[reverett123]

Sometimes trying to make sense of all I have learned about PD over the last ten years makes me feel like a beagle at a rabbit convention. It is hard to stay focused. Yes, once again I have been chasing a rabbitt. Maybe an important one.

NeuroTalk is unique in many ways. One is that there are a few old warriors here. The other forums are filed with Newbies asking things like "Does Mirapex have side effects?" But here are some of us dealing with advanced PD, whatever that is. As a result the picture from here is a little more complete than anywhere else. So I'm going to ramble on here a bit and describe what I think I see and ask if it sounds right to the rest of you.

I see a disorder that is first noticed in midlife as a collection of problems with control of the conscious functions of our muscles. Gradually it draws in the unconcious functions as well. Then it creates problems with our inner being, our ability to cope.

This latter is the rabbit of the day. The feeling that we could handle the world much better if only we had someone to hold us like a child has been expressed more than once. And a sense of extreme fragility seems common as well. As we advance we have increasing difficulty maintaining balance or homeostasis as it is called. This is endocrine territory and the land of the adrenal.

These feelings are no illusion. Many of us are ready to fall apart at a moment's notice. I began this iine of thought lying helpless on the floor from stress overload a couple of months ago. I was too weak to raise an arm. It was not the rigidity of the muscles. Quite the opposite. They had no tone at all. After an hour or so the extra meds my wife had brought began to work, or so I assumed. Now I am not so sure. Another time in the same period, I was unable to get out of my chair. Again an incredible weakness came over me. That time I was rescued in minutes by a potassium supplement. I have not been able to reproduce that miracle although there have been hints. And still another incident in the same period began with a 2:00 AM wakening to a warning of a tornado in the area. I heroically roused my wife and was mobile, then suddenly I was on the floor, helpless. Forget the idea that I would rally to the adrenaline. Luckily it was a false alarm.

I did not used to be this way. I have acquired this at some point in the last ten years. Actually, I think that it was what sent me to another neuro in 2000 after a dx of essential tremor in 1993. My lower legs began to give me trouble at times. Requip and sinemet seemed to fix it for four or five years, but then I began to have spells which seemed to be triggered by MSG. Like the more recent attacks, complete loss of muscle tone.

So what IS going on and is it just me? Or is it part of the mix as time goes by? An extreme fragility. I remember discussions about blood sugar and its importance. Rosebud, in particular, had studied it. (Rosebud, ifyou still lurk, PM me.) I found that mine had a weird little drop that coincided with going off. Or so I thought. Again I am not so sure.

There are more links in this chain, but it is late. So let me cut to the chase on this rabbit. I have been learning about a family of inheritable disorders called "Periodic Paralysis". There are a half-dozen or so, none of which fit my profile. At least that is true of the known ones. The first was discovered in 1984 so there is frontier here.

These PP are essentially a hypersensitivity to change, particularly of blood sugar and particularly of minute changes. They speak of "attacks" as the body overreacts to "triggers" and moves electrolytes out of the bloodstream and stores them in the muscles similar to the way it stores glucose. This disrupts the electrical charges within the cells which go limp until things dribble out and balance is returned.

The most common triggers are interesting. A high carb meal. Stress. Adrenaline. I would add the wearing off of sinemet. And I wonder too, cannot a move of these ions trigger a rigid muscle response as well?

I suspect that those latter stage problems of fragility may be just that - fragility.

Here is a link to a very readable piece by a doctor at Mt. Sinai who has one of these himself. Well worth a read.
http://www.translational-medicine.com/content/6/1/18

[bandido1]

Rick: check with Paula, Lindy, Peggy or Pam and ask them if they think I may be a clone of the rabbit you are looking for. Perhaps I can provide you some input through our forthcoming publication. Bandido Bob C

[soccertese]

Erratic gastric emptying of levodopa may cause "random" fluctuations of parkinsonian mobility
http://www.neurology.org/cgi/content/abstract/38/3/419

[soccertese]

http://www.bentham.org/ccp/openacces...-3/0006CCP.pdf

[reverett123]

Sorry. Only rabbit joke that I could think of. Except for the classic, "There was a fine bunny from Burma; this bunny could not get much firmer; etc" but everyone has heard that one (you see why they only let me out in the wee hours ) But I digress.

