Episode 452: The Clinical Unknown Series – Young lady with dizziness

[MUSIC] Welcome back clinical problem solvers, Maddie and Yusuf here. At CP Solvers, our mission is to make clinical reasoning accessible to learners worldwide. We invite you to join us for our live virtual morning reports, where we break down cases and sharpen our diagnostic reasoning together. Now over to you Yusuf. Thanks, Maddie. Just a quick reminder, this podcast is for educational purposes only, and is not a substitute for medical advice. Patient details haven't modified to protect their privacy, and the views expressed your own, not those of our employers. Now, let's dive into the case. Enjoy the show. [MUSIC] Hello everyone, welcome to another episode of the clinical no series. My name is Deborah. I'm a Brazilian graduate on Argentina, and I am currently living in North Carolina, studying to apply for residency. I'm here with my dear friend Noah. Hey everyone, I'm Noah, a Brazilian physician, and now internal medicine resident in the states. We also have Mark here. Hey everyone, my name is Mark. I'm from New Jersey and I did my medical training in Philadelphia, and I'm currently a second year hospital set Stanford. The clinical on no podcast is a series that have us three as leaders, and in the podcast we present a medical case in Nalicot to a guest that has no details about the case. The guests go sharing their thoughts and insights. Our brilliant guests are part of our team. Besides the podcast, we also have a website with diagnostic schemas and illness scripts. We also host daily free Zoom-based morning reports, where guests present clinical knowns to our team live, much like our podcast. The links go out on a mailing list found on our website. We also have the clinical problem solvers Academy, who is a group run by medical students, residents, fellows, and attendants, whose mission is disseminate and democratize the teaching of clinical reasoning. We are a nerdy but fun group who will love to talk about medicine, clinical reasoning, medical education, life, and all things in between. We invite people that are active in our virtual morning reports to join the CP Salvers Academy and learn together. Visit our website to learn more. Welcome back clinical problem solvers. This is Noah and I'm excited to be hosting another clinical and known episode. And today we have a special guest, Ethan. Ethan is a graduate from Taiwan. He's completing his post-graduate training, and he's planning to apply to internal medicine. And he's also an Academy member for what about two years now, Ethan. Fun fact, Mark, I actually reviewed Mark's first case to the CP Salvers, and I was just talking to Ethan before we started the recording. I actually discussed Ethan's first case. So we definitely go a long way back. Ethan, I'll let you say hi, and then you can pass it on to Mark and Deborah, so they can introduce themselves again. Yeah, thanks for the introduction and Noah. Yeah, it's been a while. I think it's about one and a half year, all two years since I joined the CP Salvers, and just very grateful and glad to be around these, these bunch of smart and kind people. Yeah. And Noah, Mark and Deborah are the ones that I really look up to, and it's such a pleasure and honor to be in this space to present a case to you all. Yeah. It's a very kind words, Ethan. You always bring incredible cases to our Academy. This is a shout out for all you guys listening to join us on VMR, and hopefully one day you guys can be invited to the Academy and train on cases that Ethan presents. He always brings not only complex clinical reasoning cases, but management reasoning cases. He always asks great questions about antibiotics and intensive care patients, and it's just, yeah, it's a very nuanced question. So I'm always a big fan of this case, so I'm sure that I'll come out today. How you doing, Deborah? Hey, everyone. Oh, I'm really good. Happy to be here with you all. Thank you, H&F, for accepting our invitation. I just want you to reinforce what Noah and Mark said. He's always participating in the Academy and bringing interesting cases and images to you. So we really appreciate you being accepting our invitation. So I just, before we start with the case, I want to know from you all what are you guys expecting from a future soon, when if anything happened, anything that you have some expectation? I can answer, and I, next month, I'll go to Bruno Mars concert, and I'm really, really excited. I love him, and he will be doing a tour, and nothing. I think it's going to be awesome. What about you, Noah? Bruno Mars concert, that's crazy. My parents went to it, and they said he had such good stage presence, so they didn't take me. I was working, and they just left me back in my home city. Something I'm looking forward to. Andrew was actually in town. So Andrew was one of our beloved Academy members. He has his own podcast, "agnostic ATPNL," and he's actually coming here to St. Louis to, you know, for some personal reasons, and we're meeting him up for dinner, so it's going to be me, Marcella, Curtin, and Andrew later tonight. So I'm looking forward to that. What about you, Mark? Wow, I might have to book a flight to St. Louis. That sounds like a whole lot of fun. Yeah, and I got a lot coming up in the next month. I guess me and my wife just bought our first home, so we'll be moving in next month. And then we'll have our baby shower, because my wife is pregnant, and the housewarming gathering at the same time. So really, really excited for that. So yeah, a lot of big life events coming up. So super excited for that. How would you be thinking? Congratulations, Mark. Yeah, I know you're gonna be the best dad ever. And excited to go into the new trouble of your life. Not much in my life, but I'm a huge baseball fan, so right now when we're recording the World Baseball Classic, it's going through. Hopefully, I think when this podcast came out, we'll re-know who the winner is or not. But I think the atmosphere is all of World Baseball Classic, just amazing and just looking forward to, like, watch those games. Yeah. I'm a huge baseball fan, too. The US is doing pretty good right now. My favorite baseball player, Aaron Judge. Had a home run on his first event out of the World Baseball Classic, so I was really excited about that. Maybe our team, so I'll match up soon. All right, y'all. Should we get started? Ethan, are you ready? Yeah. So I bring a very, I think a very interesting case for you all. So basically, I have divided this case into six L-Equats, and the final L-Equat will reveal the diagnosis. And in the first L-Equat, we have a 18-year-old female with a chief complaint of intermittent dissonance for one month. So she basically has no non-matical history and a unremarkable social history, just well. Basically, unremarkable social history, family