Exploring the Gut-Brain Connection and Photosensitivity

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Questioning anyone's integrity is irrelevant when we're only talking about a fact he taught me: that glucosamine is made into sialic acid in the liver which binds to cells and blocks inflammatory lectin.

So, glucosamine supplements and dietary consideration seems like a good thing, but may be just a band-aid in light of microbes degrading sialic acid with their own enzymes, then making their own lectins which bind to our cells . . . wreaking havoc including the blocking of glucose which leads to diabetes. Microbes such as bacteria coat their own bodies in sialic acid, apparently stealing it from our cells.

Glucosamine is not just from bones and crustacean shells as most believe, probably derived via microbial fermentation in the gut from lots of foods. Have you ever heard of vegetarian glucosamine via fermented corn or wheat?
jointhealthmagazine.com/vegetarian-glucosamine-get-your-building-blocks-from-corn-instead-of-sea-shells.html

The point is glucosamine isn't just about diet, but microbial fermentation in the gut. And because of the way the gut affects the eyes and brain, we shouldn't be surprised to see in the news that eye problems are rapidly rising all over the world. In India there is a glaucoma epidemic.

Also, there's a knee replacement epidemic which cannot be explained by this 2012 study: "Population growth and obesity cannot fully explain the rapid expansion of total knee replacements in the last decade, suggesting that other factors must also be involved." The reason may be explained by malabsorption of nutrients such as glucosamine and the gut-knee connection. http://jbjs.org/article.aspx?articleid=334913

Experts say 600% increase by 2020 for total knee replacement. 2020 CDC projection: as many as 1 in 3 diabetic in USA, enough to cripple our economy based on cost of healthcare. How many amputations will it take and how many will go blind from diabetic retinopathy before we respect our status as superorganisms? Science itself is blind, chalking-up the matter to genes, caught in the headlights. http://abcnews.go.com/Health/Diabet...isk-2020-unitedhealth-group/story?id=12238602

Like most things, you can apparently get too much glucosamine (SIBO?) causing diabetes: http://www.sciencedaily.com/releases/2010/10/101027111349.htm

So, with a body fermenting too much glucosamine there may be too much heparin releasing too much DAO enzyme causing low histamine which causes a lot of stress and neurological issues:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635574/

There doesn't seem to be much science about low histamine, it's more like astrology. Antihistamine side effects include blurred vision, worsening glaucoma and constipation.
 
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Karen, have you ever researched activated charcoal? It has similar adsorptive properties to clay, though I found gelatin a more powerful tool for absorption. Still, activated charcoal is the first thing a hospital uses in event of some poisonings including histamine poisoning via fish.

But then there's also the concern of low histamine (over-methylation) where it may also apply, I'm not so sure about that . . . it's very puzzling that in obesity, for example, where microbial overgrowth is known, that low histamine is found in the brain. H3 histamine receptors are blocked.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861740/
http://www.ncbi.nlm.nih.gov/pubmed/19624751
http://www.nature.com/nature/journal/v458/n7239/full/nature07777.html

But in the gut of Celiacs, histamine is high:
http://www.ncbi.nlm.nih.gov/pubmed/3728211

Activated charcoal is also used as antiviral as viruses stick to it (adsorb) and can be safely carried out of the body.
 
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Be careful with activated charcoal. I used it once when experiencing a bout of food poisoning. It tears you up inside (figuratively). Don't overdo it or you will regret it.
 
Jon is quite lean, with a BMI that hovers slightly above being underweight (chronic diarrhea and Zonegran doesn't help). Due to his propensity to allergic reactions (ant bites, eggplant, air pollution), I would guess that his histamine level is high rather than low.

Saw his neurologist yesterday, who ordered a whole lot of new blood tests to check his levels on a lot of things, and also, an MRI is being scheduled (with specific protocol to check for a Hypothalamic Harmatoma). In the meantime, yet another med was added in, which I am less than thrilled about. It's Keppra, and my guess is that it has about a .0002% chance of working, since Jonathan has previously failed 9 AEDs, INCLUDING Keppra (he was on it when he was a baby). But the neurologist convinced us to give it a 2 week trial, and if it doesn't work, then take it back out.

