Temporary paralysis I need your Insights

[anciendaze]

@anciendaze the doctor I saw today is mainly an academic researcher so I'm hoping that could mean he has the curiosity and tenacity to follow the trail to some sort of destination. I was a bit worried that he mentioned the limits of medical science though. I realise this is very true, but an expectation of whether the answer is findable will probably influence the nature of the search for it.

For the leg/walking/standing issue I've put that down to POTS for the last couple of years (it usually comes with feeling lightheaded) but the two lying down tests I couldn't do today wouldn't be that, as not standing/sitting. The leg issues fluctuate quite a bit so I'll probably try those tests again on a good day.

I've been seeing a correlation between POTS and some autoantibodies. All the patients I've communicated with who test positive for antibodies to N-type calcium channels also exhibit POTS, though the converse is not true. These also exhibit dyspnea, (shortness of breath,) under orthostatic challenge. Patients with antibodies to GAD65 who have both sleep issues and problems with legs have also turned up, though I don't know much about how this works. The temporary nature of your severe problems makes me suspect either autoantibodies which increase during flares, or an ion-channel disorder affected by electrolytes, but it is appropriate to rule out mechanical problems with things pressing on nerves at this time. I'm assuming this is one approach the doctor will follow.

It would be reasonable to also check for an autoimmune disorder or a traditional metabolic problem before you get into research questions.

I'm afraid I've forgotten any clues you've mentioned about triggers. Right now I'm wondering if you are especially sensitive to carbohydrate loading or changes in electrolytes. Known sensitivities to medication can also be a valuable clue.

 

[Jenny TipsforME]

Electrolytes seem to be related, but it improves with a balanced electrolyte solution so if that it's likely hypo something rather than hyper.

I discussed autoantibodies with him, although more in relation to pwme and POTS having AChR-ab. I'd actually be surprised if I'm not in that subgroup but whether we find the relevant one/s is another question.

They did some blood tests yesterday for myasthenia gravis, that antinuclear autoimmune one, electrolytes, creatine kinase (I've had high before), thyroid and the standard vitamins etc. Waiting for those results and an EMG appointment now.

 

[Gingergrrl]

Any ideas about this neuro exam? e.g. @anciendaze @Valentijn @Gingergrrl @kangaSue

Thanks for tagging me @Jenny TipsforME and apologies for my delayed reply. I do have some ideas and it sounds like overall, your Neuro was pretty decent (compared to some horrible neuros that I have seen)! Did you feel that he was interested in dialogue and will follow up and try to help you?

He's testing me for myasthenia gravis ab, some general blood tests and an EMG as a first step to working out what is going on

I am glad that he is testing you for MG antibodies as well as doing an EMG. Do you know if he will test you for some of the more rare autoantibodies? In your case (from your episode of temporary paralysis) would he be willing to test you for the Potassium autoantibodies and send your blood to Dr. Angela Vincent's lab or to Mayo in the U.S.?

This was one I couldn't do at all. Can you do it?!

I can very easily do this test and have no issues with moving my legs (moving the opposite leg from knee to heel and back like in the picture you posted). My issues relate to breathing & autonomic stuff while standing.

@anciendaze the doctor I saw today is mainly an academic researcher so I'm hoping that could mean he has the curiosity and tenacity to follow the trail to some sort of destination.

That would be awesome, Jenny, and am hoping this Neuro has the intellectual curiosity and human decency to figure this out (or at least try).

I've been seeing a correlation between POTS and some autoantibodies. All the patients I've communicated with who test positive for antibodies to N-type calcium channels also exhibit POTS, though the converse is not true. These also exhibit dyspnea, (shortness of breath,) under orthostatic challenge.

@anciendaze, I know I am one of the people that you are mentioning (which is totally okay and it is not a secret!) but I was very interesting to learn that you have communicated with other patients who have the autoantibodies to the N-type CA+ Channels beside me and that they also have POTS and dyspnea when standing! How did you find these other people?!!! I belong to an amazing FB group for people with this antibody (and some do have POTS) but as far as other symptoms, we are very diverse and all over the map.

