February won't cut us slack.

Bertrand coming out of anesthesia in post-op.

He'll be going under AGAIN later this month for his endoscopy.

That's general anesthesia 3 times in little over a month, but who's counting?

After the medical triathlon we'd been running the past several months, we expected a break in February--a chance to settle into a routine with Bertrand's new preschool and therapies. No such luck. Here's a quick recap of Bertrand's week.

Ophthalmology

After being diagnosed with a corneal infection on Monday and going through Same Day Surgery for a biopsy and diagnostics, Bertrand was placed on a full spectrum antibiotic. At his follow-up appointment on Wednesday his eye was pink rather than red and the Doctor pronounced him improved but "not out of the woods". Since then, Bertrand's eye has improved both in color and the white puss patch covering his pupil has shrunken! He has a follow-up on Monday morning where, after a weekend of continued recovery, we hope he will receive the all-clear to resume school, therapies and other outings.

Neurology

We received the medical reports from Bertrand's visit to Cleveland Clinic. (I'll try to condense these in a separate blog post.) Bertrand uneventfully completed his Zonegran wean! He also unintentionally completed a wean from the Ketogenic diet without incident, but we are still holding our breaths. We plan to keep steady over the next 1-2 weeks to give his body time to find its balance after the weans, infection and whatnot. We're waiting to hear back from Bertrand's neurologist at Primary Childrens' Medical Center in regard to initiating a Keppra wean or an increase in Lamictal, but I'll probably have to ping her again within a few weeks. We also have a follow-up with her in early April.

Gastroenterology

Bertrand's gastroenterology appointment on Thursday was the first time he's been congratulated on his weight! He is down to 85 percentile! The GI doctor was also pleased with Bertrand's continued reduction in liver function values. He tentatively approved valproic acid (Depakote) treatment for seizures contingent on continued carnatine supplementation. Given Bertrand's vomiting black chunks (most likely blood clots) during his sickness last week, the doctor would like to conduct an endoscopy to check for stomach ulcers and check for pancreatitis. Both these conditions are very common in "neurologically complicated children" like Bertrand given the number and quantity of medications. New labs will be drawn for liver function, etc. during the endoscopy, and I am waiting to hear back on the scheduling of this proceedure. Assuming--fingers crossed--that the endoscopy is unremarkable, we will follow-up with GI again in June/July.

Genetics

We should be hearing the results of Bertrand's genomic sequencing at Duke in early March.

Bertrand looking a bit shellshocked but grateful to be out of surgery.

Cleveland Clinic MRI Report

EDIT: The "lay interpretation" is that this is about as good a report as we could expect. Findings are mostly, and confoundingly, normal. :)

* * *Final Report* * *

DATE OF EXAM: Jan 6 2011 1:32PM

MRI BRAIN WO CONTRAST
MR SPECTROSCOPY OF THE BRAIN

PROCEEDURE REASON: Epilepsy and recurrent seizures

INDICATION:
Intractable epilepsy and neurodevelopmental delay

RESULTS:
There is bilaterally symmetrical, nonspecific T2/FLAIR hyperintense areas noted in the periventricular deep white matter adjacent to the atrium of bilateral lateral ventricles, extending to the occipital lobes. Compared to multiple prior outside MR studies, there has been interval increase in size of these abnormal periventricular lesions. Small T2 hyperintense white matter foci are also seen within the left front centrum semi ovale (series 5, image 7), nonspecific in nature. No other parenchymal mass, mass effect or extra-axial fluid collections are identified. Diffusion weighted images demonstrate no evidence of restricted diffusion.

The ventricular system is normal in size, shape and configuration. The cortical sulci are unremarkable. No abnormal intra- or extra-axial fluid collections are identified. The midline structures are unremarkable. The cerebellar tonsils are above the foramen magnum. The myelination is appropriate for age.

The major intracranial vessels are patent. The visualized portions of the orbits, paranasal sinuses, and mastoid air cells are unremarkable.