I just feel like we're sinking into a very deep black hole.
 
Sorry about having try yet another med. Maybe a miracle will occur and the Keppra will help without hurting...
 
Abstract reviewing relationship between gut bacteria and brain
http://www.ncbi.nlm.nih.gov/pubmed/23010679
http://www.ncbi.nlm.nih.gov/pubmed/22968153
"Accumulating data now indicate that the gut microbiota also communicates with the CNS - possibly through neural, endocrine and immune pathways - and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders."

http://www.ncbi.nlm.nih.gov/pubmed/15133062
This study tested the effects of gut microbes on hypothalamic-pituitary-adrenal (HPA) reaction to stress, and it's subsequent effects on inhibitory neuronal function.

Impact of Omega 3 oil on hypothalamus: "ω-3 fatty acids, which are also known to enhance parasympathetic activity and increase the secretion of anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as well as acetylcholine in the hippocampus, may be protective."
http://www.ncbi.nlm.nih.gov/pubmed/22913633
 
I have used activated charcoal with good luck. Nothing negative with my use. Perhaps the brand matters?

KarenB - you don't have to agree to the third med. Especially if you have seen an increase in seizure activity with anticonvulsants. You might want to continue with your current plan for a while longer. Of course you will be expected to have a darn good reason as to why you are not following the doctor's recommendations.
 
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I know...but it's only a 2 week trial...so I guess we can give it a try, and if no improvement, then dump the Keppra, and go back to the other plan. I think doctors feel like they have to do something

I'm hoping the MRI will give us some answers (although our Neurologist isn't expecting it to) -- hopefully a lesion that got missed on the previous MRI that can be easily resected. If it's a Hypothalamic Hamartoma, that's really bad news...there is a surgery to excise it done at Barrows in Phoenix, and one or two other places, and usually provides seizure freedom, but then a lot of kids have a relapse in about 2 years. And the surgery causes quite a few problems.
 
Abstract reviewing relationship between gut bacteria and brain
http://www.ncbi.nlm.nih.gov/pubmed/23010679
http://www.ncbi.nlm.nih.gov/pubmed/22968153
"Accumulating data now indicate that the gut microbiota also communicates with the CNS - possibly through neural, endocrine and immune pathways - and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders."

http://www.ncbi.nlm.nih.gov/pubmed/15133062
This study tested the effects of gut microbes on hypothalamic-pituitary-adrenal (HPA) reaction to stress, and it's subsequent effects on inhibitory neuronal function.

Impact of Omega 3 oil on hypothalamus: "ω-3 fatty acids, which are also known to enhance parasympathetic activity and increase the secretion of anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as well as acetylcholine in the hippocampus, may be protective."
http://www.ncbi.nlm.nih.gov/pubmed/22913633

Karen, thanks for these hot-off-the press papers, great research and very hopeful. I've added them to a couple of explorations, one about about gut-brain and the other about fetal gastrointestinal tract affecting brain development:
http://www.facebook.com/photo.php?fbid=10151102028290602&l=2f13bcf3a5
http://www.facebook.com/photo.php?fbid=10151452581435602&l=11f7c860f7
 
Add apple pectin to the list of good gut conditioners, probably absorbing toxins. I still believe gelatin tops the list due to strong mechanical effect. But the expression "an apple a day keeps the doctor away" may be attributed to pectin. In fact, pectin was the first thing I attribute to halting a seizure cluster in my dog after failing with things like rectal valium, standard procedure. Pectin was the first ingredient in a product used for intestinal cleansing along with clay and other natural things which halted what would have been a horrific cluster after one seizure.

