Informal Survey re: IVIG

[Gingergrrl]

Thanks @justy and ITA and will keep all the IVIG stuff in this thread and not on the bench! Will post future updates in here. Headache not totally gone but greatly improved.

 

[Groggy Doggy]

Hi @Gingergrrl

I was able to locate the information, regarding the manufacturing of Gamunex. Since the human contribution is 10%, I wanted to understand what other chemicals were introduced.

http://www.rxlist.com/gamunex-drug.htm

"GAMUNEX is made from large pools of human plasma by a combination of cold ethanol fractionation, caprylate precipitation and filtration, and anion-exchange chromatography. Isotonicity is achieved by the addition of glycine. GAMUNEX (immune globulin intravenous human 10%) is incubated in the final container (at the low pH of 4.0 – 4.3), for a minimum of 21 days at 23° to 27°C"

I bolded Ethanol, Caprylate, and Glycine. Could you read each link to see if you think any of your positive reactions or side effects could be related?

Ethanol - https://en.wikipedia.org/wiki/Ethanol

Caprylate - https://en.wikipedia.org/wiki/Caprylic_acid

Glycine - https://en.wikipedia.org/wiki/Glycine

The ingredient that struck me the most was Glycine as a neurotransmitter:


"As a neurotransmitter
Glycine is an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. When glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential (IPSP).Strychnine is a strong antagonist at ionotropic glycine receptors, whereas bicuculline is a weak one. Glycine is a required co-agonistalong with glutamate for NMDA receptors. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the (NMDA) glutamatergic receptors which are excitatory.[20]"


Since we don't know how much ethanol, caprylate, or glycine you actually received, I don't konw if it was a co-factor in the temporary improvement of your symptoms or a co-factor in your headache. I had suggested contacting the manufactterer in my previous post. Do you think that would be helpful?

Since you have the other thread (ME/CFS test), and a discussion regarding acetylcholine, I thought I would tag @anciendaze
to get her/his opinion too.

Thanks,

GD

 

[Gingergrrl]

Hi GD, Honestly all of this is completely over my head but thank you for posting it in this IVIG thread vs. the burnout bench!

Both my ME/CFS and my MCAS doctors are absolutely certain that my headache was due to the infusion speed being too fast which will not happen again. My MCAS doc said that every brand has some kinds of additives but in his history of prescribing IVIG for patients with MCAS, Gamunex is the best tolerated.

I tolerated it well in the sense of no allergic reactions and at present, my MCAS is the best it has ever been with the last two weeks being able to eat foods that I literally never dreamed I would eat again in my lifetime! I wish I could give a better answer but it is above my knowledge level to even try.

 

[Groggy Doggy]

Hi GD, Honestly all of this is completely over my head but thank you for posting it in this IVIG thread vs. the burnout bench!

Both my ME/CFS and my MCAS doctors are absolutely certain that my headache was due to the infusion speed being too fast which will not happen again. My MCAS doc said that every brand has some kinds of additives but in his history of prescribing IVIG for patients with MCAS, Gamunex is the best tolerated.

I tolerated it well in the sense of no allergic reactions and at present, my MCAS is the best it has ever been with the last two weeks being able to eat foods that I literally never dreamed I would eat again in my lifetime! I wish I could give a better answer but it is above my knowledge level to even try.

It's way over my head too. Since you were not at the autoimmune dosage, how do you account for the temporary and ongoing improvements? I am now curious about the benefits receiving Glycine via IV.

http://genf20plus.info/l-glycine-benefits-and-risks.php

 

[Gingergrrl]

It's way over my head too. Since you were not at the autoimmune dosage, how do you account for the temporary and ongoing improvements? I am now curious about the benefits receiving Glycine via IV.

I can't account for it at all and wish I understood it better. My thought is that b/c I typically do well with very small doses of meds (which is a question that @Strawberry asked me in the other thread) is it possible that the smaller dosage of IVIG is acting as if it is an autoimmune dose for me?

