Catatonia

Transcript

• 00:00Alright so we will get started on this top on Catatonia.
• 00:05So there is nothing about Catatonia that is not peculiar when you see it. You just know that there is something unique something bizzarre, something altered about the individual and will unpack psycho motor here in just a moment but first off? What is catatonia an kind of to put it in a phrase broadly speaking thinking about the 20,000 foot view a potentially fatal Psycho Motor Syndrome again will talk about.
• 00:37Psycho motor sentiments, but is potentially fatal if it's accompanied by if it's accompanied by autonomic instability. So we would call that malignant Catatonia with hypo hyper in para kinetic variants. So too little, too much or not quite normal. Motoric variants related either to mental illness or secondary causes. So it can be something that presents an mood disorder, psychotic disorders, what have you.
• 01:07And also it can be the presenting symptom or phenotype of a range of physical symptoms in patients without any mental health history previously.
• 01:19So it was originally described as tension insanity by calling in 1874 roughly 150 years ago.
• 01:28Why does that matter well it's interesting first off because the word insanity was just a catchall term for mental illness. It did not mean? What we think about insanity. Currently, the word insanity? Is obviously become a byword or pejorative. In many different ways insanity just meant not healthy in without Sano's being hygiene or cleanliness or just health. So it just meant unhealthy. In fact, the American Journal of psychiatry is because the American insanity.
• 02:01It was first in first inaugurated on the first issue the first of many issues and so tension insanity simply meant the insanity. The mental illness. That was characterized by Motoric or muscular tension all it really was trying to say.
• 02:18Tension on denotes motor and so obviously there's something kinetically different and specifically insanity in this context, really refers to volition or will there was something where the will is hijacked or altered or distorted in such a way that very often that person has anagnos agnosia of deficit and they don't realize that they're doing, it and very often when they get out. The other side, there's still kind of bewildered by it.
• 02:50It doesn't quite register with them that they were incapable of completing certain willful acts during the time that they were catatonic.
• 03:02So again Psycho Motor syndrome that's kind of the broadest broadest framework. I think that that we would put it in. It's often bizarre an inconsistent the inconsistencies are notable because a lot of times. People say, Oh, well. They got up and use the restroom. They can't be catatonic false. They absolutely can be there's something primitive about having to go use the restroom. It could just well be a learned behavior that is deep enough or well ingrained enough that they were able to use the restroom and they'll go right back and.
• 03:35Have psychological pillow and you know be rigid or posturing and all sorts of things so people can often be even experienced clinicians can be fooled into thinking Oh, they're just faking it when they are clearly and utterly catatonic, so again. The inconsistency is just part of the syndrome very often much of the evidence on the biology of motoric abnormalities derives from Stuporous Catatonia.
• 04:05In schizophrenia, especially work by Northaw and so it's really difficult to know how much a lot of the literature. We read literature on the biology of this, or kind of what exactly it is, and phenotypes. It's very difficult to ferret out how much of that is related to the historical Association between Catatonia as a stuporous condition. The mute variant. If you will in schizophrenia. So it's very difficult to know how much that generalizes and whether we're looking at different phenotypes or?
• 04:38Whether or to what extent these are distinct entities that just simply happen to have the same look and feel.
• 04:46Convergently, speaking.
• 04:48So where does it go in the DSM 5 well, thankfully. It's not only a subtype of schizophrenia fact we don't have subtypes of schizophrenia anymore than you but it can be a Catatonia Specifier. So Catatonia associated with another mental disorder. So mood disorders and schizophrenia and related disorders are the most common ones that we should think about and then catatonic disorder due to another medical condition, notably and we talked about earlier Delerium would be a rule out for this you can't diagnose this.
• 05:21In the context of delirium because again delirium is the universal rule out however. I think it matters. And we should still think about catatonic features in the context of delirium and look at that phenotype as a composite hole that deserves clinical attention and it says something about diagnostic and treatment potential.
• 05:46And then finally unspecified pattern is great, you have Catatonia you're not quite sure where it fits you can say unspecified Catatonia and then provisionally and then revise the diagnosis if you get cleaner clear information.
• 06:01So how do you diagnosis it at least 3 of the following 12 and this is going to approach the organization on this is an approach taken by a paper in press right now at The Lancet psychiatry. I believe first authors. Walthers should be out shortly but effectively you have 3 different types. So you have observation. You can see an agitation. The hyperkinetic variant, which is UNCC huge their agitated for no reason.
• 06:28Then the parrot kinetic or kind of the odd behavior, so stereotypies. Witcher purposeless kind of repetitive stereotyped behaviors mannerisms, which are purposeful things done. Audley sort of walking they walk on their tip toes instead of talking. Normally with regular cadence, they might do a sing song Y or lilting or robotic speech. So those would all be odd ways of doing things that are purposeful posturing, which is active they assume.
