Sunday, February 12, 2017

A Funeral, A Birthday, 2 IEPs, and Ophthalmology

I truly don't think the last 10 days could have possibly been any busier. My head is still spinning from the non-stop, tumultuous few weeks we have been experiencing here. Unfortunately, it all started off with the passing of Sarah's uncle Jamie, who was a huge part of Sarah's life growing up here in Kansas City. He was an incredibly thoughtful person, making you feel involved and important with every encounter you had with him. He was engaging and sincere - he will be missed dearly by everyone in our family.

With Jamie's passing and the funeral mid-week, our days and evenings were occupied, gathering pictures and exchanging stories with relatives that managed to make it in town. On Wednesday, we attended the funeral and luncheon afterward, which trickled into the late afternoon, eventually leading into Eli and I spending the evening at his 9th grade enrollment activities, at his future high school. I cannot believe I am going to have a high school age child in another 6 months. Eli had an equally busy week, with mid-week enrollment choices and then celebrating his 14th birthday tonight! He has been saving up the money to build his own computer, researching and buying the parts over the past 6 months and with the birthday presents he received tonight, his build is nearly complete.
Prior to the funeral, we had 2 IEPs, sandwiching the weekend - one on Friday for Mira and another on Monday for Jonah. Both were fairly uneventful and there weren't a whole lot of changes for either one of them from last year. However, we did discuss Mira's diet some, coming to the conclusion that she should have the opportunity to try some of the school lunch offerings. The cafeteria staff has to puree her foods, as they do with some of the other students in her class, but it would give her the chance to eat with other kids in the cafeteria. This past week they started initiating this plan and Mira has been able to sample a variety of different foods, including broccoli, mashed potatoes, and a few desserts. Her teachers and paras noted that she was very enthusiastic about it all too. We have had our reservations in the past of pureed foods, as she used to gag on some of foods we offered, so we eased up years ago and kept her primarily on a bottle diet. Speaking of which, Mira seems to be gaining some weight since we upped her calorie intake. I can't give an exact amount, but it is visible in her legs and arms - she is looking fuller and certainly feels heavier when we are transferring her. Yes, not a very clinical analysis, but I can assure you, she has put on weight, which is great.

To finish off our insanely busy week, we had an ophthalmology appointment for Mira on Friday morning. Right after getting settled into the exam room, Mira had a huge tonic-clonic seizure, knocking the bottle I was giving her clear across the room, dousing the nurse with a spray of rice milk and protein powder. Mira was post-ictal during the exam, which made it a little challenging for the ophthalmologist to get an updated script for her. It took us months for us to get an appointment on the books, thus it was all just unfortunate timing that Mira has an enormous seizure right then. By the end of the exam, Mira was still having some dystonia and odd movements, but they were able to give us an update on her vision. Basically, her astigmatism is slightly worse and her vision overall is slightly worse, but perhaps not enough to warrant getting a new pair of glasses. Based on the discussion we had the week before with the vision specialist and our most recent conversation with the ophthalmologist on Friday, the recommendation was for Mira to have an ERG done, as she has not had one for 8 or 9 years, when she was being monitored in Saint Louis for retinal toxicity while she was taking Vigabatrin. The feeling was that is would be a good idea now to monitor her retinal activity and for us to understand where she is at in terms of her overall vision picture.
Mira had a rough day after leaving ophthalmology - she continued to very lethargic and altered, having an afternoon of dystonic movements and small seizures. We ended up keeping her home the rest of the day and ultimately, we had to intervene with Diastat to try and break the cycle of seizure activity by mid-afternoon. She has had many of these episodes over the years, with a spike of activity over the past 2 years. Fortunately, the dystonia never seems to last more than 24 hours and Mira quickly rebounds. She was a little lethargic on Saturday but we had spectacular weather (60 degrees, breezy, and sunny) so Mira and I spent a lot of time outdoors going on walks. We did the same today, although it was colder and overcast. Mira didn't seem to mind. 
Jonah was battling a fever and cold most of the week, missing school Thursday and Friday, thus we ended up taking him to Mira's appointment with us. His fever broke on Saturday and today he is back to his old self. I could tell you that the next two weeks are going to be easier, but I would be lying. I have to head to New Brunswick this week and Virginia the week after, which leaves Sarah to hold down the fort while I'm gone. 

