Channelopathy/MG/CMS/LEMS for Stellatum
 

Abby,

I've given your situation a lot of thought now. I am not any kind of medical professional and none of what I say should be construed as advice!! It is simply the musings of a creative mind.

I honestly believe that you have either MG, CMS, LEMS or some kind of channelopathy (or a combination). You definitely have fatigable weakness. Have neurologists confirmed that with a clinical exam? The reason I'm asking about that specifically is that electrolyte imbalance can cause muscle weakness that waxes and wanes according to when the deficiency or overabundance is occurring but it does not show up as "fatigable" upon a clinical exam.

You have a history of seizure and of migraines. Those two conditions have fairly recently been connected with channelopathies. They were thought in the past only to be related to circulation and blood vessels (mainly). There are some C-Ops (I can't write that word over and over again!) that have an onset of migraines or seizures in the first or second decade of life, like your son and you had (seizure).

In addition, the heart is very sensitive to changes in fluids and electrolytes. The heart is also affected by some C-Ops.

I hope that when you see your doctor, you will ask for a comprehensive metabolic panel, including magnesium and phosphorus. Sometimes they don't include those 2 in the test. You need to see how you are right now. A serum osmolality (hydration level) is revealing as well. All of these are best done fasting, first thing in the morning, as your endo might tell you. ;)

So you began the HCTZ due to the migraines. HCTZ does more than reduce fluid retention and potassium. Have you read the entire insert of the drug? It doesn't last 24 hours and that might correlate to some of your symptoms. Try to journal that. And I really think you need to look at what food you intake in terms of fluids and electrolytes, in relation to what's going on.

http://www.drugs.com/pro/hydrochlorothiazide.html

http://cardiosmart.org/HeartDisease/CTT.aspx?id=2374

You really need to understand how a drug works. Hdrochlorothiazide (HCTZ) increases secretion of sodium AND chloride, for those 2 electrolytes "move" together. There may be some loss of potassium and bicarbonate. You may get dilutional hyponatremia if you drink a lot of water or a lot quickly. You could also become hyperglycemic. It could also result in lowered magnesium (hypomagnesemia). It can also decrease calcium.

The drug comes with a lot of potential electrolyte disturbances! Fluid and electrolyte balance is a very complex topic. The effects of any imbalance can cause all sorts of problems for "normal" people but particularly those with MG. It not only affects muscles but our overall metabolism and respiratory system.

The reason I was wondering if you have a C-Op is that you have migraines and the HCTZ stopped them. I don't think it's the fluid reduction that is the key to that but the sodium reduction (lower sodium uptake by the kidneys). Personally, I think that's a HUGE clue about what could really be going on with you.

I completely understand PVC's (premature ventricular complex/contraction). I got the very bad kind when the BCP I was on was switched without my docs knowledge to a generic. I got PVC's that were the kind that could lead to V-Tach. Not good. Anyway, that is interesting that the lowering of sodium affected the PVC's as well.

So you "may" have 4 conditions (migraines, PVC's, seizure (perhaps) and MG/CMS/LEMS) that may improve with the lowering of sodium in the body. That's a lot of coincidences! ;)

I think with some more basic tests like electrolytes, talking to your primary doc and doing some more journaling of symptoms with the timing of the HCTZ onset and end time, you might have enough to discuss with your neurologist!

I also think you should do some digging around as to what organization is truly the best one to go to about channelopathies. Could there be docs in MO (from the WUSTL website) who know enough about all of this to help you? If it were me, I'd want to know the entire truth. It would bug me too having all of these questions and not enough answers.

I think you deserve a better answer, given that you have so many "clues" that point in areas other than just MG. You can have MG and a C-Op. Acetylcholine has it's own "channel" too. ;) And, as with everything else in the body, you can't have one thing go whack without another being affected.

So those are my thoughts for now. I haven't had enough coffee to put any more pieces together. :thud:

What do you think?

Annie


Ion Channels

http://neuromuscular.wustl.edu/mother/chan.html#SCN4A

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883924/

While this is somewhat taken out of context, this is what I was thinking with your periodic states of weakness. It reminded me of what channels do, as in some CMS's and other Ion channel disorders. Also, check out the normokalemic periodic paralaysis section.