Concerning hypothalamic inflammation related to photosensitive seizure and seizure in general there are some very interesting connections to the gut. First of all, it's known in obesity which is a matter of gut dysbiosis, i.e., SIBO and overgrown lactobacillus. It's also known gut dysbiosis in obesity poses significant risk of birthing children prone to autism, itself strongly associated with IBD where the worst forms suffer a 40% epilepsy rate. Hypothalamic inflammation seen in obesity:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030571 (this study seems to support omega 3 fish oil in reducing hypothalamic inflammation.)
http://www.jci.org/articles/view/59660

There's also the factor of the interthalamic adhesion. "In casts of the ventricular system, a small 'hole' may be seen in the body of the third ventricle. This is formed where the two thalami are joined together at the interthalamic adhesion (not seen in all people)." Third ventricle at center: http://en.wikipedia.org/wiki/File:Gray734.png

Unique to the third ventricle, "the interthalamic adhesion is found in 70-80% of humans. It is present more often in females and larger than in males by an average of 53 percent." http://radiographics.rsna.info/content/31/7/1889.abstract

"In 1889, a Portuguese anatomist by the name of Macedo examined 215 brains, showing that male humans are approximately twice as likely to lack an interthalamic adhesion as are female humans. He anecdotally attributed the finding to a "prevailing feature of people deprived of [the interthalamic adhesion] is to present in their psychical acts a remarkable precipitation, joined to a certain dysharmony between internal and external feelings." "In non-human mammals it is a large structure." "It contains nerve cells and nerve fibers." http://www.tandfonline.com/doi/abs/...d=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed&

Maybe this significant gender difference (existence of interthalamic adhesion) along with different hormonal levels (estrogen important for immune response) explains why boys are 5x more likely to be autistic. Prenatal brain development affected by gastrointestinal flora is discounted by a scientific community holding belief the fetal GI tract is sterile amid knowledge that PUFA deficiency affects brain development where PUFA is a matter of biosynthesis via microbial enzymes (∆6 and ∆9-desaturase).
http://www.ncbi.nlm.nih.gov/pubmed/21459495 (supports fish oil in pregnancy for fetal brain development)
http://onlinelibrary.wiley.com/doi/10.1002/9780813820637.ch18/summary
http://www.mdpi.com/2072-6643/4/7/799/htm

Hypothalamic inflammation may affect CSF flow in the third ventricle associated with seizure, i.e., hydrocephalus also connected with autism:
http://www.jbiomech.com/article/S0021-9290(09)00566-1/abstract
 
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The hypothalamus regulate appetite, so a hypothalamic disorder can result in insatiable hunger, and thus obesity. This is commonly noted AFTER surgery for hypothalamic hamartoma, because sometimes the surgery for the tumor damages the hypothalmus it's attached to.

Yes, I did already find that study about fish oil and hypothalimic inflammation, and that makes me wonder if it's why the fish oil seems to have such a dramatic effect on his seizures.

Jon's autistic traits did not manifest until age 6 when he began having frequent seizures. Then, when he was seizure free last year, he did not have autistic traits. I don't think what he has is true autism. In fact, I just discovered that some of the vocalizations he has been making that I was considering autistic in nature may in fact be a type of gelastic seizure (a sort of a repetititive grunt, combined with wincing and smirking and a kind of forced grin).

Day 5 of Keppra -- no change in seizures -- no great surprise.
 
To clarify, Karen, I generally and frequently cite autism as example as it's closely associated with both epilepsy and IBD. I wasn't referring to Jon, but based on what you've written in this thread and your profile page, I do tend to believe the behavior stems from gut dysbiosis and is reversible.

It appears there's much to learn about gut origin of hypothalamic inflammation along with optic neuritis as cause of photosensitive seizure. Here's a 2010 paper about vision and hypothalamus including retinohypothalamic tracts:
http://www.optometryjaoa.com/article/S1529-1839(09)00611-3/fulltext

"The retinohypothalamic tract is one component of the optic nerve that transmits information about environmental luminance levels through medial and lateral branches to four major terminal fields in the hypothalamus."
http://www.sciencedirect.com/science/article/pii/S0165017310001086

This 2011 paper talks about the retinohypothalamic tract which arises in the eye, providing input to the Suprachiasmatic Nucleus (SCN) of the hypothalamus which then connects with multiple targets across the brain including some of the most important relays involved in the epileptic network.
Chronobiology of Epilepsy: Diagnostic and Therapeutic Implications of Chrono-Epileptology
http://static.aws.pdf-archive.com/2011/08/12/chronobiology-of-epilepsy/chronobiology-of-epilepsy.pdf
Here's just the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/21399517

