Okay, good morning everybody. Happy 8 a.m. Welcome to New Orleans. We have the pleasure of kicking it off at this bright and early morning talking about medical conditions mimicking psychiatric disorders versus psychiatric disorders mimicking medical conditions, also known as medical mimics. I am pleased to be here with my co-attending at Inova Fairfax, Dr. Mariam Ferris, and then we have Dr. Truitt sitting next to her, and Dr. Asar, your current two graduating fellows right now. So we have no, none of our presenters today have any financial relationships to be disclosing. And I'm going to start off by just giving a little bit of a brief introduction to set the stage for the three cases we're going to go over today. So during the course of our training, there's a lot of effort that's put into teaching our residents about the recognition and treatment of primary psychiatric disorders. But there's less exposures to cases that appear to be primary psychiatric disorders but are actually due to some sort of underlying medical condition. Despite these being pretty common, things like infection, hypoxia, autoimmune disorders, electrolyte imbalances, neurological disorders, just to name a few, medication side effects, these are just some of the very common reasons that patients can present with what we call mimics of primary psychiatric disorders. Awareness of these mimics, which we can also call psychiatric disorders due to another medical condition, can often appear as treatment-resistant psychiatric disorders and can be responsible for excessive utilization of medical resources and healthcare dollars, as well as being the sources of mounting frustration and misunderstandings for a lot of our medical colleagues. Requests for psychiatric involvement is not unusual in these cases, especially when medical workups thus far have been negative. So as is tradition for our fellows graduating from the CL program at Inova Fairfax Hospital, every year we give a talk to you about medical mimics with some kind of a theme, and this year it's going to be COVID-19. We're going to hope today that you were able to highlight some common presentations of psychiatric disorders that are seen with COVID-19 infection, explore some confounders associated with diagnosing mental illness during a concurrent COVID-19 infection, and describe different treatment approaches for psychiatric illnesses experienced in the setting of COVID-19. Just to give you a little background, from early 2020, a link between COVID-19 and neuropsychiatric symptoms became apparent. As we have observed the trends, it has become clear that the relationship is bidirectional. It's estimated that patients that have a previously given psychiatric diagnosis are at 65 percent increased risk of COVID-19 infection, while 18 percent of individuals that have been diagnosed with COVID-19 receive a psychiatric diagnosis within three months following the infection. Reporting information additionally has identified trends that show disparities amongst both diagnosis of COVID-19 and association with psychiatric disorders. While the field of psychiatry may appear as being somewhat removed from the front line of the COVID-19 pandemic, this information very much confirms that there is an overlap and that the field has been significantly impacted, not only by the social and emotional aspects of the pandemic, but also the biological aspects of the infection. We've seen a number of neuropsychiatric sequelae of COVID-19, and these are just a few of them. While much of the data surrounding COVID-19 and its associated complications is still being collected and reviewed, it's become apparent that several neuropsychiatric symptoms are present, both in the acute phase of the infection, also following its resolution in a phenomenon now being called long COVID. Complications include anxiety, depression, fatigue, sleep disturbances, mania, psychosis, catatonia, many others. They've been linked to COVID-19 infection. Though several biological mechanisms have been described as contributing to these findings, it should also be noted that there are a number of emotional and social confounders that cannot be corrected for. I'm going to briefly touch on some of the neuropsychiatric etiologies that we are seeing underlying some of these presentations. A number of hypotheses have been proposed to explain how these disturbances have been developed, and while there's a lot of variation in the vulnerability of each individual, you can also see that the effects, again, of the infection itself can vary greatly. While much of the research is still needed, we can infer that biological factors, including imbalances and electrolytes, organ dysfunction and inadequate oxygenation may influence the delirium, possibly also cognitive dysfunction, anxiety, and so on that we see with the infection. Social isolation has also been the focus, particularly as a link to depression, anxiety, and sleep-wake cycle dysregulation. The loss of regular social interactions, our daily structure, and access to medical providers or the medications have been described as being distressing among several general populations, and the isolation required for quarantine has also been noted to be stigmatizing and also linked to anxiety and depression. An immunological basis can account for some of these neuropsychiatric symptoms. An inflammatory response has been widely described as part of the acute phase of the infection, which overlaps with the proposed theories for affective and cognitive disorders. Blood-brain barrier dysfunction has also been observed, and this can account for some of the neurological overlap and sensitivity that we see in this population, and direct immune cell infiltration may also lead to tissue damage and subsequent sequelae, depending on the location. Coagulopathies have also been widely described with COVID-19, primarily with the acute infection, but also with prolonged sequelae. Symptoms are being seen, including strokes or end-organ damage, for example, pulmonary emboli, and are widely known to be linked to neuropsychiatric consequences also. And lastly, direct CNS invasion through the cribriform plate and the olfactory damage from it have also been noted in these populations. I am now going to turn over the mic to my colleague, Dr. Fares, who's going to start with case number one. Hi, good morning, everyone. My name is Mariam Fares, and I'm a CL psychiatrist at Inova Fairfax Hospital, and I'll be taking us through our first section here today, which is the overlap between anxiety and COVID-19. So we'll start off with a case. So here we'll meet Ms. L., who's a 74-year-old female who initially presented to the emergency department with cough and shortness of breath. She was having some nausea and vomiting, and this had been progressive over a 10-day period. So she was in the hospital and was ultimately admitted for hypoxia because she was found to be saturating in the 80s on room air and was distressed at that point. She didn't have any significant medical history and didn't have any kind of formalized diagnoses aside from hypertension or mitral valve prolapse, and hadn't been on any medications aside from atenolol or HCTZ prior to presentation. She also had no prior hospitalizations. She hadn't been seen in the emergency room for at least 10 years, really wasn't following with any medical provider other than a primary care doctor for management of the hypertension. So we'll go over her hospital course just a tad. So she was brought into the ED with the aforementioned symptoms. Because she was hypoxic, they swabbed her, and she was found to be COVID-19 positive at that point. She was admitted to the medical floor just for respiratory monitoring and support, and although medical providers had initially recommended that she be treated with remdesivir and steroids, she initially refused this intervention. Unfortunately, within the first two days of her hospitalization, her respiratory status further decompensated, and she had to be escalated to the ICU. And again, the remdesivir and steroids were revisited at that point, at which point she accepted. So they did do a very thorough medical workup for her. So she had a leukocytosis, fairly