View the June 2022 neuroscience grand round. Featuring presentations from Justin Sporrer, MD, Dalia Lorenzo, MD, and Diego Torres-Russotto, MD, FAAN.
Alright, it's 7:02. So we'll get started with the first presentation. I was asked to give a brief talk about something that we're doing new here at baptist, which we're very excited about called high intensity focused ultrasound. Um So it's a new way that we're able to cause an ablation in the brain to treat many types of tremor, but mostly essential tremor. And we'll talk about more of that in a second. So ultrasound, you know, has existed for decades. Well, actual ultrasound waves have existed probably since the beginning of time, but in medical setting it's existed for decades in both diagnostic and therapeutic ways. Um Most people are familiar with a fetal ultrasound um that you have to use the jelly and you're able to get a very good image. But there's also therapeutic ultrasound where we can use ultrasonic waves to actually increase the energy and the temperature of tissues uh and cause abrasions at a high intensity energy at focal point will increase. And so I tell patients it's kind of like a magnifying glass if your hand is just under it, um it won't hurt. But if you bring that focal point right to the skin, then all of that light is concentrated on a pinpoint, the energy increases at the temperature that increases and therefore you're able to burn or kill abnormal cells. And so we use the fancy word ablation but it is burning those cells. It has been used for some time to treat abdominal tumors such as in the liver or the uterus. Um But we have come to the point where there was a brain problem. You know the idea of potentially causing an ablation in the brain existed. The idea existed but more accurately it's called the skull problem. You know How do we get these ultrasonic waves to maintain their energy and accuracy across a three layered hard surface. And so you can think of kind of cortical bone and then medullary bone and then another layer of cortical bone um as these barriers to ultrasonic waves. And then once it gets through then it's got to travel through brain as well. So it's all these different mediums that the wave has to travel through. And as you know um you know these different mediums absorb energy that are for lowering it. And it also refracts energy bending it. Um Which will talk some more about because obviously we do not want those uh that focal point to be in the wrong position causing ablation in the wrong position. Uh Tell people it's kind of like it's not easy to hear sound through a two pane window. So if it's a single pain you can yell out waves hit the glass and then travel on, you can actually hear it. But when somebody has a window with air and then another window is very difficult to hear on the other side. So um we'll talk about high intensity focused ultrasound A little bit more. Um in terms of everybody that is being considered for that procedure needs to get a special C. T. Scan. Looking at the density of their skull 5% of the population about has a skull density that won't allow for these ultrasonic waves to pass. And so every patient makes the same joke. Well I got a dense skull and you know there's no way and that I'm going to be a candidate and really doesn't have to do with the overall density. Is the ratio of how much of that medullary bone they have to cortical done. Okay. Again to use that to pane window analogy. And so the the other brain problem is how do we know if the energy that we are introducing is actually changing the temperature and then if we are changing the temperature do we know if it's enough to cause an ablation And then if we are causing an ablation is it in the right place? And if it's in the right place is there a beneficial effect? And so that's that's a lot of ifs when we're talking about you know making a permanent change in the circuitry of the brain. And so the ultrasound machine that we use obviously there's various settings that we use to determine the amount of energy being input. Um And then we use the M. R. I. Machine simultaneously while the ultrasound is being delivered um to perform? M. R. Thermometer which I wasn't very familiar with prior to you know starting this. Um I'm still kind of blown away that the physics of it. But essentially the M. R. I. Um that is going at the same time is able to give us a real time or at least every three seconds. Picture of every spot in the brain and what the temperature is at those spots in the brain. And so you know as we're introducing the ultrasound we're getting real time feedback that yes we are you know increasing the temperature at this one spot or no you're actually increasing the temperature at this other spot. And so we're getting this real time feedback. The analogy that I give to patients is you know if you have a gun with a site on it um You know the first thing you do is check it out, shoot it See if what you were aiming at was actually hit and if it's off by 2" to the left then you have to adjust the site. Um And so the M. Arthur mama tree allows us to adjust the site of the target for these ultrasonic waves. Math physics is able to calculate that a certain temperature for a