Not new here but it has been a while ... 10 y/o losing seizure control

[jjb]

Hi all. I am not new to the forum (was more active on the old EPA forums).
Benard I hope you come along and post.

My daughter is 10 years old and was Dxd with seizures prior to age two.
At age two had her first prolonged seizure and went on trileptal with not much help.
We switched EPIs who recommended Lamictal and LGIT.
Things improved some but eventually got a rash with Lamictal and we had to stop.
She did ativan for six weeks along with LGIT and got great control. We decided to just to LGIT which worked well. We still had 2 to 4 complex focal seizures a year, but that control was good.

This past October she had a status seizure which was very difficult to stop and had to go the the ER first the first time in 8 years... very scary.
In December we agreed to try the drug ONFI (my daughter also has a lot of daily spiking)
Shortly after getting to the max dose of ONFI, my daughter had tonic clonic status (first time in 8 years). We thought that we probably forgot the nighttime dose (though not 100% sure).
A week later had some strange morning episodes but not sure if they were sz. or sleep paralysis. two weeks later had focal status seizure (total paralysis with left side convulsing). A week later had more unusual sensations ... possible SPs (feeling attached to bed an unable to move).
Last week had another focal seizure (first paralysis and them tonic).
A few days later more sensations of feeling stuck to the bed and unable to move.

We have never had this many seizures so close together. She is at the age of hormonal changes, but I don't know that it would cause such drastic increase as we are seeing now. I am more so feeling like it is ONFI that is causing this.

I am not entirely sure what to do next re treatment.

Here are my thoughts:
Keppra, Vimpat, prednisone (since she has the daily spiking), full KETO, CBD oil.

Any thoughts or experiences with these treatments for refractory seizures?

 

[masterjen]

First, welcome back to CWE!
I know it is Bernard you are wanting a response from, but I just thought I'd throw in my thoughts.
-How long since her last EEG and MRI? Could be that there are some neurological changes (such as a new seizure focus, for example) that are responsible for the new seizures.
-Has your daughter been labeled as having refractory seizures? I know that the rough guideline is if the first couple of medications don't work, then seizures are considered refractory, but I sometimes think this definition is used too loosely since so much comes down to whether or not the truly correct medications were attempted in the first place, were the dosages and dosing correct, and were the seizures/seizure type correctly diagnosed. But, that is just my opinion.
-You're correct that hormones can aggravate seizures, and the neurologist and pediatrician should be able to assist you in this regard (some women opt for hormone treatment to even out the hormone fluctuations, but I don't know if this is done is someone as young as 10)
-You say you are not sure what to do about treatment. While it is important to be informed, the weight of determining the options should not fall on you. Your daughter's neurologist should be the one searching out the options, and then helping you decide on the best course to take. If your neurologist does not do this, or you do not have faith in his/her ability to do this, find another neurologist. It is very important to have trust and confidence in your neurologist (any doctor for that matter).

 

[jjb]

Thank you for your reply.

EEG in December.

Has always been multi-focal (suffered a stroke) ... the problem I think is her threshold has fallen and we need to try and understand why.

Probably meets criteria of refractory E, yes.

RE treatment decisions. I do not leave decision making re treatment solely on the doctor. Had I done this with our first neuro my daughter might not be here today. Same with the second neuro (an epileptologist). Our third epileptologist is one of the best in the world. Our current EPI team helps us to make informed decisions, we all decide together but nothing is decided if I am not comfortable with it.

RE hormones, generally speaking when it comes to hormones related to puberty I think the typical age these changes begin are around 7 to 13. Statistically speaking, 33 percent of children get better, 33% get worse and 33% stay the same.
Still, I don't simply think my daughter falls into the 33% who gets worse and thats it ... I am not even sure hormones are the culprit here. Again, maybe the drug. In general she has never done well with drugs.

 

[Kgartner]

Ugh, I am sorry you are having such a difficult time right now.

