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Good evening.

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thank you no doubt for

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Thank you Nora, for making possible this's evening's

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hopefully dialogue. Chronic fatigue syndrome

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is arguably one of the most

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controverted, misunderstood, misperceived

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fields in medicine today. Although

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it is clear that the health of millions of people

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has been compromised significantly by this disease,

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still, in medicine, we face situations

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where an extreme, even in our own medical community--

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the diseased is not believed, that it is real.

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Which is a shame. So the one thing, if there is one thing

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of anyone in this audience here today, that I would like to

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have us a point to take home, of your family members, your friends, or yourself,

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is to not kid yourself--this is a real disease.

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And what I would like to do tonight is share with you

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the evolving understanding

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that here at Stanford we have put together. What we tell you today

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may not be true tomorrow, but what we tell you today

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hopefully is better than what we had as a model or as an understanding

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yesterday. And it is evolving. It's changing.

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But we have a simple goal, is--one day,

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one day, have CFS,

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a history of the past, so we do one day be able

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to conquer the disease, and be able to bring relief finally to the many patients

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who are suffering.

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I do not have the time frame for this, but trust me,

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we are working hard in making that time frame

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the shortest possible. Allow me to start the

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presentation with a real case. This is a patient--

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I don't know if she's in the audience or not--but it's a 53-year-old woman

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who came to see us in 2008

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because she had had disabling fatigue

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of treatment. And what they found, if they gave

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the drug or placebo--so they would randomize to drug

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for month-and-a-half, or placebo for month-and-a-half,

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what they found is that there was no difference. But just

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put that in the in the back of your brain. The fact

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that that patient, those patients, got a month-and-a-half

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of antiviral treatment, or acyclovir.

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So the one thing that we changed at Stanford about

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seven years ago, was that we

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brought a new model. And we

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thought if the patients have been here for a long period of time,

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and if it's possible that an infectious agent is behind the symptoms

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at a chronic level, will it be possible that

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if we intervene with the appropriate agent--and finding that appropriate agent

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may be a really

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daunting task--is it possible that then long-term,

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with appropriate anti-microbial interventions, can improve the symptoms

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in subsets of patients, not to repeat the mistakes of the past,

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of treating all the patients as the same homogeneous group.

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And to our surprise, when we took patients and--

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it's beyond the scope of tonight's conversation on how we

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ran into this surgroup--we found that if patients had high levels

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of antibodies against Epstein-Barr virus, the same virus that has been

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clearly tied to the onset of CFS, and another virus

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called Human Herpesvirus-6, if they have high levels against

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those two viruses, it looks like when we gave them

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another drug called Valganciclovir

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for six months in this abscissa. You have

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a year's, so goes all the way to six months, half a year here,

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and in the same abscissa, but for when the patients were starting before therapy,

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you have all the way up to twenty years. So the patient may have been sick for

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eighteen years,

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one year, five years--no matter how long they were sick

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when we gave this drug for six months,

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total surprise to us. They had this remarkable

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improvement in their physical and cognitive

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function. And to our surprise as well,

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the initial reaction to

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them was, they got worse. And then they improved.

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The worsening was a complete surprise to us. And we made a mistake initially

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because we let people believe that for patients to get

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better with this intervention who had these markers in the blood,

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they had to get worse. And that later on

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turns out to be not correct. There are patients who can get better

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without significant worsening, but still we see patients who get worse

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with the initial treatment. Now, we cannot

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be certain that this would have not been done because we perhaps

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validated the patients; we

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listened to them, so that we were doing a placebo effect.

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It's hard to argue that this is placebo when somebody has been sick for

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twenty years,

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or eighty years, they get an intervention for six months, and they suddenly get better.

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But granted, we have to go to what is called a

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randomized, placebo-controlled double-blind

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pilot study, to see if we could give the drug

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to patients when they didn't know they were getting the drug,

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or the sugar pill, and we the physicians

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will not know the same thing. So: double-blind.

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And we were fortunate to have the sponsorship.

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The answer for many of the questions we face

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with chronic fatigue syndrome is doing clinical trials, but those are

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very expensive things to do, enterprises to do,

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and we were lucky that we had the sponsorship from the manufacturer

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of the drug in this case. Like any

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intervention, we do need a team.

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Nothing can happen these days in research without having

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an outstanding team. And what we did is

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randomized the patients to two areas: to either placebo,

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sugar pill, or valacyclovir for six months,

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and then for three months we stayed blind still.

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At nine months, we took the data, put it in

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three CVs, shipped it to three different,

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three different places, so that nobody could touch the data

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after the blind code was broken,

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and then we broke the code and see how the patients did

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on the drug versus the sugar pill.

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This is a graph that shows what happened

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to the patients who are either on the

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placebo in red, or who are on the treatment

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in green. And in this scale,

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going down means you are getting better.

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So the patient who went on the treatment went down,

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meaning they got better, and that

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trend of going down was

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according to this statistical model, it's statistically significantly

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different than those in the placebo, suggesting here

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that the benefit that we have shown before, when we were giving this drug to

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patients,

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is mediated by something that the drug is doing, and not something that they

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are doing

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themselves through placebo. We also assessed

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their cognitive function, meaning we asked the patients

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how they felt in terms of their cognitive performance.

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And they say, I feel 100 percent, which no one will tell us

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when they were sick, or they will say 10 percent or 50 percent and so forth.

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That is very hard to correlate, because it also depends on how

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good their sleep (is) or what other medications they are taking.

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et cetera. So when we looked at

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what happened with their cognitive function--self-reported,

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but remember, under double-blind conditions, not knowing if they were

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getting treatment or placebo--

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the trajectory also for those who went into treatment

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was better that those who were in the placebo.

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Now is one of those things--

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the research--never stops either surprising you or fascinating you.

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The randomization for this study, meaning we allocated the patients

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to either group by pure chance--

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the allocation of the patients to the two groups

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was done by somebody in Geneva, in Europe. So we will see a patient

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and we'll say, "That patient is a candidate for the study."

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We didn't allocate them to one group or the other. We will call Geneva, to a

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group there,

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and they would give us the answer the next day, or whatever time difference it was,

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and they would tell us, "This is the group the patient should go, group X."

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And they would call pharmacy and they would give us the appeals for that

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patient and so forth. Yet, despite that it was

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totally by chance and by pure randomization,

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if you'll notice, here, the baseline

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levels of cognitive function for the treatment group is slightly lower

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than the placebo. We were fortunate that that this was not statistically

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significant, but the patients in the treatment group started with a slight

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disadvantage

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over the placebo. And the same thing actually was for the fatigue.

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Remember that in this scale, I mentioned to you that the higher the worse,

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and again, the patients,

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well in this case, you know, the lower is the better, so the treatment is

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started at the right place.

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And then the other aspect that we did was to see how the cognitive did by

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a questioner. So the previous light was how they did

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with self-reported cognitive function; this is how they do

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with a questioner that assesses their mental capacity,

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and in this case, going down again is improving

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and again the treatment group is slightly worse

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than the starting place for the placebo,

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yet the trajectory of the treatment group

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is statistically significantly better--going down it's better--

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than the placebo group. So in this study we

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offer perhaps what are the first

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evidences that if you intervene with an appropriate drug,

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with a specific biomarker in black like titers

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elevated against those two viruses, it appears that we can make

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a significant difference in these patients' physical

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and cognitive status, independent of placebo.

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We were not just happy with

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just seeing this and not being able to explain it. We wanted to go beyond that.

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And we have noticed that in patients who received the drug,

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these cells, called neutrophils, increase in a statistical manner,

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that is not seen in the patients who get placebo.

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So something is associated with neutrophils that

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maybe, maybe, (is) one potential explanation of why they get better.

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The other cells that change

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are the monocytes, in this case they go down in the patients who get the drug,

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and not in those who get the placebo. At at the same time,

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we took the serum of these patients, and through a

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technology that is available here at Stanford, and in collaboration

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with our colleagues in the immunology department, we were able to measure

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through this technique that is called Luminex technology, where you can

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measure a hundred cytokines, a hundred analytes, in a single well

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of a single patient at the same time, we were able to measure what we call

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cytokines. Cytokines are molecules

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that the immune system uses to talk from one cell

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to the other. And through this technology we were able to show

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that in those patients at baseline that I show you that they were slightly worse

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for the treatment group, we show that the certain cytokines were higher

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in those who were worse, than in those who were better--initially,

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like IL5 and IL17. And more importantly,

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over time, the patients on the treatment,

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on the Valganciclovir, on the drug, have

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elevation in cytokines that were not seen

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as much in the patient in the placebo. Cytokines like

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IL5, IL17, cytokines that attract neutrophils--the same cell

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that I mentioned to you that is elevated. Or cytokines that had to do

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with monocyte communication, the same cell that I mentioned to you

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that it goes down. And the drug was safe

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during the period of administration. And we concluded then

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that if the patients have high levels of these antibodies against

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HHV-6 and DBV, giving them

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Valganciclovir for six months

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appears to correlate with an improvement in cognitive and physical

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that is independent from placebo and we have

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a mechanism, proposed a mechanism

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through immunomodulation, meaning that sometime the drugs work;

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not necessarily through the fact that they are killing the organism,

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but by the fact that they are making the immune system (go) one direction

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that is beneficial to the patient. So...

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But I want to emphasize two things.

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Not all the patients have those blood markers. So not everybody will be

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in theory a candidate for that intervention. And unfortunately, not

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all the patients with the markers necessarily improve.

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so that let us, or has led us,

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at Stanford to identify what we call

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sub-groups of patients with CFS, those who

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meet that profile of the HSV-6, EBV,

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we have found other patients that have what we call the herpes simplex one

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or two sub-group. Patients who

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absolutely tell you that their CFS worsened

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when their oral herpes, the famous

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fever blisters, the oral blisters, or genital herpes,

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that when those exacerbate,

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and manifest in the way of painful lesions, those patients

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actually, their symptoms get much more worse,

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or that their disease began when they have the outbreak, the first outbreak

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with one of those two viruses. So that's what we have called a

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herpes simplex sub-group. We have had some Brucella

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patients, others with Q fever, like the ones that they

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found in Australia, mycoplasma, chlamydia,

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and we have found patients who have low titers

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against HSV-6, but have very high levels

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of this HSV-6 virus that

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have also clearly been associated with significant fatigue in these patients,

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and those patients are the ones that we call chromosomally

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integrated human herpes virus six. So this is another

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completely different sub-group. And it's a tougher group

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00:35:49,910 --> 00:35:54,490
to treat. I'm sure you remember the first patient that I

249
00:35:54,500 --> 00:35:58,530
told you. The 50 year-old woman who came in 2008

250
00:35:58,530 --> 00:36:02,760
to see us, with the hope that we could find something,

251
00:36:02,760 --> 00:36:06,710
and we did all these titers, and they were low, or negative,

252
00:36:06,710 --> 00:36:10,900
but she's one of the patients who was found to have very high levels

253
00:36:10,900 --> 00:36:14,800
of the human herpes virus 6 in her blood. She one of the patients

254
00:36:14,800 --> 00:36:18,510
that we call, that the virus has found at clever way

255
00:36:18,510 --> 00:36:22,520
to get into the actual genome, into the genetic material

256
00:36:22,520 --> 00:36:26,900
of her own cells, in a clever way to hide,

257
00:36:26,100 --> 00:36:30,640
and to perhaps to produce the damage. So the patient that I mentioned to you

258
00:36:30,640 --> 00:36:35,520
in 2008, we were studying her--and this is a way to measure

259
00:36:35,520 --> 00:36:39,200
her fatigue and her cognitive abilities.

260
00:36:39,200 --> 00:36:42,300
Being 100 is being in complete misery.

261
00:36:42,300 --> 00:36:46,740
It's really being sick. The CDC has done studies with this questionnaire

262
00:36:46,740 --> 00:36:50,598
for physical and cognitive dysfunction. Most of the CFS patients

263
00:36:50,599 --> 00:36:53,920
are around 60. Being completely well

264
00:36:53,920 --> 00:36:57,760
is around 10. So if you are (a) 60, you are really sick.