history, and operational history. She's also a term baby who has a vaccinated up to date with normal growth and developments. So what she mentions is that she has been feeling intermittent dissonance and with spinning sensation for the past month, with a frequency around two to three times per day, and each duration around 30 minutes to an hour. And it would be relieved after sleep. And the symptoms are accompanied with a nausea and vomiting, occasional diarrhea and photophobia when she was experiencing the dissonance, as well as bilateral tynitis. And she mentioned that the symptoms are getting severe, that she would sometimes even fall when walking. And she was a swimming player in high schools. And recently when she came into the ER, she mentioned that she also has a right-like pain. And mentioned that, and for the past month, she has once developed a fever up to 38.2 degrees Celsius. And before she went to the ER, she also went to the E-Antiplanet before and was prescribed with some symptomatic drugs, but with no improvement. [ Pause ] Well, that's a lot of information. And an interesting patient population, 18-year-old female, before we dive into the complaints, I'm going to just briefly talk about the way I think about young patients. So whenever there's a young patient, there's a mnemonic that we can see piece over as a like to use, which is bad luck, bad genes, or risky behavior. And that kind of reflects that younger patients have a different epidemiology than older patients. Right? So I really like that Ethan brought up the prenatal history, because you know, as the younger you are, the more relevant it is. I don't get a sense that she was unhealthy before although symptoms begin, it seems like they began about a month ago. And it's been slowly progressive. So maybe less likely a genetic component, although some genetic causes can have a later onset. And I can really think of any risky behavior, exposure wise, that would cause someone to have this constellation of symptoms. Maybe she just has bad luck. Now, for the symptoms, it seems like she has a syndrome of dizziness, and she also has a bunch of different associated complaints. Dizziness is very interesting. I think it's a very hard thing for patients and for doctors to characterize well. And I think a bunch of different complaints get conflated into a single syndrome. I appreciate the Ethan kind of characterized the spin and sensation. So that points me more towards vertical than something like lyhydenes or orthostatic symptoms. With that in mind, Deborah, do you have any thoughts on dizziness and the way she's presenting? Great thoughts. So yeah, at the beginning, while Ethan was giving us some details, I thought, OK, maybe dizziness, like she could-- she's a young patient. Maybe everything that you said, bad gyms, bad luck. Could maybe she not be eating well, could be like a diabetes, could be like a vitamin deficiency or are eating disorder, but then like going through the case, we have some red flag, like the falls, the progressive eating of worse in with time, the leg pain and the fever. So make me think, could be a central cause, could be a inflammatory disease, could be like an infection. And I would definitely like do like a full neurologic exam like to see if there's something related, like to the neuro system. And yeah, that's what I have been thinking. Yeah, dizziness is really hard, I would say. I think that there's a lot of studies that show that it's really hard for patients to describe their symptoms. No, you're saying kind of like, that spinning sensation kind of points you more towards vertigo, which it does the same thing for me too. But just through like seeing a lot of dizzy patients and just kind of looking at the literature a little bit, it's still like really hard, I think, to pinpoint that. I think sometimes patients will have that same sensation, but it'll be more of a, orthostasis picture or what we call, you know, the secret liberium. So I think it's a really hard. I think that there's this wonderful approach by this neurologist at Hopkins. You guys have probably heard about it before. It's called tight trait. It's essentially this approach to dizziness and Akram stands for timing, triggers, and target exam when someone has dizziness. So that's the timing and triggers or really how you can make the most progress. And again, that's the tight trait in the monocle. I think it's Dr. Newman-Toker, I believe, from Hopkins. And that's one of the first questions I ask when a patient has dizziness. What is the trigger? Or is there a trigger? There might not be a trigger. So for instance, the classic example, BPPV, right? The patient is laying in bed, they wake up, they turn their head, they get really dizzy. For a couple of seconds, they're up to a minute, right? That's a classic triggered, we'll be called the Stibular Syndrome. That maps on really well the BPPV, right? And then that's kind of gets at the timing too, right? Like this BPPV only lasts a couple of seconds to a minute, right? This is lasting 30 minutes to an hour. So that is kind of making it even more concerning because a lot of the more benign causes of dizziness will be very short lasting. So I would definitely be asking, kind of, even is there a trigger? Ethan Ernie kind of described the persistence of this or that actually it not being persistent over the last month. Because the way that Dr. Newman-Toker, the Toker also kind of buckets dizziness is like an acute or persistent vestibular syndrome. You'll have seen a literature like AVS acute vestibular syndrome or episodic vestibular syndrome, EVS. And this would be more episodic vestibular syndrome because it hasn't been constant for the last month. And then you do a targeted exam. And that's really the hints exam. Now I'm definitely, I'm trying to get better at the hints exam at the neurologist and emergency room doctors are very good at the hints exam, but it's a way to kind of say, is this dizziness syndrome or vestibular syndrome is this more central in origin or peripheral? So you can do that when you see this patient. Now I'll say this patient has red flags. They're very, very concerned about. They have nausea, vomiting, photophobia, right? I'm concerned is this nausea and vomiting, is this central malls of vomiting and this patient has increased ICP, right? Especially in their cerebellum, do they have some cerebellar pathology? That's leading to increased intercretial pressure and a dizziness syndrome, photophobia, right? So I'd be kind of really running to that neurological exam and have a low threshold for neuroimaging. The last thing I'll talk about, and then maybe I'll pass maybe the fever to know it too to kind of layer on with this neurological symptoms, is the tinnitus, right? I think that also gives us some, that kind of can go either way. Like there's a