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Your Brain on Viruses: Study Finds Even Common Viruses Cause Cognitive Declines

The ‘Manhattan Project’

The Northern Manhattan Study is an immense project that’s taking a deep look at health in Northern Manhattan, New York . The project consists of  analyzing basic health characteristics of several  thousand people over time and it’s spinning out studies at a dizzying rate.  The project is not on chronic fatigue syndrome, but because it’s  looking at factors that have shown up in ME/CFS it may shed  some  light on what’s happening there.  In fact it may shed a lot of light.


The ‘Manhattan Project’ is examining health issues in a wide swath of the population. Several findings may have relevance to ME/CFS/FM

For instance, each of the studies below looked at a factor that’s been found (in at least some studies) in ME/CFS and  each of the findings seemed to make sense what we know of ME/CFS.

Increased IL-6 levels were associated with cognitive declines in one study, and increased  soluble tumour necrosis factor receptor 1 (sTNFR1) levels were associated with increased  mortality in another.  Increased levels of daytime sleepiness in the elderly were associated with increased risk of stroke, heart attack and vascular events in another.   Metabolic syndrome was associated with cognitive declines in another. Eating a Mediterranean diet was associated with  reduced ‘white matter hyperintensity volume’ a marker of small blood vessel breakage in the brain and reduced vascular events such as stroke.

Infectious Burden

Neurology. 2013 Mar 26;80(13):1209-15. doi: 10.1212/WNL.0b013e3182896e79.Infectious burden and cognitive function: The Northern Manhattan Study. Katan MMoon YPPaik MCSacco RLWright CBElkind MS.

The most applicable study to ME/CFS, however, is clearly the latest one which determined if infectious disease burden was associated with cognitive declines.  In this study the researchers tested  blood from a broad swath of the population in New York  for antibodies to common bacteria and viruses (three of them herpes viruses) and gave the participants  cognitive tests.  Then they created an index of infectious burden (IB) and determined if more infections meant more problems with cognition…and found they did; the more active infections present, the  worse the cognitive impairment.


This study suggested that having more infections, active or latent, are associated with reduced cognition.

No ME/CFS studies have attempted to associate pathogen load with cognitive declines but given the increased  rate of infections Dr. Peterson and other immunologically oriented ME/CFS  doctors have found and the documented cognitive impairment in ME/CFS, the finding made sense. Cognitive impairment is  associated with brain issues but the researchers didn’t zero in on the brain; instead they focused on cardiovascular problems which interfered with blood flows to the brain.

It turns out that studies have linked common infectious agents to inflammation, coronary artery disease and stroke and a past ‘Manhattan project’ study found  that high infectious burdens  were associated with an increased risk of stroke and increased carotid plaque buildup.

Many viral pathogens in the herpesviridae family, characterized by latent or persistent infection, were implicated in increased stroke risk.

It appears that chronic infections often play havoc with cardiovascular functioning. Infectious organisms can impact cardiovascular functioning in various ways. They can directly invade the vascular walls. C. pneumoniae and H. pylori DNA was found in aetherosclerotic lesions in 26%  and 37% of cardiac bypass patients in one study.  With regards to pathogens commonly found in ME/CFS, high rates of active HHV6 infection  found in Italian cardiac patients who did not have aetherosclerosis suggested the virus may play a role in heart patients who have idiopathic heart disease.

Cardiovascular Issues

At the 2008 HHV6 Symposium in Baltimore, a German researcher, Dr. Lassner reported that heart biopsies he’d done in German heart patients commonly revealed parvovirus B-19, HHV-6, enterovirus and/or Epstein-Barr Virus infections.  He noted that HHV-6 infection of the blood vessel walls results in the production pro-inflammatory cytokines which can constrict the blood vessels, impair capillary production and reduce heart blood flows. HHV6’s ability to trigger blood vessel wall constriction is intriguing given studies suggesting it may play a key role in ME/CFS.