265
00:36:57,760 --> 00:37:00,940
She was around (an) 80. This is the same woman,

266
00:37:00,940 --> 00:37:05,609
patient, wife, mother, that I talked to you at the beginning.

267
00:37:05,609 --> 00:37:09,890
We started with the antiviral, and you can see how

268
00:37:09,890 --> 00:37:13,150
by different antivirual interventions of certain kinds,

269
00:37:13,150 --> 00:37:16,599
finally she has some relief here. Where

270
00:37:16,599 --> 00:37:19,670
her level of function going from 80

271
00:37:19,670 --> 00:37:24,210
to almost 25 is significantly improved.

272
00:37:24,210 --> 00:37:27,290
She went from not been able to run errands,

273
00:37:27,290 --> 00:37:31,990
to now go out, and travel, and enjoy the graduation of her

274
00:37:31,990 --> 00:37:35,959
daughter, et cetera, et cetera. However, those drugs,

275
00:37:35,960 --> 00:37:39,000
for us to be able to achieve this resolution

276
00:37:39,000 --> 00:37:42,640
we had to give them at very high doses, and you can only go

277
00:37:42,640 --> 00:37:46,859
with this drug so long. So we have to move her to other medications that are not

278
00:37:46,859 --> 00:37:47,640
so effective.

279
00:37:47,640 --> 00:37:51,250
And unfortunately she has relapsed recently.

280
00:37:51,250 --> 00:37:55,740
For her, we're going to try hopefully a clever way

281
00:37:55,740 --> 00:37:59,310
to measure what is in her blood that changes that makes her feel

282
00:37:59,310 --> 00:38:02,660
so much better, going from 80 which is

283
00:38:02,660 --> 00:38:06,240
near hell, to around 20 which is near

284
00:38:06,240 --> 00:38:09,490
health. So hopefully we'll be able to

285
00:38:09,490 --> 00:38:13,649
achieve that, but I just want to show you this as an example

286
00:38:13,650 --> 00:38:17,339
that there is something there that we can improve.

287
00:38:17,339 --> 00:38:20,940
All we have to do is devote resources and more people

288
00:38:20,940 --> 00:38:24,430
to be able to unveil this mystery.

289
00:38:24,430 --> 00:38:27,759
So that has been, so far, our experience.

290
00:38:27,760 --> 00:38:31,760
I would like to mention two things quickly because I'm sure you have

291
00:38:31,760 --> 00:38:33,500
questions about it.

292
00:38:33,500 --> 00:38:36,810
It is what recently has been reported as the famous

293
00:38:36,810 --> 00:38:40,560
XMRV virus. The XMRV virus

294
00:38:40,560 --> 00:38:44,770
was--that, and the Lancet study about degraded

295
00:38:44,770 --> 00:38:47,890
exercise. So I'm going to comment on those two things, because they are very

296
00:38:47,890 --> 00:38:52,420
timely. So the XMRV is a virus that was found

297
00:38:52,420 --> 00:38:56,480
in prostatic tumors, and it was thought that it could be associated with

298
00:38:56,480 --> 00:39:00,750
prostatic cancer. But then the surprise came in 2009

299
00:39:00,750 --> 00:39:04,550
when it was reported by a group from Nevada that patients with

300
00:39:04,550 --> 00:39:10,490
the disease had 70 percent--it's 67 percent, but you can't remember a 70 percent--

301
00:39:10,490 --> 00:39:14,720
the CFS patient had the virus. Well yes, only four percent

302
00:39:14,720 --> 00:39:18,310
of healthy controls had it. So that caused a major splash

303
00:39:18,310 --> 00:39:21,570
and hope of the possibility that this agent

304
00:39:21,570 --> 00:39:25,470
could be behind, also, in addition to the other ones that I showed you,

305
00:39:25,470 --> 00:39:29,629
and in addition to the ones that we are going after at Stanford.

306
00:39:29,630 --> 00:39:33,700
The problem has been, that following that study,

307
00:39:33,700 --> 00:39:37,109
there have been two others supporting those findings

308
00:39:37,109 --> 00:39:41,600
and about six others that show that the association

309
00:39:41,600 --> 00:39:47,359
is not there. So there is one, this is one study from the U.S., the 70 percent

310
00:39:47,359 --> 00:39:50,730
versus the four percent that I mentioned to you

311
00:39:50,730 --> 00:39:55,630
that have the 70 percent in the patients versus four percent in the controls.

312
00:39:55,630 --> 00:39:59,119
The other study that was positive is a study from Boston

313
00:39:59,119 --> 00:40:03,420
when it was not 70 percent, it was almost 87 percent,

314
00:40:03,420 --> 00:40:06,520
and in controls it was about 7 percent.

315
00:40:06,520 --> 00:40:10,509
All the other studies, all the studies in Europe have been negative;

316
00:40:10,510 --> 00:40:15,210
the other studies, other than those two in the United States, have been negative,

317
00:40:15,210 --> 00:40:21,329
except one small one that has not been fully reported that was also positive from New York City.

318
00:40:21,329 --> 00:40:25,450
so it is a mystery, it's a challenge, it's a controversy,

319
00:40:25,450 --> 00:40:28,649
and we just have to step up to the challenge and solve it

320
00:40:28,650 --> 00:40:33,500
for the patients and not shy away and not take a position

321
00:40:33,500 --> 00:40:36,970
he has been really disappointing to me to see how

322
00:40:36,970 --> 00:40:40,930
colleagues who do not find the same thing that others do

323
00:40:40,930 --> 00:40:44,910
step up to the podium and said, "The other findings are wrong;

324
00:40:44,910 --> 00:40:49,200
we find the truth," et cetera. We are not going to be able able to solve this disease

325
00:40:49,200 --> 00:40:53,390
through taking dogmatic positions like this. So it is controversial

326
00:40:53,390 --> 00:40:56,910
but no group has produced proof

327
00:40:56,910 --> 00:41:01,180
that the association is there; nor any group has produced proof

328
00:41:01,180 --> 00:41:06,210
that it's not there. The retroviruses--this is a retrovirus--

329
00:41:06,210 --> 00:41:09,839
they have a great capacity to hide and to do

330
00:41:09,839 --> 00:41:13,910
bad things, either in a long period of range

331
00:41:13,910 --> 00:41:17,700
or very short. It's the same group with the HIV virus

332
00:41:17,700 --> 00:41:21,210
but it's not HIV. A kind of

333
00:41:21,210 --> 00:41:25,500
unique life cycle where they can get very cleverly

334
00:41:25,500 --> 00:41:28,960
inside the cell and they can integrate into the human

335
00:41:28,960 --> 00:41:32,000
genetic material, hence their ability to hide

336
00:41:32,000 --> 00:41:35,700
and to cause, in a very sneaky way,

337
00:41:35,700 --> 00:41:39,359
disease (in) us. There are several kinds;

338
00:41:39,359 --> 00:41:44,600
this XMRV virus came from mice--no question about it--

339
00:41:44,600 --> 00:41:48,890
and some of those viruses have mutated to the point that they are only

340
00:41:48,890 --> 00:41:49,819
able to stay in humans;

341
00:41:49,819 --> 00:41:53,190
there are others that can be in mice and humans,

342
00:41:53,190 --> 00:41:57,109
and there are others that cannot be in humans. So there are different kinds,

343
00:41:57,109 --> 00:42:00,609
but the reality is that the question is out there

344
00:42:00,609 --> 00:42:04,339
and it needs to be solved. And we as America

345
00:42:04,339 --> 00:42:07,640
and the scientific community need to step up and

346
00:42:07,640 --> 00:42:12,569
solve the mystery. There are different ways to measure the virus, so that's

347
00:42:12,569 --> 00:42:16,740
possibly part of the problem. There are ways to measure the actual virus;

348
00:42:16,740 --> 00:42:20,848
with measuring the nuclear acid to look at the proteins,

349
00:42:20,849 --> 00:42:23,990
to look at the cultural dividers, to look at

350
00:42:23,990 --> 00:42:29,740
how the antibody responds in humans to the virus, as a way to detect the virus--

351
00:42:29,740 --> 00:42:33,439
So there are different methods that make it a little bit more difficult, but not

352
00:42:33,440 --> 00:42:37,530
impossible, to understand what is happening. Also,

353
00:42:37,530 --> 00:42:40,890
people, or different laboratories, using different

354
00:42:40,890 --> 00:42:44,348
reagents; they use different

355
00:42:44,349 --> 00:42:49,329
positive or negative controls; the virus appears to be in very small amounts,

356
00:42:49,329 --> 00:42:52,990
so that makes it hard for people to find it.

357
00:42:52,990 --> 00:42:57,959
And also, the studies come from different geographical areas.

358
00:42:57,960 --> 00:43:01,100
Infectious diseases is characterized by this.

359
00:43:01,100 --> 00:43:05,900
There are infections that present only in the United States and ever seen in Europe.

360
00:43:05,900 --> 00:43:10,569
There are infections that are only seen in Latin America, never seen outside

361
00:43:10,569 --> 00:43:14,170
the Americas. So this is not news--

362
00:43:14,170 --> 00:43:17,290
that an infectious agent could be restricted to certain geographical

363
00:43:17,290 --> 00:43:21,890
locales, and it could be the case in this situation as well.

364
00:43:21,890 --> 00:43:25,200
So what is the bottom line? What is the bottom line with this

365
00:43:25,200 --> 00:43:28,609
XMRV virus? It can be present

366
00:43:28,609 --> 00:43:33,310
in people who have no disease. And it could be, according to the study so far

367
00:43:33,310 --> 00:43:37,650
up to seven percent. It can be present in patients with prostate cancer:

368
00:43:37,650 --> 00:43:41,750
up to 27 percent. It can can be present in patients with CFS:

369
00:43:41,750 --> 00:43:47,230
up to 87 percent. All the European studies have been negative so far.

370
00:43:47,230 --> 00:43:51,390
In the study from Boston, there were patients who were positive

371
00:43:51,390 --> 00:43:54,480
in blood samples that had been taken fifty years

372
00:43:54,480 --> 00:43:58,390
ago--they went to those patients again, they got blood again, and they were

373
00:43:58,390 --> 00:43:59,710
positive again.

374
00:43:59,710 --> 00:44:02,780
so we know that the virus can be there

375
00:44:02,780 --> 00:44:06,890
for long periods of time. And obviously

376
00:44:06,890 --> 00:44:09,520
we need to have the right studies

377
00:44:09,520 --> 00:44:13,670
in a smart way and we are fortunate, the Stanford group is fortunate,

378
00:44:13,670 --> 00:44:18,000
to be associated now with a group at Columbia

379
00:44:18,000 --> 00:44:22,990
with directions, and the directions of the NIH, to hopefully be able

380
00:44:22,990 --> 00:44:25,220
to provide the right kind of data that will help

381
00:44:25,220 --> 00:44:29,578
to support one way or the other. And another possibility

382
00:44:29,579 --> 00:44:34,130
is to do a specific intervention, because the drugs that work against a virus

383
00:44:34,130 --> 00:44:38,490
are very specific. In the next few minutes,

384
00:44:38,490 --> 00:44:44,149
I would like to share with you how at Stanford we have tried to put this together

385
00:44:44,150 --> 00:44:47,680
as a model of pathogenesis of this disease.

386
00:44:47,680 --> 00:44:52,180
So as I told you before, it is known that some patients start with infection

387
00:44:52,180 --> 00:44:55,440
and that the more severe the infection at the beginning,

388
00:44:55,440 --> 00:44:59,290
the higher is the chance that they go into chronic fatigue syndrome.

389
00:44:59,290 --> 00:45:03,690
Most of the infections that have associated with

390
00:45:03,690 --> 00:45:07,180
chronic fatigue syndrome are intracellular: they hide

391
00:45:07,180 --> 00:45:11,328
inside the cell. They like to go to the brain;

392
00:45:11,329 --> 00:45:15,230
they like to go to the lymph nodes. So I think that they are telling us something

393
00:45:15,230 --> 00:45:19,390
there from a mechanistic point of view. Several

394
00:45:19,390 --> 00:45:22,720
infections can do the same thing; they can

395
00:45:22,720 --> 00:45:26,189
trigger CFS. I think that this is telling us

396
00:45:26,190 --> 00:45:29,190
that what is most likely responsible for

397
00:45:29,190 --> 00:45:33,490
the problem it's not the organism itself attacking the patient, but it's the

398
00:45:33,490 --> 00:45:35,980
immune response to them.

