Loren Cordain on Autoimmunity and Nightshades

… experiments in animals confirm that organ specific autoimmune diseases can be caused by injecting a self-antigen with a powerful adjuvant such as Freund’s [33, 34]. Neither the adjuvant alone nor the self-antigen typically results in autoimmunity in animals [33-35].
…

33. Fairweather D, Kaya Z, Shellam GR, Lawson CM, Rose NR. From infection to autoimmunity. J Autoimmun. 2001 May;16(3):175-86.

34. Fairweather D, Frisancho-Kiss S, Rose NR. Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis. Rev Med Virol. 2005 Jan-Feb;15(1):17-27.

35. Fairweather D, Rose NR. Women and autoimmune disease. Emerg Infect Dis 2004;10:2005-2011.

Charles Darwin

He consulted with more than 20 doctors, but, with the medical science of the time, the cause remained undiagnosed. He tried all available treatments, but, at best, they had only temporary success.

Sounds familiar? I'm afraid the medical science of today isn't so much further, with regards to ME/CFS, and probably other diseases as well...

"The loss of the vaccine would be devastating. But we need to clean it up as soon as possible."

A majority of an advisory committee for the US Food and Drug Administration (FDA) today voiced support for the continued use of a contaminated rotavirus vaccine now under FDA suspension, arguing that the vaccine's benefits far outweigh the theoretical risks of the contaminant.

However, members of the Vaccines and Related Biological Products Advisory Committee also recommended studies of possible long-term risks of the vaccine in question, GlaxoSmithKline's Rotarix.

"On the whole, the vaccine seems to have a spectacular record for safety and efficacy," said committee member John Coffin, PhD, professor of molecular biology and microbiology at Tufts University in Boston, Massachusetts. "The loss of the vaccine would be devastating. But we need to clean it up as soon as possible."

"The benefits are so big the risks would have to be enormous to outweigh them," added Harry Greenberg, MD, senior associate dean for research at Stanford University School of Medicine in California. "So far, we see only theoretical risks."

John Coffin says reasonable things. I think I have to apologize to him.

But I have to disagree with Harry Greenberg: Just because you see only theoretical risks, doesn't mean that aren't actual risks. Yes, the benefits far outweigh the risks, but that is no reason to puh-puh the risks.

A wild guess

So, if we assume that an Enterovirus causes ME/CFS (and Gulf War Illness) and I had to take a wild guess which one, I would pick Echovirus 30 and Echovirus 11.

Data from: Enterovirus Surveillance --- United States, 1970--2005 (cdc.gov)

You can see one wave/peak in the early 1980ties ("Osler's Web"), and one more after 1990 (Gulf War). Two different viruses could explain two different illness presentations (e.g. with/without POTS).

But this is just a wild guess...

Polio Vaccine

There are two types of polio vaccine, both of which were developed in the 1950s. The first, developed by Jonas Salk, is a formalin-killed preparation of normal wild type polio virus. This is grown in monkey kidney cells and the vaccine is given by injection. It elicits good humoral (IgG) immunity and prevents transport of the virus to the neurons where it would otherwise cause paralytic polio. This vaccine is the only one used in some Scandinavian countries where it completely wiped out the disease.

A second vaccine was developed by Albert Sabin. This is a live attenuated vaccine that was produced empirically by serial passage of the virus in cell culture. This resulted in the selection of a mutated virus that grew well in culture and, indeed, in the human gut where the wild type virus grows. It cannot, however, migrate to the neurones. It replicates a normal infection since the virus actually grows in the vaccinee and it elicits both humoral and cell-mediated immunity. It is given orally, a route that is taken by the virus in a normal infection since the virus is passed from human to human by the oral-fecal route. This became the preferred vaccine in the United States, United Kingdom and many other countries because of it ease of administration (often on a sugar lump), the fact that the vaccine virus replicates in the gut and only one administration is needed to get good immunity (though repeated administration was usually used). In addition, the immunity that results from the Sabin vaccine lasts much longer that that by the Salk vaccine, making fewer boosters necessary. Since it elicits mucosal immunity (IgA) in the gut, the Sabin vaccine has the potential to wipe out wild type virus whereas the Salk vaccine only stops the wild type virus getting to the neurons.