Or was the IVIG enough to modulate my immune system back toward the center, and away from the crazy allergic reactions, so I am able to tolerate foods and smells again without reactions since it is an immune modulator at any dose (if I understand it correctly)?

As far as the temporary improvement in arm strength, my guesses are either that it did something to the auto-antibodies (which was fleeting but enough to notice b/c I was able to fold laundry while seated and tasks that had been impossible for me prior to IVIG such as opening the patio door, etc.)

or is there something in the IVIG that can reverse even a portion of the damage caused to my arm from the Levaquin injury? All are guesses and all could be wrong. I just know if it were not for that ten day headache from the infusion speed, it is the best intervention I have tried in 3+ years.

ETA: I did not get to read your links yet so will comment more later after I do.

ETA #2: I looked at the Glycine link and have no doubt it could be beneficial for the right issues but that in my case, the reactions that I experienced were from the actual IVIG vs. additives. Although if I had been allergic to it, high chance it could be one of the additives.

 

[Groggy Doggy]

I can't account for it at all and wish I understood it better. My thought is that b/c I typically do well with very small doses of meds (which is a question that @Strawberry asked me in the other thread) is it possible that the smaller dosage of IVIG is acting as if it is an autoimmune dose for me?

Regarding the Glycine IV, I was trying to think of a way to enhance the benefits of your future IVIG treatments, certainly not replace them. We are in unchartered territory here, but know there are smart people on PR that have a good understanding of the biology/physiology aspects.

 

[Gingergrrl]

Regarding the Glycine IV, I was trying to think of a way to enhance the benefits of your future IVIG treatments, certainly not replace them. We are in unchartered territory here, but know there are smart people on PR that have a good understanding of the biology/physiology aspects.

Thank you and I think for now I just want to stick with the Gamunex, D5 Dextrose solution, and all the pre-meds without adding another factor into the mix. I just want to see if lower infusion speed can avoid (or at least reduce) the post IVIG headache.

But no doubt there are some super smart people on here who might know more re: your glycine question.

 

[anciendaze]

If you find someone super-smart let me know, I could use some insight.

What I can say about the above material without much in the way of smarts is that Gingergrrl's antibodies to GAD65 are related to an imbalance between glutamate and GABA. That enzyme, glutamic acid decarboxylase, is needed at an important step in the biosynthesis of GABA from glutamic acid. Generally glutamates are excitatory and produce sympathetic activation, while GABA is more likely to produce parasympathetic activation, and calm things down.

NMDA receptors are a special class of glutaminergic receptor which also require glycine to function. What is more they control ion channels. In two books, "Brain on Fire" and "The Girl on the Sixth Floor", we learned that antibodies to NMDA receptors can produce just about any symptom of mental illness you care to mention, plus some you might not imagine. Blocking the glycine portion of the receptor can also have very bad effects. One toxin affecting both acetylcholine and glycine receptors is strychnine. You really don't want anything to do with that.

We are dealing with lots of things here which can affect receptors for neurotransmitters and ion channels. Neurological symptoms? Blood Pressure? Heart rate? Changes in muscle function? These are all possible.

 

[Groggy Doggy]

I

If you find someone super-smart let me know,.

I find you to be highly intelligent and value your opinion. You have exposed me to another angle of looking at this. Thank you!

 

[Gingergrrl]

What I can say about the above material without much in the way of smarts is that Gingergrrl's antibodies to GAD65 are related to an imbalance between glutamate and GABA. That enzyme, glutamic acid decarboxylase, is needed at an important step in the biosynthesis of GABA from glutamic acid. Generally glutamates are excitatory and produce sympathetic activation, while GABA is more likely to produce parasympathetic activation, and calm things down.

I tried (just for one night) to supplement with GABA but did not find it helpful at all and it actually kept me awake all night like a paradoxical reaction. But I know my problem is more complex and an Auto-Ab is attacking the process of converting glutamate to GABA that just taking a supplement cannot fix.

One toxin affecting both acetylcholine and glycine receptors is strychnine. You really don't want anything to do with that.

Eek! Don't worry and I am not messing around with things b/c I lack any knowledge to safely do it. Will just be continuing with IVIG as planned for now.