399
00:45:35,990 --> 00:45:38,500
Several of them can do it; the severe ones seem to be

400
00:45:38,500 --> 00:45:43,140
doing it more successfully, so it's likely that is the immune response against them

401
00:45:43,140 --> 00:45:46,339
what is doing it. It's possible

402
00:45:46,339 --> 00:45:49,900
that it is doing it because they all share something in common

403
00:45:49,900 --> 00:45:53,000
that triggers the same immune response that is damaging

404
00:45:53,000 --> 00:45:56,810
or that they00:02:18,150 --> 00:02:21,330
for 23 years.

405
00:02:21,330 --> 00:02:24,940
Twenty-three years. She had a wonderful life;

406
00:02:24,940 --> 00:02:28,780
she has a supporting and loving husband--

407
00:02:28,780 --> 00:02:32,319
still he's with her--who works for a high-tech company,

408
00:02:32,319 --> 00:02:37,470
two super children, enjoy her full-time jobs as a sales manager

409
00:02:37,470 --> 00:02:42,450
and as a housemaker. Being a housewife or a housemaker, as you know, is

410
00:02:42,450 --> 00:02:43,950
a full-time job on its own.

411
00:02:43,950 --> 00:02:48,738
She had two full-time jobs. And she was the source of constant joy

412
00:02:48,739 --> 00:02:53,120
for her family and friends. She had probably achieved what many will call the

413
00:02:53,120 --> 00:02:54,900
"American Dream."

414
00:02:54,900 --> 00:02:57,879
In 1985, that dream came to a stop.

415
00:02:57,879 --> 00:03:02,140
At the age of 30, and after giving birth to her first child,

416
00:03:02,140 --> 00:03:06,679
she developed fatigue--fatigue that became worse over the

417
00:03:06,680 --> 00:03:10,340
next 23 years, becoming disabling

418
00:03:10,340 --> 00:03:14,100
in 2003. She can only do 30

419
00:03:14,100 --> 00:03:17,329
percent of what she was capable of doing before she fell ill.

420
00:03:17,330 --> 00:03:20,730
Even running small errands, like going to grocery

421
00:03:20,730 --> 00:03:25,230
shopping, has become a major ordeal. Here we have

422
00:03:25,230 --> 00:03:28,768
a life that has come to a standstill:

423
00:03:28,769 --> 00:03:33,610
Thirty percent of what she's capable of doing for 23 years.

424
00:03:33,610 --> 00:03:38,209
So I want you to carefully weigh everything that is being presented to you; this is

425
00:03:38,209 --> 00:03:39,430
a real case.

426
00:03:39,430 --> 00:03:43,120
So how is it possible to live with a disease

427
00:03:43,120 --> 00:03:47,129
that makes you be thirty percent of who you are, and still

428
00:03:47,129 --> 00:03:50,409
be able to live with that for 23 years?

429
00:03:50,409 --> 00:03:53,579
In addition to that primary, persistant

430
00:03:53,580 --> 00:03:56,939
fatigue, she develops other worrisome symptoms:

431
00:03:56,939 --> 00:04:00,870
Brain fog. It's not uncommon for patients to tell you

432
00:04:00,870 --> 00:04:06,300
they have brain fog. And it's expressed by significant cognitive impairment--

433
00:04:06,300 --> 00:04:11,430
all the way to 30 percent. So 70 percent of her brain function

434
00:04:11,430 --> 00:04:14,459
was taken, or has been taken, by her illness.

435
00:04:14,459 --> 00:04:20,250
mental tasks leave her fatigued; compiling information became extremely difficult;

436
00:04:20,250 --> 00:04:25,330
she feels jumbled and confused. She in addition has had headaches,

437
00:04:25,330 --> 00:04:28,960
cough, sore throats, unrefreshing sleep.

438
00:04:28,960 --> 00:04:32,210
She wakes up in the morning as if she would have not slept--

439
00:04:32,210 --> 00:04:35,710
she had not slept the night before--with the same level

440
00:04:35,710 --> 00:04:41,390
of tiredness as when she bed. Post-exertional malaise.

441
00:04:41,400 --> 00:04:46,540
Not many diseases--and I see respectable physicians here in the audience--

442
00:04:46,540 --> 00:04:51,320
not many diseases will give you what the patients with chronic fatigue syndrome

443
00:04:51,320 --> 00:04:52,330
experience

444
00:04:52,330 --> 00:04:56,650
when they overdo it. And overdoing it can be just running a small errand.

445
00:04:56,650 --> 00:05:00,710
Overdoing can be walking a mile. But after that

446
00:05:00,710 --> 00:05:04,000
level of exercise, or that level

447
00:05:04,000 --> 00:05:07,889
of, of putting the body through that stress--and it could be mental,

448
00:05:07,889 --> 00:05:11,440
could be emotional, cognitive

449
00:05:11,440 --> 00:05:14,680
or physical--they go into a crash

450
00:05:14,680 --> 00:05:18,380
period. It's not the physical

451
00:05:18,380 --> 00:05:21,630
sort of strain that you experience when you go and run

452
00:05:21,630 --> 00:05:25,639
a whole mountain, around miles when you are healthy, your feel tired afterwards

453
00:05:25,639 --> 00:05:26,370
but you have the

454
00:05:26,370 --> 00:05:29,690
endorphin kick that makes you feel good because you did a lot of

455
00:05:29,690 --> 00:05:33,160
exercise or physical activity. It is not that.

456
00:05:33,160 --> 00:05:37,110
It's a crash where the patient feels sick, many times with the feeling

457
00:05:37,110 --> 00:05:40,180
of having a flu. In addition to

458
00:05:40,180 --> 00:05:44,330
post-exertional malaise, she feels muscle pain,

459
00:05:44,330 --> 00:05:48,440
joint pain. Her primary care provider

460
00:05:48,440 --> 00:05:52,560
is arguably one of the best internists in the Bay Area.

461
00:05:52,560 --> 00:05:57,360
And she has been fortunate to have him, because he has been there for her

462
00:05:57,360 --> 00:06:01,680
for all this period, being sure she doesn't have a cancer,

463
00:06:01,680 --> 00:06:05,270
low thyroid, a rheumatological disease--

464
00:06:05,270 --> 00:06:10,130
he has been so careful in being sure that we don't treat her as (having) chronic fatigue syndrome

465
00:06:10,130 --> 00:06:13,990
when in fact she could have had something else that can be put in a box,

466
00:06:13,990 --> 00:06:18,539
and it can be treated from, you know, day one to day X.

467
00:06:18,539 --> 00:06:22,289
And, most importantly, he believes that her

468
00:06:22,289 --> 00:06:26,370
illness is real. I cannot tell you that--

469
00:06:26,370 --> 00:06:30,900
--whatever we are doing at Stanford that may have worked, and we are

470
00:06:30,900 --> 00:06:34,720
pleased with those results, may have worked for some patients--

471
00:06:34,720 --> 00:06:38,169
it could be still (up) for debate. We still have to do a lot of more work

472
00:06:38,169 --> 00:06:38,789
to understand

473
00:06:38,789 --> 00:06:41,900
what are we doing to the patients, that some of them have

474
00:06:41,900 --> 00:06:46,698
gotten better. But the one thing: a hundred percent of--and not all of the

475
00:06:46,699 --> 00:06:48,330
patients get better, unfortunately--

476
00:06:48,330 --> 00:06:51,340
--but the one thing that I can tell you, that a hundred percent of the patients

477
00:06:51,340 --> 00:06:52,530
are grateful,

478
00:06:52,530 --> 00:06:56,490
is when we tell them, "You have a real disease."

479
00:06:56,500 --> 00:06:59,990
And they break down there. Because for the first time they find somebody in the

480
00:06:59,990 --> 00:07:01,740
medical community

481
00:07:01,740 --> 00:07:05,990
telling them, "You are not lying, you are not faking, you are not malingering;

482
00:07:05,990 --> 00:07:09,940
you have a disease you have no control on."

483
00:07:09,940 --> 00:07:14,219
And then, then they feel at least validated. So it's very important for--

484
00:07:14,220 --> 00:07:18,849
hopefully, one day, my dream is that our medical community

485
00:07:18,849 --> 00:07:22,830
will produce a formal apology to the patients

486
00:07:22,830 --> 00:07:26,280
for not having believed them all these years, that they were facing

487
00:07:26,280 --> 00:07:31,309
a real illness. It's true that currently we don't have a single way

488
00:07:31,310 --> 00:07:34,610
to determine that somebody has CFS in an objective way.

489
00:07:34,610 --> 00:07:37,660
It's true that we don't have a single treatment, but

490
00:07:37,660 --> 00:07:41,840
the patients do have a real disease.

491
00:07:41,840 --> 00:07:44,948
The fact that the patients give you so much

492
00:07:44,949 --> 00:07:48,940
history of suffering, and that is incapacitating,

493
00:07:48,940 --> 00:07:53,160
that when you try to look for objective signs that

494
00:07:53,160 --> 00:07:58,300
that, that correlates with what they are telling you--that dichotomy between

495
00:07:58,300 --> 00:08:01,330
they telling you, "I am so sick, I cannot

496
00:08:01,330 --> 00:08:04,780
even leave the house." But then when you do testing,

497
00:08:04,780 --> 00:08:08,680
when you examine them, you do not find anything that is

498
00:08:08,690 --> 00:08:11,810
palpable or tangile, that is not new.

499
00:08:11,810 --> 00:08:15,759
Even back in the 1900s, when physicians

500
00:08:15,759 --> 00:08:19,340
who had this special skill

501
00:08:19,340 --> 00:08:24,200
for having, for finding diseases in the physical exam, like William Osler

502
00:08:24,200 --> 00:08:28,620
famously said, "In all forms there is a striking lack of accordance

503
00:08:28,620 --> 00:08:32,140
between the symptoms of which the patients complain and the objective

504
00:08:32,140 --> 00:08:36,990
changes discoverable by the physician." So it has been more than two hundred years that

505
00:08:36,990 --> 00:08:42,760
that discordance is known, but what is sad is that it has been equated

506
00:08:42,760 --> 00:08:46,339
to the patient has something that is in their head, something that they have

507
00:08:46,339 --> 00:08:50,250
control, just with their minds. So CFS

508
00:08:50,250 --> 00:08:53,830
is a real disease. It's experienced by

509
00:08:53,830 --> 00:08:59,620
one to four million Americans, perhaps 17 or more million people (it's worldwide);

510
00:08:59,620 --> 00:09:04,459
there are no diagnostic tests that can identify with certainty

511
00:09:04,459 --> 00:09:09,199
the patient. Pneumonia: pneumonia, for example,

512
00:09:09,200 --> 00:09:12,360
is an infection. And when a patient has cough,

513
00:09:12,360 --> 00:09:15,899
and fever, and tired, and sore throat,

514
00:09:15,899 --> 00:09:19,209
we do a chest X-ray and we see something. We see

515
00:09:19,209 --> 00:09:23,699
a shadow in that chest X-ray, and we say the patient has pneumonia.

516
00:09:23,700 --> 00:09:27,790
We don't have the equivalent to that shadow in CFS.

517
00:09:27,790 --> 00:09:31,899
We desperately need that, and this is one of the goals that we have set

518
00:09:31,899 --> 00:09:35,980
our group at Stanford, is to one day be able to tell our patients,

519
00:09:35,980 --> 00:09:40,230
"Yes, you have a shadow in your chest X-ray, CFS disease,

520
00:09:40,230 --> 00:09:43,810
and yes, that validates you. There are no

521
00:09:43,810 --> 00:09:46,890
definitive treatments, and I'll tell you the

522
00:09:46,890 --> 00:09:50,890
small progress that we have made at Stanford with some groups of patients in

523
00:09:50,890 --> 00:09:51,959
this regard,

524
00:09:51,959 --> 00:09:55,290
and it's true that some patients spontaneously improve,

525
00:09:55,290 --> 00:10:00,579
but after a certain period of time, their rate of improvement really is small.

