Phoenix Rising desperately wants someone to report back to us on how this conference and, in particular, this presentation went. If you’re going please e-mail me at email@example.com.
News From Dr. Natelson - Those who have followed CFS Research may know that Dr. Natelson has been the most prolific CFS researcher over the past five years. In this brief presentation Dr. Natelson talks about the status of his research into CFS and reveals some intriguing findings. Thanks to Tom Kindlon for providing this.
Diagnosing CFS Clarified - Jodi Bassett, a CFS sufferer, has combed through the voluminous papers concerning diagnosing ME/CFS and produced a simple (at least as simple as possible) guide to diagnosing CFS. You can access it at her Hummingbird’s Guide To M.E. website http://www.ahummingbirdsguide.com/testingforme.htm
The AACFS Goes International, Next International Conference Date and Location Set - The American Association of Chronic Fatigue Syndrome (AACFS) which puts on the large Conferences on CFS every two years has changed its name (International Association of Chronic Fatigue Syndrome) to better reflect the international nature of CFS research and issues. This organization which used to be restricted to physicians and researchers has also opened it doors to patients as well. You can visit this organization and become a member by clicking here.
The 8th International IACFS Conference on Chronic Fatigue Syndrome, Fibromyalgia and Other Related Illnesses is just a year away and will take place from January 11-14, 2007 at Ft Lauderdale Fl.
“This four day scientific medical conference will focus on integrative themes such as fatigue, pain, sleep, cognition & brain function. Each session will ask what is the science of the area (e.g. fatigue, pain etc), and close on the practical applications in the art of clinical medicine. There will be a panel discussion on the new pediatric case definition, and lectures on latest research, newest clinical protocols, a session on what genes can teach us and other innovative recent advances.” Is it not time for a yearly conference?
RemedyFind Newsletter Available- This newsletter has several patient stories plus pictures and great graphics, as well as an overview from a recent paper examining Omega 3 oil levels in CFS. The newsletter is at
http://www.remedyfind.com/newsletter_archives/Jan_06_CFS.html The RemedyFind site also has a page where you can rate treatments according to their effectiveness and to find out how others have rated them.
Invest in ME newsletter available - The first two Invest in ME newsletters are now available online. It’s nice to have this very professionally done newsletter available. Check out the news on the upcoming Invest in ME conference.
Maximize Your Support of CFS Research - (this ran in last month’s newsletter but that’s no reason not to run it again – it’s an excellent opportunity to assist the research efforts going on MERGE. The links in the last message, however, were wrong, and that demands another posting.)
We all want our charitable dollars to go as far as possible. As CFS patients we in fact need to be able to maximize our contributions. Three CFS patients in the U.K. have just made it easier to do so. These three individuals will donate money every time someone sets up a ‘standing order’ (monthly contribution) to MERGE, the outstanding CFS research group in the U. K., from February through the end of May. MERGE, which receives no governmental funding, relies completely on charitable donations to continue its work. The way I see it – the more work MERGE does, the better I chance I have of getting well before I hit the grave. You can access their announcement by clicking on the below url , and download the standing order for MERGE by clicking on this URL http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0601B&L=CO-CURE&P=R1797&I=-3
and access MERGE’s standing order form by clicking on below
Online ME/CFS Program ‘A Hidden National Scandal Exposed’ available on ME in the U. K.
From the press release – “Invest in ME (IiME) is publishing on its web site the ITV Meridian programme which shows the devastating affects of ME on whole families. In a programme made by Meridian Television severely affected sufferers explained the devastating effect the illness has had on them and their families. Despite the vast number of sufferers…the Government has given no money for bio-medical research, choosing instead to squander £11.2 million by setting up ME/CFS centres to deliver programmes of Cognitive Behaviour Therapy (CBT) and Graded Exercise Therapy (GET). Doctor Jonathon Kerr of Imperial College, London has recently found that in people with M.E. there are 15 genes which are 4 times more active than in healthy people, which indicates that their immune system is working overtime. In the programme he says he is confident that he will have a cure within a year.
To see the programme on-line and for more detailed information on the condition and problems faced by Suzy and Lauren and thousands like them, visit www.investinme.org or go direct to the Meridian link at http://www.investinme.org/Mediatelevision.htm#Meridian_TV_-_ME_Expose
RESEARCH - Unless otherwise noted the research summaries are by Cort Johnson, a CFS patient, whose ‘expertise’ such as it is, extends mostly to subjects of CFS pathophysiology. Submissions from others with knowledge of other fields (psychology, epidemiology, etc). or of any aspect of CFS pathophysiology are gratefully accepted. Comments, suggestions, clarifications, etc, negative or positive, only add to the editors and others understanding of CFS. Please send them to Phoenixcfs@yahoo.com).