Thursday, February 2, 2017

Vision Specialist

Today we met with ophthalmologist expert here in Kansas, who specializes in children with significant visual issues, particularly  Cortical Visual Impairment (CVI).  CVI is basically a disconnect between what the eye(s) see and the brain interprets - it is more of a neurological impairment than an actual visual one. Mira was diagnosed with CVI when she was very young and ended up receiving services through CCVI (Children's Center for the Visually Impaired) here in Kansas City, until she aged out of the system and entered the school district. Because of her constant neurological flux (hypsarrhythmia) it is extremely difficult for Mira to focus on much, if anything, for an extended period of time. Coupled with her extreme myopia, her actual visual processing ability is speculative at best. We do know that she can focus on her toy - the bright lights and motion are able to capture her attention, when she is in the right mood. The vision therapist she saw today was able to look at Mira's background and history to see if she could benefit from other alternative therapy approaches, so that Mira can reach her full visual potential. There wasn't any significant revelations during the appointment, however, it was great to hear someone else's expertise on how we might be able to help further her skills. Mira was able to maintain her composure throughout most of the appointment, although is slowly mastering her slouch in her new chair. An hour into the meeting, she had pretty much checked out and was ready to move on. We have an ophthalmology appointment next week, which will be interesting to find out if Mira's vision has changed at all over the last 12 months.

Tuesday, January 31, 2017

Mira's New Chair

Mira's new chair arrived today! While it is technically the same chair (a Quickie Iris) and only slightly larger to accommodate her future growth, it feels like it it so much bigger. Perhaps it is our tiny house with narrow doorways, or the new tray attachment, but it just feels enormous. Her tray and easel are certainly wider than her current chair and they barely fit through the doorway to her room. Her easel has adjustable knobs on each side, which allow it to tilt on the tray, but unfortunately, they protrude out much farther than her old tray, and they nearly hit the door jambs and the narrow hallway to her room. The new headrest feels more secure and has more of a curve to it, for better head support on the sides. The footrests are also very stout and did not come with foot pads. Mira kicks with her heels so much on the footrests, that she has destroyed her last set, so we figured it didn't make sense to get any on her new chair. She kicks with the heels of her feet just for sensory input, so the pads weren't necessarily providing any real protection. The biggest change is perhaps, the color - it is dark purple in color, much darker than her current pink chair, which we couldn't get because they no longer supply the Quickie in that particular color. The process with the seating company went very smoothly this time, a far cry from our last interaction with her previous chair, over 4 years ago. The company has since changed names and ownership, all for the better. While we met with the same sales rep before, however the communication and exchange was fairly painless this time.

Monday, January 30, 2017

Melissa Officinalis (Lemon Balm)

While we are continuing on this theme of alternative herbs, I wanted to offer up lemon balm (melissa officinalis or I will use the acronym LB) is often lumped into the same category as bacopa monnieri. LB is recognized for having a calming effect, often categorized as a natural anti-anxiety treatment. In terms of seizure control, most of the articles that I have come across are limited to animal studies, including this one, and this one, and even this one. While the effects of LB have all been positive in every study, there are few human trials that have been documented, although the conclusion reached from all of those studies were that there was 'insufficient evidence to support a well-established use monograph'. Also, while no adverse effects were recorded in any of the human trials, the half-life of melissa officinails seems to be very limited, offering little extended protection beyond a few hours, in terms of effective seizure control or as an anxiolytic. One of the most promising trials I have read in regards to LB is located here. The phytochemical mixture used in the study (Cyracos) can actually be purchased OTC by a variety of suppliers. The efficacy of this particular LB mixture was much more effective at alleviating symptoms of anxiety, at a higher 600mg dosage. Lemon balm didn't appear to be much of an option for Mira, as most of the anecdotal data I have read has to do with it being an anxiolytic and perhaps not effective for seizure relief. Nonetheless, it might bring some value in reducing Mira's irritability.

