So, what IS going on?
 

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

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

maybe we need to get back to basics, gastric emptying
 

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

The Pharmacokinetics and Pharmacodynamics of Levodopa in the Treatment of Parkinson’s
 

Eh, what's up Doc?
 

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 :D ) 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. :D

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?

to a T
 

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

Bingo!!
 

" 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.

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]

sounds more like a communications problem
 

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.

Something like this, but more...
 

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. :eek:

Laura

Laura, darling, I could hug you! I could have written almost your entire post! And our little group just may have stumbled onto something important. Maybe VERY important.

First, let me outline what I see as the core experience, because it comes in a half-dozen variations. The distinguishing characteristic shared by all the forms is that extreme loss of muscle tone. Those of you who have not experienced it yet will have a hard time imagining it. The closest thing to it is the way my arms used to feel after a day of working with a chain saw had vibrated my arms to jelly. That is what differentiates it from standard PD. From there the different forms add their own details.

Of the things mentioned, I relate to these:
"...although freezing still comes into play, what we are experiencing is far different. "

"...I am so "relaxed" that I can barely stand or walk."

"...this is what I am like for a good 2 hours. Sinemet does not seem to touch it; ..."

"...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. """

"...I sense a profound absence of all muscle tone or contraction-..."

"...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..."

All of that could have been written by me. There are a few others who have this experience. Bandido 1 has hinted that he does. Tom Isaacs, whom some of you know as the head of England's Cure Parkinson's Trust and I talked yesterday and confirmed that he has it. I have had it for at least five years and maybe ten. Laura indicated that she has had it for two months. Now we know that it can develop where it did not exist before.

I trace my recent worsening of it directly to the wall of stress that fell on me over the last six months. Twice I have found myself lying in the floor unable to so much as raise an arm and once I found myself in a chair and just as weak.

At least I was until my wife brought me two potassium tablets that had me back on my feet in minutes and this mystery first began to yield up some clues for me.

This is going to take some typing so, rather than chance losing it at a critical point I am going to post it "periodically". :D

We are looking at something new that we should not be seeing and which could be very important.

Debi, please pay attention. I know that I kid around a lot but I'm dead serious on this and someone needs to put it in front of the right people.

We are looking at some type of what is known as a "periodic paralysis." The first one was discovered in 1984, so this is still the frontier. There are a half-dozen or so types known. With one exception they are genetic. Usually they are extremely rare, show up before the age of 20, affect Oriental men, or otherwise should not even affect one, single person on this forum! And yet we have roughly a half-dozen!

There are two possible explanations and both are exciting. One is that we all have the variety that is not genetic but, instead, results from thyroid problems. Statistically, there should not even be one of us in a group this size. And this would mean that the place of the endocrine system needs to be looked at in depth and post-haste.

The second is that PWP can develop a hitherto unknown disease of this type either as part of the disease or as a side effect of medication. That latter possibility needs an even faster look since it could yield dramatic QOL improvement at almost zero cost.

These are what are known as channelopathies or ion channel disorders. They are being researched but without any particular importance. That needs to change.

Before I go on, let me emphasize one thing- If this is indeed what we are seeing THERE ARE EFFECTIVE TREATMENTS ALREADY ON THE SHELF!! That is, those of us who are already dealing with this as well as those who are destined to deal with it have aid available right now that may do more for QOL than sinemet or anything else! Again, it depends on the nature of what is leaving me confined to a chair for eight or so hours per day right now, but the odds are high that something dramatic could come from this.

Now, I am going to paste in some resources for everyone to think over. But do remember, this is new territory and we may even be looking at a new "species" so don't rule anything out until we get looked at.

http://www.translational-medicine.com/content/6/1/18

This is an article by Dr. Jacob Levitt of Mt. Sinai Hospital and discusses one type of periodic paralysis (PP) which he happens to have himself. Some quotes:

"The time from premonitory symptoms to full blown attack is often very short, on the order of minutes. For that reason, a sufficient dose of potassium to prevent and relieve an attack should be kept in various places at all times, including: at the bedside, in a pocket of coat, in the car, in the pocketbook, and in the suitcase. Potassium should be kept on the person at all times.