The attenuated Sabin vaccine, however, came with a problem: back mutation. This may result from recombination between wild type virus and the vaccine strain. Virulent virus is frequently isolated from recipients of the Sabin vaccine. The residual cases in countries that use the attenuated live virus vaccine (about 8 per year in the US until recently) resulted from mutation of the vaccine strain to virulence. About half of these cases were in vaccinees and half in contacts of vaccinees. Paralytic polio arises in 1 in 100 cases of infection by wild type virus and 1 in 4 million vaccinations as a result of back reversion of the vaccine to virulence. This was deemed acceptable as the use of the attenuated virus means that the vaccine strain of the virus still replicates in the body and gives gut immunity via IgA.

The vaccinee who has received killed Salk vaccine still allows wild type virus to replicate in his/her gastro-intestinal tract, since the major immune response to the injected killed vaccine is circulatory IgG. As noted above, this vaccine is protective against paralytic polio since, although the wild type virus can still replicate in the vaccinee's gut, it cannot move to the nervous system where the symptoms of polio are manifested.

By the way, today Polio vaccines have been further improved – and Polio hopefully eradicated soon.

Post-Polio Syndrome and Tinitus

Do you have [post-polio syndrome and] tinitus or roaring sounds in your ears?

26.5% - No.

21.3% - Yes, all the time.

27.7% - Yes, often.

10.4% - Yes, sometimes.

13.8% - Yes, rarely.

Low carbohydrate diets slow tumor growth and prevent cancer initiation

Low carbohydrate diets slow tumor growth and prevent cancer initiation

(via)

Vitamin D Supplementing Gotchas

Is there a evolutionary adaptation to lower UV radiation at northern latitudes?  Gerdes has hypothesized that apo E4 allele carriers have less of a need for UV radiation derived vitamin D due to internal adaptations to preserving vitamin blood levels and maximizing intestinal absorption from dietary sources.
…
For those supplementing vitamin D exogenously, care and caution for adverse effects should be monitored. Sunlight derived vitamin D can be shut off -- we have enzymes and systems that control blood/cellular levels, however for supplementation just as taking a birth control or exogenous hormone medication, what goes in, stays in. Previously I listed contraindications for vitamin d supplementation ((a) hypomagnesemia -- get mag up before supplementation because vitamin D will lower serum Mag; (b) sarcoidosis or other condition associated with elevated 25OHD or 1,25OHD3). Now I would add those with E4 should like monitor closely and avoid supratherapeutic levels which probably need to be addressed on an individual basis. With E4 there may be suggestions that intracellular 1,25OHD3 may be higher and this would not necessarily be reflected in serum levels (just like Mag levels are not, intracellular $$$$$ tests are required to accurately assess). Supratherapeutic needs to be individually defined... 

Translation and protein processing by picornavirus

Translation and protein processing by picornavirus

The picornavirus RNA binds to ribosomes and makes a single polypeptide, therefore the virus has just one gene. This polyprotein has regions that have proteolytic activity (they are cysteine proteases) that cleave the polyprotein to three precursor proteins (P1, P2, P3). P1 is cleaved to a VP0, VP1 and Vp3 plus a leader peptide of unknown function. VP0 gives rise to VP2 and VP4. P2 and P3 do not give rise to viral structural proteins. One of the proteins that comes from P3 is the VPG that is found at the 5' end of the viral RNA while other proteins from this precursor are the viral replicase and enzymes that modify the behavior of the host cell. P2 is also cleaved to give other cell-modifying proteins. Details of some of the cleavages are still vague.

Once the various viral proteins have been made in the infected cell, the replicase (also call a transcriptase or protein 3Dpol) copies the viral plus sense RNA to negative sense RNA. Other viral proteins are also involved in this process. As new positive strand RNAs are made, they can also be translated into more viral protein. There may be as many as half a million copies of viral RNA per cell. Some of the proteolytic events outlined above take place as the nucleocapsid is assembled. This is especially the case with the VP0 cleavage to VP2 and VP4. P1 protein is the precursor that gives rise to the four structural proteins of the nucleocapsid. Five copies of P1 first associate. Endoproteolysis then occurs to form VP0, VP1 and VP3. Twelve of these pentamers than associate to form an empty capsid (procapsid). The viral RNA now associates with the capsid and at the same time, VP0 is cleaved. Release is by lysis of the host cell.

