Answering Your Rare Disease Day Questions!

Episode Transcript

Dr. Correa:
From the American Academy of Neurology. I'm Dr. Daniel Correa.

Dr. Peters:
And I am Dr. Katy Peters, and this is the Brain and Life podcast.

Dr. Correa:
Welcome back to the Brain and Life podcast. Now, we're here today and we have been getting so many great questions and today is Rare Disease Day, so we wanted to focus in on some of the questions we've been getting or requests for conditions where we may not have found a guest yet, or we're just seeing a lot of discussion about, and we want to make sure to get you that information now. So, that's where we're going to start today. Katy, I think you have one of the most commonly talked about questions in our community and on social media now.

Dr. Peters:
Yes, I think it's a common question on our rare disorder. So, I think that's important to tell our listeners is that these rare disorders, they can often come to awareness because maybe somebody famous has it, maybe there's something else in the media about it. Maybe there's been a movie or a book about it. So, it piques people's curiosity.
So our first question is from Jill S. And it's, I keep hearing about stiff person syndrome all over social media since Celine Dion spoke about her diagnosis. It is very confusing to me, can you explain what it is? So, I think that's a great segue to again, what's out there. We hear about it now commonly because there's a famous person, but it is a rare disease.
So, stiff person syndrome is a rare autoimmune neurologic disorder that comes with muscle stiffness, spasms, and rigidity, and it can lead to really significant morbidity and disability. It usually affects the muscles of the trunk and the core, and also the arms and the legs can also be involved. And what can happen is your flexor muscles and your extensor muscles can be activated at the same time, so it can be very painful for a patient. So they can have difficulty with movement and posture, and unfortunately, the condition can be very progressive and can worsen over time.

Dr. Correa:
Yeah, I mean, our bodies are an amazing balance of coordinating systems, and in this included is the coordination of all of our movements between flexion and extension muscles, and this is one of the issues where there's a disruption in that. Over time, someone with stiff person syndrome might develop a inward curve of their spine, or what's called a thoracolumbar hyperlordosis, another one of those big names and words we'll throw around. But in this situation it's just an increased curve in their spine or an S-shaped spinal curve that worsens and can lead to even more prolonged muscle contractions. That's one of the things that can change, but many people have a lot of disruption even before then.
This stiffness is different from what can be seen from other injuries to what we call the upper motor neuron system, which is sometimes affected with strokes. Other neurologic conditions like the rigidity that someone has when they have Parkinson's disease and we've talked about in other episodes, the muscle spasms and stiff person syndrome can be very painful. They can be triggered by emotional distress, anxiety, other sudden stimuli, that muscle jerk or that startle response that we'll have to things can be amplified a lot in these individuals. And these spasms can occur in episodes or what some people would describe as attacks, that can last for hours and in severe cases can have a lot of discomfort and might end up requiring the person to see emergency care, either because of the pain or even if it's starting to affect how well they're breathing.
Now, in my case and at our center, we've actually treated some individuals with stiff person syndrome who have an overlap with other medical conditions. Within our epilepsy center, that is one of the specific conditions that can come along with it. They can have either seizures or some of their events have to be distinguished from whether or not it's a movement problem or a seizure.

Dr. Peters:
Yeah, it's very interesting, that stiff person syndrome. It's that you have autoimmune phenomenon and it can come with other autoimmune phenomena, and sometimes it can be a form of epilepsy, sometimes it can be problems with their cognition or even a neuropathy.
What I think is really particular for this condition is that because of these spasms and these muscle contractures, those patients can develop very specific or task-specific phobias, or even what we call triggered dystonias, that when they go to a situation where their muscles have to be activated. So you can imagine if you have to go into a crowded place and you have to walk, or maybe you want to use an escalator or maybe you're trying to do some type of professional activity like dancing or singing in the case of Celine Dion, these actually can bring on a phobia or an even challenging dystonia, which is an abnormal movement associated with those conditions. It's thought that those could be a component of anxiety, but also in addition to anxiety, it may also be that the muscle itself has sort of a heightened reaction and it could be associated with the disease and even the underlying autoimmunity.

