Exploring the Gut-Brain Connection and Photosensitivity

[epileric]

What they have shown is that they found 5 cases of acidosis after a seizure. That is so few that even though it should be documented is doesn't show a correlation and even if there was a correlation it does not show that seizures have a purpose. Can you actually cite something that says lactate might be used as fuel?


Can you quote your link where it says pH in the body is a mechanism for halting seizures? I didn't see it say that anywhere.

But again this changes the topic. These do not show how the immune system is associated with epilepsy. Even if what you said is true it has nothing to do with the immune system. You just keep changing topics.

 

[Keith]

Our results identify ASIC1a as an important element in seizure termination when brain pH falls and suggest both a molecular mechanism for how the brain stops seizures and new therapeutic strategies.

Lactate is called the most significant gluconeogenesis precursor. In essence, a seizure may be considered forced exercise in order to release lactate from muscles. But there are also other substrates used by the liver to make glucose including microbial fatty acids where one can have too much of a good thing leading to wild swings in blood sugar:
http://www.pearsonhighered.com/mathews/ch16/c16gs.htm

Have you heard of microglia in the brain? They are an important part of the brain's innate immune system, found neuroprotective:
http://medicalxpress.com/news/2014-...l&utm_source=facebook.com&utm_campaign=buffer

microglia can help synchronize brain firing, which protects the brain from TBI and may help alleviate chronic neurological diseases.

They found that when chemically activated, microglia migrate to inhibitory synapses, connections between brain cells that slow the firing of impulses. They dislodge the synapse (called "synaptic stripping"), thereby increasing neuronal firing and leading to a cascade of events that enhance survival of brain cells.

 

[kirsten]

I'm not the first person to believe seizures actually have a purpose. One theory is to raise lactic acid where lactate is used as fuel to raise blood sugar in gluconeogenesis, ameliorating hypoglycemia.
http://onlinelibrary.wiley.com/doi/10.1034/j.1399-6576.2003.00115.x/abstract



So, the question becomes, what's causing blood sugar and pH imbalances to begin with? Who's toying with the immune system? Imbalanced gut flora is strongly implicated. Of course, this doesn't apply to all forms of epilepsy, but I'd bet a very large percentage, even over 50% considering such a large percentage of intractable epilepsy of nearly 40%.

All we have from your two papers (did you read the first one, or just the abstract?) is that seizures make muscles work hard (duh) which causes lactic acidosis (again, a natural response to muscles working hard. Why take a run when you can just have a good seizure?) which may, your researchers guess, reduce excitability in the brain. So what are you saying is the purpose of seizures? To prevent more seizures, according to your studies.

Doesn't make much sense, does it?

Seizure also lowers pH in the brain which is the mechanism for halting seizure.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673408/

No, 'notion' is the word your paper uses--someone has the 'notion' that pH might lower in the brain.



Keith, why is it that you can't discuss one topic? You keep changing the subject every time your argument is proven to be baseless.
You do realise this is a discussion forum? As such, it's quite rude to simply ignore comments and then continue on another topic. People are taking the time to read through your many, many studies. Surely it's only polite to address what we say?
And for the third time, why are you asking us to read studies you have not read?

 

[kirsten]

Lactate is called the most significant gluconeogenesis precursor. In essence, a seizure may be considered forced exercise in order to release lactate from muscles. But there are also other substrates used by the liver to make glucose including microbial fatty acids where one can have too much of a good thing leading to wild swings in blood sugar:
http://www.pearsonhighered.com/mathews/ch16/c16gs.htm

Why do epilepsy patients need more exercise than people without epilepsy? Do you think all people with epilepsy fail to exercise enough? We have a member who is a personal trainer. Despite all that exercise, she still has seizures. Can you explain that?

Most seizures are not tonic clonics, and many epilepsy patients never have any tonic clonics at all. Therefor most seizures don't affect lactic acid at all.

Why do epilepsy patients need extra blood sugar stabilization? Do you think all people with epilepsy have diabetes?

How does the body give itself epilepsy in order to get more exercise and blood sugar stabilization?