"Inactivated channels do not immediately pass back into to the resting state after hyperpolarization, but require a certain amount of recovery time to do so."

Under "Medication of skeletal muscle sodium channelopathies" is this:

"However, diuretics such as hydrochlorothiazide and acetazolamide can decrease frequency and severity of paralytic episodes, probably by lowering serum potassium and perhaps by shifting the pH to lower values."

And thank goodness for Oxford University and Oxford Journals.

LEMS

http://qjmed.oxfordjournals.org/content/92/3/133.full

The Neuronal Channelopathies
http://brain.oxfordjournals.org/content/125/6/1177.long

Pain As A Channelopathy

http://www.jci.org/articles/view/43158

Brief but to the point about the relation between channelopathies and migraine and epilepsy (seizures too).

http://www.ncbi.nlm.nih.gov/pubmed/9642539

Electrolyte Imbalances Information

http://www.fpnotebook.com/renal/sodium/Hypntrm.htm

http://www.fpnotebook.com/renal/Calcium/Hypclcm.htm

http://www.fpnotebook.com/renal/potassium/Hypklm.htm

http://www.fpnotebook.com/renal/Magnesium/Hypmgnsm.htm

http://www.fpnotebook.com/renal/lab/abgintrprtn.htm

Annie, you've outdone yourself. These are indeed some new clues, and the timing is good, because I have an appointment with my neuro on Monday. I want to talk to him about the HCTZ, and especially whether the way the HCTZ stopped my migraines could be a clue. I am quite sure, though, that the migraines were strongly associated with my period. They would start two days before, and end at ovulation.

I have been doing a lot of reading about hypo- and hyperkalemic periodic paralysis. I just can't make it fit. I'm almost never weak in the morning, and my weak spells come at 5:30 whether dinner's at 5:00 or 6:00.

Some intense journaling is definitely called for...

Let me work on the rest of what you've written.

Thanks, as always, for your loving care of a stranger.

Oh, one more thing I wanted to talk about: your question about a clinical diagnosis of weakness. My regular neuro has me push on his hand, or stand up and sit down repeatedly. I don't think he notices any fatigability. But the neuro who diagnosed me did something different: he had me push on his hand and just keep pushing for a long time--until I felt the muscle just quit. It surprised me.

More later!

Abby

I think you should ask for a redo of the LEMS blood test. The pattern of "okay at first, worse after some exercise and then better" is classic LEMS.

Did you ever have migraines during times when you didn't have a period? Simply because something makes a migraine worse does not mean that it is the cause. It could be an aggravating factor. You can't separate the CNS from the endocrine system. They are completely interrelated. In fact, some researches are now calling it the neuroendocrine system.

Yeah, periods can increase fluid retention but that whole system is related. ;) More hormones, more fluid. But that doesn't happen in everyone (especially not men). :cool:

Well, I have no idea what is going on but there are too many signs that would make a good researcher want to nab you and not let you go until they figured it out!

Some CMS's are also like what you described with your doctor's exam. They don't fatigue as easily but when they do, they go downhill fast!!! Then they rest and recover. You won't like the RNS they normally do for that. It's a RNS for ten minutes. Or as long as you can take it. I've had it and the doc was amazed I lasted as long as I did. But this is why you need a CMS expert! They can usually figure all of this out. Read the PDF. It's an interview done about CMS with UC-Davis. I'm glad I kept it.

I hope you have a great conversation with your neuro. I'm sure he wouldn't want to miss anything. Make sure you reassure him, especially about the Imuran. If this ends up not being autoimmune, he'll want to know that he didn't "harm" you in any way. ;)

I love a good mystery. I hope this helps you too, Mike or anyone else battling these questions.

