[reverett123]

from http://sciencelife.uchospitals.edu/2...ning-disorder/

physicians despite being largely unexplained. Levodopa (L-dopa), the most commonly-used treatment for the symptoms of Parkinson’s disease, is meant to replace dopamine, the neurotransmitter lost as the disease progresses to its most severe stages. Clinicians recognize that the benefical effect builds up slowly over weeks despite the same dose of medication. In addition, after a patient’s L-dopa is stopped, the relief of a patient’s motor symptoms can persist partially for weeks, long past the time it takes to clear the drug entirely from one’s system. Though this effect has a name - the “long duration response,” or LDR - nobody’s quite sure what causes it, though physicians are happy to put it to use in patients.
-------------
But is it simply that one needs dopamine to move, or do you need dopamine to learn how to move? It’s a hard question to experimentally test, Beeler said.

“If you can’t perform something, in a sense you can’t learn it,” Beeler said. “On the other hand, if you can’t learn it you can’t perform it. It’s a chicken and egg thing.”
-----------------------------
“Clinically, if dopamine is necessary for learning, it changes the philosophy of treating these symptoms,” Kang said. “The usual philosophy is that we’re just providing a symptomatic treatment by dopamine; therefore, you usually take a conservative approach of waiting until they’re more bothered by the symptoms before you treat. But if it’s affecting your learning, and that lasts a long time, we should be treating more aggressively as soon as we know the patient has a deficit in dopamine.”

[paula_w]

I don't understand this one. If i went off l-dopa, i would be so rigid i wouldn't even be able to breathe in one day, even with a residual in me. I am sorely aware that this is addiction but what's a person to do other than surgery? These kinds of statements baffle me. I know how to move but the bones will literally break if i tried to do it without ldopa. it isn't a cure, so why would we want to get addicted even sooner. it isn't going to stop the cell death but wouldn't it stop the production of your own dopamine? confused.

[Conductor71]

This seems like the perfect spot to resurrect a thread we started on muscle memory this past spring and how it feels like we have forgotten how to move or that we have to coax our muscles back to life in the morning through moving. Please especially see Fiona's thoughts.

http://neurotalk.psychcentral.com/sh...=muscle+memory

I wonder though how much of this is due to learning disorder? I would say it is a long term memory feedback loop interruption or a dyslexia of movement. We rely on our working or procedural memory to piece the many small incremental moves that comprise one fluid larger one- isn't in essence, failure to launch into walking really an example of how our working memories now fail us? It is not surprising we end up with freezing of gait- our body is waiting for our brain to give muscles their first command, and without it how do our legs know what to do...

Maybe freezing results as our brain's way to say "hey, I'd like to help you but without knowing the proper switch to throw the best I can do is get you shuffling or dragging your feet" Actually it can do better as we can still easily break into a bourré or hustle, walk backward, skip to my lou, or ride a bike with no problems. The bigger question for me is why is it our ingrained everyday, ho hum, walking that is affected most?

More questions...

Hey, why can the mice still walk? Why would they show impairment in some sort of roller bar test but be able to walk over to the bar? Isn't that the reverse of our paradoxical movement?

One other thought, our movement impairment often stems from inability to initiate, what's to say this is isn't a weird expression of apathy or a malfunction in our reward center? Think about it...who gets rewarded for walking? Yet we can all still easily initiate running, dancing, skipping, etc. - these moves are less automatic and require more complex sequencing- if this is indeed a learning disorder why are we not impaired when it comes to more complex movement? There is more of an intrinsic performance component to these other moves; it actually requires more effort so why is it not impacted?


Thanks Rick, for always finding the unusual and challenging questions for us!

Laura

[imark3000]

Originally Posted by paula_w

I don't understand this one. If i went off l-dopa, i would be so rigid i wouldn't even be able to breathe in one day, even with a residual in me. I am sorely aware that this is addiction but what's a person to do other than surgery? These kinds of statements baffle me. I know how to move but the bones will literally break if i tried to do it without ldopa. it isn't a cure, so why would we want to get addicted even sooner. it isn't going to stop the cell death but wouldn't it stop the production of your own dopamine? confused.

Paula: Like you, I can't quite figure it out ... perhaps Rick will come to our rescue?
My best shot: that it is a sophisticated version of "use it or loose it".
Every time we move the right way, we reinforce this knowledge of how to move right as if we are learning it again. (My one year grand child started recently to walk or learn to walk and I could see that his walking or learning to walk is a continuous closed loop process ... attempt to walk - learn how -walk and so on).
What is new is that Dopamin is involved in learning process..and the lack of it implies loosing the learning re-enforcement process and in time, we loose the skill of walking correctly.
That is my best interpretation of still unproved theory. My challenge is how come that we retain skills learnt at childhood like skating or cycling even after many years of not practicing it ?????????????
My worse suspicions is that new research is faked to encourage consumption of sinemet
Imad

[lindylanka]

Laura,

our movement impairment often stems from inability to initiate, what's to say this is isn't a weird expression of apathy or a malfunction in our reward center?