If you are saying that you have similar symptoms, I would very much like to discuss them. In fact, I have a four-week followup with my new neuro on the 30th. It would be great if I could produce additional specimens. He was open enough to suggest that I use the four weeks to test the potassium to see if it had any effect on the "attacks".It did not, at least not at the doses I was willing to risk (max has been 60 MEqv).

However, I do think that one of my triggers is sodium. That would explain my reaction to MSG, a high sodium source. I also think that glucose/sugar is one for me. Emotional stress is another. And I suspect tornadoes.

I am going to adopt the convention of defining an "OFF" as a state of non-response to Sinemet and defining an "attack" as a temporary collapse of one's ability to maintain homeostasis.

Using those, I am going to lay out a rough draft of a new hypothesis using my own case as the test.

So here goes- In 1992, when I noticed a slight tremor in my right hand, my wife and I were just coming off a stint as the primary caregivers to my four grandparents. That's an eight year stint that began with a request to aid transporting one of them to the doc and ended with the passing of the fourth one. We had lived with the last one as he checked out. No privacy but we needed the roof overhead due to the two house fires, both being total losses. And since one had been a Halloween arson, we had just gone through an audit. Passed with flying colors after two days of tension.

Oh, yeah- mobile home #1 was an older model that we had gutted and remodeled using the profit from the old farmhouse we had also remodeled and gutted. Shortly before my abusive, alcoholic father's suicide but a few years before my younger brother dropped dead of a coronary. So MH#1 had a lot of work and equity in it and very little insurance.

So we borrowed a small tow behind camper and lived onsite while we began Home #2. At least until the temperature dropped and we realized how cold that little camper could get. So I began making the 30 minute commute to the site where I was building a real home. A big, real home. With salvaged material with the nails still in it. With the help of friends who quietly began to slip away. It was dried in by the following Halloween when it was probably burned by a drunken poacher.

I had a small office in my uncle's basement. The one who thought that if there was anything wrong with chlordane that God would not have put bugs in that basement.

To no one's surprise, my poor wife was by this time dealing with a stress related problem that had her in a wheelchair for six months. And I think there was a bout of flu in there somewhere. Did I mention that we were running a Mom and Pop business with six employees through all this?

I guess it should have been no surprise when I noticed that first tremor.

<I've got to pause for breath. Seeing that listed out on the screen is a mind blower! That all came down in about a 12 year period! It's a wonder I'm flippin' alive!>

I think it is safe to say that stress had something to do with my developing PD. And I think it likely that some part of me seeks stability and holds it with an iron grip. So I am not comfortable with change for its own sake. And I have no desire for bungee jumping. And everything in my closet is blue. And I go to the same restaurants and order the same things. And I don't like things that change the neighborhood.

And I don't like it when something like fluctuating glucose or sodium or potassium or similar ions change my internal neighborhood. I feel fragile or brittle and if I am touched roughly I may shatter like a large sheet of glass.

===

OK, that is the first draft. Anyone relate?

[paula_w]

Yes bob, rick has described you close to perfectly. We do become fragile because we develop postural instability and then it's a constant need to make sure you don't fall. I don't back myself into any corners so to speak and always have to watch that my right side has room to recover if it decides not to go with my torso as i head off in that direction.

Also my bones are weak and i won't take the medicine for it - fosomax or whatever it's called. more reason for fragility. Weight loss is a problem for me, i've gained some back with nortriptyline, but I think i'm going to have to discontinue it [another post ].

Bob is an inspiration to us. I don't want to give any of his story away now because it's ongoing and will be in the book. He has a strong mind and he's coping extremely well to some major life changes to say the least.

But he's walking and he wasn't before his last fall, so exercise [physical therapy] should be a given for pwp.

Rick you have described it pretty well, but I am not sure what comes first and you know that too. i can't remember when i noticed my right arm didn't swing as much as my left. i feel like it never did.

Weakness is lousy. We'll be confused now that we have reached the age of higher health risks and natural weakening of teeth, bone, etc. but a normal aging person won't feel the kind of weakness that we feel until they are very elderly. our voices become weak and we don't have the feedback to recognize how low we are talking. Thus the Lee Silverman direction: "Think loud."