One helpful exercise, especially for those individuals experiencing a high frequency of attacks, is to make a diary of attacks. They should document whenever they get an attack, paying attention to what they ate within the 24 to 36 hours preceding an attack, what activities they did within the preceding 24–36 hours prior to the attack, and what medications they took or forgot to take. As some triggers are completely individual, they are only identified by careful attention to the details surrounding the attacks. Once triggers are identified, the patient should avoid them. Sometimes one can relate a series of attacks over consecutive days to one large triggering event."

" Numerous triggers have been reported to induce attacks of paralysis. The most consistent are rest after exercise and high carbohydrate meals. A high carbohydrate meal causes a spike of endogenous insulin release, resulting in a potassium shift from outside to inside myocytes. The potassium shift triggers inappropriate activity of mutated voltage-gated ion channels, resulting in membrane depolarization, and manifesting as paralysis.

Sodium intake triggers some, but not all, patients. It is important for salt-sensitive patients to discover the amount of salt that induces attacks for them. This amount varies from person to person, and indeed, from day to day. Patients must be aware of the amount of salt in the foods they eat, preferably prior to eating them. For those patients that like to salt their food, potassium chloride (available as NoSalt®), rather than sodium chloride, can be used.

The remaining list of triggers vary for individual patients, but patients and doctors should be aware of what types of things to look out for: cold, upper respiratory infections (both viral and bacterial), fever, lack of sleep/fatigue, Chinese food – with or without monosodium glutamate (presumably a trigger because of high starch content), alcohol, dehydration, startle, any medications – some with a physiological explanation (insulin, beta-agonists, corticosteroids [9]) and many without (determined by trial and error), menstrual cycle, change in humidity or barometric pressure, and change in daily activity patterns (i.e., going from regular exercise one week to being sedentary the next week and vice versa)."

I would add the wearing off of PD medication to the triggers for me.

--------------------

This is a backgrounder on the non-genetic type
http://www.med.ucla.edu/modules/wfse...?articleid=287

------------
http://www.hkpp.org/faq/hyperkalemic...paralysis.html
A site for PP with technical sections for docs.



I will post more later. The basic picture is that the patient has a unusual sensitivity to a wide range of potential triggers (fragility?). If activated the body reacts by moving electrolytes such as potassium out of the blood and into the cells the same way it moves glucose in response to insulin. With the electrolyte balance disrupted the muscles of arm and leg go limp until the ions trickle back. That can be a couple of hours or more.

Summer reading list...
 

Rick,

A big hug to you for being fearless enough to post these kinds of personal details; most shy away from that. I know that since there are a few of us sharing here, there are many others out there who go through this too. I am beginning to think we do all need to start reporting the weird stuff to our doctors anyway...maybe when we figure out what is really going on, they'll think back and say "maybe we should have listened a bit more."

A few more potentially significant things to add...

- Thinking back, I believe this was slightly more gradual. I remember reading your experiences before and about the potassium levels. I was having milder, not as lengthy attacks earlier, so there was a more gradual change, and it only seemed to hit at night when I was winding down for the evening. As my stress at work has heightened, so have the attacks.

-Prior to this troubling loss of muscle tone...it is the opposite of "fight or flight" Wikipedia describes it as "rest and digest", at night, I would have an off period, not very long, marked by more noticeable rigidity and stiffness- this was unusual for me as I usually just have a tremor, a little slowness, and a lean.

-Now it seems these episodes might happen more unpredictably which really concerns me. I had it start to happen toward the end of my day...I will say that adrenaline kicked in and nipped it in the bud as I was determined not to freak out my students.

-I note it can happen in the AM in a milder way in that meds resist kicking in and muscles don't come to life. Usually my mornings were noted for too much muscle tone in form of dystonic foot. I am also vulnerable in late morning and late afternoon.

So we have Colonel Mustard with the lead pipe in the Conservatory...

really, it is only potassium? I just tested with normal levels, so I wouldn't think I needed a supplement...

does it correlate with diurnal Cortisol levels?

You presented with a tremor as well? Is it the right side? I am still mainly hemispheric, or right side impact only? I wonder if this experience correlates with a subtype?

