A possible way to find new anticonvulsants

I’ve had glaucoma for years.  (Free medical advice — if you’re over 40 you should have your eye pressures checked every 2 years or so.  The pressure can be high enough to permanently damage your vision without producing any pain).  Usually my pressure is well controlled, but every now and then it isn’t without any change in lifestyle, medical history or medication to produce it.  My ophthalmologist says that’s the way glaucoma acts.

That’s the way epilepsy acts as well. Sometimes a seizure will break through in a patient who is very good about taking their meds with no change in lifestyle, medical history, psychosocial history etc. etc.   Unlike glaucoma, we do know several things that will make seizures more likely.   The number one  is sleep deprivation.

Absolutely every drug for epilepsy (anticonvulsant) I was able to use caused drowsiness.  This may no longer be true for the newer ones since I retired.

We’re still learning about sleep.  Rapid Eye Movement sleep (REM sleep) was discovered in the 60s.   The glymphatic system was discovered less than 10 years ago and it may explain why we need sleep at all (something that has mystified us for years)  For a lot more detail about the glymphatic system please see — https://luysii.wordpress.com/2013/10/21/is-sleep-deprivation-like-alzheimers-and-why-we-need-sleep-in-the-first-place/

Fluid flows through the brain a lot faster during sleep through the glymphatics, essentially washing it out, and presumably removing toxins.

It’s not much of a stretch to think that the lack of washout during sleep deprivation allows toxins and metabolites to build up which make us sleepy.

It is at least possible that some of the molecules being washed out during sleep increase the chances of seizures, explaining the well known protective effect of sleep on epilepsy.

It is even possible, that some of the sleepiness produced by the anticonvulsants I used increased the washout, without actually putting my patients to sleep.  This would be easy to study.  Perhaps someone has.  I haven’t kept up with that literature.

So here is a modest proposal.  Measure spinal fluid molecules (probably metabolites) before and after sleep deprivation.  Study the molecules increasing in spinal fluid after deprivation and test them for their ability to produce seizures.  If one such is found, test ways to decrease the molecule’s formation or ways to destroy it.  If found, it would be an entirely new way to treat epilepsy.

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