mild, but indicative of an active infection, which we can guess. She had a hyponatremia of unclear origin. Ferritin was high, indicating an inflammatory process. LDH and lactic acid were also high, indicating tissue damage. CRP and D-dimer were normal, and her chest x-ray had showed atelectasis and bilateral low lung volumes. Her vitals did vary at different points throughout her hospitalization. However, she was noted to be intermittently tachycardic and have a respiratory rate that was, for the most part, normal, but elevated at times. And as noted before, her oxygen saturations were low pretty consistently. So during her hospitalization, she was described by providers to be intermittently confused. So she was making comments about how she was concerned that she was in an animal hospital, that she felt like she was a cat and that she was being experimented on. She felt that she was having some adverse interactions with staff, and she did have periods of agitation that were described by nursing notes. There was some verbal aggression towards certain individuals and refusal of certain PPE guidelines set forth by the hospital. But on the fifth day of her hospitalization, she had an acute worsening of her anxiety, and that's when we were roped into her care. So we were consulted on the CL service for management of anxiety and evaluation of this paranoia because of the concerns that she was kind of confused and thinking that she was in an animal hospital. So we'll do a brief aside over here, just kind of an overview of anxiety and COVID-19. The rate of anxiety in individuals that have been diagnosed with COVID-19 is estimated to be between 5% and 55%. As we can see here, that is a very, very broad range. What we see with this is that the studies that have looked at the reporting of anxiety have really had different reporting guidelines. For certain ones, there was a DSM diagnosis that was required in order to be included, and other ones, it was more so subjective reporting of anxiety and the experience of it. So while we do have a fair range here, we really need to hone in on kind of what the real prevalence is. But in hospitalized individuals, which is kind of what we're seeing with this case, the rate of moderate to severe anxiety is estimated to be at nearly a third of patients, which is very, very significant. And this is also post-discharge when we see this number. You know, the rate of moderate to severe anxiety in non-hospitalized patients is also noted to be around 44%, which is, once again, very significant. And amongst these individuals who have been COVID-19 positive and had active symptoms, there have been rates of acute stress symptoms and obsessive compulsive symptoms that have been elevated compared to the general population as well. So when we look at the risk factors associated with COVID-19-related anxiety, there have been, again, many, many different symptoms that have been reported. And these are kind of the ones that come up the most in the literature. So being female, having pre-existing mental conditions, lower socioeconomic status, increased exposure to infections. I think health care workers, this is very common, younger age, illness severity, reduced quality of life, persistent dyspnea, most notably with the long COVID symptoms, close relatives with COVID, and a decreased sense of smell. So again, kind of looking at the prevalence of anxiety in the COVID-19 pandemic, I do want to just highlight here that this is not only amongst infected individuals. This is general population as well. So we can kind of see the general population as the midpoint here with rates around the 35% mark, probably around 33%. And unsurprisingly, university students and health care workers have elevated rates, likely due to kind of the nature of the jobs and the settings that they're in. But something that I didn't necessarily expect is that teachers, parents, and pregnant women were actually noted to have lower rates of anxiety compared to the general population. So coming back to our patient, Miss L, so we were, like I said, looped into her care for evaluation and management of anxiety and paranoia. And when we did our psychiatric evaluation when she was in the hospital, we had noted that she had been diagnosed with a remote history of depression and anxiety by her primary care doctor. She had actually never been assessed by a psychiatric provider, no psychiatric admissions. And although she had a history of treatment with bisperone for anxiety, escitalopram for depression, and tracitone for sleep disturbances, she wasn't on any psychotropic medications prior to hospitalization, and hadn't been for about seven to eight years. So during our assessment of her, she was cooperative, but she was visibly anxious and was very, very worried about the ramifications of a psychiatric consult while she was in the hospital. She was requesting to see provider's ID badges, which notably did not align with the donning regulations set forth by the hospital. And in talking with her, she expressed concern that she was receiving treatments that didn't necessarily have correct indications, that she felt like she was being forced to accept treatments at times, and that she wasn't truly understanding what the treatments would do for her or what was going on. She did have a fear of decompensation. She was a DNR-DNI status, and had expressed concern that she would eventually kind of succumb to the illness, which was something that was obviously very distressing to her. And she was dissatisfied with the lack of continuity amongst providers, just with the transfers between services and from the emergency room up to the floor and whatnot. She also acknowledged periods of confusion, particularly in the nighttime hours of the which coincided with what the teams were telling us as well. And along with her psychiatric assessment, she also had some requests that came along too. So she had expressed interest in pharmacological management of anxiety during her hospitalization. She wanted some level of consistency amongst providers, both with the psychiatric team and the medical team, and clear discussion about the treatment options and indications. But most notably, she wanted the documentation about her unvaccinated status removed from the EMR. She felt like that was something that was contributing to some of the adverse interactions that she was having. Now, this is a bit of a busy slide, but stick with me here. So just a rundown of how she was appearing during our assessment. The highlights here that she was restless. She was psychomotorically agitated, though she was engaged and able to provide good information throughout the encounter. And her attention and concentration were conversationally intact at the time that we were speaking with her, though she was not able to tolerate formalized testing. So in looking at the differential diagnosis for Ms. L, we wanted to include as much as possible here. So obviously, with the reports of confusion and the periods of agitation, particularly in the evening hours, we wanted to consider delirium. And that was something going into the consult that we were most concerned about. Adjustment disorder with anxious features was also a consideration of ours, just given the correlation between her anxiety and these agitation periods that she was having with these stressors. Anxiety due to a general medical condition, given that her anxiety was linked to periods of respiratory decompensation. And given her history of anxiety previously, we did have to consider generalized anxiety disorder as well. Okay, so this will take us into our next segment here of the treatment of COVID-19-related anxiety. So we can break it down. And first, we'll go into non-pharmacologic interventions. So you can see here, there are a number of interventions that have been studied in the general population for management of anxiety. And we can extrapolate that this might be helpful in the setting of COVID as well. That being said, some of them might be difficult to truly enact in different settings, just given the social isolation that's needed, but also the respiratory compromise and medical conditions that might limit engagement in some of these