2012, Circadian profiles of focal epileptic seizures: A need for reappraisal
This new paper sounds the alarm, talking about how the retinohypothalamic tract from the eye connects to the SCN which connects to amygdalas via the paraventricular nucleus of the thalamus (PVT). SCN also connects to the hypothalamic-pituitary-adrenal axis (HPA).
http://www.seizure-journal.com/article/S1059-1311(12)00086-6/fulltext
(per Karen's research above, HPA stress response is regulated by gut microbiota: http://www.ncbi.nlm.nih.gov/pubmed/15133062)

2011 book chapter:
http://books.google.com/books?hl=en...ge&q=retinohypothalamic tract seizure&f=false
 
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Thanks Keith for continuing to provide some interesting food for thought and research.
 
Yes, I know about the link between autism and epilepsy -- in fact, I drug up some research at one point that indicated that epilepsy can apparently CAUSE autism in children. But the brain pathways and actions are apparently very similar.

I guess there's various types of hypothalamic issues -- one is a hamartoma attached to the hypothalamus (or actually growing inside the 3rd ventricle, which is there from birth. Children with this tumor seem to have 3 seizure "hotspots" during their life, with quieter periods in between -- during infancy, during mid-childhood (age 6 to 9) and then once again at puberty. However, the tumor also often causes precocious puberty, so the infants or school children experiencing increased seizures may be experiencing the typical seizure increase that puberty causes for many other children with epilepsy. With this tumor, all types of seizures are evident, but notable for "laughing" seizures -- gelastic. Also, rages/violent behavior are very common. It appears that adults with this tumor have fewer seizures, but more of the rages.

Now, I have been interested in other types of hypothalamic dysfunction, which might manifest in a variety of symptoms such as diabetes, insatiable hunger, severe sleep dysfunction, body temperature dysfunction (overly sensitive to cold or heat), photosensitive epilepsy, etc. It seems that this type of problem seems to occur more in middle age and elderly population. I'm quite interested in the link between hypothalamic dysfunction or general metabolic dysfunction and epilepsy -- especially intractible epilepsy. After reading through a lot of the threads in this forum, I note a trend in a lot of the adults with intractible epilepsy to other diseases such as diabetis, thyroid disfunction and other metabolic issues.

So Keith, I think there's extreme validity in your point that doctors always treat epilepsy from the neck up (although, of course, the hypothalmus is located above the neck). But the problem seems to be that we are treating the symptoms and not the cause. And, as for the cause, if a lesion or something doesn't show up on an MRI, which is the case in probably at least half of epilepsy victims, then it's listed as "unknown etiology" and no further investigation seems to be done.

But there HAS to be a cause...and the cause may be located elsewhere in the body. I would like to see more research targeting the causes of intractible epilepsy of unknown etiology, because I rather suspect the cure will be in something other than AEDs.
 
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OK, I'm working my way through this study that Keith posted - Vision and the hypothalmus
http://www.optometryjaoa.com/article/S1529-1839(09)00611-3/fulltext

It has these quite interesting charts on all the parts of the hypothalamus, and their related peptides and the effects of these peptides.

So..for instance...we see that epilepsy could be affected by the Arcuate nucleus region of the hypothalamus, or the suprachiasmatic nucleus, or the hippocampus.

But..after reading about the effects of the various peptides...it begs the question...could it be the other way around??? Could some sort of hypothalmic dysfunction be CAUSING not only epilepsy, but also gastrointestinal problems??? For instance, the following peptides are related to gastrointestinal function:
Angiotensin II, Cholecystokinin (CCK), Corticotropin-releasing hormone (CRH), δ sleep-inducing peptide (DSIP), Met-enkephalin and endorphins, Oxytocin (OT), Substance P, Tachykinins (NKA, NKB, NPK, NPγ, tachykinin 1)

A number of these same peptides also are related to sleep and/or the immune system.