certain amount of time causes an ablation and it's just like cooking. Um you know if you have a very high temperature you know you only need to do it for a very short amount of time. In the case of ultrasound Kalamata me 57°C for one second. We know is an ablation or 54° for three seconds. You can even go lower than that. But you know that you would be delivering ultrasound for maybe minutes at a time. And there is somewhat of a cumulative effect such that if you don't get a full ablation on the first go round you can do it again. And those two will um ad and then lastly the neurosurgeon or neurologist can check for the effect by testing the tremor or the lack thereof. So now we have magnetic resonance residents guided focused ultrasound. We use haifa which means high intensity focused ultrasound. It's easier to say than american fuss. But we get a real time heat map of that target area. And the M. R. I. Allows us very specific target. Um So you can see here's a rendering of the thalamus. You know it's about the size of a small egg. Um And I tell people it's kind of like a relay station for the brain. You know if if one part of the brain has to communicate with with another one cortex has to communicate with another. Most often it's gonna somehow go through the thalamus. Um You know all roads lead there um including sensory fibers, memory fibers, motor fibers. Um And so we're trying to aim for a subset of a subset of this of this already small target. And that's called the intermedia intermedia. Um So essential tremor. I call it the perfect high food disease. And there's three main reasons. Number one essential tremor has very few symptoms besides tremor. So, you know, a person with Parkinson's disease for example will have difficulty with walking and they have slow movements and some difficulty with speech. And so people with essential tremor, it's just tremor and it only really occurs with activity. You may not even notice it at rest. Number two is that the treatment is very small. A well known target in the brain which I alluded to earlier ventral intermediate thalamic I say. Well known because we've known for many decades um that an ablation or stimulation in the case of dBS will cause improvement in tremor. So the idea here is not new in terms of causing an ablation. You know, the thing that is new for this technology is how we get there with no incisions. And then the third thing is it has a very testable symptom to look for an immediate effect and if necessary, make adjustments. And so I guess the the example here would be people have said, well, you could you could cause an ablation in a circuit that causes some sort of mental illness, depression, for example. But that's hard to test in real time. You could go in and check their mood real quick but that's kind of an overall gestalt that you would need to, you know, survey and take a long history to see, you know, if it's having an improvement or not with tremor, it's tremor or no tremor and you can see it within seconds. So here are two pictures of the one on the left is a picture of someone's brain inside. I don't know if you can see it or not, but inside of the ultrasound machine. So see this halo or nimbus, that is the ultrasound machine, which it looks like a hemisphere. I tell people it looks like a like a lady's hair dryer in the salon. Um And so what is interesting to me about this is that you have to have the target at the focal point of that hemisphere. So imagine a spot at the very center in all directions of that hemisphere, that that machine. And so that the waves cannot really be bent more than a few millimeters. You know that that adjustment can only can only be a couple of millimeters in any direction. So once you have the patient position, there's all these calibrations that we do to move the patient's head, one millimeter to the left, two millim, 2 mm to the front to try and line up the target with the focal point. And then the picture that is on the right side is actually a postoperative MRI which we always get a day after and you can see hear that there is an ablation, this dark area, correct? So this is a T. One image oftentimes on the T. Two. Pretty much always there is a signal around here indicating a Dema around the spot of the ablation and we'll talk more about that in a in a minute. So the test drive, what I think sets apart high intensity focused ultrasound is that it allows us to deliver a lower energy first enough to raise the temperature and enough to stun these abnormal tremor cells but not yet causing permanent damage. And this is super important because we're able to raise those those cells to You know, let's say 51°C. Remember that inflation will occur at 57. Um and so then I'm constantly going in and out of the room and talking with the patient and testing them out. We have them drinking from a glass, drawing, drawing a spiral writing their name, doing finger to nose. And in the case of tremor dominant Parkinson's disease, it's even easier than that. I just have them hold up their hand to look for the tremor. And so if we are in the right spot then the tremor will be better. Okay, just by stunning those cells. But we haven't made any permanent changes yet. Um And I also