I discussed autoantibodies with him, although more in relation to pwme and POTS having AChR-ab. I'd actually be surprised if I'm not in that subgroup but whether we find the relevant one/s is another question.

I suspect you will be in the autoimmune subgroup (or whatever we want to call it) and I am hoping you can get tested for other auto-antibodies in addition to MG. Did he say what potential treatments might be (like IVIG or RTX, etc) or is it too early to even discuss that? My EMG was considered "normal" even though other doctors later felt it wasn't. I wish I had the opportunity to re-do it but since it would not change my current treatment plan, I am not focusing on it.

Also, did your Neuro mention that certain autoantibodies can be linked with paraneoplastic syndromes so it can be good to do cancer checks (once you know which auto Abs you are positive for)? Just to be safe and NOT b/c I think you have cancer.

 

[Jenny TipsforME]

@Gingergrrl am I right in remembering that Justin had paraneoplastic syndrome? Earlier in this thread (sorry I know that's difficult to think of) he seemed to be saying he had similar paralysis episodes and also the throat constriction. It didn't come up as a likely thing in my appointment but it is on my radar as a less likely issue.

For obvious reasons my doctor wants to start with the conditions that are likely and easier to find. This was particularly a comment in relation to periodic paralysis which he said there's so many types of it can be like looking for a needle in a hay stack. He also thought I'd probably have had more episodes, starting younger if it was that. He said the EMG would give info for PP too though.

 

[Gingergrrl]

@Gingergrrl am I right in remembering that Justin had paraneoplastic syndrome? Earlier in this thread (sorry I know that's difficult to think of) he seemed to be saying he had similar paralysis episodes and also the throat constriction. It didn't come up as a likely thing in my appointment but it is on my radar as a less likely issue.

Justin had a specific autoantibody that correlated with a specific type of cancer so there was a good chance that his symptoms were due to a paraneoplastic syndrome. However, to the best of my knowledge, at the time that he passed away, no actual cancer had been found but there were more tests to be scheduled. Am happy to chat more via PM if I can be of help. Although I am confident that if his situation could help someone else like me or you, he would love for that to occur, just like the internship that will be in his name.

He also thought I'd probably have had more episodes, starting younger if it was that. He said the EMG would give info for PP too though.

This is where @anciendaze is the expert IMO and I am not sure how frequently someone with PP would have episodes or at what age they might start. I do not have PP but have an antibody that blocks the calcium channel. I honestly do not know when I developed this antibody (and all of the others) but suspect they were all post-viral.

I had an EMG that was specifically for "LEMS" b/c this correlates with my autoantibody and was told that it was negative. I believe that it was b/c my overall symptoms do not really match with LEMS although some of them did. All I know for sure is that I had neuromuscular weakness (never paralysis) and autonomic problems (POTS and hypotension) that affected my breathing and not getting enough blood/02 to the heart and lungs when I stood up and I was unable to pass any PFT or spirometry test.

These issues are so new for most doctors and I am really hoping and praying that the Neuro that you saw will want to get to the bottom of it and figure out what is going on.

 

[anciendaze]

...
This is where @anciendaze is the expert IMO and I am not sure how frequently someone with PP would have episodes or at what age they might start. I do not have PP but have an antibody that blocks the calcium channel. I honestly do not know when I developed this antibody (and all of the others) but suspect they were all post-viral...

I'm not an expert, but I know someone who is. This subject is a work-in-progress, and I am encouraged that this doctor said there are many different forms of periodic paralysis. This is much better than claiming it does not exist.

I'm now rethinking some previous assumptions after learning about "nutcracker syndrome" or "superior mesenteric artery syndrome", though I have no idea if this applies here. "Real cases", in the minds of doctors, tend to involve both pain and hematuria. This is a combination of a serious complaint with a conspicuous clinical sign. Nothing in nature demands this. My guess at the moment is that a great deal of variability in presentation is due to immune response to occult bleeding. (Localized ischemia causing sterile cell death may also provoke an autoimmune response.)

Powerful immune responses to cancers of the ovaries or testes are known to cause paraneoplastic syndromes. I am speculating that bleeding in the same organs could provoke an identical response.

W.R.T. age at onset of PP, this typically shows up in late teens. Most patients go years before recognizing triggers, so clinical presentation tends to be very uneven, depending on what they were doing just prior to seeing a doctor. Most patients find some pattern of behavior which minimizes problems before getting a professional diagnosis. (Some have gone 30 years without a correct diagnosis.) Not all of these behaviors makes sense, and some may be like a gambler's lucky socks. Others are definitely connected with problem foods or activities. You don't have to psychoanalyze the patient to find out why they are generating new behaviors in response to a condition that leaves them paralyzed.

Early studies in Europe suggested there might be identifiable genetic causes in 30% of cases. Studies extended to North America, with a highly-varied and more mobile population, have recently found only 10% with identified genetic factors. You can't depend on genetic testing any more than you can in type III Ehlers-Danlos Syndrome. Response to changes in electrolytes, carbohydrate loads and/or exercise, seen on objective tests, will clearly distinguish patients with life-threatening disease, but we are still in the dark about the incidence of less severe conditions.

 

[Jenny TipsforME]

I've been a bit disheartened because my difficulties walking are getting more severe around the house and seem to maybe be associated with starting midodrine. You may remember that I felt the paralysis and heavy legs are strongly connected to POTS so my expectation was that midodrine would help.

Interestingly I had a milder episode like the May paralysis one on Saturday (that time was 7hr only able to move fingers/toes and head then 4hr also wrist and ankle movement) . It was nowhere near as alarming but felt the same and had basically the same trigger. The midodrine had initially given me a noticeable improvement taking standing showers. I don't feel like I'm about to faint. In the process of washing on Saturday I got hot water on my abdomen and that appeared to be the trigger for the weakness coming on. Again I got to the bed although I think this time I needed help. It felt the same eg tingling on right side of face, hard to describe overall oddness. This time I kept the use of my lower arms and legs (not just fingers and toes) and my trunk area wasn't completely immobilised (the previous time I couldn't adjust my position at all). It did feel qualitatively the same just not as severe.

I feel like if I wasn't foggy I could work this out. Does anyone have ideas? Eg @Jonathan Edwards @alicec @JaimeS @anciendaze @lnester7 @Hell...Hath...No...Fury.. @taniaaust1 @Gingergrrl @kangaSue
I see that muscle weakness is a possible side effect from midodrine but does anyone understand the mechanism for that? I also feel quite sleepy on midodrine so it probably isn't going to be a wonder drug for me anyway, (@zzz suggests this is to do with oxytocin on another thread). Could my response to midodrine point to what is going wrong? The heavy weakness is happening even when midodrine should have worn off, so it could be an indirect/knock on effect. I've thought of PEM from doing slightly more, but the shower heat thing seemed too immediate for that (and heat trigger chimes with a hot shower before the 11hr episode, usually I avoid hot water).

In terms of ongoing investigation, doctors seem to want to rule out if I have a primary muscle disorder. I'm not expecting that outcome due to how much my muscle strength can fluctuate, although I think some myopathies can fluctuate.

The blood tests the neurologist took on a bad heavy legs day were normal including electrolytes and creatine kinase (I've previously had high creatine kinase on a bad myalgia day). Still waiting for the EMG.

 

[Jenny TipsforME]

The obvious thing is it is to do with blood flow/vasodilation. The hot water makes this go haywire. If this was the reason though wouldn't I get normal movement back once normal temperature restored? Also why would midodrine increase it, shouldn't it decrease the problem? I've checked my blood pressure a few times and don't seem to get a paradoxical reaction (it's either low or normal in a way I'd expect for me, but I also haven't had a high BP reading on midodrine).

Might it be to do with the para/sympathetic nervous system? To do with a activation of the alpha-adrenergic receptors? I'm not feeling well enough to read this type of thing http://jpet.aspetjournals.org/content/298/2/403.long#sec-10

As you might expect, I've decided to lay off the midodrine for a few days and see if I return to my normal. Today without midodrine I'm still having increased "concrete legs" inability to walk. I just missed a parcel for the 2nd time (redelivery) because I couldn't get to the front door. Of course it is possible it isn't related to midodrine but the frequency is dramatically worse for the couple of weeks I've been taking it. My partner (an academic who is quite cautious about attributing patterns) also thinks it is linked to midodrine.

