After doctors are unable to prevent her daughter's daily seizures, Tracy Dixon-Salazar decides to take matters into her own hands.
Dr. Tracy Dixon-Salazar is a neuroscientist, geneticist, and, patient advocate. Her desire to get her Ph.D. was inspired by her daughter who developed Lennox-Gastaut Syndrome (LGS) at the age of 2. She did her Ph.D. and post-doctoral work at UC, San Diego where she studied the mechanisms of brain development and synaptic plasticity, identified genetic causes of rare disorders in children, and researched precision therapeutics in stem cell and animal models of pediatric disease. During her research tenure, and after 16 years of watching daily, unrelenting seizures in her child, she uncovered the driver of her daughter’s illness and identified a novel precision therapy that improved her child's life. Dr. Dixon-Salazar is an accomplished scientist, proven thought leader, highly sought-after speaker, and staunch advocate for genomic medicine, patient-centric research, and patient engagement.
This story originally aired on August 21, 2019 in an episode titled “Power of Patients.”
Story Transcript
So 24 years ago I was a very young stay-at-home mom. I had two kids, a four-year-old son, Talon and a two-year old daughter, Savannah, and I was just living life, minding my own business. My kids were great. They were not advanced. They were not behind. They were just typical kids.
One morning, I was woken up in the very early morning hours, it was still dark outside, by the sound of my husband screaming my name from my daughter Savannah’s room, my two-year-old. I ran in there frantic. I had no idea what was going on. And I saw him frantic as well. I had no idea until I looked and I saw Savannah.
She was laying on the bed. She was stiff as a board, her arms at her side and completely rigid. Her eyes were rolled up into her head and stuck there. She was blue, like she wasn’t getting enough oxygen. She wasn’t breathing. And she had bubbles, foam, drool, something coming out of her mouth. There are really no words that I can use to describe how I felt in that moment. It was this whole body terror that just took over every aspect, every fiber of my being. I thought she was dying or dead.
My husband shouted something like, “I think she's choking. Call 911.” So I ran back to the bedroom and I dialed 911.
I talked to the operator and she said, “I want you to stay on the phone until the paramedics get there,” and I said, “Okay,” but the phone cord won’t reach to the bedroom, because it was that long ago. I just wanted to get back to Savannah but I couldn’t.
So I stayed on the phone and I vaguely recall shouting things to my husband, “How is she doing,” and then relaying it. “Is she breathing?”
“No.”
“Okay.” Relaying it back to the operator.
I remember at one point becoming so overwhelmed, so afraid, so shocked that I started to feel hot and dizzy and I had to kneel down and then I had to sit down. Then at one point I was lying face first on the cold tile floor of the bedroom with the floor here and the phone here, weakly, still trying to communicate between my husband and the operator, the stupid phone cord that wouldn’t reach, and try to stay conscious because I was so overwhelmed that my daughter was dead.
I have no idea how long it took the paramedics to get there. I remember hearing the sirens come up and getting closer. And then I remember finally getting off the phone with the operator and we ran downstairs. My husband had her in his arms and she was limp, still blue. She had saliva mixed with blood running down her face.
And as he handed her over, she took in a deep breath, like a [inhaling] noise and it was the first time that I realized that she was still alive.
The paramedic took her to the living room and examined her and she was sort of coming out of it at that point. Her color returning, responsive. And we described this choking incident.
He said, “You know, her airway is clear and she's fine now. What you describe sounds just like a seizure.”
Then I said, “What’s a seizure?”
We had no idea. She had been completely fine and this was out of the blue. That was our harsh introduction into the world of epilepsy.
A few weeks later, she had another seizure and we saw the doctors. It took them six months for them to tell us that she had epilepsy, because they didn’t want to label her with that horrible word.
And they assured us, “Epilepsy is not a big deal. Even though we’re afraid to tell you that that’s what it’s called, it’s not a big deal. She’ll live a normal life. She might outgrow it.”
There are all these famous people that have epilepsy. Prince, Picasso, Dostoyevsky, all these people that we are best friends with and meet every day, right?
“And then she’ll just go on medicine. There are all these medicines that can control seizures. This is not going to be a problem. And don’t worry. Even though she's turning blue, seizures do not damage the brain.”
None of that was true for us and we lost a lot of trust in doctors after that. We felt lied to.
By the time Savannah was three, so six months after the first seizure, she was having seizures every day. A good day was five to ten seizures, a bad day was hundreds. I stopped counting after a certain point, too many to count.
She was getting injured all the time, falling usually on her face from the seizures. And delays in her development were becoming very, very apparent because of all the seizures that she was having as they did damage the brain.
Everything we tried, drugs, diets, devices, alternative therapy, supplements, vitamins. We even considered brain surgery, she wasn’t a candidate.
“We’re sorry, Mrs. Salazar. Your daughter is not a candidate for brain surgery.” We didn’t know whether to be devastated or relieved.
But nothing worked.