But then there's the question...what's causing the hypothalamic disorder? It could be a cogenital tumor, but in adults, more likely to be overeating and certain types of infections and inflammation.
 
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Gut-brain is definitely a two-way street. Thanks for the education, Karen. I wonder if hypothalamic hamartoma itself may be of gut origin, a result of inflammation which may be the case in hamartoma in eyes and intestine.
http://www.retinalphysician.com/articleviewer.aspx?articleid=100087
gut.bmj.com/content/27/8/964.full.pdf

I'm embarrassed to provide examples of my experience in trying to resolve my dog's seizure disorder because there really is no comparison to a child. I've spoken with a closed Infantile Spasm Facebook group about gut origin and they kicked me out of the group because I used my dog as example. Moreover, they choose to trust their doctors and focus on the brain. They were extremely offended to even consider gut-origin. And who can blame them under such excruciating circumstances?

In the case of epilepsy, I believe the medical establishment may need a bit of embarrassment as they disregard gut-origin of seizure. I traded email with a world famous neurologist who still believes the brain controls the gut without ever having considered the opposite, even though the main gut diseases list seizure as symptom. This is hardly new information. Leading funding organizations such as CURE (Citizens United for Research in Epilepsy) have yet to receive a funding request to study gut origin of epilepsy.

In trying to identify the obvious gastrointestinal source of seizure in my dog, I went through several theories over nearly four years, actually beginning with ear mites! Then, last May, I began focusing on clostridium bacteria based on endoscopy images of May 2011 where doctors had no idea what they were looking at and didn't even consider sending the images to an expert, nor did I. I stumbled on endoscopy images on the internet of C-diff and began researching pseudomembranous colitis. I had ordered an endoscopy to confirm suspected intestinal cause of seizure when vets suggested MRI and spinal tap. Here's a photo confirming ulcerative IBD/overgrowth and discussion:
http://www.facebook.com/photo.php?fbid=10151940595510602&set=o.191464044230064&type=1&theater

But a couple years before this focus on spore-forming clostridium bacteria, I was focusing on things like protozoans (amoebic dysentery) and flukes (schistosomiasis). Based on treatment, she actually went four (4) months seizure-free. It was such a blessing. I didn't know exactly what I was treating as all vet tests were inconclusive. But I attribute this long freedom of seizure to two things: colloidal silver and praziquantel. Now I'm sure Eric is getting all hot under the collar wanting to save people from turning blue from colloidal silver and he's probably never even heard of praziquantel. The fact is pharmaceutical antibiotics actually cause gut dysbiosis and promote antibiotic resistance where there is no resistance to natural antimicrobials such as oregano oil. The point is that treating her gut worked, but it's more art than science these days and I probably didn't do the right things long enough to create homeostasis, if that was even possible. It's not important what I used and people should be very cautious in treating gut dysbiosis. There are many considerations, not least of which is accessing infection through biofilm.

In hindsight, when I thought I was treating her for worms, I was actually killing clostridium bacteria with colloidal silver, especially the ionic form. It was used for, I believe, a couple months in 1-2 tablespoon doses a few times/day. When she was experiencing intestinal flares with inflammation and skin issues such as manic itching (preictal!!) I gave her a dose of praziquantel (the world's #1 dewormer for people and pets) and this got her through without seizure! At the time, I knew praziquantel also had antiprotozoal activity, so I was covering my bases. Little did I know it's thought to be effective in killing worms due to altering intracellular calcium and this appears crucial to interrupting inflammation caused by clostridium toxins.
http://www.ncbi.nlm.nih.gov/pubmed/16569296
https://darchive.mblwhoilibrary.org...45/neuromuscreviewplusfigs-new.pdf?sequence=1

On intracellular calcium and clostridium toxins:

http://www.sciencedirect.com/science/article/pii/S0171298508000648
http://www.jimmunol.org/content/163/10/5183.full