Saturday, January 28, 2017

This Week with Mira

This week was a busy one for everyone, but most of all for Sarah. On Tuesday, I had to leave for Boston and didn't return until Friday evening, which left Sarah to hold down the fort for 4 solid days. Since the kids didn't have school on Friday (teacher work day) it made the stretch toward the work week finish line even more of a challenge. Mira was very up and down for the entire week - some days she was in decent spirits, but her shifting moods have been difficult to predict, and to try and redirect. For instance today, we had one of those days where nothing would satisfy Mira's fussiness for more than a a  few minutes, unless of course, you were walking. Thus, we took several walks today, all in the afternoon, when she was at her lowest. We ran some errands this morning which she tolerated for awhile, but soon expressed her lack of interest by squirming in her chair, while getting increasingly upset. She couldn't stand not being in constant state of motion. On our walks, she would only get irritable whenever we stopped. We went down to the village (our local shopping area a few blocks away) and with each stop, in each store, she raised the cranky bar one more notch, until we were back on the sidewalk. She ultimately settled down after dinner, but at the end of it, this Saturday was just 'one of those days' for her.

Vitamin D + Vitamin A

There is a lot of research that exists on vitamin D, particularly in relation to depression, autism, seizures, and a host of other neurological manifestations, that supposedly stem from having low vitamin D levels. Referred to as the 'sunshine' vitamin, vitamin D is a fat-soluble (can be stored in the body) and its main function is to promote calcium and magnesium absorption in the gut. I won't go into the specifics, as they can be explained much more thoroughly on this site than I could ever do justice.

I have always maintained a certain level of skepticism with vitamin D, since to me, it really isn't a vitamin at all - it's a steroid, that ultimately can affect hormone levels in the body, which in turn affect the entire equilibrium of the endocrine system. Touting vitamin D as the savior for combating all of these different illnesses raises a number of questions for me and there is certainly an endless amount of literature to address my inquiries. Just search through Pubmed and you will discover enough reading for all of 2017. Vitamin D is implicated, in terms of epilepsy alone, in everything from hypocalcemia to influences on AEDs.

Vitamin A on the other hand is a bit of an anomaly when it comes to the implications on seizures and autism. Vitamin A is also a fat-soluble vitamin, nearly synonymous with, on every single health website imaginable, the word 'vision'. While its importance to the cornea cannot be ignored, the vitamin's influence on other organs should not be understated. Just like vitamin D, vitamin A can also influence hormones.

So what is the potential connection between D + A? I have been asking this same question, as I have gone through a ton of anecdotal stories regards the efficacy of both vitamins, on seizures and autism. Some medical professionals have even gone so far as to develop a high dosage protocol for the treatment of autism in particular, for both vitamin D and vitamin A. There are message boards that have extensive threads on this very subject, most of which reference one single source: The Vitamin D Council, which is less of a populated 'council', as it is the compiled research of one person, Dr. John Cannell,  and you should note with full disclosure, he specifically endorses one particular brand of vitamin D, developed by Biotech Pharmacal. I'm not sure exactly why this particular balance of vitamin D3, vitamin K2, magnesium, zinc, and boron are considered an exclusive proprietary blend that they need to be endorsed, with Cannell potentially being compensated for, as there are hundreds of supplements on the market, but I digress. Regardless, Dr. Cannell's commitment to researching the effects of vitamin D should not go unrecognized. His agenda seems very simple - most of the general population is deficient in vitamin D and everyone who is deficient, should be supplementing to some degree. In terms of vitamin A, no such council exists as far as I can tell, thus there is no single unified source of literature to comb through.

