Rare Epilepsies, SUDEP, Advocacy, & Neurology Career - Dr. Phillip Pearl, Boston Children’s Hospital, MA, USA
Dr. Phillip Pearl, Harvard neurologist and author, shares his journey through rare metabolic epilepsies, SUDEP, and what patients and clinicians need to know.
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Episode Highlights
What rare epilepsies teach us about neurology
Why SUDEP research is critical
The human side of epilepsy care and diagnosis
About Dr. Phillip Pearl
Phillip L. Pearl, M.D. is Director of Epilepsy and Clinical Neurophysiology at Boston Children’s Hospital and William G. Lennox Chair and Professor of Neurology at Harvard Medical School, specialising in metabolic epilepsies.
Full profile phillip-pearl
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Intro
00:00 Phillip Pearl
“When the young students come up to me now to talk to me about a career in neurology, I don't steer them away from adult neurology, I steer them toward adult neurology because we need more people in the field of dementia!”
00:12 Torie Robinson
When most people think of epilepsy, they think of seizures alone. But what about the causes, and if they run deep; tied to our metabolism, genetics, or even the way our bodies process vitamins? Well, today we’re joined by the brilliant Dr Phillip Pearl - Chief of Epilepsy and Clinical Neurophysiology at Boston Children’s Hospital and Professor at Harvard Medical School. He’s taking us on a journey through inherited metabolic epilepsies, from stories of vitamin B6-responsive epilepsy to the exciting world of genetics, diets, and even gene therapy!
If you haven’t done so already, please press the thumbs-up in this episode, comment below, and subscribe to our channel, so that we can get way more people around the world - clinicians, patients, and the general public - learning facts about the epilepsies!
About Phillip
00:56 Phillip Pearl
I'm Dr. Phillip Pearl. I'm the chief of epilepsy and clinical neurophysiology at Boston Children's Hospital, and I run the Division of Epilepsy, which is composed of nearly 30 (depending on who you count), paediatric epileptologists. So, it's a very large program
Why be a neurologist?
01:17 Torie Robinson
What kind of keeps you going in this sphere? Because bad things happen, right? And when they happen with children, can just, well, if it happens with adults, it's heartbreaking, but with kids especially… what keeps you going today?
01:30 Phillip Pearl
On the one hand, it is difficult because these are ultra-rare diseases. So you could spend your whole life… I mean, they say more people got their PhD on Tay-Sachs disease and actually had Tay-Sachs disease.
01:43 Torie Robinson
Oh, that's ridiculous! Haha!
01:43 Phillip Pearl
It's a funny statement, but it actually means something. It's like you could spend your whole life studying a disease that affects so few people that you won't really make any impact. But the truth is: 1, parents have become much more advocates in my career than they ever were before, right? It's not even close. So, there's a lot of prodding and advocacy and pushing (and I don't mean pushing in a bad way, but in a constructive way) to make progress in these ultra-rare diseases that affects their kids. So that's like one thing. And the power of advocacy is pretty amazing. The next thing is, anything we learn about these diseases, we end up learning, in my view, fundamental things about the nervous system. That really excites the scientist in me. So, the parents that I'm involved with, the advocates, that really excites the clinician in me. And the implications for understanding the foundation of the brain, of neurology and neuropathology, and physiology - that stimulates the scientist in me. And on a social level, I mean, these discoveries we're making in rare diseases are ultimately going to be applicable to much more prevalent diseases. And diseases that affect not just the newborn and the infant and the child and the adolescent, but the adult. And quite frankly, the biggest scourge of our time with the aging of the population, people living longer, is dementia.
03:18 Torie Robinson
Mm-hmm.
03:19 Phillip Pearl
When the young students come up to me now to talk to me about a career in neurology, I don't steer them away from adult neurology; I steer them toward adult neurology because we need more people in the field of dementia! And so, as much as I think it's wonderful to go into paediatric neurology, which I did, why did I do it? I always wanted to be a paediatrician. I'll be totally honest. I mean, it's funny, when I was in fifth grade or maybe, yeah, I think fifth or fourth grade, I read this book called Stories of Great Physicians. And it was about Hippocrates and Madame [Marie] Curie and Louis Pasteur and Sabin and Salk. And I just thought… and I love science and I love school, actually, at that point in my life. I was in fourth grade, fifth grade maybe.
04:04 Torie Robinson
Hahaha.