I am a cross between a person who has had some drinks [is that better rose?] and an elderly lady. This is with sinemet and on. When off, i am actually a better talker and different muscles are at work in dystonia. this gives me a tilted to one side condition, a shuffling, dragging, zombie like gait and it ends down on the floor.

I used to feel so weak i just felt i was going to stop altogether. But that was during a time of great emotional stress and upheaval personally.

If you don't take an anticholinergic, i would recommend trying one. Nortriptyline is excellent for weakness, plus an anti depressant. But i am having back spasms that are like pains of childbirth. i just cry out and have to drop to my knees. waiting for mri results after months of physical therapy has not helped. it is possible for muscle cramps to occur due to meds, and maybe when the cholinergic system malfunctions or changes. Because i saw the possibility of cramping and at least one site mentioned some interactions with other drugs i am on, i am afraid i am going to have to give it up. but i will ask for artane or cogentin and say good bye to clarity and hello paranoia . Maybe i could take it at bedtime.

Stalevo, in the meantime, is working very well. i have reduced my sinemet and although i still talk poorly as the day goes on, i have fewer offs by just supplementing with a quarter or a half of 25//100. i hope it works for a long time.

i am doing research now on several of the major neurotransmitters, acetylcholine, glutamate,seratonin. dopamine, norepinephrine, and NMDA receptor antagonists.I want to know what each and every med i take does to my neurotransmitters. Guess it's about time huh? there are conflicts that we have to discover ourselves. i trust no one to be reliable about meds...0.

or it could be all a big placebo! i wish....

i have been looking so many things up and working hard lately with a video, book , and sham surgery workshop planning, that i can't remember where i read this, but a doctor's advice to someone was to have chelation to remove any removable metal from your body right after diagnosis. That's the first thing she would recommend.

anyone recognize that statement? this should be in olsen's thread.

anyway rick, the coping and hoping are soooo important and this forum is a first, along with the PIEN listserve, to develop into such a fabulous resource for both.

ok main point i wanted to make is that when weakness is mentioned, it's important to eliminate your meds as the cause. My father almost died from a med, they were making the arrangements for him..turns out he was on digit--something or other don't want to badmouth the wrong med. he quickly recovered.

I'm working on glutamate now and it is also toxic in high doses. glutamate and acetylcholine are linked to Alzheimers disease. Namenda works on keeping glutamate regulated but my advice to anyone who has both these things going on:

1. taking alzheimers drugs - aricept, and other chlolinesterase inhibitors, or namenda -regulates glutamate which becomes GABA- not sure what exelon patch does.

Gaba is a very extensively dispersed inhibitory transmitter that is being targeted by neuologix gene therapy trial and which Dr. Levesque speculated he had aroused in his autologous cell experimentation.

2. body weakness, not off . but accompanies it. the kind of weakness that renders you useless, can't even pick something up.

...is to either try an anticholinergic to regulate your acetylcholine, or drop your cholinesterase inhibitor [like an alzheimers med] to see if it goes away. you can go back on if you notice a difference in cognitive functioning and can stop anticholinergics if they don't help.

of course i am not recommending you do anything without your doctor being informed. but they don't know about all the med interactions. my doctor says his other patients with pd take alzheimers meds with no problem. and how many are there? how old? how severe is their cognition? if you are taking alzheimers meds like you would azilect for mental clarity i'd make sure they are helping. i recently heard a doctor on a news show say nothing really works with alzheimers but socialization.

and pwp are not lacking or overproducing the same way that alz are. we don't need more of what they lack.

ok this is a repeat of several updates together to kind of respond to rick. i get going when pwp tell me they feel weak. i have not felt that weak feeling since nortriptyline so i hope other actual anticholinergics do the same.

excitatory and inhibitory are important words in discovering the causes and mechanism of pd syndromes. i feel like i've always been in an excitatory state; isn't that what 'wound tight" means, really? I have to medicate myself to break through to slow down and relax and sleep. i screamed for 6 mos with colic and have been distrustful and speaking out ever since! lol

[reverett123]

" body weakness, not off . but accompanies it. the kind of weakness that renders you useless, can't even pick something up."