• 06:59The position without you're helping them so you walk in and their arm is like up or like a scarecrow or whatever and grimacing which is in a sense, one could argue it's actually a posturing of the face so but it's Schnauss Crump. So kind of a puckering on the lips, which has to do its historical germanic term. German term it should say hypokinetic you would obviously see if their stupor is.
• 07:26On interview you would assess whether they have echolalia, which is echoing what you say or echo faccia echoing? What you do and then whether they have mutism in response to your questions and then negativism which has been variously defined either as doing the opposite of what you say or not doing what you say so. Broadly speaking the lack of engagement and negativistic responses? Let's say just say no in a stereotype fashion to basically everything you say no.
• 07:56Can you do this? No no or whatever you ask no it's always oppositional response?
• 08:02And then finally on physical exam, you should you should always do a brief physical exam for other features of Catatonia, 2 in the DSM or waxy flexibility.
• 08:15This is interesting 'cause it has 2 definitions as well in the DSM. I believe it refers to consistent resistance over the course of passive movements are moving the arm around but there's resistance, but it's always the same. The Bush Francis, though describes that there's initial resistance and then it kind of gives way like you're bending. A candle and then it just leaves residual some kind of residual rigidity, which would be would be assessed on the Bush Francis.
• 08:46As a separate item so the bush. Francis makes a distinction between those two of the DSM. I believe uses waxy flexibility is a standing for rigidity.
• 08:56And then catalepsy, which is where you can position them and they keep it that happens, you know you have Catatonia but effectively the passive version versus the active assumption of postures, which is posturing so that would be the distinction there and then there are many other features. This is just a sampling and I've tried to keep the same general presentation. So the hyper kinetic side have impulsive iti or combativeness, which would not formally be in the DSM, although may make.
• 09:26May meet kind of May satisfy the agitation criterion, depending on your sense of that behavior interview. You might get clanging associations actually historically was likely to K, which means sound in German and then parrot connecticon observation by psychologic pillows. They hold their head off the pillow, but they're actually lying down. But it's like there's a pillow. But there's no pillow. It's kind of interesting it's type of pottery.
• 09:56Denuded in behavior much more common in Catatonia. Most people realize they're trying to take their clothes off consistently.
• 10:03I almost my mind goes to catch it. Not that it is Catatonia might immediately goes there because it's so commonly described in these kind of Parrot. Connecticon something different hyper kinetic states of Catatonia Festa Nation or bizarre walking which you might argue is a manneristic way of walking at the toy movements or dyskinesia's.
• 10:25In terms of interview for Perry kinetic automatic obedience. Hey, I have a needle here. I need to stick in your tongue would you stick your tongue out for me and if they just reflexively stick their tongue out for you, you kind of know that.
• 10:37Abnormal.
• 10:39Verb iteration perseveration or different refrigeration is the same word or phrase given again like a scratched record like I was, I was. I was the same thing. It's a repetitive like there's a scratch on a record. It's just doing the same loop.
• 10:57Versus Perseveration, which is the same word or topic. They just keep coming back to the same topic or give you that same word repeatedly in response to different context or different questions where it's no longer appropriate.
• 11:09And then physical exam, Gegen Halton, which is a logical terms para tonic rigidity, so the resistance is equal to the force applied that mocking one should say mid gay him ha. So Mid Knockin is say don't move your arm and then you push a little bit and they let you move it. So it's kind of it's kind of the opposite of automatic obedience. Gehin would be like an angle poise lamp so you see the lamp like in.
• 11:42Pixar and like this, the kind of lamp that you push and it kind of goes up a lot higher so you just get a little push and don't move your arm and then it just kind of goes up almost on its own. I've only seen that twice was delightful. I did it several times, just to make sure I was actually catching it was like Nope this is Catatonia.
• 11:59So when you see this pretty striking anamba tendency is when you get kind of stuck so you're like don't shake my hand and then they reach out to the social cue, but then they don't and then like wait. I don't know what to do or it's like there in the middle of something and they just kind of get stuck in that position for what it's worth it's kind of a mix between posturing and the will again the will is really being disrupted frontal release signs can be seen, especially in patients who have delirium in catatonic features.
• 12:30And then the hyper kinetic form you can get withdrawal. So not eating or drinking for days and days and days so this is a real big medical risk.
• 12:38I put Tampa tendency here, too because sometimes you'll just see it happen without actually doing a physical exam and asking them to do something. So it's kind of it spans a few staring with decreased blinking you would just see that an evaluation and then in its own category. Autonomic activation very commonly seen can happen as well. See in a moment can happen in hypoactive or hyper hypo kinetic and hyper kinetic state doesn't matter you can get malignant features.
• 13:08In either again, the stuporous or excited variants of Pantone.
• 13:14Have to meet with the Bush Francis Catatonia rating scale and screening instrument because this is really the standard instrument that people use clinically to get a good sampling of the catatonic features that are present.
• 13:30Print it out get it on your phone use. It use it all the time it's again covers a good range of then there's actually by the way. There's also a kind of a prescribed Catatonia interview. That's also in the same publication. So it kind of walks you through how to assess them again, thinking about observation thinking about.