lot of benign causes of tinnitus. Obviously, many patients with tinnitus just have idiopathic tinnitus and there's kind of different historical questions that you can ask to increase the likelihood of a more, you know, or some red flags that will make you get some neuroimaging. I always ask about the pulsatile tinnitus, right? That can kind of get at a vascular etiology if the patients are hearing that like wishing sound. And then also, it being, you can, did you say if it was, oh, bilateral, okay. Bilateral kind of makes it in terms of red flag symptoms, unilateral, it's definitely a little more concerning than bilateral. So I'm curious, like, is this an issue also that's not only affecting the vestibular system or the central nervous system, but is it also affecting the churnal nerve eight as well? So I'm almost like rushing towards neuroimaging in this case, in this end patient, but I'm curious, Noah, what do you, what do you think about the fever too? How does that, you know, we're talking, a lot of CNS syndromes don't have fever. So I'm curious where you think about that. - Yeah, I really liked this approach. I had not heard of the tie trade, but I have it open right now. And yeah, like you said, they separate by the timing and the triggers and we're right on the spontaneous episodic vestibular syndrome, the EVS that you mentioned. Very, very interesting approach. And I was about to say this before you asked about the fever. One thing that we are kind of all doing, and I want to make explicit for the younger learners in the audience is that we took this whole history and it seems like we're placing the center of gravity in the dizziness. So we're only mainly talking about dizziness here. And the reason for that is basically the duration of symptoms. I'm taking note of the fever and if it becomes more relevant later in the case, then we can tie it back to the history. But for now, it was just one episode of 38.2 once this past month, while she's been having progressive symptoms of dizziness. So it's something that is just kind of floating around there and if it becomes relevant later, then I'll put more weight into it. 'Cause you know, patients can have multiple disease at the same time, maybe she had some problems, some like a viral illness or something. Now, if she does end up having like something localizing to the right leg on exam, if it is persistent, then I think that becomes more relevant in this case. Ethan, I think we're ready to learn more. - Yeah, wonderful, I'm the more approach. Never heard of the tight trade approach. But I think that's great. And I really like how you guys focus on the proportionality and the red flags of the syndromes and not too rush into tying everything at the first and at the first glance of the patients, yeah. So the second thing I got, I'll give you the newer exams. So we are unable to perform a very detailed, a pupils and extracurricular muscle exam because the patient would feel very unsporthofobics and gaze upward because she was so uncomfortable during the ligate examinations. But she showed a gaze evoked misdiagnos. And when performing the new exam, actually she has no tannitus and no hearing impairments. And other positive findings including a positive finger to nose finger test for dysmetrias. A rhomburg test was negative though because when without closing her eyes, when standing she was already on studies. And she also has shown a truncoatexia. But no other sensory findings and no other autonomic system findings. She was urinate well and suffocates well. So yeah, and additionally about her right leg pain that I mentioned earlier in the first L-across, we got an X-ray of her right leg which showed a fracture of right fibula, possibly a consequence of the following episode that she experienced before. And upon track review, she visits our neurology clinic seven years ago, also with business in the charts. And a MRI of brain was ordered that time actually, and it was normal at that time. - Wow Ethan, a lot of abnormal neurological findings here. I was very worried on the HPI, and now I'm very, very, very worried on the physical exam. And thank you for this really detailed physical exam. I mean, if I were to just summarize this physical exam, I am really worried about the cerebellum, right? And the reason I say that is that, you know, you can give us our classic cerebellar signs, our finger-nose finger test, positive, bilaterally, right? Dismetrae is one of the, you know, neurological assessments we do for the cerebellum. And then also we have trunkal ataxia, right? Now ataxia is tricky, because you can have, you know, central ataxia, or more, or like cerebellar ataxia, and then you can also have peripheral and central ataxia. But really trunkal ataxia is definitely more suggestive of a cerebellar etiology. When people have peripheral ataxia, let's say one of those common etiologies would be very severe diabetic neuropathy, right? Patients, you know, when they're just like end-stage diabetic neuropathy, very uncontrolled diabetes, they just have no control over their limbs, right? Like they just don't feel their limbs, they have no proprioception over their feet and, you know, just a very common etiology. But this patient can't control their trunk. And I remember that, too, it's like the cerebellum is in like kind of the back in the center of the brain. It's not really on the periphery of the brain. So it controls the trunk. So I'm sure that when Ethan examined this patient, if you sit this patient up in the bed, they're kind of swaying. And I've seen this before. I've seen this a couple times. Actually, the one time I saw it in medical school was when a patient presented with an acute dizziness syndrome, very, very acute. I think it was over like two days. A lot of nausea, a lot of vomiting like this patient. We talked about where, you know, being worried for increased central cranial pressure. And I sat the patient up. And they sat down in the exam table. And they couldn't sit up in the exam table. They fell to the right every time. They were so unstudy. We got a stat CT at the head. And they had a cerebellar hemorrhage, massive cerebellar hemorrhage. So it fit really well. Luckily that patient did well. But it really made me remember that connection between trunk white taxi and the cerebellum. I think the time course of this illness is very, very interesting. Now, this patient on chart review, you know, this patient had dizziness seven years ago. And you might say, okay, now this patient has a very chronic intermittent syndrome. And that's probably true because this patient had similar symptoms at least a dizziness seven years ago. But I will say dizziness is very, very common. You know, what if this patient had dizziness because they were orthostatic or anemic or any of the other hundred common causes of dizziness at that