Blood vessels

Pathogens can affect the cardiovascular system and cardiovascular problems appear to be rife in ME/CFS.

Lassner, interestingly, found antivirals (IVIG-parvovirus, interferon-enterovirus) to be effective in virus infected heart patients, but reported much the same treatment response  pattern found in many ME/CFS patients; improvement while on antivirals followed by relapse when off them.

Infections can also turn on the macrophages which help create the dangerous plaques, they can confuse the immune system into attacking parts of the body and they can help an inflammatory state that is damaging, etc.

These observations, along with the results of this current study lend support to the notion that past or chronic exposure to common infections, perhaps by exacerbating inflammation, may be an important etiologic factor of atherosclerosis.

Simply the presence of active herpesvirus or other infections  can contribute to an inflammatory mileu that can be detrimental.  Katan reported that an inflammatory state could lead to aetherosclerosis, ‘subclinical stroke’ and dementia. Subclinical strokes (ie transient ischemic attacks from which patients recover) primarily effect executive functioning, one of the cognitive processes known to be impaired in ME/CFS.  Changes in mood and  the ability to organize and take on multiple tasks could be a sign of a ‘subclinical stroke‘.  Other symptoms can include feelings of numbness or weakness, double vision, dizziness/vertigo, confusion, inability to speak, loss of balance or coordination.

Cardiovascular issues have been found in ME/CFS and more and more attention is being given to this area. Cardiovascular control is impaired,  reduced cardiac vagal tone is associated with cognitive declines, impaired blood pressure variability,  reduced cerebral blood flows, reductions in stroke volume and cardiac output (all this in the past year and a half)  provide ample evidence of impaired cardiovascular functioning in this disorder.  Interestingly autonomic nervous system issues similar to those found in ME/CFS were correlated with cognitive declines in fibromyalgia.

All in all the finding of decreased cognitive functioning with increased infectious burden in the  Northern Manhattan Study findings may not be surprising for many people with ME/CFS. At the most recent HHV6 Conference in Paris Dr. Peterson reported on several ME/CFS patients who’s cognitive abilities rebounded remarkably following Vistide infusions for herpesvirus infections and Dr. Lerner has reported similar results in his herpesvirus infected patients.


The latest Manhattan project study should be helpful in highlighting not only the cognitive declines but the cardiovascular risks that are associated with common or  chronic latent or active infections. Since active infections are part and parcel of ME/CFS, this study’s important association of decreased cognitive function with increased infectious burden suggests that measuring both those factors in ME/CFS should be routine, and may offer objective measurements of treatment efficacy.

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  • Anna wood

    April 22, 2013 at 5:35 pm - Reply

    A fab article. Thanks. I have always seemed to suffer comparitavely more from cognitive rather than physicadisfunction both when mildly affected and working and now as a severly affected sufferer. So many studies seem to focus on the physical affects it is nice to see attention being given to cognitive problems

  • Richard P

    April 22, 2013 at 6:18 pm - Reply

    If a CFS patient is found to have an HHV6 issue, what are chances he will recieve Vistide? Nil?

    • Cort Johnson

      April 22, 2013 at 6:34 pm - Reply

      My guess is that would really depend on your Doctors willingness to use that drug. Not all doctors test for HHV6 and those that do might or might not be willing to go through the transfusion process. My guess is that many doctors that do test for pathogens would try other drugs first.

  • HTree

    April 22, 2013 at 7:44 pm - Reply

    Hi Cort,
    Thanks for the write-up. Do we know how other antivirals compare with Vistide in terms of effectiveness in treating herpesviruses (latent/ intracellular reactivated)? Compared to oral Famvir, or oral Valcyte for example — For HHV-6, and EBV? Thanks!

    • Cort Johnson

      April 22, 2013 at 7:57 pm - Reply

      I don’t know. I know Vistide tests out well in effectiveness generally and my guess is that it would be used more if its wasn’t for the need for infusions and the blood tests but I really don’t know how it compares to the others. Maybe someone else has an idea.