• 13:52I'm clinical interview and then the physical exam, so the first office greeting instrument is kind of the front side of it. The first 14 items and if two atoms are present recommendation is to go and complete the entire rating scale, so score the back as well. The rating scale assess is symptom severity. But I just want to mention it does not provide a diagnostic cut off, so diagnostic cutoff would have to be based on the DSM and I'm not a huge fan of the way the DSM.
• 14:22Has it right now, it it certainly could stand to be more structured. But the fact is the reason? Is the way it is, is that the data just aren't clear quite yet and so in the absence of clear data guiding us. We've kind of been left with kind of what we have right now and it's less than ideal, but diagnostic cut off really should be looking at something like the DSM bush. Francis does not provide that.
• 14:49So this is what the Bush Francis looks like if you want to find a PDF of it. You just have them bush. Francis Catatonia rating scale space file type no spaces. Colon PDF no spaces and all of that and then Google will only return PDX and then you'll get this is like the first or second hit you'll have the Bush Francis.
• 15:11I like to think about Catatonia in the context of combinations of symptoms, so if you think about it.
• 15:18There are 12 possible symptoms and any three symptoms will give you the diagnosis of Catatonia. We call that Poly Thetic by the way and you know the diagnosis of major depressive episode is Poly Thetic. You have to get a certain number of a certain number or dig fast mania certain number of a certain number right? That's called a Poly thetic aspect of diagnosis.
• 15:42But.
• 15:44If you think about it here there are 4017 possible symptom combinations.
• 15:53Out of the 12 features.
• 15:55That's kind of complicated.
• 15:57You kind of wonder whether index criteria might help simplify or streamline or clarify our diagnostic approach again. The data just aren't very clear about how we would do that. And if you think about every three symptom case of Catatonia. So let's say a patient, a over here and they meet criterion 1. Two and 3 in mobility stoop mutism and withdrawal will say they have that.
• 16:27And then on the other side will say Echo Lalia and then you have 9 symptoms remaining. There are 466 possible symptom combinations of those remaining 9 symptoms that would share no symptom in common with this first patient.
• 16:42And yet we call them both catatonic I find that a bit chaotic in its diagnostic approach just to think about the combinations and the possibilities so again, notably there is a great deal of heterogeneity in complexity right now in our clinical phenotypic approach to Catatonia diagnosis.
• 17:03There are a few other limitations. Video Sen won the time periods, not specified, although 24 hours is often presumed by the way kind of presumed in delirium work as well, 24 hour period for the disorder air quotes.
• 17:16There are no index symptoms, which means that the 12 features are entirely. Poly Thetic in our approach. It presumes similar catatonic presentation, regardless of associated condition. So it presumes that the Catatonia presenting due to anti NMDA receptor antibody encephalitis would be the same clinical phenotype that you would get if you had bipolar disorder manic with catatonic features.
• 17:45Maybe it is maybe it isn't but again that's a presumption. That's not entirely justified by clear data in support of it.
• 17:53And again as I mentioned you can't diagnose Catatonia during delirium? Which.
• 17:59Clinically, I think there's value in keeping the 2:00 is distinct constructs in your mind.
• 18:06So, in terms of the structure of Catatonia.
• 18:09If you break it up into hypo hyper anpara kinetic variants.
• 18:13You really only explain about 1/3 of the variance in clinical phenotype, which are really suggests again a great a great muddiness when you're thinking about what Catatonia is case. Wise and the complexity within that phenotype again. We still have some ways to go in clarifying this.
• 18:35So broadly speaking stuporous and excited Catatonia can go back and forth. Excuse me, either of them can become malignant if it develops autonomic activation or instability.
• 18:48And then there is a separate diagnostic approach in kind of the German approach to psychopathology so ver. Nikki Kleist Leonard tradition. They talk about the periodic Catatonia versus systematic. Catatonia isn't the systematic. Catatonia is there are many different subtypes. These would likely I mean in our modern terminology be would be smattering of them both in the Stuporous and the excited Catatonia.
• 19:20Which may or may not bleed into malignant catatonia but I do mention this specifically because this idea of periodic catatonia remains kind of an interesting curiosity in diagnostic systems because some people get to Catatonic and between catatonic episodes. They have Inter episode recovery in their asymptomatic so whether people can have just a pure periodic. Catatonia kind of interesting question have a slide on that in a moment.
• 19:46So looking at each of these.
• 19:48By itself, so stuporous Catatonia kind of common prototype that we think of when we think about Catatonia.
• 19:55Other terms include retarded, Catatonia kinetic mutism coma vigil both of those have other definitions and other conditions associated with them. So probably not the best terms to use here benign stupor also. Maybe not the best term to use call bomb syndrome fair, but we don't really use that but it's all that much nowadays and delirious melancholia or depression supers. Catatonia tends to be. I think the most common terminology here. So basically this is a mobility mutism and often bizarre posturing where they?