MR Spectroscopy: Multi voxel MR spectroscopy images demonstrate normal pattern. No evidence of abnormal neuronal activity or increased lactate formation is identified.

IMPRESSION: Bilaterally symmetrical, periatrial T2/FLAIR hyperintense deep white matter signal abnormality. There has been mild interval progression of this abnormality compared with multiple prior outside MR_s. No specific associated MR spectroscopic changes. The MR features are nonspecific and the differentials include metabolic, mitochondrial and dysmyelinating disorders. A contrast enhancement MRI may be performed if there is clinical concern for adrenoleukodystrophy.

Cleveland Clinic Wrap-Up

Bertrand coming out of general anesthesia, post-MRI.

Bertrand was transferred from the Pediatric Intensive Care Unit Thursday afternoon and discharged from the Pediatric Epilepsy Monitoring Unit late that night. He is fully recovered from his urinary tract infection and almost fully recovered from his hectic 4-day hospital stay. (A restful sleep in a comfortable bed can do wonders!)

As expected, we came away with no answers, diagnosis or prognosis, BUT a treatment plan has been put into place! While in some ways we learned little from our time at Cleveland Clinic, in many ways we learned a LOT--starting with the importance of proper EEGs, serum medication level monitoring, medical team communication and attention to detail.

Bertrand was asked to return for follow-up in 6-12 months. We'll aim for sometime between August and October at the latest. (Can you tell we've been scarred by all the winter flight delays, cancellations, and reroutings?! Matthew, who was supposed to arrive early yesterday evening, is currently stuck in Phoenix!)

THE RESULTS
Bertrand was seen by experts in epilepsy, neurogenetic/metabolic conditions and movement disorders. He had an MRI, an MR Spectroscopy, over 3 days of EEG monitoring, and blood work.

The preliminary reading of Bertrand's MRI stated that it was unchanged from his December 2009 MRI. The myelination of his brain white matter has neither improved nor worsened.

According to the EEG, Bertrand's main seizure type is myoclonus. He has them in clusters awake and many in his sleep. Many of his atonic episodes were actually large myoclonus. His random laughter is not a gelastic seizure, but rather a reaction post-seizure because it feels good somehow.

Most of Bertrand's abnormal movements are in fact a movement disorder. They are called stereotypies: repetitive or ritualistic movement, posture, or utterance, found in people with mental retardation, autism spectrum disorders, tardive dyskinesia and stereotypic movement disorder.

A few drugs could help a little with the movements, but they wouldn't eliminate the movements entirely. The same drugs also greatly reduce seizure threshold, which is why they should be approached with caution.

Since seizures prove the greater hurdle for development and learning, over the next few months, Bertrand's current drug & diet regimen will be optimized for maximum seizure control and minimum side-effects. This means frequent blood draws to check serum medication and liver function levels.

Speaking of liver function, Bertrand's AST was 83 and ALT was 98. These values are still elevated slightly but FAR lower than the 600s at which they once were! We're not sure if this is simply part of their downward trend (like his AFP), the result of his ursodiol/actigall regimen, or the result of his stem cell infusion last August.

This makes the ideal medication for Bertrand's seizures a combination of lamictal and depakote (valproic acid), or perhaps even just lamictal or depakote. Bertrand was just raised to 100mg daily of lamictal and will need his serum levels drawn for that. We need to keep tracking his seizures.

In the meantime, we will proceed with a zonegran wean, then a keppra wean and then a ketogenic diet wean (or vice versa). All three treatments caused severe sleepiness, reflux, constipation issues, elevated heart rate, bone density loss, and possible kidney stones. He may be able to drop his prevacid (for reflux but causes bone density loss) and miralax along with these.

(I can't even begin to imagine what it would be like! 2 medications instead of 6 plus countless supplements?! Bertrand being able to eat a cupcake at his own birthday?! Without seizing?! It sounds like a pipe dream, but hey, we'll give it a whirl!)