My daughter is also on Onfi. She was on Onfi alone for a few months, and during that time her seizures did worsen. However, we believe that that is due to her underlying condition worsening, not due to the Onfi (for a bunch of reasons which I can explain if you would like). Currently she is on Onfi and Vimpat - she was doing much better for a while once we added the Vimpat, but in the past 2 weeks her auras have increased a lot and she is now having them daily so I am concerned we are losing seizure control again .

However, because of the fact that her seizures worsened after starting Onfi I did ask her neurologist whether he thought the Onfi could be to blame. Have you asked your doctor about that yet? Our doctor said that Onfi is not known to be a drug that increases seizures in people; the main issue with Onfi is developing tolerance, but your daughter's response was so soon after the initiation of the Onfi that does not seem to be the case here.

On the other hand, I do have an online friend who saw new and worsening seizures in her son after he started Onfi, and he did improve when he weaned from it, so paradoxical reactions may happen from time to time. Onfi is a dicey drug for many reasons, and it may be worth trying something different. Even if it isn't worsening her seizures, it sure doesn't sound like it's working very well!

What type of seizures does your daughter have? Certain types of focal epilepsy are often progressive (particularly mesial temporal lobe epilepsy which is what my daughter probably has), so you could be seeing disease progression . But if you could switch off of the Onfi that would help you figure things out. Vimpat has been a good option for us. It hasn't stopped her partials (and as I said above it may be losing its effectiveness), but she hasn't had a tonic-clonic seizure since starting on it 2 1/2 months ago.

 

[jjb]

Oh yes, please do explain all of the reasons for worsening of ONFI.

I so wanted it to work …. I thought it would since we saw such good improvement with ativan way back when.
I am very detailed minded and have been trying to figure out why ONFI could potentially cause a worsening. I think on the original study (posted by the drug company), they did show that 10% had a worsening of seizures (drops). I emailed the company to see if they had an explanation as to why they think this could have happened.


I am concerned EPI wil want to add a drug w/o weaning from ONFI and then ONFI will sabotage the new drug (Vimpat or Keppra) My gut feels we should wean from the ONFI even though that might cause another increase in seizures.

My daughter mainly has focal seizures, both simple and complex. She has scarring from having had a stroke …. so I think she has seizures now due to residual inflammation where the scar tissue is.
Her main seizure symptoms are paralysis, loss of speech, autonomic symptoms and occasionally repetitive myoclonus. She has though had some of the personality changes, confusion etc.
We have never captured an actual seizure on EEG (just the spiking which used to be at almost continuous day and night but is now down to 30 or so % of the time)
Seizure symptoms and location of spiking though suggest she is multi-focal including temporal lobe … including and unfortunately I think medial temporal lobe.

 

[Kgartner]

No problem! I hope this is helpful - although what I was saying was that as far as we can tell her worsening was due to disease progression, not due to the Onfi.

She had her first seizures in September 2013, and had good seizure control on Keppra although horrible side effects. She was very good about taking her meds, but did miss doses of Keppra from time to time with no seizures. It seemed that her epilepsy was going to be pretty easy to get under control. We discontinued the Keppra in April 2014 due to side effects, and actually did not replace it with another AED because we were hoping that what had happened in September (3 seizures in one day) had been a one-time event.

However, she had another seizure in June, and she was first put on Trileptal (allergic), and then Onfi. The Onfi worked great for 3 weeks at a low dose (20mg/day), but then she missed one dose in July and had a tonic-clonic seizure 2 hours later; she had another one that day, and then 3 more the following week. We increased the dose from 20mg/day to 40mg/day that week.

At that point she started having simple partial seizures that did not progress to complex partials or tonic-clonics. This was new for her - up to that point she had only had "big" seizures, although in hindsight she might have had auras 3 or 4 times the previous year (we didn't really know what they were). In August and September her auras got worse and worse, until she was having them almost daily. In October she had two tonic-clonic seizures due to one missed dose of just 10mg the previous night; then in November she had a tonic-clonic seizure without missing a dose and we realized we had completely lost seizure control.