Exactly what I"m talking about. I agree that it is different than OFFs and they do intertwine. Useless, indeed. Impossible to even type.

That is what happens when the potassium in your blood is moved into the muscle cells in a manner similar to the way that glucose is moved in a similar manner. If I am weak, I think it is a periodic paralysis (PP) attack. It will not respond to PD meds. All I can do is wait. Mine last about two to four hours. Sometimes people have them that last for days.

Some other things that describe the experience-
The weakness begins in the extremities. The lower legs the first to go followed quickly by hands and forearms. The trunk is barely affected.

From first hint of the impending storm to paralysis takes fifteen minutes.

About the midpoint, the turnaround is announced by the bladder as the kidneys work at balancing something. The legs remain weak but can now be moved a little. They can be bent more easily than they can be straightened.

As the attack runs its course, what I call the "squirmies" set in as the muscles demand to be stretched. Then suddenly it is like the ice breaking on some great river and in less than five minutes it is over.

Again, this describes what I believe is a form of paralysis associated with PD or sinemet. As Paula said, it can run parallel with OFFs. The key difference is muscle tone. Low in an attack. High when OFF.

This has some important things that go with it, including a near cure. I am, as I said, a creature who needs stability in these things. Everyone does, I just need it more than most. The body has exquisite control of this area for that reason. Each cell operates by storing molecules of one or the other electrolytes within the cell somewhat like we might inflate a balloon by storing air molecules in it. Where we might use our lungs as pumps to fill it, so too does the cell ha ve tiny pumps to move the different ions around to create pressure differences. And just as we can release the neck of the ballon and send it flying, so too can the cell get things done by opening tiny gates and unleashing the pentup energy.

All this elaborate system of pumps and gates requires energy and lots of it. Each of our cells has floating within it thousands of tiny Honda generators called mitochondria. And in PD they need the spark plugs changed. And so, they are forced to try this balancing act with undependable tools and they just can't do it. Some of youmay remember the story last year about methylene blue (that one died quick, didn't it?). These tiny, messed up generators was what that was all about.

Dr. Ames did that work. But he has also published a lot more on doing the same thing with the common supplements acetyl-L-carnitine and alpha lipoic acid. I have taken it for years but with a bit of faith and guesswork on dosing. These two will give your mitochondria a tuneup if you get the dose right. That will, in theory, then give your cells the energy to run the machinery and maintain that critical balance.

I doubled my dose starting yesterday and have been tickled pink. I was having three attacks per day but had only one yesterday and none today.

[reverett123]

1. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.

Mitochondrial decay in the brains of old rats: ameliorating effect of
alpha-lipoic acid and acetyl-L-carnitine.

Long J, Gao F, Tong L, Cotman CW, Ames BN, Liu J.

Institute for Brain Aging and Dementia, University of California, Irvine, CA
92697-4540, USA.

To investigate the mitochondrial decay and oxidative damage resulting from aging,
the activities/kinetics of the mitochondrial complexes were examined in the
brains of young and old rats as well as in old rats fed R-alpha-lipoic acid plus
acetyl-L-carnitine (LA/ALC). The brain mitochondria of old rats, compared with
young rats, had significantly decreased endogenous antioxidants and superoxide
dismutase activity; more oxidative damage to lipids and proteins; and decreased
activities of complex I, IV and V. Complex I showed a decrease in binding
affinity (increase in K(m)) for substrates. Feeding LA/ALC to old rats partially
restored age-associated mitochondrial dysfunction to the levels of the young
rats. These results indicate that oxidative mitochondrial decay plays an
important role in brain aging and that a combination of nutrients targeting
mitochondria, such as LA/ALC, could ameliorate mitochondrial decay through
preventing mitochondrial oxidative damage.

