 All right, so this issue of iGabat, you know the question at this point with his child when he was came down here from Montana was is there evidence of iGabat and toxicity and We typically do an exam under anesthesia do electrophysiology It turns out that many years ago when this drug was studied Don Creel and I were among the investigators That participated in gathering data That brought to the fore the issue of iGabat and toxicity in children and In this child that is you know definitely an issue and the thing that was striking with our exam under anesthesia was these changes depigmented areas from Mid peripheral retina out to the periphery The optic nerve notably looks Healthy we because of issues getting test accomplished did not get an OCT during our recent exam in our anesthesia But we did do the electrophysiology that you saw and the thing that struck me with that electrophysiology was that the cone ERG the flicker response, which is predominantly a cone response All we saw were stimulus flight spikes. That was a grossly abnormal Electroretinogram the manufacturer of sabral has recommended That testing be done every three months including electrophysiology and all children on the medication We have held the line in doing it here every six months recently incorporated doing OCT It turns out that retinal nerve fiber layer thinning has been identified as another Component of this toxicity in looking into this There are a couple of things with this kid and I want to show you some of the pictures. These are these areas of depigmentation that are present and Fortunately the posterior pole looks relatively normal One of the questions here is is this sabral toxicity and I apologize for the flashing I have no idea how to operate this when it works let alone how to troubleshoot it So if anyone has a clue, please jump in Any of the residents as far as is you know, if we were to consider other things, what else should we consider? You've got an abnormal electroretinogram in an infant who's got Borderline poor vision and some pigmentary retinal changes RP could be some sort of retinal dystrophy The other question in a child who's got abnormal neurologic function is is in my mind was is there some evidence of a metabolic Disease it turns out that we have him scheduled to see dr. Longo who is our pediatric geneticist metabolic specialist So we will hopefully have answers on that in the interim the plan Quite, you know forcefully to pediatric neurology was let's taper him off of vi gabatron while we were sorting this out We are going to bring him back at our next exam. We will do an OCT and we'll have more information in terms of looking into this What have we learned and what have I learned and putting this together for you? It turns out that vi gabatron is an irreversible inhibitor of GABA. I mean O transferase and When you have increased GABA you have decreased seizure activity Where is it most frequently used at least 90% of the patients that I see this medication used in Have tuberous sclerosis Why is it the magic bullet for seizures and in TS? That is an unknown Now the ERG changes that dr. Creel identified years ago include a decrease in the cone B wave Decreased in flicker amplitude and the thing that most people remember is Absence of oscillatory potentials those little spikes you see on the elevated portion of the B wave in the electro retina gram nasal Retin optic atrophy and nasal retinal kind of segmental Retinal atrophy were described by Ray Bunsik at hospital for sick kids in Toronto back in 2004 for monitoring again electro retina gram fundus photos and OCT now One thing I learned that I was not aware of is this has been associated with a cumulative dose greater than 1,500 grams of drug So we're going to need to start recording that when we see kids. We've not been doing that The other issue is question of does this have long-term implications? And there are at least two papers suggesting that it indeed does in adolescence with Documented several toxicity early in childhood when they were seen later when one could do a goldmine visual field and Do OCT looking carefully at nerve fiber layer thickness? There are abnormalities seen in adolescence from documented toxicity early in childhood Years down the road and and this is really opening a can of worms and then the other issue is these authors and this is a French group of investigators published in pediatric neurology presented VEP and ERG stimuli to Selected parts of the retina and what they found were that there were issues in the peripheral parts of the retina that they were there were abnormal when presenting these this Flashes both VEP and ERG In school-aged children who had been exposed years earlier and these were school-aged children who had been on the medication That did not have documented toxicity So there's real question about this and reason for us to be following these kids closely and so now Setting that aside. I want to wonder a thing. You're in clinic It's very busy you get a text and the text is from one of your radiology colleagues And the text basically just says what is this and do you need to see the patient today? and Here is the scan and and this is the only image I got and yes It was this fuzzy on my cell phone And you see what looks like a lens here and lens here and not much of an anterior chamber and so I'm wondering is this a child with anterior segment dysgenesis that they've discovered say tell me more about the patient It turns out that the patient is a healthy 12-year-old girl Head injured CT from an outside hospital