Going back to my old example, when I almost drowned, did my body think I was going to have blood sugar level problems and be a lazy exerciser in the future and use the near drowning opportunity to create scar tissue in my brain so that it could produce lactic acid during seizures? Or do I have seizures because a faulty bunch of cells is misfiring?

 

[kirsten]

Have you heard of microglia in the brain? They are an important part of the brain's innate immune system, found neuroprotective:

They haven't been found to be an important part of the brain's innate immune system in humans, or found to be neuroprotective in humans. In rats, preliminary studies suggest there is the possibility that that might be the case.

When we say 'something has been found to be...' it's because there is a body of evidence to suggest it. For example, we can definitely say that epileptic seizures have been found to happen because neurons misfire in the brain. We can certainly say that temporal lobe resections have been found to be an effective solution for 70% of TLE patients. We can certainly say that Tegretol, epilim, and lamitrogen are effective treatments for epilepsy.

Because there are important physiological differences between rodent and human brains, and because it is challenging to impossible to get a clear understanding of what is going on in a rodent's brain due to size, these studies are used as a precursor to human trials, with an understanding of their limitations. The more scientists learn about the human brain, the more limited brain research in rodents becomes. We cannot say that microglia have been found to be neuroprotective. It's fallacious to automatically assume that a rat study generalises to people. Because your rat trial is a preliminary one that hasn't been repeated, we can't even say that it has been found that microglia are neuroprotective in rats. Because the researchers are only making educated guesses about the neuroprotective properties of microglia as a potential explanation for their observations, the only responsible way to reword your statement is this: Researchers suspect that microglia might have neuroprotective properties after observing X in a preliminary animal trial.

 

[Keith]

Going back to my old example, when I almost drowned, did my body think I was going to have blood sugar level problems and be a lazy exerciser in the future and use the near drowning opportunity to create scar tissue in my brain so that it could produce lactic acid during seizures? Or do I have seizures because a faulty bunch of cells is misfiring?

If your near drowning incident is truly the cause of your epilepsy, kirsten, then it would appear gut origin of epilepsy doesn't apply to you.

Eric, on the hand, believes his epilepsy is caused by a lesion on his brain which may actually be of gut origin as he hasn't stated otherwise.

Thanks so much for bringing attention to the issue of gut origin of seizure activity as I believe it's severely underdiagnosed.

Here's an article about a recent review paper about microglia, the brain's immune cells:
http://medicalxpress.com/news/2014-...l&utm_source=facebook.com&utm_campaign=buffer

Perhaps the most definitive, and intriguing role of MG is their critical part in the segregation of inputs from the eyes within the visual system.

Perhaps the purpose some seizures is to prevent brain damage via enhancing survival of brain cells.

 

[epileric]

Eric, on the hand, believes his epilepsy is caused by a lesion on his brain which may actually be of gut origin as he hasn't stated otherwise.

How the heck can a lesion on the brain originate from the gut?

Thanks so much for bringing attention to the issue of gut origin of seizure activity as I believe it's severely underdiagnosed.

Maybe it's not being under-diagnosed but you've assumed it to be more relevant than it is. I tend to think there's a reason it hasn't been diagnosed as a cause in epilepsy.

Perhaps the purpose some seizures is to prevent brain damage via enhancing survival of brain cells.

There is absolutely no reason to think that a mis-firing neuron happens to prevent brain damage, for that matter they've been shown to decrease memory & cognitive function.

Your memory process can be interfered with by epileptic seizures. Or an underlying disorder in the brain, which causes the seizures, may be what is disrupting the memory process. It may be the effects of your anti-epileptic medication. Or it may not actually be a memory problem at all.

http://www.epilepsymatters.com/english/lwememory.html#whymemory

Where do you pull these ideas from?

 

[Keith]

How the heck can a lesion on the brain originate from the gut?

we found hyperintense focal white-matter lesions in the brain in 20 of 48 (42%) patients with Crohn's disease, in 11 of 24 (46%) patients with ulcerative colitis, but in only 8 of 50 (16%) healthy age-matched controls

Focal white-matter lesions in brain of patients with inflammatory bowel disease
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(95)90013-6/abstract

 

[epileric]

Focal white-matter lesions in brain of patients with inflammatory bowel disease
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(95)90013-6/abstract

I'm afraid my lesion is in the hypothalamus- not the white matter.

