[imark3000]

I am recovering from 2 weeks flu. During this time my PD symptoms (mainly tremor) became notably worse and did not improve as I am recovering from the flu.
Any body had similar experience?

Imad

[girija]

Yes! Flu virus is nasty and induces a lot of inflammation in the body and that makes PD symptoms worse, A while back there were a few reports on flu and PD>
here is a summary of one:


Avian influenza can cause a predisposition to PD
published Aug 2009 in the Proceedings of the National Academy of Sciences.

Epidemiological studies done in the 1980s showed that survivors of the 1918 Spanish influenza, a pandemic that killed more than 50 million people worldwide, had a greater incidence of Parkinson's disease later in life than the general population. Recent studies have suggested that the currently circulating strain of avian influenza has similar pathology to the 1918 flu. Though the subtypes of the viruses are different (Spanish flu shares the H1N1 subtype with the current H1N1 swine flu, whereas avian influenza has an H5N1 subtype), both viruses appear to enter the central nervous system (CNS) and can cause encephalitis, or inflammation of the brain.

Girija


QUOTE=imark3000;631930]I am recovering from 2 weeks flu. During this time my PD symptoms (mainly tremor) became notably worse and did not improve as I am recovering from the flu.
Any body had similar experience?

Imad[/QUOTE]

[RLSmi]

Smeyne, the scientist leading the recently-published study in which the H5N1 bird flu virus produced PD-like symptoms in mice just visited our institution. He gave a seminar yesterday on this work, along with more recent unpublished data from this project.

He described at least two results that surprised me:

1) The virus-treated mice which developed PD-like symptoms (bradykinesia, forelimb tremor, difficulty initiating movement) about a week after intranasal innoculation, actally appeared to be recovered after another 2 or 3 weeks and remained free of symptoms up to 90 days!

2) Virus particles, detected first in the lungs of the innoculated mice, subsequently appeared in the enteric sympathetic ganglia, the vagal nerve, the vagal nucleus of the basal ganglia, then the rest of the midbrain, including the substantia nigra and the striatum. Virus were seen to enter neurons and microglia, but not astroglia. Most surprisingly, the infected neurons appeared not to be lost, although infected microglia did clearly appear to be activated, indicating an inflammatory process. Furthermore, the microglia retained their activated morphology even after the mice no longer displayed neurological symptoms and virus particles were no longer detectable!

The mouse experiments seem to nicely recapitulate certain aspects of PD. Most intriguing is the progression pattern of the viral movement, and its similariy to the Braak hypothesis of development of idiopathic human disease. Although the absence of neuron loss and their apparent recovery is inconsistent with what is thought to occur in human PD, the persistence of microglial activation definitely suggests what could be an initial step in a "two-hit" disease process.

Robert

[girija]

Robert,
This information you provided is so interesting. What you described in your #1 point seems like what a vaccine would do! Since the virus used in their experiments is active, symptoms were visible, I can easily see if the viral potency is reduced or using viral peptides can make the same into a vaccine. It would be very exciting to see how these mice would respond to H5N1 infection a second time. I am so sure that T regulatory cells are involved in this.

#2 With the data like that, I think PD needs to be redefined... Once again these observations fit so well into T cells being the killers of neurons. Neurons are infected but not killed because regulatory cells are in charge and killer T cells are under control or tolerised to be precise. Microglia once activated probably will remain so, because of the persistent antigen, i.e, the viral proteins etc even when there is no viral infection. Some in the field have argued that dendrritic cells always have a trace of the antigen they have encountered as long as they live and thats the reason for such good immunity to viruses. In this case, I bet microglia remain somewhat dormant because of T reg cells or may even be astrocytes.

[HTML]Although the absence of neuron loss and their apparent recovery is inconsistent with what is thought to occur in human PD, the persistence of microglial activation definitely suggests what could be an initial step in a "two-hit" disease process.
[/HTML

Just to simplify the whole thing and give an explanation: Neuronal loss is prevented by silencing the T cells that kill neurons, and in the absence of severe inflammation, neurons can recover......so there is hope for the stem cell therapies. Twio hit hypothesis seems to be the way PD develops similar to cancer. So if you caanot stop the initiation of PD (no control over genetics), atleast you can stop or slow down the progression of PD with T cell based therapies.

This is very exciting info for me! May be because it fits into my hypothesis!!
thanks for posting it.

by the way, how did Dr.S explain his findings????

girija

[RLSmi]

Girija, he really did not have any ready explanations. Some immunologists in the audience seemed to be thinking about the T cell possibilities, but Dr. S did not really pick up on that.

[reverett123]

I invite everyone to read my blog post on this study.

There is some brilliant work and a possible Nobel there. And the St. Jude's work is pretty good, too.

I do think it is a little more complicated than you see thus far. It is not that the flu virus causes PD. What it does is to "prime" virgin microglia or "activate" previously primed ones. Other things can have the same effect. Other virus. Bacterial toxin LPS (lipopolysaccharide). I suspect that a number of things can, if they get past the BBB, trigger activation of the primed cell. Pollution, household chemicals, ultrafine soot particles, are all likely goads.