I believe that your analogy of a kind of movement 'dyslexia' to be spot on...in fact we do not have a good vocabulary for these things because the current one was coined by people observing us from a position of thinking they understand what is happening.....

If you live every day or work every day with some of the following, dyslexia, dyspraxia, autism, aspergers, ADD, and even conditions like cerebral palsy in it's milder forms, you cannot help but see that the things that these people are experiencing have some parallels in PD......... so much so that I observe my dyspraxic, probably high functioning autistic, son and look out for the things I can see as solutions to his difficulties, and apply them to myself, which is much harder to do.....

But all these are damages or differences, some say that autism is having a brain wired differently, that the neurotransmission is fundamentally different, and of course that there are genetic things involved too..........


Day before yesterday an news item was published about bacterial meningitis and the possibility that there is a genetic susceptibility to this awful killer disease... Well it is more than a possibility, I should not be in denial about this, they reckon they have isolated the specific gene.......

That there could be a genetic component has opened a lot of questions, my mother died young of stroke, both my boys have 'brain' stuff going on, my grandmother had PD, one first cousin with MS, another with bi-polar and more highly intelligent dyslexic boys, all, and way back another who developed a devastatingly fast type of anorexia, well before anyone even knew about it, so brain related that she was took her own life at 16 from fear of what was happening to her....... it seems to me, a way above average incidence of brain related conditions for one relatively small family..... and then there is also my lovely almost ten year old daughter who died of bacterial meningitis in 1988, and it too is now deemed to be genetic......... I may be emotionally extrapolating here, but it was very hard not to wonder, with a family history like mine, whether there were things that went unnoticed...........

It made me remember some of the hypotheses I have read here about viral or bacterial causes of PD, and speculation about susceptibility. And genetics and bacteria, that there can be both components, at the same time..... I had not really thought about that before............

Sometimes I think I am slowly, ever so slowly becoming autistic, that I am moving from neurotypical to neurodiverse faster than I can develop strategies for.......

Imad, your comment about consumption of sinemet is also on the money, they definitively know that slow delivery of tiny amounts of sinemet (duodopa pump) works incredibly well, giving people back their lives, why then are they pursuing the development of 'one a day' variants, that will lead to more ldopa floating around and giving people dyskinsias and a reduced quality of life........ isn't this one of the failings of stalevo....... along with the not inconsiderable extra money they can charge for a 'new' drug.......

[paula_w]

lindy, I know how painful the resurrection of your daughter's story had to be. I agree with you 100% and in another post somewhere i said the same thing. my brother thinks he is a high functioning autistic and believes we are all on the same scale. my mother had him in counseling throughout his childhood and he is a successful teacher...another wound tight but totally funny and witty. He borders on panic much of his time and has OCD.

About movement and learning, i can't see it yet but do see us learning thru adaptation. I have trouble initiiating movement with my right foot and if course when i am off with dystonia I toe walk, I can talk my foot down by actually thinking the command heel first , heel toe. But I know what to do so still not understanding the learning being behind the movement problem. To me it feels more like a lack of initiating and conversely, perseveration; not being able to do something or not being able to stop.

[reverett123]

"our movement impairment often stems from inability to initiate, what's to say this is isn't a weird expression of apathy or a malfunction in our reward center?"

I'm going to have a go at trying to put together a hypothesis that covers as much of our various experiences as possible and I'm going to use Lindy's sentence above as a starter. There are several possible explanations for an inability to initiate movement or, in other words, to be "frozen". One, in particular, is when data is coming in faster than it can be processed. Incoming volume and processing speed vary with circumstances, so what might make one freeze in one instance might not under other circumstances.

For example, a standard test used in research is to drop a mouse in the middle of a big, open table and see what he does. Aptly called an "open field" test, the response is usually either to run or to, yes, freeze. In the latter case, the little fellow is trying to process the data to no avail. His head is filled with thoughts like "Who ARE these guys?? WHAT do they WANT??" Unlike his differently wired brother, he freezes. Like a rabbit in the headlights.

Or like a PWP attempting to walk. Or to negotiate a narrow hall or pass through a doorway. Or like an autistic child bombarded by his environment or one dealing with a learning disorder that makes the classroom a cacophany of noise. Sensory overload. I'm coming back to that in a minute.

