Visit From Dr. Narayanan

I just wanted to let you know that while we were staying at the Ryan House this past Thursday night, Dr. Narayanan stopped by to give us a quick update on where we are with the sequencing.  He said that he continually bugs the team to get the results to him ASAP.  I truly think that the TGen team will be very glad once our sequencing is finished.  :)  Anyway, Dr. N said that the current sequencing is complete and the team was working on getting all of the data compiled onto a one page spreadsheet.  Dr. N told them that he would like to have it done by Friday (yesterday) night so that he could take it home with him and begin analyzing it over the weekend.

That is all the news that I have so far, but I just thought I would let you know.  Hopefully soon we will have some more news/information.   We continue to pray for positive results!

Annalise's Results

Last Friday, Annalise had her MRI tests.  A couple of hours ago, I got an email from Dr. Narayanan.  Seriously, does that man ever sleep?  Anyway, here is the official report he got from the radiologist:

MRI is normal, MRA is normal, and MRS (spectroscopy) is normal.

Yes, you read that right.  Normal, Normal, and Normal!  Fantastic news, right?  Yes!  It is, don't get me wrong.  I am thrilled that, like Bryce, she too has shown progress in her myelination.  It gives me a new hope (again) that maybe our children don't have anything seriously wrong with them.  That maybe there is an easy answer and maybe even a cure!  I want to hold on to this hope, to not think any further.

But then I look around and the frustration sets in.  I want so badly to believe that everything is NORMAL with our children, but if this is the case, why is Bryce in a wheelchair, why can he no longer chew, suck, and swallow correctly, why does he stop breathing at times, why does he have to speak with me using his eyes instead of words,  why is he lying on the floor or sitting in a special supportive chair while watching his brothers run, ride their bikes, play ball, play video games and all the other things a NORMAL 6 year old boy would be doing?   Why do I still have two children in diapers?  Why is my daughter unable to run like she used to, why is it getting harder to understand her words instead of easier, why does she wake in the night because of pain and the inability to roll herself over or to get in and out of bed on her own like any NORMAL 4 year old can?

If everything is normal, why is it not?

Dr. N went on to share his thoughts:

"When I look at the MRI - I still have the feeling that there is some problem with the pace of myelin development.  There has definitely been some progress in myelination between 18 months and now; but just not at the normal rate I think.
This is also the same feeling I had when reviewing Bryce's latest MRI.  There is also the report compared to his prior MRI which suggested delay in myelination.  They say that the myelination patter is symmetric, and improved.  They also noted subtle prominence of the cerebellar folia (spaces between the ridges of the cerebellum).

I think this takes us out of the Aicardi-Goutieres syndrome group of disorders.  All the other classical leukodystrophies have been ruled out.  Still can't ignore the mild elevation in CSF neopterin in Annalise.Clinically, they both look like they have some white matter disorder."

He went on to tell me that he has one more hunch and will have to do some work to figure this out.  Didn't tell me what that hunch is, which of course makes me crazy curious and yet at the same time I don't want to know what he is thinking or I will research something else for hours and hours only to find out that it leads to another dead end.  He says that he thinks the best shot is to wait until the exomes on me and John are completed and then we will have a better idea.  I think he is right.  Hopefully this will be available in the next few weeks, he says.  I hope he is right.

I want to stay positive.  I'm trying, I really am.  I don't want to sound negative because the news that we have gotten about the myelin truly is wonderful news!  Definitely a blessing!  I am so thankful that this is what is happening in our children's brains.  

We truly have been blessed with a wonderful man as our children's neurologist.  He is working so hard and coming up short and never giving up.  Even though in so many ways, it feels like we are still so far away from knowing what is going on with our children, there is a part of me that believes the answers are right in front of us.  I can feel it!  If only we knew how to reach out and grab them.  

I know that when the time is right we will know.  I know that the Lord knows.  I know that we have family and friends on the other side helping us...both in finding the answers to our mystery and in helping us be patient until that time comes.  I definitely cannot see the whole picture.  I don't understand why our children have to go through all of this...especially if we do find out that it is something that can be solved, that with some small thing our children can be healed.  Wouldn't that be wonderful!  Oh how I hope and pray that this is the answer that we finally, someday soon will be given.  