Do we all share a common med like use of an anti-depressant?

Do you think this a special type of PD?

Oh, and I totally relate to the squirmies as our muscle reconnect; it is oddly a feeling of release or relief and lasts for seconds. At times it doesn't happen at all.

I can sometime avoid an attack if I keep active...clean the house be

Food can actually break the attack; especially if protein-centric!

Well, I just finished teaching for the school year, and I daresay in adding these articles I have the most unique summer reading list around ;) I will put all this together and discuss with my neuro next week. Has your doctor chimed in on this at all?

-Laura

Laura-
First, let me reiterate that it is not limited to potassium and in some cases potassium would be exactly the wrong thing to take. Could even be fstsl.

Second, I have a brand new neuro. Saw him for the first time two weeks ago and due for followup in two more. I ratsed this issue and he was going to do his homework and I mine. That is one reason that I was glad to know that it wasn't just me.

Hi Rick,
I too recognise this pattern of 'paralysis' which I have related to as part of the wearing off process, that increases withe each successive daily dose, with the strongest effect in the evening. In other words, that is when I am feeling the weird relaxation the most. Also can confirm the bladder pattern is part of this. Have also found it a strange phenomenon as it is the diametric opposite of rigidity, and actually sometimes follows a patch of extreme rigidty in which my muscles visibly bunch. This is not something my neuro would even get close to discussing!!

I followed through your Periodic Paralysis topic with a little research on the net, hopping from one thing to another, the other day, and in a strangely synchronistic way arrived at GABA, unfortunately can't remember how I got there, but it was related to a condition in which PP can be a feature (PD mem strikes again). Why I say strange is because not that many days before I did the NT questionaire and very surprisingly came up as being a GABA type, and this NT has not really come up on my horizon before..... I expected of course that I would be a dopamine type.....could this be part of the imbalance we have all been interested in finding out about...

I have been hovering around thinking of this sequence of symptoms as being part of the progression of 'medicated PD' or symptomatic of NT imbalance, so am interested in other hypotheses, and was fascinated to read Laura's concise and clear description. I do not think that the bladder aspect is TMI at all, it seems to me a very significant indicator that something is happening, something measurable.

This is a classic example of a discussion that only PwP could have, we are again in uncharted territory - no I will amend that to newly charted, because we are all describing the same thing, it is only the cause that is as yet hypothetical.

Thanks for all you do to keep us on our mental toes,

Lindy

PS Please all readers heed Rick's warning on meddling with potassium levels, it is something for the experts and even they can sometimes get it wrong. A very close friend, in hospital for something completely unrelated, died when a junior medic decided that this was what was needed.

This is a "typical" that I was working on for my doc with some comments added:

“A typical episode will last from one to four hours. It comes on in a time period of fifteen minutes or so from the first hint to incapacitation. From there it is a slow climb back to an on state over the remainder of the period.

The first signs are a loss of fluidity in my movement. This quickly (say five minutes) progresses to freezing where each step is a struggle and exhausting. At times I have been forced to lie in the floor and wait it out. At others I have been forced to crawl in public to a safer location. Falling is a real risk.

Subjectively, cognition slows and I feel like I am at the back of a cave seeing the daylight some distance away. Brain fog. Physically, even typing is near impossible. My legs feel as though there is no life force in them and often my arms do too. Conversation is almost physically painful.

While the wearing off of meds seems to be a trigger, taking them once it has begun has no effect. Even triple dosing is useless once the cascade starts. However, taking them well before it begins seems to head it off.

At about a third of the way through, I sense a shift, usually in the form of transient energy waves in my legs. Very fleeting at first, they become more pronounced as the second third of the process passes. Toward that endpoint, hesitant stretching helps.


Then the fun begins. Still unable to walk, I have to urinate. I mean REALLY have to urinate. I struggle to the bathroom sometimes, use a urinal others, and occasionally have an accident. Then I relax for five minutes and repeat the whole process. Three to six times is typical. The urine is copious and almost clear.

Each trip is a little easier and the brain fog dissipates. Finally at the end, intense stretching speeds the turnabout. Extra meds taken earlier now appear and take effect.

