Hi, uep. I normally like to research answers before posting but it sounds like this is time-sensitive so I'm going to tell you what I think off the top of my head and then get back to you with more information later.
1) Could a recent change to a low-carb, moderately ketogenic diet have aggravated or provoked the condition?
I doubt it. I don't recall seeing any warnings in the epilepsy literature about a change to ketogenic diet aggravating extant epilepsy. Many epileptics have initiated a ketogenic diet under medical supervision and much has been written about them. What I have read about the ketogenic diet for epilepsy has often had a very conservative/skeptical tone--searching long and hard for signs of harm being caused by the ketogenic diet, which is reputed among epilepsy researchers to be an unnatural, difficult, and potentially dangerous medical therapy. So if there were any evidence of ketogenic diet initiation triggering or exacerbating seizures, I think they would have emphasized it.
Nonetheless since my own bias is quite the opposite (ketosis is natural, easy, safe, and healthy), I might have missed, ignored, or forgotten any such warnings, so I'll try to find some.
2) What is known about the mechanism by which a ketogenic diet helps epileptics, and is it applicable to adults (or specific to forms that arise in children)?
Last I checked, nobody has high confidence in their theories about the mechanism, even though the efficacy of ketogenic diet as a treatment for epilepsy is well established. The theories that I have heard, which people seem to have started writing about only in the last ten years or so, focus on energy production in the mitochondria. I have heard various ideas about it. Mitochondrial energy production on ketones is more efficient than on glucose, produces fewer reactive oxygen species (see Lucas Tafur's blog http://www.ketotic.org/2011/05/bioenergetics.html ), and perhaps it is more robust against some kinds of mitochondrial damage -- if you're running on glucose and your mitochondria suffer certain forms of damage then the flow of energy is disrupted but if you're running on ketones this kind of damage won't interrupt energy production. Dr. Emily Dean's summary -- http://evolutionarypsychiatry.blogspot.com/2010/08/your-brain-on-ketones.html -- emphasizes that ketogenic diet should reduce the ratio of glutamate to GABA, if I understand correctly.
I will come back and give you more references later.
By the way, you mention ketogenic diet for adults vs. for children and this is a good example of how weirdly sophomoric this whole field is. Someone (sorry, I forget exactly who and when -- this whole "posting without researching" thing feels weird) made some observations in the early or mid 20th century which led them to believe that the ketogenic diet as a treatment for epilepsy only worked in children. Then for many decades people didn't try the ketogenic diet in epileptic adults. Then, in approximately the last decade (sorry...) people realized that there wasn't really any strong evidence that it would be ineffective in adults, and started trying it, and what do you know--it is effective in adults.
This whole pattern is really frustrating to me: for about a century the ketogenic diet as a treatment for epilepsy has been regarded as difficult, dangerous, "last resort" sort of option. Even today, after the Charlie Abrahams revival, the standard treatment is to first try two or three anti-seizure drugs and only then try the diet. This seems insane to me! Why would anyone risk taking an unhealthy and dangerous drug like carbamazepine, gabapentin, or any of the others when you could first try a nice healthy zero-carb diet instead? :-)
Anyway, even this may be changing, in large part due to the successful experiments of Dr. Eric Kossoff.
3) What is the single most relevant paper or researh that you would present to a neurologist to convince them of the merits or significance of diet (and paleo / ketosis in particular) in their field.
So it depends on the milieu your neurologist is from. :-)
a. They're from the pre-Charlie-Abrahams-revival. So basically they got their training before 1994 and haven't been keeping up. Honestly, if this happens maybe you should just get a different neurologist? I don't know how common this type is nowadays.
b. They're from the post-revival, pre-Kossoff era. I would assume this is the current standard model of neurologist. They should not require any prompting from you to know about the efficacy of the ketogenic diet. (If they do, then maybe you should get a different neurologist.) They might think of the ketogenic diet as a difficult and dangerous last-ditch option to try after drugs have failed. They might think that a ketogenic diet requires calorie-restriction, protein-restriction, drinking cups full of medium chain triglycerides, or water restriction. They might be worried about side-effects of eating a high fat diet such as heart disease or osteoporosis (haha). They might think that a "ketogenic diet" means living on a medicalized "nutritional product" such as KetoCal™ (made from corn or soy, of course) instead of eating real food.
c. They're on the cutting edge of the modern (Kossoff) era. They're well aware of the therapeutic potential of ketogenic diet, and they might think that basically just going into "Atkins induction mode" and staying there is more or less as good as the traditional, medicalized "ketogenic diet".
So your task is probably not to educate your neurologist on the efficacy of the ketogenic diet, but to navigate the subtleties of your wife's case in particular and the various options of drugs and diet that are now available.
Hope this helps!
I'll come back with more references later. Feel free, everyone, to request clarification from me or challenge what I've said. I'm no expert on these matters and I might have made mistakes above, and I would hate for my mistakes to go unchallenged and contribute to harm to uep's wife. I'll probably find it easier to come up with specific references to research papers (which is what uep asked for) if asked more specific questions.
By the way, you didn't ask for general advice (you asked only those three questions above) but there could be a world of difference between your wife's "paleo" diet of the last 2-3 months, of which you didn't give any details above, and a very strict ketogenic diet which carefully eliminates everything which isn't necessary and which might be contributing to the epilepsy. If it happened to me, I would go on a strict all-meat diet as practiced by the folks on the Dirty Carnivore forum. Well, actually, I already am on such a diet, more or less, so if it happened to me I would start by eliminating the exceptions that I occasionally indulge in. I would also take up intermittent fasting.
There are plenty of people who suffer from epilepsy and a ketogenic diet doesn't help them, or doesn't help them enough (around 50% of patients), so I'm not saying it is a cure-all. I am saying that it is the best first-line option, and that what your wife has been doing for the last 2-3 months may or may not have the same effect as a strict ketogenic diet. Note that those people who suffer from epilepsy and a ketogenic diet doesn't help them may be suffering from different types of epilepsy than your wife is, often have very bad additional complications, and are in most cases taking in the medicalized, calorie-limited version of the diet. So your wife may have a better chance than they do.
Good luck! I hope your wife heals quickly and doesn't have any more seizures.
Oh, and one more bit of advice: if my brilliant wife, Ambimorph, has anything to contribute then listen to her. :-)
uep: I just found this review article by Dr. Kossoff (whom I earlier mentioned):
- “SpringerLink - Neurotherapeutics, Volume 6, Number 2,” http://0-www.springerlink.com.skyline.ucdenver.edu/content/k168n1262138823w/.
This is the best thing I've seen yet as an introductory point for a neurologist. It summarizes a lot of experiments in animals, clinical reports in humans, a couple of experiments in humans, some possible mechanistic explanation (which seems to mostly emphasize the efficient energy production in mitochondria when on the ketogenic diet). It also briefly describes alternatives to the traditional (medicalized) ketogenic diet, namely "Modified Atkins" (which I think is basically just: stay in Atkins Induction Phase and try to get plenty of fat), and low-GI (about which I am modestly surprised that it is ANY USE AT ALL). It also mentions that the former beliefs that the diet is unsustainable, loses efficacy over time, and doesn't work in adults is unjustified.
Now here is "the ketogenic diet HOWTO for neurologists", also by Kossoff:
- “Optimal clinical management of children receiving ... [Epilepsia. 2009] - PubMed result,” http://www.ncbi.nlm.nih.gov/pubmed/18823325.
Of course, the best situation would be if your neurologist is already intimately familiar with both of these documents. :-)
Hope this helps! Please do keep us informed of how things go.