04:04 Phillip Pearl
I said "This is the best thing to be. I'm gonna be a doctor.". And my own paediatrician was a role model for me, which is interesting because the changes in demographics… people have to recognise, role models are important even for young, young children. I have to say, the following year I read a book about great supreme court justices, and if I'd read that first, I might have gone into law school!
04:26 Torie Robinson
Huh!
04:26 Phillip Pearl
So, the young mind is very malleable. And then, as I got older, I wanted to be a musician, and I ended up… I do play music semi-professionally, even now. And my dad was a professional musician, so that was an influence, you know, both nature, nurture thing, it was all going on for me with that. But on the other hand, I worked like seven straight summers as a camp counsellor, I loved kids. So, I wanted to be a paediatrician. Now, once I got into college, I grew up in Baltimore, Maryland, and really couldn't afford to go to any fancy, expensive place, but I ended up going to Johns Hopkins for undergraduate, which was…
05:04 Torie Robinson
That's not so bad!
05:04 Phillip Pearl
…pretty sensational.
05:06 Torie Robinson
Yeah!
05:06 Phillip Pearl
And I got inspired there by taking a course in medical ethics. And in that course, I was placed in the birth defects clinic at Johns Hopkins Hospital. And I was under the tutelage of a Dr John Freeman, who at the time was the chief of paediatric neurology at Johns Hopkins Hospital. And I was just mesmerised by the whole thing. So, at that point, I pretty much fell in love with paediatric neurology. Although I was still undecided when I went to medical school, the most fascinating condition I ever encountered was schizophrenia. Because, how does a genetic condition do that to a person? We can have a young, bright person, and once they go to college, they completely fall apart with paranoia, hallucinations, and it's whether we call it psychiatric or not, it's clearly a degenerative disease…
05:51 Torie Robinson
Yeah.
05:51 Phillip Pearl
…(which is where psychiatry and neurology are combined). The problem is, when I did my psychiatry rotation in medical school, the last thing I wanted to be was a psychiatrist. It just wasn't for me, and that's a whole other story. But I just wasn't that interested in a lot of what these people had to deal with. However, then I sort of rediscovered neurology because I did my neurology rotation in medical school and completely fell in love with the discipline and neuroscience. And I almost did adult neurology, but then I kept going back to my initial thing as a kid - I wanted to be a paediatrician, so I became a paediatric neurologist.
What the future holds for people with a metabolic epilepsy
06:25 Torie Robinson
What does the future hold for children and, well, potentially adults, and metabolic epilepsies? I mean, you said that, you know, genetics, you know, neuroscience is taking us places. Are the lives of people going to improve? Do you think we will be able to control people's symptoms at a much earlier age and prevent cognitive regression and things like that?
06:50 Phillip Pearl
Their lives are going to improve, but it's going to be a long, hard road. And we're all excited about these discoveries, but as a parent once observed in a meeting on Angelman syndrome “It's a good time to have Angelman Syndrome for a mouse.”. In other words, you can go to a meeting after meeting and hear about the mouse model of this and the rat model of that. Like we're doing a mouse model of SSADH deficiency, which is the particular disease where I'm focused. It's a disorder of GABA metabolism. And everything's in the mouse or whatever animal. And we’ve got a long way to go before a lot of this is going to be applicable to humans. Now, on the other hand, there's a disorder called AADC deficiency that you may have read about…
07:30 Torie Robinson
Mmm.
07:30 Phillip Pearl…
…because I was involved in the clinical trial here, and now the gene therapy has been FDA approved, and it was approved by the EMA (European Medical Association), about two years ago or even more now. And there have been about 60 people now in the world who received this gene therapy - at least in the putamen. There's another entry mechanism into the substantia nigra. So there are two ways of placing it. But the point is, it goes directly into the brain, into the parenchyma, the tissue of the brain, and it makes a huge difference - for at least the young ones (we're not sure about the older ones). But there's even one adolescent patient who came off a tracheostomy because of the gene therapy. So, we're treating all ages because it's been approved for all levels of severity in all ages. Basically, well, when I say all ages, from 18 months to 65 years. So basically, all ages by the…
08:16 Torie Robinson
Hehe, yeah.
