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.
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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
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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.
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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.
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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%. ..."