At the same time as viral protein synthesis is occurring, host cell protein synthesis is shut off. The host cell mRNAs however remain fully functional when assayed in an experimental system, so selective degradation of cell mRNAs is not the reason for protein synthesis inhibition. One way host cell protein synthesis occurs is via the cleavage of initiation factor eIF-4, one of the cap binding proteins of the host cell's ribosomes so that cellular mRNAs cannot bind to the ribosomes. Association with cap-binding proteins is a prerequisite for the translation of most cellular RNAs. Thus, only uncapped messages such as that of the picornavirus are translated. Note that most viruses express capped RNAs similar to normal mRNA and so this mechanism of shutting down host protein synthesis is not available to them. The viral proteins also change the permeability of the host cell, altering the ionic composition of the cell and inhibiting cell mRNA association with ribosomes. Moreover, the large number of copies of viral RNA simply out-compete the cell's mRNAs.

Picornavirus causes MS in mouse model

Multiple sclerosis is an autoimmune disease; the body produces antibodies that attack and eventually destroy parts of the myelin sheath covering our nerves. The cause of MS, like HUS 40 years ago, is unknown, though it's thought to be a combination of genetics and environmental influences. Going through the literature, it seems like almost everything has been implicated as playing a causal role at one point or another: pesticides, environmental mercury, hormones, various other "toxins," and a whole host of microbes, including Chlamydia pneumoniae, measles, mumps, Epstein-Barr virus, varicella zoster (chickenpox), herpes simplex viruses, other herpes families viruses (HHV-6 and HHV-8), even canine distemper virus. They've done this looking at both microbe culture (from blood, brain tissue, CNS, etc.) as well as using serology and DNA/RNA amplification in various body sites. None have shown any strong, repeatable links to the development of MS--much like the spurious associations that were seen with adenovirus and HUS.

Although no microbial agent has been convincingly implicated to date, there are tantalizing hints that MS is caused by an infectious agent. There have been "outbreaks" of MS; the most famous occurred in the Faroe Islands in the 1940s. Studies of migrants show that the risks of developing MS seem to be tied to exposures in childhood, suggesting a possible exposure to an infectious agent as a kid. And one of the most common mouse models used to study MS has the disease induced by infection with a virus called Theiler's murine encephalitis virus (TMEV). If it can happen in mice, why not humans?

What I find interesting is that TMEV is from the picornavirus family, the same family to which enteroviruses belong. So if an picornavirus can cause MS (albeit in a mouse model of the disease), I think it is possible that enteroviruses could cause ME/CFS. After all, ME/CFS has been called at times "atypical MS" and some suspected outbreaks of MS (like Punta Gorda in Florida) might have been ME/CFS outbreaks.

It took 30 years to find out what causes hemolytic uremic syndrome

As I've laid out this week, the realization that a fairly simple, toxin-carrying bacterium could cause a "complex" and mysterious disease like hemolytic uremic syndrome came only with 30 years' of scientific investigation and many false starts and misleading results. Like many of these investigations, the true cause was found due to a combination of hard work, novel ways of thinking, and simple serendipity--being able to connect the dots in a framework where the dots didn't necessarily line up as expected, and removing extraneous dots as necessary. It's not an easy task, particularly when we've had mostly culture-based methods to rely on since the dawn of microbiology. (via)

Leukemia caused by an infection?

Both Kinlen’s ‘population-mixing’ hypothesis and Greaves ‘delayed infection’ hypothesis summarize the considerable evidence that childhood leukemia may be the consequence of an abnormal response to a common or uncommon infection(s).

From:
Unusual space-time patterning of the Fallon, Nevada leukemia cluster: Evidence of an infectious etiology (via)

ME/CFS Differential Diagnosis Gotchas: Lyme

I was dx'd with ME/CFS for 17 years before finding out I had Lyme, Bartonella and Babesia last November. Since being on treatment for the last 7 months, my life is returning. I am getting my life back after 17 years. My passion now is to ask all of my ME/CFS friends to consider getting retested for Lyme Disease. Even if you had tests and they were negative (mine was three times from 1993-2004), and/or even if you cannot recall being bit by a tick, or think you cant have it because you don't live in a "Lyme" state. Lyme tick distribution in the US is growing past the old borders on the east coast. And there is evidence that Lyme can be gotten in other ways (See the page "First things first..." question #1 on the web site)

The standard (CDC's of course) test given (the ELISA test) to test for Lyme is 50-59% wrong Always. You need to get a western blot test at a reputable Lyme lab to accurately test you.