• 20:25These are the 3:00 that dominate the eyes often suggest alertness so the eyes are kind of roving around and responding in kind of doing different things. It's not like there just just asleep. There is a semblance of again alertness, but again there's not moving or not moving much not speaker not speaking much and it's often difficult to distinguish it from hypoactive delirium. But if you give Adam and they wake up and they start talking normally then you've just done it and then.
• 20:56I kind of think about it as a car whose motor is running but it's a neutral or perhaps with the emergency brake engaged. The motor is on, but it just can't go it doesn't have it doesn't have the capacity to go.
• 21:11For what it's worth.
• 21:14Excited Catatonia other terms bells mania, which came out of McLean hospital. Oh Niagara Frania, which means kind of dream mind and the delirious mania, so this is often there's often presents as purposeless often bizarre activity. Mannerism stereotypies and echoing with a lot of agitation. Just kind of constant movement. When have you often francon precipitated agitation and as I mentioned earlier alternate with supers catatonia?
• 21:44It's a kinda modern descriptions of excited delirium syndrome. This is a term that they are increasingly using in Ed Medison Emergency Department, Madison and.
• 21:57There are these individuals who will use kind of some modern stimulants where they just have just unremarkable strength. Unrelenting agitation and ultimately die of exhaustion so that was kind of how a lot of the historical presentations were documented so the question to be honest. I think a lot of historical publications might have actually been identifying cases of autoimmune encephalitis and we just had no idea what to make of it because we didn't know to look for a lot of different things.
• 22:27And or other things like malarial fevers and stuff that present with confusion agitation and catatonic type features so for what it's worth an alignment. Catatonia scouters or Saturday. Look at a leaf of a disconnecting means not always lethal and so maybe malignant might be a little better term, although probably not the best term, but it is the term that were given so it can be super excited with autonomic instability. Often it's accompanied by hyperpyrexia so really high.
• 23:01Temperatures Leukocytosis Rahab Doe Kidney injury.
• 23:06In Ms in Serotonin syndrome considered by many beyond the spectrum. It is potentially fatal. I mean, this is something where very often, they get up to the ICU you are just throwing benzos at them really if you can get ECT 2. ECT if it all possible if it's medically feasable sometimes. You just have to be kind of put into a medically induced coma let it kind of save your life from the autonomic storm. That's happening. So I'm getting very, very dangerous condition when it presents some can be pretty harrowing.
• 23:38For everyone involved.
• 23:43Yeah, not you're right now, you're absolutely right. Sometimes that does not even do it, which is why ECT if at all possible. ECT is really definitive as definitive treatment are going to get but you're absolutely right does not always does not always manage that very well.
• 24:01Periodic Catatonia also I'm not sure if it's gessinger guessing syndrome, but anyway. This was an individual. In the mid 1900s? Who did a bit of work on it, and described it, so kind of categorized named after him for the work that was done on this is characterized by recurrent episodes of Catatonia with Inter episode recovery and perhaps autonomic AutoZone will dominant transmission. There have been some families where the probe and and then you looked at other individuals, oh wait actually it was in such and such and it was delivered.
• 24:36There are a few mutations that have been associated with this, which is kind of fascinating haven't seen much recently but early 2000s, there were a couple of reports about that.
• 24:47In certain pedigrees and then it has been associated with finished TSH response to.
• 24:54I would releasing hormone.
• 24:56Some interesting thyroid findings.
• 25:01It's an unfair.
• 25:03There are a lot of questions that remain but it also I think should be kept in the back of our minds as a potential entity as a unique type, perhaps of Catatonia.
• 25:15The neurobiology and interesting Lee there aren't many good pictures in the literature. This is one of the better ones, that I'm aware of the big thing that I always think about is.
• 25:24I like it to the opposite of I like it to the opposite of why you give stimulants for ADHD.
• 25:34So if you think about the brain like a second grade classroom or first grade classroom kindergarten classroom. The Subcortex is the horde of unruly children right and you have a pre frontal. Cortex that's there like a teacher to keep everybody in their seats and on task.
• 25:54And then you have for instance, with.
• 25:59If you have ADHD and the child is hyperactive. It's kind of like the kids are all running around, but the but the teacher is asleep at the desk. You give the stimulant wake up the teacher, the kids sit down.
• 26:11They focus good Catatonia is kind of the opposite. It's kind of, well at least the stuporous variant. Now, how this applies to the hyperactive or I should say the excited variant. I'm actually not sure. I haven't heard a lot of great descriptions of this neurobiologically speaking, but at least the stuporous type. It's kind of like the opposite. The Subcortex is there and it wants to kind of. They want to engage they want to pay attention to the class. The class schedule or the lecture or whatever.
• 26:44They want to be engaged, but the teacher. She he or she is a bit strict and there is no there is no one talking 'cause. They are walking on egg shells. So you really kind of have to soften the teacher down a little bit and then maybe they are able to engage they feel a little more liberated and they can participate. That's kind of my way of thinking about why we would give a gabaergic agent that would preferentially work on the prefrontal cortex so as to therapeutically disinhibit the person.
