A "fail" for Phenytoin

Haya and me walking in the kitchen seven days
after we stopped the Phenytoin

One week after starting her on 100mg/day of Phenytoin [background here], Haya had a couple of horrific days, seizing terribly and for hours on end. Nothing I gave her stopped them.

On the second horrific day, after five hours of that hell I wrote her new neurologist about it. But even before her response, I just stopped administering it.

 
She emailed us, agreeing that in rare cases this drug can exacerbate instead of improving the situation. 

I pointed out to her that on the day of five hours worth of convulsing, Haya also had a bloody nose and her menstrual period. Now, she never gets the former, and hasn't had the latter in about a decade. The neurologist attributed the bloody nose to our dry weaather. I doubt that; we often have dry weather but, as I noted, never a bloody nose. The menstruation stumped her. 

Well, the nose dried up quickly. The period, though light, is still ongoing. All very strange.

 
So we're back to square one with medications. 

The neurologist hasn't suggested any others to experiment with. I hope she won't jump to the second option she mentioned after medications: the Ketogenic Diet. I haven't got the stamina for that anymore. 

I was some twenty years younger the last time we attempted it. We persevered then for 10 months and only ditched it when Haya began vomitting several times a day from the high fat content. 

The neurologist was pretty eager for us to try it when we visited her two months ago. But she seemed even more eager about the Vagal Nerve Stimulator surgery. The idea of surgery leaves me positively cold particularly since a surgeon warned us a couple of years ago that it would be "complicated" in Haya's case. She has had an old, non-functional VNS stuck in her neck since 1999. It is undoubtedly coated with all sorts of tissue by now.

So Haya is back to seizing quite a lot and functioning poorly. It is a bleak situation and her new diagnosis of Epileptic Encephalopathy Early Onset 11 due to an SCN2A de novo mutation only bleakens it more.

The academic articles about her syndrome which we receive thanks to Google Alert make it clear that there is currently no salvation our there for Haya.

This last one, for instance, taught me that her current seizure situation qualifies as Status Epilepticus.

Next Up: Phenytoin!

Haya's first dose of the new med last night

Very excited to share that Haya will finally try out a new anti epileptic - one that has been found successful in a significant percentage of EIEE11 cases. It's the first med change we're making since her diagnosis with that syndrome three months ago (see "At last - a pretty solid diagnosis")

I loathe giving her three anti-epileptics at once. But as the neurologist emphasized, the cardinal rule is one med change at a time. Once Haya's settled into the therapeutic dose of Phenytoin (also sold as Dilantin and Phenytek), the doctor promises to remove at least one of the others. 

She even asked me whether I thought either of them is effective. I told her I couldn't judge but did remember which was added last, Vimpat (lacosamide), and didn't think it had made a difference. 

The truth is, her other med, Keppra (levetiracetam), isn't anything to write home about either. 

I got the script for Phenytoin yesterday. And the photo above shows Haya getting her very first Phenytoin pill sold here as Epanutin.

When Haya's pediatrician heard that this was the drug selected by the neurologist, he was surprised. "When I was doing my residency, back in prehistoric days", he recalled, "we had only two anti-epileptics to administer: phenobarbitol and phenytoin. There are so many new ones on the market now." 

But those new ones just don't help Haya. Wikipedia says:

Phenytoin was first made in 1908 by the German chemist Heinrich Biltz and found useful for seizures in 1936. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.

Here's hoping that stellar reputation will prove well deserved!

Welcome to my SCN2A world

From a 2017 overview about the current knowledge
of SCN2A disorders, presented by Dennis Lal
of the Stanley Center for Psychiatric Research at the
Broad Institute of Harvard and MIT [via YouTube]

After a hectic period laden with stressful but (thank G-d) joyous events, I can finally refocus on this blog. 

First, to recap.

We now have a pretty firm diagnosis for Haya's symptoms after a 24 year hunt. 

While it is a de novo mutation of the SCN2A gene i.e. not hereditary (yay!), it has been an otherwise distressing discovery. That's because there is simply no effective treatment for it. 

The mutation causes a particularly severe and refractory epilepsy: Epileptic Encephalopathy Early Onset 11. It's sometimes called Early Infantile Epileptic Encephalopathy Type 11, and sometimes EIEE11.

Available anti-epileptic drugs are almost invariably useless, something we'd already concluded on our own after Haya's 24 years of relentless seizing.

Nonetheless, last month we brought Haya to a pediatric neurologist whom our geneticist had recommended highly. (She's booked up for the next year).

At that visit, she assured us she would study Haya's EEG's and her history and would then suggest medication changes as a first step. True, after the years of the med failures we've had, any new ones have no more than a 3% chance of success - but that isn't zero, as the doctor noted. 

So we all agreed it's the wisest first step.