526
00:10:00,580 --> 00:10:04,440
It could be as high as seventy, eighty percent

527
00:10:04,440 --> 00:10:09,190
in the first year of disease, but it becomes really much lower

528
00:10:09,190 --> 00:10:12,870
as the years come (pass).

529
00:10:12,870 --> 00:10:16,950
So what makes CFS such a difficult challenge?

530
00:10:16,950 --> 00:10:20,990
We have, of course, compassionate colleagues and

531
00:10:20,990 --> 00:10:24,459
people who are extremely smart in our schools and

532
00:10:24,459 --> 00:10:27,859
in offices, but what makes it so hard

533
00:10:27,860 --> 00:10:31,690
not to see it many times as a real disease, for one side,

534
00:10:31,690 --> 00:10:35,930
is the fact that there are so many symptoms coming from so many angles.

535
00:10:35,930 --> 00:10:40,290
We physicians have this thinking that if you give us a symptom,

536
00:10:40,290 --> 00:10:43,310
we try to look for what organ it's coming from.

537
00:10:43,310 --> 00:10:46,790
So the cough could be coming from the lungs,

538
00:10:46,790 --> 00:10:51,560
from the heart, from a medication, occasionally from some area of the brain,

539
00:10:51,560 --> 00:10:55,420
so we start to see where the organ that is involved.

540
00:10:55,420 --> 00:10:58,550
And many times the symptoms sort of like,

541
00:10:58,550 --> 00:11:02,670
are [related] to a single system, to an organ, but when the patient

542
00:11:02,670 --> 00:11:07,180
gives you, with validity, the symptoms coming from so many organs:

543
00:11:07,180 --> 00:11:10,349
muscle pain, joint pain, brain fog,

544
00:11:10,350 --> 00:11:14,899
fatigue, et cetera, then it's hard for a physician to take,

545
00:11:14,899 --> 00:11:18,649
"What do I do with this?" So it's the constellation,

546
00:11:18,649 --> 00:11:22,430
it's the complexity, it's the fact that they are so hetereogeneous

547
00:11:22,430 --> 00:11:26,510
that has made this disease difficult to deal with.

548
00:11:26,510 --> 00:11:29,680
And things will only get worse when we have

549
00:11:29,680 --> 00:11:33,479
health care systems that only allow physicians for the first visit

550
00:11:33,480 --> 00:11:37,680
45 minutes or 60 minutes, and for follow-up, 15 minutes or 20 minutes.

551
00:11:37,680 --> 00:11:38,459
That's going to get

552
00:11:38,459 --> 00:11:42,250
only worse. The disease is disabling,

553
00:11:42,250 --> 00:11:46,589
the combination of symptoms--not only is the fatigue the central core

554
00:11:46,589 --> 00:11:50,519
of the symptom, but what I refer to you as brain fog.

555
00:11:50,519 --> 00:11:53,950
Unfortunately, the name "chronic fatigue syndrome"

556
00:11:53,950 --> 00:11:57,589
has not served well the disease or the patients.

557
00:11:57,589 --> 00:12:01,000
There are other symptoms. It's not just the fatigue.

558
00:12:01,000 --> 00:12:04,850
And the most and the recognized symptom in patients with chronic fatigue

559
00:12:04,850 --> 00:12:07,000
syndrome is the cognitive impairment.

560
00:12:07,000 --> 00:12:11,339
It is real. It is there. It incapacitates patients.

561
00:12:11,339 --> 00:12:14,380
Patients say that they have difficulty concentrating,

562
00:12:14,380 --> 00:12:18,230
finding words; they cannot produce the same level

563
00:12:18,230 --> 00:12:21,230
of executive function that they used to exercise,

564
00:12:21,230 --> 00:12:24,540
and they cannot sustain those activities for much.

565
00:12:24,540 --> 00:12:29,120
They also have sleep problems and pains in the joints and muscles.

566
00:12:29,120 --> 00:12:33,200
They usually have the disease for six months or longer.

567
00:12:33,200 --> 00:12:37,610
So we are trying to differentiate those situations where you get the fatigue

568
00:12:37,610 --> 00:12:41,490
and fortunately it goes away

569
00:12:41,490 --> 00:12:45,860
within a short period of time. So it has generally been agreed upon

570
00:12:45,860 --> 00:12:49,820
that if you have the fatigue for more than six months is when you have to worry

571
00:12:49,820 --> 00:12:53,190
about the possibility that initial illness

572
00:12:53,190 --> 00:12:56,470
could have been the beginning of the nightmare

573
00:12:56,470 --> 00:13:00,160
that will ensue months or years later.

574
00:13:00,160 --> 00:13:03,920
Many patients--many patients will tell you

575
00:13:03,920 --> 00:13:07,240
that their nightmare began with a

576
00:13:07,240 --> 00:13:10,389
viral-like illness. They will tell you that. They are--

577
00:13:10,389 --> 00:13:13,930
you know, the way I see this disease is that,

578
00:13:13,930 --> 00:13:18,469
it is speaking to us. It is telling us the clue--it's giving us the clues,

579
00:13:18,470 --> 00:13:21,649
we just have not had the patience

580
00:13:21,649 --> 00:13:24,980
and the time

581
00:13:24,980 --> 00:13:28,000
to really listen to the clues that the disease is giving us there.

582
00:13:28,000 --> 00:13:31,350
But they tell us, "I was totally fine."

583
00:13:31,350 --> 00:13:35,220
And they give you the month. Sometimes they give you the date,

584
00:13:35,220 --> 00:13:38,490
the day of the month, and the year, when their whole

585
00:13:38,490 --> 00:13:42,600
life crumbled, like the patient that I illustrated to you.

586
00:13:42,600 --> 00:13:47,240
It is important, however, every time that somebody says that they have

587
00:13:47,240 --> 00:13:47,949
chronic fatigue syndrome,

588
00:13:47,949 --> 00:13:51,760
that we rule out other potential explanations

589
00:13:51,760 --> 00:13:55,370
that are more circumscribed to a single

590
00:13:55,370 --> 00:14:00,880
ideology or cause that can be fixed relatively quick.

591
00:14:00,880 --> 00:14:04,709
This is this study that validates what the patients have been telling us

592
00:14:04,709 --> 00:14:08,239
all along. This is a study that was done in Australia,

593
00:14:08,240 --> 00:14:12,649
where they have the capacity and resources, that as soon as somebody gets

594
00:14:12,649 --> 00:14:14,500
diagnosed with acute

595
00:14:14,500 --> 00:14:18,720
infectious mononucleosis, or Epstein-Barr virus infection,

596
00:14:18,720 --> 00:14:22,250
or another infection that they have common in Australia called

597
00:14:22,250 --> 00:14:25,290
Q fever. Q fever can go into the lungs,

598
00:14:25,290 --> 00:14:29,939
can go into the heart. It's called Q fever, caused by an organism called

599
00:14:29,940 --> 00:14:31,649
Coxiella burnetii.

600
00:14:31,649 --> 00:14:35,610
Or another infection they call Ross River virus.

601
00:14:35,610 --> 00:14:39,790
For the purposes of this conversation, these physicians in Australia have the

602
00:14:39,790 --> 00:14:40,990
capacity

603
00:14:40,990 --> 00:14:45,149
to register and capture patients who have been dianogised

604
00:14:45,149 --> 00:14:48,320
with acute infection of any of those three

605
00:14:48,320 --> 00:14:51,699
kinds: either infectious mononucleosis,

606
00:14:51,699 --> 00:14:54,939
Q fever, or the Ross River virus.

607
00:14:54,940 --> 00:14:58,889
And to their surprise, the people who,

608
00:14:58,889 --> 00:15:02,610
the patients who were followed over time prospectively--

609
00:15:02,610 --> 00:15:06,310
and this is the participants that remain

610
00:15:06,310 --> 00:15:09,899
having fatigue after the acute infection

611
00:15:09,899 --> 00:15:13,790
was diagnosed here--so in the, in the

612
00:15:13,790 --> 00:15:16,949
X axis . . . you can follow

613
00:15:16,949 --> 00:15:21,250
the time after acute infection, six months, twelve months after,

614
00:15:21,250 --> 00:15:25,149
and here in the . . . Y axis,

615
00:15:25,149 --> 00:15:29,600
you can see the patients who have fatigue, and you can see obviously patients

616
00:15:29,600 --> 00:15:30,459
getting better,

617
00:15:30,459 --> 00:15:34,149
and less having fatigue, but look at the proportion of cases

618
00:15:34,149 --> 00:15:39,540
that remain fatigued after 12 months. And they follow those patients later;

619
00:15:39,540 --> 00:15:42,759
Eleven percent of the patients

620
00:15:42,759 --> 00:15:46,680
develop chronic fatigue syndrome after these acute

621
00:15:46,680 --> 00:15:50,219
infections. Our patients were telling us that

622
00:15:50,220 --> 00:15:55,680
all along. And a study had to be done to prove that they were right.

623
00:15:55,680 --> 00:15:59,420
So it looks like at least in some cases of CFS

624
00:15:59,420 --> 00:16:03,149
there is an infectious insult at the beginning

625
00:16:03,149 --> 00:16:06,980
of the illness. Whether it's the infectious agent per se

626
00:16:06,980 --> 00:16:10,870
or the immune response against that agent, what (affects) it that much

627
00:16:10,870 --> 00:16:14,829
is unknown at this time. But hopefully one day we'll be able

628
00:16:14,829 --> 00:16:18,130
to solve that puzzle.

629
00:16:18,130 --> 00:16:21,509
This is another study done in the United States

630
00:16:21,509 --> 00:16:25,910
Similar idea. These are other lessons--these are kids.

631
00:16:25,910 --> 00:16:30,959
They have also been able to capture them at the time they had the acute infection

632
00:16:30,959 --> 00:16:34,508
and they find that about four percent after

633
00:16:34,509 --> 00:16:39,240
24 months--four percent--they have had but they have met the criteria

634
00:16:39,240 --> 00:16:42,769
of chronic fatigue syndrome. So clearly

635
00:16:42,769 --> 00:16:45,920
there is now proof

636
00:16:45,920 --> 00:16:50,600
that a patient can go into this mysterious disease, an illness,

637
00:16:50,600 --> 00:16:53,170
after they have had an acute infection. And

638
00:16:53,170 --> 00:16:56,509
please note that many of those infections

639
00:16:56,509 --> 00:17:00,220
also have what we call an asymptomatic phase. In other words,

640
00:17:00,220 --> 00:17:05,890
people, patients, can get those infections, and not have symptoms.

641
00:17:05,890 --> 00:17:08,208
What they have found is that in general,

642
00:17:08,209 --> 00:17:13,750
the more acute, severely ill the patients are, the more severe the disease is

643
00:17:13,750 --> 00:17:17,348
at the time when they have developed for the first time,

644
00:17:17,348 --> 00:17:23,539
the higher is the likelihood that they will go into chronic fatigue syndrome.

645
00:17:23,539 --> 00:17:28,600
So it is really important, and this is just to make one point--

646
00:17:28,600 --> 00:17:31,719
is that before we declare someone

647
00:17:31,720 --> 00:17:36,890
as having chronic fatigue syndrome, not only that six months have passed,

648
00:17:36,890 --> 00:17:40,620
for now--maybe in the future we will learn to identify

649
00:17:40,620 --> 00:17:43,789
those who will go into chronic fatigue syndrome very early so we can

650
00:17:43,789 --> 00:17:45,600
intervene early--but for now,

651
00:17:45,600 --> 00:17:48,709
the only way we can do it is by waiting. We don't have a way to

652
00:17:48,710 --> 00:17:49,490
distinguish those

653
00:17:49,490 --> 00:17:53,340
except that you can say, the more severe cases perhaps, you will have to pay more

654
00:17:53,340 --> 00:17:54,830
attention to them.