Annie

Abby my neuro-muscular Dr at the ALS Center gives me a bunch of tests. Just to name a few:
1. hold my arms out like wings then he tries to push them down (3-4) times
2. from sitting position hold up one knee he pushes down and I try to keep him from pushing
3. Walk down hallway about 30ft as fast and straight as possible (both ways)
4. makes me say "ticker ticker" as long and as fast as I can
5. hold my head straight and stare at his finger above my head (to tire my eyes)
6. stand up with feet together and turn 360 degrees both directions.
7. Asks me to smile
8. takes his little hammer and checks all my reflexes including hands and feet

The whole time I'm doing this he has a stop watch and is timing all this. I'm sure there are other drills he puts me through just can't think of them all. Every appt he draws 12-15 vials of blood to be sent off. Only problem with him is he has bedside manner of a junkyard dog.
Mike

Now you have me thinking. I suspect that there is a lot of stuff that is not known yet. People like those of us that are seronegative might actually have something totally different; it may or may not be an autoimmune disorder.

There are two different conditions in horses that cause severe muscle weakness that hit in "spells" sort of like what we tend to do. One is due to an inability to use carbohydrates correctly. The second is a genetic disorder that screws up potassium use. The potassium disorder can all be traced back to one horse, a stallion named "Impressive".

The closest thing to the "Impressive" problem that I could find in humans is hyperkalemic periodic paralysis. Interestingly enough, it responds to hydrochlorothiazide. Hmmmmmm.

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001359/


http://www.vet.k-state.edu/depts/vhc...e/tying.up.htm

http://www.foundationhorses.com/impressive_syndrom.aspx

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001359/

Abby, I thought of a couple more things. If something does run in your family and it's a CMS, it's more likely a dominant inheritance (versus recessive). Though if I've learned anything about this "family" of diseases, it's that they have not even skimmed the surface of the gene pool yet.

Also, there's a classic sign in some of the CMS's called a Repetitive Compound Muscle Action Potential. It's an extra little blip that some doctors would miss.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924514/

Not that you'd want another test again!

Thanks, Celeste. If I have to have a weird, incurable disease, I'd like it to be named "Impressive Syndrome." :)

I've looked into hyper- and hypokalemic periodic paralysis. It's unheard of for it to begin when my symptoms did, at age 43. Still, I don't rule it out. But there's just too much that doesn't fit--for example, the way I feel almost normal in the morning and have trouble in the evening. But I'm going to do some careful journaling of food and symptoms.

Abby

Some things will probably remain a mystery.

Thinking more about hypokalemic periodic paralysis. Maybe it's a better fit than I'd thought. Today I ate breakfast at 8:00 and had to rush out at noon for an appointment, and didn't eat lunch. At about 1:00, I got weak. This is unusual for me. Usually I get weak at around 5:00...which is five hours after lunch. So I'm wondering whether it's the five-hour fast that is triggering the spells. What's confusing is that sometimes I get weak before eating, and sometimes after. I had concluded that eating therefore isn't the cause. But HypoKPP can be triggered by getting to hungry, or eating a carby/salty meal--or by eating after being too hungry.

Another trigger is resting, especially after exercise. Sitting in a movie theater or in church almost always triggers a spell of weakness. I walk in just fine, but can hardly walk out. This is not typical of MG. What confuses me is that I spend a lot of time on the computer at home (I do editing), and I haven't noticed that that makes me weak. Can anyone make sense of that?

HypoKPP is a dominant genetic disorder (though about a third of diagnosed patients are new mutations). But the symptoms can be so mild that it's never diagnosed in one family member, but severe in another. So my healthy parents and seven healthy siblings don't necessarily rule it out.

If I have HypoKPP, then HCTZ is the wrong drug for me. I wish I could remember when I started taking it for migraines. It could be that my symptoms appeared at that time.

I have a question about fatiguability, but I'll ask it in its own thread.

Thank you, thank you, thank you to all of you who are helping me with this.

Abby

P.S.: I never eat popcorn at the movies. Or in church, for that matter.

A.

Annie, I have to apologize. It looks like we've been through this already. http://neurotalk.psychcentral.com/thread150297.html
I forgot about it. Found it again while googling. I have to move on this and stop going around in circles. I shouldn't keep bringing it up, putting everyone through advising me, and then forgetting about it for a while--and then starting all over again. Sheesh.