There are connections between D + A and they revolve around the mechanism of action. The one that I started focusing on was the idea that both vitamins can influence voltage-gated calcium channels (VGCCs). You've probably heard me mention this in the past, as VGCCs are the supposed mechanism of action of Lyrica (pregabablin) which is a medication that Mira has been on for years. The function and pharmacology of VGCCs are nicely organized in chart here, which as you will read, influence everything from nerve terminals to endocrine cells. VGCCs have been the focus for therapeutic studies for some time - here is an extensive technical paper on the subject. If vitamin D can affect the 'fluidity' (so to speak) of VGCCs, are there antagonists that do the exact opposite? As it turns out, there has already been some research regarding the antagonistic relationship between vitamin A and vitamin D. I also found a great article that highlighted the concerns of excessive or even additional supplementation of vitamin D in relation to autism, from more of a historical perspective.

Saturday, January 21, 2017

Bacopa Monnieri

I have researched a number of alternative therapies for the treatment of epilepsy and one of the more interesting ones I found was bacopa monnieri (BP or just bacopa). Bacopa is a flowering herb, with supposed medicinal properties that is more commonly used in Ayurvedic medicine, for the treatment of everything from seizures to asthma. The investigated chemical(s) within bacopa that provide the actual therapeutic effects are bacosides, which are often recognized for their neuroprotective qualities. The bacosides have also been researched for their effects on blood flow, memory, antioxidant activity, and acetylcholine levels in the body.

I was most interested in the research on bacopa's effect on seizures, which is fairly limited in terms of solid human trials. There is a brief abstract here, but most of the other studies I came across were only animal studies. This full article and references can be accessed here, which offers some interesting details on the effects of bacopa on a host of different neurological issues. In the studies that actually listed the extract details, the range seemed to be anywhere from 30-60% bacosides, which is comparable to what you would find in any OTC bacopa supplement. Most supplements range from 20-50%, depending on the extract and/or manufacturer. In terms of seizure control, based on what I read, the effects of bacopa were all over the place, somewhat speculative, and again, limited to studies primarily on rats. The mechanism or potential actions included:

Raising serotonin (5-HT) levels in the brain
Reduction of oxidative stress
Prevention of glutathione reduction in the body
Potent antioxidant (greater than vitamin C)
Possible dose-dependent metal chelator
Glutamate excitotoxicity mediator

Out of all of these proposed positive impacts on cognitive processing and/or development, I found the elevation of 5-HT levels to be the most interesting. There seems to be a strong relationship with epilepsy/autism and serotonin. Despite the fact that all of these studies were only animal studies, there is convincing evidence that whatever the catalyst is (bacopa, tryptophan, 5-HTP, etc.) for altering 5-HT levels, whether directly or indirectly, has an effect on the neuroprotective capabilities of the brain and central nervous system.

Friday, January 20, 2017

Friday

Mira has had an up and down last few days. She is fairly quiet and in a decent mood in the afternoon and around dinner time, but the mornings have been a little rough. She has been refusing to drink more than one bottle at most, when she usually has two, which means that she ends up getting hungry at school much earlier than usual. It seems to throw her whole internal clock off for the rest of the day and she ends up being cranky by dismissal time, which ultimately means she is cranky on the bus ride home, as she was today. Yet, she won't drink enough in the morning and she gets fussy, for whatever reason, so she ends up back in her bed until a few minutes before the bus arrives until she calms down. It's a vicious cycle. Ultimately, she has been ending the last few days on a high note, drinking a ton for dinner, then having some extended toy time before bed. Tonight in fact, she went almost a solid hour of playing with the toy, before getting worn out. We have had some very positive success since reintroducing the toy - she hasn't had any seizures or even twitches when playing and it certainly isn't acting as a trigger as it used to in the past. We will continue with it, unless we start to see some familiar patterns emerge. Sarah is in Cincinnati visiting her sister, so I will be holding down the fort with the kids until Sunday afternoon, so we will all be trying to find some fun things to do for the weekend. Wish me luck!