• 27:17To be able to engage clinically interpersonally and in terms of their function.
• 27:24I'm a general general way of thinking about it.
• 27:28Conditions associated with Catatonia this is a very simplified breakdown looking at just a range of study so I wouldn't be able to point to one specific study where this is the obvious answer, but general general take on the literature is about half of patients have a mood disorder.
• 27:46At 1/4 have a medical condition with or without delirium about 15% with a psychotic disorder and then this other smattering of other an unknown like autism spectrum disorder. The neurodevelopmental disorders can present with Catatonia there. Other conditions that have been described but.
• 28:05And broadly speaking this is this is the breakdown of causes, or associations.
• 28:12And then I did a review the.
• 28:152 years ago and I came up with this. Akron mindset thinking about what are the medical causes of Catatonia that have been described is going to review the literature looking at this?
• 28:27And this was the way that I divided it miscellany about 20% inflammation of the CNS mostly in South validity's 30% in neural injury or Nordic generative conditions about 20% demyelination so forth or other let's see dementing illnesses where it might present in that, like a vascular neurocognitive disorder. Developmental didn't find any of that. But I was focusing on the adult literature. And so I wouldn't have picked up a lot of the pediatric and adolescent literature.
• 28:57On structural or space occupying so a lot of primary or secondary tumors so metastatic disease as well.
• 29:05Epilepsy about 10% and toxins and medications about 10% and.
• 29:11If you look at just the internal ones, and exclude miscellany and there aren't any toxins or medications involved.
• 29:182/3 of the conditions that cause Catatonia medically are CNS specific now not just CNS because of his delirium effects of CNS 'cause you're confused so the brains involved, but these are CNS specific like the insult. The injury, the functional impairment, the issue.
• 29:37Is chiefly inside the calvaria that's where we're talking about so they would include again encephalitis in or degenerative developmental neurodevelopmental structure space occupying an epilepsy so again really it. Prioritizes a neurological work up when you see or consider Catatonia in the altered patient just a general thing focus focus on that.
• 30:04So the clinical approach first off you really need to have high clinical suspicion. If you do not have. I clinical suspicion. You'll miss it. I mean, if you don't think about Catatonia. You you just won't find it. So you always have to hold in the back of your mind. The hope that your patient has Catatonia or the possibility that they have Catatonia in order to identify it and in fact, I think a lot of Catatonia is just just not appreciated or the broader spectrum of Catatonia is just not appreciated and it kind of goes under other names.
• 30:38Clinically so when you are diagnosing it.
• 30:43Adam and challenge should be thought of his diagnostic and in fact.
• 30:48We've at our hospital, we created.
• 30:54Treatment guidelines for Catatonia in psychiatry and we frame. The Ativan Administration, or low. Raza Pam I should say sorry the generic as diagnostic because if you give law Raza Pam and they have a dramatic response. I mean that's really, really clinches the diagnosis. You're like oh that's what we're dealing with, and because once they kind of are liberated very often, you'll notice that they are manic.
• 31:25They are really despondent and depressed.
• 31:28Are there really, really confused you often will see that once they're able to now communicate with you in a little bit more conversant way just say that.
• 31:40So, in terms of next steps. I would say prevent complications. I really like this review from 2014 and it goes through very concrete recommendations as to how to prevent medical complications associated with Catatonia because we already said it's potentially fatal and it is dangerous, and it can again be very.
• 32:06Cause complications in the short term, but it can also be fatal so thromboembolic disease is big multi focal or multiple PS that can be fatal. I've seen that it's it's really, really, really frightening D cubitis ulcers if they're not getting up and moving obviously contractures or possible so passive range of motion, making sure they don't develop contractures. If it all possible. Aspiration ammonia malnutrition generation. They're not eating or drinking because withdrawl again is a feature of this syndrome.
• 32:41To think about.
• 32:42And when you're really kind of going through this. A few other considerations. You know how they had a stroke are they just a phasic do they have locked in syndrome? I mean that's so obviously your brain imaging will be helpful to determine whether they might have developed that osmotic demyelination. What have you. The other reasons or stroke. Parkinson plus syndrome? This just presenting with a great deal of rigidity and some other kind of odd or nonstandard symptoms and then.
• 33:13Thinking broadly about minimally responsive states or persistent vegetative states. In fact, we saw a delayed demyelination event that looked like Catatonia, but then ultimately in retrospect. It really was delayed hypoxic demyelination is what it ended up being really was kind of a minimally responsive state more appropriately given just the vast demyelination that happened in that patient so.
• 33:43And then find the cause and so that's where we'll get to in just a moment. So obviously think about what is the associated conditions so is it a primary mental illness or is it a secondary presentation of a medical or neurological condition broadly speaking.