This has gone on for ten years and has increased in frequency and intensity but not in nature. It is not unusual for me to have three such episodes on a given day.”



I've been thinking about what might serve as a flag to indicate that this should be suspected. So far, I suggest:
1- A familiar worsening of symptoms including gait problems that does not respond to meds but resolves with time.
2- A weakness of the muscles of the legs and arms when at rest and rigidity when forced to respond (i.e. by walking).
3- A predictable pattern in time (i.e. every day around lunch) or circumstance (i.e. sudden stress).
4- Sensitivity to blood sugar fluctuations.
5- Polyuria.
6. Sensitivity to declining levels of PD medications that is not countered by additional medication.

http://www.ncbi.nlm.nih.gov/sites/en...m_uid=13239022

It seems that an over active thyroid could be causal.

Am I onto something here...
 

My particular "brand" of this led me straight away to research the parasympathetic nervous system because I noticed at first more a regular, pronounced relaxation of muscles involved in voiding - my peak involves either bladder or bowel (ick- graphic but may be relevant). After this, if I "listened" to my muscles, I could return my system to a state of relative harmony.

I told my dear brilliant cousin, who also happens to be a nurse, and immediately she asked me if I had been checked for Myasthenia Gravis, er, well no, but in what I have learned I wonder if we are in uncharted territory of a new sort of movement disorder. This could all be crazy, over simplistic leaps but let's keep an open mind....

Myasthenia Gravis manifests as extreme muscular weakness. It as autoimmune disorder that results when our T-cells develop antibodies for our...drumroll for Paula...acetylcholine receptors. The T-cells either destroy or block the receptors.

Sound vaguely familiar? There is a newish theory that PD happens to be autoimmune as well. Furthermore...

Symptoms...unstable or waddling gait, weakness in arms, hands, fingers, legs, neck, a change in facial expression, dysphagia (difficulty in swallowing), shortness of breath and dysarthria (impaired speech, often nasal due to weakness of the velar muscles).

The severity of weakness fluctuates during the day, usually being least severe in the morning and worse as the day progresses, especially after prolonged use of affected muscles.


Key difference...we have absence of tone- not induced by use.


Factors that worsen myasthenic symptoms are emotional upset, systemic illness (especially viral respiratory infections), hypothyroidism or hyperthyroidism, pregnancy, the menstrual cycle, drugs affecting neuromuscular transmission, and increases in body temperature.

Of particular interest to me is the mention of estrogen- I have noted that pregnancy often results in worsening of PD - same thing with MG.

Patients with anti-MuSK-antibody positive MG may have focal or regional weakness and muscle atrophy that are more suggestive of motor neuron or muscle membrane (myopathy) disease.

Interesting to that neurology has noted links between PD and MG. With people having one disorder then developing the other. How about seeing them both essentially as one disorder with people experiencing varying degrees of impact on various neurotransmitters?

So all this leaves me wondering have we either seriously f***ed up our other neurotransmitter receptors OR are the two together somehow one other option in a spectrum disorder?

What I find interesting in all this is that I think it is highly indicative that we also have an autoimmune disorder that maybe attacks more than just dopamine uptake?

Common treatments for MG include steroids, antibiotics, anti-inflammatories...hmm, haven't we been lamenting how PWP might also benefit from these same treatments?

I am going to stop here because it is mere speculation and most likely has been researched. I keep losing my posts these days, so will leave this for further commentary or not. I just want to stress that I think what we are experiencing is more than dopamine dysregulation.

Please note: all italicized portions are directly from the Myasthenia Gravis Foundation site.

PLM lists 2400 people claiming stiffness as a major symptom and only 49 claiming weak legs.

try the braverman for the heck of if?
 

For the "wound tight"
http://www.nutritional-healing.com.a...A%20deficiency


My weakness was accompanied by a panicky feeling, my husband was always wrapping my legs with athletic bandages for strength. Always in the evening, my friends know this.

http://www.naturescountrystore.com/p...dpanicattacks/

there's more but i'm kinda off. one includes the potassium condition if not these i will post it when on more.