I find you to be highly intelligent and value your opinion. You have exposed me to another angle of looking at this. Thank you!

Agreed!

 

[Gingergrrl]

I wanted to post an update and figured my IVIG thread is the best place. I was supposed to have my second IVIG infusion tomorrow (8/10) but we postponed it to 8/20 so I'd have at least one week headache-free before infusion #2 which I agreed with my doctors on.

Yesterday I was so tired but was trying to stay awake b/c my daughter was coming home from airport after visiting with relatives all summer and really wanted to see her. I was not paying attention and stupidly had a little accident with my motorized wheelchair. It ended up going in circles and then crashing into bathroom sink. My mom and husband were there and I was okay but the chair moved one way and my head/neck moved the other causing a whip-lash type reaction.

By last night my severe headache was back but even worse than before. I was in excruciating pain but couldn't truly say it was b/c of the initial IVIG headache coming back vs. this stupid accident. In either case, pain meds, ice, heat, etc, were not helping and I was up all night praying for the pain to dissipate.

Finally today we went to Urgent Care to get a shot of Decadron to reduce the inflammation. This is what I'd gotten at the ER for the IVIG headache and it helped and I tolerated it really well. Sadly, it turned out that Urgent Care only had one type which contained two preservatives that I am allergic to with MCAS so I had to decline the shot. I've learned from this experience that "single use vials" (in hospitals and ER's) are usually preservative free but multi-use bigger vials like at an Urgent Care are not.

So the whole visit was useless and I left with no pain relief. The doctor said that IVIG headaches can take 2-3 weeks to dissipate and it can take two shots of something like Decadron to reduce the inflammation plus having the whiplash injury. She was not worried I had meningitis and I was not either. I communicated with my main doctor b/c I was starting to worry about strokes from IVIG but he said that this is a different issue and there is no link between the headache which is notorious in IVIG and stroke.

The stroke comes from the blood clot risk (I have none of the risk factors based on pre blood work or in general) and it also comes from getting a large dose of IVIG in one sitting (like 50 to 100 grams) which I did not do and only got 24 grams. So this was a relief and if I am ever able to increase the dose, it will be in divided doses and not in one sitting. But for now, my second IVIG remains at 24 grams.

Am getting a pill form of Decadron from the compounding pharmacy (with no dyes or preservatives) and it will be for post-IVIG headaches (if I should have one) so I don't have to go to the ER. Am only getting a few pills and this will NOT ever be something that I take on a regular basis b/c it's a strong steroid. But to quickly reduce the inflammation it works very well as a one-off kind of thing (or once a month if needed post-IVIG.)

Have had improvements from this treatment that I am not willing to give up on b/c of the headache but am kicking myself for what happened with the wheelchair which was stupid on my part and will never happen again..

 

[justy]

@Gingergrrl sos orry to hear about the accident and the return of the headache from hell - how awful for you!

My M.E Dr has no idea how the low dose SCIG is helping me. But we know it keeps me out of being bedbound so I keep on with it. Like you it is one of the few treatments that has ever helped me. Myers cocktails with glutathione also helped a lot, but only if taken regularly which I cant do back here at home. Am still trying to ramp up my SGIG dose so I am now on half the prescribed dose- it has taken me ages to get to this point, but I was so ill from a herx when I took the prescribed dose and I don't want that to happen again.

Hope you have some relief from the pain soon.

Is there any chance that the pre med steroids are helping as much as the IVIG? I had to have steroids a while ago and all my MCAS symptoms went away for about a month, even continuing for a bit after the steroid was stopped - I could eat literally anything, so it was a shock when the itching came back and I had to deal with that again.

 

[Gingergrrl]

Thanks @justy and I don't think the improvement was from the steroid that I got as a pre-med before my one infusion of IVIG b/c it was just Solu Cortef and I've been taking (pill form) Cortef for over a year without these improvements. But I guess anything is possible!

