Some days it seems hopeless, like I am searching for an answer that will most likely, never be found. Other times, I am optimistic that I will stumble on something that may shed some light on Mira's situation, in the hope that it will help her in some capacity with her seizures, her irritability, or her overall quality of life. In the absence of finding why she suffers from relentless daily seizures, I continue to read and research. It has simply become part of my day.
About 2 months ago, I stumbled on a fascinating article, having to do with Pyridoxine Deficiency (PD), located here. It was a simple, three sentence abstract through PubMed, written 30 years ago. I found this article interesting for a host of reasons, as I have read quite a bit on PD over the years, and because Mira had done the 'pyridoxine challenge' when she was about 4 months old. I remember at the time they did the test, I found it miraculous that a lack of a vitamin B6, could have such catastrophic implications on the body, particularly the brain. Years later, I had since read much on PD and BD (Biotinidase Deficiency) along with a host of other metabolic syndromes, which a lack of or a surplus of vitamins that cause havoc on the nervous system. Pyridoxine, as it turns out, performs over 100 different functions in the body, from aiding neurotransmitters to protein metabolism.
PD is very well documented, even being researched as far to suggest there is an EEG pattern associated with PD. If you do a simple search for PD on PubMed, you will pull up 556 articles related to it, dating back to 1945. Some of these I am very familiar with, but I decided to read further into the idea that a response to PD can be delayed for months, based on the original abstract I read. Down the wormhole I went, which led me to a definitive chapter from Genereviews, which is a collection of chapters having to do with specific genetic conditions. The chapter on pyridoxine, written by Dr. Sidney Gospe, is an exhaustive collection of information and links regarding PD. Gospe, who is physician out of the University of Washington School of Medicine, seems to be the authority on PD, as his name has surfaced on so many different articles I have read.
There is a brief discussion in the article, which describes and references 'atypical' presentations of PD, particularly with these findings:
- Late-onset seizures (age ≤3 years)
- Seizures that initially respond to anticonvulsants and then become intractable.
- Seizures during early life that do not respond to pyridoxine but that are then controlled with pyridoxine several months later.
- Prolonged seizure-free intervals (age ≤5 1/2 months) that occur after pyridoxine discontinuation.
I found this utterly fascinating and frankly, possibly relevant to Mira. Again, when Mira had done the pyridoxine challenge, she was around 3 or 4 months old. The test essentially involves an injection of 100mg of pyridoxine, administered during an EEG. In many cases, the EEG will normalize within minutes of metabolizing the B6, but is sometimes delayed for a few hours, Thus, continuous, timed injections of pyridoxine are administered, up to 500mg, to see if any change is noted on the EEG or with the child's symptoms. This I had read about, but I had no idea that the delayed response to pyirdoxine can actually be months, not hours. Nothing had happened to Mira's EEG when they tried B6, so she was considered a non-responder. Just this past year, Mira had even completed a comprehensive epilepsy panel, which tested for ALDH7A1, one of the primary genes associated with PD. There is also a lees common PNPO genetic association.Yet not all children with PD test positive for mutations in ALDH7A1 (or PNPO), so it does not exclude her from having PD.
After reading all of this information, I went back to see when we had started a trial with Mira on B6, as I remember trying it at one point, but I don't remember to what degree, nor when that exactly was. As it turns out, it was around August 2007. Unfortunately, I did not document how long we had tried pyridoxine, at what dosage, and when we actually stopped it. I can tell you though, that Mira became seizure-free in November 2007, about 3 months later. She continued to be seizure free for around 5 months, when we slowly started seeing her familiar seizure patterns develop again. This pattern of seizure freedom and pyridoxine may or may not be relevant, but intriguing enough to pursue the idea.
This is complete and utter speculation, but it is what I am theorizing at this point - it might be possible that Mira actually is atypical PD and potentially has a very delayed reaction to supplementation. Her period of seizure freedom could be chalked up to this as well, based on the articles I read. I don't have any recollection of how long we kept doing the B6 in 2007 and it could all be coincidence, yet I don't want to completely rule it out. Again, it is total speculation at this point, but it is possible. At the time, the only thing we could associate Mira's seizure-free stretch with was the Lyrica. It seemed to be the miracle drug for her, stopping all of her seizures within a couple weeks, which is pretty miraculous, considering she had failed 14 different medication trials before that. Her seizures slowly crept back and she never had a seizure-free time again and she is still taking Lyrica, 8 years later.
After reading this article by Dr. Gospe, it became apparent that we should revisit the pyridoxine potential, so we started a low-dosage of it in the beginning of June. Right now, she is holding steady at around 20mg/kg, which is a medium range dosage for PD. I have read articles that have administered up to and beyond 100mg/kg, but a majority of the articles consistently stay within the 10-30mg/kg range. There is little to no risk with pyridoxine, with many reports from the 1980's even being falsified or misleading (see Chapter 11 and the Schaumburg reports), so I am not worried of any risk at this dosage, especially if this theory proves to be wrong and we stop using it after 6 months. Besides the fact that we have tried 20+ different pharmaceuticals with questionable safety and efficacy ratings, I think it is only fair to Mira to try something simple and non-toxic.
We are going to hold steady at this dosage for awhile and wait it out for a few months. If history repeats itself and my theory is true, as it has already started to, Mira could potentially hit a seizure-free date of around the beginning of September of this year. We haven't seen much change in seizures or irritability since we started the pyridoxine, yet based on the theory of her having PD, she wouldn't be seizure-free until the end of August. Ironically, we have seen a minimal amount of seizures since Friday, not seeing any yesterday or today. On the fussiness side, she was very fussy yesterday and has been up and down today. I'm staying cautiously optimistic about this right now, but there certainly is some logic behind this that could prove to be life-changing for Mira.