655
00:17:54,830 --> 00:17:58,899
But it's important that a very good internist, primary care provider,

656
00:17:58,900 --> 00:18:02,910
family medicine physician, does a comprehensive

657
00:18:02,910 --> 00:18:06,200
job looking for alternative explanations--

658
00:18:06,200 --> 00:18:09,129
psychiatric, psychologic, neurological--

659
00:18:09,130 --> 00:18:13,160
Because those can be relatively easily fixed. Be sure that we don't have a

660
00:18:13,160 --> 00:18:14,929
cancer that has not been diagnosed

661
00:18:14,929 --> 00:18:18,140
that is causing the fatigue, that is not a low thyroid,

662
00:18:18,140 --> 00:18:21,830
hormone production. Once that has been done,

663
00:18:21,830 --> 00:18:25,850
then we look at patients who have had the fatigue for more than six months

664
00:18:25,850 --> 00:18:30,230
and who have other symptoms. Unfortunately, there is no other way

665
00:18:30,230 --> 00:18:33,789
to do it. We don't have that shadow in the chest X-ray

666
00:18:33,789 --> 00:18:36,940
that (lets) you see pneumonia--yet. And

667
00:18:36,940 --> 00:18:40,260
We couple the fatigue that has lasted for six months

668
00:18:40,260 --> 00:18:45,270
plus four of any of this impaired concentration of the brain fog,

669
00:18:45,270 --> 00:18:48,299
sore throat, lymph nodes that are enlarged

670
00:18:48,299 --> 00:18:51,330
and painful, muscle pain, joint pain,

671
00:18:51,330 --> 00:18:56,270
new headaches, the unrefreshing sleep, and the post-exertional malaise.

672
00:18:56,270 --> 00:18:59,490
They are often with symptoms of depression.

673
00:18:59,490 --> 00:19:03,640
It's not that the depression causes chronic fatigue syndrome.

674
00:19:03,640 --> 00:19:07,300
It's that they are depressed because their lives have been been ruined,

675
00:19:07,300 --> 00:19:10,639
their life has been taken away, and they want that life back

676
00:19:10,640 --> 00:19:14,610
and they cannot have it. So it is unfortunate that

677
00:19:14,610 --> 00:19:17,879
we tend to see the periphery and not see how

678
00:19:17,880 --> 00:19:21,650
it evolved. Clinically,

679
00:19:21,650 --> 00:19:25,900
those patients, their fatigue is not

680
00:19:25,900 --> 00:19:28,350
alleviated by resting,

681
00:19:28,350 --> 00:19:32,439
and it's not the result of, because they are doing something

682
00:19:32,440 --> 00:19:36,630
something and they are not stopping. And in many cases,

683
00:19:36,630 --> 00:19:39,950
they lose their previous levels of occupational,

684
00:19:39,950 --> 00:19:43,470
educational, social, or personal activities.

685
00:19:43,470 --> 00:19:47,320
It's very important to note that many of them

686
00:19:47,320 --> 00:19:51,129
give you neurological symptoms

687
00:19:51,130 --> 00:19:54,320
that are hard to put in any category.

688
00:19:54,320 --> 00:19:58,580
At a meeting we were participating last night

689
00:19:58,580 --> 00:20:02,260
in, in the Washington area, we were sitting with

690
00:20:02,260 --> 00:20:06,870
neurologists and other physicians, and it became very clear

691
00:20:06,870 --> 00:20:10,490
that everybody's seeing the same thing.

692
00:20:10,490 --> 00:20:13,330
Not only the fatigue, not only the brain fog,

693
00:20:13,330 --> 00:20:18,100
but these funny tremors, twitches, that we call

694
00:20:18,100 --> 00:20:22,250
myoclonus fasciculations, things that normally will trigger the possibility of a

695
00:20:22,250 --> 00:20:23,169
neurlogical disease--

696
00:20:23,169 --> 00:20:27,230
these patients are having something in that area.

697
00:20:27,230 --> 00:20:31,390
so again, it seems like the disease is speaking to us

698
00:20:31,390 --> 00:20:35,450
in soft tones, and we're just not able to listen to it

699
00:20:35,450 --> 00:20:39,419
in a careful way. So it is a real disease,

700
00:20:39,419 --> 00:20:43,100
but it's an infectious, it is immunological,

701
00:20:43,100 --> 00:20:47,289
it's endocrine, neurological, cardiac, psychiatric,

702
00:20:47,289 --> 00:20:50,480
and so everybody seems to be looking at it from the wrong angle

703
00:20:50,480 --> 00:20:53,820
depending on what their area is. And

704
00:20:53,820 --> 00:20:57,350
hopefully one day will be able to see it three hundred and sixty

705
00:20:57,350 --> 00:21:01,719
to be able to comprehend better what is really is, what it's doing--

706
00:21:01,720 --> 00:21:05,690
the disease to these patients. And part of the problem

707
00:21:05,690 --> 00:21:10,150
is that, as I said, it's a constellation of systems, so it's a systemic

708
00:21:10,150 --> 00:21:15,419
challenge; it lasts! It can go on for decades.

709
00:21:15,419 --> 00:21:20,190
Is it possible that the CFS that one patient has is different than the other?

710
00:21:20,190 --> 00:21:21,809
Of course it could be possible.

711
00:21:21,809 --> 00:21:25,639
Like in pneumonia, you have this same shadow in two patients

712
00:21:25,640 --> 00:21:28,730
but it's caused by a different organism.

713
00:21:28,730 --> 00:21:32,490
So when you study CFS patients in the air, in general,

714
00:21:32,490 --> 00:21:36,380
it could be that you are studying different subgroups, and as you try to

715
00:21:36,380 --> 00:21:37,409
make it a one,

716
00:21:37,409 --> 00:21:41,159
your findings could be diluted for that reason.

717
00:21:41,159 --> 00:21:44,390
Also is very likely that the disease evolves.

718
00:21:44,390 --> 00:21:47,980
It changes. The patient who has illness for less than a year

719
00:21:47,980 --> 00:21:52,900
possibly will have a different kind of test, positive or negative,

720
00:21:52,900 --> 00:21:58,408
than someone who has had the disease for ten or twenty years.

721
00:21:58,409 --> 00:22:01,789
I have to bring up this study. Because in

722
00:22:01,789 --> 00:22:05,640
our infectious diseases community--so I told you that many patients tell you

723
00:22:05,640 --> 00:22:07,210
that there is an

724
00:22:07,210 --> 00:22:11,270
infection at the beginning of the illness--this is this study that has been

725
00:22:11,270 --> 00:22:16,940
cited as a study that shows that an anti-microbial intervention

726
00:22:16,940 --> 00:22:20,570
does not work for patients with chronic fatigue syndrome. It was a study that was

727
00:22:20,570 --> 00:22:22,129
published in the late 80s,

728
00:22:22,130 --> 00:22:27,940
where they took 27 patients. They had high titers against Epstein-Barr virus

729
00:22:27,940 --> 00:22:31,230
virus; they had been ill for at least seven years;

730
00:22:31,230 --> 00:22:34,610
and they gave those patients acyclovir for thirty

731
00:22:34,610 --> 00:22:37,908
days. So they got IV for seven days,

732
00:22:37,909 --> 00:22:41,250
and oral for thirty days. So no more

733
00:45:56,810 --> 00:46:00,730
similar mechanisms of damaging, or immunopathology,

734
00:46:00,730 --> 00:46:07,140
as also is known. The fact that the disease can be pressing for so many years

735
00:46:07,140 --> 00:46:10,598
is telling us something. It's whispering to us something.

736
00:46:10,599 --> 00:46:14,810
The fact that somebody could have a disease and not die of it

737
00:46:14,810 --> 00:46:19,109
for so long is giving us clues of the mechanism.

738
00:46:19,109 --> 00:46:22,339
If it's an infection that is doing it, it will mean

739
00:46:22,339 --> 00:46:26,390
that the infectious agent is capable of coming out of the hiding place

740
00:46:26,390 --> 00:46:31,400
at a low level. And the immune system attacks the infection,

741
00:46:31,400 --> 00:46:34,290
successfully puts that pathogen back in the hiding place,

742
00:46:34,290 --> 00:46:37,859
but it's the same immune response perhaps that is making the patients sick.

743
00:46:37,859 --> 00:46:41,670
Ad it just perpetuates the cycle. The patients tell us,

744
00:46:41,670 --> 00:46:45,450
they had been telling us for years,

745
00:46:45,450 --> 00:46:49,399
"I get this fluctuating level(s) of disease."

746
00:46:49,400 --> 00:46:53,240
And I think the immune system is acting as a double-edged sword;

747
00:46:53,240 --> 00:46:57,290
it's putting that organism back in (its) hiding place, but it's making the patient

748
00:46:57,300 --> 00:46:59,420
possibly sick.

749
00:46:59,420 --> 00:47:04,290
So the other observation is that most of the patients are women;

750
00:47:04,290 --> 00:47:07,349
most of them get better during pregnancy

751
00:47:07,349 --> 00:47:10,640
and most of them get worse after birth.

752
00:47:10,640 --> 00:47:13,670
Remember that patient that I mentioned to you: that she got the disease

753
00:47:13,670 --> 00:47:17,170
after the birth of her son. So that suggests

754
00:47:17,170 --> 00:47:21,540
an autoimmune disease, or an HLA association. Many diseases

755
00:47:21,540 --> 00:47:24,670
that have been found to be autoimmune had that exact

756
00:47:24,670 --> 00:47:27,950
same behavior. Lastly,

757
00:47:27,950 --> 00:47:32,290
I wanna comment to you, comment with you,

758
00:47:32,300 --> 00:47:35,869
the highly publicized study

759
00:47:35,869 --> 00:47:39,790
that came out of London where they

760
00:47:39,790 --> 00:47:42,920
did what is called adaptive pacing therapy,

761
00:47:42,920 --> 00:47:47,440
cognitive behavior therapy, or graded exercise therapy,

762
00:47:47,440 --> 00:47:50,960
or simply, a specialized medical care

763
00:47:50,960 --> 00:47:55,590
for patients with chronic fatigue syndrome. Adaptive pacing therapy

764
00:47:55,590 --> 00:47:58,550
is to tell the patient, "Do what you feel, but do not

765
00:47:58,550 --> 00:48:01,780
overdo it. Cognitive behavioral therapy

766
00:48:01,780 --> 00:48:05,270
is they work with a counselor, with a psychologist,

767
00:48:05,270 --> 00:48:10,470
to be sure that they overcome the fear of doing things, because they would crash,

768
00:48:10,470 --> 00:48:13,759
but they also get the same message: avoid the crashes.

769
00:48:13,760 --> 00:48:16,930
But this time they do it under cognitive

770
00:48:16,930 --> 00:48:21,400
behavioral intervention. Graded exercise therapy

771
00:48:21,400 --> 00:48:24,690
is they work with physical therapy individuals

772
00:48:24,690 --> 00:48:28,880
with the same goal--not to crash--but they do have some kind of

773
00:48:28,880 --> 00:48:32,440
schedule, graded exercise activity.

774
00:48:32,440 --> 00:48:36,100
in all the groups, either adaptive pacing therapy,

775
00:48:36,100 --> 00:48:40,200
cognitive behavior, graded exercise therapy, the main goal was to

776
00:48:40,200 --> 00:48:43,640
avoid the patient crashing, however the idea

777
00:48:43,640 --> 00:48:47,348
was to achieve that through these different means that I described to you.

778
00:48:47,349 --> 00:48:51,490
And a fourth group, a specialist medicare care--

779
00:48:51,490 --> 00:48:55,459
those patients simply got a good physician who new chronic fatigue syndrome

780
00:48:55,460 --> 00:48:58,500
but did nothing other than just provide general medical care.

781
00:48:58,500 --> 00:49:01,710
And this is what was found.

782
00:49:01,710 --> 00:49:05,809
So. The patients who got the adaptive pacing therapy

783
00:49:05,809 --> 00:49:09,880
just don't don't crash, trust your instincts--

784
00:49:09,880 --> 00:49:13,339
basically did not, so, in this score--

785
00:49:13,339 --> 00:49:16,869
in this score, going down is getting better.

786
00:49:16,869 --> 00:49:20,380
and really, these patients are really

787
00:49:20,380 --> 00:49:23,450
Sick. And in this case...