By the time she was five, we got yet another diagnosis. She had evolved into something called Lennox-Gastaut Syndrome or LGS. This is a rare pediatric epilepsy syndrome, it’s a group of symptoms, that have a really horrific prognosis. The prognosis is continued seizures, progressive intellectual disability and premature death. And we still had no idea why.
During all this time we became prisoners in our own home on purpose because it was just easier. We spent all our time trying to keep this kid safe, trying to keep a young kid who’s active and mobile and perfectly typical who was having seizures all the time from not running around. If there was a brick fireplace within a five-mile radius, her face would find it.
I remember asking the doctors, “What happened? She was fine. She wasn’t advanced, she wasn’t delayed, what happened? It’s out of the blue.”
They said, “Well, no. Most people with epilepsy don’t know the cause.”
So welcome to the majority. Congratulations. It was so dogmatic the way they said it.
And I have heard a lot of really dumb things in my life but that didn’t make any sense, especially in light of all the things that she had tried and failed.
I was, “What if we knew what caused it then maybe we could treat that?” It was as if nobody was looking.
So this is when I started reading scientific papers about what could cause epilepsy. I would go to the library and check out internet time for an hour. That’s how long ago this was. And I would get whatever papers were on the internet back then, usually things that were really old and obscure. And I had no idea what the hell I was reading.
I thought I just want to know what causes epilepsy. I don't understand this. I need to go to college and take some English classes. I hadn’t done well in high school. I'd never been to college but I have to go take some English classes because I need to understand this.
It turns out that my English is fine and that scientific papers are not in English. It’s a whole different language. And medicine is yet a third language.
So I enrolled in some scientific classes and I fell in love with the subject. I specifically fell in love with genetics. Here were these things called genes that turn on and off in synchrony across brain development and they regulate everything from the color of your hair to what you look like to how you behave. This was something, finally, out of everything that I'd heard, everything that I'd read that could explain why I had a healthy kid one day and why I didn’t.
So I stayed in school. I stuck with it. I kept at it. I couldn’t help my kid but, dammit, I could study. So every seizure she had I would study harder.
I wanted to quit often with school. I always thought, like everyday I'd go, “But I have to quit tomorrow because I’m not going to be able to juggle all this.”
I mean LGS is a lot. And then life, life is just a lot without all the seizures. But my husband wouldn’t let me and our journey up until that point wouldn’t let me. I couldn’t help Savannah but I could try to help the next generation of Savannah’s. It could not be this bad for the next group of families.
So I stayed in school despite the urging of many of my family members that thought I should be at home taking care of my daughter. Four years later, I got my Associate’s Degree. I did mention I hadn’t done well in high school. It took a long time to remediate. Three years after that I got my Bachelor’s. Two years later I got a Master’s. And twelve years from the very time I started school I earned a PhD studying neuroscience and genetics.
I was doing my post-doctoral fellowship in UC San Diego where I had done all my training and, guess what? Genes play a huge role in early life epilepsies. My job was to find genes in kids just like my daughter, and we did. We found more than a hundred. I was part of this global team. I was this one tiny piece. And when we found the genes, we tell the families, making it better, I hope, for the next generation.
I wish I could tell you that things were great back home. They weren’t. Savannah was a mess. She was having seizures every day, still. She was having about 75 seizures a week and she was going into these non-stop seizures weekly where they wouldn’t stop on their own. So we would intervene.
We’d have to intervene with emergency rescue therapies. This started with a rectally administered drug at home. When that didn’t work, we would take her to the emergency room where she would get intravenous drugs. And when that didn’t work, the doctors would put her into a medically-induced coma.
That was our life. So this caused me to study a lot harder, but there was no relief for her. And everything we tried, all the drugs and everything just didn’t work.
By the time she was 18, the seizures had done so much damage to her brain that she was the mental age of a three- to four-year-old. At that time, she was on a special diet, one device, seven different anti-seizure medicines, of which we have no idea how they interact, with horrific side effects. Everything from cosmetic side effects like overgrown gums and excessive facial hair to the more severe side effects such as increased seizures, worsening and psychotic behaviors, liver failure, kidney failure. Horrible side effects.
And we really had no hope. I remember I was leaving work one day and I ran into my postdoc adviser in the hall and he just casually asked me how I was doing. Poor guy. And I burst into tears.
Now, I didn’t ugly cry but if there is a hell for postdoc advisers, I’m pretty sure it’s one of your postdocs bursting into tears when you're talking to them.
He said very calmly, he said, “You know, we should sequence Savannah’s DNA and look at her genes.” He goes, “We do that here in the lab. Now, we've done it. This is your job, Tracy. We've done it in families that have only had a family history of epilepsy up to this point, and Savannah doesn’t have that, but maybe we’ll find something.”
And I said something like, “Okay, that’s a great idea.”
So we did. We sequenced Savannah, myself, my husband and my son and we did the analysis and we didn’t find a damn thing. None of more than a hundred genes that had been identified at that point were mutated in my daughter.
This actually really wasn’t surprising. Those of us living with LGS are pretty used to getting our hopes up about a new therapy or a new test and then utterly being punched in the gut, again, by LGS when we don’t see any results from it. So we go through life with 1% cautious optimism and 99% yeah, this isn’t going to work so don’t get your hopes up.