From a testing standpoint, the neurogeneticist seemed pretty impressed with all the testing done so far. For glycogen storage diseases, Bertrand's testing to date had been for carbohydrate deficiency transferase & oligosaccharides--markers for those diseases. While these markers had come back negative repeatedly over the past 2+ years, a new genetic panel for this family of diseases had come out--all 30 can be tested quickly and cheaply--so this was sent out to be done.

Two more X-linked diseases, CDLK5 (another form of Rett Syndrome) & ARX, were put on the table, but since these will be covered by the genome sequencing being done by Duke University (results due late this month or next), these tests were held off on.

We'll stay in touch with the team at Cleveland Clinic while we implement Bertrand's seizure treatment changes. And, when we return in a few months, they'll be able to address more of the movement disorder and neuropathy/demyelenation aspects of his condition. (He'll see FOUR neurologists at Cleveland next time!)

Wordless Wednesday

A Slight Detour

Matthew comforts Bertrand.

Bertrand has a habit of keeping things interesting for medical personnel, and he wasn't about to cut the staff at Cleveland any slack!

After sleeping most of the morning away, this afternoon Bertrand woke up with some labored breathing, and proceeded to pee some blood. Twice. (Urine cultures are pending.) His pulse and heart rate were elevated. Upon checking his O2 saturation, it was between 82 and 86%. The respiratory therapist didn't like the look or sound of his breathing. He was put on oxygen. (Bertrand is at 95% with 1.0L.)

The pediatric team was called in. Also not liking Bertrand's breathing, the sound of his lungs and elevated heart rate (165!), the pediatrician and attending neurologist admitted Bertrand to the Pediatric Intensive Care Unit (PICU). Chest x-rays have been taken, blood has been drawn, IV fluids have been started (Bertrand has refused to eat or drink since 1pm), and a urine catheter will be started.

He has since had another diaper with a bloody casing. The working theory is that at best Bertrand has a urinary tract infection. At worst Bertrand is developing kidney stones--on the ketogenic diet and on zonegran these are very common. It's not pleasant, but Bertrand is in as good a spirit as could be expected. And, if there were ever a time and place to get sick, while inpatient at the Cleveland Clinic, one of the world's best hospitals, is it!

Mission Impossible? Or Mission I'm Possible?

Bertrand wasn't glad about all the measuring and attention to detail, but mom & dad sure were!

We arrived at the Cleveland Clinic on Sunday afternoon, had our first appointments on Monday, and last night was Bertrand's first night staying inpatient. (His room is M52-05 in the Pediatric Epilepsy monitoring unit.)

THE HOSPITAL

Before arriving at the Cleveland Clinic, we'd heard it described by friends as "medical Disneyland", so our expectations were set pretty high. The Clinic hasn't disappointed!

It is a MASSIVE, multi-block medical complex, interconnected by skyways (extensively peppered with flat screen TVs) with optional patient shuttles.

The main hospital building could double as a museum with its soaring architecture and world-class art exhibits. (I could dedicate a post to this aspect alone!)

The specialty gift shops--yes, plural--include a bookstore, spa shop, clothing boutique and typical gift shop. They are larger than your average grocery market.

Much to Matthew's delight, dining options include everything from gourmet caffeteria to McDonalds, Starbucks and Au Bon Pain to the award-winning restaurant, Table 45.

And, the four lodging establishments located on the medical campus run the gamut from Ronald McDonald House to the Intercontinental.

The prior amenities are just scratching the surface.

I'm surprised I haven't seen a waterslide--then again, I probably just haven't found it yet.

Obviously, the most attractive feature of the Cleveland Clinic--the one that has us & people from all over the world traveling here--is the world-class medical staff.

NEUROMETABOLIC / NEUROGENETIC SPECIALIST

Bertrand's first appointment of the day yesterday was with Dr. Sumit Parikh, and I'll be upfront by saying I came out of that appointment with a crush on him. ;) Heck, I think Matthew, Diane (Bertrand's nana) and even Bertrand himself came out of that appointment with a crush! It is unbelieveably rare to find such a combination of expertise, attentiveness and compassion.

