Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And joining me today is Dr. Mary Keen. With over 40 years of experience in Pediatric Physiatry, she's a Pediatric Physical Medicine and Rehabilitation specialist at Northwestern Medicine Marianjoy Rehabilitation Hospital.

In today's episode, we're delving into the fascinating world of rare pediatric conditions. Dr. Keen, thank you so much for joining us today. Can you give us a bit of an overview of some of the rare conditions you've encountered and treated? How did you first come across these rare conditions in your practice?

Dr. Mary Keen: Well, thank you, Melanie. It's a pleasure to be here. Yeah, over 40 years, I have encountered literally dozens and probably hundreds of rare conditions. When I first began my practice, the patients would come in with a vague diagnosis or cerebral palsy or intellectual disability or something that looked syndromic, but 40 years ago, we had nowhere near the knowledge we have today about genetic disorders.

So, when I started, I had to accompany more patients along this journey of trying to find out what the disorder is. Among the disorders that I took care of way back when included channelopathies, epilepsy syndromes, leukodystrophies, including the very rare birth-onset, Pelizaeus-Merzbacher syndrome.

My patients with rare disorders have stimulated me to learn so many things. And one of the most exciting topics that my patients got me interested in was mitochondrial disorders. Mitochondria disorders are individually rare, but they are not uncommon when you look at them as a whole. But most often, they're not even recognized until they've progressed quite a bit. We now know that about 20-30% of Parkinson's disease and Alzheimer's, for example, are related to mitochondria disorders. But I think most doctors don't know that unless they've gone to a mitochondrial conference.

Melanie Cole, MS: This is such an interesting discussion, Dr. Keen. So, what are some of the biggest challenges you faced in diagnosing these rare conditions as you spoke? It's interesting to hear that now parents are so much more informed. Well, I mean, it's easier for us to find information now, but what are some of the challenges with diagnosing some of these things? Do you have the technology, the imaging? Tell us a little bit about diagnoses.

Dr. Mary Keen: Diagnoses can still be challenging, but it's less challenging than it used to be. Over the years, I've had patients whom I've sent to the Mayo Clinic or Vanderbilt and other places to kind of get a diagnosis. And they had no more luck than my patients physicians here in Chicago.

Then, I found out about the Undiagnosed Diseases Program that the NIH sponsors. The National Institutes of Health has an Undiagnosed Diseases Program, it really is that UDD. And they accept submissions from doctors across the country. And if the patient is accepted, the NIH will pay for patient and parent transportation, housing and a hotel, and for all the additional testing that they want to have done. So, that's a wonderful resource that I would like our listeners to be aware of. It has been helpful for probably half a dozen of my patients.

Another thing I'd like to share though, besides making the diagnosis, what do you do about some of these patients when you don't know what's going on? Well, I have found it really useful to go to conferences that are outside my usual realm. For example, I've gone to many of the International Mitochondria Disease Conferences, and I found out something there that has served all of my subsequent patients with mitochondria disease, and that is that exercise. As a physiatrist, that's one of our favorite treatments, exercise can actually help repair sick mitochondria. Exercise can actually help improve the brains of people who have mitochondria disorders. Exercise can improve the functioning of the GI tract and not just the muscles, but all of these other systems. And that was a very exciting and it still is an exciting opportunity that rehab doctors have. Many of us were taught in medical school that there's really nothing you can do other than supportive care, but there is more that we can do, and it's really exciting to be able to make a difference.

Melanie Cole, MS: Dr. Keen, as an exercise physiologist myself, I do understand exercise is medicine. And while you're thinking about that and telling us about these rare pediatric conditions, when you say exercise, how are you working with patients? Tell us a little bit about the multidisciplinary approach. Who's all involved? What types of exercise are we doing? Physical therapy and OT? Is it more aerobic? Tell us what you're doing with the patients that's helping.

Dr. Mary Keen: Believe it or not, that's a complicated question because there is such a variety of patients. When a patient is able to walk, standard physical therapy may be all that we need. But some patients have strokes, other patients have very rapid fatigue. Other patients with mitochondrial disease, for example, have ataxia. Therefore, we're really fortunate at Marianjoy to have our Tellabs Clinic where we have technology that can help patients even when they have rare disorders and severely disabling conditions. For example, we have the ZeroG, which allows a patient to be able to be supported while they're walking. We have our Mayo devices that allow us or an occupational therapist to strengthen specific muscles and improve particular motor patterns. And we have other wonderful devices that can help even if a patient can't walk or has difficulty moving. There's a huge range of disability amongst individuals who have mitochondria disease.