Rating The Months Research- The thesis of this newsletter is that the most important studies deal with the pathophysiology of CFS. Each month is graded according to the following criteria;
A - several difference making papers on CFS pathophysiology
B – a difference making paper on CFS pathophysiology plus several important ones
C - several important papers on CFS pathophysiology
D - 1 or no important papers on CFS pathophysiology but several on other aspects of CFS
F - no important papers on CFS
December Research Rating – B
|Total Number of Papers – 14||Country of Origin|
|Immune – 5||United States|
|Clinical – 4||United Kingdom|
|Psychological/Behavioral – 3||Belgium|
|Fatty Acid Metabolism – 1||Netherlands|
|Orthostatic Intolerance – 1||Australia|
‘Paper of the Month’
Every month the editor picks out what he, based on his admittedly limited understanding of CFS, believes to be the most important paper published that month for an in-depth examination. In this month’s paper we find that investigators are getting at the source of the natural killer cell dysfunction present in CFS patients.
Immune Cell ‘Burnout’ in CFS Patients
Maher, K., Klimas, N. and M. Fletcher. 2005. Chronic fatigue syndrome is associated with diminished intracellular perforin. Clinical and Experimental Immunology 142, 505-511.
While attempts to find a single pathogen responsible for CFS have failed, there is considerable evidence (increased markers of lymphocyte activation, and increased production of pro-inflammatory and Th2 cytokines) that the immune systems of CFS patients are reacting to something. Some indices of immune system functioning have been difficult to replicate but impaired Natural Killer Cell (NK) functioning (cytotoxicity – cell killing ability) has consistently been seen.
This study measured both NK cell numbers and cytoxicity and attempted to ascertain the cause of the reduced NK cell killing ability in CFS patients by assessing the levels of perforin, an important killing agent.
Natural Killer (NK) cells and Perforin
Natural killer cells are a white blood cell (lymphocyte) involved in the innate immune defense system. They troll the bloodstream looking for cells that display signs of cancer or infection. Unlike T and B cells which need time to mount a response NK cells are always on the alert and are ready to attack. They are amongst the first immune cells invaders typically encounter and they are responsible, among other things, for keeping the invaders in check before the adaptive immune response involving T and B cells kicks in. They are typically activated by cytokines produced either by infected cells (interferons) or by macrophages.
Patients deficient in NK cells prove to be highly susceptible to the early phases of herpes virus infection. Mice engineered to be perforin deficient are less able to clear viruses and tend to produce autoantibodies that attack the mouses tissues.
Both NK and cytotoxic T-cells kill cells by injecting their cellular membranes with granules containing perforin and granzymes. Once inside the cell membrane perforin polymerizes to form a hole in the cell. As the contents of the granule (granzymes) pour into the cell to activate its apoptotic machiner,y the contents of the cell begin to leak out, and the cell soon dies. Studies have shown that perforin is the critical cytotoxic ingredient found in these granules.
This study found evidence of both immune activation and immune dysfunction in CFS. The lymphocytes of CFS patients were found to be highly activated relative to those of the healthy controls (p<.001). Lymphocyte activation is determined by measuring how frequently markers of activation (CD26+CD26+) indicating contact with a pathogen were found. Accompanying this immune activation were two signs of immune suppression: NK cell (CD5-CD56+) numbers were significantly lower (P<.04) and NK cell cytotoxicity (i.e. killing ability) was greatly lowered (p<.001). NK cell cytotoxicity is measured by putting NK cells together with cells they normally kill and seeing how many of them die. The NK cells from CFS patients were only able to kill about 50% of those that NK cells from healthy controls killed. So we have a double whammy here! Not only were NK cell numbers lower but those that were still alive were lousy at killing pathogens. Why did the CFS patients have such wimpy NK cells? Further testing revealed that the main killing agent in NK cells, perforin, was significantly lower (p<.01) in the CFS patients that in the healthy controls.
Since perforin is also a key component of the killing machinery of cytotoxic T cells (CD8+) the researchers also measured the perforin content of these cells. They found that CFS patients exhibited a ‘trend’ towards low perforin levels in those cells (p<.06).