First, though, there is what I and Laura seem to have been dealing with. I'm going to avoid adding to the new terms and describe it as potassium being shifted around improperly as the result of unusual sensitivity to fluctuations in insulin levels which move with glucose intake. Let me run through that again- I eat a candy bar. Insulin pours into my blood. My long muscles obey the insulin signal and suck up the glucose into storage. The innocent bystander potassium gets sucked in as well. My muscles go limp until the potassium leaks back out of the cells and into the serum again.

Potassium is essential to muscles. And neurons. Neither will work without it being where it is needed. You are frozen and unable to move. It is a matter of genetics, so one would expect a lot of family involvement. Maybe like Lindy's story. Another form can be acquired as the result of thyroid problems associated with stress load. And I have a sneaking suspicion that after a few years of Ldopa one can develop a similar form. They all cause potassium problems.

Freezing. Sensory overload. Family tragedy. Hard to capture potassium problems. Especially once they've been written off and labeled as PD, ADD, ADHD, and all these others. I don't know if it is true or not, but "the little grey cells" are quivering.


1. J Child Neurol. 2007 Dec;22(12):1408-10.

Hypokalemic sensory overstimulation.

Segal MM, Rogers GF, Needleman HL, Chapman CA.

SimulConsult, Inc, Chestnut Hill, Massachusetts, USA. jcn@simulconsult.com

This report describes 2 generations of a family with symptoms of sensory
overstimulation that exhibit a potassium sensitivity similar to that seen in
hypokalemic periodic paralysis. The sensory overstimulation is characterized by a
subjective experience of sensory overload and a relative resistance to lidocaine
local anesthesia. The sensory overload is treatable with oral potassium
gluconate, with onset of the therapeutic effect in approximately 20 minutes. The
effect of potassium is reminiscent of its effect in the channelopathies
underlying hypokalemic periodic paralysis, and the resistance to lidocaine
applied peripherally suggests a peripheral sensory localization to the
abnormality. The phenotype overlaps with that of attention deficit disorder,
raising the possibility of subtypes of attention deficit disorder that have a
peripheral sensory cause and novel forms of therapy.

PMID: 18174562 [PubMed - indexed for MEDLINE]

[lindylanka]

Rick , those are Lauras words not mine, I forgot to put the quotes around them when I made them bold.......

I found a great page on mucuna that describes some of the things you talk about from the ayurvedic perspective...... interesting reading I'll post it when I find is again......

Lindy

Sometimes when I have had trouble starting an action, I've realized that it's really that my body was still "stuck" trying to do the last action and wasn't really ready to do the thing my brain was trying to get accomplished.

Just another observation that I've found helpful.

[Conductor71]

Lindy and Rick,

I think you are both onto something here. What i thought most interesting in the initial article Rick shared was the idea that freezing may be some sort of learning deficit or dyslexic movement, but I think the researcher needs to nix the dopamine aspect. Here is why. Not all akinesia or freezing is dopamine related. The hypokalemic type Rick and I have been experiencing is non-responsive to Sinemet. Furthermore, there are now identified akinetic syndromes that do not respond at all to levodopa....one is called Pure Akinesia and the other is Primary Progressive Freezing of Gait.

I have also read that even when FOG is present as a PD symptom, it does not always respond to levodopa. I would argue that this might yield clues to our different disease etiologies...apparently, freezing is now even considered atypical for PD, so something unique is happening for some of us. My feeling is that it indicates some sort of channelopathy that may have a strong genetic component. I have been experiencing a type of freezing that seems more like a stat of catatonia. Levodopa plays a prominent role because it can throw our electrolytes into disarray leaving us "frozen"- not for minutes like in PD or rounding a corner FOG, but say knock you down for two or three hours. When experiencing this type of immobility, it is not the same thing as FOG. I do not respond to any of the visual cues or tricks we are to use. I also think it is, as Rick said, tied directly to our limbic system and how we react to acute or maybe even chronic stress. Stress is a key trigger as has change in air pressure of all things.

I can totally relate to the mouse. I so do not want any confrontation; my instinct is to avoid or flee, but I never get past being caught in the headlights. It is almost as if my brain and body are disconnecting for a short time as a survival mechanism or a way back to homeostasis- it is saying "overload or tilt" and shutting off the the flippers on my pinball machine.

We all have highly attuned stress receptors, but do we still need them? Though I no longer gather berries, while my mate hunts for game, I still have a primitive stress reaction. In other words, the sky isn't falling if I am late for my yoga class, but my Clan of the Cave Bear brain sees it otherwise. Why haven't we adapted and evolved in this regard, I wonder? What in the world does this have to do, beyond anxiety, have to do with loss of dopamine? Do our brains remain in a more primitive state in some ways?

Laura