as well. And when we look at pharmacological management, we can break it down into two subcategories here. So scheduled medications, like antidepressants or buspirone, gabapentin, or as-needed medications, like hydroxyzine, antipsychotics, benzodiazepines, or even trazodone. And we'll go into more of the scheduled medications first. So the first up here, the antidepressants. So SSRIs are generally accepted as the first-line agents for the management of anxiety. They provide longer-term coverage, which can be very, very helpful. They're relatively safe. With certain agents, they have pretty minimal drug-drug interactions. And although we don't have a range of time that is accepted as management of COVID-19-related anxiety going forward, there are a number of providers that are comfortable managing these medications if somebody is not hooked in with a psychiatrist in the community. There's also the potential benefits from the antiplatelet effects that these medications have, just given that COVID-19 produces a hypercoagulable state. And other antidepressants, like TCAs and SNRIs. So we do have to keep in mind that they do have noradrenergic activity, which might be a little concerning in the setting of some vital sign abnormalities in a lot of these patients. But all medications have a time and place. The downside to use of antidepressants is that they do take a while to work, right? So we can expect that four- to six-week time frame to really see the effects of it, which limits the use in the acute setting. And although many of the medications don't have potential drug-drug interactions, some of them do. And some of them do have very significant ones that we need to keep in mind when somebody is in the kind of acute phase. Next up, we'll go into buspirone. So again, this is a medication that's really commonly used for anxiety. Again, in pretty minimal drug-drug interactions, it's accepted as being non-sedating. However, there's a delayed onset of action with this medication as well. And it may impact respiratory drive. It's been described as increasing respiratory rate and providing a subjective feeling of shortness of breath as well. But it also has mixed efficacy amongst individuals who have used it. And lastly, we'll talk about gabapentin here. So again, minimal respiratory impact, which is something that we are very much interested in in the setting of a respiratory illness. And it could be beneficial in certain populations, particularly those that have concurrent alcohol withdrawal or benzodiazepine withdrawal when they are in the hospital. It does require ongoing renal monitoring. So it is renally excreted and has the potential for buildup and sedation if somebody's kidneys are not functioning as they normally would. And unfortunately, it's only been showed to have mild to moderate success in the management of anxiety. So something that is very helpful, especially in the acute setting, is as-needed medications. So hydroxazine is an H1 antagonist, which is very, very commonly used for the management of anxiety, both in the hospital and outside of the hospital. It is FDA approved for the management of anxiety. It has minimal respiratory effect as well. It does have a wide dosing range, which can be very, very helpful. Some people can tolerate it better than others. However, we do have to consider in certain populations if the use would be beneficial. So it does have anticholinergic effects, which might be a concern in the setting of delirium, particularly if somebody is experiencing it or if they are high risk for it. And there is a possibility of sedation with this medication as well. Antipsychotics is another class of medications which might be very helpful in the management of anxiety and COVID-19. Again, they are pretty commonly accepted as having minimal respiratory effect. And they could be helpful in the setting of agitation that is concurrent with the anxiety. We want to minimize polypharmacy as much as possible, as well as the kind of drug-drug interactions with that. So if somebody does have periods of agitation or is getting worked up, we would preferentially use an antipsychotic to just kind of simplify the medication regimen. There are also multiple medication administration routes with these medications, which is very, very helpful if somebody has limited PO intake or hasn't been cleared for oral intake. Several of the medications, so several of them are second generations, and that's kind of the generally accepted class for the management of anxiety. Trifluparazine is the only antipsychotic that is FDA-approved for management of anxiety. However, just given the limitations of the use at this point, we don't see that much. But Seroquil, like quetiapine, or olanzapine, even risperidone have all been used as good augmenters for the management of anxiety. And then benzodiazepines, I'm sure we are all fairly familiar with. They're effective treatment for short-term management of anxiety. They do have a rapid onset of action and can be given in multiple routes. However, they do come with a risk of respiratory depression, and that's something that is quite concerning in the setting of a respiratory illness. There is also the risk of dependence with longer-term use that we do need to take into consideration. And lastly, trazodone. Again, this is a little bit more controversial, maybe. There is some remote evidence of management of anxiety and depression with trazodone at lower doses. Also, it has minimal respiratory effects and a fairly rapid onset, but its use is generally limited by sedation. And there really is limited evidence for longer term use as well. So when we choose a treatment option for our patients, we do have some considerations. And like everything in life, it is a balancing act. So complete anxiolysis might not be beneficial. It is a physiologic response to indicate that something is wrong. So if somebody is not breathing properly, is not saturating well, it can be helpful at least to have somewhat of a response to indicate that something is going wrong. Anxiety is mediated by biological but also social mechanisms. So although we can take care of the biological part with medications, we cannot take away the social stressors that contribute to it as well. The COVID-19 virus may impact various organs, which can absolutely affect metabolism of these medications, but also interactions with other medications that can be used. And COVID-19 treatments may mediate anxiety as well. So steroids are very, very commonly used in the setting of COVID-19 acute infection. And that is very commonly linked to anxiety as well. Metabolism and clearance of the medications might be altered. And although the medications that are generally used to treat COVID-19 are known to have pretty minimal effects between like antipsychotics or antidepressants, it is something that we would need to kind of monitor on a drug to drug basis. Okay, so taking it back to Ms. L. So our consult recommendations, we opted to go with quetiapine just on an as needed basis because she was having those periods of agitation. And we did have concern for delirium and Seroquel does have some evidence of use in delirium as well. We opted to involve family as much as possible, which was a bit challenging with the visitor restrictions. However, we were able to set up virtual meetings with them and have an iPad brought to her room so that she can meet with them regularly. And this was something that was very comforting to her. We involve spiritual services, which was something that was again, very comforting for her. And we worked with her on relaxation and stress management, just brief therapy. We continued the assessment of her oxygen saturations and we worked with the medical team to optimize her supplemental oxygen. And we also added melatonin nightly to help regulate her sleep-wake cycle, just given the concern for delirium. And for the rest of her medical course, she did end up improving her respiratory status, got significantly better in the days after our assessment. She was downgraded to the medical floor three days after our consultation and was ultimately discharged home on no psychotropic medications. And then she followed up with her primary