A finding is termed to be ‘significant’ if statistical analyses indicate it has only a 5 chances in 100 (p<.05) of being due to chance. Anything slightly higher than this such as p<.06 is considered notable but not significant and is called a ‘trend’. Anything much higher than that is considered not-significant and is discarded. Thus, if a statistical analysis indicates a finding has a 1 in 1O chance of being due to chance it is dismissed, no connection is established and the theory, whatever it was, is considered unproven.
Cytotoxic T-cells (CD 8) provide one of our major defenses against viruses, bacteria and cancer. The cytotoxic T-cell killing process begins when organelles inside cells called proteasomes chop up pathogenic or cancer derived proteins into peptides and display them on MHC molecules on the outsides of cells. The presentation of these peptides prompts the production of an army of antigen specific cytotoxic T-cells that swarm out of the lymphoid organs looking for the invaders. While this is kicking in (it takes several days) the body uses NK cells to keep the pathogen in check. Once the cytotoxic T-cell attack begins few pathogens are able to overcome it. For more on cytotoxic T-cells click on the following URL: http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/cellular/cmidefense/ctls/ctldefense.html
This study indicates that the perforin content and thus the killing ability of two major immune cells are reduced in CFS patients. The immune activation seen in conjunction with the reduced cytoxicity exhibited by both the NK and T-cells in this study suggested to these researchers that the NK and T cells had essentially suffered burnout! The authors proposed that the lymphocytes in CFS have been activated for so long – and have presumably killed so many infected or damaged cells – that they have basically begun to run out of ammunition.
Studies examining NK cell function in chronic hepatitis C and HIV found that just this process has occurred. HIV researchers have gone so far to as to examine perforin expression in different subsets of cytotoxic T-cells. Since HIV is a disease of immune suppression HIV patients often support different types of pathogens. Since cytotoxic T-cells are pathogen specific it is possible to segregate cytotoxic T-cells according to the type of pathogen they are primed to attack. In this case HIV researchers found that perforin expression in HIV patients was low only in cytotoxic T-cells that were primed to attack HIV, not those primed to attack a less virulent pathogen, cytomegalovirus (CMV). This demonstrated that reduced perforin expression in these patients was probably due to ‘overwork’. (Isn’t amazing what you can discover when you have sufficient funding?)
Other potential consequences of reduced perforin levels – Increased pathogen levels are not the only potential consequence of reduced perforin levels. Two disorders characterized by very low perforin levels, hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS), result in increased T lymphocyte and macrophage levels and activation. Researchers speculate that increased pathogen levels due to poor NK cell functioning could result in an excessive antigen driven T-cell activation; simply put, the failure of NK cells to dampen down an infection results in an exaggerated T-cell attack when it occurs. T-cells produce a number of cytokines (IFN-y, granulocyte macrophage stimulating factor (GM-CFS)) that could result in high macrophage activation.
MAS is found to at least some degree in many rheumatic (joint and muscle) diseases, and, of course, CFS patients often are plagued by joint and muscle problems. In MAS, the destruction of red blood cell precursors due to high levels of activated macrophages in the bone marrow, results in low red blood cell levels, anemia and, at times, an aplastic crisis. CFS patients do not undergo aplastic crises but do sometimes exhibit reduced red blood cell mass. Could the reduced red blood cell mass in CFS be due to perforin dysfunction and chronically increased levels of activated macrophages in their bone marrow?
Another Possible Cause of Reduced Perforin Levels in CFS? – Although the authors did not mention it, a different cause of low perforin levels is found in patients with atopy (hypersensitivity to allergens; i.e. asthma, hay fever). Reduced perforin in atopy patients appears to be due to perforin ‘hyperreleasability’ in their NK cells, i.e. their NK cells release enormous amounts of perforin when stimulated.
CFS patients do not appear to have asthma but they do often have shortened breath, high rates of allergy and ‘bronchial hyperresponsiveness’ and both CFS and atopy patients are believed to have a predominantly Th2 cytokine profile. CFS patients with BHR had, intriguingly, higher numbers of activated cytotoxic T-cells than those without it, which we have just seen may be a consequence of low perforin levels, and also suggests the CFS patients with BHR were battling an intracellular pathogen.
Enhancing perforin levels – The authors do not mention ways of increasing perforin levels in NK cells but researchers have been able to do so in AIDS patients. Doing so requires taking interferon, a drug with numerous side effects, one of which can be debilitating fatigue! Readers of the last newsletter may remember, however, that Dr. Chia has used this drug to some effect at least temporarily in CFS patients. IFN-a administration in AIDS patients returned both the percentage of NK cells producing perforin and the mean perforin concentration in those cells to normal (Portales et. al. 2003). Portales believed that enhancing NK cell function in AIDS patients could allow them to reduce their HIV loads as well as the opportunistic micro-organisms also found.