Note: medical science does not understand the true mechanism for how many pharmaceutical drugs work, including what is perhaps the most popular class of antibiotics used in C-diff and other infections, Fluoroquinolones, which is also thought to be effective via intracellular calcium. This class of drug is abused by the medical establishment in treating things like C-diff and has led to antibiotic resistance.
http://www.ncbi.nlm.nih.gov/pubmed/21607983
http://jcm.asm.org/content/48/8/2892.short
http://www.biomedcentral.com/1471-2334/11/187
http://well.blogs.nytimes.com/2012/09/10/popular-antibiotics-may-carry-serious-side-effects/
 
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For a good general article about antibiotics and gut issues and how the gut may affect other areas of the body, I recommend the article called "Germs Are Us" in the latest New Yorker. It discusses among other things, how the loss of certain gut bacteria in western societies may play a role in the rise of disorders like asthma and obesity. The full article is only accessible to subscribers, so I can't provide a link to it, but the intro found here http://www.newyorker.com/reporting/2012/10/22/121022fa_fact_specter does say in passing: "Recent research suggests that they [bacteria] may even alter our brain chemistry, thus affecting our moods and behavior..."

I can't wait for the research in this area to get to the next level.
 
A hypothalamic hamartoma is a congenital birth defect -- like cleft palate or whatever. It doesn't develop.

But other types of hypothalamic inflammation can develop --
http://www.ncbi.nlm.nih.gov/pubmed/22417140
"Under conditions of brain and hypothalamic inflammation, which may result from overnutrition-induced intracellular stresses or disease-associated systemic inflammatory factors, extracellular and intracellular environments of hypothalamic cells are disrupted, leading to central metabolic dysregulations and various diseases"

So...it seems that overeating is one culprit in hypothalamic disorder, along with inflammation from disease.

Which leads back to treating epilepsy through treating inflammation.
 
Keith, I'm sorry you got kicked out of that Facebook group. And what a shame that those parents are only apparently putting their hope in AEDs for their babies' spasms. The Ketogenic diet is perhaps the BEST treatment for this type of epilepsy -- and the success rate of the Keto diet for this group of epilepsy victims is much higher than the general epilepsy population. For kids with other types of epilepsy, studies at Johns Hopkins show the success rate is around 10% complete seizure freedom, and 50% significant seizure reduction, but in babies with infantile spasms, the seizure free rate is closer to 40%, and significant improvement is seen is about 2/3 of the babies.

While these parents are dilly-dallying around, their babies are suffering irreperable brain damage -- what a tragedy.

We know that the Keto diet alters brain chemistry, but it apparently does so through altering a number of body systems, including the gut.
 
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With regard to gut pathogens, Jonathan was tested for most of the usual suspects, but everything came back negative. I went looking for that culture report, to see what exactly he was tested for, but must have misfiled that test.

But I did note that on his most recent CBC (August 2012) his WBC was slightly high, when in all previous blood work since initiating the diet, it has been on the low end. This suggests a low-grade infection of some type, somewhere. His consistently higher glucose levels, even when in high ketosis, also suggests some sort of systemic infection or inflammation somewhere.

Furthermore, in the 6 months prior to initiating the Ketogenic diet, when seizures started to get really bad, Jon was frequently ill with ear infections, pneumonia, stomach flu, etc. -- he had more illnesses in that 6 month time frame than he had in his previous 6 years of life! Of course, illness can trigger seizures, perhaps through inflammation. The interesting thing is that AFTER initiating the Ketogenic diet, he had one bad sinus/ear infection 6 weeks in, and then after that very few illnesses -- just a couple mild colds that cleared up in about a week.

So...was there some sort of underlying issue that was compromising his immune system and causing a low seizure threshhold? Did the Ketogenic diet "cure" or at least suppress whatever that underlying issue was? And did the bad stomach virus in March 2012 reactivate whatever the underlying problem was?

With careful attention to diet, we got Jon's diarrhea almost cleared up recently, but now that he's started Keppra, he's had multiple bouts of diarrhea every day. The tonic seizures haven't gotten worse (in fact, now we're seeing slight improvement), but gelastic seizures have picked up, along with extreme hyperactivity and destructive behavior. Not sure if this is a side effect of Keppra or the worsening diarrhea.
 
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