care doctor about two months after her hospitalization. And at that point, she had indicated continued remission of anxiety. So just a couple of take home points here. So COVID-19 related anxiety is a very, very common occurrence. There are biological, social and emotional factors that contribute to it. Management should always be tailored to the patient and the setting in which you're treating. And providers will need to consider the potential effects and interactions with other medical comorbidities and treatments. Okay, now I'll hand it over to Dr. Asar. Good morning, everyone. My name is Ahmed Asar. I'm a Consultation Liaison Psychiatry Fellow at GW Inova Fairfax Hospital. Today we'll be talking about psychotic disorders as a presentation in patients with COVID-19. So to start off, we'll start with a case presentation. Mr. K, who is a 37 year old with no past medical or psychiatric history who presents to the hospital with new onset psychosis in the setting of COVID-19 infection. So looking back at his chart, it was significant for two hospitalizations occurring in the prior two weeks to his current presentation. He had the first hospitalizations two weeks prior to his current presentation. He was hospitalized for mild COVID-19 infection presenting with fever, myalgia, cough, and diarrhea that lasted one week prior to his presentation. He was found to have sodium level of 127, which was corrected, and ultimately patient was discharged home after three days. During that admission, patient was started on Trazodone 50 mg at bedtime for insomnia, which seemed to help him with sleep, but was stopped shortly afterwards as the patient was experiencing sleepwalking. One week prior to the current presentation, he was hospitalized again. This time he was presenting with confusion. CT of the chest showed bilateral lung infiltrates suggestive of pneumonia and antibiotics were started. Patient started to feel better, but still continued to feel a bit confused. Earlier during that admission, psychiatry team was consulted for insomnia and confusion and recommended Cotopin 20 mg nightly and an additional 25 mg as needed. The choice of Cotopin in that case was for mitigating behavioral disturbances occurring in the context of delirium and insomnia, which would help in regulating sleep-wake cycle, which would ultimately improve delirium. Later during that hospitalization, neurology was consulted and they recommended MRI of the brain and EEG, which came back negative for any acute issues. Typically in delirium cases, we would be looking for generalized slowing on EEG and with EEG being normal in this case, it might be very likely that his delirium had improved by the time EEG was done or the patient was not delirious. His COVID-19 testing was negative on discharge. And then coming to the current presentation, this time he presents with psychosis and his COVID-19 testing was positive again at this time. He was exhibiting disorganized behavior as provided by collateral history, which was provided by the patient brother. He stated that he blugged the router of the internet thinking that he was being spied on, was talking bizarre, tried to jump out of the window. On the day of presentation, the patient jumped into the stream with his clothes on while he was on a walk with his brother and he was brought to the emergency accordingly. During the current hospitalization, he was seen spreading his arms wide open and attempting to jump out of the window. He was observed to be banging his head against the glass numerous time. He was reportedly having auditory hallucinations as he was observed to be talking to himself, what appears to be kind of talking to God. He was noted to be yelling at the staff and paranoid towards them as well. Additionally, he presented with cognitive symptoms, reporting that he has difficulties with his memory. His mental status examination was remarkable for having a guarded attitude, being easily distractible, psychomotor agitation. His affect was noted to be mood incongruent, appearing dysphoric, anxious. His thought content was showing persecutory and religious delusions and his thought process was demonstrating flight of ideas. He was noted to be responding to auditory internal stimuli. However, he appeared to be alert oriented times for, but he struggled with memory that he had, he was able to recall only three out of five items after five minutes and he had limited insight and judgment. So on the review of systems, patient denies headache, visual changes, neck pain, focal neurological weakness or sensory changes. He didn't have problems with walking or gait though. Past history, he has no past psychiatric or medical history other than being non-vaccinated for COVID-19. He was not reported to have prior social or occupational decline. He has finished high school education, been married with one child, working full-time. No reported history of smoking, alcohol or illicit substance use. There was no reported history of suicidal or homicidal false or attempts. He has never been hospitalized for psychiatric disorders. He has no history of smoking, alcohol use or illicit drug use. Family history was significant for bipolar disorder in his father, but otherwise not remarkable for other family members. So moving to the medical workup, it would be worthy mentioning that the patient was initially agitated for the first couple of days which precluded pursuing further medical workup. This ultimately warranted administering multiple psychotropic medications as we're going to highlight shortly during the hospital course, but for understanding the differential diagnosis, it would be essential to go through the medical workup first. He had unremarkable CBC-CMP inflammatory markers, his vitamin B12 urine analysis, thyroid function tests. His urine drug screen came back negative. There was no acute findings on repeat brain MRI or EEG. His CSF analysis was unremarkable including cytology, culture and sensitivity, virology including HSV, West Nile virus, VZV, EBV and CMV as well as autoimmune encephalitis panel. So this is a little bit busy slide, but we're gonna stay longer here. Based on what we know so far, let's have a quick highlight of possible differential diagnoses. So starting off with delirium, during the first hospitalization, patient was reportedly confused with low sodium level which would highly suggest a clinical picture of delirium, but during the next two admissions including the current one, he was noted to be alert, attentive and oriented times four with no fluctuating course and unremarkable EEG as we highlighted earlier, making delirium less likely in this case during the current admission. Next, we have substance or medication-induced psychotic disorder. So basically, our patient didn't have past history of substance use and his urine drug screen was negative. And more notably, when he was given steroids, his symptoms didn't really become worse. And moving next to our next differential of CNS pathology including TBI, encephalitis, seizures or autoimmune encephalitis. So our patient didn't have obvious neurological deficits on examination. His MRI and LP came back unremarkable and again, his EEG was normal. He had the negative autoimmune encephalitis woke up in his CSF and there was no recent reported history of TBI. And next, we've got a bipolar disorder. Most recent episode, manic or hypomanic or first break psychosis. So our patient has a family history of bipolar disorder which might increase his risk but he has no prior past psychiatric history and he didn't appear to fulfill full criteria for the aforementioned diagnosis. And finally, with regards to psychotic disorder due to another medical condition, our patient was found to be COVID positive during the first and very recent presentation. So that being said, let's delve a little bit deeper and overview how far we know of many on psychosis in patients with COVID-19. So the patient in our case was presenting with features of easily destructibility, increased psychomotor activity and had a risk factor of positive family history of bipolar disorder but nevertheless, he didn't seem to fulfill full criteria for a bipolar disorder. Looking into the current literature