Dr. Correa:
And one of the things that makes it difficult to understand as we're hearing about it in social media and other individuals with stiff person syndrome become more public, is that we actually don't understand and know exactly the cause of stiff person syndrome. We know that it involves the autoimmune system and the inflammation system in the body, and the body's immune system seems to mistakenly attack the central nervous system, the nerves and wires of our brain and spinal cord. And specifically, it targets something called the GABAergic system. This is the system of chemicals and receptors that help regulate muscle relaxation and activation. Like we talked about, that flexion and extension, that coordination needs to happen for all types of movements.
In stiff person syndrome, they have a higher level of these antibodies that are against an enzyme that's crucial to regulating the communication between muscles, something called GAD, and these antibodies can disrupt this system, the GABAergic pathway, and lead to hyper-excitability of these neurons, these muscle neurons. And so the coordination we've talked about before, between relaxation and activation, between flexion and extension, gets all disrupted. And this can lead to many of the symptoms that are occurring with it, but we don't really exactly know the role of the antibodies in the whole process or what leads to the antibodies. And so, this is what leads to some of the confusion that's out there and misunderstanding both in the scientific community, but also it's harder when you can't just point to the issue and then it becomes a much clearer process for everyone to understand.
Some important things note also for people who live with stiff person syndrome and some overlap, is that it can be associated with other autoimmune diseases like type one diabetes or thyroiditis. There are autoimmune types of diabetes and thyroid disease and they can have often an overlap with stiff person syndrome, in addition to the epilepsy I mentioned previously. And there's a whole category of conditions out there called paraneoplastic syndromes and conditions. These are the conditions where a tumor or the process that leads to a tumor can start to form antibodies to other parts of your body, or as your body tries to attack a tumor, some of those antibodies can get mixed up, and these are called paraneoplastic. And so in some rare instances, the stiff person syndrome may be a part of an underlying cancer.

Dr. Peters:
You know what's really interesting, Daniel, is given that if it is a paraneoplastic condition, it's often we find these conditions first before we ever find the initial cancer. And so, some of the testing that may include if you get diagnosed with this, ultimately with this disease, is to look for something, but first, you have to make the diagnosis. And it used to be that we didn't really know much about these conditions, like when I first started training, which was a long time ago in a land called long time ago, but now we have blood tests that can actually look specifically for the autoantibodies for that anti-GAD antibody.
You can also do what is called an EMG, which is a test of the muscle activity to see if those muscles are actually activating. And one of the key tests is actually to see that both flexion and extension are activated at the same time in the patient's muscles. And then again, you want to do those imaging testing, whether you're concerned about an underlying cancer or maybe there's something else going on in the brain.

Dr. Correa:
And going back to the thing that we mentioned before, since we don't know the exact cause, that makes identifying a cure incredibly difficult. And like many other situations when we don't know the cause, there is not currently a cure for stiff person syndrome, but there are treatment options that help manage the condition. Unfortunately, there also isn't a treatment option that affects the progression of the disease. It still progresses, what we can do is limit or slow that at times, and that's something we often call as disease modifying in other medical conditions.
And so, some of the medications that are used and like we saw in the documentary with Celine Dion are muscle relaxants that can help reduce the stiffness and the spasms. Sometimes some muscle relaxant effects can also come from anti-seizure medicines, if the person also has seizures. Then there is the immune therapy. We talked, we know that there is a disruption in the immune system. And one of the most common and first ones that's tried for people is something that many of our listeners may know of from other medical conditions, called intravenous immunoglobulin or IVIG. And another treatment process called plasmapheresis, where they take your plasma out and try to wash out the antibodies. And so, these may help modify the immune response. There's a few other ones that affect your immune system.
And then there are the other aspects. Pain management, the other anti-seizure or anticonvulsant medications. And when pain is very significant, then all the different options for pain management. And key here, since we're talking about movement and function, is the physical therapy and the occupational therapy. Each person needs to cope with the changes that they're having in their abilities.