As I said before, that is a very small study and is still just as preliminary as it was a couple of days ago. It also implies a higher likelihood of brain lesions in people with Crohns disease and ulcerative colitis. No mention of epilepsy.

 

[kirsten]

If your near drowning incident is truly the cause of your epilepsy, kirsten, then it would appear gut origin of epilepsy doesn't apply to you.

What of epilepsy caused by brain surgery, brain tumours, lack of oxygen to the brain? 45% of epilepsy cases have known causes such as these. These cannot be of gut origin. Of the 65% of epilepsy cases that have no known cause, such as this one

Eric, on the hand, believes his epilepsy is caused by a lesion on his brain which may actually be of gut origin as he hasn't stated otherwise.

there is an obvious physiological abnormality like a lesion that is visible on MRI. In other cases, it's easy to pinpoint the exact location of the structural abnormalities that are misfiring using an EEG. In still others, genetic causes have been traced.

A lesion is an area that has been injured, kind of like what ever scars you have on your body. I'm quite sure you don't believe that your scars are caused by your gut, even when you can't remember how the scars were caused. I'm also quite sure that you don't try to get rid of your scars by taking probiotics, so suggesting that people such as Eric do so to get rid of their scars is absurd.
That leaves you with a negligibly low percentage of epilepsy cases that you might like to say are of gut origin, many of which might end up showing themselves to be structural abnormalities in the brain as doctors increase their use of fMRI for mapping. If you agree that people who have similar situations to my own, or obvious physiological abnormalities, have epilepsy caused by brain damage, your premise of epilepsy being of gut origin has been proven to be unfounded. You have been proven wrong. And you have accidentally admitted to it. So again, will you please state which types of epilepsy you believe to be of gut origin and which you don't so that we know what we're discussing and so that epilepsy patients that this doesn't apply to can carry on with their days.

http://brain.oxfordjournals.org/content/121/9/1661.full.pdf

Here's an article about a recent review paper about microglia, the brain's immune cells:
http://medicalxpress.com/news/2014-...l&utm_source=facebook.com&utm_campaign=buffer


Perhaps the purpose some seizures is to prevent brain damage via enhancing survival of brain cells.

Clearly you have no idea how much brain damage is done by seizures. Of status epilepticus:

Alarmingly, mortality was also high in elderly people: 14% for young adults (16–59 years) and 38% for elderly people (60 years and above). Many changes in gene
expression are the result of seizure-induced neuronal death, and of the resulting neuronal reorganisation. Some are the result of plastic adaptation to seizure activity, but because status epilepticus profoundly inhibits brain protein synthesis,65 many of the acute changes in gene expression are not consolidated. http://2093.rh.dk/artikler/Lancet_Review_Statusepil_2006.pdf

You can't use a seizure to help brain cells survive if seizures kill brain cells quickly enough to cause brain death within an hour.

As to Crohns and Celiac coexisting with epilepsy, we have discussed this before. We found that in the wildly low percentage of patients with digestive disorders who have epilepsy, those disorders produced symptoms that directly damaged the brain. Please review what has been discussed in this thread so you can get an idea of what progress has been made. I would hate you to have to go over the same material over and over again only to run into the same reasons your material doesn't make sense over and over again. This week seems to be a bad one. You've tried to research three different premises that you already realised months ago don't hold any water.

You still haven't answered my previous questions.

 

[Shelley]

http://tinyurl.com/lqmxp93

Perhaps this will help

 

[Keith]

I'm afraid my lesion is in the hypothalamus

Thank you very much sharing that, Eric. That's generous and kind. Do you know how it occurred? Have you considered excess glutamate which also causes seizure? Glutamate as cause of lesion in the hypothalamus appears well-studied. MSG is known to cause hypothalamic lesions.
http://jn.nutrition.org/content/130/4/1032S.full
http://www.ncbi.nlm.nih.gov/pubmed/663939?dopt=Abstract

On page 22 of this thread we talked about endogenous glutamate and ammonia as seizure trigger. I stated:

Ammonia build-up from a cellular view related to glutamate toxicity: what happens when the body has excess glutamate due to intracellular organism interference with the Krebs cycle where microbial transaminases, enzymes such as ALT, cause cells to kick out more endogenous glutamate?