To him, an expert in neurometabolic, genetic and mitochondrial disorders, while Bertrand appears to have a genetic disorder, he appears neither metabolic nor mitochondrial!

Given the early onset of B's condition, his liver function improvement, and relatively stable condition, if it were a metabolic condition Bertrand would be far worse--if not dead--by now.

As far as a mitochondrial condition goes, while we could consider a conclusive muscle biopsy, Bertrand lacks several key chemical and physical indicators (lactic acid, hypotonia, etc.).

PEDIATRIC EPILEPTOLOGIST

The following appointment was Bertrand's first ever with a REAL epileptologist, Dr. Deepak Lachhwani. Dr. L has experience with children seemingly similar to Bertrand!

Since he was a last minute substitution to Bertrand's medical team, he hadn't yet read Bertrand's medical file--this is a PLUS. I couldn't be happier that Bertrand's seizures will be viewed through a fresh set of eyes, untainted by potential metabolic, mitochondrial, genetic or other considerations, especially after our meeting with Dr. Parikh.

He will proceed as if intervention, pharmacological and/or surgical, is still an option. (Many of Bertrand's prior doctors discounted intervention right-off-the-bat on the assumption that nothing would work effectively in the case of an inborn error of cellular metabolism.)

After reviewing Bertrand's prior MRIs, he may order a new MRI or PET scan if indicated.

ELECTROENCEPHALOGRAPHY (EEG)

Bertrand had 3 EEGs in 2009, 6 EEGs over the course of 2010, and his first ever EEG done right in 2011. I'll admit to feeling simultaneously shocked, incredulous, awed and furious.

Bertrand isn't your typical kid with a febrile seizure or epilepsy. An EEG should do more than prove "yup, he had a seizure". (NO DUH. He has seizures.)

An EEG should provide information--usuable information--on where his seizures are originating, how/if they generalize, how they manifest... A potentially MAJOR puzzle piece.

This seems obvious, right?

Wrong.

At other locations, which shall remain nameless, they just slap leads on haphazardly without measurement, never check if equipment is working, there is never a nurse response, video isn't adjusted, techs aren't monitoring the child remotely, conductive gel isn't reapplied, results take weeks... I could go on and on but I get enraged thinking about it!

At noon today, an entire team of doctors will come in to speak to us personally while Bertrand is still inpatient to discuss his EEG--which they have already read!

(Anyone who knows me can probably visualize how this makes me want to tear my hair out, bash my head against a wall AND hug someone all at the same time. I'm not dramatic at all.)

NEW YEAR'S RESOLUTION GONE BUST

I happen to LOVE making new year's resolutions. Every year I make just one resolution and I keep it. This year, my resolution was "no expectations".

I spent most of 2010 horribly disheartened by shattered hopes--disappointing ketogenic diet results, ACTH, hospitalizations, broken bones, zonegran, miscarriage, etc. 2010 was not a bad year, but having to pick myself up repeatedly after each instance was HARD.

So, by "no expectations" I meant that I would continue to do my best without emcumbering myself with a set expectation or any false hope. Unfortunately, I may have made a resolution I can't keep.

Apparently, I am hardwired for hope. Subconciously I grasp onto any shred of possibility and I make camp in crevises of ambiguity. The past 24-hours at Cleveland, I did more than make camp--I built a castle.

Doctors haven't even read Bertrand's EEG and in my dreams I was seeing Bertrand with some seizure control, taking him off of keto, weaning his zonegran AND keppra, & feeding him finger foods in his high chair. I woke up wanting to scream at my trecherous dreams!

I can say "no expectations" all I want, and spout off about the importance of quality of life all I want--my subconcious knows the truth. In the face of the impossible, I'm still trying to "fix" my baby.

I guess that makes me a mom.

"Prepare for glory!"

