According to the dictionary, the word paradox means….A statement that seems contradictory or absurd but is actually valid or true. Epileptic seizures appear to be the pinnacle of paradox but in actuality there is truth behind the madness. The problem is, that we vets, have not desired to find the truth in the paradox. Until now.
Seizures, a symptom and not as disease, occur when the brain is firing too many neurons (messages) to the body and the body reacts to these messages. When the brain sends messages to the body, they pass through the cerebellum and like a traffic cop, the cerebellum allows them to pass through and sends them on their way. When a seizure happens, there are so many messages at once, the cerebellum is overwhelmed and there is no restriction or direction and the body responds in a series of muscle contractions we call tonic-clonic activity.
The brain has a hypothetical ceiling for brain activity. We call this the seizure threshold. As long as the brain is firing messages below this level, a seizure will not occur. If the brain is stimulated to fire too many messages and they cumulatively hit the seizure threshold, the seizure occurs. So, logic tells us that the more excitable the brain activity, the more potential for a seizure to occur. We see this in some dogs who seizure during over-exitement periods.
The paradox with most epileptic dogs that seizure is that most of them seizure while sleeping or during the waking phase from sleep to awake. During sleep, the brain activity is at its lowest activity phase, hence the paradox. Why would a dog with a low brainwave activity have a seizure? It took me a while to figure it out even thought it has been an itch I haven’t been able to scratch for many, many years.
After back to back phone consultations with caretakers whose dogs were having epileptic seizures, I started trying to scratch that itch again. Why is this happening? To answer this we first have to look at the disease, epilepsy. What is epilepsy and what causes it? We don’t know. That is why we call it an idiopathic disease. We know that it happens in younger pets (and children) and that when we run every test from blood work to brain scans, everything appears normal. If the test are all normal, we diagnose the patient as an epileptic and if the seizures are bad enough, we put them on anti-seizure medications that often come with a lot of nasty side effects. Oh, and the drugs only work to raise the seizure threshold and do nothing for what is causing the brain to be hyperactive.
So, lets get back to that paradox thing. I was thinking back in the old days when we used older drugs to induce anesthesia. Drugs like phenobarbital or pentobarbital were given IV to move the patient from awake state to anesthetic levels so that we could intubate them and maintain them on gas. The problem with these drugs were that they were very slow acting and in some pets, we would see them moving through the phases of brain activity as it moved towards deep sleep or anesthesia. During this period, many dogs would go through a hyper-excitability brain phase. For a short period, they would look like a pet having a seizure. We could also see this phase while many pets were coming out of anesthesia. In my research, it appears that the same thing would happen in humans when these drugs were used. We would also see this phenomena when we would treat a dog for seizures using IV phenobarbital which is the standard treatment for stopping a dog that is seizing (status epilepticus). I have seen more than one veterinarian confusing the excitability phase coming out of phenobarbital as another seizure, leading to the vet giving another injection of phenobarbital instead of waiting a few minutes for the pet to come through this phase.
Knowing that this was happening in both pets and people, I turned my attention on human research, where we find a lot more research money spent for humans versus animals. Fortunately, for us, they use animals in their research. What I found out was that these patients that were going through this phase and showing symptoms of seizures were people who were deficient in the amino acid, gaba amino benzoic acid (GABA). Come to find out, GABA is a neurological inhibitor that keeps the brain from over-reacting to this transition from sleep to wake. These human patients were given GABA and their brain overactivity potential stopped. Guess what, the same thing happens in pets.
Again, turning to human research, they have found that many epileptic children have a deficiency of GABA, usually due to the body developing antibodies against its own GABA or just a deficiency in GABA. This most likely is the same in dogs and cats. Both of the dogs that I mentioned that I did phone consultations for were placed on supplemental GABA and both stopped having seizures.
If there is a loss of GABA in pets that appears to explain the paradox of most epileptic seizures in pets, then how can we explain this happening? Not too difficult if one takes the time to look. The answer is leaky gut syndrome. Research tells us that leaky gut syndrome not only leads to a deficiency of GABA but also an improper utilization of the amino acid. Come to find out, some of the normal gut bacteria (flora) actually produce GABA and when we get leaky gut, the imbalance of gut microbes leads to GABA deficiency. If all of this is true, and it appears to be so, then the way to resolve epilepsy starts with gut healing and repairing the gut biome. Also, leaky gut leads to immune hyperactivity which could explain the production of antibodies for GABA as the immune system would identify the GABA as a foregin chemical and develop protective antibodies. More and more is being learned in human medicine about the gut-brain connection and unfortunately, little of this information is being trickled over to our pets.
This is my latest theory that seems to hold water with the two patients that I have treated. I don’t see a lot of vet research in the future that will likely prove this wrong, so it might not hurt to start supplementing GABA for epileptic seizures and start working on healing the gut. We might indeed be solving this paradox.