time. And now they have an unrelated cause of dizziness. Because it seems like, you know, maybe that was a more benign cause of dizziness and they may not have these neurological symptoms or they would have, you know, got prompt medical attention or even like maybe an incision admission. And there would have been kind of more urgency for the diagnosis. But I'm kind of tracking two different differentials. Is this a chronic, very chronic, you know, seven years intermittent cerebellar syndrome? I'll label it as a cerebellar syndrome now. Or is this more a subacute cerebellar syndrome going over the last month? And this seven years ago was just a complete red herring. So I think that pops to mind when you think of like a intermittent neurological syndrome that can occur in a young patient over like a seven year time period is multiple scolars. So, right? And now I know the McDonald, you know, I haven't memorized the McDonald criteria as an internist, but I know that the McDonald criteria that criteria for multiple scolars is moving towards kind of being able to diagnose patients on their first neurological event, especially if it's classic to get patients treatment very early on, cause we have really great treatments for MS now. But even to tell us that there was any demilaning region seven years ago, which would be more suggestive of MS. So I'm very curious now if there's any demilaning regions. But, you know, I guess I'll pass to Deborah kind of to discuss maybe what a subacute cerebellar syndrome, like maybe what could be on the differential for a month, but I really want some neuroimaging postpatient like STAT. I'm very worried about this patient. Pretty think Deborah. Great thought Mark. Yeah, definitely like I was thinking about multiple scrolorosis like you said, because she's a young patient, she's having like some neurological symptoms and even like a normal MRI can happen. I was thinking it could be like a tumor too, like maybe a medlobalestoma, something that I see more studying for these steps, but can be in young patients and can cause like the symptoms of ataxia, nistagmus and dysmetria. So that was one thing that I was trying to allow to, but definitely like here we will need another imaging to see if we see changes and to try to get close to a diagnosis. Noah, what are your thoughts? Well, my thoughts is that I'm out of my depth. As an internal medicine resident, it's not very common that I see patients with like a sirabella syndrome. So I really like what Mark and Deborah have said already and I'm gonna comment on two things. First is is there any way we can tease out if it is a chronic syndrome versus a subacute? And I think this is where kind of tangential, but more detailed story about this patient's life would be useful, right? Did she have full resolution of her symptoms after the episode seven years ago or did she have like limitations in her life and then she kind of self compensated? 'Cause seven years ago she was 11, right? People there are 11 years old, they're very plastic. They can learn to live of limitations, but they may not be able to do the full range of activities that healthy 11 year old would do. So I think that would be a great piece of information if we can actually say, okay, she did have those symptoms, they kind of went into remission spontaneously and she was like fully normal and then now she's presenting again versus, oh yeah, she didn't have those symptoms, maybe she felt dizzy like here and there over the past seven years, but this is like worse than her usual attacks of dizziness. Versus, oh yeah, she had the symptoms, she had some residual symptoms and now they're like progressing and getting much, much worse and she's not able to compensate. I think that's the first thing that I wanted to comment on. The second thing is speaking to when I'm out of my depth, this is something that will come up very often in medicine, right, medicine is huge and it'll be very, it happens very commonly that I encounter a patient or a diagnosis that I had not seen before or a problem that I didn't know how to approach. And whenever that happens, I like to think about things that can go wrong, right? So cerebellum is in the CNS and what can go wrong in the CNS? So Mark already alluded to any vascular events. So either Schemia or hemorrhages, sure. Deborah said about masses. So what masses have a preference to the posterior portions of the brain in this epidemiology, medlelublastoma, I love that, maybe a lymphoma, also another possibility. What else can go wrong in the CNS? Audimune conditions, so MS or other demolinating conditions. Any toxins and that can be either intrinsic or extrinsic. So any medications that the patients are taking, chemotherapy agents or even intrinsic toxins. So patients with cirrhosis can develop like a hepatocerebellar syndrome or deficiencies, brinnekes, right, they can present with a taxa, maybe we'll learn that this patient is actually bulimic. She's been vomiting, she's not taking another enough nutrition and she just has brinnekes now. Or infections, right? It'll be kind of unusual to have a acute bacteria infection less than a month and her being relatively healthy otherwise, but a subacute viral or a fungal infection in the CNS definitely can cause a syndrome like this. There were some other specific entities that came to mind, which just kind of stuck to my mind because they're kind of interesting. One is Hashimoto and Sephalopathy. She's the right age and the right gender to have Hashimoto's. And then Celiac disease can also cause and Sephalopathy and can be the initial symptom, the initial presenting symptom. And if we do get imaging and we see Brombo and Sephalitis, then I think they already mean bucket. There are some specific diagnosis that I find interesting. I don't know where this patient's from is area of bishops, but bishops can cause like, there are bishops can cause Roman Sephalitis and kind of a similar cerebellar syndrome. So kind of scattered, but I think it's helpful to lay out all the different categories and kind of lay out all the different diagnosis that you can think of because if you don't think of them, you're not gonna look for them and you're not gonna find them. So I think generating as many different diagnosis is always useful whenever you're stuck, basically. All right, any closing thoughts Mark and Deborah before we hear more from Promethin? - I love your guys' approach. And no, I really like what you're just like, what's not over complicates this? Like what can happen to a young patient in the central nervous system, right? 'cause that allows us to cast a wide audience. net because this patient has so many different neurological findings and also some systemic findings too. I'm going to loop back to the fever and vomiting. So you're like, "I'm going to put my neurologist's head on, but I'm also going to still put my internist's head on a castel-wide net." And I kind of just want to go back to the HPI. I think it's important always to do that especially when you're at like a diagnostic time out or there's some diagnostic challenges. And I still think the intermittent nature of this syndrome is very interesting and maybe even will clarify that this became persistent and that's why the patient came to the hospital. But I am really concerned overall for a cerebellar syndrome with possible increased intracurricular pressure. Those two things usually create a persistent syndrome. When you have increased intracurricular pressure, that's not intermittent. That's just constant. Now patients perceive symptoms in different ways and they're like, "They're like young patients, so their brains are very plastic so they can compensate." So maybe classically in adults an increased intracurricular pressure in a cerebellar syndrome would be persistent. But for this young patient, they compensate and it's actually just intermittent. But I'm just keeping an eye on that because I think those intermittent and a persistent syndrome really do drastically impact the differential diagnosis. And then I also don't want to lose track of the tinnitus. It's pure cerebellar syndrome. So shouldn't it really cause tinnitus? So I really want to take a good look at that cranial nerve-8 and the brainstem. And there are some syndromes that can impact the cerebellar and the brainstem. And I actually really want to ask, "Each and actually this patient recently got a vaccine." Now I want to say, "Vacines are amazing." They're very, very important. But in a young patient, you actually always have to consider the very, very rare side effect of a vaccine that being ate them, acute dissemination and stuff on my lightest, that can impact the cerebellum and the brainstem. Also I can't believe I had to say that. But it's just, you know, the reality. But yes, I would be very curious if this patient was given a vaccine recently. And then going back to the nausea or the diarrhea and the fever, in kids actually host viral. And I'm going to totally butcher this word cerebellaritis or essentially just inflammation of the cerebellum, most classically described in varicella infection. And maybe that's why Ethan gave us the vaccine history because his patient was probably vaccinated against chickenpox or got chickenpox. But post viral, even from influenza. So maybe some of these GI symptoms and fever was a viral infection and other patient has a post viral seeing that syndrome too. So I don't want to lose track of the tinnitus because that doesn't match perfectly to this cerebellum. I don't want to lose track of those systemic symptoms, especially like no image unless it's a broad net. And then I don't want to lose track of this being intermittent too. But at the end of the day, I need some neuroimaging. So Ethan, I hopefully you give us some neuroimaging or are going to be lost. Yeah, of course. Wonderful thoughts. And I just love how you guys go back to the physiologies. I'll first give you the basic labs. So white canvas 11.3 human hoping was 13.7 and a plate of 255,000. A normal creatinine sodium potassium. Liver panel was only notable for a mildly elevated ALT of 56 and a normal CRP and a normal total proteins. And we got a brain MRI which showed a dilated cordially co-bane in the right temporal regions, which radiologists said was likely just representative of a normal variant. And upon reviewing of the old imaging seven years ago, it's basically stationary so nothing has changed. And we also got additional labs. So she had normal B12 and homeostean. We don't have MMA here. So that's what we all have. And we have a normal TSH and a normal 3T force. So at this point, we are also considering a peripheral vertical etiology. So we consulted EMDs and they suggested to do some more workups, which including a 10 10ograms, which showed a normal mid-earth function on both sides. A SSEP of the hands and the legs were normal as well. A vestibular evoke myogenic potential was abnormal and was suspicious of a right superior vestibular neuritis. So EMD was consulted and was they thought to be favoring a manniar's disease. And vestibular evoke myogenic potential studies were comfortable with that as well. So she was treated with a diazotin IV infusions, as well as combinations of macluzins and thiphandel in his first admissions. And her symptoms partially improved and was discharged and back to outpatient fallop. However, after this charge, specifically her vertical and truncule texia persisted and even got worse. Now it's existing all the time and she could barely walk, which in their interval she also visited psychiatrist because the symptoms were so debilitating and she was diagnosed with adhesives by the psychiatrist and now under metheophanyndate as well. And she was admitted again for further evaluation. Thank you so much, Yaten. Yeah, I think now it's a good time for us to step back a little bit and try to do a problem representation. We have a 18 year old female that present with disinist associated with some red flags, like nausea, vomiting, diarrhea, photophobia. And in her physical exam, we could see that she has some cerebellar signs, some dysmetria and a texia. And going for the imaging, DMRI was normal. With what Yaten said, I was like, okay, we were really expecting something to present the MRI, but nothing show up. So I was thinking with this, the labs like the WBC and the CRP, I was like maybe an infection or inflammatory disease, like could be rolled out. It's less likely. And the normal MRI make me think like maybe this can go against like a tumor or a stroke. But didn't make me roll out the like a demilination process like multiple sclerosis because I know sometimes the MRI can be normal. But from here, I would definitely need some neurology consult to help me because I don't know how to make a lot of progress. No, what are you thinking? Yeah, Deborah, I love your thoughts and one thing that you did that I think it's very remarkable is that you included the normal MRI and the problem representation, right? Because that is an important finding and exactly for the reasons you mentioned. It is unexpected. I was expecting to see like some, you know, enhancement and the cerebellum or maybe like some patching enhancement or something to pop up positive in MRI. And that being negative, I think it is a value. I think like you said, any big short-term cause kind of is less likely now, especially if we get an interval MRI during her second admission to see if there was something that was small before and now it's bigger. Any of the inflammatory diseases that we mentioned are less likely given the lack of enhancement. And I'm thinking that those findings could be compatible with something that's more subtle and