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It's critical for you to get a Western Blot Lyme Disease and it's Co-infections test. This is performed by many labs, but some of the labs have different standards of interpreting the tests. In order to get the most accurate results, there are reputable Lyme labs you should consider getting tested from. IGeneX, Fry labs and a few more are listed on this blogs Good Lyme Lab Page:

Good Lyme Labs 

Are whole grains healthy?

Studies show that whole-grains are healthier than refined flour. But are whole grains healthy? Or is refined flour simply unhealthier? And are there studies that show that grains are actually unhealthy?

I'll keep saying it until someone listens, but ingestion isn't the same as absorption.  Simply stating that whole grains are rich in anything, be that antioxidants or otherwise, simply fails to account for the fact that whole grains are also rich in plenty of substances that make their nutrient composition all but unavailable for absorption.  My suspicion, as far as reduced oxidative stress goes, is that a refined carbohydrate intake induces a high degree of oxidative stress, and by comparison, whole grains do not - mistakenly interpreted/marketed as whole grains being high in antioxidants.
…
The authors set the study up by highlighting the evidence 'supporting' the use of whole grains for diabetes prevention. What the authors fail to disclose is the fact that this 'evidence base' invariably reads something like "compared to eating a really crap refined flour and sugar diet, eating less crappy whole grains gives you less diabetes, more slowly".
…
It becomes clear, after reading through the paper, that the whole grains looked their most positive at about two months into the experiment, as there is constant reference to how much better all the parameters measured looked at this time point. Unfortunately for the researchers, all of the whole grains groups sucked as equally as each other and the craptastic sugar/casein/sunflower oil diet, by the five month mark.
…
The authors try to paint a picture of whole grains with high antioxidant capacities being better than those with low capacities. In reality, it translates to one type of grain being not quite as bad as another. That is, they all increase oxidative stress compared to sugar, but some not quite as bad as others.
…
Again, the authors look for the positive by pointing to the grains with the higher antioxidant levels not being as bad compared to those grains with a lower antioxidant capacity. To me, this is too much like suggesting that those that were seated at the rear of the Titanic were better off than those at the front.

Historic ME/CFS Outbreaks: Los Angeles 1934

Names used:
Atypical Poliomyelitis (Gilliam, 1938)
Epidemic Neuromyasthenia (Ramsay)

Location and Date:
Los Angeles County General Hospital, 1934

Described by:
Alexander Gordon Gilliam (1938) – Epidemiological study of an epidemic, diagnosed as poliomyelitis, occurring among the personnel of the Los Angeles county general hospital during the summer of 1934

Symptoms:
First considered as poliomyelitis (polio).

Initial symptoms similar to polio, but some features differed from polio:

• Localized muscle weakness in 80% of cases, yet no muscle wasting (unlike polio)
• No evidence of damage to the lower motor neuron
• Sensory symptoms (persisting far longer than in polio)
• Muscle pain, tenderness (persisting far longer than in polio)
• Fatigue on walking short distances
• Lapses of memory
• Loss of concentration
• Sleep disturbances
• Emotional lability (with "hysterical episodes")
• Reoccurrence of both systemic and neurological symptoms, some cases more disabled by recurrence than by original illness
• No mortality, but high morbidity (55% of staff off duty six month after peak of peidemic)
• Vaso-moto and trophic disturbances
• Excessive sweating or abnormal dryness of the skin of the extremities
• Coldness and cyanosis
• In more severe cases exfoliation of the skin
• Hypertrichosis and brittleness of the nails, with retardation or acceleration of growth

The outbreak in the Royal Free Hospital in London in 1955 was an almost exact replica of this outbreak according to A. Melvin Ramsay.

Source:

A. Melvin Ramsay – "Myalgic Encephalomyelitis – The saga of the Royal Free disease", page 12

.

Other historic synonyms.

Relation: Infection with Polio to Post-Polio Syndrome

Outcomes of poliovirus infection

Outcome	Proportion of cases
Asymptomatic	90–95%
Minor illness	4–8%
Non-paralytic aseptic meningitis	1–2%
Paralytic poliomyelitis	0.1–0.5%
— Spinal polio	79% of paralytic cases
— Bulbospinal polio	19% of paralytic cases
— Bulbar polio	2% of paralytic cases

.