KarenB replied:

(Yet another) potential mechanism of the Ketogenic Diet is that it enhances the conversion of glutamate to glutamine.

Glutamate is a major excitatory neurotransmitter (and thus too much can trigger seizures).

The brain in ketosis efficiently converts glutamate to glutamine -- thus reducing glutamate levels in brain.

Ketosis also enhances the conversion of glutamine to GABA, which is a major inhibitory neurotransmitter.

This mimics two important actions of a number of anti-epileptic drugs, without the horrific side effects.

Not so sure how this relates to the gut-brain connection, other than what one eats has a significant impact on the brain.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722878/

Then on page 25 we discussed gut origin of excess nitric oxide (NO) as the prevalent problem in epilepsy due to NO inhibiting glutamine synthetase which would otherwise clear glutamate.

Yesterday on page 27 I talked about cannabinoids inhibiting release of glutamate.

The GARD diet is about restricting dietary levels of glutamate, but I believe endogenous glutamate a more important factor based on gut flora balance where removal of most grains in the GARD diet shifts flora in the right direction.

 

[Keith]

What of epilepsy caused by brain surgery, brain tumours, lack of oxygen to the brain? 45% of epilepsy cases have known causes such as these. These cannot be of gut origin. Of the 65% of epilepsy cases that have no known cause

kirsten, that's good information, thanks. So, 65% of epilepsy has no known cause. That's massive. What I'm trying to make people and doctors aware of is the potential that seizures are of gut origin so that it can be addressed before damage occurs and healing can begin. Instead, doctors are clueless and can only prescribe anticonvulsants without addressing underlying cause.

And, yes, I do believe lesions and adhesions (scars) of the brain can be caused by the gut.

Of course, I understand seizures can damage the brain, but I also believe there may be purpose in seizure leading to homeostasis. I also believe in halting seizure ASAP by giving the body what it needs, such as CO2. And I'm the only person I know who developed a way to halt clusters in canines using gelatin, addressing the gut-brain. I was able to halt clusters in my dog several times to one seizure to avert what would have been horrific three-day clusters, risking brain damage.

 

[masterjen]

What I'm trying to make people and doctors aware of is the potential that seizures are of gut origin so that it can be addressed before damage occurs and healing can begin . . . And, yes, I do believe lesions and adhesions (scars) of the brain can be caused by the gut.

Keith - have you considered that in those with diagnosed digestive disorders (ex. celiac, Chron's, etc.) that it may not be the inadequacies of the digestive system causing seizures but instead whatever has caused the development of the digestive disorder also caused the development of epilepsy?

 

[epileric]

Thank you very much sharing that, Eric. That's generous and kind. Do you know how it occurred? Have you considered excess glutamate which also causes seizure? Glutamate as cause of lesion in the hypothalamus appears well-studied. MSG is known to cause hypothalamic lesions.
http://jn.nutrition.org/content/130/4/1032S.full
http://www.ncbi.nlm.nih.gov/pubmed/663939?dopt=Abstract

Keith, time & time & time again you've been told how different rodents brains are from humans. Both your studies are on rodents & neither makes any mention of using controls.

 

[kirsten]

What I'm trying to make people and doctors aware of is the potential that seizures are of gut origin so that it can be addressed before damage occurs and healing can begin. Instead, doctors are clueless and can only prescribe anticonvulsants without addressing underlying cause.

And, yes, I do believe lesions and adhesions (scars) of the brain can be caused by the gut.

Doctors do address the underlying cause, very successfully at that.

http://www.nejm.org/doi/full/10.1056/NEJM200108023450501
http://www.ncbi.nlm.nih.gov/pubmed/21838505
http://emedicine.medscape.com/article/251449-overview
http://www.neurology.org/content/60/4/538.short
http://jnnp.bmj.com/content/75/11/1589.fullhttp://jnnp.bmj.com/content/73/5/486.full
http://brain.oxfordjournals.org/content/136/6/1889.full.pdf
https://www.aesnet.org/sites/default/files/file_attach/Guidelines/Neurology-2003-Engel-538-47.pdf


These are long term randomised human trials, with techniques that have been assessed post market for a decade. I could pull 100, or more of these trials, and I could pull 100 in all the other types of resection, and more on lobectomies. There are meta analyses and knowledge about the likely outcome of each technique for every type of epilepsy, age of epilepsy onset, and the region of the brain that is affected.