Dr. Peters:
This is a fascinating area of research, because there was so much done in what we call immunotherapy to sort of look at harnessing the immune system or how to dampen the immune system. So there's a lot of research being done with newer agents. The consideration for even doing stem cell transplantation for really severe cases has been considered. Also the use of something called chimeric antigen receptor T-cell targeting therapy. This is something we're actually in the oncology world to modify the immune system to help attack the cancer, but it may be beneficial in these really rare refractory cases of autoimmune conditions.

Dr. Correa:
And that's what they call a CAR T-cell therapy, right?

Dr. Peters:
Yep, that's what they're called, CAR-T. Sometimes it's T-CARS, it matters what car you're driving

Dr. Correa:
And the progression, as we've talked about, can vary for each person, depending on the car. In some cases the condition can be stable for many years on treatment, or maybe we don't know the exact cause for that person and if that cause gets removed or stopped, then things can stabilize. In others, it could rapidly worsen and lead to significant disability. So, that's where I think the whole workup and looking for all the possible causes and things that might be overlapping are important.
And there's the most important thing is early diagnosis. If you're seeing this combination of symptoms or you're concerned with it, then bringing it up with your doctors. And at least while we don't know the causes exactly, we know that there is a good treatment pathway and a good diagnostic pathway.
Now, I wanted to distinguish, so in this last topic and everything, we were talking about a condition where we don't understand a lot of the aspects of it, but we do know that there's a disruption in the immune system and that that immune system affects and attacks specific areas of the neurologic system.
We got a question from Aurora that I think is going to be very helpful in distinguishing it from other situations and some of the conversation that's had about Celine Dion and people living with a stiff person syndrome. Aurora wrote to us sharing that, "I have a functional neurologic disorder, FND. How do I explain it to my friends and doctors? No one seems to understand and I really feel like people don't believe me."

Dr. Peters:
Well, Aurora, thank you for this question. I'm really intrigued by this question because it's not just the condition of the functional disorder that she's asking about, but rather, how do you explain it to family, friends and providers? Now, Daniel, I know as a seizure specialist you encounter patients with functional neurologic disorders. Can you tell us a little more about it?

Dr. Correa:
Yeah, and first I wanted to acknowledge, thank you so much for sharing your situation. And functional neurologic disorders can have a wide range of symptoms and can be unique to each person. So, some people with a functional disorder may experience non-epileptic seizures like we talked about, and what we see. But functional neurologic disorders are the second most common reason to see a neurologist, after headaches. And so, even though they are still rare as a diagnosis, so that's around 1.2 or fewer people per 10,000 each year, that it's also higher in those who live with psychiatric conditions, about one to two people per 10,000, but they are still rare conditions.
And so, a functional neurologic disorder, for among the scientific and clinical community has been described as a condition that's caused by changes in how our brain networks respond to stressors, or that work in those responses. It's rather than a change in the structure of the brain itself or including the receptors and everything else that we describe as we see in some other neurologic disorders. Effectively, it's a disruption in how your nervous system is regulated. And the treatment focuses on empowering and strengthening an individual or person's physical and psychological coping tools to restore a balance in how you respond to stressors for your neurologic system. It can often be best to achieve this with physical rehab and psychological interventions, and some medications to help with the symptoms. And so, sometimes it's also important to note that functional neurologic disorders can come alongside other neurologic conditions and medical diagnoses that may have their own medical conditions and treatments and rehabilitation goals, so everything has to be balanced together.
Now, that was the more detailed and even in that explanation and all the time I took, I can totally understand how it's challenging to explain to your friends and family. So, let me try a simplified version, and as we would try to share or as I often think of, like, how would I explain it to my niece and my aunt and my grandma? And so, functional neurologic disorder is when there's a problem in how your brain sends, receives, and processes signals, but there's no damage or structural dysfunction to the brain itself.
So, you can think of it like this. Your brain has many networks that communicate with each other. When you get physically or mentally stressed, in this situation, these networks can get mixed up. And that mix-up can cause problems in how your body moves, feels and responds to things. But thankfully in this situation, as a diagnosis has been occurred, they've been able to rule out that there isn't a specific disruption or injury or structural damage to parts of the brain, spinal cord and nerves. So, instead of fixing something broken in your brain, the goal is to retrain your brain on how your body and brain work together. So the goals are to do this through exercise, physical and mental health therapy and sometimes medication to help with other symptoms. It's about helping you manage and handle stress and strengthen your body and mind connection. So, sometimes functional neurologic symptoms can come with other health problems, and then that brings in the importance of balancing and working alongside your doctors to help manage things.
So, hopefully those two versions help you find the words that feel true to your own experience. What do you think, Katy?