about mania and bipolar disorders in patients with COVID-19, it would be worthy mentioning that earlier studies around 2020 were suggestive of possible steroid-induced association. And then among the reported cases, mania has not been commonly reported though many reported case of psychosis include the manic-like features and with delirium not being entirely excluded. And that being said, that will bring us to the topic of new-onset psychosis and in patients with COVID-19. So the current level of evidence is case series with by definition would include a significant amount of selection bias. To add to that, delirium was not entirely or reliably excluded in most of the cases up to 40% of some of the case series. Symptoms of psychosis usually include delusions, hallucinations, disorganized thinking or behavior and catatonia. The clinical presentation in general most commonly corresponded with brief psychotic disorder with a mean age of presentation in the mid-40s. And finally, it would be worthy mentioning that some studies show approximately 30% of those who are infected by COVID-19 and experienced a more severe course also developed psychiatric complaint and suggest a molecular mimicry of NMDA receptors which may contribute to neuropsychiatric symptoms in the setting of severe COVID-19 cases. So basically autoimmune encephalitis in short is an autoimmune-mediated encephalitis associated with antibodies against the neuronal cell surface or synaptic proteins. It might not be very typically applicable to our case here given that our patient had only mild symptoms but with features of memory and cognitive deficits in particular and along with like the psychomotor agitation and psychotic features, this might be a part of COVID-19 itself or might be as a result of an autoimmune reaction resembling autoimmune encephalitis. So our patient had a negative CSF autoimmune encephalitis panel. However, a negative result in the CSF does not exclude autoimmune encephalopathy and sensitivity and specificity of CSF antibody testing can be further enhanced by testing both serum and CSF. So the current level of evidence as well here is like case series with symptoms occurring primary symptoms occurring primary in adults up to 80% and more than half of them are above age of 55. Their clinical presentation was of diverse phenotype including altered mental status, psychomotor agitation, memory and cognitive deficits as well as psychotic features and seizures. 75% of the reported cases occurred concurrently with COVID-19 infections and 20% occurred post-infection. After navigating through this case, exploring possible differential diagnoses and highlighting the current level of evidence of case series, it would be prudent to consider potential confounders while considering psychotic symptoms occurring in the context of COVID-19 infection. This includes delirium as it was reported, it was not reliably ruled out in up to 25 to 40% of the cases. And in the presence of delirium, it would be really challenging to parse out possibilities of primary mental illness given the altered sensorium and a wide array of presenting symptoms. Additionally, medication side effects including steroids, antibiotics and antivirals, past psychiatric history substance use were not considered in the majority of the reported cases. Also COVID status, whether it's active or recent. Our patient had a positive COVID test initially, then a negative on the second hospitalization and finally he was found to be positive one third time on the current presentation, which would be false positive occurring in the, which would be, I mean, during the second hospitalization, a false negative occurring in the interim and less likely a repeat infection as the current time interval is not typical of re-infection, which usually occurs after an average of 90 days. Also it would be worthy as mentioned earlier with the current level of evidence of case series like the selection attribution, bias related to the current quality of evidence. And finally, the stigma related to the COVID-19 and mental illness in general, either under-reporting or over-reporting. And so back to the hospital course, what happened to Mr. K? As mentioned earlier, the patient was initially agitated for the first couple of days, which precluded pursuing further medical workup. He was paranoid, agitated for the first couple of days. And then he was becoming increasingly agitated. And historically given the limited utility of behavioral interventions and trials of quetiapine as corroborated by the patient wife as well, a decision has been made to select a relatively higher potency medication, which would also help with the patient's sleep like olanzapine, reaching a dose of 10 milligrams daily. By the third day, our patient appeared relatively very appropriate and cooperative. He reported that his anxiety and delayed mental processing has improved. He was agreeable to diagnostic workup and medical treatment. He was empirically started on methylprednisone, one gram for five days and IVIG for a total of five days as well. And as we mentioned earlier, he reported that his symptoms was improving in the context of steroids and IVIG administration. At that time, patient was reporting that melatonin worked very well for his sleep, which might reflect the possible limited insight about his condition at that time. By the seventh day, patient reports that his cognition and memory returned to near normal. His anxiety has also improved. He started getting better sleep, like average of six hours of sleep. And we decided to decrease olanzapine to like five mg nightly. He was reported, or he was denying hallucinations, no longer paranoid at the staff at that time, within less than seven days. On the 10th day, patient was ultimately discharged and within less than one month after discharge, olanzapine was discontinued as an outpatient. So that being said, it would be worthy highlighting after presenting this case that with the current level of evidence, it would be essential to understand the relationship between COVID-19 cases and psychotic symptoms. It's not very well studied with the current level of evidence and bearing potential confounders. And the clinical picture of psychotic disorder in the setting of COVID-19 often resembles a brief psychotic disorder and to consider primarily like potential confounders while diagnosing primary mental illness in patients with COVID-19. And now I'll hand over to my colleague, Dr. Truitt. Thank you. Great. So good morning, everyone. My name is Colin Truitt. I am also one of our CL psychiatry fellows at George Washington University in Nova Fairfax. And I have the pleasure of capping off our presentation today with what could probably be considered a combination of anxiety and psychosis. And that would be with catatonia in the context of COVID-19. So like everyone thus far, I want to introduce my patient, Mr. B. This is a 60-year-old male with a past psychiatric history of PTSD symptoms that had been well-managed. And he was not currently being treated with psychotropic medications at the time of admission. He was also previously diagnosed with a cerebellopontine-angled tumor whose subsequent resection and pathology report led to a diagnosis of neurosarcoidosis who presented with a recent COVID-19 pneumonia to RED with worsening restlessness, confusion, and recurrent fever. And as I will go on to describe the case in more detail, it was a rather protracted case with approximately 18 to 20 days prior to our actual consultation, okay? And he was admitted briefly to actually multiple outside hospitals before ultimately we received our consult order for restlessness and confusion. So to provide a little bit of context about this individual sort of his historic course and through his life, relatively healthy individual from birth to middle age in 2001, successful military career as a commissioned officer. Unfortunately, he developed some PTSD symptoms and was formally diagnosed around 9-11 related events. He did go on to receive subsequent treatment and was not receiving significant psychiatric care at our, again, at our time of admission. In 2008, however, he begins to develop focal neurological deficits leading to some imaging and the diagnosis of a CPA tumor, as I mentioned, and that resection would lead to a diagnosis of neurosarcoidosis. And for the rest of his life, he will be receiving monthly to Q6 weeks infliximab infusions and has four neurosarcoid flares, required occasional steroid bursts. And so that leads to a bit of a tumultuous course between 2008 and 2021, and ultimately his presentation to our service where he would have multiple depressive and manic episodes mostly related to the actual steroid bursts themselves. He had a significant neuropsychiatric response to them and ultimately did require four psychiatric hospitalizations for mood stabilization. However, after each subsequent hospitalization, he was able to be tapered off of those medications. So I will provide context for day zero is the patient's symptom course, or course of illness rather, and I will give context of when he actually is admitted to our hospital and seen on our service. Okay, so day zero is 18 days prior to his presentation to our hospital. He was admitted to an outside hospital with some respiratory symptoms and generalized fatigue, body aches, fever, and ultimately had a positive COVID-19 pneumonia. He was shortly discharged after a brief OBS period, feeling that he was safe enough to be sustained at home. However, on day three, it's clear that his health is beginning to deteriorate as he has a syncopal episode that lands him in the emergency room with a facial laceration, sort of in the living room on the coffee table that ultimately required sutures, still sent home. Things are rocky between that and seem to get worse. At day 14, patient is ultimately hospitalized at an outside hospital with worsening weakness, is having some word-finding difficulty and general confusion. They felt that this was likely based on chest imaging in the course of his presentation, that he had a secondary bacterial pneumonia following his initial COVID-19 pneumonia, and he was discharged on seftonir. Does not make it home for more than 24 hours and ultimately is brought back to our emergency room by EMS as his wife is concerned for increasing pacing, refusal of all PO intake, having some word-finding difficulties, again, as a recurrent theme, and then beginning to have recurrent fevers. And so he is brought to our hospital just to kind of keep things simple. I just want to highlight some of the either odd findings or pertinent medical findings and just a little bit of brief context about his medical state in general at the time of admission. So unsurprisingly, I mentioned that he was receiving, you know, Q6 weeks to monthly infliximab infusions. He was also on a daily immunosuppressant agent, a mycophenolate. He was taking some lorazepam, BID, more PRN as a basis of occasional anxiety management as well as management for insomnia. This was managed by a primary care physician. As far as his objective lab workup that was obtained on admission, he did have a transaminitis that was of mixed relevance. There was some hepatic steatosis on right upper quadrant ultrasound. This was not felt to be reflective of his acute presentation, but I noted anyways because it was abnormal. He was still testing positive for SARS-CoV-2 on PCR testing at the time of this admission. So what we would still consider an active infection for this individual. Vital sign disturbance is notable for some borderline oxygenation as well as pretty significant tachycardia and a Tmax of 101 Fahrenheit on admission. QTC showed no, or excuse me, EKG showed no abnormalities and his QTC was below 500. So for us CL folks, safe. His CT head was not notable for any intracranial process and I will note that his MRI that we would later push for would go on to show no evidence of an acute neurosarcoid flare. So of course, you might see that there's discrepancy between the day that those objective findings were from and the day we actually examined him. That's because he was a bit abundant when he first came in after receiving some behavioral PRNs in the emergency room. However, on our repeat evaluation, he was alert enough to engage in a full mental status exam and I have highlighted some of the pertinent findings in red here. So there was some obvious psychomotor slowing. His speech was just latent and decreased in spontaneous output. The phrases that he did had multiple syntax errors which were incongruent with this person's level of education. He did derail frequently and was highly distractible when you actually would try to get him to engage or answer a question. But also, there was just a paucity of spontaneous thought content. Some of the most interesting findings though, I think are really looking at some of the language deficits and abnormalities that occurred. So there was a significance of neologisms, particularly convegra for spoon, which I thought was pretty logical actually. He also had multiple reverberations. So he would repeat the phrase fishy fish out of context about five to six times, sometimes when answering a question and out of context to the question that was answered. When providing like a qualifier for an answer of a question, he would repeat always approximately six to seven times. And there was mild and intermittent anomia. So it was not consistent across objects or trials. And his insight into where he was, why he was in the hospital was very poor. So based on the psychomotor slowing, based on the latency, and probably as you gathered from the context of the title slide, I decided to do a Bush-Francis-Catatonia rating scale. So his overall score on this was 20 and I have again highlighted some of the pertinent findings, some of which should not be surprising to you from the mental status exam. However, given the fact that of course this individual is quite ill and we would be concerned for elements of hypoactive delirium, I wanted to also highlight that there were some very specific features to Catatonia that were notable such as his rigidity, his waxy flexibility. He did have some significant mitcahen and then was also notable for a grasp reflex. And the refrigeration was sort of wax and wane at the time of this exam. It did not warrant, it sort of wasn't consistent across all answers. So it seemed he was quite catatonic based off that score with the general of a greater than 10 being worth an ADVAN challenge, so he had a score of 20. But I like to step away and think about the differential diagnosis particularly in the context of consultation liaison psychiatry, right? So you see organic versus primary psychiatric ideologies and I want to emphasize that I'm putting heavy quotations around the word organic, right? We all understand that there is a biomedical basis for primary psychiatric illnesses. But in the context of this service, we're oftentimes asked to see patients and they wanna know, is this a psychiatric issue? Do they need to go to psychiatry or is this something that we need to be working up more in sort of the medical context? And so I just highlighted maybe the most relevant differential that I felt like to this case, okay? So based off the presentation with catatonia in a case of a medically ill patient with a known viral infection, of course we're thinking, is this some kind of viral encephalitis? Not necessarily limited to COVID-19, he's had vital sign abnormalities, he's had a recent infection and so not out of the realm of possibility particularly with rigidity, is this some kind of confounding neurological factor though the rest of his neurological exam was relatively unremarkable? Is this an autoimmune encephalitis? Again, thinking of the course and has been discussed in sort of the psychotic portion of this presentation, we have a period of infection and is this an autoimmune reaction that's following it? Certainly temporal lobe epilepsy is like our great masquerader among psychiatry, so is there something that we need to be concerned about there? Knowing that he's on benzodiazepines and not getting a clear history from him, I'm also concerned, is there a benzodiazepine withdrawal element of this catatonia? Not knowing if he's taking them appropriately or if there were maybe more surreptitious use of those prescriptions. Immunosuppressant toxicity, tacrolimus