The following transcript is automatically generated and may contain typos or misspellings. Please listen to the episode for the most accurate language.

Host  0:07  
Hello, and thank you for joining us. I'm Jaren Crump with the Lupus Foundation of America. In this episode of The Expert series, Dr. Anca Askanase, Professor of Medicine, and the director of the lupus center in the Division of Rheumatology at Columbia University, will be sharing more with us about her role in the successful treatment of a catatonic woman who awakened after 20 years. More details about the story can be found in a June 1 2023 article in the Washington Post written by Richard Sima. 

And I just wanted to add Dr. Askanase that when someone told me about this article that was in the Washington Post, and they said that there was a breakthrough related to lupus, I thought, if there was some sort of big lupus news, I'm sure that someone who was involved with someone, at least a name that I recognize or someone that I know. And when I read it, and I saw your name, I said, Oh, I was so excited. I'm like, "Oh, I know her! I work with her!" So very excited to be here and to have an opportunity to talk with you. So welcome.

Dr. Askanase  1:06  
Well, first of all, I'm excited to be here and talk about the story. I think it's an amazing story, its a success story, it's a story where nobody thought it would be possible to reverse or improve upon terrible psychiatric symptoms that have been around for decades. So it feels like it's a miracle of science. And it's a miracle, to have been able to be a part of this, you know, this woman's journey, so...humbled and honored to be thinking about this and humbled and honored to have been a part of this story. 

Host  1:55  
It's an honor to have you here, Dr. Askanase. Can you summarize how April's lupus was misdiagnosed as schizophrenia?

Dr. Askanase  2:04  
I think that it comes down to the fact that in the absence of physical symptoms, the psychiatric illness kind of takes over a person's life. And you know, as a physician, taking care of such a profoundly ill patient from a psychiatric point of view, it's hard to think about anything else other than taking care of the psychiatric illness. 

None of us were there when this all started, though, Dr. Markx my colleague from psychiatry, had run into this patient earlier in his training. But you know, like, if you're not thinking about the possibility of a different etiology for the psychiatric illness, it's impossible to do anything other than address the symptom, which is in the situation, the schizophrenia. 

So, you know, it's easy to be smart in retrospect, right? I mean, and that's kind of what happened here. Because, as he saw the patient, again, he was intrigued by the fact that her psychiatric symptoms were somewhat atypical. And that's how the quest for looking for something else came about. And we were lucky enough that the first thing that was checked was routine bloods, and an ANA and that ANA came back positive. So we all had a moment of like, well, "what if", right? So and then we send more antibodies, and the double stranded DNA, the anti-histone antibodies came back positive. So all of the story came together as in, oh, maybe this is an auto antibody driven attack on the on the nervous system. So getting a little more to know her and evaluate her, it also became clear that she had some joint deformities, and we're like, oh, well, maybe this was arthritis at some point. So is our minds open to the possibility of this being something else, the diagnosis came together a lot more easily. 

So we also, you know, did some brain imaging and we did a little bit of, you know, evaluation of the spinal fluid. So, all of these things kind of came together, suggesting that we may be right that this is not just psychiatric illness. And as we started treating, we were also very lucky that the family was very supportive, of of the possibility of treating and reversing some of that, you know, extraordinary damage. I shouldn't use the word damage because damage is irreversible. Some of the terrible situation that the patient was in. So we were able to have full partnership from the family, which allowed us to actually investigate and start on the correct treatment. 

So over the years, Sander Markx the director of precision psychiatry at Columbia and me work together on several other patients, none of them as dramatic as April's story where the treatment resulted in a significant improvement in the condition. So, you know, she went from very disorganized minimal interaction with the world to having full engaged conversations with us and the team and, and her family. So this felt like, you know, somebody coming back from a long lost state of non functioning, intellectual function. So, you know, it was it was both rewarding and extraordinary. And we all felt that there was a, such an amazing story that happened in front of us. 

And the other story that was described in the publication is a story of a young woman that was diagnosed with both lupus and psychosis at a very young age. There, things were a little more simple, the the trouble came that family situation and the psychiatric illness kind of got in the way of being able to treat the newer psychiatric symptoms. So once we were able to put together a team of physicians to help navigate scheduling, the treatments, the infusions, and and optimizing psychiatric management, that story also resolved in just a wonderful and positive way. And I think that the story of Devine is another uplifting story that kind of makes you rekindle hope, in, in the future of, of medicine, and in our ability to be better at taking care of mental illness. 

So I think that these are just wonderful stories where the team of physicians was able to address the problem. We are able to take care of the psychiatric issue, and the brain inflammation, and give these patients a different life. So it's just a wonderful and amazing opportunity to be involved in the care and to be part of the journey.

Host  7:43  
In the article, you're quoted saying, "I think we found our girl". And that's something that you said to Dr. Markx, could you just let us know a little bit more about what led up to that moment and what types of things were going through your mind when you realize that you might have found someone that could, you know, potentially lead to groundbreaking discoveries?