Doctors have successfully treated the cause of epileptic seizures (that is, the aetiology of epileptic seizures, since we can't treat the scalpel, stroke, etc that created the seizure focus to begin with) for many years.

You can't make that claim. The efficacy rate of your combined treatments over five years is 0%.

It thus sounds a little odd that you're calling doctors clueless. Lets look at the facts.

Here is the leader board thus far

Long term efficacy
Doctors: up to 70% remission over five years, with up to 6% of patients showing no improvement whatsoever
Keith: 0% success rate over five years.

Evidence
Doctors: Hundreds of controlled randomised human trials of up to five years published in peer reviewed journals
Keith: 20 pages of uncontrolled, un-randomised rat trials lasting up to 3 months.

Knowledge and Experience
Doctors
100 years of collective knowledge, with practices treating 20 human patients daily. Full understanding of physiology, chemistry, pharmacology, diagnostics, surgery gained from med school, post doc etc
Keith: No knowledge of basic physiology.

You don't know enough to make an assessment as to whether doctors are clueless.

So, 65% of epilepsy has no known cause. That's massive.

No, it isn't massive at all. These 35% of newly diagnosed epilepsy patients know that it was that stroke in 1984, or that surgery in 2001 that caused their epilepsy. There are causes that are less dramatic: severe fevers, accidents that didn't seem to cause any damage at the time, illnesses that didn't instantly induce seizures...Of those 65% who don't have a cause at the time of diagnosis, doctors can later figure out what the cause was. As I said, and as you ignored, doctors later trace the problem back to issues such as genetics. Only 20% of epilepsy cases are cryptogenic. In other words, you have only 20% of epilepsy cases to discuss. All others have an understood, obvious, or known cause. Among that 20%, we have cases where doctors can view the damage and determine what sort of trauma would have caused the lesion/focus/etc. That leaves you, again, with a negligible percentage of epilepsy cases that you might like to hypothesise have their primary origin in the gut. But you're left with one last challenge: most epilepsy cases don't get worse. If you have a primary gut origin, you'd assume that the brain trauma would get worse, or better. Neither happens without medical treatment, and you are left with very, very few epilepsy cases to play with.

http://www.epilepsysociety.org.uk/sites/default/files/attachments/Chapter01Neligan.pdf

 

[kirsten]

Limitations of rat model in epilepsy research:

--The efficacy of treatments for brain disease in animal trials translates into effective treatments for humans as little as once in every 500 successful rodent trials. That is 0.02% of successful rodent trials in rats end up being of use to humans. Add to that the fact that unsuccessful animal trials are less likely to be published than unsuccessful clinical trials.

-Rats are less likely to have generalised seizures than people are due to larger, more disorganised CA2 regions responsible for generalisation in humans.

-Rat neurons are more effective at inhibiting seizures than people's are.

-Older rats are not generally used because the cost of keeping them long term is too high. In human epilepsy, we see that there are some epilepsy treatments that are vastly more effective in children than adults and some treatments for adults that are just not a good idea for kids.

-Naturally occurring epilepsy is seldom studied. Epilepsy is generally chemically induced in lab rats. Types of chemicals induce different types of epilepsy. Whatever treatments are shown to be effective in rats with epilepsy are only effective for rats with chemically induced epilepsy, and are thus unlikely to apply to people who don't have chemically induced epilepsy.

-Naturally occurring epilepsy in rodents behaves vastly differently than epilepsy in humans: rodents might have a seizure due to drafts, new environments, or simply being handled. People with epilepsy are triggered by different things.

-Seizures in rats are induced in the lab by blowing in rodents' faces. Many neurosurgeons will not even induce seizures in humans during EEGs and tests because they believe these kinds of seizures don't precisely mimic naturally occurring seizures.