what can be more subtle than a molecule or the lack of the right. So I think going back to the toxin bucket that I mentioned and just making sure we do our due diligence in terms of ruling out all the associated conditions. So I like that Ethan and everything got the B12. I'll go back and get the vitamin E, get the Celiac antibodies making sure that this patient doesn't have any risks for burniches or even treating her empirically for burniches with thymine and seeing if there is any improvement. I think just making sure we got our eyes and cross our teeth. What about you Mark, where is your had at? Yeah, I think my head is right where you guys are at. I like how Deborah said, and you said this too, it's like MRIs are good but they're not perfect. No tests in medicine is perfect. Biopsy is not perfect. It's really hard to diagnose Hodgkin's lymphoma on a biopsy because it's really hard to see if there's a red stirmer of cells. We think about gold standard tests and having 100% sensitivity. I've been fooled so many times. I will never say negative MRI doesn't mean this is a central etiology. I think like Deborah really highlighted, there are some things that really should show up. This patient doesn't have a cerebellar mass. Cerebellar mass causing this persistent and severe symptoms, you're going to see it. I think that's less likely. A hemorrhage is less likely. But I think many of the other things you guys mentioned are still on the table, demilaning lesions. You would expect to see them, but I think that depends on the radiologist too. If they're subtle, they're definitely not as prominent as a mass or a hemorrhage. I still think the multiple sclerosis, the acute dissemination and cephalomyelitis, that's still on the table. I think an interval MRI, especially given the symptoms were intermittent and the other persistent. like Noah said, maybe the. the lesion, we're just saying a lesion or a molecule is was small and now because the symptoms are persistent, it will become prominent now on MRI. So I think you could probably make an argument from a cost effective standpoint, like should we get another MRI, but I think it's probably worth it. I know I'm glad that you talked about molecules and nutritional deficiencies, like really any patient like this that's admitted should probably get IV thymine, the first time they're admitted, you know, IV thymine is cheap and has absolutely zero side effects. Now Ethan didn't tell us on really any risk factors for thymine deficiency. Ethan mentioned that this patient had some GI symptoms, but it wasn't like, his patient wasn't having nausea and vomiting because they had gastroparesis for three months before the neurological symptoms, which would definitely be more toxic for thymine deficiency. And some of these neurological symptoms are definitely not as classic for thymine deficiency, but I still think I would just give this patient IV thymine low cost to low risk. And then I'm glad that you brought up CLEX disease. No, I really see that disease is really a systemic syndrome. I think we're learning more and more all of the extra GI manifestations and it's actually called, there's the neurological manifestation is called CLEX ataxia, or I think it's also called like gluataxia or something for some odd reason, maybe I'm thinking some other condition, but it actually does have a pre-delection for the cerebellum. And I would be surprised if like many MRIs and CLEX disease are negative. And then, you know, Ethan again, I'm going back to the GI symptoms. Ethan told us there were some GI symptoms. Again, I thought they were maybe from increased intercranial pressure, but that's something that you're not going to miss with an MRI. So this patient likely doesn't have increased intercranial pressure, but maybe, you know, Ethan goes back to the bedside as a dietary review and every time this patient eats, gluten, they feel really, really crumbling, right? And I think also it's important to think about what are the three big neurological tests, right? EG MRI LP, right? I think EG probably not too helpful in this case, but I think a lumbar puncture could be helpful to see if this patient has any oligoclonal glands, any whites, any, you know, abuminal cytological dissociation, any just evidence of inflammation that, you know, we can consider a post viral like we've been talking about, or does this patient need immunosuppressant for a deep mildening or inflammatory CNS syndrome, NOS, right? So yeah, very tough case Ethan. I'm still kind of like yeah, MRI, get the MRI, don't get the MRI, I probably would, but definitely I would get a lumbar puncture if the patient is okay with that. Ethan, I think Mark with this, with this proposed workup, you're hitting on something that Robbie has taught us already, which is more applicable in the space of AMS, but I guess this can be kind of applied to other neurological syndromes, which is whenever you don't find something in the essential nervous system or essential nervous system syndrome, you do two investigations at once, right? You go deeper into the essential nervous system and you look elsewhere in the body. So going deeper is repeating the brin and MRI, lumbar puncture, EEG biopsieft, anything shows up and then looking elsewhere is making sure that we get a full complete reveal systems and we also address any other causes that would kind of be sneaky. And the sneaky ones in AMS are kind of gut related. So the silly act, the de-lactate or any other ingestions, like kind of subtle ingestions that the patient may be exposed to. I think in this case, the more applicable one would be the silly act disease. All right, Ethan, tell us more, what did you learn about this patient? Yeah, perfect. So, echo number four. So we did got a repeat MRI, which was normal again. And we also sent HIV, which was negative, an RPR, which is also negative. And AMA also was negative as well. A repeat, a B12 and homoses in level was normal as well. We also sent a serial plasma, which was low, a normal value being 18 to 54. And per level was 17. However, the copper level was low as well. So 61.3 with the normal range being 80 to 155. However, a 24 hour urine copper was low. So like we are representing a not representing a Wilson disease and field type. And a repeat TSS and 3-T4 was normal as well. We also sent N-type TPO, like because of the suspicious of Hashimoto and Sepulitis that know I mentioned before, which was elevated at 39.72 with a normal value being less than 5.3. And a vitamin E level, which was normal. And we also got additional workups. A GAT antibody was mildly elevated at 55.2. And as you guys mentioned, we also think about her symptoms and about diarrhea as before. And we also notice that her symptoms morphed after breakfast, which she liked to eat bread. So we also sent CDX disease workup. So for the CDX antibodies, the