in particular and there are a few case reports with mycophenolate that would suggest that there's a relationship between the immune system and the development of catatonia and so is this some kind of form of toxicity to those medications? And then finally, the low hanging fruit of this presentation is of course, is this a neurological sequelae of his COVID-19 or some form of neuro-COVID? I'm not going to go through the other more primary psychiatric etiologies because based on the history I've provided you, there's really just no context for any of this. There is the possibility that maybe he's in the early stages of a major neurocognitive disorder, but in the setting of acute illness, that would be really hard to suss out. And there was no sort of prior history from his wife at home that there'd been any recent decline other than this acute illness. So I think it's worth reviewing what is catatonia? And so catatonia is a potentially fatal psychomotor condition, right? It is a syndrome that combines both changes in our neurovegetative state as well as our motor states and it involves the initiation of behavior. And so most causes of catatonia really may be secondary to medical causes. Unfortunately for us, the literature is mostly done in the acute inpatient psychiatric setting. But in the bit of literature and reviews that exist both on the CL service and then in the general medical settings, if you look at the prevalence of catatonia among mood disorders in the inpatient setting, anywhere from 13 to 31%, that kind of closely mirrors what we see due to medical illness, four to 46%. And one of the most recent studies done in the journal Lancet, looking specifically at the incidence of catatonia as witnessed on the CL service, says it could be anywhere from roughly one to 9% in the patients that are encountered on the CL service. So the way that I kind of interpret all of this is, is catatonia, especially when we get into the pathophysiology of it, is it something that can come about in just the form of severe disease in general? Is it ultimately sort of a hyper-inflammatory response or some kind of end line to severe psychiatric disease as well as severe medical disease in a harbinger that we really need to intervene? It's also key that we'd be looking for it in the medical setting, knowing that like one out of 10 patients on the CL service could be seen. So the history of catatonia is actually relevant because it affects both our conceptualization and how we've actually studied it and maybe some areas of further study that need to be highlighted. So we've all probably, at least for boards, gotten the history lessons in our general psychiatry residency right of Carl Cobham first describing catatonia in 1874 with this sort of 26-person case series where he describes a tension insanity that's characterized by rigidity, mutism, food refusal, the waxy flexibility. Kraepelin would go on to subsume this concept as part of his formulation of a dementia praecox. And ultimately, this would pave the way for catatonia sort of as the way we conceptualize it to be subsumed for a while as a subcategory of schizophrenia, right? And so there's this real association in our history of how we have studied this with a primary psychiatric etiology. And yet, between 1916 and 1918, we obviously had the outbreak of the Spanish flu epidemic, and there's a physician by the name of Constantin Venneconomo who coins this phrase encephalitis lethargica or post-encephalitic Parkinsonism based on this post-infectious course that he sees in some patients who contracted and were thought to have recovered, at least initially, from the Spanish flu. And what he would find is that they would go on to be rigid, to be mute, to refuse food, to ultimately pass away because they weren't having any significant PO intake, they stopped interacting with their environment. And he also had the foresight to do some autopsies on these patients. And what he would discover is that, at least grossly, there seemed to be damage to the midbrain structures, right? The basal ganglia, the midbrain, the hypothalamus, all these kind of associations that we would start thinking about with some of the actual presentation of catatonia. And so there is this basis in our history of catatonia being witnessed in a medical setting, but because of sort of the way we nosologically developed, we've only sort of recently come back around on looking at some of the pathophysiology and sort of making this more biomedical connection. So we don't entirely have a good unifying hypothesis on actually what is the exact pathophysiology of catatonia. It's been hypothesized that there are these GABAergic and dopaminergic alterations that we see in this mouthful, the corticobasal ganglia thalamocortical circuits. What does that mean? These are the circuits that refine our behavior both from a motor perspective and from an affective perspective, right? These are the things taking the signal from the cortex, running it through these modifying agents and toning the signal down in the thalamus and back to the cortex to make sure it all works before it goes out, right? And so what we have been able to suss out from this is that these circuits are involved and that there are cytokines that are associated with alterations in the GABAergic tone and the dopaminergic tone within these regions of the brain. And so from that, we can hypothesize that a hyperinflammatory state occurs in this part of the brain and causes the disruption in signals that we see ultimately as the end result of the movement selection, the control and initiation and timing issues that we see with catatonia, right? We're thinking mitgahin, we're thinking ambitendency, we're thinking waxy flexibility, these signals. And maybe from the clinical level, what we've been able to observe is that we can look at inflammatory markers perhaps as a way to help us if we're on the fence of this diagnosis, sussing out is this catatonia maybe versus a hypoactive delirium. And so we're looking at D-dimers, CRPs, and ferritin levels that can be elevated in these patients. So we've made the connection through history that yes, catatonia has been seen in this post-infectious course and that there is probably some sort of basis for the inflammation that's caused by a significant infection. But where does that leave us with the literature of catatonia and COVID-19? And like much of the other literature that we've discussed today, it's primarily restricted to case reports. That being said, there have been a surprising number of case reports to come out over the past two years in case series looking at catatonia in the context of COVID-19. The first case that I was able to find was submitted on July 7th of 2020. This was an elderly individual with a significant history of schizophrenia. I've highlighted their Bush-Francis catatonia rating scale. And unfortunately, in this case, they were faced with his worsening respiratory condition and inflammatory markers. And while he would ultimately respond to a lorazepam challenge, his tenuous respiratory course would make treatment not viable. There was not ECT access at this individual's particular hospital. Ultimately, he would go on to pass as a result of his COVID-19 infection, and they just weren't adequately able to treat the catatonia in that context. They were able just to get that sort of initial response. And so this is kind of consistent with what we've discussed so far, particularly in the previous section with psychosis, right? A history of primary thought disorder, primary psychotic illness, or primary mental illness, as well as just being more vulnerable in general with age, potentially some neurocognitive impairment. But when you look at the case series that follow, it's a relatively heterogeneous population with both people with a history of either psychotic or some form of psychiatric illness, as well as major neurocognitive disorder, but also relatively younger patients who have no significant psychiatric history at all. And in fact, in some of these cases, there seems to be the neuropsychiatric presentation is the only presentation of COVID-19. And so there have been some studies, not particularly with