• 34:02So clinical valuation history exam hetero anonymizes when you talk to friends and family is the name Anna needs to be the individual hetero any studies when you're talking to other people, so history representing illness try to get a sense of how it presented like that. Just happen like overnight is this something that's been going on did they have a really protracted prodrome of melancholic depression? Do they have a history of prior manic episodes or were they?
• 34:32Buying everything you know for weeks, and weeks online and not sleeping and starting new businesses and writing books and playing the lottery anyway would give you some clinical sense as to what we might be dealing with psychiatric and substance use history often have to get this from family or the chart or other records developmental history again, certain developmental disorders and developmental disorders might be relevant here radio systems in so far as you can get it, maybe even family members can provide a little bit more of what those complaints that the.
• 35:03Patient was telling them leading up to this presentation family history. Is there a family history of certain things like go check out periodic Catatonia might be might be passed on in some pedigrees and some families genetically.
• 35:19And then the physical examination really this is the one time that I would say We as psychiatrists.
• 35:27Really need to be thinking about our neurological exam, so insofar as Catatonia is concerned definitely immaturity evaluation cranial nerves makes good sense and frontal release signs all of them. I think are going to be really important. Now, if you wanted, a full neurological exam go for it. Certainly, a valuable piece of information to be able to track both tracking.
• 35:52And I it diagnostically kind of clarifying the picture of #2. What gets better with treatment and what does it you'd be able to actually create kind of a temporal correlation in relation to your interventions?
• 36:04And then I said, this earlier finally associated conditions. A mood disorder, psychotic, so Developmental Center and medical Catatonia, which would include another medical condition. We've looked at the kind of smattering of causes a moment ago and substance induced so there are a number of medications that can or have remotely been implicated in it, one that I'll just note that I've seen a couple of times is alcohol or benzo withdrawal confusion. Confusional states so I've actually published a couple of years ago, the idea that? Maybe.
• 36:36DTS might represent a catatonic's syndrome, or catatonic spectrum syndrome, so the one delirium that we reliably treat with Benzodiazepine's the only one that we really always treat with Benzodiazepine's and I have seen patients present in that context with Catatonia pretty clear Catatonia in a broader see of of encephalopathies so again.
• 37:02Certain states to consider so the work up. I'll just walk through this briefly so let's see broadly CBC CMP you a chest X Ray talk screen. TSH B12 syphilis. AA with reflex so you're looking at specifically the pattern, but also things like antibodies for Sjogren's syndrome. Rowan law, so forth so the reflex will pick those up.
• 37:30I would say anyone with Catatonia probably should have those just generically speaking if they have Catatonia. I almost always recommend if they don't get immediately better an I think there's any chance that they could have a medical Catatonia. I get iron because low iron is a risk factor for NMS and so, if you're going to give them the Neural Eptic, they receive neuroleptics. It's an increased risk.
• 37:51For developing Ms I often will often recommend ESR CRP CPK to see if they have wrapped oh now whether they're developing it whether they're getting better. Just to know your baseline and then obviously women of childbearing age being evaluating for pregnancy status.
• 38:12Looking at medications so.
• 38:16Serotonin syndrome as we talked about earlier and lithium in its syrup synergic activity can cause in toxicity can cause serotonin syndrome, which is thought to be a Catatonia spectrum condition. D2 blockade itself can cause obviously MS&S being. Catatonia spectrum conditions so and that includes medications for vomiting, too right. So there are a lot of medications that are used in that context as well, and I still frame is also been reported.
• 38:46As a cause of Catatonia.
• 38:49We don't see it. I saw from very much for good reason, but anyway, just think about it, there and I sold for him stop it. I mean, there Catatonic, so they're not drinking so just stop it. Alright then second lights at this. I kind of consider these pretty first thing that there is no formal guidance in the literature. This is kind of a general clinical approach to this and your clinical sense of positive iti or not. I defer that to your clinical judgment.
• 39:18But again there's no formal guidelines on how to approach this. Unfortunately second line. I would say EG an brain MRI if you're going through imaging in Catatonia. I think there is no reason to head CTF. You can't get in because they're agitated try to get them com medication. Wise and then get an MRI because I mentioned earlier a lot of the causes are CNS specific in many if not most of them.
• 39:45That are structural and what have you like demyelination events and so forth they would not be picked up well on NCT so if you're going to get brain imaging on Catatonia to look for causes think brain him alright.
• 40:01And yeah, so it's gonna be much more sensitive and EEG obviously would be valuable to pick up weather epileptiform activity as well as event diffuse slowing you would not expect to see the few slowing in depression with catatonic features or mania with catatonic features. But if you see that if you slowing you're really thinking OK. Now we're really thinking about a secondary or a medical Catatonia and it might embolden you to keep looking or hunting for a medical cause because?
• 40:31You would not expect to get a pretty severe medical condition and you talk about likelihood ratio. So obviously all of these are Bayesian statistical approaches to clinical care, but you wouldn't expect to get a stone cold normally EG in a secondary Catatonia. They all tend to be in several opathic states, which would lead to that most of them do.
