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Calcium channel clues? Seizures, nimodipine, inositol and oxaloacetate.

Messages
97
Location
UK
TLDR: partial TLE seizures since the onset of ME, nimodipine stopped them. Inositiol and oxaloacetate provoke them.
Just posting here to see if this ties in with anyone else's experiences or research really. Calcium channels would seem to be key. All theories and tidbits welcome!


I've suffered from simple partial temporal lobe seizures since the onset of ME, which was most likely EBV-induced, but I also suspect some mito issues since birth. I've always had visibly low muscle mass and was unable to do normal kid things like climbing, monkey bars or opening heavy doors. Though nothing showed up in mtDNA testing.

The seizures weren't diagnosed until 2015 but they're 'textbook': 30 secs+ of nausea, rising sensation, nose sensation and unusual odour and deja vu, with right-sided face and arm tingling, right-sided vision loss plus hissing in ears. I'd get clusters ranging from 1-10+ per day, usually only a few days per month. Bad days would be accompanied by a constant nauseous migrainous state. There didn't seem to be a cyclical/hormonal pattern.

I found that taking 2-4g/day of inositol would provoke these seizures and leave me in the constant nauseous state having multiple seizures every day.

I then discovered nimodipine for ME and to my amazement this stopped the seizures completely, I've not had one in about 3 or 4 years, save for the odd hint of an aura a few times a year. I re-challenged with inositol and have since been able to take it without issue now I'm on nimodipine.

I couldn't figure out if the nimodipine worked by dilating a structural issue in the brain vasculature that was causing hypoperfusion, or whether the calcium channel-blocking effects were responsible independently of vasodilation.

Fast forward to last week when I began oxaloacetate/Benagene at 300mg AM and 200mg PM. Within days I was hit by sudden nausea and headache about 30 mins after taking it in the morning which persisted all day, though I didn't make the connection. Today, I was hit with a seizure about 30 mins after taking.

I feel like these things are potentially huge clues to the underlying pathology but I lack the depth of knowledge of biology to make more sense of it, I'm rather hoping someone here might know something or have made similar discoveries of their own.

I was able to find that "Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals."
And this, which links oxaloacetate to mitochondrial calcium efflux- can anyone with a better understanding of cell biology tie any of this in, maybe?

Thanks for reading!
 

alcasa

Glutamate +ATP pantheist
Messages
8
I'm sorry to hear what you're going through. I cannot assure you that your issue is exactly the same as mine, but if I had to bet, I would say that many, indeed very many patients with CFS (probably half or more) have problems in the metabolism of the neurotransmitter glutamate in the CNS. Nimodipine, as you know, is a quite potent blocker of calcium channels, which strongly antagonizes glutamate. Everyone in science knows that the glutamate-GABA imbalance, especially in an environment of excess glutamate, leads to epileptic excitation.

Regarding oxaloacetate, it occurs to me that supplementing it exogenously could significantly increase or decrease glutamate levels. Oxaloacetate is closely related to glutamate because, in the brain, glutamate is converted into oxaloacetate through an anaplerotic process. Supplementing it exogenously could eliminate this need by increasing the available glutamate pool. However, it could also reduce it (clearly not in your case) because the increase in oxaloacetate might enhance TCA cycle activity and therefore the complete oxidation of glucose and glutamate, consequently increasing the activity of the Na+/K+ ATPase pump, which is very relevant for clearing glutamate.

In my opinion, yes, calcium channels and more specifically, glutamate-mediated excitation and NMDA, as well as the metabolism of glutamate itself are key in many patients with Chronic Fatigue Syndrome. Bajito subnormal.

Pd: No idea abt inositol
 

sunshine44

Que sera sera
Messages
1,184
Following. I’m dealing with increasing seizures since covid 3 months ago. I had them before but they had mostly ceased but now are back with avengeance. My home healthcare nor pCp have any suggestions or ideas beyond to get 4 people to transport me via medical tarp to a neurologist in October. Sounds lovely. Modern medicine really puts human life first and forefront.

Anyways, following as I’m trying to navigate this realm myself. I often think I have something with my calcium channels as well. My body gets really weird when I take vitamin k etc.
 

Violeta

Senior Member
Messages
3,009
This calcium efflux is happening in the endoplasmic reticulum?

Calcium efflux from the endoplasmic reticulum (ER) is triggered by a number of second messengers, including calcium, inositol 1,4,5-trisphosphate (IP3), and cyclic ADP ribose (cADPr).

This following paragraph may be a little confusing, but it looks as if taurine could help if glutamate is involved.

We [33] and El Idrissi & Trenkner [20] reported that one of the pathways by which taurine reduced glutamate-induced elevation of [Ca2+]i is through inhibition of Ca2+ influx via the reverse mode of Na+/Ca2+ exchanger. At the resting membrane potential, Na+/Ca2+ exchanger functions to move Ca2+ out of the cell. However, under depolarizing conditions such as under glutamate stimulation, it reverses its function to facilitate Ca2+ influx [34]. ⬇️

Cultured rat astrocytes possess Na(+)-Ca2+ exchanger​


https://pubmed.ncbi.nlm.nih.gov/7890336/
 
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Violeta

Senior Member
Messages
3,009
Also, this may have something to do with TRPM3.

Human Trp3 forms both inositol trisphosphate receptor-dependent and receptor-independent store-operated cation channels in DT40 avian B lymphocytes​


Agonist-dependent regulation of intracellular Ca2+ levels in most cell types involves modulation of Ca2+ release from intracellular stores, stimulation of Ca2+ entry from the outside through Ca2+ channels in the plasma membrane, or both.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC58806/
 
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Zebra

Senior Member
Messages
893
Location
Northern California

sunshine44

Que sera sera
Messages
1,184
Ugh. While you are awaiting this appointment 5 months away, would your PCP consider getting the ball rolling with some preliminary blood work?