We have been talking for a while now about looking into Make-a-Wish for Annalise.  Bryce had his wish granted back in 2010, one month before Annalise was "diagnosed".  It was wonderful and truly a blessing to Bryce as well as the rest of our family.  Something we will cherish forever!  Annalise loves Micky Mouse.  She loves water.  She talks about swimming with dolphins.  I think we will hold off just a bit longer.  Who knows, maybe she won't even qualify for a wish!  Wouldn't that be crazy...and wonderful!

All I know is that through this journey I have met some incredible people.  People who, very likely, I never would have met otherwise.  I have learned things that I never would have learned.  I have become a person who I never would have become without this part of my life.  My husband and all of our children have done the same.  I feel like everyday, even as I continue to learn, the less I know.  One thing I do know for certain though is that there is something so much bigger than us out there.  I know that we have a loving Heavenly Father who is fully aware of who we are and what we need.  There is a plan and every single one of us has a very important role in that plan.   

Not Leukodystrophy

Okay, I know I said in my very last post that I was not going to be continuing with this blog.  Guess what?  I have changed my mind.  I need to continue with the updates on our quest here on this blog...at least until we have some answers.  I will keep the facebook page going because it is a great place for quick day to day updates, pictures, and videos.  This blog will be used more specifically for updates and news on the actual journey to find answers to this mystery.  Then our family blog will be used for, well, everything, including more of my thoughts and feeling on the information I post here!  

So, on to the latest updates.  Bryce had an MRI/MRA last Wednesday.  Thursday morning when I woke up, I found that I had an email from Dr. Narayanan.  He had compared this MRI/MRA to the MRI's done in 2008 and 2010.  He had also read the official report.  He let me know that the MRA was totally normal.  Great news!  This was the first MRA Bryce has had done, so it was good to know that everything looked good on that.

Then things got interesting.  He said that the report stated that the MRI did not show significant abnormalities in myelin, and showed signs of continued myelination!  That is huge.  Do you know what that means?  Somehow, Bryce's brain is actually growing myelin again!   Awesome!   Totally unexpected, but awesome!

Another comment was that the folia in the cerebellar hemispheres were slightly more prominent than before-these are like the sulci in the brain.  I had to google that one and ask some additional questions of Dr. N, but yeah, it appears that this is good news too.

Then Dr. N shared his feeling on the results:

1)  Even though the myelination is improving, it doesn't quite look like it should for a 6 year old.
2)  Not a Leukodystrophy
3)  Still waiting on exomes from the rest of the family.

He then kind of thought out loud for a bit and said, "back to the drawing board".  He asked me to contact our pediatrician and get all of the neurology consultation notes from before Nov. 2010.  He is going to start again from the beginning, rethink through everything, and look at all the data again.

Since this email left me with a few new questions, I emailed Dr. N and got another email back.  I'm posting it here, because it is full of information and helped to explain a bit more of what is happening with Dr. N and the sequencing at TGen.

Dear Tammy:
The latest from TGen.
1.  In the first sequencing runs (whole exome sequencing) they did Bryce and Annalise.  They identified the same SAMHD1 variant that we knew about already.
2.  Based on our feeling that this was too much of a coincidence (clinical suspicion of AGS, elevated neopterin in Annalise; absence of calcifications), we decided that the next step was to see if there was a difference in the expression of the SAMHD1 genes (levels) between dad and the two affected children. We chose dad, because he also has the one SAMHD1 variant.  The idea was that if in the children, the levels of normal SAMHD1 was way low, then this could be why they had symptoms of white matter disorder, without us finding a second mutation.  The RNA sequencing on dad, and two affected children is done; still being analyzed, but a quick look at SAMHD1 levels shows that they have normal levels of the copy that they inherited from you (mom).  so this is not the answer.
3.  We had planned on sequencing (whole exome) mom, dad, and one unaffected sibling.  The preparation has been done, and they will go onto the machine next week, and we should have results in 3-4 weeks.  When we get this, we will analyze the entire family from scratch - without a preconceived notion that this might be AGS or might be linked to the SAMHD1 variant.  Just that it is autosomal recessive, and causes spasticity.
4.  The MRI result on Bryce just makes me question everything - including the idea that this is AGS; it doesn't look like a classical leukodystrophy. But his symptoms with loss of skills, spasticity, fits the AGS model.  Maybe something new.