Dr. Askanase  8:01  
It's an endearing quote, and it's a young woman, you know, she's the age of my children. So it made sense that I would think of her as a child, and as someone that needs the attention and care of the world to get better. She came to me as a lupus patient with psychiatric illness, well, can you assess and make sure that we're treating lupus appropriately. And it became clear that while you know in terms of the non-psychiatric pieces of her lupus, things were not very severe. But it also became clear that she had enough evidence of autoantibodies, and enough evidence of CNS pathology, that we absolutely needed to do better, and return Devine to her family, to her life, and bring it back to society, which we are enormously fortunate to have been able to do.

Host  9:09  
Thank you so much for that. Can you share with us the critical turning point that led you in the team to identify lupus as the underlying cause of April's condition, despite her symptoms being clinically indistinguishable from schizophrenia?

Dr. Askanase  9:23  
So the ANA was the first clue, right? The second clue was the fact that she had changes on the brain MRI that were suggesting of the possibility of inflammation, and then that her spinal tap also showed evidence of inflammation. So it was the confluence of the serologic, the autoantibodies, the brain MRI, and the spinal tap. And also we actually had done an FDG-PET that helped us all put this picture together and And and proposed somewhere, you know, kind of gave us the eureka moment that this is probably an inflammatory brain problem. And then, as we learned about the possibility of, of the arthritis, and the more complete autoantibody profile, it all became clear. 

Was there an aha moment? So I believe that it's clear that there was an aha moment. And I think that what quenched it was when that double-stranded DNA came back positive, I think that was the quench moment like, yes, all these things are suggesting that there is some inflammatory autoimmune mediated process, and then double-stranded DNA was positive and see that that was the moment I said, You know what, it's gotta be brain, you know, it's got to be neuropsychiatric lupus, it's got to be brain lupus. And we were lucky enough that we were correction, with treatment, things improved. And that also, sort of, in a way, added to the burden of proof, you know, the fact that she got better with treatment, made it even more likely that we were correct. 

Now, all this is sort of in parallel with addressing the psychiatric illness. You know, this is not in a vacuum. We stopped everything. We only gave her, you know, steroids and cyclophosphamide. And she got better, we kept treating both illnesses. And I think that there is a, you know, an important body of literature that suggests that for people that have neuropsychiatric illness, that's the correct way to do it. Now, the other piece that, as I'm thinking about the story was that I have consulted with colleagues, you know, to just get a better sense of like, Hey, let me tell you the story, how interesting, how different, how extraordinary the story is. And I consulted with John Hanley, from Halifax. And he agreed that this sounded like we were on the right track. But these are situations where you have to doubt yourself, right? I mean, you know, none of us hold the absolute truth in our hands. So every little piece helped. And the turning point for me was a double stranded DNA, but I really needed this team around me, the community of lupus doctors to come together, I needed the psychiatrist and a neurologist to work with me and kind of like, help Crispin have this picture come together. And I'm very grateful to my colleague and my friend, Dr. Sander Markx for bringing the story to my attention, because you need someone to say, this doesn't add up from either side, right. I mean, either from the rheumatologist side, or from the psychiatry side, you know, this case was him saying this case doesn't add up. For the other case that was described in, in that famous Washington Post publication was a case of lupus. That wasn't making sense. So it's, it's a team effort. And it's a it's a bringing together of the minds to come up with the right diagnosis, the right treatment plan, and make a difference.

Host  13:33  
Thank you so much. How does your discovery about the connection between autoimmune diseases like lupus and psychiatric disorders, such as schizophrenia impact the way these diseases are diagnosed and treated?

Dr. Askanase  13:44  
While I'd like to take credit for discovering this, this is neuropsychiatric lupus as part of the spectrum of lupus. So I feel fortunate that I was able to make a difference for these patients, and that we were part of this increased awareness and moment of refocusing the attention of the world on the possibility of psychiatric illness being inflammatory in nature. So I think that this is the discovery of the lupus community. These are patients that are part of the spectrum of lupus. These are patients that maybe sometimes fall through the cracks and we never get to them. But this is built on to decades of under a better understanding of lupus and I give credit to my lupus colleagues and the work of John Hanley that started shedding light on neuropsychiatric lupus.

Host  14:45  
Thank you so much for that. Can you discuss the potential challenges and ethical considerations that arise when treating patients who have been institutionalized for years like April for psychiatric illnesses that may have an autoimmune cause? 

Dr. Askanase  15:00  
I think this is a very important question. And I think that this is at the heart of the matter. Unless you have the support of a family that is interested in understanding what happened, unless you have the option to probe into the stories, you're going to be left with unknowns. And you're going to be left with inability to help people that could possibly be helped, and where the chronic psychiatric illness can be turned into an episode that is, has reversibility. 