Abby

I think that is fine. It doesn't hurt to take a fresh look at this crazy disease.
Mike

I thought that it was an interesting discussion. Besides, with all the memory issues I have had, who knows whether we discussed it? :eek:

Well, no, Abby, you don't need to apologize. Maybe you have "guilt disease." :rolleyes:

Your situation has been bugging you for a long time. You have the right to know what "the" answer(s) is.

The best way to solve any problem is through this kind of tossing out of ideas. Doctors aren't always comfortable with creative thinking - they're more left-brained. And they're often not comfortable in the land of "I don't have a clue." No offense to our dear Veterinarian! You have major doctor savvy. The majority of doctors I've seen simply aren't that great at creative problem solving.

I don't see this as repeating information but zeroing in on better connections of information. There's no ego involved. Only the truth matters. And until you feel comfortable with a truth, bug away! ;)

You might simply have MG that is not as classic as what others have. Until I found the antibody test that had been hidden from me for nearly 7 years, I wasn't completely satisfied with the VERY obvious evidence that I had MG. CMS is still in the mix for me, in addition to MG, and since some not very nice doctors won't do the simple blood tests for CMS, I'll still be sort of vexed. The treatments really wouldn't be much different in my case, however, if I have a CMS in addition to MG.

If this gets to annoying, just tell me to bugger off. I think I'm done for now, though. It's up to your docs and you at this point.

:hug:
Annie

Abby this sorta reminds me of my family DNA test. When I applied our Admin asked me who my immigrant was. It was a choice of 2 men and had been an on going debate for over 25 years. I told her I didn't care I just wanted the truth. Well when my results returned it turned our family history upside down. But heck I just wanted the truth and finally got it.

Annie what is the simple blood test for CMS? Does it go to Mayo?
Thanks
Mike

Thanks, Annie. What I'm trying to avoid is stirring everything up, getting lots of advice, not following it, and then, after a while, stirring everything up again and making people give me the same advice. But I do think we're getting somewhere--I mean that every go-round we add something new. The paradigm for this process is a helix (the shape of a spring). We're not going around in circles--we're spiraling up. Yay for helices!

I am going to bring all this up to my neuro on Monday. I also need to talk to him about my mother's sister, who has, whaddayaknow, sudden weird balance issues and double vision but it wasn't a stroke. They tested her twice for MG (negative). So if there's a blood test for CMS, I'd like to hear about it, though I think what my neuro will do is send me to Mayo. He's offered before. I also want to talk to the doctor in Boston who did the SFEMG that diagnosed me. I want to ask him if my test is consistent with CMS and if it's consistent with HypoKPP.

I'm also going to try eating low-carb, small meals every three hours, because my spells seem to come either after not eating for five hours, or after getting very hungry and then eating. This is the HypoKPP idea. But HypoKPP is caused by a dominant mutation. My parents are unaffected. It's possible that one has a mild case, which expressed itself more severely in me--but my seven siblings are also unaffected, and so are my 35 nieces and nephews on that side (though one little boy seems to have ptosis in some photos--haven't dared to ask my sister-in-law about that!). AND I have seven kids, the youngest of whom is 9. You'd think that this would have shown up in someone besides me by now, if it were a dominant gene. Same thing goes for the CMS idea. With such a large family, we're in a better position than most to trace the genetics.

Thank you, all you lovely people, for being interested, and caring. I will keep you updated, and please, please tell me if you have any new ideas.

Abby

Has your aunt been checked for normal pressure hydrocephalous (NPH)?

Wow, it's so amazing you bring that up! My grandmother (mother and aunt's mother) had Alzheimer's. My mother (age 69) has been having some weird symptoms of mild dementia, but doesn't have a diagnosis of Alzheimer's. She has speculated that my grandmother didn't have Alzheimer's at all, but NPH, especially since she had a shuffling gait. NPH is evidently hereditary. I'm going to write to my mother and aunt right away.

Abby

Abby, If your Mom and Aunt have not been tested for a B12 deficiency, get them tested pronto! And don't take a low reading - even in the normal range - as normal. A B12 deficiency begins even at higher levels. Pernicious anemia is also a thought. Homocysteine (mine was high during my def.) and methylmalonic acid can be elevated during a B12 deficiency and that alone can cause neurological symptoms.