      I would say that Dr. Peterson’s results were pretty darn good for this disorder, and, of course, we need placebo controlled, double-blinded studies to really validate them. I’m not worried about the placebo effect; my laymen’s guess is that most of his patients have been around, have tried many different treatments and they’re not the type of patients who are all of sudden going to have a strong placebo effect.

  • Deborah Waroff

    April 23, 2013 at 5:47 am - Reply

    Cort, doctors who have used Vistide with Aids patients remaln always nervous. They say it can knock down a kidney one, two three, with no advance warning. It is something used with much cautiousness and some fear. I admire Peterson greatly for going ahead despite the worries, as Chimerix approach to getting the supposedly benign version, CMX001 to patients has been tomorrow and tomorrow and tomorrow. Peterson was supposed to get some for testing three years ago but it never materialized. I was supposed to join a Mt. Sinai run group that disappeared into the fog.This drug was developed under a $35 million government contract to develop a counter terror weapon in case of a bioterror attack using smallpox.Some of our military stategists have been watching too much television.

    • Cort Johnson

      April 23, 2013 at 8:27 am - Reply

      Right and in this case maybe some military paranoia will turn out to be a good thing.

      I imagine Vistide is a pretty much a drug you use after you’ve tried other ones. One past patient of Dr. Peterson on Vistide took daily blood tests at first; Dr. Peterson was watching him closely…

      • Deborah Waroff

        April 23, 2013 at 12:00 pm - Reply

        Well put Cort on “after … other ones”

  • mary c silvey

    April 23, 2013 at 8:05 pm - Reply

    This new medication needs to be ‘fast tracked’ for the patients. Among several others, so damage can be avoided. Cardiac insufficiency is also a result of dysautonomia, which can be diagnosed fairly early. Yet there are still studies that suggest structural changes to the heart as a result of this illness, so physician education must be the highest priority. Just from this blog, there are many asking for the Vistide today. Not indefinitely in the future…

    I understand Deborahs’ frustration in dealing with Mount Sinai, and find it remiss not to have given her a proper explanation and referral to another clinical site and study. Yet, I did not understand the government creating a drug to fight smallpox, when we are all vaccinated for this. Only raises more questions as to the validity of this claim, as in are they really expecting smallpox or retrovirii yet to come? I am not sure if Mount Sinai was one of the facilities given large donations, as there were three in NYC, and then we were told online that they were psychiatric studies. I believe there is a need for psychiatric studies, yet not in an overwhelming sense of this financial proportion. The stress that results from cognitive dysfunction can be deadly, so care of our hearts must be presented often and easily understood. Thanks, Cort.

  • Kelly Latta

    April 29, 2013 at 4:26 pm - Reply

    Cort – There is also research that significantly connects cognitive issues with the immune system. Although not ME and CFS there may be a connection.

  • Cort Johnson

    April 29, 2013 at 5:00 pm - Reply

    Thanks Kelly!

  • Carol Olsen

    April 30, 2013 at 4:09 pm - Reply

    Cort, Thanks so much for the “heads up” on Vistide. It is indeed a medication to be used with great restraint, but was also highly beneficial to me, especially cognitively. At that time, I was told it was especially useful for those who became ill in an outbreak, as I had. It was interesting that no patient panelists mentioned it at the recent FDA conference. I did comment from the floor after the panel spoke. Two doctors who have worked with Vistide and HIV/AIDS believe it should only be used for short periods and extreme caution.
    One of these doctors’ opinions was that CMX 001, the oral form, should also be used very cautiously. There is great potential there, but also risk.

    • Cort Johnson

      April 30, 2013 at 4:25 pm - Reply

      Thanks Carol for your letting us you know your personal experiences with Vistide. I hope CMX will be available ‘soon’ and will more effective and have fewer side effects. Hopefully if its more effective it will be able to be used for a shorter time period.