• 40:55And then finally third line if suspicion is adequate or high enough.
• 41:02LP, including send out antibody panel at this point, often S pepper. You pep are ordered to look for bands.
• 41:11Other tests to consider that I've seen reported in the literature in case reports and so forth so looking at Anka for certain masculinities ceruloplasmin HIV. Maybe that would be first line for certain individuals vitamin levels, a certain vitamin deficiency states have been reported as causes very rarely for Catatonia Secondary Catatonia blood smear an cryoglobulins these so again just.
• 41:42Other considerations where you might actually find 'cause that you had not previously identified based on your routine 1st and perhaps even second line work up.
• 41:53So what do we know about the management of Catatonia Unfortunately? Well, not as much as we like there is one. Randomized clinical trial in all the literature on Catatonia and it's on catatonic schizophrenia.
• 42:07And it was Stone Cold negative like negative negative like there's negative and then there's like negative like there was no not even a trend like Adam, an up to 6 milligrams versus placebo did not help and it was a randomized crossover trial. Same patient right so just did not help so it's really a question mark about whether and to what extent benzos help.
• 42:31Certain types of Catatonia maybe they maybe it generally spend some authors will report it doesn't matter. The cause, they're always equally effective. There are however, number of reports in literature. This being a classic example of where schizophrenia or Secondary Medical Catatonia's do not have as high a response rate to Benzodiazepine's as primary Catatonia due to mood disorders. I'll say so just to note.
• 43:02The underlying cause may influence the likelihood of responsiveness mutism. There was a case series of mute patients. Where was randomized to emo barbital or placebo and half of the patients responded to me barbital but no one responded to basically to sailing so as a result.
• 43:26This is like the only benzos for acute catatonia like presentation literature, oddly that's placebo controlled. You think there'd be another one, but there's not and then there's one study.
• 43:38Which is kind of a double dummy study? I think is what you describe it as ECT plus the sibo versus sham. ECT plus risperidone. So basically ECT versus risperidone. They both improved. But the ECT folks improves more and more rapidly. In general, so ECT does work, but again no not the literature in terms of RC TS not terribly robust. Unfortunately, however.
• 44:08There are dozens and this is a great review. Dozens of positive open label studies and quite frankly if someone's not talking. It hasn't been talking for like 2 and 3 days. Then you give them out of in and they start talking within like 20 minutes, it kind of have the answer so.
• 44:27Very interesting question about whether you really need an RCT. I think probably should but an example. You wouldn't need an RCT demonstrating that parachute saves lives.
• 44:40I mean, you don't need to do a RCT on that right so depending on the obviousness of the effect in the time course one might.
• 44:49One might come up with different scientific arguments for or against.
• 44:55So we'll end here at treatment and I'll make a few comments after that, but treatment. I liked this treatment approach flow chart that is in a review by Beach and colleagues in 2017. I think was General Hospital psychiatry. This is a review of all treatment studies and reports outside of benzodiazapines for Catatonia. So basically they looked at every single thing that has been reported for the management of Catatonia aside from benzos.
• 45:26And then they reviewed it in a large and impressive table.
• 45:30And based on that they offer this general approach to managing Catatonia. The syndrome so first off start with Ivy Raza. Pam typically it's a 2 milligram challenge called the Ativan Challenge. Yes, that's the brand name, but low Raza Pam Challenge Ivy push.
• 45:53If they can't, they don't have an Ivy or their agitated and photos and they can't get an Ivy you could do it, I am.
• 46:00You could do it P oh, but if they're not talking. The other problem to get it. You could do in G tube. I've seen that done a couple of times if for whatever reason, they do not have access and can't have it.
• 46:12So starting with Out of it, they they are old and or frail they off you can lower the first dose to .5 or one milligrams, not uncommonly lowered but then you can always repeat. You can always give more you can't take out once it's given so you'd give that dose response is. By definition a positive. The Raza Pam Challenge is a reduction 50% reduction in the bush. Francis kind of a standard definition of a positive.
• 46:41Lorazapam challenge if they get.
• 46:45Better you typically will schedule it so 2 milligrams Q82 milligrams. Q 6 or whatever. The dose was that worked schedule at Q6 or Q8 around the clock if they don't get better or they only have a partial response very often, you give a little bit more to see if maybe that dose was inadequate and then if they get better with that dose. You might schedule it or if not, maybe you just schedule 2:00 and perhaps overtime. The effect I've seen people get better.
• 47:16After 24 hours of scheduled doses of Ativan, but didn't get a whole lot better. Initially it was kinda slow and kind of indolent improvement.
• 47:25And then if that doesn't work within about 24 hours by the way that.
• 47:30Case reports suggest you can give patients with Catatonia are remarkably resilient to the effects of benzos. You can crank it up very often. Be careful be cautious think about other medications and respiratory status.
• 47:44But.
• 47:46Case reports of 1820 milligrams or more in a day in somebody who is benzo, naive and they tolerate it. It's really remarkable.