An immunomodulator used in France for over twenty years called Biostim may also enhance NK cell functioning. One study found Biostim increased the NK cytotoxicity and tumor cell clearance. Biotism also appears to enhance neutrophil, macrophage, T and B-cell functioning. Its apparently pretty cheap as well. Probably since it enhances immune functioning the manufacturer does not recommend those with autoimmune diseases use it. As always use with caution. To access the manufacturer’s webpage click here. To visit a company that sells Biostim click here. (Thanks to Christine Emmanuel for providing this information).
Ongoing Research – None known.
Portales, P., Reynes, J., Pinet, V., Rouzier-Panis, R., Baillat, V., Clot, J., and P. Corbeau. 2003. Interferon-a restores HIV-induced alteration of natural killer cell perforin expression in vivo. AIDS 17, 495-504.
‘Slowly We Go’ or
How it Took Almost Twenty Years To Do What Should Have Been Done in Five;
The History of NK Cell Research in CFS
NK cell dysfunction has been of interest in CFS from the beginning. The first paper describing NK cell dysfunction in CFS was only the second paper ever published on CFS*. Since then reduced NK cell functioning has been one of the very few immune abnormalities consistently seen in CFS. There has been much huffing and hawing in the scientific community over the inconsistent study findings in CFS and how heterogeneous the patient population is, etc. and one could understand some reluctance to commit precious research funds to such a confusing disorder. But poor NK functioning has, with only a few exceptions, been consistently been found in CFS. One might expect that when researchers found something consistently abnormal in CFS, the public research institutions would take note of it and focus on it. One might think that twenty years later the cause of this distinctive dysfunction in CFS would have been well researched by now.
But this is not so at all. There has been no coterie of researchers chipping away at the question of NK cell dysfunction, no research group intensely focused on why this part of the immune system is impaired in CFS. Research into NK cell functioning has exhibited the same slogging, mediocre pace of most of the other research efforts into CFS. Instead of a concentrated widespread effort we have a small group of researchers that have been intermittently but innovatively chipping away at this problem. We are very lucky to have them – we depend on them and groups like them for so much! – but it has taken us far too long to get to where we are today. Only now, almost twenty years after we discovered NK cell functioning is a problem in CFS, are we beginning to get at the source of that problem, and we really are just at the beginning. Now that we know the NK cells in CFS patients are low in perforin we need to find out why and find ways to resolve it. In how many other diseases would this have taken so long? Twenty years is a long time to be ill. That’s a lot of water under the bridge – a lot of suffering by a lot of people.
Read the timeline below and weep. This is one reason why you and I are still ill today. Histories like this occur when public research institutions are not serious about resolving medical issues. They occur when too few research funds are spread among too many researchers. In CFS NK cell research must compete with a vast number of other research interests including genes, gene expression, protein expression, cortisol, DHEA, serotonin, HLA markers, acetylcholine, RNase L, orthostatic intolerance, corticomotor excitation, oxidative stress, cytokines, vascular abnormalities, red blood cell levels, low blood volume, cardiac abnormalities, etc., etc. not to mention the tremendous amount of money going to epidemiological research and cognitive behavior type studies and psychological research! The funding pie is simply too small and our research needs too large for any but the really hot topics to move on at an acceptable pace. This is why it can literally take decades to accomplish in CFS research what takes a few years in other well-funded diseases.
This is why we need to be as vocal and supportive as we can be with our time and our money in ensuring that public research institutions display the commitment and private research institutions such as the CAA, MERGE and the CFS Research Foundation have the money they need to uncover the cause of and treatment for this illness. Do we want to wait another twenty years for the next breakthrough in CFS to occur?
Two of the studies listed below (Tirelli et. al. in 1994, Ogawa et. al. in 1998) found abnormalities in other aspects of NK cells (NK cell subset abnormalities, L-arg enhanced NK cell activity). Normally one would expect that ‘successful’ studies, i.e. ones that in which their thesis was proved correct would receive a follow up, but this has not been true at all.
*Caligiuri, M., Murray, C., Buchwald, D., Levine, H., Cheney, P., Peterson, D., Komaroff, A. and J. Ritz. 1987. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J. Immunol. 139, 3306-13.
