What requirements to explain PD?
 

I have been thinking about what must be explained by a theory or hypothesis that claims to have solved the PD riddle. I have 15 so far. Can you add others?


There are some characteristics of PD that any hypothesis must explain if it is to be valid. Some I would list include:
1) It is most prevalent in the US and least in the Third World.
2) Historically rare, it seems increasingly common.
3) Traditionally a disease of the old, it seems to strike younger than it once did.
4) Until recently, motor symptoms predominated but now a whole new group of non-motor symptoms unrelated to the substantia nigra are being worked in.
5) The cause must be common since it is so evenly distributed on the macro level, yet it must be rare since it is so unevenly distributed on the individual level.
6) It does not appear to be inherited, yet family clusters occur.
7) Inflammation has a role.
8) Early on, stress response seems unremarkable. Later on they can incapacitate.
9) It is more common among farmers and those who drink milk.
10) It can be intentionally brought on by specific toxins, yet most PWP never encounter them.
11) PWP seem to have experienced unusually high levels of stress pre-adolesence
12) It is commonly preceded by an unusual stress event, such as influenza or loss of a spouse.
13) While a sub-set, there really is a group with a "Parkinson's" personality.
14) Chronologically, symptoms appear in this order- a) loss of olfaction; b) motor; c) stress related.
15) Symptom sets differ greatly and, yet, later stages converge.

There are others, of course, but if a hypothesis is to be complete, it must either explain or dismiss as error these 15 at a minimum. Just a way of saying that Truth wins in the end.

Rick - my first, gut reaction is to your references to stress. They seem too specific (early exposure, etc). I believe stress plays a huge part, but my particular experience is much different.

I would reduce stress to a major factor, but all encompassing, at different times, rather than so specifically linked as you have it now.

Also, wondering if exposures to environmental related elements can be reduced to rural vs urban living rather than milk or diet related? Have you looked at well water vs water system related?

Interesting list!

my experience suggests
 

a combination of events/situations: early childhood trauma - (riding my tricycle down the stairs at age 2 1/2 ) incurring physical injury, emotional trauma and the ensuing emotional changes - fear, loss of trust, etc. I think subsequent injuries/traumas patter after the original , creating specific personality traits . (the pd personality) set all this ina specific genetic background OR family derived personality/ behavior traits. All of these things change hormonal patterns. I am certainly rambling... Basically wanted to say I think we havemore accidents than we used to - with less care/appreciation of the body...auto accidents extreme sports, atheletics, non-supportive lifestyles..

in regard to joop's post, i spend a hugh part of my day deciding what and when to eat in relation to doping...and due to my extreme thiness, have developed the habit of stuffing my self to try to maintain weight...even tho it clearly isn't working. i am eating 2-3 times what i used to - and losing weight.

thanks for starting this thread - it's critical!

Point !
 

Could it have been historically rare because it was unreported because it was thought to be just part of getting older? In the past 60 would have been considered old .

Let me stress the importance of stress...
 

:)

I see PD as a two-part disorder. One part is the result of fetal exposure to maternal bacterial infection, specifically the toxic remnants known as LPS. This exposure can simply arise from common things like gum disease or vaginosis. but there must be more or more would have PD.

One "rate limiting" factor is timing. The exposure has to occur at the right time and the "windows" can be short. There still must be more, however, for the same reasons.

But that is enough to set the stage for the next phase resulting from hypersensitivity to routine exposure to LPS and a chronic problem with microglia in the brain. The result is inflammation. This has been pretty well established by J.S. Hong, Bin Liu, PM Carvey, etc and is the immune system foundation of PD. But there has to be more to fit the patterns we see.

We come to a fork in the road here. One is the immune system (inflammation) and the other is the endocrine system (cortisol). Along the former we find that LPS is everywhere and inflammation is constant; that LPS can make us more vulnerable to rotenone, mercury, aluminum, manganese, etc In short, LPS sensitivity can account for a lot of the peculiar aspects of PD.

The other fork is more interesting. The natural reaction to inflammation comes from the endocrine system in the form of a natural steroid, cortisol. Mess up your knee and your doc uses a steroid to bring the swelling down. Your body does the same thing once the inflammation has fulfilled its role. Flooding the area with cortisol is the equivalent of the referee's whistle on the ball field.