Next, if we find Haya to be in the 97% majority med-wise, this doctor recommended we re-try the Ketogenic Diet. We had Haya on that diet some twenty years ago with minimal success and dropped it after 10 months because of serious, uncontrollable vomiting. 

 
But, as the doctor noted, we had had no professional guidance in calibrating the diet. So giving it a second shot with good medical intervention this time sounds wise.

If that diet fails again, she recommends going with a second VNS implantation. 

That was also a failure back in 2000 and we were bereft of sound medical guidance then too. So while I'm reluctant to subject Haya to surgery but if there's no alternative, we'll try it.

I also set up a Google Alert for the SCN2A gene and Epileptic Encephalopathy Early Onset 11. Not one of the journal articles I've been sent so far are relevant or helpful. Most weren't even about that gene! Are you listening Dr. Google?

Now a request.

The new neurologist, when I asked her, said she has no other patients with this syndrome. Our Haya, I think, may well enjoy the distinction of being the only such person in Israel.

If you know of anybody afflicted with it, please let me know. I will give you my personal details if requested in a blog comment.

At last - a pretty solid diagnosis

Let's hear it for the whole exome sequencing (WES) test and the Ministry of Health! (After all, it picked up the tab.)

After 24 years, we finally have a pretty solid diagnosis for Haya's symptoms; idiopathic has been officially deleted from our lexicon.

What was found is a mutation on the gene SCN2A. We learned the news in the geneticist's office which we entered and exited in 15 minutes.

A couple of weeks later, we received a more detailed summary of the findings which told us, among other things that a genetic variant was found which is designated VOUS or Variant of Unknown Significance on the gene SCN2A on Chromosome 2, exone 5

Mutations elsewhere on this gene are known to be the cause of Early Onset Epileptic Encephalopathy Type 11 (or EIEE11), a syndrome with symptoms identical to Haya's. 

While Haya's variant is on a spot where no other person is known to have one, the geneticists concluded that because 

"her clinical picture matches the clinical picture described in the EIEE 11 Syndrome, we are inclined to say that there is a high probability that the variant found in checking SCN2A which is described in the gene exome constitutes the cause of her illness... The laboratory in Germany that carried out the test concurred that the finding is a possible identification of the cause of her illness... It can be said with high likelihood that the parents and their offspring are not in any increased danger of a repeat of this anomaly in future pregnancies."

The geneticist recommended we consult a young local pediatric neurologist who might have some fresh treatment suggestions. She also promised to send Haya's file to a neurologist in California who is researching this very syndrome.

But trusty Google has provided precious little further info. We now know that this diagnosis is rare, still being researched and that at this point, no reliable treatments are known. 

We're hoping that one of those two new neurologists will help us. It's the nearly two and a half decades of clueless doctors that I've been vividly recalling. Clueless and arrogant.

There was the developmental pediatrician who was the first specialist we consulted. He summoned his entire staff at the Center for Child Development, which he headed. into his office one morning while he examined Haya. With utter confidence, he declared to his audience that she had been infected and damaged by CMV in utero. The trouble was, the blood test which I subsequently had proved him just as utterly wrong. I hadn't had CMV during my pregnancy.

That didn't phase the guy. Several months later, he declared to me with the same utter confidence that Haya had Rett Syndrome. At the time, there was no blood test to contradict that wild guess. But her then-neurologist pronounced it a false diagnosis. She didn't have any of the major symptoms, one being the "hand-washing" which had prompted Dr. Andreas Rett to classify this group of children as distinctive. 

A few years later, Israel's chief Rett expert examined her and declared that her gait indicated that Haya was indeed a Rett child. But when new blood tests finally appeared on the scene, they proved definitively that Haya did not have Rett.

I also recall another neurologist's declamation to me when Haya was about a year old: 

"She does not look like a child with a genetic disorder. It's not genetic." 

He also advised us to "send her away to an institution."

By now I'm sure it is clear why I am not a huge fan of neurologists. (You can read more about how I developed that distaste for them here: "A hospitalization journal".)

The silver lining to this bleak news is that the mutation is de novo. That means it wasn't inherited and, consequently, is of no concern to our offspring. Its de novo-ness was confirmed by doing the same whole exome test for me and my husband which proved that neither of us carries that mutation. 

One article I read posited that the most severe SCN2A cases are the de novo ones. A cloud in the silver lining?

One article that our son-in-law, a doctoral student of genetics, found us reports surprisingly encouraging results with unusual drugs. Conventional anti-epileptic drugs, it seems, actually exacerbate seizures for some Early Onset Epileptic Encephalopathy 11. 

But two drugs that are not intended to treat epilepsy were effective. Could that be why we find that Paracetamol helps her during a string of seizures?

In the meantime, here (above) is Haya showing slight progress with pushing her switch to play music.