788
00:49:23,450 --> 00:49:27,790
In this case, it was clearly that the patients did not improve

789
00:49:27,790 --> 00:49:31,509
by simply telling them, "Trust your instincts."

790
00:49:31,510 --> 00:49:34,700
The patients who had the cognitive behavioral therapy,

791
00:49:34,700 --> 00:49:38,430
they actually improved their performance

792
00:49:38,430 --> 00:49:41,500
but they did not get cured from CFS.

793
00:49:41,500 --> 00:49:45,250
It is so sad that this study is being cited

794
00:49:45,250 --> 00:49:48,390
as "cognitive behavorial therapy is curing CFS."

795
00:49:48,390 --> 00:49:53,660
It's not true. The patients simply got better, and it's good that the patients got better,

796
00:49:53,660 --> 00:49:57,828
it was statistically significant, but they were far from going back to

797
00:49:57,829 --> 00:49:59,260
their normal levels.

798
00:49:59,260 --> 00:50:03,500
The same thing with the graded exercise therapy--they got better

799
00:50:03,500 --> 00:50:07,650
in a statistically significant manner, but they were far from being completely well.

800
00:50:07,650 --> 00:50:11,540
And the same thing, the same findings were for the physical

801
00:50:11,540 --> 00:50:15,940
function in that regard. So that the

802
00:50:15,940 --> 00:50:19,700
same authors of the papers said, "Our finding that

803
00:50:19,700 --> 00:50:23,890
(the) study treatments, like those, were only moderately

804
00:50:23,890 --> 00:50:26,529
effective," they are not saying that they are curing CFS,

805
00:50:26,530 --> 00:50:32,430
also suggests that researching to more effective treatments are needed

806
00:50:32,430 --> 00:50:37,569
and that the fact that behavioral intervention means that patients get better

807
00:50:37,569 --> 00:50:40,680
by no means means that this is psychological in nature.

808
00:50:40,680 --> 00:50:45,900
And I have to say that, because I had a very sad conversation with a family

809
00:50:45,100 --> 00:50:46,530
member of a patient who

810
00:50:46,530 --> 00:50:49,720
was doubting that our patient had the disease,

811
00:50:49,720 --> 00:50:53,200
and cited this study to say that now

812
00:50:53,200 --> 00:50:56,160
there was proof that "CFS was psychological"

813
00:50:56,160 --> 00:51:00,240
and that with psychological intervention, the patients "could get cured." This is far

814
00:51:00,240 --> 00:51:01,109
from truth,

815
00:51:01,109 --> 00:51:04,839
from the actual findings of the study. So I think we have

816
00:51:04,839 --> 00:51:08,819
lots of work to do; we need

817
00:51:08,819 --> 00:51:13,160
all the best minds at Stanford, and we are gathering the best minds at Stanford

818
00:51:13,160 --> 00:51:16,920
around the team. We need to find an objective,

819
00:51:16,920 --> 00:51:20,430
a form of saying, "yes,the patient has CFS";

820
00:51:20,430 --> 00:51:23,558
we need to find black levels--

821
00:51:23,559 --> 00:51:27,740
biomarkers that can identify the situation; we need to find ways to

822
00:51:27,740 --> 00:51:31,580
identify the subgroup, which is the pathogen behind--

823
00:51:31,590 --> 00:51:35,579
it's possible that there are patient with CFS that are not infectious as well.

824
00:51:35,579 --> 00:51:39,520
We need to find those agents and to the right trials.

825
00:51:39,520 --> 00:51:43,109
The attitude that was have taken at Stanford

826
00:51:43,109 --> 00:51:47,529
reminds me of what we want to do, is similar to what's found in this

827
00:51:47,530 --> 00:51:50,790
late 70s movie (The Wild Child) from Francois Truffaut:

828
00:51:50,790 --> 00:51:54,450
they have found this child in the forest of France.

829
00:51:54,450 --> 00:51:59,439
it was wild. Did not know how to speak, perhaps couldn't even hear.

830
00:51:59,440 --> 00:52:03,869
Basically it was a wild child with an entity of behavior

831
00:52:03,869 --> 00:52:07,329
that was not understood at all. However,

832
00:52:07,329 --> 00:52:11,690
when he was brought to a room where a physician who wanted to really

833
00:52:11,690 --> 00:52:14,890
help him and understand him, was trying to describe

834
00:52:14,890 --> 00:52:19,890
the length of his hair, teeth, numbers of scars in his skin,

835
00:52:19,890 --> 00:52:22,160
et cetera; made, uh,

836
00:52:22,160 --> 00:52:25,308
(an) observation. The kid

837
00:52:25,309 --> 00:52:28,420
did not react when a heavy noise

838
00:52:28,420 --> 00:52:31,730
was produced in the room. And he said, "Did you notice?"

839
00:52:31,730 --> 00:52:36,590
He didn't react to that loud noise. He's deaf.

840
00:52:36,590 --> 00:52:40,300
Then, another man who has seen the kid in the wild,

841
00:52:40,300 --> 00:52:44,200
from the village, says, "How can he be deaf

842
00:52:44,200 --> 00:52:47,430
when in the large I've seen him turn around

843
00:52:47,430 --> 00:52:50,770
when a nut was cracked behind him?"

844
00:52:50,770 --> 00:52:55,400
So the physician who is trying to make the observation says, "Write this:

845
00:52:55,400 --> 00:52:58,900
Indifferent to loud noises... whereas he turns around

846
00:52:58,900 --> 00:53:02,170
when a nut is cracked behind him." So

847
00:53:02,170 --> 00:53:06,339
it's really having a candid attitude towards this disease:

848
00:53:06,339 --> 00:53:10,200
observing what is there, what the disease is telling us, what I think that one day,

849
00:53:10,200 --> 00:53:14,790
hopefully, we'll be able to (use to) make a difference. And that would not be possible with a team.

850
00:53:14,790 --> 00:53:18,819
So we're very grateful to the Brennan and Taskey families for their support;

851
00:53:18,819 --> 00:53:23,359
Lindsey Merrihew, who is right here in the room--none of these things

852
00:53:23,359 --> 00:53:27,140
trust me, would have been possible without Lindsey. She's really the head

853
00:53:27,140 --> 00:53:31,290
and the mover and the doer in the team. And all the people

854
00:53:31,300 --> 00:53:35,460
below her: Jane Norris, Amber Ruiz, Dr. Marzie Zinn, who is also here,

855
00:53:35,460 --> 00:53:38,540
Dr. Marcie Zinn has given the challenge of

856
00:53:38,540 --> 00:53:42,500
helping us to understand the brain fog and how to measure.

857
00:53:42,500 --> 00:53:45,780
So none of those things would have happened without the intervention

858
00:53:45,780 --> 00:53:51,910
of this great team. Thank you.

859
00:53:51,910 --> 00:53:55,420
[Question asked] Now the doctor has asked the question that,

860
00:53:55,420 --> 00:53:58,470
you know, obviously, this,

861
00:53:58,470 --> 00:54:01,490
uh, we have a problem.

862
00:54:01,490 --> 00:54:04,609
And it's the waiting time. Lindsey, what is

863
00:54:04,609 --> 00:54:08,430
the waiting time now?

864
00:54:08,430 --> 00:54:13,440
Two to three years. So we are trying to desperately try to,

865
00:54:13,440 --> 00:54:16,609
um, to to cope with the high demand.

866
00:54:16,609 --> 00:54:20,440
There is a physician in the area, in El Camino Hospital,

867
00:54:20,440 --> 00:54:23,980
[Dr. Andreas Kogelnik]. So [K-

868
00:54:23,980 --> 00:54:27,690
0-G-E-L-N-I-K.]

869
00:54:27,690 --> 00:54:30,240
And Lindsey and I can give you his contact information,

870
00:54:30,240 --> 00:54:33,970
who is seeing now patients with chronic fatigue syndrome, with an approach

871
00:54:33,970 --> 00:54:37,649
similar to ours. So that has helped us, to

872
00:54:37,650 --> 00:54:40,900
have patients being seen by him.

873
00:54:40,900 --> 00:54:44,599
Thank you, yeah, you are correct, it's right here, his name:

874
00:54:44,599 --> 00:54:48,230
Kogelnik, actually. K-O-G. Kogelnik.

875
00:54:48,230 --> 00:54:52,190
Um, so, but... you know, our hope,

876
00:54:52,190 --> 00:54:55,790
our goal, in addition to one day

877
00:54:55,790 --> 00:54:59,220
be able to understand the disease and erradicate it,

878
00:54:59,220 --> 00:55:02,868
in addition to that dream, is that we need to desperately bring

879
00:55:02,869 --> 00:55:06,319
education our colleagues, medical students,

880
00:55:06,319 --> 00:55:09,720
fellows residents, so they can perpetuate that

881
00:55:09,720 --> 00:55:12,730
model. [Question asked] So the question was made that,

882
00:55:12,730 --> 00:55:17,309
what was the dose that was used in the study that we cited in the late 80s,

883
00:55:17,309 --> 00:55:20,849
where patients with chronic fatigue syndrome were treated with acyclovir,

884
00:55:20,849 --> 00:55:23,859
and the answer is that they used the standard dose

885
00:55:23,859 --> 00:55:26,930
for that time, that were not high doses.

886
00:55:26,930 --> 00:55:30,710
And what is striking is they used only five weeks,

887
00:55:30,710 --> 00:55:34,400
yet they went out and made that as the Bible,

888
00:55:34,400 --> 00:55:38,329
that antiviral intervention does not work for CFS.

889
00:55:38,329 --> 00:55:41,670
[Question asked] The question is, if valgancyclovir is available.

890
00:55:41,670 --> 00:55:46,150
Yes. It is available; it's approved by the FDA;

891
00:55:46,150 --> 00:55:49,470
when we did the trial, we went to the FDA,

892
00:55:49,470 --> 00:55:53,589
got the permission at the FDA to use it for this other indication.

893
00:55:53,589 --> 00:55:56,630
It needs medical supervision--

894
00:55:56,630 --> 00:55:59,950
there is a safety issue with the blood cells, but

895
00:55:59,950 --> 00:56:03,529
if you have proper supervision, that usually is not an issue.

896
00:56:03,530 --> 00:56:06,990
There is a question mark on the long-term use about,

897
00:56:06,990 --> 00:56:11,529
in animals, it can cause cancer, we do not know if that happens in humans, but it

898
00:56:11,530 --> 00:56:12,900
has to always be

899
00:56:12,900 --> 00:56:16,890
discussed with your provider in that regard.

900
00:56:16,890 --> 00:56:19,339
[Question asked] So the question is, like--could people, knowing

901
00:56:19,339 --> 00:56:24,569
that some of these infections can do that devastation, can you do something

902
00:56:24,569 --> 00:56:28,359
in a prophylactic manner, to prevent that [you're] going to that

903
00:56:28,359 --> 00:56:32,390
unhealthy cascade. Not that we know of.

904
00:56:32,390 --> 00:56:37,848
If we were to write something in a magazine, in a journal, we

905
00:56:37,849 --> 00:56:41,619
would have to say "nothing is known." If we were having a

906
00:56:41,619 --> 00:56:45,910
coffee table conversation, then you could say some things like,

907
00:56:45,910 --> 00:56:50,149
"Please don't--you know, there are many patients who, when they are sick, they try

908
00:56:50,150 --> 00:56:53,900
to go to the extreme, they try to to back to work naturally.

909
00:56:53,900 --> 00:56:57,740
I would suggest that common-sense measures of rest when they have the

910
00:56:57,740 --> 00:56:58,759
acute illness

911
00:56:58,760 --> 00:57:03,859
be exaggerated, in fact--that they take more time to rest.

912
00:57:03,859 --> 00:57:07,790
The other thing that we have found, but this is totally anecdotal, is some of the

913
00:57:07,790 --> 00:57:11,710
kids of our colleagues at Stanford who have come down with the acute

914
00:57:11,710 --> 00:57:15,160
infections, and we have measured the [levels] and they had been positive;

915
00:57:15,160 --> 00:57:18,299
we had given the antibiotic right there

916
00:57:18,299 --> 00:57:21,780
and it seems like--but it's very anecdotal--that they

917
00:57:21,780 --> 00:57:25,329
recover. But, anecdotal. [Question asked] The question is about

918
00:57:25,329 --> 00:57:28,980
the levels of HSV-1, or HSV-2,

919
00:57:28,980 --> 00:57:33,730
and even with HSV-6--do they travel travel together?