So yes, her seizures worsened when she started the Onfi, but I think in her case that was coincidence because:
- Up until November the only time she had big seizures on Onfi was when she missed a dose; to me that tells me the Onfi was working pretty well, although not well enough to give us a little bit of leeway with dosing. Up until November we could avoid big seizures by making sure that she never ever missed an Onfi dose.
- While the partials only started happening regularly after we increased her Onfi, I think that was more likely due to the 5 tonic-clonic seizures she had the previous week, not the medication increase.
- We did a VEEG in November; her doctors reduced her Onfi by 40% and she had 3 tonic-clonic seizures within 36 hours of that reduction. Again, to me that says the Onfi was working to prevent seizures, not that it was causing them.
- Finally, we seem to be seeing the same pattern on Vimpat that we saw on the Onfi, where it works really well at first and then gradually stops working. So far no big seizures, just lots and lots of auras but I am very concerned that they will be back soon.

My conclusion, and the conclusion of her neurologists is that her epilepsy worsened between June and July, and her seizure threshold got so low that missing one dose of her meds (which had been no problem before) now caused her to have a seizure. Then she had 5 tonic-clonics within one week - which either then caused more damage, or was the result of it. After that, the Onfi worked enough to suppress seizure spread (so no more tonic-clonics as long she didn't miss even one dose), but no longer worked well enough to suppress the initial seizure activity (so lots and lots of auras). And then unfortunately by November it wasn't even working well enough to stop the big seizures.

We are in the midst of having her evaluated for surgery - a left temporal lobectomy. If that is an option we will probably go in that direction, but I'm not 100% certain yet.

Hope this helps! Good luck to you!!

 

[jjb]

It does help and seems quite similar to what happened and is happening to my daughter.
After 1 suspected missed dose she had a tonic clonic. She has only ever had one of those in her life and that was 8 years ago.
Because ONFI has a long half-life, It should not happen so quickly (in fact ER doc thought it could not have been from missed dose because it was too soon) … but the fact that it did happen told me my daughter had quickly become MORE dependent that what is typical (remember ONfi is a benzodiazepine) and suffered withdrawal symptoms harshly.
Following that episode she had more than usual focal seizures including possibly many many more simple focals than ever. So my feeling is she has just become so dependent on ONFI in this short amount of time and the only way to prevent symptoms is to just keep going up and up and up on the dose …. which is not good for this type of drug. So the more I think about it, the more I think my daughters threshold has been directly lowered by the addictive qualities of ONFI.

 

[jjb]

This is what I think may be happening re the ONFI:
This info is re long term exposure to benzodiazepines (but I think the same can happen with even when use has not been long term)

Despite taking a constant therapeutic dose, long-term use of benzodiazepines may lead to the emergence of withdrawal-like symptoms, particularly between doses.[

This is from ONFI info:

In clinical trials cases of dependency were reported following abrupt discontinuation of ONFI. The risk of dependence is present even with the use of ONFI at the recommended dose range over periods of only a few weeks. The risk of dependence increases with increasing dose and duration of treatment. The risk of dependence is increased in patients with a history of alcohol or drug abuse1

I think in general, some people are inherently more vulnerable to physical dependency of certain types of drugs.

 

[Kgartner]

It does help and seems quite similar to what happened and is happening to my daughter.
After 1 suspected missed dose she had a tonic clonic. She has only ever had one of those in her life and that was 8 years ago.
Because ONFI has a long half-life, It should not happen so quickly (in fact ER doc thought it could not have been from missed dose because it was too soon) … but the fact that it did happen told me my daughter had quickly become MORE dependent that what is typical (remember ONfi is a benzodiazepine) and suffered withdrawal symptoms harshly.
Following that episode she had more than usual focal seizures including possibly many many more simple focals than ever. So my feeling is she has just become so dependent on ONFI in this short amount of time and the only way to prevent symptoms is to just keep going up and up and up on the dose …. which is not good for this type of drug. So the more I think about it, the more I think my daughters threshold has been directly lowered by the addictive qualities of ONFI.