Progress to post-polio syndrome

Initial polio symptoms	Progress to post-polio later in life
Asymptomatic	?
Minor illness	?
Non-paralytic aseptic meningitis	14% to 42%
Paralytic poliomyelitis	25% to 50%

12 year polio incubation in immune-compromised patient

Analysis of poliovirus recovered from the stool of a patient with fatal poliomyelitis revealed that she had been infected with the virus 12 years earlier, probably when one of her children received the oral poliovirus vaccine. This case has the longest known incubation period for vaccine-derived poliomyelitis, and highlights our still rudimentary understanding of how poliovirus causes disease.
…
This case emphasizes the need to continue research on poliovirus. Our knowledge of how the virus causes disease is still rudimentary – as is evident by our failure to understand the 12 year incubation period of the case described here. Although the polio eradication campaign has had excellent results, it can be compromised by vaccine-associated disease. Individuals with B lymphocyte deficiencies will be a reservoir for the virus and can lead to infections if immunization levels drop. It would be highly beneficial to identify all individuals with chronic poliovirus infections, and treat them with antivirals. Unfortunately, such compounds do not exist – underscoring the need to continue research to identify drugs that can be used to treat poliovirus infection.

Post-Polio Syndrome

Post-polio syndrome (PPS, or post-poliomyelitis syndrome or post-polio sequelae) is a condition that affects approximately 25–50% of people who have previously contracted poliomyelitis—a viral infection of the nervous system—after the initial infection. Typically the symptoms appear 15–30 years after recovery from the original paralytic attack, at an age of 35 to 60. Symptoms include acute or increased muscular weakness, pain in the muscles, and fatigue. The same symptoms may also occur years after a nonparalytic polio (NPP) infection. The precise mechanism that causes PPS is unknown. It shares many features with the post-viral chronic fatigue syndrome, but unlike that disorder it tends to be progressive, and as such can cause a tangible loss of muscle strength. Treatment is primarily limited to adequate rest, conservation of available energy, and supportive measures, such as leg braces and energy-saving devices such as powered wheelchairs, analgesia (pain relief) and sleep aids.

Increased activity during intervening healthy years between the original infection and onset of PPS can amplify the symptoms. Thus, contracting poliomyelitis at a young age can result in particularly disabling PPS symptoms.

Numerous theories have been proposed to explain post-polio syndrome. Despite this, there are currently no absolutely defined causes of PPS.

Diagnosis of post-polio syndrome can be difficult, since the symptoms are hard to separate from complications due to the original poliomyelitis infection, and from the normal infirmities of aging. There is no laboratory test for post-polio syndrome, nor are there any other specific diagnostic criteria. … In general, PPS is a diagnosis of exclusion whereby other possible causes of the symptoms are eliminated.

Sounds like CFS to me! I wonder what happens if you have post-polio and fall into the hands of the psychobabblers: CBT/GET for you! After all, without a definite cause, it must be psychosomatic (sorry for my sarcasm).

But there is some training that should and can be done:

Muscle training at aerobic levels without maximum exercise is useful to maintain muscular function and ameliorate fatigue13 and muscular training in warm water seems to be particularly useful. … Inactivity increases the risk of obesity, diabetes, cardiovascular, and muskuloskeletal problems and so polio patients who take part in physical activity have significantly less symptoms than physically inactive patients. All polio patients with or without post-polio syndrome should therefore be advised to take part in physical activity, but they should not be performing static muscular training at maximum effort (anaerobic level) and they should allow intermittent breaks.

Elisabeth Farbu: Post-Polio Syndrome – Diagnosis and Management

No anaerobic training – same as in ME/CFS.

By the way:

Factors that increase the risk of polio infection or affect the severity of the disease include immune deficiency, malnutrition, tonsillectomy, physical activity immediately following the onset of paralysis, skeletal muscle injury due to injection of vaccines or therapeutic agents, and pregnancy.

And:

The molecular mechanisms by which poliovirus causes paralytic disease are poorly understood. Early symptoms of paralytic polio include high fever, headache, stiffness in the back and neck, asymmetrical weakness of various muscles, sensitivity to touch, difficulty swallowing, muscle pain, loss of superficial and deep reflexes, paresthesia (pins and needles), irritability, constipation, or difficulty urinating.