Thursday, January 19, 2017

Biotinidase Deficiency

Very similar to Pyridoxine Deficiency (PD) there is another very treatable cause of epilepsy in children, called Biotinidase Deficiency (BD). As children with PD require extremely high dosages of vitamin B6, infants and children with BD require large doses of biotin (vitamin H) typically in the 5-10mg a day range. The recommended daily intake for biotin is 5mcg, thus a dosage for someone diagnosed with BD is 5,000-10,000 times the RDI for the vitamin. Once a child has been diagnosed with the deficiency, they must stay on this high dosage of biotin for life - the lack of this enzyme requires a consistent high dosage to maintain proper levels in the body. All of the symptoms for BD are very similar to Pyridoxine Deficiency, including hypotonia, ataxia, seizures, developmental delay, eczema, and hearing loss. The enormously wide spectrum of epilepsy can have many causes - Biotinidase Deficiency can be one of those causes and has a very simple treatment. Early recognition of BD is critical, as delays in diagnosis can lead to developmental delay and can sometimes have permanent damaging effects.

Back in 2005, when Mira was born, Kansas had not adopted newborn testing for BD, thus Mira was not actually tested at birth. I happened to stumble on BD in all of my readings soon after her diagnosis and brought it up to her neurologist who thought it would be a good idea to have her tested. A simple blood draw ruled it out - her levels were normal, but she obviously had many of the symptoms of BD. Prior to the testing, we went ahead and put her on a large dosage of biotin for a few days until the results came in, but it did nothing for her seizures. We ruled out BD very early on in Mira's journey with epilepsy, nonetheless, I was glad to have found this very treatable cause of epilepsy as a potential cause, early on.

Wednesday, January 18, 2017

The Ketogenic Diet

The Ketogenic Diet (KD) is a specfically designed diet for the treatment of epilepsy, developed nearly a century ago, in the Mayo Clinic. It was a popular and successful treatment option for epilepsy, especially in children and young adults, but it fell out of favor in the 1940's, as AEDs began to flood the pharmaceutical market. It is still used today, typically started through the direction of a medical professional in a hospital, requiring a fair amount of monitoring to initiate. Equally as difficult is continual compliance with the diet, because of its strict guidelines on the fat to carbohydrate ratio. The KD can be very difficult on the body as well, with many children stopping it due to kidney stones, diarrhea, severe constipation, and/or the inability to tolerate the limited food choices the diet has to offer in general.

How does the diet work? Once the diet is initiated, the body eventually goes into a state of ketosis, where the primary source of fuel for the body is fat and protein, which in turn, affects how the brain functions, in a very simplistic sense. The traditional KD uses little to no carbohydrates as a source of energy, instead uses fat to break down into ketone bodies. The Modified Atkins Diet (MAD) is similar in structure, yet allows more carbohydrates into the overall ratio of caloric intake. It could be referred to as the 'Ketogenic Diet Light' in a sense. The typical KD however, is fairly rigorous, with the ratio of fat to protein and carbohydrates being in the range of 4:1 to 1:1 (4:1 being obviously the most aggressive and rigorous end of the diet) in order to try and gain seizure control. On a 1,000 calorie diet, only 8 grams of carbs would be allowed on a 4:1 ratio, which makes it very difficult to meal plan around such a limited amount of carbohydrates.

If you consider the foods that have zero or nearly zero carbs, you won't get a hand cramp writing them down: eggs, heavy cream, butter, most meats, most cheeses, mayonnaise, coconut oil, and MCT oil. There are a host of vegetables that have low carbs, including spinach, cauliflower, and even broccoli, but they still contain some carbs, so the ability to weave them into the diet is challenging. When you are limited to 8 grams of carbs a day, it makes meal planning very difficult, yet very predictable. Again, there are less strict ratios for the diet, but the basic idea is that you are substituting a large percentage of your typical intake of carbohydrates and protein, with fat and calories.