Rick, many people with stiffness get diagnosed with fibromyalgia. Some of these seem to differentiate over time into other diagnoses, and a few of us wind up here....... along the way people are often told you are too young for this, or you can't possibly have that, but nevertheless time shows differently. Is this stiffness, that features so large for us as rigidity, a start point in a process of health deterioration......

Lindy-
What I think is shaping up, for me at least, and I suspect for many of us, is a hyperactive thyroid triggered by a high-stress incident that, in turn, sets up this hypersensitive condition that causes these electrolyte problems and the attacks that started all this.

Another molecule in another part of the brain could explain it
 

http://esciencenews.com/articles/201...nsons.research

This could definitely cause our dopamine dependent and acetylcholine dependent muscles much confusion.

All,
many researchers believe pd becomes an autoimmune disease, but there is probably an iinitial insult first.

myasthenia gravis is, at least in some cases, from not enough acetycholine if i understand it correctly. here's a statement about it:

In an autoimmune response, the immune system turns against the “self”, developing antibodies against its own antigens and destroying its own cells. For example, in myasthenia gravis, the person’s immune system destroys the acetylcholine needed to transfer nerve impulses across the synapses."

From NINDS:
http://www.ninds.nih.gov/disorders/m....htm#153553153

What causes myasthenia gravis?

Myasthenia gravis is caused by a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction - the place where nerve cells connect with the muscles they control. Normally when impulses travel down the nerve, the nerve endings release a neurotransmitter substance called acetylcholine. Acetylcholine travels through the neuromuscular junction and binds to acetylcholine receptors which are activated and generate a muscle contraction.
In myasthenia gravis, antibodies block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction which prevents the muscle contraction from occurring. Individuals with seronegative myasthenia gravis have no antibodies at all to receptors for acetylcholine and muscle-specific kinase, which is involved in cell signaling and the formation of the neuromuscular junction. These antibodies are produced by the body's own immune system. Thus, myasthenia gravis is an autoimmune disease because the immune system - which normally protects the body from foreign organisms - mistakenly attacks itself.

From http://www.hkpp.org/faq/periodic_paralysis.html
The Periodic Paralysis News Desk-

"The periodic paralyses are a group of rare inherited disorders that cause temporary episodes of muscle weakness or paralysis. Periodic Paralysis is found in all races and in both sexes. Attacks can begin at any age. Some patients have their first attack within minutes of birth, but a few don't have symptoms until they are in their 60s or 70s. The paralysis can be mild, and confined to one limb, or so severe the patient cannot breathe on their own. Attacks can last only a few moments or go on for days, depending on the type of periodic paralysis the person has. Some forms of periodic paralysis include muscle stiffness or rigidity as part of the attacks. Some forms include permanent muscle weakness which happens over a period of many years."

(Note- This is an extensive website addressing a dozen different PP with a special section for professionals.)

"Commercial labs only test for the two or three most common gene mutations found in Hypokalemic Periodic Paralysis and one or two genes in Hyperkalemic Periodic Paralysis when more than 30 mutations have been identified. In addition there are mutations which have yet to be identified. This should make it obvious that a negative DNA test does not rule out a diagnosis of periodic paralysis"

" In periodic paralysis the ion channels fail to regulate the flow of ions under certain conditions, and the electrical signals which keep the muscles moving come to a standstill."

"There is a secondary type of HypoKPP which is associated with an overactive thyroid gland. This type of HypoKPP is called ‘Thyrotoxic HypoKPP’ (TPP). "

"Patients with HypoKPP typically begin showing symptoms in the first or second decade of life...but first symptoms have been documented in patients as old as 60-70 years."

"Weakness most commonly affects the muscles of the arms and legs but may affect the trunk as well. Weakness occasionally affects the eyelid muscles (causing droopy lids). "

"During episodes of muscle weakness, potassium flows from the bloodstream into muscle cells, affecting the ability of the cell to contract properly. Potassium levels usually fall during attacks but are normal between attacks."


"Many episodes of weakness are triggered by food. Food triggers include sweet or sugary foods or starchy foods. ...... Insulin drives potassium from the blood into the cell, which triggers weakness. Salty foods, like burgers or potato chips, are a trigger for many HypoKPP patients. Getting too hungry, or eating a large meal (especially if you are very hungry) triggers episodes in many patients.