I'd also like to mention cortical vision impairment. Cortical vision impairment is probably one of the most commonly undiagnosed impairments among children and adults in the United States. Cortical vision impairments happen in almost any injury to the brain because 40% of our brains have something to do with vision. When we look at our parietal cortex, our association cortex, our occipital cortex, the optic radiations, all of our brainstem nuclei that have to do with vision, we should always be aware of any patient who has any sort of neurologic disorder, that cortical vision impairment could be part of it. And at Marianjoy, we have a device called the BITS, which can help patients compensate for visual field loss or inattention, and some other aspects of cortical vision loss.

Melanie Cole, MS: What's exciting in your field right now, Dr. Keen? Have there been any real innovative treatments or therapies that have significantly impacted your approach to treating these rare pediatric conditions?

Dr. Mary Keen: There have been some wonderful new treatment approaches that have improved outcomes for my patients. One, I'd like to mention is brain cooling. For children who have suffered ischemia or lack of oxygen, at the time right before delivery or birth, brain cooling has absolutely changed the whole picture of these youngsters who used to almost all the time have terrible outcome with severe CP and intellectual disabilities. And now, children are coming with much less severe problems and a lot more potential for improvement and change over time.

There are other treatments that are on the horizon as well. I've had a few patients with stem cell treatments for metachromatic leukodystrophy, and their prognosis is improving, as well as for disorders like cerebral palsy. There are tremendous things on the horizon will be helping pediatric patients as well as our adult patients.

Melanie Cole, MS: Because this is such a unique situation with these rare conditions, how do you manage the family's expectations and communication when you're dealing with rare and often misunderstood conditions? I mean, families are terrified. This is something that nobody knows that much about. How do you work with the families and manage their expectations?

Dr. Mary Keen: It's important, in my opinion, to let them know that we'll be on a journey together. I have some patients for whom we've never figured out the diagnosis. I've had other patients in whom the diagnosis was made at autopsy. I want my patients to know that whatever the situation is, I and my team will do our best to help them move along whatever the trajectory is. I really want to find the diagnosis when possible because there are treatments for some rare disorders if we pick them up on time.

For example, I have one little girl who has an unusual disorder with the ability to process glucose. She doesn't have a glycogen storage disease, but a very rare metabolic disorder that has largely reversed many of her symptoms just by going on a ketogenic diet. So if I don't have a diagnosis for a patient, we will still talk about what's going on and look at alternative options to try to figure out what is going on.

There is another resource I'd like to share with our listeners. There is a Neuroimmune Foundation that offers an annual course on Neuroimmune disorders, which include things like PANDAS, but there are many other autoinflammatory or neuroinflammatory conditions. They offer a monthly seminar for individual patients that any physician can request to discuss symptoms, symptom management, and look at diagnostic possibilities. I have used that for three of my patients and found it to be extremely helpful. I think we're fortunate as physiatrists. We have learned to be humble and rely on our team, acknowledge when we don't know something, and seek out help. And the Mitochondrial Disease Foundation, the Neuroimmune Foundation, the National Institutes of Health Undiagnosed Diseases Program are three wonderful resources that I hope my colleagues will consider taking advantage of.

Melanie Cole, MS: Dr. Keen, as we wrap up, are there any recent developments, clinical trials in Pediatric Physiatry that you find particularly promising that you'd like other providers to know about? And while you're doing that, please offer your best advice to young physiatrists who may encounter rare conditions in their practice.

Dr. Mary Keen: The most exciting clinical trials that I'm aware of in pediatric rehabilitation have to do with the transition of children with cerebral palsy into adulthood and their ongoing care as they age. There are a couple of groups that you can access through the American Academy of Physiatry, and the American Academy for CP and Developmental Medicine that are collecting data on children and adolescents and adults so that physiatrists, not just pediatric physiatrists, but adult physiatrists who will be assuming care for our children as they grow up, as well as community physicians, primary care doctors. We'll be able to better serve our patients with cerebral palsy and all the complications that are associated with them.

And my advice for young physiatrists is, if they're pediatric physiatrists, they should join the American Academy for CP and Developmental Medicine. They should consider referring their patients with CP to these new organizations that are following patients over time and collecting data that will be very important for ongoing care, as well as contribute to the knowledge base about the conditions that we serve. And in regards to the rare disorders, my advice is don't be afraid to accept them in your practice. You always will have something in your toolbox to improve the quality of life of the individuals that you accept and care.

Melanie Cole, MS: Thank you so much, Dr. Keen. You're a great guest as always. Thank you so much for sharing your expertise with us today. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/rehabilitation to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole.