Autoimmune Encephalopathy

Transcript

• 00:00So this talk will be on autumn units up allopathy broadly defined.
• 00:06That includes encephalitis and rheumatic conditions with neuro psychiatric symptoms. This is a very broad and even even today continues to expand its pending topic of altered mentation, So what kind of generally cover what it is the scope and how we approach it.
• 00:31One of the big questions that I've always had asked of me.
• 00:36When I see patients who are confused.
• 00:39Is well you want brain imaging? Can we just get ahead see T and I say to them? Well you know there are a lot of things that I had see T won't pick up that a brain MRI would or might or at least stands a much greater chance of picking up so I took it upon myself to create a list of those so that if anyone asks me. I have is a smart phrase why I think a brain MRI is more comprehensive in the number of types of conditions.
• 01:12That.
• 01:13That might be detected now it's not now, it's not that every.
• 01:20One of these would be detected by a brain MRI and it's not that every one of these would be missed. If it's severe by ahead CT, but brain mris have a much greater sensitivity for each of these conditions.
• 01:39In general and of these this is all will be talking about right now, so encephalitis, cerebral vasculitis and a few other conditions that kind of fit, broadly within it. We really won't be talking. A lot about D myelinating disease. But some of these do contain D myelinating events be they monophasic or polyphasic. And so forth so some of that will be will be covered as well so a few fun facts terms, cerebral spinal.
• 02:09Versus Cefalo rickety and ones Latin Ones Greek. Historically they used to use Cefalo rickety in a lot.
• 02:16We've got rid of that fun other terms if there's too much or too little.
• 02:22Glucose or protein in the CSF that would be called hyper or hypo. Glyco rakia or protein. Iraqia not used very often, but use those terms. They're fun. People will love them. The last see what they mean.
• 02:35And then of note, Lucho encephalitis would be an encephalitis, chiefly limited restricted to the white matter, although obviously very often includes both.
• 02:47There's polio and stuff out his polio means gray so poorly with lattice gray matter involvement and then parrot encephalitis is a broad term in the literature and other things that I was reviewing which refers to white and gray matter involvement, not not that those terms are profoundly unique or specific but.
• 03:08I thought that they were interesting to note.
• 03:10I want to also provide some general sense of how antibodies was a lot of this going to be antibody associated encephalitis.
• 03:18I think Sjogren's syndrome, primary shogren offers an interesting parallel by which to understand how antibodies might be associated with different diseases.
• 03:32On the first of these sections in Roseanne AR SSA SSB.
• 03:39These are disease markers and they are not thought to be directly pathogenic an you get rid of the antibodies. It's not that the disease itself immediately remets or even really improves all that much, which is why we don't do things like Plex or IVIG in patients who have these conditions.
• 04:01Second autoantibodies can have very specific clinical manifestations.
• 04:07Mechanistically, because of where they go and what they do so for instance, cryoglobulins when they precipitate. They can lead to necrotizing changes in terms of the very small vessels where they build up the extremities when it's cold.
• 04:24And then finally autoantibodies can have a directly pathogenic rule where they bind their active site binds some epitope binds some antigenic.
• 04:39Compound or what have you moiety?
• 04:42And changes let's say an enzyme function or changes. A receptor such that it's a channelopathy and the channels function changes so again. I just want to go out there antibodies. We think about them will be some distinctions to be made may have a variety of mechanistic relationships.
• 05:03I'm in Association with the diseases themselves.
• 05:08So broadly speaking there are encephalitis, plural inset validity's will look at them by definition location cause and then secondarily. We have dramatic conditions with neuro psychiatric features among them include collagen. Vascular diseases specifically other vascular titties and there are a few outliers that kind of difficult to place elsewhere so we started with encephalitis.
• 05:36The generic term of encephalitis, which I don't want to say precedes anti. Today, receptor antibody encephalitis is kind of generic definition of encephalitis consensus definition, so the major criterion would be 24 hours of altered mental status, which defined often as change in Arousers operationalize. This change in Arousal or personality pretty broad.
• 05:58And then a minor criteria the minor criteria would be possible or probable greater than equal to 2 greater equal 3 respectively. And they would be fever within 72 hours new onset focal neurological finding seizures, not attributable in full to a previous seizure disorder. CSF elevations and white blood cell so pleocytosis. Taner imaging findings consistent with encephalitis and then EG findings, which may range based on the specific condition.
• 06:28That's causing it so broadly speaking this is encephalitis and we would obviously care because changing personality. We might get consulted for that. And I had been consulted and we've seen them. We've helped get these diagnose so that's important that's important.
• 06:45But then there was in 2016 and Lancet neurology? What has become kind of quickly quickly become.
• 06:54I think the last author was down low right so this is the guy who does this stuff kind of the Guru and created just put out several operationalized definitions for how to make these diagnosis, so these have I think I checked yesterday. This paper has already been sighted like 750 times in just a couple of years, so it is definitely caught the eye of the community and possible autoimmune encephalitis.
• 07:26Propose definition would be sub, acute onset less than 3 months of any of the following and that is exactly how it's framed and I love. It psychiatric sentence? What kind I don't know. Whatever you feel that day. Anxiety guess that would count I mean. This is painfully poorly defined from a psychiatrist perspective because it kind of broad but at the same time, it's kind of broad so we need to be thinking broadly as well.
• 07:56Because they can present these conditions can present with a really broad range of symptoms.
• 08:04And then at least one of the following so new focal CNS finding seizures. Not that should eat not attributable entirely dip are epilepsy. Play Cytosis or MRI features specific to or suggestive of consistent with automated. Cefal ritis so hyperintense. T2 flair of medial temporal polls. We've got limbic encephalitis or multi focal consistent with email nation or information and then a quote reasonable exclusion of alternative causes, although not.
• 08:37Exhaustively defined in that paper and I can't find elsewhere. It's kind of based on clinical suspicion.
• 08:44So encephalitis by location, so encephalitis broadly speaking and this is kind of phenotypic if you will can be thought of as either diffuser. Focal diffuse encephalitis might be multi focal might be meningoencephalitis. If it's kind of tracking into or I should say involves the mending certain engines, which would cause meningismus and then encephalomyelitis if it goes down into the spinal cord itself.
• 09:12And these will cause global changes in mentation typically delirium not uncommonly seizures and again if the meninges are involved. Meningismus these would be typically infectious but also in India. Receptor encephalitis can cause a diffuse encephalitis, focal and we'll talk about each of these in turn in the subsequent slides, but you would have limbic encephalitis, limbic encephalitis.
• 09:42Has a triad of delirium seizures and intergrade amnesia? Which I'll make sense because the input campfires in the medial hippocamp IR in the medial temporal lobes.