Other common triggers include unusual activity or exercise - usually the day before the attack, but sitting still for too long may also trigger episodes. Patients learn that pacing their activities is absolutely vital to gaining control. Sleep is a potent trigger, and many patients wake up paralyzed. Getting too cold (or too hot) makes some patients weak. Weather changes trigger episodes in some patients.

A little bigger picture
 

Hyperthyroidism is an overactive thyroid. Grave's Disease is the most common form. As I mentioned earlier, it can also cause the most common form of periodic paralysis (10x all the others combined). An attack leaves you weak as a kitten. PD is NOT required. But it makes a hell of a combination.

So here are three disorders. The PP element is the rarest. The combination of PD and hyperthyroid is much more common. There has been very little research done since the advent of L-dopa. A Medline search of Parkinson's + hyperthyroid turns up two hits. Change it to Parkinsonsism + hypothyroidism and you get 45 or so ancient "no abstract available" hits with a sprinkling of full text.

The consensus as best can be told from the texts and titles is that bringing the thyroid under control made a major improvement in PD symptoms. But nobody followed up.

Hyperthyroidism is another one of those hard to diagnose items, even when it rises above the preclinical stage, as it does under severe stress.

Two things have shown themselves effective at straightening out the problem. One is acetyl-L-carnitine (4 gr/day) and the other is lemon balm. I started both evening before last after having had two of my all time worst days ever. Yesterday was much better and today is starting off very well.

For what this is worth. I took in a cat that was going to be euthanized because her 10 yr lifelong owner had died.

She is hyperthyroid [found out after i adopted her] but of course had bonded with her as well. She was a really timid and strange cat and ran around all night jumping up and eating anything that might be left on the counters. She was playful for a 10 year old cat. It took months to get her to do these things because she literally hid in a bedroom till she got used to her new home. But she was ravenously hungry all the time it seemed which didn't match the fact that she had no muscle or fat - was skin and bones. At age ten she weighed 7 lb.

i'm leading up to something. OVerall she is a very smart cat - my other one who must be 19 yrs old is my best buddy but she isn't that smart.

ok so i took her to the vet for a bump on her cheek and a fever. they discover the hyperthyroidism and now she has to take medicine just like me for my hypothyroidism. thank heavens its chewable and flavored, she loves them.

what i wanted to say about all this is her entire personality changed wth thyroid medicine. She is calmer, doesn't play too much but is starting to again a little (after two months is she adjusting to the medicine?} And altho still gobbles down her food without chewing half of it, she no longer goes on kitchen counter night raids.

so if the thyroid can change the personality of a ca that much, what is hyperthyroidism doing to people? Combine that with too much epinephren [excitatory] acetylcholine [excitatory] and low GABA (inhibitory) and low dopamine [excitatory but has some inhibitory effects] you have a wound tight creature, impulsive, compulsive and weak brakes. That was me with a hypothyroid so I'm not saying the exact same thing as Rick but there is a relationship with the thyroid....and hormone deficiencies that also leads to illness.

Last point - my physical therapist, when i asked her if she had ever seen pd in children, said no but that many have metabolic conditions that were not common in the past - future chronically ill? Future pwp?

i think of loulou's post about the American diet at this point in the sergey thread. Agree with rick that much of what we are talking about with metabolic and transmitters also is old, outdated.

Is it really just a reaction to stress?
 

Hey all,

Spoke to my neuro yesterday regarding my "episodes" which are very similar to those who have reported here. He is an intellectually curious guy and he was intrigued by what was going on and did state that he hadn't heard of anything quite like this before.

Of course, that is as far as it went, but it was rather nice to be taken seriously and listened to even if he could not offer any insights. He did say kind of what I expected; it is his opinion that I am experiencing deep stress induced offs. He claims that stress is the only time he has seen meds not have any effect like this.

One huge insight I have gained from this whole PD experience is that stress and bottling up negative emotions over the course of decades will make us sick. I always acknowledged that as possible when reading of it, but never thought things were so out of control for me. My childhood was less than ideal, but who has a perfect one? I have realized that I have made a life habit of suppressing my emotions, and it has got to stop. It is interesting to note that when I do have these episodes, I feel a tremendous amount of anger. Rick, Lindy, do you have a weird sense of something eating at you too- it is so the opposite of what my body is doing that I sometimes wonder if these periods are my body's way of compensating for the fact that I have lived far too long in fight or flight mode.