SARS-CoV-2, but with other coronaviruses in the past that have been done retrospectively, where IgG seropositivity to certain coronavirus strains, particularly during the MERS outbreak, and if you think of the previous SARS outbreak that we've had that were linked to an increased risk of psychotic symptoms in patients at that time who had no previous psychiatric history until their infection. And this is a busy slide, but the takeaway is there's at least a logical hypothesis of why catatonia can happen as a result of SARS-CoV-2 from sort of the way SARS-CoV-2 disseminates in the body. So we think about that direct CNS invasion that we are all familiar with, with the going through the olfactory bulbs. And if we look at that route of invasion, the virus itself can directly go through the endothelium, through the blood-brain barrier breakdown that's probably caused by the infection, and ultimately end up right in those midbrain structures. If we think about just the peripheral aspect of it, the hyperinflammatory state, the immune response, some of those cytokines that I mentioned that were elevated in previous studies, we again see that we think about, well, what's vulnerable from the periphery, and that would be the area of prostrema, so blood-brain barrier breakdown there. And then again, we're in the substantia nigra, the other aspects of the midbrain and the basal ganglia. So there is at least a logical route based on what we know about how this virus interacts and what we know about the pathophysiology of catatonia to at least make this connection, though obviously more formal study is needed. Unfortunately, the literature also doesn't change what we already know about our treatment options with catatonia, so our GABA agonists, particularly a benzodiazepine, remain first line. Lorazepam is mentioned several times in the literature. It's still being maintained as the first line, partially because of its metabolism. So when we're in these critical care settings where there's a lot of other medications on board, we just have less risk of drug-drug metabolism. Again, this has to be weighed against the risk of respiratory compromise, which in some patients is, again, as I described, the neuropsychiatric symptoms are the primary presentation. In other patients, they are more critically ill. ECT also sort of remains as a co-first line, particularly in severe disease. If you are worried about respiratory depression, again, the discussion around ECT becomes a safety of the staff administering ECT and the level of PPE that is required, as well as thinking of potential airway protection for the patient should they decompensate. After that, our second-line agents are rather second line. We don't have a lot of good evidence just to discuss, but what we do know is that there is some evidence that the NMDA antagonist, as well as some of the anti-epileptic agents, particularly valproic acid, may be worth it as an augmenting agent when you're trying to fully lyse catatonia, or as a second-line treatment for a patient who has failed sort of initial benzodiazepines, ECT, or cannot tolerate those treatments due to their medical condition at that time. So fortunately, back to our case, what happened to Mr. B? He had a very successful response to his Ativan challenge, one milligram IV, decreased his Bush-Francis catatonia rating scale from 20 to 10 within 30 minutes. We then started him on one milligram IV three times daily, and within the next few days, his Bush-Francis catatonia rating scale trended down to almost negligible at that point, and he was able to tolerate a transition to PO lorazepam without any significant rebound in his symptoms. There was an element of delirium in the background of all this. He still had executive function deficits. He was impulsive, short-term recall remained poor. His EEG would go on to be noted for generalized slowing. They would do an LP, but again, there were no signs of acute neurosarcoid flare and other really notable abnormalities in his lumbar puncture. So his delirium would continue to kind of wax and wane. He was a bit aggressive at times, and certainly not back to his baseline self. So in order not to risk worsening his catatonia or having a return in it, and also trying to help manage some of his impulsivity and behaviors, we ultimately elected to start him on valproic acid 500BID with some improvement, particularly in his aggression and sleep-wake cycle disturbance. However, his executive functions deficits did seem to persist, and ultimately he was discharged to acute rehab facility, not quite back to his baseline mental status. So the take-home points for this is that new onset catatonia, especially without a significant history of serious mental illness, warrants a medical workup. And I would argue in many cases warrants a medical workup because there are so many potential causes of it that may go unaddressed. Early recognition and adequate treatment of catatonia is crucial. These are kind of the quietly delirious patients, or at least that's what may be assumed, that oftentimes get missed on the medical service. There at least seems to be a logical basis for the connection of catatonia and COVID-19, possibly due to a direct viral encephalitis or hyper-inflammatory state, and our treatment remains as we typically would expect it to be. And with that, our references, and we are open to questions. Thank you to my co-presenters. I know there's overflow. I am not sure what the best way for questions is going to be for them. But for the time being in the main room, we're gonna take questions through the mic for the next 10, 15 minutes. Just giving you guys our names and our areas that we spoke about today, just to give you a little more context. Hello, sir. Hi, I have a question about case number two. What is the handoff between the hospitalists and the outpatient doctors? How did you communicate to the outpatient doctor? When can you discontinue the olanzapine? Was it the CL doctor who gives a detailed recommendation on that? How does that work? Thank you, sir. Thank you for your question. Basically, the patient on discharge, we made sure he's scheduled for a follow-up, and it was from within the same institution. Follow-up was scheduled, and he had followed up twice over a span of one month, and basically it was on a patient request. He didn't really want to be on antipsychotics longer than that, so we made sure there is no acute risk or anything in that sense, and the decision has been made ultimately. Do you want to come up to the mic, sir, just so that everyone can hear your question? I can speak loud, I think. Sure. I work in the geriatric service in the state hospital, and recently I had two catatonic patients, and I found they responded well to lithium. Lithium combined with Ativan and Modoceracol. Yeah, so this is a gentleman who was just speaking. I'm reiterating for you, but this is a gentleman who was just speaking. So this is a gentleman who was just speaking. I'm reiterating for the people in the other room. Works for geriatric service, had success with lithium, and in addition to lorazepam, I believe is what you said. Yeah, I think the thing that didn't necessarily get highlighted in Dr. Truitt's talk is that catatonia is a symptom. It's not necessarily something that you can treat without treating the underlying condition, and so I would wonder if his success with lithium might be partially because of the underlying etiology getting addressed in that situation. Yeah. Okay, if there's no further questions, for people in the overflow, I will give you my email. It is my first name, B-R-E-N-N-A, and then a dot, and then the last name, Emery, E-M-E-R-Y, and it is at innova, I-N-O-V-A, dot org. Thank you so much. Please enjoy the rest of your conference, everybody. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you Good today. Thank you so much. Good. Thank you Thank you guys. Thank you. Good night. Thank you. Good night. Thank you. Thank you. Good night. Good night.

medical conditions

psychiatric disorders

underlying medical conditions

infection

COVID-19

anxiety

non-pharmacological interventions

psychosis

differential diagnosis

autoimmune encephalitis

mental health symptoms