• 47:55If that doesn't work, though when optimized dose doesn't work. I think about is open M, so there are case. Reports of soap in him. It is more selective for Alpha one containing Gaba, a receptors, which are topa graphically preferentially located in the prefrontal cortex.
• 48:17And so I've seen people respond as open him better. Some patients or some better does open him, then to low Raza Pam just throw it out there.
• 48:25And then you could schedule that as well.
• 48:28If you don't get a complete response.
• 48:31Or they are medically unstable would have you start the proceedings for ECT if at all possible? Get the ball rolling start having a conversation with the family members.
• 48:44Try to start to see if you can't medically just do an evaluation primary teams. They were thinking about this just to let you know, sometimes it takes a little while to get to ECT some sites or easier to get to than others, but really ECT should really be thought about pretty early on if not getting better or if they're medically unstable or autonomic instability supervenes surface is.
• 49:07As you're doing this, you're undisciplined first step will go into further steps in a moment 'cause. This will kind of dovetail with it.
• 49:16You're also thinking about managing the underlying conditions so to whatever extent you have a sense what you're dealing with treat that as well. So if it's a severe depression and have a history of Catatonic Depression and they've not been anti depressants recently started anti depressant with this because sure you might treat this syndrome with Ativan and might get a reasonable response.
• 49:41But there's still an engine underneath driving this thing right there. Still, the underlying contributing factor or if they have an autoimmune encephalitis start, giving steroids or IVIG or whatever the intervention might be that's appropriate for that condition.
• 50:01And glutamate antagonists there a number of authors that suggest Amantadine or man team trials for this. Some authors have reported good response is. There some case reports and series out there, so certainly worth the try.
• 50:18And then the anti epileptic drug. I think of these and people, especially who have a manic disorder bipolar disorder history. Or maybe I think their manic and in particular or if they have epileptiform activity. Obviously is the underlying condition that might be presenting as Catatonia so that really gets into both treating the disease or disorder. The associated condition and also the phenotype so there's kind of a link there.
• 50:46And then
• 50:47Also kind of at the bottom of this is atypical antipsychotics.
• 50:52Typically given with law Raza Pam to prevent the risk of NMS.
• 50:56Literature on a typical suggest that they might be a little bit less risky in terms of possibilities. In a mess. But even still it could happen. Check iron and by giving Ativan with it, you're kind of also treating the possibility for NMS.
• 51:12As well so.
• 51:13In general and the physiological approach you really should be thinking about managing the dysautonomia, reducing inflammation. If there's evidence of inflammation often will do things. If someone has significant instability. Maybe not Clonidine or something like that again just mechanistically thinking about that. Not that there's any profound data in support of it, but kind of rational psychopharmacology or beta blocker or something if there's reason to think about that in managing this.
• 51:45Now, as should be obvious with this. This is all acute management. The data on Lanja Tude Inal Management is virtually nil. I mean, we just do not know how long to continue the benzo or when did consider tapering the benzo or when we just don't know there are so many unanswered questions about the Natural History of Catatonia that admittedly you will find this and invariably I could ask questions about that.
• 52:15I just don't know I've seen all sorts. I've seen Catatonia resolve and then to the best of my knowledge remained resolved for an extended period of time. I've seen it recur. I've seen relapsing remitting if it relapses room its remits in the relapses, then I think about are we talking about some neurological condition that was just not diagnose previously so polyphasic illness with demyelination syndromes like Ms or
• 52:47Conditions like again automated Sufal Ritis, another immune related encephalopathies polyphasic illness has been reported with Polyphasic Catatonic presentations. So I've seen. I've seen a couple of cases like that, so again. It's very difficult to know and there is much work to be done about next steps in managing Catatonia, but anyway, keep it on the differential.
• 53:11Think about the cause and then treat this syndrome, while also considering what that mechanistic associated cause is.
• 53:22And I think that's it.
• 53:26Any questions.
• 53:30Yes.
• 53:37Yes.
• 53:42No, you're absolutely right. No, you're absolutely right so.
• 53:46You would need a clinical correlation, so Delta waves is never normal and anybody.
• 53:53So if you got down to a frequency of 6 hurts.
• 53:585 hurts for Hertz, you probably need to be looking. There are invariably the bane of my one of the Banes of my existence are those equivocal results where you just don't know and in dementia. Many dimensions are associated with additional slowing on the EG. You're absolutely right. So you need to be thoughtful about that and there is a parallel body of literature without clear.
• 54:28Without a clear and conclusive answer about whether certain states of schizophrenia, especially when they are in acute psychotic decompensation might present with various.
• 54:45Changes on the EG the literature is old and I don't know a very clean an good and sophisticated analysis of that.
• 54:54But that also throws a wrench into the picture, but I don't know of them ever, causing Delta waves or if you saw extreme Delta brush. Your not going to call this schizophrenia. You would be like OK. We gotta find. We just start the steroids right now, so I would say that there are there are interesting possibilities there.
• 55:16Agreed.