checked to see if they have any abnormal or negative side effects that would indicate that we are stimulating in this case were stunning the wrong cells. And so for example, uh if they say, oh I have some tingling in my face or my hand. Any para seizures that would indicate we're about two millimeters too far back alright in the vpl or the V. Um V. P. Of the of the thalamus. So that means that we're in the wrong spot. But really by two millimeters and that's okay because we haven't made any permanent changes yet. So we move our target forward until we get good effect on the tremor with no side effects. Interestingly if you're in the right spot, people will often say that while the ultrasound is being delivered they feel like they are falling backwards like doing a backflip which can be very disconcerting. Um At least if you tell the patient about it, they don't get scared about it but it doesn't make it any more pleasant. We do give anti nausea medicine to every patient now in anticipation of that sensation which can cause nausea. Um And so I just described if there's no improvement, we may need to move the target. If there is good improvement, then we go back out to the machine, increase the settings, increase the energy and cause a permanent ablation. Uh And then pretty much done so the advantages um it's not invasive that's super attractive to patients since we've started doing this. I you know for completeness sake. Present all options and alternatives to patients with essential tremor including deep brain stimulation. But it's a hard sell to have somebody say we're gonna do this awake brain surgery to a burr hole etcetera when they know that this exists. And the other thing is if there was a huge difference in effectiveness, um then maybe you could you could make that argument, but it had, we've been able to find that super effective. There's no hardware to worry about. So, you know, people with DBS, they're always worried about, you know, if I get dental cleaning, am I going to get an infection of the hardware, Do I have to get my battery replaced every few years, those types of things? And then this test drive ability, I think that is a huge advantage. So one way to cause an ablation um you know, it has in the past has been ionizing radiation, stereotyped radiosurgery, but but you can't see the effect right away and if you're in the wrong spot then it's too late. It's already it's already been done. Um so it kind of merges the best of both worlds in that sense. The drawbacks. So I start with this in clinic, I say, you know, we have to shave your head. So I haven't had anybody back out because of that. But some are a little bit surprised by that. And the reason for that is because hair follicles tend to hold on to air bubbles and air bubbles when exposed to high intensity focused ultrasound will, you know, raise temperature and maybe turn into steam. So we don't want, you know, one of those cartoon things where the steam is coming out of the ears. Um And so the other thing is I would say it's not an easy alternatives to the deep brain stimulation procedure. Some people say well you know I don't have to go through brain surgery, I'll just go through this. Um I try to make sure that they are aware that that's not really the case. We have gotten very efficient at it and thinks about an hour on the table but the head ring application is and be painful. We use local anesthetic. Um But that's not very pleasant and then they have to be flat on their back for the duration of the procedure. Whereas with deep brain stimulation we're in like a reclined position. You know they're in a more comfortable actual situation. Um and then during the procedure people will say that their head feels warm but not uncomfortable and then we talked about that that feeling of falling backwards or nausea that people can get. And so some people you know interestingly will say oh that was that was cool, that reminds me of the 1960s or whatever. But other people say get me out of this thing, I cannot tolerate it for another 30 seconds or another sonic ation. That's what these ultrasound deliveries are called. Um And then the other drawback is it's not modifiable after the treatment. So the beauty of deep brain stimulation for example is that you can turn the settings up or down. You can even change the direction of the stimulation with certain technologies. So, you know, as their tremor progresses, which it will with time it's a degenerative disease. You can change the settings to match match their tremor and still get tremor relief. And then the other drawback, which is thank goodness luck. Usually temporary are all these side effects of numbness in the face or hand. The biggest one would be difficulty with balance and walking. Um And so I tell people That if we're causing an ablation about the size of the tip of a cigarette and you you put the cigarette out on your skin, it would be about eight wide. But if you look at that same burn the next day, of course you would have the burn plus all this redness and edema surrounding it. And the same thing happens in the brain. You know that energy spreads and there is swelling or edema in those parts of the of the brain, in the thalamus no less. And so guess what? Those those parts do other things such as sensation, difficulty walking and you know, as we've gathered more and more experience. I'm less and less surprised by any any uh complaint that the patient has and one that we've seen is kind of some slowness of speech. The good news is as that a demon recedes or goes away. Those symptoms go away. And the only thing they're left with is tremor suppression at the site of the inflation. And then lastly it can only be done on one side. Um, and so when they have done it on both sides simultaneously in other countries, it's not FDA approved here balance problems that I just mentioned are you know compounded to the point of not, you know, not being able to walk. So um, that was not FDA approved. Now there is a trial that has already been completed. The data has been submitted to FDA where if you separate the two sides by six months, give one side a chance to kind of heal up and then do the other side. That those negative consequences can be mitigated. And so every, I mean almost every patient, their first question is when can we do the other side, which is a testament to how satisfied they are with the treatment. Um, but also, you know, I say I'll put you on a waiting list and as soon as the FDA approves it will well maybe proceeding. So the shaved head. Some people don't want to look like this final points. Um, Tremor is not just normal aging. I was speaking with our our guest yesterday who's a tremor expert and uh, I think that the public needs to be educated. Physicians. Yes, neurologists. Yes. But the public needs to be educated. The tremor is not just, oh I'm getting older and so they should seek some sort of treatment because it exists. Essential tremor can be treated first with medication, especially milder essential tremors and the two main medications are president and prepare to law. Um, but high intensity focused ultrasound is a new safe and very effective treatment before tremor. I'm excited for where this could go. Um, It's more recently used for Parkinson's disease, particularly tremor dominant Parkinson's disease. Uh And research is being conducted on, we talked about second side tremor as well as other movement disorders and psychiatric conditions. You know, the whole idea is that you're disrupting a brain circuit and the cases of these diseases, there's some abnormality of the brain circuit and we're stopping that. And so I think that there is a lot of potential for this technology and it's very well tolerated. I forgot to mention, you know, sometimes Somebody might be interested in deep brain stimulation but you know, they're 85 years old. They have medical problems. This is a safer alternative in in my opinion. And that's what I thank you very much. Hey Justin Sheriff Sudani from radiology. Great talk. Thank you very much. Two quick questions when the iconographic waves are delivered. Are they delivered like throughout the skull or just from one entry point? No. So there are up to 1000 transducers Based on the surface area that we're able to expose. Um, you know, we'll get anywhere from 800 to 950 of them are usable. So the ultrasound cannot go through reliably go through a sinus for example. So we have to shut those down or if there are classifications up near the top of the skull, you have to shut those off as well. So basically you start with 1000 and then you have to start off a certain amount. But they're coming from all directions at this one local point. And the system itself adjusts for the different like density and hypothesis of the bone from different actions. Yes. Um So you know, I don't faint to understand all parts of it, just a neurosurgeon. But the physicists have figured out how to develop a system that is not only delivering ultrasound but also listening for acoustic interference and then being able to somehow, you know, retroactively calculate well if it's quote unquote noisy ultrasound on this side, then there must be something wrong over here and turn those off or modulate the amount of energy coming from this side. And so yeah, it accounts for all of that. And another question is, if you do this surgery, you dBS is no longer an option. If the patient deteriorates correct? If this does not work. Yes. Well, no, because if we do cause an ablation, like we actually kill those cells and then they don't get better. Number one, I'd be worried about my diagnosis. Um And then number two, those the cells that we would target with deep brain stimulation are gone or there's an ablation there at least. So so that you wouldn't get a reliable stimulation. I have had people who say well if I can't get the second side with the ablation, can I get D. B. S. On the other side? Yeah the answer is yes but you couldn't go in the other direction. You can't get dbs on one side and then get the ablation on the other. Because now you have this hardware in your brain that we can't use the ultrasound or the M. R. I. Uh to to to do it. Thank you. Fantastic talk. Thank you. Thank you. Justin this is captain. Great talk great overview on everything since you just touch that subject with doing D. B. S on the other side after you. Do you know an ablation on the other one. Do they have a