Dr. Peters:
I think you did a great job. Kudos to you, Aurora. It's spot on. Seriously, this is a really good response. I'm going to use it. Is this going to be recorded somewhere? Yes it is, it's going to be on a podcast. So, I think specific to your question, Aurora, I was really intrigued by it because I was like, how do you communicate this? And this is something that I get from my patients a lot, like, what do I tell my family and friends? What do I tell the curious about what's going on with me?
And so specific for this, I had to do a little research. I found a really nice website, it's called neurosymptoms.org/en/, and it was a really nice resource on the functional neurologic disorder and it provided a great deal of information. But I felt in reading the website and going through all the pages, not only did you have information, it had a lot of support and understanding. I really felt that it was really there for the patient. And they actually had a specific section on how to communicate with family, friends, employers, maybe your school system, and also those curious people.

Dr. Correa:
Yeah, and a few other resources that I've found, and I have referred people and community members to, is FND Courage, that's at FNDcourage.org, and FND Hope, also their website is FNDhope.org. And you mentioned your providers, and so I think the importance there, and at least from our perspective of course as providers, it's important to be open and honest about your medical conditions, including a functional neurologic disorder diagnosis. But also, having a summary letter or even just a copy of your last visit and note with the specialist that diagnosed your functional neurologic disorder can be very helpful for other health providers to understand and see where it fits in with your other medical conditions or the current issues and symptoms that you're seeing them for.

Dr. Peters:
I think that's great advice.
And for our final one, it's a rare, maybe it's a rare but also commonly thought of condition. And it's a question from Carl R. It says, "Hi, I'm writing to ask about face blindness. Thanks, Carl R." So face blindness, also known as facial or visual agnosia, also known as prosopo agnosia, is the inability to recognize faces, whether they're familiar or unfamiliar. This term derives from the Greek words, prosopon for face, and agnosia for lack of knowledge. And normally, a person can recognize many, many different faces, but this condition can actually impair that ability to recognize a familiar face.

Dr. Correa:
Yeah, I mean, prosopagnosia was initially described really based on strokes and other structural injuries to the brain. Though, we've seen since that there are different types of facial and visual agnosias that can come with other conditions. And as we've increased our understanding, we also see that there are varying degrees of prosopagnosia or these visual agnosias. And so, some might just be the inability to recognize, maybe discriminate, or identify faces, and a more extensive sense, even your own face in a mirror or from a photo. And others might be difficulty distinguishing faces from the surrounding objects, which can even further complicate the challenge if faces are next to a sign, and having that clear understanding and the cues of shapes. And those people often have to cope with relying on cues of movement, voice, and other shapes they recognize from individuals or people, or that they can distinguish people and individuals from inanimate objects or other animals. It can be quite a challenge for individuals.
However, those strategies may not be enough for the individual. They may need and may lead to social and psychological challenges that affect their mental health, whether that's depression, anxiety or just a severe extent of social isolation. And they may struggle even following and watching TV shows or movies. And so it may limit the types of cultural experiences that they can have.