• 09:53Which is why you would get the intergrade amnesia the temporal lobes are always particularly epileptogenic if you have abnormal activity and delirium because there's information in the brain.
• 10:04But can be caused by a certain infections as well as autoimmune conditions. You should roll out Glioma because the imaging findings can be very similar.
• 10:13And then brainstem encephalitis or ram encephalitis where you tend to get lower cranial nerve involvement Mya clonus. Autonomic nervous system dysfunction potentially locked in syndrome arrange of things that can cause that and then Basil Ganglia. Encephalitis very poorly. Defined condition currently but there's increasingly discussion about it, but nothing nothing huge Unfortunately yet.
• 10:37Diffuse encephalitis, so it broadly affects.
• 10:42I should say it effects the brain broadly.
• 10:44So the prototype might be considered in the receptor antibody encephalitis, it more commonly presents as a diffuse picture. The T2 Flair findings typically diffuse or scattered white matter lesions in the EG Classic. Lee shows global slowing but there are unique findings like extreme. Delta brush and so forth, which will talk about when we talk about that condition specifically.
• 11:08Limbic encephalitis as I mentioned earlier has a triad. This is both testable and also clinically notable because when you see this triad. Then you should be thinking about the condition.
• 11:21There are proposed diagnostic criteria for this which includes again fairly broadly sub acute onset short-term memory deficit seizures or it's an or not, and psychiatric symptoms, suggesting limbic system involvement to bilateral T2 Flair changes medial temporal pole specifically medial temporal polls.
• 11:44But pet is more sensitive.
• 11:47And at least 1 of Pleocytosis and the CSF and or EG changes findings with epileptic waves. Epileptic changes a platform changes or slow waves.
• 12:01Over the temporal loads so generally speaking, this is how you would diagnose it.
• 12:07These are just some pictures to show the general regions where the badness is. I forgot to put an arrow signed in here right. These regions you guys are going to be reading it. We would be calling neurology or getting neuro radiology involved. I wouldn't trust myself with reading these but it's pretty grossly abnormal in those pictures.
• 12:30And then brainstem encephalitis or ram encephalitis interesting, Lee review found that.
• 12:37You know, depending on whether it's infectious para neoplastic or Bechet disease or Bichette's I've heard both Bichette disease. You actually get differences in the general presentation, so whereas changing arousal might be uncommon in the paraneoplastic cause the brain stem and stuff like this, it might be common infectious and Michelle so just notably an interesting with feno type. Not that you need to memorize this. But the phenotype itself might also differ based on the specific type of cause.
• 13:07I find fascinating so it it probably has some tropism to very specific regions in the brain stem relative to specific epitopes and so forth.
• 13:19And so again similarly you see abnormal findings.
• 13:24In the brain stem, which you shouldn't see tracking down anyway is what it is brainstem encephalitis. You would get typically T2 Flair is going to show inflammation.
• 13:37And then finally Basil Ganglia encephalitis, which will cover a little bit later as well, but again, it's very poorly understood in interesting. There was a study back in the day where they looked at OCD. Patients with OCD and in fact, I think like 1/3 of them had antibodies to Basil. Ganglia epitopes, which is fascinating so there's something about these antibodies or antibodies that might target various Basil Ganglia or structures.
• 14:08That might present with dystonias parkinsonism, Korea Psychiatrically OCD ADHD and the like.
• 14:19It's probably good point good time to mention this as well. Much of this that. I'm presenting comes from the neurology literature, not a lot of this comes from the psychiatric literature and.
• 14:31As a result, there's a lot of sophisticated discussion about the movement disorders. And so forth, not a lot of sophisticated discussion of the psychiatric fino types.
• 14:42Which I you know I want to know that right? That's what I want to know to know what to look for Unfortunately. The literature is just not very replete with good examples of very clean psychiatric cases to really know what to look for it. Just kind of general a general theme across the literature here. Alright so that was by definition by location and now by cause so idiopathic.
• 15:1260% there was a large series out in California. I think there probably still doing at the California encephalitis project or something and they were just collecting hundreds and hundreds of samples of cases of patients with encephalitis and getting their CSF and testing for these things and you know, there were there on the hunt. People are on the hunt for new antibodies. I mean, you can get your name associated with that. I mean, you're like set your cool. I guess you can find a new antibody and define a new and Sepa Lytic.
• 15:43Presentation but the idiopathic category generally appears to be shrinking generally appears to be shrinking as we're identifying were kind of carving into that and we're being able to identify more specific causes.
• 16:01But then will move into the non infectious or antibody associated this seems to be expanding as we're identifying new antibodies.
• 16:12So antibody associated autoimmune encephalitis, there are 2 broad.
• 16:172 broad categories here, you can have an antibody to a neuronal surface epitope.
• 16:25So they might cause neuronal surface antibody syndrome.
• 16:29These tend to be non paraneoplastic if it's going to change the function of the neuron. It is more often than not not always, there can be cancers associated with them, but generally, those are non paraneoplastic. The antibodies that target intracellular episodes be they an enzyme or so forth.
• 16:50They tend to be paraneoplastic and so those are very often called uncle. Neural antibodies because of their much closer Association with cancer in general again and saying in general, there are exceptions.
• 17:07So the first category the neural neuronal surface antibody syndrome is the features include that there are extra. Sellier episodes the antibody alters the function or structure of the Antigen. It causes reversible typically reversible downstream effects and then it also corresponds with genetic or pharmacologic models of disruptive antigen activities, so there is kind of dysfunctional model. We know if the antibodies. There it causes. This you get rid of the body. It doesn't cause that you put the antibody and somebody.
• 17:37Else and it causes the symptoms so they're different kind of conceptual ways of thinking about it, I'm very often, though.
• 17:45These antibodies are precipitated by Ectopic Neural Neural tissue as in teratomas or perhaps at times due to molecular mimicry after an infection like perhaps to the HSV infections. There is thought that that might actually cause molecular mimicry an lead to anti today. Receptor antibodies interesting Lee in its wake. Then you have the second category. These are antibodies typically as tumor biomarkers.
• 18:16And are not directly pathogenic is again the targets are intracellular. How are the enemy is getting into the cell to target them? Well, that's a good question they're typically not pathogenic. But the inflammation and damage is usually characterized in general by cytotoxic T cell responses in general.
• 18:38So this is a this is probably one of the better tables. I found of this, but it is a bit outdated 2010. So it probably would stand to be updated in general, you see intracellular antigens. The percent of antibody positive patients without cancer. So this isn't flipped but basically all of them have a high proportion of cancer, so anywhere from 89 to 98% cancers identified Anti Hue Yo MA 2, so forth.
• 19:04Anybody can cell surface antigens on the other hand, much higher. So the answer. The anti acetylcholine. Receptor very rare voltage gated potassium channels very rare NBA, receptor antibodies. It's not as rare but a lot of these have teratomas, which are not necessarily there like cancer tumors so the tumors were included. I believe in that number so anyway.
• 19:31In general general rule, so these are the neuronal surface antibodies. These are the broad categories. There are a few others that I don't think I've included in here on this list since I originally put this together, they've discovered a few more of them, though most are autoimmune channelopathies, which is to say that they are not only targeting just random receptors, but actually receptor epitopes that are in Association with or part of.
• 20:02Surface channels an by binding, they actually change channel function, so they would also be called autoimmune channelopathies in terms of their activity.
• 20:14So let's look at them specifically I'm going to highlight some kind of more salient factors but not get into excruciating detail of each because again we'd be chasing rabbits if we did.
• 20:28So the anti MDA receptor encephalitis or anybody encephalitis typically it's diffused to antibody. The NR one subunit of NMDA receptors and you should also notably have high suspicion for this, if there's a prior HSV encephalitis, so again. There's some thought that there might be an Association with.
• 20:52HSV encephalitis as a residual syndrome demographics, median age is still fairly young 20s issues changes when they get more reports out, but the reports range from one to more than 80 so it's been found.
• 21:09In a remarkably broad swath of individuals and there's generally speaking, this is still true a female predominant.
• 21:18That we know of again.
• 21:21There is some bias based on where we are detecting and where we might be missing it. So it might be that they have other phenotypes. In other populations that we're just not thinking about it in or not thinking about it consistently enough to even recognize it.
• 21:37So I've seen 2 different categories of 3 stages just A&B. So you can start the viral prodrome. The psychiatric phase and the movement phase that kind of bleeds into dysautonomia hypoventilation half of patients and Catatonia.
• 21:53Or if you take out the viral prodrome. You can start conceptually. The psychiatric stage seizures delirium movement disorders and then move into more of kind of the disastrous dysautonomia hypoventilation and coma stage so well. This is kind of broken up into 2, here and they take out bioproducts. I've seen it defined as 3 stages in both in several publications. So I'm not sure there's a formal way. But that's generally the progression that it follows.
• 22:22Diagnosis so MRI is abnormal. Only about half of patients. In fact, I've seen it normal once in an abnormal again or abnormal initially and normal afterward.
• 22:31The consistency of positive findings on a brain MRI might not be as consistent as we might want them to be for detection say.
• 22:41CSF will show a lymph acidic pleocytosis more often than not 80% onset and if you take a series of CSF samples 95% will demonstrate it during the disease process during the acute phase.
• 22:58Hyper protein iraqia.
• 23:01Oh, that should be a see in a third and oligoclonal bands in 60%. EG findings vary widely, but slowing and epileptiform changes or the Communist.
• 23:15There is this unique finding an anti me interceptor anybody encephalitis called extreme. Delta brush in 1/3 of patients, which some have suggested that the number of adjustment is all but pathognomonic for the condition? What is extreme Delta brush you have slow waves or Delta waves?
• 23:34Kind of in the background and then a top that is superimposed fats Alpha waves.
• 23:40But this is interesting, Liane, a presentation that is seen.
• 23:45Commonly in infants, I understand and early life, a development. It is not normal in an adult. So when you see it in an adult usually media. I mean, the the EG readers probably. I bet this is dot, dot, dot, but I think I've seen that one. It's not a terribly common thing. But it's fascinating when you see it that that's a reasonably testable question right there and then about half of the tumor, mostly women, but ovarian teratomas are the most common so again.
• 24:16Tumors not cancer, but it is a Tera toma should be removed if it's present.
• 24:21Very rare malignancy it's just a range interesting Lee of cancers that been associated with it.
• 24:29Proposed criteria also from this grouse dot, dot, dot delmo article. Probable all three you have to have all 3 definit. At least 1 of Criterion, One and igg to this particular epitope.
• 24:48So you have the antibody an at least one of these that clinches the diagnosis, as a definite now. I've made these 5 of them read for a reason. So cognitive symptoms change in speech. We can include hyper or hypo verb ality if you will decreased arousal.
• 25:09That is delirium.
• 25:11Everybody basically as delirium with any hypoactive component. Those are the first three you get the first three with delirium virtually every time.
• 25:21Then movement disorders, including dyskinesia's and rigid abnormal postures sounds a lot like Catatonia, so if you see diagnostically if you see delirium with catatonic features your mind should go to an autoimmune encephalitis. You should think about it and in fact, as I showed on the previous presentation about 30% of secondary or medical Catatonia's were related to.
• 25:52And then Seth a lytic process or in brain inflammation so again if you see delirium with catatonic features.
• 25:58Pretty prominently speaking and there's a lot of other obvious cause I would be thinking of this.
• 26:04Additionally, seizures might be seen and then autonomic dysfunction and central hypoventilation. Both of which I mean, getting into baited is very, very, very common can be disastrous and hypo. Natri M.I.A is also not uncommonly seen so at least one of the following EG with basically anything anything. Abnormal and CSF. Pleocytosis are all good portal bands. One of these and the reasonable exclusion so these are the diagnostic criteria for.
• 26:35The condition.
• 26:37This is I think still to date. I don't know of a larger series. This was Atlanta. Neurology 2013, so about 5 years ago, or so kind of a general breakdown of female patients with and without tumors male patients with and without tumors male patients with tumor are dark blue you don't see many dark blue anywhere.
• 26:59If you had a guy with this very often, you don't even hunt for the tumor with a guy unless there's a substantial reason. We don't always I've seen clinically neuroimmunology and neuro radiology and they're discussing this, if a guy gets this diagnosis. There's actually some somewhat of a debate. At times that I've seen about whether even do a hunt for the the tumor for women. I mean, the prevalence of tumor is so high basically.
• 27:30Late adolescence adolescence and then kind of into adulthood that you should definitely look for tumors in women. That's the big reason I've shown.
• 27:38This particular bar graph.
• 27:41And the breakdown in terms of what are the most prominent features so if you're talking about an adult behavioral is this blue is most of them seizure seizures and behavior account for the the greatest proportions of symptoms that we will see so again this is our category in psychiatry right behavioral change.
• 28:07Alright treatment consider testing.
• 28:10For aquaporin 4:00 or emoji antibodies will talk about emoji in a moment, a little later. If a typical features such as demyelination optic nerve. Ritis or prominent dyskinesia is to rule out IMO or neuromyelitis. Optica spectrum disorders. Tumor excision of present and immunotherapy now prognosis. They say 80% of a good prognosis.
• 28:34But this is using the modified Rankin score which has to do with strokes and so when you're talking about strokes outcomes don't get very granular at that stage. Unfortunately and so by good outcome. They mean 0 to one which is anywhere from no symptoms to slight disability functional independence, but unable to perform all prior activities so.
• 28:55The outcomes can be significant endurable. Unfortunately, most have some lasting cognitive change, plus minus frontal lobe dysfunction that 1/4 have a relapse and in general. It's thought that the earlier you get to it in the earlier you initiate treatment. There's a general trend that people show.
• 29:17In large case series that the earlier you treat the better the outcomes are because you're not leaving the inflammation unchecked, so as to cause neuropathology.
• 29:29Lasting.
• 29:33And patients with tumors do much better because you can excise. The thing that's generating the antibodies. But yet in general. Thank you for mentioning that yes tumor.
• 29:43Yes.
• 29:45So I'm anti voltage gated potassium channel complex encephalitis. There are 3 subunit targets at least.
• 29:55That have been kind of clinically defined for voltage gated potassium channel antibody related in several entities. One is LGI one which classically presents with limbic encephalitis or new onset seizures or a fun unique seizure, which I'll describe in a moment.
• 30:12Largest K series to date at the time I put this together and last reviewed it. There were no tumors found I'm not saying that it can't be tumor associated but very limited Association with tumors if at all. Casper 2 limit encephalitis more vans syndrome. Onoro myotonia about 1/3 head. Daimon lives largest series to date. When I put this slide and recently reviewed it and then contact into has been described but it's a very it's very rare epitope in terms of its?
• 30:43Immunogenicity so we'll look at each of these in the next slides.
• 30:47So LGI one antibody syndrome median age 60s with a male dominance, notably and it causes this unique type of seizure. A Fatio Brachial dystonic seizure. I'm going to the next slide to show you so this is a picture. It actually go here and you find a video of it, but basically the arm twitches up and face kind of Winces on that side facial brachial face and arm, they twit and like that's it like that's that's the semiologie of the seizure it's so interesting.
• 31:18I've never seen it.
• 31:20But I think videos of it and if you have that you're pretty much the shoe in that's what you're dealing with. In fact, I've seen one patient who demonstrated that in the neurology team saw it somehow someone reported it to them like we know what this is they look for just that antibody and lo and behold, they found so it's a pretty pretty tight Association between that antibody and that particular type of seizure activity, it can, though also this antibody campers with limbic encephalitis.
• 31:50Hyponatremia is common and R.E.M sleep behavior disorder has been reported which is kind of fascinating but the thing.
• 31:59You typically will get medial temporal lobe signal changes with example atrophy, but you can have a normal MRI in about 40% general rule of thumb with a lot of these about 50% sensitivity for brain MRI if you look at all of them as a whole now 50%, sensitive is bringing right.
• 32:16And the CSF is nothing nothing really huge if it is abnormal. It tends to be a mild change uncommon oligoclonal bands treatment immunotherapy and aids.
• 32:31Prognosis from what I understand what this is actually pretty good. I don't have. We don't have huge case series, but my understanding is the prognosis with this tends to be better because it tends to be much more focal rather than again with Anthony Receptor antibody. Stuff like it's tends to be kind of diffuse inflammation.
• 32:49Alright so again the wonderful picture of everybody in process of having an epileptic event.
• 32:58The Anti Casper 2 encephalitis. These antibodies is also a male predominance. There is this condition called more fan syndrome that can be the presenting feno type. It's a triad of Neuromyotonia M.I.A Crimea and encephalopathies and for the life of me neuromyotonia and Myokymia are. I'm not quite sure how to differentiate them very well. I've actually spoken to movement disorder specialist about this you have a better answer I'm happy to.
• 33:28Here it but friend of mine back in the day, it was a movement disorder specialist and it sounds like to me. Neuromyotonia is kind of a bag of worms look under the skin. It kind of looks like the muscles are kind of almost like might be like the kafir the thigh or the arm looks like arriving bag of worms, so that you get these fasciculations, which are visible on the surface of the skin. I think myokymia, something that you get on EMG testing so it's uh.
• 34:00The hypersensitivity to an induced impulse does that sound about right.
• 34:09For the most part, yeah, it's mainly heard on.
• 34:13Angelika Bammer sound or something I remember hearing something about a bomber sound so. So yeah, so but anyway. That's the triad that you could could see a number of other symptoms that people can have neuromyotonia.
• 34:28In isolation, limbic encephalitis as the phenotype of the triad and a history of myasthenia gravis is common among this population.
• 34:38In this page population 40% with me Geo, temporal hyper intensity. CSF good proportion of them have pleocytosis orolo. Good kernel bands bout half of the cases reported are paraneoplastic so with tumors and in general, there's a fair response immunotherapy about 1/2 relapse.
• 35:00Based on what I did this, but there might have been a recent publication in the last year or 2 that changes that.
• 35:07Anti impa encephalitis, so you can get antibodies to the glue are one or glue or 2 subunits median age of 69 to one female predominance in the big thing I'll just mention here is psychotic features tends to be the most prominent symptom clinically you. This is we're kind of getting another error antibodies and so at this stage, you're really going to be finding these when you do.
• 35:38An antibody panel and so they have different reflexes to check these and so will get into too. Kind of send out panels in a moment but again, the Association clinically for our purposes in psychiatry, psychotic features or tend to be pretty common.
• 35:56And I got a A or Anti Gaba B encephalitis, so they target to be 1 subunit common. These present commonly with other antibodies and it's not entirely clear.
• 36:09To what extent these are bystander antibodies or which ones are pathogenic and which ones are, but it's really not entirely clear, however, notably the these antibodies being against Gabba Gabba be 1 might suspect that seizures might be particularly common. And in fact that is true not uncommonly presents with status epilepticus and can be exceptionally difficult to get control over.
• 36:39From what I've read in terms of kind of breaking the seizure activity.
• 36:45Tends to affect the measure, temporal lobes predominately and a high proportion with pleocytosis or all the local bands. About half with small cell lung cancer and then treatment immunotherapy and any epileptic medications can be responsive, but again can be difficult if there coming with status epilepticus.
• 37:08Rare relapse that poor prognosis if a tumor is found in general, for tumor is found.
• 37:14In a paraneoplastic sense as opposed to the Tera Toma sense worst prognosis better prognosis. Tera toma worst prognosis if it's a cancer as a paraneoplastic syndrome in general.
• 37:30Alright Basil Ganglia encephalitis, so this has this interesting Association with encephalitis lethargica. Orvan economist at the lightest and goes by other names. It's associated or thought to be mechanistically similar to some extent with pediatric auto. I'm sorry pediatric acute neuro psychiatric syndrome. I think is what pans stands for and then the most common sub type of pans is pandas.
• 37:57Pediatric autoimmune neuro psychiatric disorder associated with streptococcal infections pandas.
• 38:04Pen is a whole lot easier to say by the way just pandas.
• 38:09Synonym Korea tourettes and OCD are very common just fino typically in this group. There are 3 subtypes. A kinetic parkinsonian form the hyper kinetic foreman off download plegic form. I've never seen this condition. We look for it once looking for D2 antibodies fi remember but
• 38:30Yeah, anyway. It's thought to be mediated again by antibodies specifically the Basil Ganglia, but it's very poorly described.
• 38:40And I'm not sure that there's any really good data on management were really at the level of just small case series. It can present with try it on the Crow sis? Which T1 you're going to find tissue is an aquatic you'll find changes typically on T1.
• 38:59Other antibiotics recently described not going to say much about these but you've got this interesting perm condition. Asocial glycine receptor. I think Alpha is Alpha. One you can have antibodies that Abbott rope glutamate receptors. You have this DPPX which is associated with a great deal. I believe of.
• 39:18Significant GI upset diarrheal prodrome because there's my enteric expression of DPX as well. And then even more recently is this cell adhesion molecule in which sleep disordered breathing and dream enactment with Dysphasia has been reported so again. It's an open field in terms of finding new new antibodies and broader broader and broader populations.
• 39:45So.
• 39:46How do we clinically approach these individuals these patients who have anybody associated?
• 39:52Encephalitis or
• 39:54Other other phenotypes encephalopathies would have you so first off find and remove the associated tumor if at all possible. I mentioned guys who have the anti MDA. Receptor antibodies might have a low prevalence of teratomas. But if you find the tumor remove it if it all possible?
• 40:12Very often the next step is 5 day methyl Prednisolone kind of a burst with IVIG. You complex but my understanding is Plex is associated with greater risk of autonomic instability.
• 40:26For what it's worth.
• 40:28This is the general first line, although some people are increasingly mixing 2nd and 1st line and it looks based on an interesting review. I read about a year ago. Regionally, it's handled differently, so they're kind of pockets of different practice and different approaches, so that really yet to establish a firm consensus. At least insofar as my understanding is nationally or internationally and how to manage these conditions.
• 40:56Pending response by day, 10, either continue supportive care alone, if they got a good response and they're making progress.
• 41:06Or consider initiating monthly cyclophosphamide, plus weekly Rituxan mab for 4 weeks.
• 41:14Regiments are changing as well from what I've read so I don't know if this is formally across the board, but Rituxan. Mab is also increasingly being included in some institutions first line approach to a number of these conditions again changing as we speak.
• 41:31In terms of their mechanism of action that is not testable for us here, but I thought I would include it for fun.
• 41:37A lot of people will use cytoxan instead of saying cyclophosphamide so the brand names. People use those clinically interchangeably often.
• 41:46It have no tumor cancer surveillance for at least 3 years and give consider giving mycophenolate Moffitt. CYLOR azathioprine for up to a year or more after the initial treatment to prevent relapse again. Some antibody syndrome's are much more closely associated with relapse and so to prevent relapses. It's not uncommon to get people on immunomodulatory treatment. If the risk for relapse is thought based on evidence to date that time that that syndrome has a high likelihood of relapse.
• 42:18And so they may then be they may then be putting people on longer term, and very often the paraneoplastic syndrome related antibodies. The cancer surveillance will pick it up in the next year or 2, so it's not uncommon for patients to get this syndrome encephalitis? What have you. The pretty plastic syndrome get the antibody. But that came 1st and proceed identification of the cancer the cancer declares itself.
• 42:47Year to couple of years later, so if you have it, you're kind of on pins and needles waiting when and if.
• 42:54In the likely event, you might be diagnosed with a cancer like you know, not not hot shooting. Bowmore small cell lung cancer or something.
• 43:02So broadly speaking pretty plastic Cena syndromes. There are classic and non classic, but the classic Cena syndromes include encephalomyelitis or limbic encephalitis.
• 43:14And these are the ones I think of greatest import at least to us in console psychiatry. Although cerebellar degeneration. Opsoclonus myoclonia sore also classic CNS syndromes are kind of defined as or categories of Classic.
• 43:27And the antibodies most closely associated with either are Huinan, Thyssen with encephalomyelitis and then several cluding. Q as well for limbic encephalitis, there tends to be a reasonable Association antibody and phenotype.
• 43:44But don't quote me on that there are outliers.
• 43:47And then there are non classic CNS syndrome is one of them. I just put here for note, which is brainstem encephalitis and the 2:00 antibodies that have been associated with that most commonly are anti re an anti mod 2, so again. There's a pretty broad range of potential antibodies and syndromes. How do you diagnose it well based on weather app cancer whether you have a classic or non classic you can get definite?
• 44:13Possible or no diagnosis, so no syndrome, no cancer. No diagnosis, but I'm sorry nonclassic syndrome and no cancer. There's no diagnosis, but depending on the way that these get paired you can get definite or possible paraneoplastic syndromes. So if you're curious. There is a kind of a formal way of making those diagnosis definite possible or none.
• 44:42Mail clinic simplifies the process and they have 4:00 pairs.
• 44:48Of panels you have autoimmune encephalography panels, you have paraneoplastic panels. You have autoimmune dementia panels where they have kind of.
• 44:57Pretty rapid onset dementia and epilepsy automotive panels where kind of the image in would have it. There's no other reason why they should be having seizures and so there's a panel for that in each of these there is the serum or CSF version. Now, which do you pick there's always a debate on this to the best of my knowledge 85% of anti NMDA receptor antibody encephalitis will be picked up.
• 45:24In the theorem 15% when they did paired tests serum and CSF 15% in a pretty large sample had only CSF antibody. So you could miss it. If you don't get CSF there might be intrathecal production of the antibody.
• 45:45With all the other syndromes there, so rare so zebra like that. The general recommendation. I find is serum is probably enough. But if you really want to get a definitive answer if at all possible, sending CSF is preferred because the yield is at least statistically and.
• 46:10I would say clinically significantly higher just to make sure you're not missing it. But I understand there's sometimes we're getting CSF is next to impossible or family doesn't approve or it. Just I understand that there are some instances, where you may end up just getting the Serum.
• 46:29So this is kind of what it looks like on their website there. There are these kind of trigger points and if they get certain ones. Then they'll kind of do reflex tests for a number of others. This is the encephalopathies autoimmune evaluation. This is the paraneoplastic evaluation of node. I usually if I recommend it. I recommend one of the 1st 2:00 because this is usually the clinical scenario. But if you look at 'em my understanding is they basically the paraneoplastic an autoimmune basically have all the same they?
• 46:59And they do change, these panels from time to time, they actually expand them from what I believe I've seen before. As new ones are being identified so they are kind of a work in progress, but I usually if I recommend it. I usually have recommended ENCEC and I say test ID that and it's a send out usually takes a couple of weeks. There are in house or local ones you can get that quicker. The paraneoplastic panel here. I believe, but it's not as broad. It's going to miss a lot, so if you want we comprehensive.
• 47:31We least that I've seen there send outs.
• 47:38Is that right OK so interesting? I like that? So it in house so postinfectious. There are post infectious in Cephalin Ities. There is a demo or cute disseminated encephalomyelitis. There's a subtype, which is really bad, acute hemorrhagic gluco encephalitis, bickerstaff, Bryant is an antibody associated so we'll talk about these.
• 48:01A damn or acute disseminated encephalomyelitis the presentation typically is a well by definition in Maná, phasing demyelination and then after an infection vaccination or transplant with onset 1:00 to 3:00 weeks after the precipitants. The range of symptoms is kind of broad but focal neurological deficit is the most common 80%. Sensory changes 70% created a policy is 45% blah blah blah going down the list.
• 48:25End cephalic involvement as far as I understand that means in Ceph Allopathy, so about 60% over half of patients who have this will present with a confusional syndrome.
• 48:40There are diagnostic criteria as with many of these conditions, definitive diagnosis. You need all 5 provisional diagnosis until Criterion 4 is met because again, you don't know if they will have a polyphasic illness. What have you so first multi focal CNSD myelinating event presumed inflammatory cause and settle up at the not explained by fever and take it back up allopathy is part of the diagnostic criteria.
• 49:09I wonder what that means.
• 49:12Flip it up interesting question, so abnormal brain MRI. They typically have diffuse or fluffy lesions fluffy. I mean, very fluffy to the patient basically that means just the boundaries around them are poorly demarcated so they're not like nice boundaries between inflammation and normal tissue. There tends to be kind of a gradient around the edge, which you kind of see here. It's kind of blends in diffusely on the edges. You can get T1 hyperintense lesions in the white matter what have you.
• 49:45Again, no new symptoms after that, and reasonable exclusion.
• 49:51So diagnosis had see T is definitely less sensitive. There are least for lesional patterns described gets a bit technical. CSF no oligoclonal bands because again with the D myelinating event, you want to make sure it's not in S, another D myelinating syndromes.
• 50:12Treatment high dose Ivy quarter mysterious followed by 3:00 to 6:00 week oral taper.
• 50:17And full recovery typically the norm, and there is, though, a risk of mortality if it's severe diffuse perhaps his diagnosed later and the disease has been allowed to progress further depending on the regions. I would imagine where it where it targets. You might have a different outcome.
• 50:39So the outcomes, I mean, the president is I should say our broad. I mean, they can be a number of viruses bacteria number of vaccinations. In fact, I put this together, one year right before I got my flu shot and I was like I really don't want to eat them.
• 50:52So I didn't thankfully. I didn't get it, but apparently it's been reported after the influenza vaccine, so anyway.
• 51:01There is a very severe in devastating form, which I just had to quote it. Western Hearst syndrome. The onset is brutal with fever coma seizures and focal neurological science. It is fallmont and the mortality can be as high as 70% leaving survivors with significant sequelae.
• 51:18I mean anytime in publication, they say brutal.
• 51:22Kind of taking out their word so it's a very bad condition. It's thought, perhaps to be kind of a very severe subtype of a dem from what I was reading.
• 51:32Some people have thought but really you get this remarkable hemorrhagic transformation in the brain and again mortality 7 out of 10. So it's a really devastating condition. It tends to be diffuse and it's.
• 51:49Sonata.
• 51:50Not a good condition. I doubt we in psychiatry be consulted on this because again we wouldn't have much to offer. I don't imagine cutely it probably need sedation so.
• 52:01There is another condition bickerstaff brainstem encephalitis, so it's technically thought to be or generally thought to be Miller. Fisher syndrome with CNS involvement. So part of the broader anti. GQ 1B antibody syndrome more common in children and can cause super coma and about 3/4 of individuals progressive relatively symmetric off Emma please and ataxia by 4 weeks.
• 52:30You can have either altered level of consciousness or parameter signs hyper reflexi or pathological deep tendon reflexes. An limb strength with 4:00 or 5:00 on medical research councils, but this is the diagnostic criteria that I found.
• 52:45So you probably are not going to be seeing this but I just know that there's also album albumin know cytologic dissociation inconsistent white matter changes again. It's part of this broader antibody syndrome, which is why I included here.
• 53:02Or pathology treatment is supportive.
• 53:05There was very fast, most mentioned this there was a 2 patients. Small 2 patient case series, suggesting the valproic acid was better at managing the psychiatric symptoms than.
• 53:19Then antipsychotics so in general.
• 53:23In general.
• 53:25Antiepileptics tend to be preferred in a lot of these cases over Anti Psychotics again just because of the risk of NMS for a lot of these patients.
• 53:3666% Commission.
• 53:40Then there are post infectious antibody associated in Cephalin Titties. So you can get it. After herpes simplex virus VZV or beta hemolytic strep. You can get anti metabotropic glue one following VZV. It's been reported or anti. D2 antibodies have been reported following beta hemolytic strep. Postinfectious is interesting. It's kind of A.
• 54:08It's not very well defined in the literature. I haven't seen good good data on it.
• 54:13But again there's this idea that after infections because of molecular mimicry. You develop this kind of abnormal or dysregulated autoimmune response.
• 54:24Outliers there a number of outliers so they include these will cover these each briefly.
• 54:30So starting Hashimoto encephalopathies or store, it responsibly associated with thyroiditis. Shree at they could have picked a better acronym like really come on like 3 at come on.
• 54:42So on sat pretty broadly 12 to 84 females predominate 4:00 to 1:00.
• 54:48Sub acute fluctuate in cognitive decline tremor Mya clonus and psychiatric symptoms. They can have a number of other features. I did remember reading one case report of someone who had had a diagnosis of schizophrenia for like 3:00 to 4:00 decades.
• 55:00Ultimately found to have anti thyroid peroxidase antibodies tried on steroids got better.
• 55:11So they can cause these indolent chronic psychotic presentations. Probably not accounting for a huge proportion of those in the community. But notably they can have those chronic presentations that look like formal thought disorders.
• 55:28So the diagnosis, the end to body either anti. TPO 85% of these patients or anti thyroid globulin 70%. One note is these antibodies occur in 10 to 20% of the population, which confounds a clear diagnosis. So is the anybody there because the person would automatically just just they have it and it's asymptomatic or do they have it?
• 55:51And that is somehow mechanistically linked or in terms of a disease marker that it suggests that you're actually dealing with Hashimoto encephalopathies. It's an interesting question had a number of discussions in patients where that was found.
• 56:04Sometimes we try to steroid pulse, sometimes we didn't sometimes the steroids worked. Sometimes they didn't. But this tends to be very responsive to steroids, but doesn't respond to steroids the likelihood that you're really dealing with it really tends to be fairly low, so normal tisu flair in 60% or non specific changes EG slowing rap left to form discharges high protein and 70% in the CSF you'll get anti TPO 75% of the time.
• 56:35Myra globulin 85% of the time.
• 56:38You do a pulse of steroids 5 days.
• 56:40Very often.
• 56:42They get a lot better pretty quickly within days, so they get better splendid boutta half relapse.
• 56:52There are diagnostic criteria. I'm not going to go through this. I will note that most people tend to be sub clinical or mild over thyroid disease, usually hypo, but you can have normal you can have you thyroid status and still have the condition so don't bank on whether or not the thyroid T4 if you will is abnormal.
• 57:18There is this idea that gluten can affect the brain or immune response to gluten can affect the brain very poorly understood. There is this idea of gluten ataxia. You can get progressive dementia. In some individuals who have antibiotics to gluten specifically the client in waiting of gluten, and vacuole or leukoencephalopathy have all been reported. Vitamin deficiencies are also notable because it effects part of the gut that involves that's involved in vitamin.
• 57:49Absorption of these vitamins.
• 57:52Then you can also get vitamin deficiency, so then you really need to be thinking about B vitamins less commonly vitamin E, but notably could play a role in cognition diagnosis. Often these white matter changes throughout the brain just kind of white matter changes and very often. These individuals will have migraines and headaches. That's kind of an interesting finding and I don't think it's on my slide here. But they have been reported to have it antibodies broadly anti translate emanates anti, individual an anti Glidden.
• 58:27There there are several types of Anti Trans contaminates it might be that.
• 58:33Anti trans goat emanates 6, I believe it is, is more directly associated thought to be with DNS changes or CNS findings because there is an epitope on neurons that cross reacts with that antibody so not all of them are pathogenic. Some are some are not.
• 58:52Training is gluten free diet cognitive impairment, though in the series and the reports that I've read tends to be largely irreversible if it has has been caused.
• 59:07Yes, I got 65. I'm mentioning it largely to say it's probably a red Herring. It's an intracellular enzyme.
• 59:15That is involved heavens gad stands for.
• 59:23Oh my goodness off to think about this decarboxylase gluten glutamic acid.
• 59:29Decarboxylase I think this one is yes. Thank you so it is a It's an enzyme involved in the synthesis of Gaba But.
• 59:38Only rarely associated tumor, so that bucks the trend that we mentioned earlier to intracellular enzyme epitope that the Antigen and it's not though associated with tumors very often. This is often found with other antibodies so it's very rarely found by itself.
• 59:59One notable fact about it well interestingly this antibody is also sort of stiff person syndrome server taxi and type, one diabetes in general.
• 01:00:08But this is the one that I'm aware of where the tighter.
• 01:00:13Has been associated with the degree of CNS symptoms. Just an interesting finding there's a lot of debate. At least I've seen in some recent publications about how did these antibodies which target something intracellularly?
• 01:00:26Cause pathology I don't know it's not a lot of good answers on that. But there is discussion and whether these are directly pathogenic or not remains at least as far as I've seen.
• 01:00:38Question mark.
• 01:00:41Then you have anti emoji. These can be found in or might some subtypes. Even cause demyelination. It's thought to be part of the broader neuromyelitis. Optica spectrum disease, which can present with optic naritus recurrent optic the rightists or myelitis also has been reported in a number of other another bunch of other inflammatory syndromes.
• 01:01:11Classically, with demyelination suffer my lightest braids encephalitis, Adam Ant, NBA and then rarely with Ms. But if founded Ms you can differentiate the 2:00 based on their phenotype to some extent in that anti emoji antibodies typically have fewer than 3 lesions in the lesions tend to be fluffy butt in Ms you typically have ovoid lesions or Dawson fingers? Which.
• 01:01:38Kind of radiate out from the ventricles. The latter vegetables or T1 hypo intensities, so there are ways to differentiate it. I wouldn't even pretend to get into Ms diagnosis decades exceptionally complicated beyond the scope of this talk.
• 01:01:57There's immune reconstitution inflammatory syndrome, probably something less relevant so just for us. Robust inflammatory response to resolving opportunistic infection. Persistent infection or auto antigens during immune reconstitution so somebody whose immune system is coming back online and it.
• 01:02:15Goes.
• 01:02:16A bit wild.
• 01:02:20I'm going to go ahead and skip that there is there is another syndrome that is more recently described in HIV. Although interestingly HIV associated neurocognitive disorders is getting increasing help. I know is getting less attention. But because HIV associated neurocognitive disorders are increasingly mild or sub clinical if you will.
• 01:02:46Which should be called asymptomatic neuro cognitive impairment or ANI? Is the subtype without clinically salient are clinically evident findings?
• 01:02:56Psychologically psychiatrically cognitively.
• 01:02:59There seems to be a lot less discussion about it in the literature, it used to be just this ravaging condition that would lead to death pretty much always so now that it's more of a chronic condition. There's a lot less discussion. But more recently, there is this subtype of HIV associated CD8 encephalitis. That's been reported and their number of theories of what exactly it constitutes but again there's the jury is still out.
• 01:03:31Crio globulin EMEA I mentioned this again just because cryoglobulinemia can be associated with a range of masculinity's kind of an outlier. It's probably not going to be causing direct immuno jonis. I mean, it's it's not going to be causing a pathogenic changes in neurons. But it can cause hyper viscosity syndrome if if it is if the counts are significantly higher so if you have.
• 01:04:01Tumor causing you know just a great deal of monoclonal proliferation antibodies. You can get hyper viscosity syndrome when you actually need to do a doppler.
• 01:04:12In those individuals to know.
• 01:04:15And and then vasculitis so if you get complex deposition and so it's really causing vascular changes in these individuals and so at that point rheumatology would be involved, but cryoglobulinemia can have cognitive and psychiatric import.
• 01:04:33And then finally there is this condition that's kind of broadly zero negative autoimmune limit himself allopathy so there aren't a whole lot of cases reported.
• 01:04:44But one wonders and there is discussion about how many of these individuals.
• 01:04:50May have a yet unidentified or difficult to isolate antibody or antibodies and in a number of these there are case reports of prompt response to steroids or IVIG and again. It's kind of fascinating question so if you get somebody who looks like they could have possible syndrome.
• 01:05:15And really you don't have anything else to go on at a certain point, it would be a Hail Mary. But I have occasionally said. Well, we have nothing else, right now at this point would it be reasonable to entertain.
• 01:05:29A pulse of steroids.
• 01:05:31We have nothing else, right now to offer might we consider that or if they have catatonic features might we consider ECT might we might we think about doing something because if not this person.
• 01:05:46You know time is brain and if we wait think about risks and benefits and sometimes sometimes we do it, so just considering that.
• 01:05:59So you can also have auto immune antibody negative, but probable autoimmune encephalitis. This is from the grouse and Elmo paper and in fact, the reason the idea is and I've said it previously but I'll mention it again here.
• 01:06:16The reason for defining autoimmune encephalitic tease.
• 01:06:21Broadly and allowing earlier diagnosis is largely predicated on the idea that early treatment.
• 01:06:29Appears to yield better outcomes, the longer you wait. I mean, it used to be there's like I don't know like there's that one case, and everyone's all could be could be could it be wait wait wait wait wait wait wait wait wait weeks go by. Oh, it is. Let's do it. Let's do steroids and nowadays were much more likely to do steroids early just to prevent ongoing accumulating damage in the brain from what I've seen and heard broadly we're moving.
• 01:06:59Increasingly Tord proactive pulses of steroids and treatment so.
• 01:07:05For what it's worth it's valuable to consider it and then broadly speaking you have infectious causes encephalitis.
• 01:07:15So, in the interest of time, I will actually not be getting into this final section because it would actually be a significantly longer duration of time, so we'll go ahead and I'll go ahead and be done with the presentation at this point but I will mention just a couple of comments about treatment.
• 01:07:38So there are no randomized clinical trials about this just don't exist.
• 01:07:47So on the one hand, they don't exist with regard to managing the underlying autoimmune process. In most instances on the ones we've kind of talked about previously but especially not for the psychiatric symptoms. That might present or the cognitive symptoms. That might be some of the primary presenting presenting reasons why we in psychiatry are being consulted so I mean number one. You obviously treat the underlying physiological disruption so whatever that is.
• 01:08:17Typically steroids typically with IVIG plus minus Plex, another immune modular. Tori treatments in terms of managing the actual syndrome itself.
• 01:08:32There is a report that I do just want to point out retrospective report looking at patients with auto antibody associated encephalitis.
• 01:08:43And.
• 01:08:45They retrospectively which is not a perspective study, but there was an exceptionally high rate. It looks like in an S like features presenting after the administration of neuroleptics in these patients something like 70% of patients who were exposed to an antipsychotic developed symptoms temporally. After that that could be consistent within Ms period that's high and so as a result.
• 01:09:17I treat this population with anti psychotics only with great caution. I will very often reach for valproic acid and be assertive carbamazepine and be assertive out of in and be assertive Clonidine.
• 01:09:36If their blood pressure will tolerate it beta blockers and so forth gabapentin if there's restlessness or akathisia like symptoms.
• 01:09:46Anti psychotics I will very rarely use by themselves and if I am I'm typically in the atypical realm. And I very often will pair that with a benzodiazepine because they often will have catatonic like features check the iron again. State wise if the iron is low. The risk is there, I have read in the literature that I believe it's rose bushes published on their experience with Catatonia after the iron normalizes it.
• 01:10:17Likely something to do with sequestration or activation with the immune response so once the iron normalizes. It looks like you're out of the window and perhaps the risk. The heightened risk of NMS may actually decline and perhaps re approximate their pre morbid risk. Air quotes of NMF so the risk goes away. So I will always check and iron and think about that very carefully.
• 01:10:44Really, it's touching go and it is Unfortunately this stage a lot of trial and error.
• 01:10:56That's what I got.
• 01:10:58What questions do you guys have?
• 01:11:13One glad that sell crystal clear.
• 01:11:16I left them speechless.
• 01:11:18Yes, accounts.
• 01:11:21Well.
• 01:11:23I do have a handout.
• 01:11:27For this, I put together so on. It just to kind of give you guys a sense of what's it. Oh, I do refer you guys to my?
• 01:11:36My publication, it really does have all this stuff in it, and on the big stuff.
• 01:11:40I'm and so it covers here. When does suspect automated self allopathy key reasons to think about it tests to order.
• 01:11:49Mayo Clinic antibodies.
• 01:11:53General approach general regiments for managing yet.
• 01:11:58And then diagnostic criteria, but then I've included and I actually went through bunches and bunches and bunches of reports and I actually pulled out clinical features that may suggest specific autoimmune encephalography's.
• 01:12:12And I mapped it onto HP I resumed systems mental status examination and the physical examination, so if you want to be comprehensive in terms of finding key features that might lead you to specific diagnosis. That's in the last part. It's also in the paper that I have in Psychosomatics. So I think there might be 1 or 2 other tables in the second. Cymatics article that included that's not in there, but anyway, it has.
• 01:12:44Was intentionally kind of a broad brush discussion in the other thing I'll just say, but broadly speaking is MSMS is autoimmune as well. But.
• 01:12:55Man we just don't understand him ass so I didn't really include a mess in this or other D myelinating syndromes because.
• 01:13:05It seemed conceptually a bit different from.
• 01:13:10From a lot of this not as part of not as part of the presentation. But I'm just looking here to see actually already already shut it down so anyway.
• 01:13:22Thoughts reflections meditations.
• 01:13:26Iterations.
• 01:13:31Yeah, oh OK interesting.
• 01:13:38Is it because they're more muscle more than muscle belly is involved?
• 01:13:42Involvement.
• 01:13:45Got it.
• 01:13:51Thank you that's interesting.
• 01:13:56Well, with that, we have finished our tour.
• 01:14:01Of our four talks.
• 01:14:03I will delete the.
• 01:14:06And let's have questions you can always email me.
• 01:14:11I'll be in Rochester.
• 01:14:13Oh, I shut down, I was supposed to log off my bad. I just I should enter so yeah, if you have questions or is that I also would just say if you're interested in the delirium peace.
• 01:14:27So my paper on the transtheoretical model of delirium kind of that.
• 01:14:32General model and thinking about neuro physiological subtypes.
• 01:14:36That's in the American Journal of Geriatric Psychiatry from early last year. I believe so it also has Maldonado on it. If you look for his name and delirium my named Delerium, you'll find that.
• 01:14:49Had the systematic review that's in Psychosomatics, looking at medical Catatonia and the distribution of causes what risk factors you might consider.
• 01:15:03I also have a paper on Catatonia vis-a-vis which I love getting that in the title. Catatonia vis-a-vis delirium and altered mental status on the value of assessing for Catatonia and altered mental status. That's General Hospital psychiatry.
• 01:15:18Just kind of covers some of the general thoughts there.
• 01:15:21Yeah, tell me about it.