Weird Parkinson's Stuff

[Simusid]

A bit of backstory. My father in law is 82 and has a 12 year history of Parkinson's. He's pretty advanced now and has reached a point of severe mobility issues, primarily when walking. If he wants a drink and needs to walk into the kitchen he can stand up from his recliner but will essentially have "frozen feet" and unable to make the motion of the first step. It takes quite some time to say "Ok dad, move your foot, lets go! go, go, go! here we go!" and slowly he'll get the foot to move, and then the other, and then off we go.

Suppose he has to go up to the bathroom on the second floor. We will have those same issues and it may take 5 full minutes to get 20 feet from his chair to the stairs, but less than 10 seconds to get up the short stairway. I happened to mention this to his neurologist yesterday (tangent - he's in the hospital post-fall that caused rhabdomyolitis, plus he has UTI). He gave me some great info about "gait initiation issues" in Parkinsons.

Here's the thing that I thought was cool/weird: He said that after he stands up and finds that he can't move, I should use masking tape (or similar) and put a straight line on the floor across the front of his feet. He called it a dynamic queue and for whatever reason, the brain will say "OK lift up your foot now"

Brain, you crazy! :blink:

 

[eprex]

Sorry to hear about your father and that is indeed weird (the masking tape).

There was an amateur chemist in the 80's that sloppily made synthetic heroine and it contained an incredibly strong neurotoxin that would effectively wipe out all of the dopamine in the substantia nigra. Many users subsequently developed crippling parkinson's; some even died. Very bizarre.

 

[mycrofft]

So it changed from a kinesthetic initiation/cue to a visual/cognitive one. Sort of like training a horse to start out of a gate with a bel, instead of a heel kick or being chased by a predator.

 

[samiam]

Sorry to hear about your father and that is indeed weird (the masking tape).

There was an amateur chemist in the 80's that sloppily made synthetic heroine and it contained an incredibly strong neurotoxin that would effectively wipe out all of the dopamine in the substantia nigra. Many users subsequently developed crippling parkinson's; some even died. Very bizarre.

Actually he was trying to make a synthetic morphine like derivative called MPPP. He incorectly added a acid to the mix which caused excessive heat which caused the final product to have a high level of MPTP contamination Which by itself is non-toxic but it crosses the BBB and is metabolized to MP+ which almost instantly kills dopaminergic neurons. He injected it to get high and got advanced PD Symptoms in a matter of days and was dead in 18 months

In response to the post PD is associated with multiple motor and non-motor symptoms. Bradykinesia which would be slow follow thru of movment and Akinesia which includes slowed/stopped initiation of movement.

The interaction betweene the basal ganglia including the substantia nigra and the VA/VL of the thallamus is fascinating. There is a very delacate ballance of tonic inhibition and excitory stimulation. When about 50% of the dopaminergic neurons in the SN are gone, there is a great increase in the tonic inhibition of the VA/VL which makes it very difficult to initiate movment. As i mentioned earler there are also non motor symptoms such as auditory reduction and cognitive imparments. The tape line most likely helps mitigate these non-motor factors and the brain recognizes and focuses on the line. Thats jusy my two cents. Just gave a review presentation on PD for a neurobiology class. PM if you have any more questions.

 

[eprex]

Actually he was trying to make a synthetic morphine like derivative called MPPP. He incorectly added a acid to the mix which caused excessive heat which caused the final product to have a high level of MPTP contamination Which by itself is non-toxic but it crosses the BBB and is metabolized to MP+ which almost instantly kills dopaminergic neurons. He injected it to get high and got advanced PD Symptoms in a matter of days and was dead in 18 months

Thanks, I was too lazy to google it myself haha. I'm not really interested in the chemistry, I just knew he was making a synthetic opiate and a sloppy mistake led to a neurotoxin being added to the mix. It's been awhile since I had to teach this story to students.

I think it's funny that a chemical can be considered "non-toxic" when it literally goes directly to your brain and metabolizes to a neurotoxin:lol:

 

[Sandog]

My Mother had Parkinson's and was confined to a wheel chair. Dementia set in and she quickly deteriorated. It was hard to watch a once strong women so quickly decline.

 

[samiam]

I think it's funny that a chemical can be considered "non-toxic" when it literally goes directly to your brain and metabolizes to a neurotoxin:lol:

Technically though it is non-toxic because it is a precursor it is actually really interesting though because MP+ is so toxic but a quick dose of MAOI's will stop the transformation and render it harmless

 

[silver]

Thanks, I was too lazy to google it myself haha. I'm not really interested in the chemistry, I just knew he was making a synthetic opiate and a sloppy mistake led to a neurotoxin being added to the mix. It's been awhile since I had to teach this story to students.

I think it's funny that a chemical can be considered "non-toxic" when it literally goes directly to your brain and metabolizes to a neurotoxin:lol:

There were actually a substantial amount of things that came out of this. Patients all popped up in the same area and they were able to determine it was MPTP. The physician who determine that later used MPTP as a Parkinsonism model in primates and then determined that levodopa or L-DOPA can be used to treat Parkinson's. Additionally some of these MPTP induced Parkinsonism patients received neural mesenchymal grafts, which cured them.

This terrible situation propelled neuro research on Parkinsons. There is a whole documentary I believe called Frozen Addicts or something like that...

 

[mycrofft]

Technically though it is non-toxic because it is a precursor it is actually really interesting though because MP+ is so toxic but a quick dose of MAOI's will stop the transformation and render it harmless

Technically speaking then most benzos are not effective, because they must be hepatically altered to yield an active effective metabolites? Or is that just Valium?

In the late Sixties cruddy LSD contained "trash lysergics" (per LA Free CLinic, 1972) which could mimic strychnine poisoning or CNS illness, notably cogwheel rigidity of arms and legs.