Dr. Peters:
As you mentioned, it can be either acquired or hereditary, and those acquired cases can come from whether it's stroke or type of brain injury or a neurodegenerative disease. I've seen it in my patients with brain tumors because they can have a localized brain lesion. It can also be hereditary, and that's a little more common. It's thought to be inherited in a autosomal dominant fashion, and affected children may have a different thing than adults. They actually may have social or behavioral challenges just because of those symptoms. And so that's something to definitely consider.

Dr. Correa:
This is kind of one of those situations where it's key that we get a picture of the brain and to understand and see what might be related to the symptom coming up, and that may also inform some of the options for helping support the individual. And so on those brain images or pictures, we might see damage or even a developmental abnormality in the brain structures that relate to perception of the face and memory. That's something called the fusiform lingual gyrus. And then other times, there's a network of that area that connects to memory structures and emotional structures, including areas called the temporal cortex and the amygdala. They're all, probably the amygdala is the one that most people hear on television more often than anywhere else, but this is all parts of networks that involve our emotion and our memory pathways that relate to vision. And when someone has a developmental or if it's hereditary and that leads to a developmental dysfunction, that may result to a disruption and dysfunction in how the brain develops this facial recognition network.

Dr. Peters:
Yeah, and to diagnose this, I think it's, you mentioned before, you could do brain imaging. You can use what is called a PET scan or also a magnetic resonance imaging of the brain itself. And they can even do particular functional imaging, where they ask you to do particular tasks like looking at faces and seeing if certain parts of the brain, such as the fusiform face area, light up. But what I think is even more interesting is really the tests that can be done by our neuropsychology colleagues. They can do object face perception tests, also known as the Cambridge Face Perception Test, and also recognition tests to evaluate for both short-term and long-term facial memory. And also identification tests, incorporating auditory and tactile cues, because we don't just use our eyes, we also use our voice and also touch to understand who's with us, so maybe those can be beneficial.
Now, no specific guidelines that exist for managing prosopagnosia, but of course if it's something that needs to be evaluated, you can have your neurologist, a neuropsychologist, and other mental health professionals can be involved. Also, this is where occupational therapists can be quite helpful. They can provide a lot of support for patients and caregivers and recommend important adaptations.

Dr. Correa:
Yeah, I mean, it's a fascinating situation and amazing to see many people manage in their life and socially.
So, I've really enjoyed that discussion with Katy, but it's a doctor's life, and so Katy actually had to just step away to help support her medical team and people getting care at her center this week. But we had one more question that I thought we really wanted to get to, so I'm going to take this one solo. Maria L. Wrote to us and told us, "My sister had a baby last May, and she has lissencephaly, or a smooth brain disorder. We have found amazing doctors to work with and are aware of what the expected outcome is for her life. This whole experience has led us to learn more about living with grief and love at the same time, I wanted to write in to shout out to other parents or loved ones going through similar things, and to ask if there are any suggested to do when it comes to mentally and emotionally dealing with such uncertainty and tragedy every single day."
Well, I mean, Maria, I think you are doing the example of what many of us should do in these kinds of situations. You're looking for the love and the joy that you have in your niece, and together with your family, and really taking appreciation for the time that you have together each day.
Now, for the rest of our listeners, I wanted to get into a little more detail and explanation on the smooth brain disorder or lissencephaly, that Maria refers to. So lissencephaly is a term that covers a variety of serious brain abnormalities or deformations. One of them can be described as agyria, which is when the brain has no folds. The brain has lots of little extra areas of folds for greater surface area. And on the alternate aside, sometimes people can have too many folds, called pachygyria. And then there's another condition where things don't fully migrate to where they need to be, called subcortical band heterotopia.
And so, lissencephaly translates to smooth brain, as Maria had laid out for us, and that's where there is the brain surface over an area or region is described to be more smooth than it should be in that normal situation. This happens when neurons or the nerve cells don't move to their proper places while the baby is developing in the womb, usually somewhere between 12 and 24 weeks of pregnancy. The irregular movement of those cells results in a way where the brain is not formed in its natural folds and creases. And children with lissencephaly can experience considerable delays in their neuronal development or their neurologic development, and mental disabilities, and that severity can vary a lot from one child to the next. It depends on how severely the brain is malformed or not fully developed and well-formed, and whether the child has constant uncontrollable seizures or other complications from this brain malformation. Lissencephaly is a condition that affects that brain development and can occur either due to a genetic cause or other non-genetic stressors to the baby's brain and development when they were in the womb.
And one thing that's important to consider is that for some children there are less severe forms. So, automatically hearing that a family member or a friend's child has a brain malformation, lissencephaly, or one of these other terms that we've used, doesn't automatically put them into the category of a much more severe result. It depends on how much of the brain is involved. They may end up having some normal areas of development and only minor learning difficulties if it's only a very small area of the brain. Additionally, a large majority of the children who have lissencephaly somewhere between 9 out of 10, will experience seizures or epilepsy during their first year of life. That's one of the most commonly associated complications associated with it.
The main goal in treatment is for those children to do as many other things that can help contribute to healthy development. And for children from the neonatal state, all the way as they're growing older, diet and sleep are often key aspects. And unfortunately, some children in this situation may have difficulty with their eating and swallowing, and that can be something that affects their progression.
And the other key aspect is if they develop the main complication of seizures or epilepsy, then getting involved with doctors to help manage those complications. The parents or families of children with lissencephaly are typically offered genetic counseling to help also and see if they have specific reasons that children in their family might be at greater risk. And this involves working with a healthcare professional who can help families understand the genetics of lissencephaly in their family and their child, and whether or not there are risks with further children or other family members.
The future health outcome for the children who live with this syndrome depends, as I said, on the seriousness of the malformation. And it's important to note that the lissencephaly can affect lots of variety of areas and parts of the brain. So like many other things, it's where it occurs in the brain that ends up describing how many issues someone might have.
But again, I'd like to go back to Maria and her point of looking for opportunities to focus on their family's health and love and the time that they have and encouragement and support of her sister, I think that's something we can all do. In times of uncertainty, we can look to the closest circle around us, where we can share and affect change and support and love in those around us, and I think that helps us give some sense of and grasp on what is going on in the world.
Thank you all, for these great questions. We look forward to many more of your suggested topics, guests, and questions, as we all look to live better with our own abilities.
Thank you again for joining us today on the Brain and Life podcast. Follow and subscribe to this podcast so you don't miss our weekly episodes. You can also sign up to receive the Brain and Life Magazine for free at brainandlife.org.

Dr. Peters:
Also for each episode, you can find out how to connect with our team and our guests, along with great resources in our show notes. We love it when we hear your ideas or questions. You can send these in an email to Blpodcast@brainandlife.org, and leave us a message at (612) 928-6206.

Dr. Correa:
You can also find that information in our show notes, and you can follow Katy and me and the Brain and Life Magazine on many of your preferred social media channels. We are your hosts, Dr. Daniel Correa, connecting with you from New York City and online at Neuro Dr. Correa.

Dr. Peters:
And Dr. Katy Peters, joining you from Durham, North Carolina, and online at Katy Peters MD PhD.

Dr. Correa:
Most importantly, thank you and all of our community members that trust us with their health, and everyone living with neurologic conditions.

Dr. Peters:
We hope together we can take steps to better brain health and each thrive with our own abilities every day.

Dr. Correa:
Before you start the next episode, we would appreciate if you could give us five stars and leave a review. This helps others find the Brain and Life Podcast. See you next week.

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