Some things simply require a ridiculous photoshop.

Tomorrow we fly to Ohio. Bertrand will see a team of neurologists at Cleveland Clinic whose areas of expertise range from epilepsy to neurogenetic/metabolic disorders to movement disorders. Going into this, we know that there won't be any answers or diagnoses or cures. At best we'll get a stopgap treatment for some of his seizures.

In 2007, the year Bertrand was born, the movie "300" was released. It was based on the tale of the Spartan king, Leonidas, who fought with 300 men to stall a Persian invasion of Greece. Knowing there was no chance of surrender, retreat or even victory, they fought anyway.

So do we.

Holiday Update

Bertrand is cuddled by his 1st Lt. Uncle John during a post-lunch nap.

Our family is spending the first half of this holiday season in Park City, Utah at Bertrand's grandparents' new house. Bertrand is enjoying every moment! He is clearly a winter sports guy if those sports include: being pulled in a sled, hiking via kelty backpack, and sitting by the fireplace. Oh wait, that last one is *my* winter sport! ;)

It's been a relief having extra pairs of hands and eyes around to care for Bertrand. The introduction of a new seizure medication, Lamictal, had me particularly worried due to potentially fatal side-effects such as Stevens-Johnson syndrome and liver failure.

However, so far Bertrand is doing great! In less than a week on Lamictal, all of his seizure-types have seen significant reductions. For example, his atonic seizures were down to 2 yesterday from 30+ daily a week ago. (Today, he hasn't had any! Knock on wood.)

Even more telling than the number of clinical seizures (since so many of his are sub-clinical) is the eye-contact, the number of smiles and daily laughter! We couldn't have received a more beautiful and perfect gift than hearing our son's joy manifest itself!

Lamictal is a drug with a long half-life, so we are no where close to seeing its full effect. Bertrand is on day 6 of taking a 25mg orally disintegrating tablet (ODT). His final dose of 100mg will be reached mid-January, and full effects won't be seen until early February.

Potentially complicating this titration are several factors: upcoming travel, hospitalization, potential sickness, changes in school/therapy schedules, and a wean from zonegran. Timing the wean from zonegran--should we start in February? or start next week?--consumes my brain.

Bertrand stands to gain as much as 6 hours of consciousness back each day since that drug has made him so sleepy without contributing any additional seizure control. But, in November, reducing the amount by 25mg caused a temporary increase in seizures while his body adjusted.

The scientist in me has no doubt that we should hold off on the wean until we can hold other factors as stable as possible. The mother in me simply wants her baby to stop suffering from the drug's awful side-effects as soon and as safely as possible. Can there be compromise?

On the non-pharmaceutical front, Bertrand will be alternating occupational and physical therapy at Shriners Hospital every Tuesday, starting the 2nd week of January when we return from Cleveland Clinic. And speaking of Cleveland, these are the updates to B's team there.

• Sumit Parikh, M.D. - neurometabolic & neurogenetic specialist
• Debabrata Ghosh, M.D., D.M. - movement disorder specialist
• Deepak Lachhwani, M.D. - epileptologist

Cleveland Clinic, here we come!

Picture from OneMedPlace

Bertrand will FINALLY be seen at the Cleveland Clinic! Cleveland Clinic's neurology program is currently ranked #1 in the US. (Coincidentally, it also performs the highest number of pediatric epilepsy surgeries in the US--not that Bertrand is a candidate.)

We'll arrive on January 2. Bertrand will be admitted on January 3rd. And, we should be home by January 7th. Among the specialists Bertrand will see are Drs. Ajay Gupta and Sumit Parikh. Dr. Gupta is an epileptologist and Dr. Parikh is a neurometabolic/neurogenetic specialist.

We don't expect a diagnosis or, realistically, even treatment. (At best we can address his seizures but not the underlying condition causing his white matter loss, liver and nerve damage.) We're just confirming that we've done everything we can for Bertrand and hoping to improve his quality of life.