Subclinical celiac disease and gluten sensitivity

Jamie Scott has some interesting things about subclinical celiac disease and gluten sensitivity:

Treat the symptoms - not the test.  If you suspect any issue with gluten anywhere on the spectrum of possibility, take it out for a period of time and see how you feel.  I really see little point in someone feeling better being gluten free but being given the green light to eat the stuff because they threw a negative tTg test...  And parts of this review also call into question the common instruction given by doctors and dietitians to not exclude gluten from the diet as this makes it harder to diagnose via biopsy.

Make sure to read the study extracts he posted.

And related to this: Is a gluten free diet the sport person’s secret weapon?

Enterovirus diagnostic gotchas

In der Serodiagnostik wird der Neutralisationstest (NT) als sensitivste und zugleich spezifischste der konventionellen Methoden für den Ak-Nachweis gegen die verschiedenen Enterovirusgruppen angesehen. Es können die aktuell zirkulierenden Subtypen B3, B4, B5 (selten B1, B2) und Echovirus 30 (selten Echovirus 7, Echovirus 11) untersucht werden
…
Der Enzymimmunoassay (EIA) mit der getrennten Darstellung von IgM und IgG hat sich in der Routinediagnostik [von Enteroviren] aus verschiedenen Gründen nicht durchsetzen können. Als solcher ist insbesondere die hohe Kreuzreaktivität zu nennen. Ein weiteres Problem stellen falsch positive Befunde bei Vorhandensein von heterophilen Antikörpern (z.B. bei EBV, Mykoplasmen) dar.

In English: Enzymimmunoassay (EIA) test for the IgM and IgG enterovirus (coxsackie, echovirus) antibody can lead to false positive results (crossreactivity e.g. with EBV or mycoplasma heterophile antibodies). A more specific test is a neutralizing test.

Sinusitis associated with fatigue and pain

I found some older studies (warning: they try to push endoscopic sinus surgery), but they are interesting nevertheless:

ScienceDaily (Aug. 14, 2003) — Washington, D.C. – A new study published in the August 11 issue of the Archives of Internal Medicine demonstrates a possible link between unexplained chronic fatigue and sinusitis, two conditions previously not associated with each other. Also newly noted was a relationship between sinusitis and unexplained body pain.
…
Through his private internal medicine practice, Chester questioned 297 patients, noting unexplained chronic fatigue in 22%, unexplained chronic pain in 11%, and both in 9%. While these numbers are consistent with previous studies, Chester observed an unusual connection between patients with chronic pain or fatigue: prevalent sinus symptoms. Sinus symptoms were nine times more common on average in patients with unexplained chronic fatigue than the control group, and six times more common in patients with unexplained chronic pain. In addition, sinus symptoms were more common in patients with unexplained fatigue than in patients with fatigue explained by a mental or physical illness, suggesting the syndrome of unexplained fatigue is more closely associated with sinusitis than are other types of fatigue.
…
15 out of the 65 patients in Chester's study met criteria for chronic fatigue syndrome (CFS), a severe form of unexplained chronic fatigue associated with body pains and other symptoms. Most CFS patients had sinus symptoms and many noted a sudden onset of their illness, similar to people with sinusitis. "We clearly need to do more research to see if sinus treatments alleviate fatigue and pain. This study does, however, offer hope for possible help in the future." said Chester.

ScienceDaily (Sep. 23, 2008) — A new analysis led by researchers at Georgetown University Medical Center suggests many patients with sinusitis have aches and pains similar in severity to people in their 80s and those with arthritis or depression. …  "We found that the daily experience of bodily pain was much more common in patients with sinusitis than in the overall population," explains Chester. "Confirmation that aches and pains occur with sinus disease is a relief to many patients who thought they had two separate illnesses."

So what did the meta analysis find?

A subgroup analysis of 11 studies measuring outcomes using the 36-Item Short Form Health Survey (SF-36) demonstrated a moderate-sized combined effect of 0.47 (95% confidence interval, 0.38-0.56; I = 0%), corresponding to a mean +/- standard deviation improvement of 9.7 +/- 3.4 units on the SF-36 vitality domain scores.