higher incidence of difficulty with balance or from what I understand sometimes cognitive issues. Um Do they increase incidents of that? Although not as great as bilateral. Uh Yeah there's not a lot of of research on it. I have I don't have personal experience with it yet because even the people who are you know Diehard want the second the second half of their body treated uh are more willing to wait for the FDA approval which could be you know five years from now than to get the Dbs. Um But you can I mean you can do dbs on two sides and um but yeah the the difficulty with the balance and and cognitive issues those you know those can be magnified definitely more than if you just got a single side. Great thank you. Justin hi it's Ron tilson um um Great talk. Um I don't know if you mentioned it but in terms of negative or side effects, have you seen anything personally? Yes. I mean not permanent. That's the good news. But I think the most common is that they feel like they feel like they got off of a cruise ship For about three days to two weeks. By the time I see them back in clinic they say yeah you know that wasn't really fun but it went away. Other people have reported some Parithi Jys um I've had probably four out of 71 people say that they had some difficulty speaking. Not not they can still communicate but it was like slow words like this. Um And then I even had a guy who had basically hemi Terraces that was like probably the second patient that we had which you know I'm thinking oh my God you know but the more I thought about it, he did not have any parasites on the day of the procedure which means we could not have burned those cells. It showed up 24 48 hours later which means it was madame. And and in fact when we get the M. R. I almost everybody has a dilemma extending into the internal capsule which is all the motor fibers coming down from the motor cortex. So I'm actually surprised that more people don't have weakness or you know difficulty with coordination but they don't. Um But you know lots of people have a team of going into the internal capsule across the internal capsule. And like if if you see a brain M. R. I like that you know outside of this situation you would say well I would expect this person to be weak. So and then and then it subsides subsides. Have you done some follow ups? Yeah well not not on purpose. So some of these people for various other reasons get memories of their brain you know that they developed some other thing they hit their head and they you know they have a subdural hematoma or whatever. Um The ablation, the edema goes away completely. The ablation itself can almost look like it's disappearing. And I don't have a great explanation for that except that I think that the brain itself is kind of just filling in the spot. Obviously those cells are gone. They're not growing back but you know kind of the whatever back pressure from the brain because it's right in the center, it's kind of filling in the spot. Thank you I think erin entirely right Justin because it's sort of like sometimes tiny lacuna in parks that somebody has you know clearly seen on diffusion weighted M. R. I. You know months or years later looking like they had an in part somewhere and it's you know totally seemingly vanishes. It's there but it's like split liking. You can't even make it out anymore. Alright. There's one question from somebody who's logged in as observer, that's me. Sorry I was a board examiner last week and I haven't changed my name yet. Alright. Thanks Ron um Justin thanks for that presentation. But great technology. Justin has done Justin has done over 70 cases since September of 2021 and will have a very large experience to analyze volumetric lee with follow up imaging sets as well as the clinical information. So very exciting. Next up is Dalia Lorenzo from first choice neurology. Dahlia. Okay. and one a second to share my screen. Okay. Oh here we go. Okay I'm trying to share the screen here, hang on a second. Can everyone see that? Yes. Okay here we go. So um so This is a case of a patient that I saw through clinic. He's a 65 year old man, a physician and a professor. Um and who came to me with a five year history of progressive forgetfulness. He had been having uh for a few months before visiting, he had started to have auditory and actual formed visual hallucinations and also the sensation of insects, you know crawling and um and he also reported that he had episodes of of clouding of consciousness. Um He would describe these as he felt like he was in a dream good function, He could drive, he could do everything. But he just felt a little d realized the patient did have um sleep apnea but was very compliant with the CPAP. Wasn't really describing sleepiness. Um He also had significant depression but was taking Lexapro and actually had been improving. He had a numerous other complaints, including imbalance. He had had a few falls, some numbness of the left eye, urinary urgency and so His his examination um I obviously I did a Montreal cognitive assessment on him which was abnormal for especially for a physician 25. Uh He did have an underlying diagnosis of of some mild dyslexia. He had increased reflexes at the knees with a bit of Conus at the ankle. And he had some diminished sensation in the left leg, which was really mostly in a Dermot o'neill distribution. Um for the L 45 derma tone, um Pertinent negatives in terms of the history. He had no no he had very smooth ocular pursuits or no psychotic pursuit, Normal full eye movements, including up gaze. Uh He could walk normally. There was no, you know, signs for parkinsonism, no attacks yet. Um exam was otherwise normal. So here is I'm just showing his his his Montreal cognitive assessment here. Um It's not going and you know, just just to show you some of the things he made an error with. He forgot the number one here on the block. Uh He made an error on calculations. He forgot a word here in the repetition. And this is the fluency test where you know how many words can you produce? And start with the letter F. In one minute. And you know he it was normal more than 11. But for for physician this is very low. So and then he did miss three of the five items. So his overall uh score was 25 abnormal. So so initially then the impression was mild cognitive impairment with psychosis, some changes in the level of awareness and depression. So the thinking was you know dementia picture or or pseudo dementia. I'm sorry the possibility of limbic encephalitis of course with a psychosis. Um There was not really the parkinsonism or ataxia but frontal temporal dementia is also possibility had a lower suspicion for seizure. So we were so I ordered some labs including the autoimmune encephalitis panel. We did an M. R. I. The brain with contrast because of the hyper reflexive. He had I also added an M. R. I. The thoracic spine. Some labs related to that. Um You know I started him on some modafinil thinking maybe you know uh the uh he needed it for hyper samba despite using cpap. He did not ever report any cataplexy or anything like that. And then you know he had findings and he already had an M. R. I. The lumbar spine that showed a compressed nerve. So ridiculous empathy. So initial uh so the initial testing that came back. He had a borderline elevated crp but his said rate was normal. Um negative tests include A. N. A. R. P. R. The ammonia. Later on we checked in anchor that was also negative. B. 12 was in you know an adequate range fully. The TSH was normal at that point. Um um You know RPR HIV am cortisol was okay. I checked this copper from hyper reflection. That was okay. Um We did uh memory of the brain which showed a pituitary adenoma and some microvascular changes. Um And an E. G. Which uh here's a picture of it. Um He was very normal good background 10 hertz. Um We also had the MRI the thoracic spine. It didn't show anything abnormal, No compression, no signal abnormality. And the M. R. I. The lumbar spine as I mentioned showed it is compressing the the L. Five year agreement on the left and CSF. Well he didn't want to have that done. I I was never able to get CSF on him. But so here is um M. R. I. Here's just a you know just one cut showing some some of the microvascular changes that that were described. There were several of these. Okay and then here this is just a cut showing the pituitary lesion. Here's another another image of it. Um It's it's sizable as you can see uh this one's with contrast. So we actually got more testing back over the following few weeks and he was found to have a positive voltage gated calcium channel antibody. Um He was also found to have positive anti glial neuronal antibody. Also no socks one antibody. And this was significantly positive. It was detected on Western blot not the actual immune fixation and it didn't seem to fluoresce in any of the neuronal tissues. Um But you know was significantly positive um uh negatives the rest of the autoimmune panel autoimmune encephalitis panel really came back negative. This voltage gated calcium is the type end. So he actually his his antibodies appear the calcium channel antibodies were the P. Q. Type. So um so anyways it comes back um his psychiatrist has increased his antidepressant. He's it's improved his mood. He's doing better that way but he's still having the cognitive issues really having trouble at work loosen. Oh sis. So the working diagnosis at that point was an autoimmune encephalitis encephalopathy. With anti glial neuronal antibodies. He was positive for this voltage gated calcium channel but didn't really have the usual syndrome of lambert Eaton my aesthetic syndrome symptoms. Uh And he has this pituitary lesion and this ridiculous empathy. So just as a reminder that uh you know just for information the antique murano antibody panel plastic syndrome is associated with small cell lung carcinoma. It's an intracellular antigen um problem and it can present with uh sarah parenting, plastic cerebellum degeneration which he had no attacks. You know no signs of this limbic encephalitis. Which you know is a possibility here um neuropathy which can be sensory or motor sensory. And it can also present with the lambert Eaton my aesthetic singing room. And then of course you know the voltage gated calcium channel parenting plastic syndromes. um these channels are large protein channels that are present in 95% of the of the neuromuscular junctions uh and obviously play