N-type T-TG and IgG was negative. A N-type DGP IgG was also negative. A N-type T-TG IgA was negative. A N-type DGP IgG was positive though. So 1+ positive. And then we subsequently get a EGD with biopsy. So the esophagus showed a mild chronic inflammation with my microscopic sections showing isophageal mucosa with congested vessels and mild chronic inflammation. Her stomach, the entrance showed chronic inflammation as well. And the microscopy showing entromycosis with edema and chronic inflammation. And no H-pylory was seen. And for her de-ognom also showed mild chronic inflammation. And the villus height appears to be mildly decreased vocally. And however the specimen was not adequately oriented and no increased intraepithylolinforcides. So less than 25 per 100-enterocytes of increased intraepithylolinforcides are seen. And the gastroenterologist interpreted this as a March-type 0. So less likely to be a EGD with biopsy that classic for celiacusids. And we also got a lumbar puncture which was clear in color this and with a white count of 7 and with 100 per cent lymphocytes. One RBC and protein level of 29. We sent also sent a PCR panels which including most of the viruses and bacteria as PCR and which was negative and the IgG index of 0.06. We also sent autoimmune and cephalitis panel which showed equivalent positive of anti-reg, anti-cv2 and anti-amp. Which most of them are described as paranoplastic hyper and she has no other somatic symptoms. So considered to be less likely to relate it to her clinical syndromes. And the next silo clot will reveal the diagnosis. Alright that's a lot of good information Ethan. We kind of review basically the big differentials that we had already mentioned. Regarding the celiac workup. So we have only one positive antibody and a biopsy that you know there is trying to be celiac but I agree it's not like characteristic or like fully diagnosis of celiac disease. One thing that I'll mention here is more on the kind of like the broad diagnostic reasoning which is we talk a lot about pre-test probability in terms of patient having a suggestive history. So let's say a young patient comes in with the Zaria. The pre-test probability of them having cestitis is very very high. Therefore I don't need as many diagnostic tests. The in this case the pre-test probability also is applicable. So if we go back to the very beginning when she first came on and we didn't have any imaging we didn't have any workup. A young patient coming in with kind of subacute, dizziness, very suggestive mayniars or maybe migraine. But the more we investigate the less likely alternative diagnosis are the more likely the remaining diagnosis become just because we don't have any other explanation. So if in the very beginning we had the celiac workup without any brain MRI imaging I would say oh this is very unlikely to be clinically significant. This is most likely something else. Now that we have kind of investigated other causes and it's less likely to be a primary CNS problem the clinical relevance of these antibodies become more and more relevant. I'm not saying this is like a slim dunk diagnosis but this is someone that I would consider doing a treatment both for Hashimoto and cephalopathy and for celiac and seeing how the patient responds in a stepwise fashion. I think this is where we're not going to get a very-- very satisfying in server-guardless, so maybe giving her like, okay, let's try this. You do a gluten-free diet for a pre-specified trial and see if you improve. And if you do improve, that's a clue. And then, or we can try a pre-specified trial of steroids for Hashimoto and cephalopathy and see if you improve. The important thing is making sure that we have like endpoints and we are sequentially testing our hypothesis because if we do both of the same time, we're going to be left okay, we don't know which worked, if any. So that's how I would approach this case in terms of management. What do you think, Deborah? Where's your mind at? I loved your thoughts and especially that you said, "Saleiac, like some time ago when I was not even thinking about, the only thing I would add was when it started talking about Cooper, I was like, oh, maybe this could be like a Wilson disease, but this patient has a very low-or-rin Cooper, so that I think go strongly against. But maybe it could be like a Cooper deficiency, like that could be causing this ataxia and erupting the patient, like showing that she has like a low, seruo-plus-main and Cooper." Yeah, besides what you said, that's where my mind is. Mark, do you want to add something? Yeah, maybe I'll just talk about it because I agree with everything you guys said of the Celiax thoughts. Deborah, I also would just repeat this patient's copter because Cooper deficiency can do everything that the tall deficiency can do and more. So I definitely would do that because again, low risk, low cost. The GAD antibody is interesting. So I actually have encountered a patient that has had a positive GAD antibody before. Now I'll say that and maybe I should be more clear. You should always remember GAD is the antibody GAD 65 for autoimmune type 1 diabetes, right? So it's the most common auto antibody. And sometimes a lot of times we actually test when we're suspicious for type 1 diabetes, so this patient is antibody positive. It also can be positive in autoimmune thyroid disease as well. So I'm just keeping an eye on that anti-TPO antibody. I will say that Hashimoto's and cephalyces is a good thought, but my understanding, and I know this disease is super not well described. And it's actually not even called Hashimoto's and cephalyces anymore. It's called street steroid responsive, something, something, something. So I think it's just such a low prevalence that I think it's not well described. But I think it's really described as a subacute kind of dementia syndrome, almost with seizures. So I think this, like a taxi, would definitely be more of an atypical presentation. But again, an atypical presentation of a disease that's not well described could certainly happen. But the other thing that GAD can be associated with is actually neurological symptoms. So I actually had a patient that had a taxi, we were worried about a perineal plastic process. And actually after reading about that case, perineal plastic cerebellum symptoms are very commonly MRI negative. So I forgot to mention that in the last adaloclot. Now, the reason why I probably wasn't tough on my mind is because like, you know, this patient's young patients can get cancers, but obviously at a lower rate than older patients. But we didn't really have any evidence or concerns from the latency at this time. But GAD antibodies are also associated with isolated neurological syndromes as well. And actually the most common isolate neurological syndrome that GAD is associated with is cerebellary taxia. The other one that you guys might have heard of before a stiff person syndrome, which GAD is also associated with, there's like, I think a laundry list of neurological syndromes that GAD is associated with. But when you think of GAD, remember autoimmune diseases, diabetes, thyroid disease, even pernicious anemia, and then isolated neurological syndromes. So I would be very, I would have to talk to my friendly neighborhood and neurologist, like what they think about that. But you know, if we still, if we still are not confident with the diagnosis, I know like I, you know, I've been, I talked about like false negative pathology and MRIs and all that. And honestly, like, EGDs and colonoscopies, like, I feel like you get two EGDs and colonoscopies one week apart with like a gastroenterologist in the same division and there will be like different reads or different pathologists. Like they're just so, they're so spotty too. And remember with celiacs disease to, to get a good sample with celiacs disease, you have to be in a high gluten diet before, for like weeks before. So if Ethan says like that, this patient like, ah, is not feeling well after the breakfast, maybe they're avoiding bread now and they're actually not eating a high gluten diet and that's why there's a false negative on the, on the celiacs. So really the best way to do it is to unfortunately give this patient a lot of gluten for weeks before and then repeat the EGD. I would also get a total IGA because that's really part of the diagnostic workup of celiacs disease. I'm sure you can might have that, but just not, might have not mentioned that because really the best antibodies for celiacs disease that optimize sensitivity and specificity that TTG, TTG, IGA, a large proportion of patients with celiacs disease actually have IGA deficiencies. You'll have a false negative TTG, IGA. Yeah, end conclusion. This is a really tough case even. Thank you for bringing in. I love Deborah, Noah, all your thoughts and I'm very curious from Ethan with the next steps in a diagnostic journey where, because I think you know in many different directions with this case. And yeah, amazing thoughts. So we also suspect gluten at a texia and suggested a gluten-free diet and also gave serrated as this is thought to be a immunologic phenomenon with sensitivity to gluten and she actually recovered a lot and about two or three weeks later after this charge with a strict gluten-free diet, she was able to walk and even back swimming. So our diagnosis was gluten at texia and I actually met her in another admissions with a recurrence of her symptoms which likely due to a non-compliant diet and it's really a multi-fectorial case that she also has psychiatric problems which makes her more anxious and the purest water for symptoms sometimes ends. Her compliance of the diets but overall based on our work cut and the fact that she has so such a good response from gluten-free diet and fluctuation of symptoms with diets suggests the diagnosis being a gluten at texia. And actually the disorders that humans have associated with gluten are a lot so maybe we can clarify the definitions for it. So we can have a gluten-related disorder. So gluten-related disorders are like group diseases, triggered by eating gluten and that includes and CLA-episees which are the well-known disease. Their metitis had perpetuformance which is also a well-known et cetera intestinal manifestation of a CLA-episees. And another thing called a group of gluten-related neurologic disorders which gluten-actexia, this under-is umbrella. So actually a very key point that I wanted to mention is that gluten and terrapathy which is CLA-episees is not a prerequisites for intestinal manifestations which means that the lack of CLA-episees or enterrapathy does not include use from gluten and texias which is actually the key point in this in diagnosis in this case. And from literature review that, for patients with gluten and texia only 10 to 15 patients, 15% of patients have G-S symptoms. And only 40% of them have the list atrophy which is the R3 type histology on TGD with BAHBC and up to 50 to 60% actually had normal biopsy which is the case here. And for the serologies the TG-IGA which was negative in this case was also the most sensitive marker for CLA-episees actually is not very useful in diagnosis in diagnosis including a texia. The most common positive antibodies in gluten-atexia was DGP-IGA which was the only positive one in our case as well. And there's a lot of research going on regarding this conditions and there's also the most specific antibodies for diagnosed in this condition is something called a TG6-IGA but I believe that not available in most of the institutions in the world. Yeah. How do you guys think? Thank you so much for bringing this wonderful case Ethan. I had a blast discussing and it really shows to me how valuable CPSO versus the only reason I mentioned the gluten and neuropathy is because I think I saw it in some of the VMRs. It was added in the differential diagnosis or the final diagnosis and it just kind of stuck to me because of the very unusual association. I am sure the patient is very lucky to have you caring for her. Deborah, any final reflections? Amazing. What a great case. I never heard about this diagnosis so I'm happy to be here and to be learning and growing my medical knowledge. So thank you so much Ethan for bringing us this case. I think we went all over the place with differential diagnosis and it was a really nice discussion. What did you think Mark? The dietary history always wins. When you don't know what's going on. gone and an undifferentiated clinical syndrome always go back to the bedside like you can did and just see how the patient's diet is. See what they're not eating, see what they're not tolerating and it could be a hint towards a disease like celiacs or some, you know, a cold nutritional deficiency that could be, you know, easily reversed with a, with a cheap intervention. Now, I shouldn't say cheap intervention for celiacs because, you know, a gluten-free diet is very taxing and life-changing for the patient. So it definitely impacts the quality of life a lot, especially if they, you know, eat a lot of gluten at baseline. But I think, you know, we really should think about celiacs, almost like we think about inflammatory bowel disease, right? Inclimatory bowel disease is a systemic syndrome and so is, so is celiacs disease. So thank you, Ethan. Incredible case. Yeah, thank you so much, everyone. And we hope to see you all on our next episode. Bye-bye. That's a wrap, everyone. Thanks for tuning in. If you enjoyed this episode and want to be part of our community, join us for our live virtual morning report, where we can present the case or discuss with us. Visit our websites for details. You would love to have you.