One thing I plan to try is rolfing. I have read that it is a form of massage that recognizes the mind/emotion and body connection and that many do improve long term through any sort of touch therapy. Has anyone tried it?

Laura

Across the Great Divide
 

We are leaving neurology behind and entering the world of endocrinology. I am convinced that that is where PD lives. Yes, we have damage to particular parts of the brain, but the causes of that damage come from here as well as the immune system. Motor symptoms result from the latter's inflammatory response. Non-motor symptoms, however, are a child of the endocrine and stress.

Long neglected because neurology didn't consider it important, the endocrine system is all about stress and emotions. We all know what an effect these have on our symptoms, but we are only now starting to wonder what they were doing to us during those "pre-clinical" decades prior to that first tremor.

A lot of us have trouble with emotional stress. It disturbs our grip on things. We like for things to be cool and calm and we embrace homeostasis with a vengence. But it cannot be avoided. A a friend once said, stress affects everything. Any picture of the human condition that omits stress is incomplete.

This all interfaces with reality via the network of glands that make up the endocrine. It really is a network with each in constant communication with the others by means of hormones released into the bloodstream. The brain influences it but does not control it.

It has incredible power. An overt example are the stories of mothers lifting cars off their child. Pure endocrine response. But far more of its actions are subtle and day-to-day. It has been running since we were first conceived, constantly monitoring the environment for danger. I wonder when it decided that things were safer when we sat with our backs to the wall? Or when we concluded that if something was important that we had better see that it was done right?

The ghosts from childhood stay with us and this is where they live. Here at the center where their influence can reach every cell. They literally inform each individual cell about current conditions by means of the blood.

There is a lot to learn here. Just over the last few weeks, both by book and experience, I have learned:
1) The thyroid is the cruise control for everything else.
2) Stress makes it go faster and we call it hyperthyroidism.
3) When one person has both PD and high thyroid, correcting the latter can produce great improvement in the former.

There is much here to lean.
-Rick

More connection to our neurotransmitters
 

Ran across this phenomenon known as "apathetic thyrotoxicosis". In these case studies, people have symptoms opposite of the classic hyperthroid presentation. Note all patients express a sense of profound weakness; one could barely walk and another bedridden. It is noted that dopamine regulation of thyroid hormone levels plays a role.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955902/

Is there a full moon?
 

Sure looks like it outside and in these forums.

When the moon is full more babies are born (really), and kids' behavior gets negative (I know - taught for 15 years), and people like us PWP - with all of our huypersensitivity get . . . er . . . hypersensitive! lol

Did you note the date this thread began? 2006 ! And yet, it's just as applicable today as it was then - probably moreso!

I have been up all night - I broke down and chewed up one-half Sinemet to kee from wiping out, and I was drawn to this computer and to harley's post then this resurrected one.

As I wrote in my journal in 2000, (paraphrased) I don't believe in predestiniation. But I do believe there is a plan given to each of us. How we travel from point A to B is an individual choice.

I don't believe in predistination, but I do believe in windows of opportunity. Step through your window and someone, somewhere in time will benefit because we did.

I think I'll go out and howel at the moon :)


Peg

Stone coyotes say we were born to howl

And underneath the white moon rising
Something's stirring, on the prowl
Can you hear coyotes crying?
Singing, " We were born to howl"

We hail from an ancient dream
We heed a different call
We sing the song of things unseen
We sing for no reason at all

Quote:
There is much here to learn.
-Rick

Rick, this is one of many brilliant threads you have triggered. Remarkable. I just printed it up so I can go offline and read it again and take notes. I have had this disease for many-a-fortnight and did not know or question much about what it was; I would not have a clue without y'all.

With all due respect (to the medical community), I think the leading researchers in the field of movement disorder and endocrinology could learn something from reading these posts.....:rolleyes:

Won't ever happen, it's just thoes silly Parkies talking again.

Silly researchers!
:eek: