Case Report. Voltage gated potassium channels ANA-dysautonomia-IVIG

Zebra

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This is great news. Did your doctor also order tests for VGKC and VGCC autoantibodies?
Hi, @Gingergrrl

I appreciate you asking. I have read through many of your older postings on PR and your symptoms, medical findings, and experience with certain specialists is very similar to mine. (Well, except for MCAS. I have been spared from that!)

I have been tested for the VGCC antibodies several times between 2015 and 2018. All blood testing was done at the Mayo Clinic and those particular antibodies always come back negative.

The main VGKC antibody has been negative as well.

Early this year I had an appointment with a *fourth* neuromuscular specialist. This one refused to repeat the 3 VGCC antibody tests associated with LEMS, but she did perform a repetitive stimulation test, which she said was perfectly normal.

I've seen the NCS/EMG results, and they don't look perfectly normal to me, so I'm going to have my local neurologist look them over. I want to make sure we definitively rule out a LEMS or Myasthenia Gravis diagnosis before moving on.
 

Zebra

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I am trying to keep my expectations very low, but if something does come back positive, I will report back here.
Well, I utterly FAILED to keep my expectations low, and all three antibodies (LGI-1, CASPR2, and DPPX) all came back negative.

I am deeply disappointed, but too physically, mentally, and emotionally exhausted to emote.

I only had my serum tested at Quest Diagnostics. If my local neuro is open to doing a spinal tap to check my CSF for antibodies, I will pursue that this summer. My understanding is that the more comprehensive Mayo Clinic Autoimmune Encephalopathy (ENS2) Panel is supposed to be run on serum and CSF simultaneously.

https://www.mayocliniclabs.com/test-catalog/Overview/92116
 

Gingergrrl

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If one has voltage gated potassium channel antibodies, would it help to supplement with potassium?
I want to first state that do not know the answer but when I first tested positive for the voltage gated calcium channel antibodies, I asked a Neuro the same question (except re: calcium not potassium). That Neuro told me that taking calcium would not hurt but probably would not help b/c the issue was not with the calcium molecule vs. the ion channel. I am probably not remembering it all correctly since this was back in 2016.

I have been tested for the VGCC antibodies several times between 2015 and 2018. All blood testing was done at the Mayo Clinic and those particular antibodies always come back negative. The main VGKC antibody has been negative as well.
If you ran these tests several times with Mayo, I would assume that the results are correct and you are negative for the autoantibodies.

I've seen the NCS/EMG results, and they don't look perfectly normal to me, so I'm going to have my local neurologist look them over. I want to make sure we definitively rule out a LEMS or Myasthenia Gravis diagnosis before moving on.
Do you remember what the NCS/EMG results said that appeared abnormal? What symptoms do you have that might indicate LEMS or MG? (and as always I apologize if you have already explained this a million times)! My neuromuscular testing (prior to any treatment) showed that my left phrenic nerve to my diaphragm was only working at 57% of normal.

Well, I utterly FAILED to keep my expectations low, and all three antibodies (LGI-1, CASPR2, and DPPX) all came back negative. I am deeply disappointed, but too physically, mentally, and emotionally exhausted to emote.
If you are testing negative for all of these autoantibodies then this is good news and means that you can eliminate several causes of autoimmunity or paraneoplastic syndromes. But on the flip-side, I do understand how it felt to finally get some answers re: what was wrong with me and a plan for treatment.
 

Zebra

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Came across this journal article from 2020. Might be useful to anyone pursuing the VGKC "complex" antibodies:

https://pn.bmj.com/content/20/5/377.long

ABSTRACT:

Autoantibodies to leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein like-2 (CASPR2) are associated with clinically distinctive syndromes that are highly immunotherapy responsive, such as limbic encephalitis, faciobrachial dystonic seizures, Morvan’s syndrome and neuromyotonia. These autoantibodies target surface-exposed domains of LGI1 or CASPR2, and appear to be directly pathogenic. In contrast, voltage-gated potassium channel (VGKC) antibodies that lack LGI1 or CASPR2 reactivities (‘double-negative’) are common in healthy controls and have no consistent associations with distinct syndromes. These antibodies target intracellular epitopes and lack pathogenic potential. Moreover, the clinically important LGI1 and CASPR2 antibodies comprise only ~15% of VGKC-positive results, meaning that most VGKC-antibody positive results mislead rather than help. Further, initial VGKC testing misses some cases that have LGI1 and CASPR2 antibodies. These collective observations confirm that laboratories should stop testing for VGKC antibodies and instead, test only for LGI1 and CASPR2 antibodies. This change in practice will lead to significant patient benefit.
 

halcyon

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Thanks for posting this @ChookityPop and thanks for bumping the thread @Zebra as I had missed it the first time around.

The focus on the double-negative VGKC antibodies was a bit confusing, but is also burying the lede a bit; the important part to me is that IVIG caused significant clinical improvement as well as dropping the VGKC titer. Off the top of my head, this is the second published case of a lab-confirmed enterovirus infection triggering an IVIG-responsive autoimmune dysautonomia, the other being Goodman (2014). This is encouraging for folks like me with enterovirus triggered ME/POTS, but also frustrating as I've yet to identify evidence that could actually get me ongoing IVIG treatment.

I've also been working on a theory that echovirus induced ME/dysautonomia specifically might respond well to IVIG. Unlike its ME causing cousins the coxsackieviruses, echoviruses utilize the FcRn receptor for cell entry, rather than the CAR receptor. IVIG is thought to work in part by saturating the FcRn receptor with supraphysiologic concentrations of immunoglobulin, so it seems possible that this could also disrupt the ability for chronically infecting echoviruses to spread to other cells. Though this wouldn't have any effect on extracellular vesicle virus spreading, which may be more significant in chronic infections. I'm just always looking for some explanation for why immunoglobulin can bring one ME patient back to life, while doing nothing for another (as in the Norwegian documentary Sykt Mørkt). Unfortunately this Eikeland paper does not mention which specific enterovirus species triggered her disease.
 

ChookityPop

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Thanks for posting this @ChookityPop and thanks for bumping the thread @Zebra as I had missed it the first time around.

The focus on the double-negative VGKC antibodies was a bit confusing, but is also burying the lede a bit; the important part to me is that IVIG caused significant clinical improvement as well as dropping the VGKC titer. Off the top of my head, this is the second published case of a lab-confirmed enterovirus infection triggering an IVIG-responsive autoimmune dysautonomia, the other being Goodman (2014). This is encouraging for folks like me with enterovirus triggered ME/POTS, but also frustrating as I've yet to identify evidence that could actually get me ongoing IVIG treatment.

I've also been working on a theory that echovirus induced ME/dysautonomia specifically might respond well to IVIG. Unlike its ME causing cousins the coxsackieviruses, echoviruses utilize the FcRn receptor for cell entry, rather than the CAR receptor. IVIG is thought to work in part by saturating the FcRn receptor with supraphysiologic concentrations of immunoglobulin, so it seems possible that this could also disrupt the ability for chronically infecting echoviruses to spread to other cells. Though this wouldn't have any effect on extracellular vesicle virus spreading, which may be more significant in chronic infections. I'm just always looking for some explanation for why immunoglobulin can bring one ME patient back to life, while doing nothing for another (as in the Norwegian documentary Sykt Mørkt). Unfortunately this Eikeland paper does not mention which specific enterovirus species triggered her disease.
Its so long ago I read that one. I now think I have an enterovirus triggered ME/dysautonomia. And with what you say I possibly have echovirus induced dysautonomia as I have high titers for echovirus 9. Chronic active echovirus 9 if I follow Dr Chias diagnostic criteria. I have immune mediated SFN and they wont give me IVIG. I want to try IVIG so bad. Can I ask what enterovirus you have? How do you plan on pursuing IVIG?
 

halcyon

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Its so long ago I read that one. I now think I have an enterovirus triggered ME/dysautonomia. And with what you say I possibly have echovirus induced dysautonomia as I have high titers for echovirus 9. Chronic active echovirus 9 if I follow Dr Chias diagnostic criteria. I have immune mediated SFN and they wont give me IVIG. I want to try IVIG so bad. Can I ask what enterovirus you have? How do you plan on pursuing IVIG?
I'm chronically infected with echovirus 30. I'm currently waiting for my results from the Mayo DYS2 and PAVAL autoantibody panels. I'm hoping, if positive for something, that this will be the evidence I need in order to receive IVIG, but I'm not holding my breath as it can be quite a fight from what I understand.