An NK Cell Research Timeline
1987 -NK cell number and cell killing ability (cytoxicity) low in CFS (Caligiuri et. al.).
1990 – High NK cell number and low NK cell killing ability (Fletcher, Maher et. al.)
1991 – Reduced NK cell levels (Gupta and Vayuvegula)
1993 – NK cell number normal (Straus et .al.)
1994 – NK cell number normal, reduced NK cell activity (Barker et. al.)
1994 – Low NK cell activity correlated with symptom expression in CFS (Ojo-Maize et. al.)
1994 – NK cell number and activity reduced (Masuda et. al.)
1994 – NK cell activity normal (Rasmussen et. al.)
1994 – Reduced NK cell number, atypical expression of NK cell subsets, increased levels of adhesion markers (Tirelli et. al.)
1997 – NK cell number and function normal (Mawle et. al.)
1997 – NK number increased (Peakman et.al.)
1998 – Low NK cell activity in family with CFS (Levine et. al.)
1998 – NK cell number normal (Natelson et. al.)
1998 – The inability of L-arg to enhance NK cell activity in CFS patients relative to controls suggests a dysfunction in nitric oxide mediated activation of NK cells (Ogawa et. al.)
2001 – NK cell number low (Racciatti et. al.)
2002 – NK cell activity reduced (Masuda et. al.)
2002 – More sensitive test for measuring intracellular perforin developed (Maher, Klimas et. al.)
2005 – NK cell number normal (Robertson et. al. )
2005 – Nk cell number and killing ability reduced, proximate source of NK cell dysfunction identified (Maher, Klimas, et. al.)
NO ORTHOSTATIC INTOLERANCE IN CFS?
(but perhaps something else?)
Jones, J., Nicholson, A., Nisenbaum, R., Papanicolaou, Soloman, L., Boneva, R., Heim, C. and W. Reeves. 2005. Orthostatic instability in a population-based study of chronic fatigue syndrome. The American Journal of Medicine 118, 1415.e19-1415.e28.
Let’s not mince words here. This is one of the most disappointing papers to appear on CFS in quite some time. A great deal of work has suggested that orthostatic intolerance (OI) – the inability to stand without having symptoms – occurs in at least a significant subset of CFS patients. Past studies have suggested that between 20% and 90% of CFS patients have OI. Several studies, some of them quite large, are currently underway trying to figure out the cause of the OI in CFS¼ .and now the CDC steps in (at this rather late date) and says, Oh, OI? It’s no more commonly found in CFS than in the general population. This is the kind of study that makes you just want to throw up your hands and scream.
The CDC measured heart rate and blood pressure (BP) during standing and heart rate, BP, oxygen saturation, respiratory rate and ECG during the tilt table test as well as various laboratory measures (plasma renin, aldosterone, norepinephrine, serum osmolality, BUN, etc.) often correlated with OI.
None of the laboratory measures or indices of orthostatic intolerance were significantly increased in CFS patients. Nor was symptom expression; the control group actually exhibited a greater prevalence of symptoms of orthostatic intolerance than did CFS patients (!). In fact, even though it wasn’t significantly different, a far greater percentage of the healthy controls had some form of OI (NMH, POTS) than did CFS patients (58-30%). When the time to orthostatic intolerance was measured CFS patients did not more rapidly proceed to neurally mediated hypotension (NMH – low blood pressure) or postural tachycardia syndrome (POTS – rapid heartbeat) than did the healthy controls.
The study also indicated that the stand up tilt test often used by physicians to assess OI in lieu of doing a tilt table test was not a good predictor of tilt table performance.
There was one bit of intriguing news. A significant correlation of serum osmolality with the time to OI in both groups indicated that low blood volume is related to orthostatic intolerance. Serum osmolality is a measure of hydration. Reduced red blood cell mass has been positively correlated with low blood volume. Decreased blood volume could be due to a variety of factors including impaired vasoconstriction and blood pooling. Since these effects can take a while to kick in this suggests a mechanism whereby CFS patients could tolerate standing at first but eventually fade over time.
We weren’t done with disconcerting news about OI, however – a report on the prevalence of OI in Gulf War Syndrome also appeared last month¼
Lucas, K., Armenian, H., Debusk, K., Calkins, H. and P. Rowe. 2005. Characterizing Gulf War Illnesses: neurally mediated hypotension and postural tachycardia syndrome. The American Journal of Medicine 118, 1421-1427.