A improvement of 10 points on the SF-36 score isn't bad, but it is not a cure to ME/CFS...

"Nothing left over"

Nothing left over: Able to carry out the work, but nothing left.
Barely able to get up in the morning, missing a lot work, feels terrible every day, tired

Lucinda Bateman about a ME/CFS patient

ME/CFS Study: EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients - A case control study

You have to hand it to Anthony Komaroff, he makes sure that his work is solid (even if that means moving the research ahead a bit slower...). Not only did he enroll 70 patients with ME/CFS (which already is a lot) and 24 patients with major depression, but furthermore he enrolled 148 (!) patients with "general fatigue" (not evaluated whether they meet CDC/Fukuda) and 390 (!) healthy controls.

EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients - A case control study
Abstract (provisional)

Frank Duffy, Gloria McAnulty, Michelle McCreary, George Cuchural and Anthony Komaroff

Background
Previous studies suggest central nervous system involvement in chronic fatigue syndrome (CFS), yet there are no established diagnostic criteria. CFS may be difficult to differentiate from clinical depression. The study's objective was to determine if spectral coherence, a computational derivative of spectral analysis of the electroencephalogram (EEG), could distinguish patients with CFS from healthy control subjects and not erroneously classify depressed patients as having CFS.

Methods
This is a study, conducted in an academic medical center electroencephalography laboratory, of 632 subjects: 390 healthy normal controls, 70 patients with carefully defined CFS, 24 with major depression, and 148 with general fatigue. Aside from fatigue, all patients were medically healthy by history and examination. EEGs were obtained and spectral coherences calculated after extensive artifact removal. Principal Components Analysis identified coherence factors and corresponding factor loading patterns. Discriminant analysis determined whether spectral coherence factors could reliably discriminate CFS patients from healthy control subjects without misclassifying depression as CFS.

Results
Analysis of EEG coherence data from a large sample (n=632) of patients and healthy controls identified 40 factors explaining 55.6% total variance. Factors showed highly significant group differentiation (p<.0004) identifying 89.5% of unmedicated female CFS patients and 92.4% of healthy female controls. Recursive jackknifing showed predictions were stable. A conservative 10-factor discriminant function model was subsequently applied, and also showed highly significant group discrimination (p<.001), accurately classifying 88.9% unmedicated males with CFS, and 82.4% unmedicated male healthy controls. No patient with depression was classified as having CFS. The model was less accurate (73.9%) in identifying CFS patients taking psychoactive medications. Factors involving the temporal lobes were of primary importance.

Conclusions
EEG spectral coherence analysis identified unmedicated patients with CFS and healthy control subjects without misclassifying depressed patients as CFS, providing evidence that CFS patients demonstrate brain physiology that is not observed in healthy normals or patients with major depression. Studies of new CFS patients and comparison groups are required to determine the possible clinical utility of this test. The results concur with other studies finding neurological abnormalities in CFS, and implicate temporal lobe involvement in CFS pathophysiology.

Over at ME/CFS forums, Forbin has made this observation:

For part of the study, they also recruited patients who complained of prolonged, unexplained fatigue (with other conditions ruled out) but who had never been worked up for CFS. About 45% of those people had results consistent with the CFS group. The paper suggests that this is broadly consistent with a previously published estimate that 35% of such a group might be expected to be classified with CFS. They speculate that “the less than 100% accuracy of our spectral coherence based classification function could reflect a deficiency in the CDC criteria for CFS...”

So it seems to me that at least a one third of "significantly fatigued patients (where no underlying diagnosis can be securely established)" (sfP) suffer from "genuine" ME/CFS – and up to two third of sfP might have something different (or might be patients with ME/CFS who are less symptomatic).

90% of patients with CDC-CFS (diagnosed by Komaroff?) have abnormal EEG. So in the right hands (and with a large enough cohort) the CDC criteria aren't so bad for research (up to 10% false positive and no false negatives), but might be better suited for clinical diagnoses than research.


From what I have read so far, I have a feeling the CCC might reject some patients with "genuine" ME/CFS (and not include false positives) and so might be better for research, especially when in the hands of less experienced researchers... It would be nice if they would do something like this: "xx% of our CFS-subjects qualified for both CDC and CCC. Hindsight analysis showed that CCC improved specificity to yy%, but decreased sensitivity to zz%. ..."