 

[anciendaze]

@Gingergrrl If you have antibodies to beta adrenergic receptors one could expect this to affect response to steroids as well as beta blockers. Unfortunately, this is not a standard clinical test.

Even if you do not consider your response to beta blockers adverse, I feel that the drop in bp you reported was greater than the vast majority of patients taking beta blockers experience. For this reason I'm guessing you do have antibodies to beta adrenergic receptors.

 

[justy]

Thanks @justy and I don't think the improvement was from the steroid that I got as a pre-med before my one infusion of IVIG b/c it was just Solu Cortef and I've been taking (pill form) Cortef for over a year without these improvements. But I guess anything is possible!

what was the pre med dose and what dose do you take daily? Yore probably right that its the IVIG - hope so!

 

[Gingergrrl]

I wanted to update this thread b/c I will be having my third IVIG tomorrow morning and when I got here, I realized that there were two posts that I completely missed! So I apologize for the greatly delayed response. My IVIG tomorrow will be 36 grams (the first two were 24 grams) so I will finally be above the immune deficiency dose but not at the autoimmune dose. I will still have a slow infusion time of a minimum of 6 hrs but slightly increased speed b/c of the increased dose.

@Gingergrrl If you have antibodies to beta adrenergic receptors one could expect this to affect response to steroids as well as beta blockers. Unfortunately, this is not a standard clinical test.

@anciendaze, when you have time could you explain what you meant re: that if I have antibodies to beta adrenergic receptors that we can expect this to affect my response to steroids? I had a disastrous 2nd attempt to taper off of Cortef and since I am assuming that I do have these antibodies (no proof yet but I assume I do), how do the two things relate? Does it make your brain more dependent on the steroid (Cortef) so it messes up the brain's natural production and ability to re-start creating hydrocortisone on it's own? Or did you mean something else?

what was the pre med dose and what dose do you take daily? Yore probably right that its the IVIG - hope so!

The pre-med dose of the Solu-Cortef for the first IVIG was 100 mg b/c we had no idea if I would be allergic to Gamnuex and wanted to be safe. For the second IVIG it was 80 mg and I had absolutely no allergic reaction so I believe tomorrow it will be 60 mg (but I don't think it will ever go lower than that to be safe). I am not certain if Solu-Cortef (IV form) and Cortef (pill form) dose exactly the same way or if the numbers line up.

My daily dose of Cortef is 15 mg which is considered low but my taper (which I wrote about in the other thread) ended in disaster and near adrenal crisis today. My MCAS doc said that the Solu-Cortef should clear my system in 48 hours so I don't believe that the 3-4 week remission that I had from MCAS was from the Solu-Cortef and there were no other new meds or variables. I do however know with certainty that my daily dose of Cortef is playing a huge role in controlling my MCAS and cannot imagine how I will ever safely taper off of it.

 

[anciendaze]

...
@anciendaze, when you have time could you explain what you meant re: that if I have antibodies to beta adrenergic receptors that we can expect this to affect my response to steroids? I had a disastrous 2nd attempt to taper off of Cortef and since I am assuming that I do have these antibodies (no proof yet but I assume I do), how do the two things relate? Does it make your brain more dependent on the steroid (Cortef) so it messes up the brain's natural production and ability to re-start creating hydrocortisone on it's own? Or did you mean something else?
...

I think all of us have problems with adrenal dysfunction as part of a dysregulated hypothalamus-pituitary-adrenal (HPA) axis. Unfortunately, this is not the same as simply a low level of adrenal hormones like those detected by beta adrenergic receptors. Many people who have had a 24-hour test of cortisol in urine have been considered "normal". The problem is that this would not detect transient responses that averaged out over a full daily cycle.

One pattern of dysregulation is a phase lag. The desired biochemical response to stress does take place, but may last for hours after the incident which precipitated it. Another pattern, which may not be completely distinct, is increased sensitivity to hormones like steroids. The problem is stability, and many of us wobble along like clowns riding a unicycle. Unless we fall off, and end up in emergency departments, the problem is not considered serious. Hormonal responses serve a purpose, and if they take place at the wrong time, or under conditions that should not elicit a "flight-or-fight" response, this purpose is not correctly served.