a role in the in the release of acetylcholine. So they present with Lamberti my aesthetic syndrome. Not usually limbic encephalitis. Okay I do have to say that in in reviewing this. There was one report in the literature for a rapid dementia with the end type voltage gated counseling channel but our patients actually P. Q. Type. So um uh you know usually lambert Eaton is diagnosed when there's a high pretest probability of it where you're finding symptoms and signs for myasthenia and you the diagnosis is doing electrophysiology studies and including and the antibody Um you know it's an important syndrome to detect because obviously 50% of of Lambert Eaton patients develop malignancy. Usually a small cell lung cancer. Um So so anyways we you know I referred him to the neuro oncology clinic and we decided to get more testing. I wanted to get an M. R. I. Uh dedicated to the cellar to look at the pituitary lesion. Well we got the ct of the chest the abdomen. We're gonna get the pituitary hormones. And then he was really not doing well. So decided to admit him to get all these things done more quickly and give him a trial of I. V. I. G. And sally mandrell. So the ct of the chest really didn't have them and really didn't show much. Some perry bronco thinking there were no nodules, no enlarged lymph nodes. He had a cyst in the kidney. Um And you know so it goes into the hospital and the hormones are drawn but they're not unfortunately some of the labs were messed up. So we we got some labs before sally meadow and I. V. I. G. At this H. T. S. H. Which were okay. But then the other labs were done after his uh first dose of I. V. I. G. Sally mandrell. His TSH now has gone down but his thyroid functions are still normal. Cortisol is elevated with the sally med role. And the prolactin was okay. Um And so we went ahead and uh had the M. R. I. Of the cellar which you know I'm I'm just showing different cuts of it as you can see here. Um the the lesion that he has that is extending into these annoyed sinus. It was 1.2 cm by 1.6. It was deviating the pituitary stock. Um But it wasn't really causing any any pressure onto the chasm to the optic chasm and he never had any visual field defects or anything. Uh And there's another picture of it and this is pretty much the same picture we saw earlier. So okay so I start giving him the I. V. I. G. And the Saudi men drove his first dose. He has a little bit of a headache on the second dose. More headache on on the I walk in it's around on him when he's receiving his third dose. And you know he just had this severe severe headache. Um He he was in the recliner. His partner was on the sofa and he was just clutching his head and just uh complaining of a very very severe headache. He had continuous vomiting. We had to even give them that event was so distressed. So obviously I ordered some additional you know imaging to see what's going on here. Um And uh so I did a ct brain C. T. A. Um Here's the ct brain um you know during the headache I mean the lesion is still there. Uh This one was red as now having a little bit of mass effect onto the optical autism. Um Here's here's the uh kurono. Um So so anyways his headache subsides but of course he becomes very you know very distressed. He's very distressed. So he discontinues anymore. Um He doesn't want to receive any more I. V. I. G. Um or sally medal because you know obviously he equates that with it. So so then he leaves hospital. He follows up in neuropsychology and gets the rest of the testing. He has the repetitive nerve stimulation to look for lambert Eaton my aesthetic syndrome. And this is negative as I would expect really based on the pretest probability. Uh He had some mild carpal tunnel. Um That was seen he gets the pet scan from the skull base down which is negative. Um There wasn't any uptake either at the seller. And the plan was to repeat the M. R. I. Of the brain and pet scan at a three month interval. So um here's the three month follow up MRI and lo and behold the pituitary lesion is gone so the tumor is missing and now we have an empty cellar. Um uh sort of pituitary is flat. Okay so he comes back to neurology clinic and he does report that with the I. V. I. G. And sally metro. For you know afterwards he did feel better. He was able to function function better at work. He wasn't having hallucinations. He felt more oriented. He hadn't had any more episodes of headache. Um uh And so he did improve. So um the diagnosis that that we came up with was that he had hypothesis itis and he has a perennial plastic um uh anti neuronal antibody encephalitis that remains under surveillance. So um just to kind of review hypothesis itis is an inflammatory it's just an umbrella term. It covers different inflammatory disorders that can affect the pituitary gland. Um There can be primary and secondary causes of the hypothesis. Itis the primary causes can include things like lymphocytic uh specific hypothesis. Itis granuloma, necrotizing is very rare, secondary causes a lot of them infection. Obviously rupture breath, Raske, cleft, cyst different um tumors, german omagh's cranium, ngoma, other neo plazas and older people you have to worry about lymphoma um drugs including the checkpoint inhibitor drugs that are increasingly used. Um And then obviously a lot of the inflammatory autoimmune conditions, Children's lupus, also diabetes, thyroid disease circling vasculitis, Histiocytosis, G. four disease and other auto needs. More recently there have been discoveries of a perennial plastic syndrome which can cause hypothesis itis and it's due to um uh antibodies that are provoked by expression in time. Omagh's of the pituitary antibodies and those patients will present with hypothesis itis as their parents plastic syndrome. Um So the presentation for hypothesis itis um is uh you know they present with symptoms and signs of pituitary deficiency. 