Hmmm. Is this your theory, or do your neurologists agree? I have spoken to at least 4 different neurologists about my daughter's situation, and not one of them has suggested this interpretation. I don't feel like I have enough of an understanding of pharmacology to really evaluate whether or not what you are describing is a possibility. Maybe you could explain further, or someone else with more background in the subject could weigh in here.

I guess I'm having a hard time wrapping my mind around the idea that a medication could simultaneously raise and lower the seizure threshold: are you saying that it was lowering her overall seizure threshold but also preventing seizures as long as the Onfi level was kept sufficiently high? I'm not 100% sure how it looked with your daughter, but in my daughter's case the Onfi was clearly working to some degree since it was keeping her from having tonic-clonic seizures (which in her case are typical for her - if a simple partial progresses at all it invariably generalizes to a tonic-clonic). I would have thought that the pattern in my daughter's case would have looked different if the increased seizures were simply due to the Onfi - like at least a few breakthrough seizures without a missed dose. In any case, in the past 1 1/2 months we have been lowering her Onfi very slowly, and that has not been correlated with either an increase or decrease in her seizure activity.

In my daughter's case I guess all of that seems rather complicated. It seems much more likely to me that her underlying epilepsy has worsened, and that any drug might have failed the same way the Onfi did. And given that we are seeing the some of the same issues on Vimpat, I'm afraid that I may be correct.

In your case, I hope that your instinct is correct and that you can eliminate the issue simply by taking her off the Onfi!

 

[jjb]

It is not so much my theory. It is my understanding of benzodiazepines in general.
But yes, one of the doctors I spoke with recently felt it is what is going on. I have not heard from our EPI yet though.
The two quotes I posted above I hoped would explain it.

Onfi is clobazam. While a bit different than other types of benzodiazepines, it is still a benzo and carries the risk of dependency. With dependency or tolerance you can see it work for a bit and then stop.

Dependency and tolerance and other negative effects can occur with many types of epilepsy drug but happens more with the benzodiazepines. Incidentally, Frisium lists possible worsening of seizures especially simple partials. Frisium like Onfi is Clobazam.

Have you heard of the honeymoon effect?
Some people develop a tolerance to epilepsy medication quicker than others. They might get good control with a little while with a drug but then lose it.
The period they see good control they call the honeymoon effect.
Again, it happens more easily with benzodazepines (ONFI, ativan, diastat etc) but it can happen with any epilepsy drug unfortunately. Over the years, I have heard from many parents whose children experience the "Honeymoon Effect" with many drugs they their children have tried.
It is a frustrating thing and I hope that it is not what we will have to deal with should we choose Keppra or Vimpat.

At a recent appt we discussed whether or not we should get off the ONFI before we try something else in the event ONFI sabotages the effects of another drug.
This is where we are now.

I hope if we choose Keppra or Vimpat they help my daughter …. but I know int reality there is probably only a 30 or so % chance that either will help.
I am going back and forth as to whether or not to just do full ketogenic as it is far more effective than for refractory seizures than most epilepsy drugs. Or if we should look into CBD oil … it too seems to be more effective for refractory seizure.

Anyway, here is a bit about the honeymoon effect:
Tolerance and the Honeymoon Effect

The other circumstance in which tolerance can be important in the care of patients with epilepsy is what many refer to as the "honeymoon effect." For some individuals, the effectiveness of medication tends to wear off over time much more than for most other people, either because of the particular way in which their bodies function or because of the nature of their epilepsy and its underlying causes. These individuals often do very well with a new medication for some weeks or, more often, some months. Then the effectiveness of the medication begins to decrease and seizure control gradually may be lost. Many patients who are said to have "medically refractory epilepsy" are those for whom the honeymoon effect is most prominent.

 

[Kgartner]

OK now I get what you're saying! Thank you!

I guess both things could be true - that her underlying condition worsened, which seems undeniable, and that Onfi was not a particularly good choice for long-term seizure control. However, I don't think that the Onfi was therefore the REASON that her underlying condition worsened. We'll just have to see how things develop going forward.

 

[jjb]

I wish you hope and luck in finding the right treatment for your daughter. Of all my daughters health issues, including the stroke, seizures are by far the worse.