So we are lucky for both of the stories to have had extraordinary family support, engaged parents, engaged siblings that were willing to provide both the consent and the family support around the stories so that we can make possible such an amazing recovery. And I think that, you know, there are ways around consent, and are there are ways around engaging patients that otherwise lack capacity, yet, it's a lot more complicated. So the fact that we had family support for these cases, was critical for our ability to help. 

Host  16:28  
From this groundbreaking case, what potential implications do you see for the future of psychiatry, particularly in terms of understanding and managing other mental health disorders that might have autoimmune groups?

Dr. Askanase  16:40  
So I think that over the past several years, there's a there's a lot more understanding of inflammation as a cause of psychiatric illness. And I think that the work of precision psychiatry team here led by Dr. Markx will help further that understanding of inflammation, autoimmunity as root causes of some psychiatric illnesses. I think that for us, we hope that awareness of the possibility of neuropsychiatric lupus, which we're very grateful that these cases brought to light as part of what we need to do. 

I think that all people that come in with a typical neuropsychiatric manifestation should have an ANA. And we'd like to be a part of making that the standard of care, especially in people where there are some, there may be family history of autoimmunity, especially in people where there is no family history of psychiatric illness. All these stories that don't perfectly add up should all be investigated. And the ANA is a simple and easy test to do. Very happy to be a part of sorting that out for as many patients as I can.

Host  18:08  
One final question. You found more potential patients. Can you talk about what next steps your team is planning for these individuals and how your work could transform psychiatric care at a broader scale? And what the response has been like from the lupus community as a whole.

Dr. Askanase  18:23  
You've thrown at me really complicated questions. And I'm grateful for that. Because I think that I think that stories like this groundbreaking stories like this should transform care. And, and I think that these particular stories will transform care. So for me is opening my eyes and my ears to all the stories of patients that are coming in with neuropsychiatric illness. That is not, that doesn't quite fit the mold. We're very fortunate at Columbia, there's a there's a psychiatric institute that's part of Columbia University. So we will be paying more attention. We will be we have put together a protocol for treatment of these cases. And we hope to be able to report soon that we have taken care of more people with neuropsychiatric lupus over the next several months. So we put together a case series of four cases earlier. In the meantime, we have two more cases that Dr. Markx and I have worked on together. And there's someone right now that is being treated for neuropsychiatric lupus. And as early as after the this first cycle, the first combination of cyclophosphamide and steroids, she's already showing evidence of a lot of improvement. 

So I do think that we'll be working hard to identify all the patients come our way, and make sure that they all have the correct treatment. Now, I think that it's for the lupus community. This is also a groundbreaking moment, I think that we're again reminded of the possibility of an immune attack at a very, very large scale on the brain, for people with lupus. And I'm hoping that this will spark further interest in better understanding that immune attack and working to find more precise ways to diagnose it, we have worked with tried to do functional MRIs and these patients, we are hoping that we'll have will soon have more data to show the world about better diagnosing this, and, and fully understanding the spectrum of brain involvement, and also document the improvement. So we're hoping that these amazing stories will be a major catalyst for both the psychiatric community and the lupus community to come together and identify all the cases, treat all the cases, and make sure that your psychiatric illness in lupus and other autoimmune conditions is fully addressed and taken care of.

Host  21:28  
Wonderful, thank you so so much for joining us to discuss this exciting article and this breakthrough in lupus treatment and research. Is there anything else that you'd like to add?

Dr. Askanase  21:41  
Some years ago when I was just starting to take care of people with lupus, I used to say everyday lupus teaches me a lesson. And I had hoped that at some point I will learn and I would have been taught all the lessons of lupus and these stories again, reminded me that every day lupus teaches us lessons. And the learning from these lessons will propel our understanding and our ability to better take care of people with lupus. 

I'm grateful to have been able to listen and I'm grateful to have been able to act. And I'm also very grateful of the support of the lupus community. Patients send me notes, Sandra Raymond, the former president of the LFA send me a note about the article. So these are important stories that make a difference. And we're hoping that we're going to be part of breakthroughs in the next years coming to people with lupus and people with neuropsychiatric lupus. Grateful to share the story and talk about my involvement with these cases. Thank you.

Host  22:55  
Thank you so much Dr. Askanase. And yeah, I guess we can end the show there. Thank you so much for listening to this edition of The Expert Series. I'm Jaren Crump with the Lupus Foundation of America.

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• Episode 4: Lupus and the Kidneys
• Episode 5: Preparing for a Doctor's Appointment
• Episode 6: Childhood Lupus and Mental Health
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• Episode 8: 5 Common Questions About Diagnosing Lupus
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• Episode 3: Mental Health and Wellness During a Time of Uncertainty
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• Episode 5: Reproductive Health and Lupus
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• Episode 8: 2021 Lupus Treatment Research Updates
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• Episode 10: Diet, Nutrition, and Kidney Health
• Episode 11: Caring for Caregivers
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• Episode 3: Recursos Financieros Para Personas Hispanas/Latinas con Lupus (Financial Resources for Hispanics/Latinos with lupus)
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