08:16 Phillip Pearl
…the FDA. Even though on the trial we only did non-ambulatory patients, we can even treat ambulatory patients. So, there's all this excitement. That's the best example I have of lives improving dramatically. In fact, the most transformational, I would say, intervention in my career has been to treat this little girl from Thailand who came to us unable to hold her head up at age two, and we did the therapy, and nine months later, she was walking. And I have videos, and our parents are very grateful, and it's been incredible. So, for the individual case like that, it's transformational. For most people, this is all very incremental, little increases. We have new therapies approved for say Rett syndrome, and there's gene therapy that's coming out. Gene therapy is available now, say for MLD, metachromatic leukodystrophy. We're working on gene therapy in one of our labs here under the guidance of my good friend and colleague, Dr. Alex Rotenberg on SSADH deficiency, and his colleague, Dr. Henry Lee, and it looks like it's really good, but that's in the mouth. We’ve got a long way to go before we get to the humans.
SUDEP
Now, on the other side of this is the darker side, which is… you and I were talking before the podcast about how epilepsy has its frightening aspects, and one of them is SUDEP, sudden unexpected death in epilepsy patients, and we talk about it more now because we've learned (in fact, we're about to publish this), we've learned that families need to know it exists before it happens.
09:44 Torie Robinson
Right?!
09:44 Phillip Pearl
That makes a huge difference in how they cope with the tragedy of it happening in their own family. Whether it's preventable or not is a little bit up for discussion. But it certainly is motivating for people to know about it and take their medicines more apparently and things like that. But the point I'm trying to make is the metabolic patients seem to be at higher risk for that. We know that certain genetic conditions like SCN1A, SCN8A, the sodium channelopathies, have a very high risk of SUDEP. It's also turning out to be true for the metabolic kids. And in fact, there's a wonderful meeting held every year with the American Epilepsy Society meeting called PAME, Partners Against Mortality and Epilepsy…
10:19 Torie Robinson
Yes, I know, yes, I know the guys, yeah!
10:22 Phillip Pearl
And my colleague, Dr. Etai Tokatli-Latser from Tel Aviv, and I (he was with Boston for three years working with me), we presented at last year's meeting in Los Angeles on SUDEP in the inherited metabolic epilepsies. In fact, we had one of the mothers of my patients with SSADH deficiency who she met me during the natural history study. They travelled all the way from Dubai to meet me, and I noticed the seizures were getting worse, so I let her know that SUDEP was a high risk in this condition, and she went home, and a few weeks later her son, she found her son dead in his bed. So, she experienced SUDEP, and she said the only thing that got her through it was [that] she heard me saying this can happen. And since then, she flew to California and gave a speech on it with all the parents there, and she's written a book on this now. So, this is not a big secret. The point is, we don't want it to be a secret, and when we're talking about conditions like this, not only are there other morbidities (as you asked me about besides seizures), but there's increased risk of mortality.
11:18 Torie Robinson
It's brilliant that you've said that “mortality”, whether it's through the seizure itself, whether it's SUDEP, whether in some people it's suicide, it can, there are many different things, right? Suicide is much higher rate amongst people with an epilepsy, correct?
11:32 Phillip Pearl
Absolutely. I have to say, at the PAME meeting, we heard as many stories about depression and suicide as we did about SUDEP, and depression is common in epilepsy; which, frankly is understandable, and suicidality is a byproduct of depression. So, the whole thing makes sense, and if people know this, then I think that can go a long way toward treating it.
Music & epilepsy
11:55 Torie Robinson
Now, Phillip, we're ending on a very positive note here: you are, as you mentioned briefly, a musician, but you are like a “musician-musician”! And I believe that we're going to have an episode about the positive impacts of music upon people with an epilepsy. Is that right?
12.11 Phillip Pearl
Well, there's a lot to talk about with music and epilepsy. We could talk about the Mozart effect…
12.19 Torie Robinson
Yeah!
12.19 Phillip Pearl
…the musicogenic seizures… The positive music therapy in epilepsy; that is gonna be a controversial one, just like it is with autism, but it does seem to have definite improvement in dementia, Parkinson's, and some of those neurologic diseases. So, there's a lot to cover when it comes to music and the brain.
Conclusion & thanks
12:28 Torie Robinson
Thank you to Phillip for sharing his incredible knowledge on inherited metabolic epilepsies and helping us understand how treatments have progressed from vitamins to today’s cutting-edge therapies. Check out more about Phillip at the website torierobinson.com where you can access this podcast, the video, and the transcription of the entire episode all in one place. And if you haven’t done so already, please press the thumbs-up for this episode, comment below, and do subscribe to our channel, so that we can get way more people around the world - clinicians, patients, and the general public - learning facts about the epilepsies! See you next week!
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