Five to ten years ago, P.M. Carvey at Rush and Bin Liu and J.S. Hong at the NIH showed similar effects using LPS in rats that had been primed in utero. It was found that injecting of LPS would activate the usual gang of defenders in the periphery (i.e. outside the BBB) plus it would activate those within the brain as well. The inflamation outside the brain lasted a few hours. That within the brain was still going strong ten months later!

Another argument for a multi-cause inflamatory process is the unfortunate case of Ilse Niehaus (sp?). She was a young lab tech who, by way of some broken lab glass, got LPS from salmonella into the wound and developed PD.

Even the stress factor that so any of us experience can be fit into this, as I explain here.

So, when the microglia were first exposed to the virus, they defeated it and "powered down" into a primed state. They were ready to react, not just to the virus, but to any of a number of stressors.

That, in a nutshell, is what Anne Frobert and I worked on for so long.

[imark3000]

Thank you Girija and Robert for responding to my thread. What you said while being technically difficult for me to fully understand but it is scary stuff .. that the flew viruses invade the brain deeply and may cause or exasperate the PD !
Actually I did not get the flu for many years and remained immune ... (I think mainly due to my intake of vitamins and antioxidants).
We moved from Jordan to Calgary-Canada 5 months ago to be near our daughter and actually we became baby-sitters for her 2 sons (one is 8 months old and the other is 6 years old) and both got the flu recently which they recovered from in few days. But their virus seems to have found a better prey in me and my wife as we are not recovered after 2 weeks ..and every time we seem to be fully recovered, we start a new cycle of the flu !!!
My daughter feels guilty but she has no option. I guess it is a little price to pay for staying close to your grand children !

Imad

Originally Posted by girija

Robert,
This information you provided is so interesting. What you described in your #1 point seems like what a vaccine would do! Since the virus used in their experiments is active, symptoms were visible, I can easily see if the viral potency is reduced or using viral peptides can make the same into a vaccine. It would be very exciting to see how these mice would respond to H5N1 infection a second time. I am so sure that T regulatory cells are involved in this.

#2 With the data like that, I think PD needs to be redefined... Once again these observations fit so well into T cells being the killers of neurons. Neurons are infected but not killed because regulatory cells are in charge and killer T cells are under control or tolerised to be precise. Microglia once activated probably will remain so, because of the persistent antigen, i.e, the viral proteins etc even when there is no viral infection. Some in the field have argued that dendrritic cells always have a trace of the antigen they have encountered as long as they live and thats the reason for such good immunity to viruses. In this case, I bet microglia remain somewhat dormant because of T reg cells or may even be astrocytes.

[HTML]Although the absence of neuron loss and their apparent recovery is inconsistent with what is thought to occur in human PD, the persistence of microglial activation definitely suggests what could be an initial step in a "two-hit" disease process.
[/HTML

Just to simplify the whole thing and give an explanation: Neuronal loss is prevented by silencing the T cells that kill neurons, and in the absence of severe inflammation, neurons can recover......so there is hope for the stem cell therapies. Twio hit hypothesis seems to be the way PD develops similar to cancer. So if you caanot stop the initiation of PD (no control over genetics), atleast you can stop or slow down the progression of PD with T cell based therapies.

This is very exciting info for me! May be because it fits into my hypothesis!!
thanks for posting it.

by the way, how did Dr.S explain his findings????

girija

[Conductor71]

Thanks Imad for a stimulating and timely topic and thanks to our forum experts in explaining this so all of us might understand. I am left with a couple of questions:

1) I noticed that, after getting the PD diagnosis, that the flu does feel different. Imad noted this too it seems. I suffered less but longer when I got the flu last fall. Is this a normal thing for those who have PD, or is it just a reflection of that particular strain as some are harder to shake than others? If we do have a more difficult time overcoming illness, does this too support the role of the immune system in PD? In other words, our immune system is still in overdrive in our brains so less help to ward off other infections- I know this is oversimplifying, pardon my naive thought process here

2) Does all this mean we should definitely get a flu shot or avoid it like the plague? I was really uncertain what to do, so I opted out on both the flu shot and the Swine Flu vaccine.

Thanks!

Laura

[reverett123]

Much of the sickness that we feel with a typical infection is not the result of actions taken by the virus, but instead, those of our own immune system. It is a way to force us to rest and lay around camp so that we can heal. With PD you get a strong immune system with the power to keep you on your back. It also protects from cancer.

Flu shot? No way in hell.

Originally Posted by Conductor71

Thanks Imad for a stimulating and timely topic and thanks to our forum experts in explaining this so all of us might understand. I am left with a couple of questions:

1) I noticed that, after getting the PD diagnosis, that the flu does feel different. Imad noted this too it seems. I suffered less but longer when I got the flu last fall. Is this a normal thing for those who have PD, or is it just a reflection of that particular strain as some are harder to shake than others? If we do have a more difficult time overcoming illness, does this too support the role of the immune system in PD? In other words, our immune system is still in overdrive in our brains so less help to ward off other infections- I know this is oversimplifying, pardon my naive thought process here

2) Does all this mean we should definitely get a flu shot or avoid it like the plague? I was really uncertain what to do, so I opted out on both the flu shot and the Swine Flu vaccine.

Thanks!

Laura

[RLSmi]

For what it is worth, I took the seasonal flu shot the previous 6 years but passed on both the seasonal and the H1N1 shots this year. I'm not aware of any changes in my PD, nor any other adverse effects in the years in which I had the vaccinations.