920
00:57:33,730 --> 00:57:37,780
Preliminarily, it seems like the EBV and HSV-6,

921
00:57:37,780 --> 00:57:42,569
they travel together in a surgroup of patients. We thought that that surgroup was gonna be

922
00:57:42,569 --> 00:57:46,420
large, the one that we allegedly found,

923
00:57:46,420 --> 00:57:49,549
but he seems like it's a small surgroup.

924
00:57:49,549 --> 00:57:54,220
It's rare to have a patient with HSV-1 and HSV-6.

925
00:57:54,220 --> 00:57:58,240
We don't know why yet. Or HSV-2 and HSV-6.

926
00:57:58,240 --> 00:58:01,490
It's not not uncommon to have HSV-1 and HSV-2.

927
00:58:01,490 --> 00:58:05,118
And the levels of antibodies seems to be high.

928
00:58:05,119 --> 00:58:09,150
We have had a surgroup of patients with

929
00:58:09,150 --> 00:58:12,260
HSV-2, genital, HSV-1,

930
00:58:12,260 --> 00:58:16,890
oral blisters, and we have intervened them with acyclovir, which is a much

931
00:58:16,890 --> 00:58:19,180
simpler drug to give.

932
00:58:19,180 --> 00:58:22,419
And after a year, year-and-a-half intervention,

933
00:58:22,420 --> 00:58:26,240
It seems that we see these recoveries that are truly dramatic.

934
00:58:26,240 --> 00:58:30,618
In a surgroup of patients. Ideally we should do

935
00:58:30,619 --> 00:58:34,720
a randomized trial; I'm trying to see how we can come up with the funds

936
00:58:34,720 --> 00:58:38,640
to do the right study, similar to the other, to prove that that's the case.

937
00:58:38,640 --> 00:58:43,500
[Questions asked] Two questions: one is, if the drugs that I show you, the one that we have used,

938
00:58:43,500 --> 00:58:48,200
if they're anti-retroviral, meaning anti-HIV drugs,

939
00:58:48,200 --> 00:58:52,140
what I have shown you--emphasize that--what I have shown you

940
00:58:52,140 --> 00:58:55,540
they are not anti-retrovirals; they are not anti-HIV.

941
00:58:55,540 --> 00:58:58,710
And the second question: if there,

942
00:58:58,710 --> 00:59:01,920
if there is like a stem cell base for the disease,

943
00:59:01,920 --> 00:59:06,339
because the virus can get into, some other viruses can get into the genetic

944
00:59:06,339 --> 00:59:09,710
code, and the answer is, "not as far as we know."

945
00:59:09,710 --> 00:59:13,420
It seems like it has to do more with the germ line cells.

946
00:59:13,420 --> 00:59:16,460
The very early cells, but not stem cell

947
00:59:16,460 --> 00:59:21,530
based. And as far as we know it's not stem-cell based.

948
00:59:21,530 --> 00:59:24,960
But there is very litle known about that part.

949
00:59:24,960 --> 00:59:29,140
[Question asked] So the question is about: if long-term,

950
00:59:29,140 --> 00:59:33,290
careful, safe, thoughtful,

951
00:59:33,300 --> 00:59:37,619
antiviral or anti-microbial intervention can result in the improvement of

952
00:59:37,619 --> 00:59:43,890
chronic diseases like this. So that's the model that we are operating. So the--

953
00:59:43,890 --> 00:59:46,890
if you see what we're doing behind, it suggests that

954
00:59:46,890 --> 00:59:50,240
infection at low levels can do a lot of stuff. That's

955
00:59:50,240 --> 00:59:53,259
the model that we are using. And then that's--

956
00:59:53,260 --> 00:59:56,410
So pressing that for long periods of time should improve. So

957
00:59:56,410 --> 01:00:00,980
the question suggests the possibility that what about if we did that,

958
01:00:00,990 --> 01:00:05,640
for the long term effects of varicella-zoster virus, or shingles virus

959
01:00:05,640 --> 01:00:09,879
in terms of pain, this is well known, that it can do this problem.

960
01:00:09,880 --> 01:00:13,670
Preliminary--but again, just two small patients, but

961
01:00:13,670 --> 01:00:18,520
highly gratifying. We have patients who had come to us for five years of

962
01:00:18,520 --> 01:00:21,720
pain, that is clearly what we call the

963
01:00:21,720 --> 01:00:24,910
"herpes without rash."

964
01:00:24,910 --> 01:00:28,470
and this woman, after like a year and a half of acyclovir, is

965
01:00:28,470 --> 01:00:29,430
back to like,

966
01:00:29,430 --> 01:00:32,930
smile, bubbly personality, normal--

967
01:00:32,930 --> 01:00:36,690
those are anecdotal. The point is,

968
01:00:36,690 --> 01:00:41,790
I think it calls for that. It calls for patients who have the shingles

969
01:00:41,790 --> 01:00:44,490
to be randomized to long term antiviral suppression

970
01:00:44,490 --> 01:00:49,598
versus not to show whether it has an impact on the post-herpetic pain

971
01:00:49,599 --> 01:00:52,690
or neuralgia. Very good point. [Question asked] What about

972
01:00:52,690 --> 01:00:57,300
families who share the same environment, who could have the same markers. And,

973
01:00:57,300 --> 01:01:01,599
the right study has not been done, though we do have,

974
01:01:01,599 --> 01:01:06,910
I think it's--correct me if I'm wrong, Lindsey, but we have four families now,

975
01:01:06,910 --> 01:01:11,490
four families, in whom they share the markers,

976
01:01:11,490 --> 01:01:14,400
and not all of them express the disease. So it looks like

977
01:01:14,400 --> 01:01:18,910
something else is needed. So we have four families who had that behavior.

978
01:01:18,910 --> 01:01:23,200
So it seems that you need more than the infection to express disease.

979
01:01:23,200 --> 01:01:26,500
[Question asked] The question is, are we testing patients for XMRV.

980
01:01:26,500 --> 01:01:30,990
So we asked the Microbiology Department at Stanford

981
01:01:30,990 --> 01:01:33,579
and they are stepping up to the plate. They are

982
01:01:33,579 --> 01:01:38,109
setting up the test. We need to find a few more resources, but they are,

983
01:01:38,109 --> 01:01:41,420
they are doing it. And some of our patients are doing it

984
01:01:41,420 --> 01:01:44,780
through the other--it is a commercial laboratory that now,

985
01:01:44,780 --> 01:01:48,170
that's it. Good question. [Question asked] The question is are there any

986
01:01:48,170 --> 01:01:52,430
clinical trials? There are clinical trials of (a) different nature and kind.

987
01:01:52,430 --> 01:01:55,848
There is, for example, a clinical trial with interferon.

988
01:01:55,849 --> 01:01:59,650
Interferon is an antiviral, and it's given to patients with the hope that they

989
01:01:59,650 --> 01:02:03,839
will recover. And that's (they are) the Nevada group.

990
01:02:03,839 --> 01:02:07,490
There are others in Europe that obviously our patients will not have access to.

991
01:02:07,490 --> 01:02:11,430
Our idea, our dream, is to have

992
01:02:11,430 --> 01:02:14,879
a whole group at Stanford that would just do

993
01:02:14,880 --> 01:02:18,440
clinical trials for these kinds of patients. But that is an

994
01:02:18,440 --> 01:02:22,839
infrastructure that is relatively large. And unfortunatel, the NIH

995
01:02:22,839 --> 01:02:26,420
does not give much money for clinical trials, and that's

996
01:02:26,420 --> 01:02:30,900
unfortunate. [Question asked] So the question is about the role of alternative treatments.

997
01:02:30,900 --> 01:02:35,180
What (I've) shown you, the role of cognitive-behavioral intervention,

998
01:02:35,180 --> 01:02:39,520
the, sort of like, physical therapy intervention,

999
01:02:39,520 --> 01:02:42,799
clearly points to the fact that there are

1000
01:02:42,799 --> 01:02:46,920
things that patients can do that could be thoughtful,

1001
01:02:46,920 --> 01:02:50,619
not expensive, that could work for the patient.

1002
01:02:50,619 --> 01:02:53,900
So there are things that the patients can do, and they can

1003
01:02:53,900 --> 01:02:57,240
be helped. The answer is yes. And they are in the alternative

1004
01:02:57,240 --> 01:03:02,288
[Question asked] The relationship--is there any any relationship between fatigue,

1005
01:03:02,289 --> 01:03:05,559
that is temporal, versus chronic fatigue,

1006
01:03:05,559 --> 01:03:08,579
because as it's pointed (out), some interventions

1007
01:03:08,579 --> 01:03:11,630
from a good cup of coffee, or provigil,

1008
01:03:11,630 --> 01:03:14,960
or ritaline, make patients with short-term fatigue

1009
01:03:14,960 --> 01:03:18,950
better. There is a subset of patients with chronic fatigue

1010
01:03:18,950 --> 01:03:22,299
syndrome that experience that temporal improvement with those same

1011
01:03:22,299 --> 01:03:23,369
interventions,

1012
01:03:23,369 --> 01:03:27,390
but they are not lasting. All of them tell us,

1013
01:03:27,390 --> 01:03:30,680
when they use those interventions, they basically lead them to

1014
01:03:30,680 --> 01:03:33,788
overdo it and crash. And it's very

1015
01:03:33,789 --> 01:03:38,000
short-term--the effect is very short-term.

1016
01:03:38,000 --> 01:03:42,300
We don't know if the same thing that causes fatigue

1017
01:03:42,300 --> 01:03:46,100
are the same mechanisms that cause chronic fatigue. Our suspicion is that there are

1018
01:03:46,100 --> 01:03:50,510
two different things doing it. Because the patient who had the chronic fatigue,

1019
01:03:50,510 --> 01:03:53,530
more than the fatigue, they have all these other other symptoms.

1020
01:03:53,530 --> 01:03:56,910
Many of them describe--it's like having a bad flu

1021
01:03:56,910 --> 01:04:00,618
going on for years, or for decades. [Question asked] So the question is, are we

1022
01:04:00,619 --> 01:04:04,200
seeing family members of patients with chronic fatigue syndrome

1023
01:04:04,200 --> 01:04:07,859
higher incidents of autoimmune problems?

1024
01:04:07,859 --> 01:04:10,980
The answer is yes. It seems like they tell us stories

1025
01:04:10,980 --> 01:04:14,900
about patients having a higher--the patients tend to have more

1026
01:04:14,900 --> 01:04:18,410
thyroid problem(s) of the autoimmune type. Um,

1027
01:04:18,410 --> 01:04:22,288
we are starting to pay attention to vitiligo, which is

1028
01:04:22,289 --> 01:04:26,200
whitening of the skin when the melanocytes are attacked by

1029
01:04:26,200 --> 01:04:29,680
antibodies. So it seems like there is another

1030
01:04:29,680 --> 01:04:33,348
clue towardas autoimmunity there.

1031
01:04:33,349 --> 01:04:36,480
[Question asked] Are the HSV-6 titers easily done and the answer is

1032
01:04:36,480 --> 01:04:40,380
yes. We don't have any commercial tie with

1033
01:04:40,380 --> 01:04:44,000
anybody. But there is a lot that we suggest

1034
01:04:44,000 --> 01:04:47,130
where the HSV-6 titers can be done, and its

1035
01:04:47,130 --> 01:04:50,609
focus, only because we are familiar with their numbers,

1036
01:04:50,609 --> 01:04:55,470
we have learned to to know what is low, what is medium, what is high.

