16.1 Encephalitis Interview with Philip Britton, MD

[00:00:00] [SPEAKER_02]: So, I'm Ethan Short, is nice to meet you.

[00:00:03] [SPEAKER_00]: Yeah, I'd like to make you two and thanks for making contact.

[00:00:07] [SPEAKER_02]: Absolutely, absolutely. It is a bright and early hearing, Louisville Kentucky. The Sun has yet to rise

[00:00:14] [SPEAKER_02]: And my understanding it is getting kind of late for you. Where are you?

[00:00:20] [SPEAKER_00]: Yeah, so I'm in Sydney, Australia.

[00:00:24] [SPEAKER_00]: About eight, thirty in the evening and we're still in winter here.

[00:00:28] [SPEAKER_00]: So yeah, it's pretty docked by it, thirty in the evening.

[00:00:32] [SPEAKER_02]: Yeah, okay. Nice. Yeah, it has been about 90 degrees plus for the last, most of the last month

[00:00:40] [SPEAKER_02]: for us here in Kentucky. So, I'm not too mad because I'm sitting out behind my house

[00:00:48] [SPEAKER_02]: in a shed aka my office.

[00:00:55] [SPEAKER_02]: Somebody get this guy some help!

[00:01:04] [SPEAKER_02]: So, Al Capone is one of the most famous gangsters in the history of the world.

[00:01:13] [SPEAKER_02]: He died at the age of 48 after in his 20s contracting syphilis from a prostitute.

[00:01:23] [SPEAKER_02]: Now this was after the discovery of a causal organism for syphilis,

[00:01:30] [SPEAKER_02]: but Capone was reportedly so ashamed that he never sought treatment for it.

[00:01:38] [SPEAKER_02]: And the reason why I bring this up is because Capone died in the 40s in prison

[00:01:46] [SPEAKER_02]: and it probably wasn't quite well known enough at the time.

[00:01:52] [SPEAKER_02]: So, the causal organism was discovered in the early to mid-19

[00:01:57] [SPEAKER_02]: hundreds the first decade of the 20th century and the effective treatment came

[00:02:04] [SPEAKER_02]: maybe within the next 10 to 15 years.

[00:02:09] [SPEAKER_02]: But I would assume that because they didn't have TikTok and social media,

[00:02:16] [SPEAKER_02]: they didn't have the internet.

[00:02:18] [SPEAKER_02]: There a lot of this information wasn't widely known or available.

[00:02:22] [SPEAKER_02]: So, Capone gradually has that syphilis virus primarily infects the genitals.

[00:02:31] [SPEAKER_02]: Secondly, infects the skin causing lesions all over the skin

[00:02:36] [SPEAKER_02]: though that process can take months to years and eventually goes to infect the brain.

[00:02:43] [SPEAKER_02]: It starts to cause behavioral changes.

[00:02:47] [SPEAKER_02]: It starts to be a contributing factor to that person having psychosis or cognitive decline

[00:02:53] [SPEAKER_02]: aka dementia.

[00:02:57] [SPEAKER_02]: So, why am I telling you this story?

[00:03:00] [SPEAKER_02]: Because it is an example of a medical or a neurologic condition

[00:03:06] [SPEAKER_02]: that is masquerading around as a psychiatric problem.

[00:03:12] [SPEAKER_02]: And I think this is probably a lot more common than we give credit for.

[00:03:19] [SPEAKER_02]: So, way back in the day, dementia itself, things like Alzheimer's

[00:03:24] [SPEAKER_02]: would have been considered psychiatric because we did not understand them to the degree

[00:03:29] [SPEAKER_02]: that we do now and I will say we still don't understand them to a full degree.

[00:03:34] [SPEAKER_02]: But we understand that when people start to display those signs and symptoms of dementia,

[00:03:41] [SPEAKER_02]: it's not that they are having this primary psychotic condition.

[00:03:46] [SPEAKER_02]: It's not that they've lived a life of sin and that's why they're developing memory loss

[00:03:52] [SPEAKER_02]: in behavioral change, et cetera, et cetera.

[00:03:56] [SPEAKER_02]: There are so many different causes historically and into today

[00:04:01] [SPEAKER_02]: where something that is requires a medical treatment or a neurologic treatment

[00:04:09] [SPEAKER_02]: people are being put onto a psychiatric unit, which then leads them to get a psychiatric

[00:04:18] [SPEAKER_02]: treatment, a neuroleptic like an anesthetic or a mood stabilizer

[00:04:25] [SPEAKER_02]: or a benzodiazepine.

[00:04:28] [SPEAKER_02]: Treatments that may have a role in primary psychiatric conditions, but there is this massive,

[00:04:36] [SPEAKER_02]: massive differential diagnosis for medical causes of altered mental status.

[00:04:43] [SPEAKER_02]: Some of them are more obviously medical than others.

[00:04:47] [SPEAKER_02]: Things like hepatic and cephalopathy.

[00:04:49] [SPEAKER_02]: Somebody's liver doesn't work well in ammonia builds up in their body

[00:04:54] [SPEAKER_02]: and eventually when there's enough ammonia starts spilling into the brain, causing weird and wacky behaviors.

[00:05:01] [SPEAKER_02]: You've got hypoxic and cephalopathy.

[00:05:04] [SPEAKER_02]: People who overdose on say an opiate, but they don't quite stop breathing in total.

[00:05:12] [SPEAKER_02]: Maybe they breathe through your four times a minute and they start to deoxygenate parts of their brain

[00:05:18] [SPEAKER_02]: because you only have so much oxygen to get out to your tissues.

[00:05:21] [SPEAKER_02]: You can have metabolic and cephalopathy where you have some sort of electrolyte disturbance.

[00:05:28] [SPEAKER_02]: Some sort of derangement that then leads the person to become altered in that fashion.

[00:05:35] [SPEAKER_02]: You're remaking cephalopathy, the kidney stop working.

[00:05:38] [SPEAKER_02]: You cannot get rid of those toxins and you have what's called your remia or the buildup of, again, nitrogen in the bloodstream.

[00:05:48] [SPEAKER_02]: Certain withdrawal syndrome, certain intoxications.

[00:05:52] [SPEAKER_02]: You can have a closed head injury where there's not an obvious injury on the exterior,

[00:06:00] [SPEAKER_02]: but the person's behavior becomes significantly altered.

[00:06:04] [SPEAKER_02]: Hyper and hypoglycemia or lower high blood sugar.

[00:06:08] [SPEAKER_02]: You can have metat, metat interactions.

[00:06:11] [SPEAKER_02]: They used to call cyphalus, general perisess of the insane.

[00:06:18] [SPEAKER_02]: It was first recognized in the 1490s.

[00:06:23] [SPEAKER_02]: Between the 1490s and the early 1900s, it was a psychiatric condition.

[00:06:29] [SPEAKER_02]: When we don't understand why something's happening, it gets dumped into the field of psychiatry.

[00:06:37] [SPEAKER_02]: Now we test anybody who has any decent reason for having contracted cephalus and presents with altered mental status.

[00:06:47] [SPEAKER_02]: It's a very easy blood test to decide whether or not somebody has cephalus as the causative factor there.

[00:06:55] [SPEAKER_02]: But back in May, when my sister-in-law called, asking about her boyfriend my long time friend from high school and why he was acting altered,

[00:07:13] [SPEAKER_02]: the alarm bells immediately started going off.

[00:07:15] [SPEAKER_02]: He did not have cephalus, but he did end up contracting one of the most occult diagnoses or conditions that I know of in all of medicine.

[00:07:30] [SPEAKER_02]: It is a condition where I have seen patients being dropped onto a psychiatric unit for treatment with an anti-cycotic,

[00:07:40] [SPEAKER_02]: despite the fact that they have an infection in their brain.

[00:07:46] [SPEAKER_02]: My friend got a likely viral encephalitis, totally out of the blue, very little warning with prominent behavioral change.

[00:07:57] [SPEAKER_02]: It was an extremely scary frightening time for everybody involved.

[00:08:04] [SPEAKER_02]: Actually I would say for him it wasn't all that scary you're frightening because he was completely altered.

[00:08:09] [SPEAKER_02]: But we didn't know what was going on.

[00:08:14] [SPEAKER_02]: You see a prominent behavioral change and it's like the doors to that person's conscious brain or the conscious parts of their brain are totally closed.

[00:08:26] [SPEAKER_02]: That's what prompted this video.

[00:08:29] [SPEAKER_02]: Now, Alex has made good progress in his recovery.

[00:08:34] [SPEAKER_02]: He had very rapid resolution of his symptoms once the appropriate treatment was started.

[00:08:41] [SPEAKER_02]: But to me it's a foreboding that my job as a psychiatrist, our job as the field of psychiatry, primarily first and foremost,

[00:08:54] [SPEAKER_02]: is to identify these people who are dealing with a condition that is not related to primary psychiatry.

[00:09:06] [SPEAKER_02]: And make sure that we screen that out before we immediately jump on the idea of bandwagon that this is primarily a psychiatric issue.

[00:09:18] [SPEAKER_02]: So it takes a lot of skepticism, a lot of questioning of your own thoughts as well as other providers thoughts in order to arrive at these things.

[00:09:32] [SPEAKER_02]: Without further ado, I want to start with this three part series on encephalitis first with in Australian expert Philip Bruton.

[00:09:44] [SPEAKER_02]: He will do our first episode talking with him.

[00:09:48] [SPEAKER_02]: The second episode, I'm going to do my first patient interview with Alex to have him tell us his story.

[00:09:56] [SPEAKER_02]: And then lastly, I will bring in my good friend and medical school classmate who is now a child neurologist.

[00:10:06] [SPEAKER_02]: Jamie's shoot, I'll bring him back to talk a little bit more about encephalitis and some other topics.

[00:10:14] [SPEAKER_02]: So I hope you enjoy and I will say in the first video, I do apologize but my part of the video cuts out.

[00:10:23] [SPEAKER_02]: So if you just see me sitting there with a face, it's because my video just isn't isn't working and I couldn't find another one.

[00:10:31] [SPEAKER_02]: So apologies for that, but hope you enjoyed the series otherwise and hopefully it helps to eliminate that there are a lot of medical conditions out there potentially masquerading as psychiatric conditions.

[00:10:49] [SPEAKER_02]: We will never catch all of them, but our job is to be aware and open to that possibility and make sure that those patients who.

[00:11:01] [SPEAKER_02]: You know, if they're not responding to typical psychiatric treatments and they've already or if they hadn't had a proper or full medical work up or if there's just other factors that just don't.

[00:11:14] [SPEAKER_02]: I seem to point the provider in the direction of a primary psychiatric problem.

[00:11:20] [SPEAKER_02]: Hopefully this helps to make sure that some of those folks get the work up that they need and that they deserve.

[00:11:27] [SPEAKER_02]: Thanks for listening, thanks for watching, hope you enjoy and appreciate any and all feedback as always.

[00:11:35] [SPEAKER_02]: So Dr. Britain, I the impetus for me doing this is actually because I was sitting at home and my sister and law called me to she lives out in Denver, Colorado to tell me that.

[00:11:53] [SPEAKER_02]: Her boyfriend about my age about 35 was having some really odd behavior and I'm going to have him on to give kind of a patient perspective within the next week.

[00:12:07] [SPEAKER_02]: So I don't want to give up too much, but he ended up having a pretty much let's say maybe not exclusively, but primarily behavioral symptoms had no insight into the fact that his behaviors were off.

[00:12:24] [SPEAKER_02]: And luckily ended up getting to the hospital, even though he didn't realize he needed to go to the hospital and got pretty rapid treatment with a pretty rapid recovery ended up being diagnosed with most likely a viral in cephalitis.

[00:12:42] [SPEAKER_02]: And yeah, we could we could talk a little bit more about why I think it was I mean primarily why I think it was a viral in cephalitis is because he broke out in a shingles rash the day that he came home from the hospital.

[00:12:55] [SPEAKER_02]: So it was a little too coincidental for me to think that it could have been anything else at that point, but it really got me wondering because this is a topic some of my cohorts in my psychiatric residency and I had talked about.

[00:13:11] [SPEAKER_02]: These people getting missed and ending up on a psychiatric unit instead of getting the appropriate neurologic work up.

[00:13:20] [SPEAKER_02]: So that's kind of the the impetus for reaching out to you and trying to learn more and educate my listeners and viewers a little bit more about this problem.

[00:13:30] [SPEAKER_02]: Yeah.

[00:13:32] [SPEAKER_02]: So why don't you I guess first just kind of give us a little bit of background on your professional experience education and kind of what you're most passionate about and interested in this stage in your career.

[00:13:47] [SPEAKER_00]: Yeah, thanks very much.

[00:13:48] [SPEAKER_00]: So look on the pediatrician by training specialized in infectious diseases and went on to do a PhD in children and in kephalitis, particularly understanding the the burden of a disease at a population level and.

[00:14:09] [SPEAKER_00]: I'm back in clinical practice mainly now but continue to.

[00:14:14] [SPEAKER_00]: Run national surveillance for both in kephalitis and.

[00:14:20] [SPEAKER_00]: Myelitis or information of the spinal cord in children across Australia, and so yeah spend a fair bit of my time thinking about these infections of the brain and what they do to children in particular and how can we improve.

[00:14:37] [SPEAKER_00]: How our diagnosis and management of those conditions, that's that's kind of my major area of research activity. I also do as many of us have infectious disease people have done a reasonable amount of work on COVID over the last few years and in fact we're just putting together a bit of a national summary of the way in which COVID can affect.

[00:15:01] [SPEAKER_00]: Who is neurological symptoms in children as well at the moment. So yeah that's kind of my background in in pediatric infectious diseases and particularly neurological infections.

[00:15:15] [SPEAKER_02]: Okay, and I saw from a couple of different websites that you are based at the Children's Hospital at Westmead and then also says that you co lead the pediatric.

[00:15:28] [SPEAKER_02]: Active enhanced disease surveillance or pets or feeds network based at the national center for immunization research and surveillance.

[00:15:39] [SPEAKER_00]: Yeah that's right so they're my major affiliations. I also work with the University of Sydney in teaching and research as well. So yeah, by still Western Sydney but really with a national network of colleagues in infectious diseases, vaccinology, pediatrics.

[00:15:58] [SPEAKER_00]: Australia is a much, you know it's a very large physical country but relatively small population countries. So the population of Australia is about 25 million.

[00:16:09] [SPEAKER_00]: You know, in contrast to the US about 350 million so much smaller than the US which means we don't necessarily have the the frequency of some of these rare conditions in the Australian population but we do have the benefit of being able to pull together a national network.

[00:16:26] [SPEAKER_00]: So we cover almost all of the major Children's hospitals in Australia contribute cases into this network that we run our studies from.

[00:16:38] [SPEAKER_02]: In that population difference almost didn't prevent you all from taking more goals from us in the Olympics swimming.

[00:16:45] [SPEAKER_02]: Yeah, yeah, that's pretty impressive when you consider a 10 fold difference in population.

[00:16:50] [SPEAKER_02]: So some of the source of national priority. Yeah, yeah absolutely how did you get interested or into researching in self-alitis?

[00:17:02] [SPEAKER_00]: Yeah, look that's a good question and like like a lot of people in life some of these things out by design I got to the end of my clinical training what you know in America would be called your clinical residency.

[00:17:15] [SPEAKER_00]: Was qualified as an infectious disease pediatrician and had planned to go into a low and middle income country and actually working tuberculosis in children of all things.

[00:17:27] [SPEAKER_00]: But for several you know reasons that wasn't going to work out and I was a little bit over loss.

[00:17:32] [SPEAKER_00]: And one of my senior colleagues at the time her name's Cheryl Jones had an interest in this area but hadn't really been able to get a project going so said to me look like you know like a lot of these things I can fund you for six months and then you've got to get your own funding but let's see if we could do this and so we.

[00:17:51] [SPEAKER_00]: We work to set up this network and and move into research in this area in 2013 and I've been at it ever since.

[00:18:02] [SPEAKER_00]: And in fact you know a bit of an anecdote one of the reasons I get so stuck with it is very early on in my.

[00:18:08] [SPEAKER_00]: Doctoral studies we had a young child come into the children's hospital at Westmead and and within 24 hours they passed away and the story was very striking this was essentially well child had a bit of a cold.

[00:18:26] [SPEAKER_00]: Mom you know stayed at home to look after this child put them on the couch in front of the TV you know with some with some you know simple pain relief and fluids came back and our later and the child was unconscious.

[00:18:39] [SPEAKER_00]: brought them into hospital and 24 hours later they had died and this child had a very prominent brain.

[00:18:46] [SPEAKER_00]: disease associated with influenza called acute necratizing and kephalopathy of childhood and this was one of the most striking, prominent tragic kind of diseases that's in my entire training.

[00:18:59] [SPEAKER_00]: And in some ways it's stories like that that have really kept me in this space because for a lot of these very aggressive.

[00:19:13] [SPEAKER_00]: diseases that cause you know both child death and disability we still don't have great answers and still don't have great treatments so.

[00:19:21] [SPEAKER_00]: That's kind of what keeps me engaged is camp we should be able to do this better and and I hope we will be able to do this better and if I can make some contribution to that that would be great.

[00:19:32] [SPEAKER_02]: Yeah absolutely I mean it is a major theme of the podcast to try to appreciate the nuance in what we do and appreciate all of the uncertainty and the unknown that exists most of the experts openly acknowledge all of the things that we don't know whereas I find some others maybe try to fill in the gaps with.

[00:19:57] [SPEAKER_02]: I don't want to call it misinformation but you know trying to sound like they know everything about that topic as opposed to appreciating that uncertainty and that unknown so.

[00:20:10] [SPEAKER_02]: Can you just tell my viewers listeners kind of what in Sephelopathy and in Sephelitis are in general and what the difference between the two is.

[00:20:21] [SPEAKER_00]: There could so.

[00:20:24] [SPEAKER_00]: In Sephelopathy as you say with the softsteewey user hard sea if stroke and kephalopathy.

[00:20:31] [SPEAKER_00]: Like that that are actually yeah well we would say that's how the Greeks would say it in kephalopathy anyway.

[00:20:37] [SPEAKER_00]: What's that that's defined really is an altered mental status and altered mental status can be an altered level of consciousness.

[00:20:45] [SPEAKER_00]: The decreased level of consciousness changing personality or behavior that's fundamentally what in kephalopathy is it's when the brains functions are impaired such that you see that work out in consciousness personality and behavior.

[00:21:02] [SPEAKER_00]: In contrast to that in kephalitis you might say is a subset of that and kephalitis is when in kephalopathy is caused by inflammation of the brain.

[00:21:13] [SPEAKER_00]: In contrast to say caused by a vascular injury a blood flow injury which is what stroke is or a traumatic brain injury where you're getting kephalopathy but it's a traumatic thing.

[00:21:28] [SPEAKER_00]: And so in kephalitis is when the in kephalopathy is caused by inflammation of the blood brain and about half of the time in children maybe a little bit more in adults about half of the time that's caused by an infection.

[00:21:44] [SPEAKER_00]: And about a third of the time according to a third of the time it's caused by an autoimmune or immune mediated mechanism.

[00:21:52] [SPEAKER_00]: And then the rest of the time we don't know what causes it and in fact if you went back 15 or 20 years people used to say 50 to 60% of incabolitis in adults and children we didn't have a cause for.

[00:22:05] [SPEAKER_00]: Now over the last 20 years with a fair bit of work in this area some improved diagnostics better understanding of the condition it's more like about 20% we don't have a cause.

[00:22:19] [SPEAKER_00]: And somewhere in the middle there we've also come to and understand that there are different kinds of inflammation of the brain.

[00:22:30] [SPEAKER_00]: So a classic viral in kephalitis occurs when the virus infects the brain structures itself and the immune system responds to that and the combination of the virus infecting the brain and the immune response causes the incabolopathy.

[00:22:47] [SPEAKER_00]: And the kind of typical cause of that is the virus called herpesinplex virus and the disease that it causes herpesinplex in kephalitis.

[00:22:59] [SPEAKER_00]: We now know that there are some conditions particularly in children where the virus doesn't infect the brain directly what it does is it causes infects the body causes an inflammatory response in the body that then the inflammatory response in the body can affect the brain.

[00:23:19] [SPEAKER_00]: Even though the virus doesn't infect the brain directly and we call those infection associated in kephalopathy.

[00:23:24] [SPEAKER_00]: So you know this these things get more complicated as we try to understand them better but fundamentally in kephalopathy is brain dysfunction.

[00:23:35] [SPEAKER_00]: In kephalitis is when that brain dysfunction is caused by inflammation of the brain.

[00:23:40] [SPEAKER_02]: Yeah and I have been trying to educate as many of my colleagues especially where I'm from about the risk of in kephalopathy.

[00:23:52] [SPEAKER_02]: From an oxick brain injury because overdose is so frequent.

[00:23:58] [SPEAKER_02]: Here in America especially and that problem is only getting worse and I kind of live in the very, very close to the epicenter of where America's addiction problems really began surrounding the Appalachian mountains.

[00:24:12] [SPEAKER_02]: The differential for this problem of general and kephalopathy is massive.

[00:24:19] [SPEAKER_02]: When you were talking about that I was curious, do you what is your opinion or what is your more scientific opinion on why that herpes virus migrates into the brain for those who don't know HSV1 lives in the spinal nerve root and it is totally dormant.

[00:24:43] [SPEAKER_02]: And when it senses any sort of chaos or stress where that that be an illness or significant emotional stress, it may break out and travel down that nerve root to the lips and cause you know what we commonly call a cold sore outbreak.

[00:25:00] [SPEAKER_02]: But sometimes it for some reason that I don't know and I know there's competing theories about it, it will go into the brain as opposed to out to the mouth and lips. What's the kind of latest on that?

[00:25:46] [SPEAKER_00]: Good question.

[00:25:47] [SPEAKER_00]: But we certainly know that in young babies with primary infection with HSV rather than the reactivation, it can get to the brain through the bloodstream more generally.

[00:25:59] [SPEAKER_00]: So, you know there might be some variability, maybe the age is an important determinant of that but we do know that it can be either all.

[00:26:11] [SPEAKER_00]: My guess is that it's probably predominantly in older children and adults that retrograde nervous transport mechanism.

[00:26:22] [SPEAKER_02]: And does that stay for the entirety of the class of herpes viruses?

[00:26:28] [SPEAKER_00]: Good question. So, there's eight herpes viruses as you know. The first three of them, the alpha herpes viruses and related biologically in several ways.

[00:26:41] [SPEAKER_00]: That's HSV1, HSV2 and various cellosostervirus or the chickenpox or shingles virus which you referred to a little bit earlier.

[00:26:50] [SPEAKER_00]: The third of those have this shared biology of infecting skin cells but also nervous cells and then being able to be transported in the nerves.

[00:27:03] [SPEAKER_00]: That's quite different to the other herpes viruses like cytomegalovirus, abstine bar virus and then I won't go on about the rest of them.

[00:27:11] [SPEAKER_00]: But those viruses predominantly affect immune or white blood cells and the white blood cell system in the body.

[00:27:20] [SPEAKER_00]: It means that they can also infect almost every organ in the body to some degree and they can cause viral in in Kevalitis.

[00:27:29] [SPEAKER_00]: But they tend to cause it mainly in people with immune suppression because of transplant or cancer in contrast to the alpha herpes viruses.

[00:27:39] [SPEAKER_00]: It's just V1, 2 and VZV that predominantly cause disease in non-immune suppressed people.

[00:27:48] [SPEAKER_00]: So, yeah, herpes viruses are fascinating family viruses and they have this, the other thing about them of course is you just described as they can cause disease in the body at primary infection.

[00:28:01] [SPEAKER_00]: But all of them have the characteristic that once you get infected you never clear them from the body they are latent and or dormant and can reactivate in certain circumstances so you can get disease with primary infection or reactivation depending on your immune circumstances and age.

[00:28:17] [SPEAKER_02]: What do you make of my friend having a C3 dermatoma rash the day after he got home from the hospital that just you know broke out it wasn't itchier anything.

[00:28:32] [SPEAKER_02]: He didn't have any of the other symptoms of shingles but he did have a dermatoma rash it was it was funny because I'm trying to revamp my knowledge on this all through the weekend while he's getting into the hospital.

[00:28:45] [SPEAKER_02]: And I'm looking up you know case reports in case series on different herpes virus and cephalitis and various cell and cephalitis and one of the first case reports that I pulled up had the exact same dermatoma rash that he ended up having in that C3 area.

[00:29:04] [SPEAKER_02]: What do you make of that how much would that.

[00:29:08] [SPEAKER_02]: Push you towards that being the causative virus in his condition that was by the way responsive to.

[00:29:14] [SPEAKER_02]: Gens cycler beer.

[00:29:16] [SPEAKER_00]: Yeah, so without committing to offer a diagnostic opinion about your brother and Laura of the internet of course which I'm I'm wary of.

[00:29:25] [SPEAKER_00]: What we do know is in some in some cohorts of particularly adult in kephalitis varicela.

[00:29:31] [SPEAKER_00]: Zostavirus is one of the top three or four causes of viral in kephalitis so that's one thing we know epidemiologically.

[00:29:38] [SPEAKER_00]: It's been shown to be a reasonably frequent cause of what's not a hugely common condition, but yes a reasonably frequent court the second thing we know is if you take people with shingles.

[00:29:50] [SPEAKER_00]: You know, and you to do a spinal fluid I mean I know we don't do this all the time but there have been studies where you take people with shingles and you do a spinal fluid you will see that virus reactivate in spinal fluid of a reasonable number of people who have shingles.

[00:30:06] [SPEAKER_00]: So those two clues together tell me that Vasilisostavirus definitely can cause brain infection.

[00:30:14] [SPEAKER_00]: And that it definitely can cause brain infection or central nervous system infection with reactivation not just with primary chickenpox.

[00:30:24] [SPEAKER_00]: And so in that setting it's reasonably plausible where somebody has a shingles episode in the context of a enkephalitis that it could be causal but by the same token one of the reasons would be cautious about being certain about that.

[00:30:39] [SPEAKER_00]: Is exactly the point that you made when you described sort of the herpes reactivation and applies to shingles too is that.

[00:30:47] [SPEAKER_00]: Other infections and immune stimuli can trigger these viruses to reactivate so it's possible it was something else that stress immune or otherwise caused his shingles to reactivate as an epiphonominor or parallel phenomenon rather than the cause.

[00:31:07] [SPEAKER_00]: One of the ways you would really go about being sure of that is showing that it really was VZV reactivated in the sadness of in the CSF of him.

[00:31:20] [SPEAKER_00]: If you have that sample and even more plausible in some ways would be to show that there was a concurrent immune response in the spinal fluid as well.

[00:31:31] [SPEAKER_00]: So we do that by testing for antibodies against that virus in the central nervous system at the time.

[00:31:37] [SPEAKER_00]: And if you had those two things they would be very strong evidence that it was the primary cause, you know the other piece of evidence you've given is a response to to a 90 viral directed against that virus.

[00:31:50] [SPEAKER_00]: Again that's a weaker kind of form of evidence now I'm giving you a very researchy type perspective on this you know.

[00:31:57] [SPEAKER_02]: It's good because we want to we want to throw cast a wide net and make sure we don't miss things and then kind of systematically knock things off that list.

[00:32:07] [SPEAKER_02]: I would say anything bacterial is very unlikely as he never had any sort of fever.

[00:32:14] [SPEAKER_02]: Unfortunately this is the American medical system and this happened in Lake May and they said the earliest follow up he could get was mid September.

[00:32:26] [SPEAKER_02]: So he was hoping to have more answers at this point but still waiting on follow up so.

[00:32:32] [SPEAKER_02]: But that whole situation you know I was described a person who had had a lot of trouble sleeping for multiple nights in a row with a lot of anxiety at night which was somewhat unusual.

[00:32:48] [SPEAKER_02]: Then followed by the the Florida presentation of altered mental status but it really strikes me because as a as a psychiatrist it is something that you know.

[00:33:00] [SPEAKER_02]: For example you know many many years ago back in the teens and in 1920s we had another diagnosis that was psychiatric that we didn't realize was really should have belonged to the field of neurology and.

[00:33:27] [SPEAKER_02]: The psychiatric condition to a neurologic condition and that to me was always something I tried to keep at the forefront of my mind in terms of how history has played out because.

[00:33:41] [SPEAKER_02]: I know psychiatry I absolutely do think that there are primary psychiatric conditions and I also think that a lot of other things are medical that we are not able to explain yet.

[00:33:54] [SPEAKER_02]: And so I think it's important to be open about all the things that could be going on medically and as I progressed through my career I hope that we're able to lift the veil on some of those other conditions and.

[00:34:09] [SPEAKER_02]: I really turn more psychiatric problems into neurologic problems but what do you make of emergency room or psychiatric providers missing this diagnosis.

[00:34:21] [SPEAKER_02]: I worry that if he was somewhere else he may have had his diagnosis missed.

[00:34:28] [SPEAKER_00]: Yeah, I mean I think we probably don't have a really good hand along just half frequent.

[00:34:33] [SPEAKER_00]: This occurs.

[00:34:38] [SPEAKER_00]: In terms of delay or missed diagnosis there certainly are case reports and case series of people who end up in psychiatric care who then went on to be diagnosed with an.

[00:34:52] [SPEAKER_00]: A viral or immune-meditated in catholitis and in particular there's one.

[00:34:59] [SPEAKER_00]: There's one particular antibody mediated in catholitis called anti-NMDAR that has become a cause.

[00:35:07] [SPEAKER_00]: I can use that language of this phenomenon so.

[00:35:12] [SPEAKER_00]: And that was really described in in great clinical detail probably about 15 years ago and then now a lot of research in that space.

[00:35:23] [SPEAKER_00]: We've shown that a small proportion of in catholitis in children viral or immune mediated will present predominantly like a psychiatric illness with delusions or hallucinations or suicide.

[00:35:41] [SPEAKER_00]: So that proportion amongst childhood in catholitis is pretty small less you know 1% or less.

[00:35:48] [SPEAKER_00]: But we have shown some of the features that tend to predict this amongst in catholitis as a whole.

[00:35:57] [SPEAKER_00]: So the group of patients with spots more subacute onset presentations where they have those psychiatric features but also there's a suggestion of seizure or there's a suggestion of fever.

[00:36:17] [SPEAKER_00]: However you know,

[00:36:20] [SPEAKER_00]: transiently those things might be present.

[00:36:24] [SPEAKER_00]: It's kind of those red flags in a psychiatric presentation.

[00:36:28] [SPEAKER_00]: The other one is a complete absence of any of any social triggers or any price psychiatric illness in somebody is a real red flag.

[00:36:40] [SPEAKER_00]: Now you know in psychiatry that completely new onset, you know psychosis does happen.

[00:36:48] [SPEAKER_00]: And the younger you get them or likely a new presentation is going to be something that will persist but certainly I think that psychiatrists should be thinking in any new onset psychosis or in any suicidal patient that doesn't have.

[00:37:03] [SPEAKER_00]: Some situational trigger that can be discerned or some social risk factors.

[00:37:08] [SPEAKER_00]: There there the patients who should be thinking could this be something different.

[00:37:14] [SPEAKER_00]: And yeah look I don't think it's that common amongst emergency doctors again I don't think we know exactly how committed is but we do know from a survey that was done by an organisation called in catholitis international based in the UK.

[00:37:27] [SPEAKER_00]: That if you ask emergency practitioners about symptoms of incatholitis and how often they would consider it as a cause that anything between a third and a half of emergency providers will not necessarily consider incatholitis even if they're presented with a patient with symptoms that could be consistent with that diagnosis.

[00:37:51] [SPEAKER_00]: And that's a survey but it was reasonably well sampled survey from Europe and the UK and Australia and amongst the respondents there was a lack of confidence and a lack of knowledge and awareness relative to what we would like to see.

[00:38:09] [SPEAKER_00]: So look you know one of the reasons we do this you know the one of the reasons I do this kinds of interviews even and appreciate the opportunities to try to push out into the communities far as we can.

[00:38:23] [SPEAKER_00]: Because we're an unusual conditions are hard for the health system there's no question about that a lot of the way the health system is developed and practice is geared towards high frequency high burden conditions.

[00:38:37] [SPEAKER_00]: And the unusual or the infrequent then gets kind of let's call it demoted either by the funders or the administrators and.

[00:38:47] [SPEAKER_00]: And so the more that you know we can advocate and and call to mind these issues both for the community as well as felt practitioners the better I think.

[00:38:59] [SPEAKER_02]: Yeah and you know I really think it's practicing a lazy form of psychiatry if you don't give serious consideration to medical causes.

[00:39:10] [SPEAKER_02]: With with that said I mean there were several attendings that you know myself and my cohorts in residency.

[00:39:19] [SPEAKER_02]: Had to educate a little bit on anti in MDAR and some lightest or in Kevlight as so.

[00:39:25] [SPEAKER_02]: It is it is definitely a newer phenomenon but you know I I got so frustrated with again what I just called lazy psychiatry somebody has a psychotic condition they come on the unit and you give them an an a psychotic or you give them a mood stabilizer without really you know thinking.

[00:39:45] [SPEAKER_02]: Could this be something else and or thinking after a few days of not responding to those.

[00:39:53] [SPEAKER_02]: That's when you really should be thinking especially like you said in somebody with no history of any primary psychiatric condition that hey maybe there is something else medical going on here.

[00:40:06] [SPEAKER_02]: But could you give a little bit more differentiation between some I guess maybe the most prominent types of in cephalitis acute onset subacute chronic and and then how you maybe you had tried to differentiate those clinically.

[00:40:21] [SPEAKER_00]: Yeah so the timeline which is what you've kind of intimated with the acute versus subacute versus chronic the timeline is important with respect to cause.

[00:40:34] [SPEAKER_00]: And certainly where you have acute very acute syndromes they're more likely to be infectious where you have subacutes in drones they're more likely to be a immune mediator chronic the chronic in kephalopathy or in kephalitis is are a very distinct group really.

[00:40:52] [SPEAKER_00]: And save for a couple of particular chronic infectious in kephalitis what the most probably the most famous of which is the chronic form of measles in kephalitis called ssp.

[00:41:06] [SPEAKER_00]: A lot of the others are still very much mysterious.

[00:41:11] [SPEAKER_00]: The timeline is important with respect to cause another thing that's very important with respect to causes age so we know for example that even within childhood if you're under one the causal spectrums quite different from one to five is quite different from five to ten.

[00:41:27] [SPEAKER_00]: And so being able to to recognize these factors that are going to push you into a different causal spectrum is very important with respect to testing and early treatment.

[00:41:42] [SPEAKER_00]: A quite a bit of work spend on it in the immune mediated space so over the last say five years there's some good clinical guidelines for the diagnosis of immune mediated in kephalitis is adults and children.

[00:41:55] [SPEAKER_00]: And in particular those guidelines are quite helpful because they've proposed features that are consistent with immune mediating kephalitis that allow you to make treatment decisions even if you don't have a diagnostic test and that's important.

[00:42:14] [SPEAKER_00]: For early treatment but it's also very important for the two thirds world out there that don't have access to a lot of the diagnostics that you might require to make these diagnosis.

[00:42:24] [SPEAKER_00]: The other thing that we talk about quite significantly from an infectious point of view is trying to put together their risk factors in terms of exposure to certain infections in different locations and with different activities.

[00:42:37] [SPEAKER_00]: With the clinical features with the neuro radiology and so we've written guidelines for Australia there's international guidelines there's guidelines for the US and the UK and France and all of them try to help clinicians see that if you can understand the clinical presentation including the timeline.

[00:42:57] [SPEAKER_00]: If you can understand the range of risk factors for certain infections if you can get the right kind of neuro imaging a combination of those factors allow you to select a productive testing approach and hopefully land on a good diagnosis but.

[00:43:15] [SPEAKER_00]: When we tried to study this in children just on the basis of clinical features and so and try to see whether any.

[00:43:24] [SPEAKER_00]: Specific clinical features could accurately predict cause what we found is that there was no simple solution there so it remains the challenging condition those know data about it quite a variety of presentations any single cause can present in a number of different ways so it is still a big challenge for clinicians.

[00:43:44] [SPEAKER_02]: Are there certain viral conditions that are it's cause more more often cause solely behavioral changes without any real focal neurologic signs.

[00:44:00] [SPEAKER_00]: Good so hope is simplex one.

[00:44:05] [SPEAKER_00]: A minority of her piece in Clevveritis but an important minority does present with effectively acute behavioral disturbance often with speech disturbance and no fever and no fitting.

[00:44:21] [SPEAKER_00]: Even though it's not it's not the most common presentation of HSV and Kevillitis we would say HSV is one of those ones that should be on the list.

[00:44:30] [SPEAKER_00]: The other reason it should be on the list is we don't actually have directed any vials for many of the viral causes but for HSV and these at V we do and and you know prioritizing those causes in people's minds that they can actually give a treatment for is very important as well.

[00:44:48] [SPEAKER_02]: What what specific types of speech changes do you tend to see with HSV in several it is.

[00:44:56] [SPEAKER_00]: Yeah now now you're pushing me because when I said I normally see it in neonates who don't talk at all right so in pediatrics but in adults you can go anywhere from effectively what appears to be a selective mutism.

[00:45:14] [SPEAKER_00]: Through to largely just this R3 our rather than language problem it's more a speech problem but it can be quite varied but you know some people some people in that those circumstances will be missed diagnosed as stroke as the key differential diagnosis up front.

[00:45:34] [SPEAKER_00]: Because they present effectively with a transynoschemic attack like presentation with dysarthria and sometimes confusion.

[00:45:47] [SPEAKER_02]: So you know I have to point out here this would be a psychiatrist saying this but I really do believe that even in people's most psychotic or altered states there are grains of truth to the things that they are saying.

[00:46:02] [SPEAKER_02]: One thing that I left out is when he was in his altered state he said multiple times that.

[00:46:11] [SPEAKER_02]: My skin is burning.

[00:46:14] [SPEAKER_02]: My skin is burning that was the other piece that really got me thinking about the VZV as the causal factor.

[00:46:22] [SPEAKER_02]: But after you know he had had two rounds of again, cyclovered and was not altered anymore.

[00:46:29] [SPEAKER_02]: He was no longer saying that so it was just kind of putting those puzzle pieces together kind of like a investigation trying to figure out what is what is giving us more details about the condition versus what is just not at all relevant but.

[00:46:49] [SPEAKER_02]: What about some of the longer term outcomes of patients and how can you kind of decipher based on their initial presentation what type of long term outcomes they may have.

[00:47:03] [SPEAKER_00]: Yeah good way.

[00:47:05] [SPEAKER_00]: And we are in fact in the middle of a piece of work taking about 400 children that we have in our registry and looking at their outcomes at 12 months after their infection which is again a piece of the research that we've done.

[00:47:25] [SPEAKER_00]: And trying to say can we discern from their acute presentation factors that predict their 12 month out.

[00:47:31] [SPEAKER_00]: So that's that's in progress but the answer the long term outcome of in Kevalitis in children in a high income setting very different in low and middle income settings but in a high income setting about one in 20 children die from their illness adults it's about one in 10.

[00:47:50] [SPEAKER_00]: In terms of long term outcomes if you think about it in terms of complete recovery in children about half of children who survive will completely recover half will have some sort of difficulty.

[00:48:05] [SPEAKER_00]: And in adults it used to be thought that the full recovery was maybe a bit more frequent but actually and more and more it's looking like it's very similar maybe half to 60% have some level of ongoing difficulty.

[00:48:20] [SPEAKER_00]: And amongst those with ongoing difficulties it's split you know in children about a quarter will have a severe rate injury essentially.

[00:48:32] [SPEAKER_00]: Whereas about a third will have essentially subtle neurococtative or learning problems but will substantially be able to function.

[00:48:43] [SPEAKER_00]: And in adults that more subtle end of the spectrum manifests mainly as inability to return to say work or study.

[00:48:53] [SPEAKER_00]: And that that was almost entirely unmashered until maybe five six years ago where people have more accurately tried to look at that.

[00:49:03] [SPEAKER_00]: And it may well be that two thirds of adults who survive their in catholitis have some level of problem and the biggest group are people have some level of assistant personality change that affects their relationships or some level of.

[00:49:20] [SPEAKER_00]: In ability to return to their level of work that they used to do before so this is a very burdensome condition over the long term.

[00:49:30] [SPEAKER_00]: If you look at what predicts that as I said, where in the middle of a piece of work, so I don't I don't have all the answers yet but across the broader literature the level of.

[00:49:42] [SPEAKER_00]: Consciousness impairment acutely the need for intensive care management just how much of the brain is affected on neuro imaging or on EEG which is a different measure of brain function all of those things likely predict long term outcome.

[00:50:02] [SPEAKER_02]: So if you knew you were going to contract in catholitis and you could set out in advance the most important treatments after the acute phase of your illness what kind of things would you set out for yourself.

[00:50:19] [SPEAKER_02]: To try to be in that third to have that make a full recovery.

[00:50:24] [SPEAKER_00]: Yeah, we think that all people who've had in catholitis should be assessed reasonably closely across the first 12 months from their illness.

[00:50:37] [SPEAKER_00]: Now of course all different health systems as we've talked about have different you know resource capabilities and opportunities but.

[00:50:46] [SPEAKER_00]: We would say that you should probably as a minimum be assessed about three months, three or four months after you've been acutely unwell and then at 12 months.

[00:50:56] [SPEAKER_00]: We know that the recovery.

[00:51:00] [SPEAKER_00]: From many a brain illness like in catholitis does continue to occur across a 12 month spectrum so what you look at this judge is not necessarily what you're going to look like a 12 months.

[00:51:13] [SPEAKER_00]: But what you look at about three or four months is giving you a bit of a sense of the trajectory of that.

[00:51:21] [SPEAKER_00]: So understanding that you do have to be fired up across that timeframe and understanding that.

[00:51:30] [SPEAKER_00]: You're effectively what you're hoping is full recovery return to base level of function so that when you're not doing that it's really important that that is brought to the attention of people as early as possible.

[00:51:42] [SPEAKER_00]: Not necessarily because.

[00:51:47] [SPEAKER_00]: They're going to be in a position to have a treatment to you know fix your problem but what we do know about rehabilitation overall is function is king and if you can identify a problem as early as possible what you can often do is provide the kinds of therapeutic inputs that allow them to build scaffolds into their life.

[00:52:09] [SPEAKER_00]: To achieve some level of resilience with that level of function and.

[00:52:15] [SPEAKER_00]: You know I'm speaking to a psychiatrist here but when people's function is impaired and they aren't offered a.

[00:52:24] [SPEAKER_00]: Rehabilitation pathway even if that is just to provide resilience through scaffolding.

[00:52:30] [SPEAKER_00]: They they are much more prone to then deviate into co-bored co-morbid mental health issues that that can then become actually.

[00:52:41] [SPEAKER_00]: Let's call them mutually reinforcing you don't do things because you don't think you can do things you get depressed which means the people around you find it harder to deal with you and in fact that's often the saddest story is people who have.

[00:52:57] [SPEAKER_00]: Not had minor relatively speaking functional problems identified and then offered ways to rehabilitate that find themselves in out of work.

[00:53:08] [SPEAKER_00]: More mental health relational breakdown and then really what what could have been deviated into a more.

[00:53:21] [SPEAKER_00]: Constructive approach to rehabilitation has not happened in that 12 months after illness and then you've lost an opportunity and often you start to get into trajectories being much more entrenched.

[00:53:33] [SPEAKER_02]: Is there any researcher data that you're aware of on the rapidity of early treatment in predicting long term recovery.

[00:53:44] [SPEAKER_00]: No, not very much at all actually so a lot a lot of the there's this very few good.

[00:53:53] [SPEAKER_00]: Control trials in in Kefalata's right.

[00:53:58] [SPEAKER_00]: There's quite there was a whole bunch to show that any virus worked for her piece of bricks in Kefalata's and then then since then there's actually been very little.

[00:54:08] [SPEAKER_00]: And all of those trials were very much focused on acute survival.

[00:54:13] [SPEAKER_00]: So can we give a treatment that can reduce the mortality rate.

[00:54:17] [SPEAKER_00]: And then there's been a real stagnation in in clinical trials to then look at what does it look like to optimize those therapies.

[00:54:29] [SPEAKER_00]: And then what does it look like to then move into that tertiary prevention space of saying okay you've survived now but what does it look like to have interventions that optimise your functional outcome.

[00:54:41] [SPEAKER_00]: So I'm so to say there's there's been a death of really good quality evidence for how to manage this so in fact a lot of what's done for in Kefalata is leveraged off evidence for other forms of brain injury either traumatic brain injury or stroke.

[00:55:00] [SPEAKER_00]: And so a lot of the models for rehabilitation are modeled off those areas rather than based on direct evidence in farong Kefalata's now I think there's there's good.

[00:55:13] [SPEAKER_00]: Or's ability for that but to to apply that evidence in that way, but it's not perfect.

[00:55:21] [SPEAKER_00]: Yeah.

[00:55:22] [SPEAKER_02]: Well I mean it certainly makes logical sense that if you have the onset of symptoms and a day later you get the appropriate treatment in have resolution of the symptoms that it would be more likely that you would have a benign long term course.

[00:55:37] [SPEAKER_02]: But obviously we would like to see that play out with more official data and research.

[00:55:44] [SPEAKER_02]: Unfortunately it is something that is you know recognizes a rare condition and therefore most research is funded by some branch of the pharmaceutical industry or I would say at least the majority of it.

[00:55:59] [SPEAKER_02]: So maybe if we talk about it enough then and it becomes enough of a in the public health awareness then there may be better information on it.

[00:56:14] [SPEAKER_00]: I would want to say there are some islands of excellence really in this area so as a fantastic neuro infections group.

[00:56:25] [SPEAKER_00]: In the UK at Liverpool University who've done some great work they've just completed a trial looking at giving steroids in addition to any virus for herpes in flex and Kefalata's those findings will be coming out soon.

[00:56:38] [SPEAKER_00]: There's been a huge amount of work in the anybody mediated in Kefalata these to show that.

[00:56:46] [SPEAKER_00]: Not just that immune modulated therapy works but they've you know starting to really develop pathways of how do escalated and in whom.

[00:56:57] [SPEAKER_00]: So you know there's there's some great work going on out there I don't want to suggest that there isn't but but the direct answer to your question is you know do I know that if I give extreme Manhattan's time point that it's a big game changer except for having.

[00:57:15] [SPEAKER_00]: You know that it seems to make you know good sense and that we wouldn't want to do otherwise I can't tell you that I know for sure.

[00:57:24] [SPEAKER_02]: Right right one of the interesting parts about the overlap of this with psychiatry you know.

[00:57:34] [SPEAKER_02]: I feel like most of the drugs that we have in psychiatry are.

[00:57:39] [SPEAKER_02]: Hiked up more than what their results actually show you know we have dozens of neuroleptics and dozens of anti depressants and the effect sizes of all of our drugs are not that great there's one drug that is very very intriguing to me I've talked about it a lot on the podcast.

[00:58:01] [SPEAKER_02]: And even in low doses I think can have really incredible ancillary benefits beyond mood and suicide prevention is lithium and you know we've known for a long time and by polar patients you know back to the 80s and 90s.

[00:58:20] [SPEAKER_02]: Gentlemen, JD Amsterdam and Janis River Cowsky are a couple of researchers that have been looking into this for a long time they and their patients notice that the ones on lithium stopped having colts or outbreaks.

[00:58:36] [SPEAKER_02]: And the ones not on lithium didn't have any change in the frequency or severity of their colts or outbreaks which again just to reiterate are related to a HSV1 or you know if you have an outbreak in the genital area HSV2.

[00:58:55] [SPEAKER_02]: I'm always a big proponent of read as much research and data as I can but I want to see that same those same conclusions that are drawn in the data.

[00:59:07] [SPEAKER_02]: I want to see those play out in my own patient populations to really bolster my confidence in in that assertion.

[00:59:18] [SPEAKER_02]: So one thing that I did about three years ago is I just started taking an extremely low dose lithium supplement and probably throughout medical school and residency I would have one to two.

[00:59:32] [SPEAKER_02]: I have seven to ten day colts or outbreaks usually at a period of time when I was got some sort of other illness or was very, very stressed.

[00:59:43] [SPEAKER_02]: About three to six months in I have not had an outbreak sense.

[00:59:49] [SPEAKER_02]: What is your familiarity with the you know lithium's ability to directly inhibit the replication of that herpes virus and do you think that there's any promise in treatment.

[01:00:04] [SPEAKER_02]: In an acute setting or maybe long term supplementation as a prevention measure for certain types of in cephalitis.

[01:00:16] [SPEAKER_00]: So you know in Australia we play cricket not baseball and in cricket we would say that's a question I'm going to let go through to the keeper.

[01:00:23] [SPEAKER_00]: Because to be honest with you it's an intriguing thought, and I but I don't I don't have any good additions.

[01:00:33] [SPEAKER_00]: But the idea of of.

[01:00:38] [SPEAKER_00]: Newer active agents potentially being repurposed as any infectives.

[01:00:47] [SPEAKER_00]: I mean that that's happened on more than one occasion.

[01:00:51] [SPEAKER_00]: So I'm not I'm not against the idea I'm open to the idea I'm intrigued by your your story, but I actually don't have any decent thoughts to add at this point in time.

[01:01:01] [SPEAKER_02]: Well and like you said I mean the patients with means.

[01:01:07] [SPEAKER_02]: Have much better outcomes with this conditions patients without means have much worse outcomes and that is at least a promising treatment that is extremely affordable that certainly does have promise.

[01:01:23] [SPEAKER_02]: I mean and it's not just the.

[01:01:25] [SPEAKER_02]: Herpes class of viruses I mean there is newer research on lithium and in covid and so it may not just be this direct anti viral effect which we've known about lithium with you know also like the HIV virus.

[01:01:41] [SPEAKER_02]: It may also be a way to kind of bolster the immune response but then also.

[01:01:47] [SPEAKER_02]: Turn down the immune response be a an immunohregulator so to speak so I don't know if who's going to pay for that research though because.

[01:01:57] [SPEAKER_02]: I prescribe a you know the the lowest prescription dose to my patient for 90 days without insurance and it costs them eight or nine dollars.

[01:02:07] [SPEAKER_02]: But it is it is it is an interesting potential treatment especially in lower income areas with less medical care available to people.

[01:02:21] [SPEAKER_02]: On that note what what about you what are you most intrigued about in the research area or her treatment area regarding in catholitis right now.

[01:02:31] [SPEAKER_00]: Yeah so.

[01:02:34] [SPEAKER_00]: The area that I've.

[01:02:36] [SPEAKER_00]: Now in a little bit on is these what I've called infection associated in catholopathy's in children so they're the ones where the virus infects the body causes an inflammatory response that affects the brain.

[01:02:50] [SPEAKER_00]: And it's an indirect process because the virus doesn't go to the brain so.

[01:02:56] [SPEAKER_00]: The the kind of typical cause of that is influenza.

[01:03:01] [SPEAKER_00]: And that story that I told you at the start about that little boy who died so abruptly and tragically he had influenza that caused his brain disease.

[01:03:12] [SPEAKER_00]: And these disorders were originally described in Japan in the 80s and 90s for a long time they were kind of largely.

[01:03:22] [SPEAKER_00]: Ignored outside of Japan and then really from the early 2000s it's become pretty clear that even though they may be more common in Japan than other parts of the world they happen all over the world.

[01:03:34] [SPEAKER_00]: And amongst the children that I see with viruses causing severe brain disease these influenza influenza infection associated in catholopathy's are the worst.

[01:03:46] [SPEAKER_00]: And so we've been trying to really start to do some of the ground work to move towards clinical trials.

[01:03:54] [SPEAKER_00]: At least to set up a paradigm of doing clinical trials for the management of these conditions.

[01:04:00] [SPEAKER_00]: And we're partnering with colleagues in Australia across Australia both in neurology and infectious diseases and and trying to come up with some good but.

[01:04:12] [SPEAKER_00]: Health system embedded and pragmatic approaches to.

[01:04:16] [SPEAKER_00]: And we're trying.

[01:04:19] [SPEAKER_00]: Therapies for these and hopefully in the process understanding them better and getting a better data and samples and.

[01:04:26] [SPEAKER_00]: So that's what I'm I'm kind of narrating on and the reason I've narrated on on these is.

[01:04:34] [SPEAKER_00]: At the severe end of those conditions that the acute mortality rate is more like 30 or 40% rather than 5%.

[01:04:43] [SPEAKER_00]: And the long term outcomes amongst survivors.

[01:04:49] [SPEAKER_00]: It's more like you know 70 80% will have some level of of long term brain injury and amongst those some will be very, very severe so it's really the burden of those disorders that have.

[01:05:04] [SPEAKER_00]: Got me to narrow in on those.

[01:05:05] [SPEAKER_00]: That totally intriguing to because.

[01:05:09] [SPEAKER_00]: How does an infection that doesn't go to the brain cause severe brain injury and through what pathways well that's one of those things that we're trying to do some work towards figuring out as as our many of my colleagues are in the world.

[01:05:28] [SPEAKER_02]: Yeah, and you may blow the doors off of a lot of other scientific or medical or neurologic questions if you can find the answer to that as well.

[01:05:38] [SPEAKER_00]: Yes, and you know that's one of the great things about working in research and science is sometimes the important findings are actually serendipitous.

[01:05:47] [SPEAKER_02]: Yeah.

[01:05:47] [SPEAKER_02]: Absolutely. I would say a significant portion of the time there's serendipitous we're looking at one thing and we we figure something out that is totally unrelated but.

[01:06:00] [SPEAKER_02]: But before we kind of wrap up here, I'm just curious so you know outside of your clinical work outside of your research work.

[01:06:10] [SPEAKER_02]: Tell me a little bit about your personal life, what do you do to get away from all of your work.

[01:06:20] [SPEAKER_02]: How do you reset how do you you know stay fresh.

[01:06:23] [SPEAKER_00]: Yeah, good so look on on on father and a husband and I've got a pretty busy life when it comes to what's going on for them.

[01:06:35] [SPEAKER_00]: Try to keep fit I run I swim a few times a week.

[01:06:40] [SPEAKER_00]: That's good and I have a completely parallel interesting clinical medicine which is clinical ethics so at the moment as as well as my infectious disease role and research life, I'm actually.

[01:06:54] [SPEAKER_00]: Doing a master's in bio ethics at the moment and I mean the middle of political philosophy at the moment so there my other interests they are very you know they interface with the clinical medicine world but also there's a lot of.

[01:07:08] [SPEAKER_00]: A lot of interesting areas to explore that have nothing to do with what I do in my day job and that's what's great.

[01:07:16] [SPEAKER_02]: Absolutely it sounds like you have a lot going on I know I know how much it is just to try to manage this podcast with my clinical work with my two small children.

[01:07:29] [SPEAKER_02]: And and you know make sure and still make time for my wife and family and other friends so.

[01:07:36] [SPEAKER_02]: I would ask you about you know to give us some perspective with the class you're taking on our current political circus that we have going on here.

[01:07:45] [SPEAKER_02]: With the election coming up but that may take another hour and yeah.

[01:07:50] [SPEAKER_02]: I understand it is pushing 930 for you and with kids you you got to find a way to get into better early because you're going to be up early no matter what.

[01:07:59] [SPEAKER_00]: That's right look I could I could say all sorts of things about politics at the moment but I think we'll call it a die.

[01:08:08] [SPEAKER_02]: Absolutely absolutely well thank you so much for coming on and educating me and my listeners a little bit more about in catholitis and now when I use the term in catholitis with my colleagues I will point out to them that it is the more appropriate way in terms of the origin of the word to say it.

[01:08:29] [SPEAKER_02]: Well there you go I've had one win today then have enough there you go there you go all right thank you so much and yeah hopefully I'll get to talk to you again at some point in the future.

[01:08:40] [SPEAKER_00]: Good on anything thanks very much.

[01:08:42] [SPEAKER_02]: See you.

[01:08:45] [SPEAKER_02]: Thanks again for watching and or listening if you're passionate about the subjects that I discuss on the channel do me a favor and like comment subscribe.

[01:08:56] [SPEAKER_02]: Do whatever you can to make your voice heard that these are problems that must be addressed in our society.

[01:09:05] [SPEAKER_02]: If you have any questions comments or concerns I want to hear them.

[01:09:11] [SPEAKER_02]: Feel free to reach out on social media or email us at renegadepsychetgmail.com.

[01:09:18] [SPEAKER_02]: And if you'd like to be a guest of the show or you have a connection to some money that you think would be a good guest.

[01:09:24] [SPEAKER_02]: Let us know.

[01:09:27] [SPEAKER_02]: Thanks again for listening.

[01:09:36] [SPEAKER_01]: Disclaimer this podcast is for informational purposes only the information provided in this podcast and related materials are only to educate this information is not intended as a substitute for professional medical advice while I am a medical doctor in many of my guests have extensive medical training and experience nothing stated in this podcast

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