Reported to have perfectly normal eye exams good visual acuity by mom and this was an artifact and I don't know in retrospect whether he sent this to me as a joke We're seriously asking a question, but you know on it when things don't look right You want to wonder about the source of the information and Back to the first case Questions comments particularly from our retina colleagues in neuro ophthalmology as far as this issue of by gabatron toxicity What percentage of all patients This is a rare occurrence it's a rare occurrence when we were doing they're doing the initial Treatment trials and we were doing electrophysiology. They're using much higher doses the doses They're using now are much lower and I Have this is the first patient in recent memory That I have recommended that they stop the medication Almost all the other patients we've been on have had good electrophysiology And we've had good stable electrophysiology and again the issue with this first ERG Understand is when you put a patient under general anesthesia It suppresses the EEG when you suppress the EEG you decrease the response that you're going to get with Electroretinogram in particular with the VEP So that anesthesia can alter it so comparing an awake study to an asleep study is Not necessarily a good thing to do and draw firm conclusions. Yes Not that I am aware of Yeah, this is if this is due to by gabatron This looks like RP and the other thing I'm going to do when we go back next with this child And they've got to come down from Montana and we have to coordinate care is I think it'd be wise to do an FA We can easily do that now with a ret cam And Glenn Jenkins has been very good about coming to do FAs for us And in helping us through that both with Pete's retina and pediatric ophthalmology services and doing an FA I think would help sort out where this is the other thing I thought as far as the metabolic disease of this could it be gyrate atrophy or something like that and But there you've got loss of coroid. This does not look to me like loss of cord It looks like simple loss of RPE I've never seen anything look just like this in any of the patients that I've either seen in person or published with by gabatron toxicity So I think the point thing is that the finding that this indeed is it can be a permanent change It well in it definitely Right Well, the other plea I would make is that Rather than having someone order the test I think that having someone Look at the eyes Carefully and thoughtfully is is highly desirable in terms of trying to sort these things out Yes, I mean the hard thing I think about Sable is it's it's an amazing drug for a lot of kids And so it's not like I mean In some cases you have to have the discussion with parents. Would you like to take them off this drug? Which is the only drug that can control their seizures or The trouble I've had with this drug is that when I put them under anesthesia and do these repeat ERG Sometimes I'll get a little lower. Sometimes they're a little higher and some of it a lot of it has to do with under anesthesia They're a little bit different and it depends on how light the anesthesia is and so I have trouble sorting that out and these are usually very Delayed children who you can't get much of an exam in clinic and so it's hard to know that but it isn't You know, it's really getting lower and you look at their exam in clinic and is it really worth putting these kids under anesthesia because These are kids with lots of other developmental problems But this is the only drug that controls their seizures It's a very it's a very difficult drug to deal with What I said that I'm impressed how kids with uncontrolled seizures Just are developmentally stalled or grass. They're in a vegetative state And they're there if you can't get the seizures under control Their life experience he goes to the teens so so this is this is often the option the parents have so I find that the parents are Often very comfortable with the risks of vision loss because their child for the first time is Developing their brain is not seizing and they're starting to eat milestones. It's so it is it's very complicated situation But then they say but you can put glasses on fix it And that's the the issue because those but this issue of Having a brain that functions is is important and it is a not agree a night-and-day difference baseline Rnfl Prior to So I think that I think that that sort of called into question because a lot of the studies are done Way later after the exposure. Yes, and it's you know Understandably a lot of patients were very young at Roman and couldn't have done a pre Treatment extensive testing right, but it's been somewhat Controversialist at the really frequency of how often this really occurs compared to the potential benefit of the drug It's tough call. We try to get pre treatment testing, you know, whenever possible In this situation we're in here Unusual for me where I've never seen the child the very first time I see them They've a been on it for a long time supposedly been tested and things don't look good And we're trying to sort out whether it's old or new which is exactly the case You know, there's just often a reason why they have a tractable epilepsy and end up on And that may definitely include a potential retinal issue Yes, rather than I'll bring additional info back that bursting Just Yes Yes It's in we're definitely they're already they're plugged into genetics Already and and hopefully we'll get some sort of answer in terms of an overall better overall diagnosis All right next