But, because of the hypersensitivity to LPS, the players tend to ignore the whistle. Long term inflammation is destructive, especially in the brain, so the cortisol keeps coming. And long term cortisol is even more destructive. But what can the body do? Inflammatory cytokines are killing the brain. Counter-inflammatory hormones are doing their share as well. And the substantia nigra is particularly hard hit leading to motor symptoms.

Meanwhile, the endocrine system is becoming more and more stressed. We can't adapt as quickly as we once did. We become increasingly fragile.

Darn, I just realized that I hijacked my own thread....:D

Rick: :Good-Post: Great Thread! Keep on bumping. Eventually someone will light the lamp.

Bob C:

PD in history
 

Yes, 60 was once old. But my first tremor showed up in 1992 at the age of 39. An awful lot of us fall into the young onset category and I believe it to be different from senior onset which may well be normal ageing.

Even YOPD seems common enough and symptoms dramatic enough that some Pope or Prince would have had it and some scribe have noted it. But the examples commonly cited are so ambiguous that it is impossible to say that it was PD.

And take Dr. P's original article describing the condition. Why did he consider it of note? More importantly, why did he only have six cases to report and a number of those (2, I think) were not people he had examined, but were instead people he had seen pass on the street and never saw again. He had continued his father's medical practice at the same London location for fifty years. If he could not cite more cases than the six, isn't that odd?

The Industrial Revolution had been going for 75 years or so. London was a smoggy mess. Workers had left the familiar and supportive rural life for a sometimes hellish urban one. (Heck, we still use the adjective "Dickensian") Stress levels were way up.

But PD is never simple. Along with the stress, there were at least two other things I wonder about. One was that British traders had in the same period made sugar affordable and common. The other was the huge increase in sooty "particulate" pollution. Ultra Fine Particulates (UFPs) are tiny nanoparticles so small that they can go about anywhere. They can even travel along the transport systems within the long neuronal fiber of the axon. Even more interesting, they can latch on to other molecules that then "piggyback" with them past defensive membranes.

So, what happens when a person born sensitized to the bacterial toxin LPS inhales an UFP wed to a molecule of that toxin which penetrates the mucal barriers around the olfactory nerve and rides the little conveyor into the olfactory bulb? No one knows but I don't like the sound of it.

Maybe a healthy person can handle it, but what of a stressed out person? I'm sure the immune system would notice and inflammation would become a factor. Of course, that would just add in to the existing stress-generated inflammation which had been tearing at the BBB.

A few decades of this and enough brain cells lost to the immune response could lead to a tremor or two. And the spinning top of the endocrine system would begin to wobble. And everyone would assume that it was a neurological disease when it was actually the nervous system being the victim of the immune and endocrine.

(Just in case I am right and win a large Swedish prize someday, I want it on record that Anne Frobert, MD, gets equal billing or blame as the case may be. :D )

MJFF, are you listening?

Oh, and another thing....
 

("For gawd's sake, somebody get a net over him and shut him up...." :D )

This is important, and then I will go quietly.

If you stress a pregnant rat at the right time, then her pups will be more stress sensitive.

If you raise those pups stress-free on silken pilows with little mice slaves peeling them grapes, when they have pups then those pups will also be stress sensitive.

I find it a little bit chilling to think about what that could mean in a society of a billion or two with constant elevated stress. The old would be the first to show symptoms, but then progressively younger. Those in the higher stressed industrialized countries would suffer more than the lower stressed third world. Sheesh, we may be the Horsemen of the Apocalypse. (Now, ain't that like a Parkie? :D )

Rick - your list is so all-encompassing; the shared anecdotes among us so common that it seems as if anyone is at risk for PD - so it must be some underlying thing - a gene, another anomaly yet to be discovered - that links all of us.

the research has said for a long time that we probably had to be exposed to some risk, but PD doesn't occur unless another unknown is present (the trigger).

regarding stress - are you referring to external or internal stress? external stress that causes internal stress? internal stress that exacerbates internal functions?

two cents
 

Could part of it be that in many third world places, people still don't live long enough to get pd? They don't survive infections and bacteria like we do? They aren't exposed to as many food additives and chemicals? A fine example of how deceiving the phrase 'more is better' can be.

paula