I have to study this all over again, and having my early notes will help me.
I hope I am explaining things clearly to you.
Hopefully, we'll have more data in 3-4 weeks, and we'll get another attack at solving this puzzle
Vinodh

So there you have it.  You know as much as I know.

Exactly 5 years from the day Bryce began showing symptoms of regression (July 2008), we are back at square one.  The journey is long.  The mystery continues...

Time for Change

I've been thinking about this for a while and I think it is time to make a slight change.  As many of you know, in addition to this blog for Bryce and Annalise, we have a blog for our entire family.  As many of you also know, I have not been doing a very good job of keeping both of these blogs updated like I would like to.  I also feel like the things that I post on this blog belong on our family blog as well since that is basically my journal of our family.  So, as part of my attempt to simplify my life, I am (at least for now) going back to just keeping one blog going.  It will be the one at www.lifeontheclaytonfarm.blogspot.com   I will be continuing to update Bryce and Annalise's journey there as well as the rest of our family's adventures.  For any of you who would like to follow our family there, we would love to have you.

Another way to follow Bryce and Annalise on their journey (without having to read all about the Ho Hum activities of daily Clayton life), is to join the new group on facebook, Clayton's Quest.  I will be using this group page to share brief updates and news about Bryce and Annalise.  Just a warning though, the Clayton Quest group on facebook will include the good, the bad, the happy, and the sad of our journey.  I know some people don't like to hear about the hard/sad things that happen sometimes, but this is our reality and the reality of so many of our friends, so the posts in this group may not all be smiles and sunshine.  Although considering it is a page about Mr. smiles himself and his adorable sister, I'm sure there will be plenty of smiles and sunshine to share!

I plan to leave this blog open and maybe still write on it occasionally, but for now, I need to just have one blog for our entire family as my ongoing journal.  As always, we are so thankful for all of you, your support for Bryce, Annalise, and our entire family, your prayers, well wishes, and all of your heartfelt comments.  Thank you!  We are excited to "see" you soon!

www.lifeontheclaytonfarm.blogspot.com
https://www.facebook.com/groups/401948456587333/

Bryce's Own Option

Ha ha!  Leave it to Bryce to find another option.  If you read my post from last night, you know I was hoping for another option.  Well, in typical Bryce fashion, he has found another one...kind of.

I received an email from Dr. N this evening.  (Yes, on a Saturday.  Any other doctor, that would surprise me...Dr. N...not so much!)  He had a chance to take a look at Bryce's EEG.  I nervously read the email which included this about what he saw:


1)      Mild diffuse background slowing – this is consistent with a diffuse process, such as a white matter disorder; nothing specific
2)      Frequent right central-temporal spike discharge – this means there is a focus that is firing intermittently on the right side; does not mean that he is having seizures, but is consistent with that diagnosis.
3)      The decision about treating him is a clinical one.


He then went on to say what his initial thoughts are as far as treatment goes which will most likely include trying some type of anti-seizure medication.  He will get the official EEG report on Monday and he wants to talk with us next week.

John and I were talking about this on our date tonight.  Frequent right central-temporal spike discharge...John said it is like Bryce's left side of his brain  is tazing his right side.  :)   No wonder he stares off, sweats, and startles so easily!  We have always known that he is a little thrill seeker.  Sometimes you just have to laugh...it's often better than the alternative.

Anyway, so there you have it.  Bryce's mystery continues!  From the very first report that we got when Dr. N looked at Bryce's first MRIs back in 2009 and declared that they, "are abnormal, but not in the normal way." to today's report of he's not having seizures, but he is not NOT having seizure type activity either, Bryce remains consistent in one thing.  Choosing his own route.  He definitely keeps life interesting.

Another Option Please

We have not yet gotten the results of Bryce's EEG although I did get an email today from Dr. N asking me which hospital we went to for the test.  He said he will look up the record and let me know the results soon.  Since it is Friday night, I am guessing that will not be until Monday.  Although with Dr. N, you never know!

Anyway since Tuesday I have been thinking about what the results could be and what I am hoping for.  At first, of course I was hoping that he is not having seizures.  Honestly, seizures scare me and I really hope that is not what is happening.

But what is the alternative?  It is just my imagination and nothing is happening?  No, I'm afraid as much as I would like it to be just my over worried imagination, these episodes are real.  Something is happening.  If it is seizures, the doctor will start him on some medication to help them.  If it isn't seizures, what is it?

After hearing from a couple of friends about what their children have gone through and lots of thinking, I've come up with a couple of other possibilities.  It could be that he is having seizures, but they were not picked up on the 1 hour EEG.  So then the question is, if this one is normal, should we do a 24 hour one to be sure?

Then the other alternative which I really don't want to think about is that it may just be a sign of further progression of the disease.  More loss of the white matter, his body shutting down just a little bit more.  I don't like this alternative because there is nothing anyone can do for that.  However, when I think about it, this possibility seems all too likely.  It seems like if it were seizures, they would have been seen on the EEG a couple of years ago when he was having these episodes the first time.  Or at least they would have continued rather than showing up then and not again until almost 2 yrs later?

So really it seems to boil down to 2 options, either 1) it is seizures which means his disease is progressing, or 2) it isn't seizures but rather episodes of something more going on with the loss of white matter or in other words, signs that the disease is progressing.   I'll be honest with you...I don't like either one of these options and would really prefer another option please!  

EEG

When Bryce and I arrived at St. Joe's Hospital for Bryce's EEG this morning and went to check in at the admitting desk, we found that they had no order for him.  They asked me if I had brought one.  I told them no and that I was just told to have Bryce there by 9 this morning.  He said that he would have to do some calling around and see what had happened.  Well, it ends up that the EEG department called us to schedule an appointment but somehow forgot to send the order for it.  So...we ended up having to wait for about an hour for them to do whatever they do...write up the order, get prior approval from our insurance, etc.  For those of you who know Bryce, you know that he does not like to sit still for longer than about a half a second!  Since we had been sent to St. Joe's instead of PCH, there were no televisions with kids shows on to help entertain him either.  So I did the best I could to keep him from screaming out in boredom.  I really need to get this boy an iPad or something to take with us to appointments like this.

One of his favorite things is looking at pictures and videos of himself.  They crack him up.  So I decided to take some pictures of him.  The funny thing though is that he and his awesome little sneaky fun side threw a little curve ball into the fun.  As soon as he knew I was trying to take a picture of him, he turned away and starting laughing.  I would try to get him to look at me and he would just move into a different position, look anywhere but at me, and laugh like he was the funniest kid ever!  He doesn't have a lot of freedom of movement to do what he wants, so when he finds something he can have control of, he loves it.  He was cracking me up.  He seriously has one of the best personalities ever!

He started it off by giving me this look as if to say, "You want a picture huh?  Well, just try and make me to look at you and smile for the camera.  I dare you!"

Then he moved on to this...

Finally I think he got so tired from laughing that he finally stopped for a moment and actually looked over at me.  He is such a ham!  I just love this boy.

So after about an hour of taking pictures, walking around the hospital, holding Bryce while he twisted himself into all kinds of strange positions, and talking to multiple people who were having fun watching Bryce, they finally got everything in order and sent us upstairs to have the EEG done.  

Bryce wasn't so sure about having things stuck to his head, but he actually did really well, much better than I expected.  

The ones on the forehead were definitely the worst for him. 

 

 All wrapped up and ready for the test.

I was sitting next to him on the bed and they wanted me to keep his hands away from his head and keep his head in this position.  Again, for those of you who know Bryce, you know that he does NOT like to be still.  Explaining to him that he needed to keep his head in this position and keep his hands off of his head meant nothing to him.  Even though I'm sure he could understand what we needed him to do, he is just not able to lie still without having something to keep his smart, little mind busy.   We looked at pictures on my phone and then luckily I was able to find a video for him that helped keep him entertained.  It was also strange for me to have to keep his hands down, because until just a couple of months ago, he would not have even been able to move his hands up to touch his head.   He lost that ability within the first few months of his regression.  That is one of the things that he has regained since we started feeding him real food.  

So overall, the EEG went well.  Of course I don't know what the results of it are yet.  Hopefully I will hear from Dr. N with those results soon.  Then we will decide where we go from there.