Mike, There are actually many blood tests for the genetic mutations of a CMS. Since Mayo was the leader in this area to begin with, they have the means to test for it more easily. Not many labs have the money to afford such specialized testing. Your neuro would have to call to see if they would just run some blood tests or if they would want to see you - AND your sister at the same time. ;)

Annie

Thanks Annie I'll discuss this with my doctor (wife)
Mike

Today I feel like I have Plain Old MG. Yesterday, I got up early and took my kids to a special Mass in a city I'm not familiar with. Then we stayed for the reception, where I was having such a good talk with a friend that I didn't want to interrupt it to tell her I had to sit down. Then we got home and I baked and decorated a fancy cake for my daughter's birthday. Then we went to a friend's house for dinner. Usually, I would only do one of those things on any given day, and not all three. By 10:00 I was in a state of utter, utter exhaustion, and had to be helped upstairs.

This morning my first try at sitting up in bed failed. My arms are tiring quickly as I type this, and while I don't have double vision, it's a strain to keep my eyes focused (hello, Mary Walker phenomenon). I hope that next time I start questioning whether activity is a trigger for my weakness, I'll remember writing this.

Meanwhile, my daughter's birthday dinner menu has changed from home-made cheddar-broccoli soup and rolls to take-out Chinese, I'm playing hooky from church, and I've decided to wait until the laundry reaches critical mass, thereby obliterating itself in a nuclear explosion before I have to deal with it. I hope that the rest of you can find a way to rest, too! And thank you so much for talking this through with me. Not only do I get excellent information and leads, but it helps me to sort out my own ideas.

Abby

So whatcha think is causing the weakness?:cool: (ducking!) I don't know if you are in a love or hate phase with the mestinon right now, but if you haven't already tried it, you might try 30 mg or so....just for an experiment.

Take care--and know I wouldn't tease if I didn't care (and understand!)

Once we had a family staying in our house (we have an in-law apartment). The whole house is heated by a central wood stove. The husband always thought I was managing the stove wrong--the different vents, etc. He wanted me to do it in a way I knew for sure wouldn't work.

So, after weeks and weeks of this discussion, both of us getting more and more frustrated, my family went away for a few days, and we left him in charge of the stove. Finally, he could do it his way! When we got back, he told us that the house had been FREEZING the whole time we were gone, because he just couldn't get the fire to burn properly. But he had an explanation: atmospheric pressure.

So, in answer to your question of what is causing my weakness today, I would say: definitely atmospheric pressure.

I have tried this experiment SO many times...I've tried it to abort episodes, and to prevent them, and to improve constant weakness and to prevent it. I've tried it for each different kind of weakness. Really, no dice.

...and I probably wouldn't take it so well if I didn't know, in my heart of hearts, how very right you are...And yet--I was so energized by my two social visits yesterday! As I know you understand, sometimes we need emotional energy even more than we need physical energy--though I always hasten to add that I have the luxury of making such choices because I never have breathing trouble.

Take care,

Abby

Abby, love your analogy

kathie

Hope the birthday party goes well! And yes, sometimes (usually) it is way more important to get out and enjoy yourself. If you'll notice, it's a crapshoot whether or not it will affect you later. I remember reading posts about how you've been a busy bee for weeks on end with no repercussions at all. Such is the nature of MG. If we could plan the weak periods, it would be so much easier!

Yes, I had a great summer--I took the kids to the ocean many times! Long drive, hot sun, long walk--and I was fine. Go figure. I started getting symptoms back in mid-August.

But today's weakness was well timed, because it came just as I was doubting whether my weak spells were really related to activity or not.

I'm not sure what I'm going to say to the doctor tomorrow!

Abby

Abby, I love your story.
I just had a similar experience with someone who thought I did everything wrong and he is now going to fix it. Well...Hopefully he will be able to mend things back to where they were before...

I fully agree with that. You can do that even if you are having breathing troubles, as long as you have a good respirator at hand.