Even when an isolated laboratory measurement indicates a simple problem, like "low cortisol" or "low insulin", this is unlikely to be the whole story because all of these biological systems have extensive feedback. A drop in levels of a hormone or neurotransmitter is likely to be offset by an increase in sensitivity to that biochemical. This certainly takes place in type 1 diabetes. Attacking the adaptive response to the problem can even precipitate a crisis, as most patients with insulin-dependent diabetes have experienced. (These are just random examples, not a diagnosis of any particular problem you have.)

Several indications convince me that a shift in autonomic function is important in ME/CFS, and quite common in MCAS. I haven't seen any evidence that patients reading this forum fail to understand such unusual references as "tired but wired", which seem bizarre to healthy people. Likewise, healthy people generally misunderstand the term "orthostatic intolerance", when patients like myself, who went a long time without even knowing there was such medical terminology, have independently arrived at hours spent upright in a typical day as a measure of how sick or healthy they are. A shift toward excessive sympathetic activation, and a decrease in parasympathetic activity, is apparent in a number of symptoms reported by ME/CFS patients.

Antibodies to GAD65 directly affect the biosynthesis of GABA from glutamate, providing one plausible cause of dysregulation of the balance between glutamate and GABA, and between sympathetic and parasympathetic activation. Beta adrenergic receptors are directly involved in both orthostatic tolerance and the "flight-or-fight" response. They are major factors in autonomic function.

All these things are evidence of pervasive systemic dysregulation. It is not likely that changing a single cause will reverse all the problems at once. You are in a pathological state which stops short of killing you. It will take time and patience to unwind the complex of problems which have occurred since your body ran off the rails of healthy functioning. You spent several years getting sicker, and acquiring secondary problems, it is likely to take years to get better, one careful step at a time.

Hang in there! If a worm in a dauer state can re-emerge into health so can we.

 

[Gingergrrl]

Hang in there! If a worm in a dauer state can re-emerge into health so can we.

Thank you @anciendaze and that is a great quote! It reminded me of a book I read last year (before losing all my books to our mold disaster) called "The Sound of a Wild Snail Eating" by Elizabeth Tova Bailey. I am pretty sure the word dauer was not used but the snail went into some kind of hibernation period just like the author and she really related to the snail. I don't want to give anything away re: the ending of the book in case people are going to read it but your quote made me think of it!

Am going to post an update re: my 3rd IVIG next and then there is a quote from @boohealth re: my IVIG in another thread that I hope to be able to find again and move over here so I can reply to it in the right place (so I will be able to find it again in this thread!)

 

[Gingergrrl]

My third IVIG:

Yesterday was my third IVIG and the dose was increased from 24 to 36 grams which is getting closer to the bottom of the autoimmune dose (mid 50's) but still quite a way to go. I love the infusion center and my nurse but sadly even with the six hour infusion time, we had to increase the speed to make it fit which was a bummer and caused some reactions. We had thought Sat was the best day to come b/c it is quiet and very few patients and you almost get a 1:1 nurse. But the downside is that they absolutely close the doors at 4:30 pm (vs. the other days 5:00 or even 5:30 pm) which would have allowed me to infuse at a slower speed.

My first IVIG was 3 hrs and I got horrible headache leading to trip to the ER and speed went up to 105 ml/hr! My second IVIG was 6 hrs with entire speed at 35 ml/hr and zero headache or trips to the ER. This third one yesterday was also six hours and first hour was 35 ml/hr, and then it sped up to 55 ml/hr (which my doctor said was okay). But the nurse realized we were not going to make it on time so the final hour was 70 ml/hr (higher than my doctor wanted) but the alternative was to throw the remainder of the Gamunex in the trash! I decided against this b/c it is such an expensive medication, I'd lose my chance to try the 36 grams before my appt on Thurs, and my insurance is still billed for 36 grams and doesn't care that I did not receive it.