This study examined the prevalence of neurally mediated hypotension (NMH, low blood pressure upon standing) and postural tachycardia syndrome (POTS, increased heart beat upon standing) in GWS patients, Gulf War veterans without GWS and veterans who did not serve in the Gulf War. The GWS patients had to meet a criteria that was similar to CFS but not as strict; they had to have fatigue plus 2 of the following symptoms; impaired cognition, headaches, joint pains without swelling, unrefreshing sleep and post-exertional fatigue.
This study found that while there appeared to be a gradient in the prevalence of NMH with GWS patients displayed the highest and non Gulf War vets displayed lowest rate of it, the results were not statistically significant. The incidence of POTS was the same in both groups.
The GWS did display some altered physiological parameters, however. Palpitations occurred in 2/3rds of them compared to 6% of controls and they had a higher respiratory rate (breathing) and lowered tidal CO2 than the non-deployed vets. The number of symptoms evoked during the tilt testing was also much greater in the GWS patients. Thus, while the incidence of OI in these patients was not increased, they did react differently to the tilt tests than did the healthy controls.
Provisos- There are some real provisos to both these studies:
(1) Many papers state the limitations of their study at the end of the discussion section but the decision of the authors of the CDC study to place theirs near the front suggests that its limitations may have been more significant than usual. The problem was the high number people excluded from these studies by the exclusionary factors. Forty-eight CFS patients (and 30 controls) were excluded from the CFS study.
(2) Another problem is that neither of these studies measured blood flow to the brain, a potentially important measure, given that many symptoms of orthostatic intolerance may be derived, in large part, from inadequate blood flows to the brain. It is not necessary to have either NMH or POTS to have reduced blood flows to the brain.
(3) There may also be a problem with the sampling procedure. In their efforts to avoid ‘referral bias’ the CDC is using a community sampling process. Several studies have indicated that the type of CFS patient recruited using this process may be markedly different from those seen in doctor’s offices. In particular, one study found that from 70-80% of these ‘CFS patients’ no longer met the definition of CFS three years later!
Dr Natelson to the Rescue?
We really need someone to rescue us here and I thank Tom Kindlon for forwarding this timely bit of information. Dr. Natelson has also found a low incidence of orthostatic intolerance in CFS and reduced end tidal CO2 levels during tilt testing. His team has also found reduced blood flows to the brain in CFS patients and he now thinks low CO2 levels (hypocapnia) could be partly responsible. He is collaborating with Dr. Biswal in a unique experiment to test this theory using functional magnetic resonance imaging. Creating an orthostatically challenging environment inside a fMR machine which requires the subject to lie down was difficult but was achieved by creating an apparatus that draws blood from the head and trunk of the body down into the legs. This study is currently underway. You can read about it byclicking here. (Update – Just a week ago Dr. Natelson published a paper showing reduced blood flows to the brains of CFS patients.).
Hypocapnia occurs when the level of carbon dioxide in the blood is lower than normal. Because hypocapnia causes vasoconstriction (narrowing) of the cerebral blood vessels it can lead to cerebral hypoxia (reduced brain oxygen levels) and this can cause transient dizziness, visual disturbances and anxiety. A low partial pressure of carbon dioxide in the blood also causes alkalosis (because CO2 is acidic in solution), leading to lowered plasma calcium ions and symptoms of nerve and muscle excitability and pins and needles, stiff muscles, etc.
A Personal Perspective - Tilt tests indicate that I don’t have either NMH or POTS. Yet I am convinced that vascular difficulties play a major role in CFS and have devoted a great deal of time learning about them. Why? One reason is that despite my apparently passing the tilt test with flying colors I felt awful during it and it took me several hours to recover from it, while my twin, who does not have CFS, whizzed through the test with no problems at all. While I do not have trouble standing unless I am very tired, activities that cause me to bend up and down quickly leave me feeling exhausted and I had to quit one part-time job because of this problem. I have other symptoms that seem to be tied to the vascular system. Surprisingly I have more problems lying down than standing. When my MCS symptoms were at their peak my midday nap often left me nauseous for hours afterwards. When I first had CFS it was lying down, not standing, that would sometimes provoke hours of forceful heart beating. For these and other reasons, it seems clear to me that the cardiovascular system is in some way implicated in CFS.
WEBSITE QUERY - Shannon Hogonbome Haggenboom (H-something?) ‘Shannon (?) from the East Coast sent me an e-mail a few weeks ago which I’ve lost. Please e-mail me at firstname.lastname@example.org
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