We tried the MAD with Mira years ago and it was very difficult on her. We initially tried to have her admitted to try the traditional KD, but her labs were so far off the charts, that the clinic felt she would not be a good candidate for the diet. Before she was even considered being admitted to the hospital, she had very elevated BHB (beta hydroxybutyrate) levels for some reason, indicating that she was already in some level of ketosis. She also had very high cholesterol levels, which no one felt comfortable starting her on the diet at that point. We agreed to start her on the MAD instead, thinking that she might tolerate the ratio better that the KD. If we saw some seizure reduction with the MAD, we could increase the ratio as we went along. Unfortunately, Mira did not tolerate the diet well - there was a lot of irritability, constipation, vomiting, and continued elevated cholesterol after several months, that we slowly abandoned the diet after 4 or 5 months. She never really could stay in a solid state of ketosis either and with all of the complications just on the MAD, going to the full-fledged KD would have been brutal for Mira. We never saw any change in seizures in that time as well, in fact, if my memory serves me well, her seizures actually worsened.

Clearly, the diet does not work for everyone, but it has helped a lot of kids with seizure control. The Charlie Foundation was developed over 20 years ago as a resource for the KD, as a result of the diet being hugely successful for a child named Charlie Abrahams, who was battling epilepsy at the time. It is a fantastic point of departure to find out information on the diet, find support, and to see other therapeutic applications the KD has to offer.

Tuesday, January 17, 2017

Back at School

Mira was back at school today, after an extended 4-day weekend. She must have sensed something was happening this morning, since she was kicking her feet 100 miles and hour, making it a wrestling match to try and get her dressed and ready. She wanted nothing but to be in her chair and moving. Based on her teacher's report, she had a solid morning, but wanted to eat lunch early - not a surprise, since her M.O. the past few mornings has been to eat a mediocre breakfast (a half-bottle as opposed top her usual 2 full bottles). She was moving so much this morning before the bus, that it made it difficult to get her to drink anything, since she just wouldn't stay still or interested long enough to finish a bottle. She was quiet this afternoon after school and during dinner, probably worn out from getting back into the school rhythm.

Taurine

The amino acid taurine was a subject of interest of mine for awhile. It is one of those supplements that is mentioned repeatedly in medical abstracts as a potential source of epilepsy relief, usually in the context of it being a 'complimentary' treatment option.

I first started investigating the basic pharmacokinetics of taurine, which were studied here, which ultimately led me to how they potentially could impact seizures, either in conjunction with mainstream AEDs or by itself. Since taurine has the ability to cross the blood-brain-barrier (BBB) and it is widely recognized as being a neuroprotectant, I figured I would be able to find some significant epilepsy studies on it. However, like vinpocetine, I couldn't track down many that involved the effects of taurine on seizures that weren't animal studies, other than a lone clinical trial, that I could not find results on. I did find some interesting facts on neurotransmission and the impact taurine has on the central nervous system, which can be located here.

Taurine acts as a membrane stabilizer, particularly with voltage-gated calcium channels (VGCCs) - the article goes into great technical depth with and explanation, which I can only digest and interpret so much of before my eyes glaze over. One of the main takeaways I read in the article, was how taurine's inhibition or monitoring of VGCCs, was also the assumed mechanism of action of Lyrica. Since MIra has been on Lyrica (pregabalin) for years now, I found it necessary to explore the potential relevance. Based on this connection alone, I kept traveling down the taurine rabbit hole. Ultimately, I found a ton of information of what taurine supposedly does, in the articles listed below, but again, not a lot of direct, conclusive studies:


Based on this article, there seemed to be a lot of interest in taurine and an anti-seizure medication, back in the 1970's. All of the references for studies were all done prior to 1979. I lost interest in reading about taurine, as I found more research in animal studies, and even more studies for taurine in relation to canine epilepsy. While I found taurine as being a simple amino acid, its relevance to cell membrane functioning was complex and confusing. Based on what I read, it had a wide range of influential activity, but not really much specific to epilepsy and/or seizure control. Please email me or post links if you can find some conclusive studies or additional information.