Check out this Autoimmune Epilepsy Panel offered at LabCorp:

https://www.labcorp.com/tests/505490/autoimmune-epilepsy-evaluation-profile


You would think!!
But no one really seems to care.
I did get her to order an ANA but I had to request it and I asked for MRI and Oximetry test. Nope. Won’t do those. No response. At least I got a few basics of bloodwork. I mean, it’s weak at best but a beginning.
 

sunshine44

Que sera sera
Messages
1,184
Ugh. While you are awaiting this appointment 5 months away, would your PCP consider getting the ball rolling with some preliminary blood work?

Check out this Autoimmune Epilepsy Panel offered at LabCorp:

https://www.labcorp.com/tests/505490/autoimmune-epilepsy-evaluation-profile


I haven’t heard of this. It’s not cleared by FDA (not that I prioritize that in any way ha!). Does that mean a new neurologist won’t even look at this most likely?

Asking bc I’ve had so many specialty tests in past that western drs roll their eyes at and won’t look at. Because they really seem to be doing such an astounding job with my case 🙄
 

Zebra

Senior Member
Messages
893
Location
Northern California
I haven’t heard of this. It’s not cleared by FDA (not that I prioritize that in any way ha!). Does that mean a new neurologist won’t even look at this most likely?

Hi, Sunshine!

This panel offered by LabCorp is almost identical to the Autoimmune Epilepsy Panel offered by the Mayo Clinic, so I do not think a doctor/neurologist would dismiss a (strongly) positive result to one particular antibody in the panel. They would likely want to re-test for confirmation, usually blood and CSF is tested simultaneously, but you have been suffering for so long, it seems like the least your PCP could do is get some blood work going.

I was excited when going to the Mayo Clinic initially seemed like a possibility for you, because IMHO I think a *neuro-immunologist* is your best option, as the specialty comprises dysautonomia, GI dysmotility, seizures, neuropathy or myopathy, autoimmune disease, etc.

If you Google Mayo Clinic Neuro-immunology you will uncover a treasure trove of information (various articles, special blood/CSF tests, etc.)

The Mayo Clinic is the leading institution in this field, BUT that doesn't mean that you or anyone else in this site can't find a neuro-immunologist at a university-based institution closer to home. They are most often affiliated with Multiple Sclerosis Clinics.

Trigger warning: When I first learned of this field/specialty and realized I should have/could have seen such a specialist 10 years ago, it unleashed an astonishing amount of grief and anger. It seems like it's too late for me, but I hold out hope that it's not too late for you.

I feel like I am taking the OP's thread off track. Let me know if you want to "talk" elsewhere in the forum.
 

sunshine44

Que sera sera
Messages
1,184
Hi, Sunshine!

This panel offered by LabCorp is almost identical to the Autoimmune Epilepsy Panel offered by the Mayo Clinic, so I do not think a doctor/neurologist would dismiss a (strongly) positive result to one particular antibody in the panel. They would likely want to re-test for confirmation, usually blood and CSF is tested simultaneously, but you have been suffering for so long, it seems like the least your PCP could do is get some blood work going.

I was excited when going to the Mayo Clinic initially seemed like a possibility for you, because IMHO I think a *neuro-immunologist* is your best option, as the specialty comprises dysautonomia, GI dysmotility, seizures, neuropathy or myopathy, autoimmune disease, etc.

If you Google Mayo Clinic Neuro-immunology you will uncover a treasure trove of information (various articles, special blood/CSF tests, etc.)

The Mayo Clinic is the leading institution in this field, BUT that doesn't mean that you or anyone else in this site can't find a neuro-immunologist at a university-based institution closer to home. They are most often affiliated with Multiple Sclerosis Clinics.

Trigger warning: When I first learned of this field/specialty and realized I should have/could have seen such a specialist 10 years ago, it unleashed an astonishing amount of grief and anger. It seems like it's too late for me, but I hold out hope that it's not too late for you.

I feel like I am taking the OP's thread off track. Let me know if you want to "talk" elsewhere in the forum.
Thank you.
I resonate deeply and really thank you for reaching out. Ive recently been looking at mayos forum and that’s where I got some of the bloodwork requests for dr. She still wouldn’t order all of them 🙄I’ve been ordering some of my own labs from walk in and private paying a mobile phlebotomist because my pcp…. Has not been interested in my case, in the least it turns out.

You remind me that maybe I can still get some answers even if I have so few willing drs that will take my case in area. I know I don’t know you well but I believe in hope for your case still. Victoria Arlen’s case reminds me that even when all lights go out, it’s not always over. But, I truly get it.

Anyways, I will be in touch and stop there for this thread.
 

kangaSue

Senior Member
Messages
1,872
Location
Brisbane, Australia
Both voltage gated calcium channel (VGCC) antibodies and voltage gated potassiun channel (VGKC) antibodies have been implicated (or at least associated) with some cases of TLE seizures so it's possible each could have an effect on the opposite element's function?
 

Violeta

Senior Member
Messages
3,009
@parabola, do you take thiamine?

"Thiamine deficiency, also known as vitamin B1 deficiency, may cause epileptic seizures in people who are already predisposed to them. Thiamine is an essential vitamin that helps the body convert food into energy and plays a key role in brain function. A 1991 study found that 16 out of 50 neurological patients with thiamine deficiency also had epileptic or epileptiform manifestations. Thiamine deficiency can also cause irritative activity on electroencephalographic recordings."
 
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