So once it sped up to 70 ml/hr, I felt uncomfortable and got minor allergic symptoms (nose running, throat itchy, etc). So I took an Atarax b/c the nurse thought there was no downside to this and I proceeded with the infusion without interruption. Then I had 2 mg Decadron as a headache preventative (which works and I have zero headache) but it gives me surges of tachycardia and makes my POTS worse. We went to dinner after the IVIG (b/c I never eat before IVIG to reduce risk of allergic reaction) and at restaurant, my heart rate spiked to 110 bpm (seated) and was just staying there. I took my normal Atenolol dose as soon as we got home and HR went down to the 90's seated and upper 80's lying flat but spiked to minimum of 120 if I just stood to transfer to wheelchair. I actually suspect this is from the Decadron vs. the IVIG and am going to ask my MCAS doctor if I can try 1 mg (vs 2 mg) or skip it and hope the slower infusion speed (by not going on a Sat next time) is enough to not need it and not get the IVIG headache.

The Decadron gives me insomnia but the IVIG gave me severe muscle cramps in my calves which would have kept me awake anyway. With infusion #2, the first night I had full body muscle cramps where everything hurt except my hands and feet but this time it was only my calves. Finally at 4:00 am I took a pain pill b/c I could not take it anymore which helped about 90% and then around 6 am I took some salt stick tablets and then the cramps disappeared and have not returned.

I finally went to sleep but when I woke up I had facial flushing like a sunburn on my cheeks and it was really hot and hurt. At the infusion center, they took my vitals before starting and my temp was only 96.9 (low even for me) but they said unless it's below 96, we were okay to proceed. My normal temp is 97.4. So today b/c of the facial flushing, I took my temp and it was 98.8 which is a true fever!!!!! I was stunned b/c even though it is very slight, I have not been able to induce a fever in 3+ years so either I am reacting to the IVIG or the IVIG is trying to fight one of my infections (EBV, VZV, coxsackie, echovirus, etc) which in doing so I believe pushes me away from the crazy MCAS reactions. I was able to eat a normal lunch and even yogurt (high histamine) with no allergic reaction (except the facial flushing which was present before I ate so food was not the cause)!

Other than the leg cramps which are now gone, and the facial flushing and tachycardia, I think I did pretty well with the 3rd IVIG and am certain I can tolerate the 36 grams if we had stuck at the 55 ml/hr speed and not had to increase to the 70 ml/hr speed. I have learned that I will have side effects for a few days afterward and then feel significant improvement so hoping this happens again. My BP (without Midodrine) is 97/67 today which is still pretty decent for me. The severe dizziness, nausea and symptoms of the failed Cortef taper are gone but I had Solu-Cortef as one of the pre-meds. I have no edema, swelling or third spacing from the IVIG and can feel the improvement in my arm strength again b/c today I was able to open some packages and envelopes on my own without assistance!

I see my MCAS doc on Thurs and my gut instinct is that we will do one more infusion of 36 grams to be safe before going up to the mid 50's (autoimmune dose) which is a split dose done two days in a row and I'd do it on two weekdays for slowest speed possible. My main doc really wants to see what improvements I have once I am on the autoimmune dose and I do as well. Every doctor I have fully supports the IVIG so I feel I am on the right track.

I have a few friends who started right off the bat at the autoimmune dose (even one who does four days in a row) but I feel this would have been a disaster for me. I am not sure yet what my MCAS doc will think of this, nor if my insurance will go for it, but I have an appt with my Neuro in Oct and if she backs me up (which I think she will) and all three docs say this is medically necessary, I think my insurance will approve the higher dose even if it means another battle.

At this moment, my tachy is gone and the only symptom I am feeling is the facial flushing but I expect more surges of tachy (or maybe other weird symptoms) over the next few days. Am trying to drink as much water as possible and am feeling really positive about this unless something unexpected goes wrong (but hoping it won't)! Thanks to anyone who is still reading!

 

[boohealth]

Hi @Gingergrrl . I would do it several days in a row to be sure it's slow. Have a cushion of several hours. Hydrate well orally and w IV before but not w isotonic saline unless you can change or flush the line. Sounds very promising