But I kept at it. Every time a new analysis tool would come out by the scientists, every time I would learn something else about brain development, every time Savannah would have a particularly bad day and I was having difficulty coping, I would re-analyze her data. One day, I analyzed it in a way I now have deemed ‘Crazy-Mother Analysis’. I’m hoping that someone will claim that and rename it something different later, but very scientifically valid.
I took all of the mutations that she had that were unique to her and predicted to be altering her gene and her protein in some way. All of us are walking around with about 300 of these unique mutations. I took them and I grouped them into signaling pathways.
There was a specific signaling pathway that had a huge number of genetic mutations in it. It’s a calcium signaling pathway. What this pathway does is it let’s calcium go into and out of cells. In brain cells, it’s crucial for brain cells being able to talk to each other. Calcium goes in, electrical activity happens and brain cells talk to each other.
This immediately reminded me when I saw this pathway that every time that Savannah would go on the vitamin calcium supplement, she would have horrific seizures. Now, she always had horrific seizures so if I’m saying she's having ‘horrific’ seizures, these are really bad. So we got to the point where we wouldn’t allow her to be on calcium anymore.
And I begin to dig. We’re onto something here, something crazy, but still. I begin to dig in each of her unique genetic variance and I became more and more convinced that she had too much calcium going into her cells based on the data. Her cells were talking to each other. They were screaming at each other and there was just too much activity.
So the next question was is there any kind of drug out there that could quiet these cells, calm them down, decrease the amount of calcium that was going in? And I found in the literature that there was. There was an FDA-approved drug on the market. It was used for high blood pressure, not epilepsy. And it acted on several of the exact genes that Savannah had in her that were mutated.
I said we have to try this. We had really no hope. We didn’t really have anything that we hadn’t tried. At that point, Savannah had tried and failed 26 different things and we may as well just been throwing darts at a board because there was no rationale or no data for why we should try a 27th thing.
So I gathered up my data and I marched over to her pediatric neurologist’s office and I said, “We need to put her on this drug. Here’s the data.”
He says, “I don't understand any of this genetic stuff here but I’m on this drug for my high blood pressure,” which I probably gave him.
He said, “Yeah, this drug has been around for decades. We know a lot about it. It’s pretty benign. Let’s try it.” He said, “Let’s run some tests to just check her out and try it.”
So we put her on this drug and within two weeks, much to everyone’s surprise, especially ours, she started to get better. She went from having 75 seizures a week to having about two or three only at night. And those trips to the emergency room, those comas, those seizures completely stopped. So if you're near wood, knock on it right now because that’s just what we do.
We were dumbfounded. We were so afraid that this was not real or that someone was going to hear and then we were going to lose the control and be struck down by the LGS gods that we didn’t talk about it for a year. We didn’t tell anyone. The only people that knew were us and the family, the physician, not even my post-doctoral adviser knew and he had sequenced her.
We finally told him and he's like, “Of course. I wish I published this,” which is what every postdoc adviser says, right?
That was eight years ago. Savannah is 26 years old now and she continues to have a 95% reduction in all of her seizures and 100% reduction in her non-stop seizures that would send her to the hospital. And she's growing and developing again.
She is walking and talking. She just learned to buckle her seatbelt about two years ago, to ziplock-close a Ziploc bag and to use a key in a door, God help us.
While she still talks at the intelligibility of a two-year-old, she can talk like nobody’s business. Talk, talk, talk. This kid talks so much, sasses us, which we mostly love. All right, we love it. And she's growing and developing again.
If you had told me that after 16 years of daily, horrific, I just can’t even find the words to tell you how awful it was, seizures that the 27th thing that we tried would have changed our lives as much as it has, I would not have believed you. No way. But it happened.
Savannah’s story inspired her doctor and other researchers what could happen if you targeted a specific medicine to the gene.
And when I reflect back on this whole journey, people ask me, “How did you do it,” I don't know. I don't know. I didn’t see my husband for 12 years. I had the day shift, he had the night shift. He'd come home and he'd be like, “I’m your husband,” and I'd be like, “Show me some ID. I don't believe you.”
We made a difference. We helped some other families find their genes and, somehow in all of this, we helped our own kid.
I’m shocked. And I promise you everyone in my high school class who thought I was the least likely to do anything, is shocked.
Most of the time, I’m really grateful. This life that we have is so different. We venture out of the house sometimes now. We’re not prisoners anymore. I’m here. Savannah is so happy and really is living her best life.
But there are times, I try not to go here too often, I think what if. What if we had found this when she was three? Would she be typical? Would she not have suffered so much brain damage? She’ll never live independently now from all the brain damage but what if we had found it earlier?
If you think about it too long and too hard, you really shouldn’t have to get a PhD to figure out what’s wrong with your kid, and to do the research yourself to find the medicine behind the science, and then convince the physicians to try that. You really shouldn’t. But a mom’s got to do what a mom’s got to do and patients got to do what they got to do until science and medicine catch up, and we’ll just keep doing it. Thank you.