 

[Seven7]

I got hot water on my abdomen

I unfortunately cannot do hot showers /bath and I am highly functional compared to most. This is like a natural vasodilator but I don't know what the deal is, for me is like I run a marathon.

When I started midodrine, I also had paralysis like episodes but in my case was that I overdid it, is hard to explain but even though you feel better on it, the activity capability was the same, so I was overdoing beyond imagination. When I scale back (and you feel like going crazy because now you can do more but really can't) then slowly increase, in my case the only way I can increase is if I walk everyday more. But I don't know how others increase capacity. I guess we all have to find what does it for each. Then you can increase slowly. See if that helps. But discuss it with your doctor in case is really a side effect you are feeling.

 

[Jenny TipsforME]

@lnester7 i remembered people on here saying a while back that midodrine doesn't prevent PEM so I've known to be careful. It would be subtle if that was the cause eg standing a minute longer here and there and that accumulating. It would explain the problem not going with midodrine wearing off though. I'm sort of hoping it's not that in that the 'useful clue' would just be pointing back to having ME, which isn't really news...

With the shower thing I was feeling fine (not my normal shower experience!) then the hot water went on my abdomen and there was an instant change in feeling the over all heaviness coming on. This seems autonomic/vasodilation- midodrine wasn't strong enough to prevent? But my feet weren't red (usually without midodrine they are when I wash unless the water feels cold). I think it could be something to with the contrast between blood pooling in my abdomen and vasoconstriction in other places?

 

[Jenny TipsforME]

I've had "concrete legs" coming on increasingly for 10 years (ME 19yrs). In general I'd say it doesn't map neatly to PEM/fatigue but is more related to POTS fluctuations. I was initially told it was fatigue but treating it as that (rest) doesn't improve it but treating POTS does. Eg the frequency initially went down a lot when I started the beta blockers bisoprolol. This benefit is either wearing off or the underlying problem is getting worse.

 

[Gingergrrl]

I feel like if I wasn't foggy I could work this out. Does anyone have ideas? Eg @Jonathan Edwards @alicec @JaimeS @anciendaze @lnester7 @Hell...Hath...No...Fury.. @taniaaust1 @Gingergrrl @kangaSue

I wish I had an idea and have been racking my non-science brain but not sure what to make of this. Were you ever tested for the potassium antibodies? (the ones linked to the Partial Paralysis issues that anciendaze was mentioning earlier in this thread).

I have taken Midodrine off and on since 2014 from doses as low as 1.25 mg per day and as high as 15 mg per day but have never had this issue from it. But we are all different so I know this means nothing! Last week I actually had some weakness/numbness in my lower legs (and had not taken Midodrine since July when I started IVIG) so we added it back in (actually for a different reason) and since adding it, the leg issue completely went away. Although it could all be coincidence.

Sorry this is not more helpful and hope you figure it out soon!

 

[Jenny TipsforME]

@Gingergrrl yes I thought midodrine would specifically help this type of issue too

I've only seen my blood test results on the screen in my cardiology appointment (the results weren't in his area but he said they were normal, at some point I'll get a printout). I haven't had loads of antibody tests yet but they did test for Myasthenia Gravis (an Acetylcholine receptor issue) and the antinuclear one.

It seems like there's a sort of order to the testing. The doctors want to rule out if I have a primary muscle disorder first. At some point soon I'll get an EMG test to see how my muscles respond under measured stimulation.

I think then they start to see if it's the messages to the muscle if the muscle itself is ok. The neurologist didn't rule out periodic paralysis but he said there's so many types it can be like finding a needle in a haystack, so he wants to start with things which would be easier to find if they're the problem.

 

[Gingergrrl]

@Gingergrrl yes I thought midodrine would specifically help this type of issue too

Sorry if you already said this but what dose of Midodrine do you take and how many times per day? The weird episode that I had of numbness/pain in my calves disappeared after 2-3 days but it was absolutely nowhere in severity compared to what you experience and I truly cannot say if there is any connection to me re-starting Midodrine vs. it going away on it's own.