-Rats don't respond in the same way to epilepsy as people. Their epilepsy consistently worsens until it causes death, whereas people hardly ever experience progressive epilepsy (if at all).

-Rats don't respond to treatments in the same way as people. Rats, for example, have reduced seizure frequency with anti-convulsants, but their EEGs continue to pick up epileptic activity. People controlled with anti-convulsants will more often have a clear EEG reading. Mice will still die of epilepsy under 100% successful AED treatment, whereas people will not.

-The cellular mechanisms affecting rat seizures are different to those of humans, resulting in seizure activity that is completely foreign to that in human patients.

-A denser hippocampus in rats makes them weirdly immune to chronic epilepsy, something that people have no trouble developing.

-There is a far higher degree of publication bias in animal studies (estimated at one third) than human studies.

-It is difficult to impossible to randomise a rat trial, given that epilepsy must be induced chemically.

I'm not going to list the physiological differences between rat brains and human brains, or rat biology and human biology, or the issues of getting clear diagnostic tests in rodents. I think this is enough.


http://www.ncbi.nlm.nih.gov/pubmed/17484760
http://neuroblog.stanford.edu/?p=707
http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000245
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155396/
http://www.hindawi.com/journals/pd/2011/658083/

 

[Keith]

Keith - have you considered that in those with diagnosed digestive disorders (ex. celiac, Chron's, etc.) that it may not be the inadequacies of the digestive system causing seizures but instead whatever has caused the development of the digestive disorder also caused the development of epilepsy?

Yes, definitely. I'm not discounting the way neurology traditionally views the gut-brain connection where the brain controls the gut. I'm just shining a light on the new way of thought where gut-brain is a two-way street. The gut strongly affects the brain.

Here are studies about hypothalamic lesions as cause of intestinal changes:
http://www.ncbi.nlm.nih.gov/pubmed/24331527
http://www.ncbi.nlm.nih.gov/pubmed/6337055
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1391120/

The question becomes what caused the hypothalamic lesions in these cases? Were they caused by the gut at some point in life due to poor diet and other environmental factors? It also seems possible the problem begins in the womb where the fetal gut develops long before the fetal brain.

 

[kirsten]

The question becomes what caused the hypothalamic lesions in these cases? Were they caused by the gut at some point in life due to poor diet and other environmental factors? It also seems possible the problem begins in the womb where the fetal gut develops long before the fetal brain.

That is easy enough to answer. They were induced by researchers using toxic levels of goldthioglucose and monosodium glutamate. (Read your trials. Then you won't need to ask.)

Above 12µg glutamate becomes toxic because neurons will begin to fire abnormally and the stress causes cells undergo a high level of apoptosis. There are a limited number of glutamate transporters and if they are overwhelmed by a high concentration they are considered to be hyperstimulated. “Glutamate binds to the receptor causing a channel to open and sodium and calcium to enter the cell. At very high concentrations of glutamate, this receptor is hyperstimulated and allows an excess of calcium to cross the cell membrane. This increase in intracellular calcium is thought to trigger a series of events including the activation of the enzyme Nitric Oxide Synthase (which creates the free radical form of nitric oxide) and the generation of reactive oxygen species (for review see reference (2)). Ultimately, these toxic substances do enough damage to the cell to bring about its demise.

http://www.glaucoma.net/nygri/glaucoma/topics/neuroprotection.asp

 

[Keith]

http://www.epilepsysociety.org.uk/sites/default/files/attachments/Chapter01Neligan.pdf

Great paper, thanks for sharing.

There are an estimated 50 million people with epilepsy in the world, of whom up to 75%
live in resource-poor countries with little to or no access to medical services or treatment.

The global burden of epilepsy is shouldered by the developing world:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61646-8/fulltext

The prevalence and burden of epilepsy is especially high in poor countries—more than 85% of the global burden of epilepsy occurs in low-income and lower-middle-income countries.

This is why I see epilepsy as sanitation issue. Please take a look at this gut-brain poster I produced nearly three years ago, Sanitation Is Sanity:
https://www.facebook.com/photo.php?....246428715601.298680.518250601&type=1&theater

I also have strong opinions about vaccination as cause of epilepsy via collateral damage to gut flora which has never been studied for any of the childhood vaccines.