PMCID: PMC2790461
PMID: 18846423 [PubMed - indexed for MEDLINE]

[michael7733]

Have you ever tried to run a program on your computer and gotten an error message telling you there was not enough memory to run the program? Stop and think about it for a moment. Is the problem really a lack of energy or is it more like a problem with...I'm going to make a word up...focusability. You know what you want uyour hand or foot or stomach muscles or mouth to do, but they seem to have forgotten how and are in need of coaxing. This is not to be confused with freezing. I am going to have to use a very personal aspect of our existence in order to explain this...the bowel movement...in a normal bowel movement peristalsis moves matter through the digestive system and into the excretory system where a final push on your part completes the elimination. For the most part that final push is controlled by you. It's no big deal....right?...unless, that is, when it comes time to push and you cannot focus in on the muscles that follow your command. It is as though they have forgotten how to push. Hopefully, in the "end" everything "comes out ok." It's not a lck of energy here, but rather, it is a lack of 'focusability'

I think it has something to do with the relatively new agonists on the market. I have no proof, but the complaint definitely corresponds with the time line.

[Conductor71]

Originally Posted by michael7733

You know what you want uyour hand or foot or stomach muscles or mouth to do, but they seem to have forgotten how and are in need of coaxing. This is not to be confused with freezing.
I think it has something to do with the relatively new agonists on the market. I have no proof, but the complaint definitely corresponds with the time line.

Yes, I definitely agree on the role of muscle memory or "coaxing". What or how do agonists factor in?

I think I have been experiencing the same phenomenon as you. I was at first afraid it was freezing, and although freezing still comes into play, what we are experiencing is far different.

My episode usually begins with a winding down so usually it occurs in the evening. I feel a release or relaxation throughout my entire body that normally I would welcome. It can be accompanied by sleepiness but not always; frankly, if this all went down at bedtime, I would most likely just go with the flow. However, for me, the relaxed sense of being doesn't stop until I am so "relaxed" that I can barely stand or walk. I also end up with a sense of disequilibrium and compounded with my jelly legs it feels much like I am trying to find my sea legs, now add in a PD shuffle, and this is what I am like for a good 2 hours. Sinemet does not seem to touch it; therefore, I think that dopamine may not play a primary role- yes, I get the sludge and slow moving legs and arms, but I think it is something else. I do notice that sometimes when the Sinemet needs help that taking 1/2 a benadryl helps, but not always.

I feel more like this a profound deficit in our ability to regulate our "what"? For me, it feels like something sets my parasympathetic system into overdrive. It's not just arm and leg movement; I have noted that at the peak of these episodes, I weirdly have a sudden, urgent need to (sorry about this TMI) void the bladder, etc. That seems to be the turning point, if I a take a second dose of Sinemet, my body will slowly start to respond. Quite honestly, it 's like Frankenstein's monster on the table as he begins to sense he has limbs.

Could this be considered catatonia? It's as if nothing exists to stop the relaxation, or to say enough is enough-- we are entering hibernation mode. I noted in the past few days the reason I feel jelly legs or noodle legs is because I sense a profound absence of all muscle tone or contraction- when I realized how freaky that is, I welcome the dystonia instead. I would much rather deal with a recalcitrant foot that leaves me hobbling for a short time than the weird feeling of being entirely disconnected from my limbs.

Rick, or anyone else out there feel anything remotely similar? I have no idea where this comes from but a few possibilities are 1) I have been under a tremendous amount of pressure from a supervisor who has been railroading me 2) starting an SNRI which emphasize norepinephrine in system, interesting this is exact opposite of crash I have been experiencing 3) I operate largely on an excess of norepinephrine these days; is this my body's way of telling me to "knock it off" 4) some weird effect of Sinemet on other receptors and neurotransmitter imbalance? The first two also correlate to when this thing began to rear its ugly head about two months ago.

I wonder if this can happen as a result of too much another neurotransmitter and the loss of dopamine which normally regulates it?

Okay, how to get back to "normal" I think this experience may be somewhat
refractory to meds as when I really go deep, meds do no touch it. I sometimes have had to add in a 1/2 tablet of 25 m benadryl, but I noticed more it is a matter of timing. Just lying there doesn't seem to help me. I have to get up and gently stretch plus try to walk around as best I can. Eventually, it feels like my muscles wake up, rub their eyes, and all of sudden I am totally back to normal. Sometimes, it seems like my lower limbs and upper limbs compete to see who gets to relax longer. Others, I get to point where muscles start to come to life and then I sink back. It is all so disturbing and bizarre.

Well, I just wanted to share my particular variety of "What IS this? Hopefully I'm not the only freak of nature out there.

Laura