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.

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).

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

Attached Files

congenital_myasthenia.pdf (53.5 KB, 408 views)

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.