There is a joke I like to tell my patients: A 60 year old healthy man comes to his physician and tells him that he wants to live to be 100 and wants his advise on how to achieve that.
The doctor asks him: Do you drink wine? the man says-of course not.
Do you go out? and the man replies-Of course not. Do you indulge on delicious whipped cream cakes every now and then? and the man again replies-of course not.
In that case, the doctor asks, why exactly do you want to live to be 100?

It took me 6 years (and a wonderful neurologist) to gradually stop feeling that "Alice in wonderland" loss of control over my life. Paradoxically, what helped me most was accepting the fact that I have no control over this illness.

It may seem funny, but understanding that what ever I do, I can't change the course of this illness gave me the peace of mind required to deal with my daily life with it. I realized that all the temporary aids I used (until I get better) actually enable me to lead a reasonably productive life.

But, this did not happen in one day, one month or even one year.

Hi Abby,

I just wanted to start off by saying I have no idea what's going on or what's appropriate in your case and this is not to be considered advice. But because you never know who's lurking and following and learning, I wanted to point out that weakness on waking after overdoing it the day before is very consistent with HKPP.

I smiled a little because you usually say that your normally stronger mornings would be atypical of HKPP, yet here you have a day with morning weakness and based on that, conclude that it's straight MG. It can be complicated; there are 3 people on the HKPP forum who are believed to have both periodic paralysis and some form of myasthenia. A fourth was originally misdiagnosed with MG, now has genetic confirmation of HKPP, but had had a positive response to Mestinon that was measurable on EMG readings. (I know you're not helped by Mestinon, I'm just pointing out how muddy the waters can get.)

Exercise can definitely be a trigger for channelopathies as well as MG. Here's an article you might find interesting. http://www.sciencedaily.com/releases...0117111844.htm

When I see the doctor in Boston, I want to ask him about HKPP. If he doesn't know anything about it, maybe he can refer me to someone who does. Thanks.

Abby

I've been trying a diet designed to reduce HypoKPP symptoms: that means not letting myself get too hungry, and not eating a lot of carbs and salt in one meal. So I eat small meals at 8:00, 11:00, 2:00 and 5:00, and I eat a low-salt, low-carb supper. I am trying to see if I can head off that attack of weakness that typically hits me between 5:00 and 6:00.

It's too early to know for sure if this is a new pattern, but it seems to me that when I do this, I get an attack at around 7:00 instead of around 5:00. Not sure what to think of that. Probably a coincidence. But I think my eating plan is sensible enough, and harmless, so I'm going to stick with it some more.

Abby

Couple of quick updates. First, my special diet (eat every three hours, small meals, no heavy carbs or salt) isn't heading off the attacks of weakness. Second, my aunt who suddenly came down with balance trouble and double vision has half a diagnosis from a neuro-ophthalmologist: Graves ophthalmology.

Graves disease runs rampant in that side of my family. Evidently Graves disease can cause double vision even in a patient whose thyroid isn't running hyper. The mechanism is that the tissue behind the eyes is just a really good fit for Graves antibodies, so they tend to collect there, and that causes double vision. The neuro-opth didn't see any signs of a myasthenic syndrome. Her balance troubles are resolved and still unexplained.

So...well, so I still don't know what's going on. I see the Boston neuro on Tuesday.

Abby

DV can cause disorientation/balance issues, especially at first. Glad your Gram found some answers and hope you do, too!

Abby, I'm sorry the diet didn't help. Thanks for telling us so we won't all go out and try it.

Celeste, there's no reason I know of to think the diet I describe would help MG. I tried it because I'm wondering if there's a chance I have hypokalemic periodic paralysis instead of MG. Getting too hungry, eating a lot of carbs at once, and eating a lot of salt at once can be triggers for HKPP for some people.

Abby

In the past couple of weeks, I've been worse, which has been helpful: it's very clear to me now that I have fatigable weakness, and not just spells of weakness. I think when I'm generally strong, I just don't notice it so much.

So for example, today I can put two or three logs into the wood stove, but by the fourth, my arms are really tired.

I am not ruling out HKPP--I will talk to the doctor about it--but I feel more like my symptoms fit well with MG than I used to.

Abby

Abby I think you are right. You have to give this crap a lot of thought.
Mike