I've only seen my blood test results on the screen in my cardiology appointment (the results weren't in his area but he said they were normal, at some point I'll get a printout). I haven't had loads of antibody tests yet but they did test for Myasthenia Gravis (an Acetylcholine receptor issue) and the antinuclear one.

Yes, definitely get a print-out of your results if you can. All of my tests for MG, myasthenic syndromes, MuSK antibodies, etc, were negative. I learned that these tests reflect an issue with the nicotinic receptors which I do not have. But my tests that measure the muscarinic receptors (the Cell Trend tests from Germany), I was positive on 7 of the 9 antibodies. Plus I have the anti Calcium Ab, etc. So my neuromuscular issues are more rare but they are no less real. I suspect that yours are also more rare and it may not be found w/this first round of testing (although I could be wrong of course)! My ANA was 1:160, speckled pattern and am curious how yours will compare.

It seems like there's a sort of order to the testing. The doctors want to rule out if I have a primary muscle disorder first. At some point soon I'll get an EMG test to see how my muscles respond under measured stimulation.

It makes sense to start with the more common things but am hoping they will test you for some of the rare stuff, too. Can you send blood to Cell Trend in Germany on your own? My other tests involved sending the blood to Mayo Clinic. I really wanted to send blood to Angela Vincent's lab in the UK (that was my dream scenario) but so far have not figured out a way to do this. But my doc is going to try to consult w/the US expert, Dr. Vernino, re: my case.

I think then they start to see if it's the messages to the muscle if the muscle itself is ok. The neurologist didn't rule out periodic paralysis but he said there's so many types it can be like finding a needle in a haystack, so he wants to start with things which would be easier to find if they're the problem.

Makes sense and I hope your EMG goes well. Mine was useless (last year) b/c the doc was only doing it to rule out LEMS and did not look at anything else. It ruled out LEMS (which I never suspected that I had) but it was not a "single fiber EMG" which is actually the gold standard test for LEMS. It showed my left phrenic nerve was only working at 57% but the doctor told me the entire test was "Normal" and would not discuss it w/me even for five minutes. Needless to say, he is no longer my doctor but it was a very frustrating experience!

 

[Jenny TipsforME]

I have to say I'm feeling alarmed at the increase in frequency of my leg problems. I'm sleeping downstairs tonight because there's no way I can get upstairs. Earlier I had to call a neighbour in because the dog was outside and I couldn't get her in or my food or her food. When I started bisoprolol a couple of years ago I got these concrete leg episodes down to once a month in terms of walking around the house. On no medication before that it had been about once a week. The last couple of weeks it's roughly half the time I want to do simple things like walking to the toilet

 

[Gingergrrl]

Jenny, am sorry to hear this and wish I had something useful to offer. Am hoping you can see the Neuro soon and that he will actually be helpful. Will be sending positive thoughts and prayers for you.

 

[JaimeS]

Does anyone have ideas? Eg @Jonathan Edwards @alicec @JaimeS @anciendaze @lnester7 @Hell...Hath...No...Fury.. @taniaaust1 @Gingergrrl @kangaSue

Responded in PM, Jenny! Ugh, this is awful. <3

 

[anciendaze]

@Jenny TipsforME

We are not ignoring you, this is clearly a real condition with serious consequences. Speaking for myself, I am waiting to hear results from tests you have mentioned. This could go a several different directions, and the wrong advice could well be harmful. This is not a condition for amateurs to treat, including amateurs who happen to be M.D.s with expertise in other areas. It requires highly-specific knowledge and experience with metabolic, muscular and neuromuscular conditions which can result in true temporary paralysis. Differential diagnosis requires information we just do not have.

 

[Jenny TipsforME]

@adreno understood. I just wish the NHS moved a bit quicker! I think the neurologist was under the impression I'd have had the EMG by now, whereas I haven't even had the appointment letter yet... And this testing is actually the follow up from the May episode not the recent worsening
At least I won't be in debt from it though I suppose. [insert cloud with silver lining emoticon]

 

[ahimsa]

@Jenny TipsforME

I'm sending you lots of hugs and healing vibes

I wish I could offer some actual suggestions but I have no medical background & no idea what's going on. But I wanted to offer my support -- no response does not mean we're not thinking of you!