1037
01:04:55,470 --> 01:04:59,240
But we have no commercial connection with them, but focus laboratory

1038
01:04:59,240 --> 01:05:02,720
appears to be reliable in giving us titers that we can

1039
01:05:02,720 --> 01:05:07,189
sort of like, act upon. [Question] So it's been said that there are,

1040
01:05:07,190 --> 01:05:11,299
there is a support group based in Mountain View,

1041
01:05:11,299 --> 01:05:14,390
that there is a sign up sheet outside here,

1042
01:05:14,390 --> 01:05:17,450
and it's important to share

1043
01:05:17,450 --> 01:05:20,618
these experiences. It's important to

1044
01:05:20,619 --> 01:05:25,180
bring this together, and as it was shown in that study in The Lancet,

1045
01:05:25,180 --> 01:05:29,379
it sounds like having interventional, behavioral intervention,

1046
01:05:29,380 --> 01:05:31,160
cognitive intervention,

1047
01:05:31,160 --> 01:05:34,279
it seems like it helps. And it's very important that,

1048
01:05:34,280 --> 01:05:38,859
that--do not let people talking to--that study proves

1049
01:05:38,859 --> 01:05:42,130
that CFS can be cured, or that that study proves

1050
01:05:42,130 --> 01:05:45,849
that it's psychological. In addition to what you said, they excluded patients

1051
01:05:45,849 --> 01:05:50,289
who couldn't come to the hospital, so the sickest patients didn't make it into the trial.

1052
01:05:50,289 --> 01:05:53,930
Though their scores were really low in terms of performance,

1053
01:05:53,930 --> 01:05:57,609
so in addition to the selection issues,

1054
01:05:57,609 --> 01:06:01,470
the study does not prove a psychological (connection) and does not prove

1055
01:06:01,470 --> 01:06:04,629
that that's the way to cure patients. [Question asked] Is there any

1056
01:06:04,630 --> 01:06:08,240
there any neurological or phenotyping difference, phenotype difference, between

1057
01:06:08,240 --> 01:06:10,709
those patients who come down with an

1058
01:06:10,710 --> 01:06:14,380
illness, with CFS, after they have an acute illness,

1059
01:06:14,380 --> 01:06:18,369
particularly an infectious illness, versus those who have their onset

1060
01:06:18,369 --> 01:06:22,619
not associated with an infection? Not that we know of,

1061
01:06:22,619 --> 01:06:26,390
but we are separating them by when we take the history,

1062
01:06:26,390 --> 01:06:29,670
and in the analysis that we are doing, looking for pathogens, or for immune

1063
01:06:29,670 --> 01:06:31,230
response abnormalities--

1064
01:06:31,230 --> 01:06:34,920
we are taking that into account. So hopefully we'll be able

1065
01:06:34,920 --> 01:06:39,880
to answer--no, I think he's asking like, independent of (whether) it's a woman or man,

1066
01:06:39,880 --> 01:06:43,750
is there a difference between those who started the illness with an infection,

1067
01:06:43,750 --> 01:06:47,700
versus those do do not start the disease with an infection.

1068
01:06:47,700 --> 01:06:51,180
It is well-known that 75 percent of the patients with

1069
01:06:51,180 --> 01:06:55,780
CFS, 75 percent are women. Now

1070
01:06:55,790 --> 01:06:59,520
if we were to take women alone, there are women who started their CFS

1071
01:06:59,520 --> 01:07:04,849
without an infection. And so the sample size on the second study was very small.

1072
01:07:04,849 --> 01:07:08,119
But women can start their CFS with not an infectious illness.

1073
01:07:08,119 --> 01:07:11,460
And the question is, are there differences between those who,

1074
01:07:11,460 --> 01:07:14,670
who tell you the precise time where they started,

1075
01:07:14,670 --> 01:07:18,900
versus those who who did not. So the question is, when the patients get a

1076
01:07:18,900 --> 01:07:20,100
viral illness,

1077
01:07:20,100 --> 01:07:23,339
some of them go into CFS and some do not.

1078
01:07:23,339 --> 01:07:28,200
The most common factor that has been associated in the study

1079
01:07:28,200 --> 01:07:31,400
(that) have looked at this, is severity of the illness.

1080
01:07:31,400 --> 01:07:34,799
So the more severe the illness, the more likely they are

1081
01:07:34,799 --> 01:07:37,940
to go into having the illness--

1082
01:07:37,940 --> 01:07:42,130
as far as it's known. [Question asked] Well thanks to the support of one of our

1083
01:07:42,130 --> 01:07:45,480
patients, we started, Lindsey actually,

1084
01:07:45,480 --> 01:07:48,920
and Mrs. Kaski are really the people who

1085
01:07:48,920 --> 01:07:52,490
we have to thank. We started a website

1086
01:07:52,490 --> 01:07:56,599
where, at Stanford, and, Lindsey, the name of the website please?

1087
01:07:56,599 --> 01:07:59,720
so http://chronicfatigue.stanford.edu/

1088
01:07:59,720 --> 01:08:03,578
...and there we are starting to put up as many resources as

1089
01:08:03,579 --> 01:08:06,950
we can, everything that we have learned about,

1090
01:08:06,950 --> 01:08:10,868
of the disease for the past few years. [Question asked] We know that some patients

1091
01:08:10,869 --> 01:08:14,630
crash. Have we measured the amount of dividers

1092
01:08:14,630 --> 01:08:17,899
or cytokines during those crash periods?

1093
01:08:17,899 --> 01:08:22,540
so we attempted to do that in the study that I showed you, where we found differences.

1094
01:08:22,540 --> 01:08:26,350
But the numbers are so small, and we didn't see any differences.

1095
01:08:26,350 --> 01:08:29,969
But I think it's a matter of just doing that.

1096
01:08:29,969 --> 01:08:34,799
The tough part of studying that is, how can you justify

1097
01:08:34,799 --> 01:08:39,890
to ask a patient, "Take this drug. It's gonna make you sick,

1098
01:08:39,890 --> 01:08:42,620
and we'll study you." So ethically it's hard. [Question asked]

1099
01:08:42,620 --> 01:08:46,799
These viruses are latent. They are there for the life of the patient.

1100
01:08:46,799 --> 01:08:50,299
So we are not suggesting that with these long-term anti-

1101
01:08:50,299 --> 01:08:53,509
viral interventions we are eradicating the

1102
01:08:53,509 --> 01:08:57,549
virus out of the body, we are trying to, if our theory is correct,

1103
01:08:57,549 --> 01:09:01,819
bring them under control. So--and you are absolutely correct--

1104
01:09:01,819 --> 01:09:04,969
I think that part of the reason it has eluded

1105
01:09:04,969 --> 01:09:09,799
our understanding of the disease, is that they are at very low levels

1106
01:09:09,799 --> 01:09:12,939
even when they are causing disease. That is correct.

1107
01:09:12,939 --> 01:09:16,108
[Question asked] It's more common in women--have we seen mothers

1108
01:09:16,109 --> 01:09:20,120
giving it to their daughters? So we have,

1109
01:09:20,120 --> 01:09:24,599
sadly, a few cases where that has been the case.

1110
01:09:24,600 --> 01:09:28,238
And mostly related to that situation, where dividers

1111
01:09:28,238 --> 01:09:32,448
integrate into the chromosome, the human herpes--so herpes viruses

1112
01:09:32,448 --> 01:09:35,689
normally do not integrate into the chromosome

1113
01:09:35,689 --> 01:09:39,669
like HIV does, like the XMRV does,

1114
01:09:39,670 --> 01:09:44,120
herpes viruses are known for not doing that. But the HSV-6 has found a

1115
01:09:44,120 --> 01:09:48,839
clever way to do it, and they--those patients

1116
01:09:48,839 --> 01:09:53,420
seem to pass their virus, particularly mothers to daughters,

1117
01:09:53,420 --> 01:09:56,929
through their chromosomes. So there are situations,

1118
01:09:56,929 --> 01:10:00,300
but that's the exception, luckily. But it's--

1119
01:10:00,300 --> 01:10:04,500
these are the tougher (cases) to deal with. [Question asked] So the question is very clever. So the same

1120
01:10:04,500 --> 01:10:05,929
way we can prevent--

1121
01:10:05,929 --> 01:10:11,909
and that is true--we can prevent HIV-infected mothers from giving HIV to their babies.

1122
01:10:11,909 --> 01:10:15,759
Can something like that be done for mothers with CFS?

1123
01:10:15,760 --> 01:10:19,800
Unfortunately, the drugs

1124
01:10:19,800 --> 01:10:22,540
can damage the baby, theratogenic, so that

1125
01:10:22,540 --> 01:10:25,890
makes it very hard to justify doing it with our

1126
01:10:25,890 --> 01:10:30,650
proper study setting. So that makes it very hard. But

1127
01:10:30,650 --> 01:10:33,670
I was at a meeting last night in

1128
01:10:33,670 --> 01:10:36,710
in Washington, with a patient who has

1129
01:10:36,710 --> 01:10:40,730
her daughter with it, and she once--her daughter,

1130
01:10:40,730 --> 01:10:44,919
through the treatment that we did, went back to complete normality after years of

1131
01:10:44,920 --> 01:10:48,940
having the illness. And they are now desperate that she got married,

1132
01:10:48,940 --> 01:10:52,990
newly married, and they want to have a baby, et cetera. How do you do it?

1133
01:10:52,100 --> 01:10:55,550
At this point there is nothing we can do. Unfortunately.

1134
01:10:55,550 --> 01:10:59,140
[Question asked] Two points: one is, do we have ways to

1135
01:10:59,140 --> 01:11:03,469
standardize what we are doing, so other physicians can have easy access

1136
01:11:03,469 --> 01:11:08,380
to doing those steps, and following the--the answer is yes.

1137
01:11:08,380 --> 01:11:11,659
And we talk to other physicians who are--

1138
01:11:11,659 --> 01:11:15,230
So many physicians had doing this now, nationwide,

1139
01:11:15,230 --> 01:11:19,590
and sometimes the patients, after they have been on the waiting list, they come to us

1140
01:11:19,600 --> 01:11:22,190
after they have been treated. And we're just fine-tuning the issues.

1141
01:11:22,190 --> 01:11:25,860
so we do have standard formats

1142
01:11:25,860 --> 01:11:29,159
that we give out to physicians.

1143
01:11:29,159 --> 01:11:32,509
And I think that I can say that, because

1144
01:11:32,510 --> 01:11:37,190
it's legal, and medically viable, we can actually put those protocols in

1145
01:11:37,190 --> 01:11:38,629
the website as well,

1146
01:11:38,630 --> 01:11:42,110
because none of the drugs that we personally,

1147
01:11:42,110 --> 01:11:45,710
we at the clinic are using, none of them are experimental.

1148
01:11:45,710 --> 01:11:49,699
They are all FDA-approved. And as you know,

1149
01:11:49,699 --> 01:11:54,849
any physician has the freedom to use any drug that is approved by the FDA for any

1150
01:11:54,850 --> 01:11:56,890
other indication that is reasonable.

1151
01:11:56,890 --> 01:12:01,179
so that is not illegal. And we put those protocols

1152
01:12:01,179 --> 01:12:04,280
in the website so physicians can download them.

1153
01:12:04,280 --> 01:12:07,730
But in the meantime, they can call us, and we give them out, and we talk to the

1154
01:12:07,730 --> 01:12:11,610
physicians as well. Regarding the equilibrium--

1155
01:12:11,610 --> 01:12:14,809
That is a drug

1156
01:12:14,810 --> 01:12:18,110
that comes from China, so we don't prescribe it because we we cannot

1157
01:12:18,110 --> 01:12:23,259
guarantee what--how many milligrams and the purity of the drug,

1158
01:12:23,260 --> 01:12:27,320
but if the suspicion is that other kinds of viruses called

1159
01:12:27,320 --> 01:12:31,920
entero- or echoviruses are behind it, we highly suggest the patient to

1160
01:12:31,920 --> 01:12:35,280
consult Dr. Chia in Southern California, because he

1161
01:12:35,280 --> 01:12:39,120
really is the one with the expertise, and that's his baby,

1162
01:12:39,120 --> 01:12:42,519
and I totally trust that what he has found is valid.

1163
01:12:42,520 --> 01:12:46,489
But we don't have the expertise with the administration of the drug.

1164
01:12:46,489 --> 01:12:47,500
Thank you. [Applause]