50% will have headache. Um And of course if they have an enlarging mass they'll they can have visual symptoms visual field uh cuts from from the mass effect. Um The M. R. I will show a thickened pituitary stock, the gland is enlarged like like what we saw. Uh Usually they have a homogeneous and intense contrast uptake which really wasn't described in our case. Um And because it's an acute situation that the seller is not usually eroded, there can be a dural tail from neural inflammation and then um you know, there there's there's this wonderful paper and I and I reproduce it here for you guys that goes over the diagnostic algorithm and treatment for hypothesis itis. Um um you know, it's a it's it's it's an involved thing that we do not have time to go over here. But essentially uh glucocorticoids are are used to treat um uh the cases of hypothesis itis and he was already on the sally mandrell. So uh so alright, you know, so this uh this article here is wonderful. Um let me leave it up. So in case anyone's interested in in in looking into that. So that's all I have is uh if if anyone has any questions. No. Um actually one of the first papers that I ever did when I was resident was on lymphocytic have no hypothesis and males, which is unusual because it's usually in women. This is another example of a male but very interesting algorithm here for the work up of this condition. Very detailed. Well, yeah, let's just show you so fantastic case. I don't think, you know, from our ideology perspective hypothesizes would my would have made it to my differential in this case but from the few images you showed this guy had frontal atrophy for somebody this young, Yes, agreed. That's one thing that I had, that's why I included frontal temporal dementia because you know, in the initial uh you know once, once I had seen his image I was like okay he does but and he did have he was reported to have some personality issues. But I think I think those were more chronic. So um you know it's still it's still in the differential. We'll have to see the fact that he improved with the treatment with the I. V. I. G. And the Sallie mae federal maybe speaks a little bit against that. But but that still remains a possibility. We'll see. Time will tell. I mean I really didn't find any of the other exam findings that I would expect. All right, thank you. Hey Dahlia, this is kevin again, great case. And actually as you know, I was familiar with this case because I read the follow up M. R. I. I'm not even sure if I read the original M. R. I. But you know, looking back on it um it's very unusual for hypothesis because it was very focal uh and almost like well circumscribed rather than hypothesis is usually diffused has thickened stock and everything. So not only was the follow up M. R. I. Like a month later ah you know the tumor quote unquote was totally gone. But even when the patient had like their pet M. R. I. Which was, I don't know a couple of weeks after it was also gone. So whatever steroids, R. B. I. G. I mean it made a remarkable disappearance in such a short period of time. Um And again even looking back on it, it's not what I would have included hypothesizes on it. Yeah. Yeah that's why I was like okay, missing tumor. Yeah. No it's it's a fantastic case. And how is the guy doing now? Well you know what I'm having a little trouble getting him back into clinic. Uh you know, but but he's been doing okay. His follow up is going to be you know, monitoring for to see if a malignancy shows up. Um But we've been contacting him to return to clinic. I'm a little worried about him develop the hypo pituitary tourism. Uh So you know I also want him to follow up with the endocrinologist. So yeah we're working on getting him back into clinic. Thank you. Alright. Any other questions from anybody? Um If not we'll take a few minute break for people to catch up on coffee etcetera and then come back at eight am sharp. Okay so um this morning we're delighted to help dr Diego Torres who is Professor Vice Chair for Education Department of neurologic Sciences at University of Nebraska Medical Center. He's the chief of movement disorders. The program director for the movement disorders fellowship and the director of clinical neurology education. And so um I'm going to just get dr Torres set up here and then we will start. Alright. Do you see that full screen then the slide full screen? If somebody could reply back verbally, that would help be helpful. They're actually seeing the present. Okay look there, that's not Okay. Thank you very much. Here's dr Torres. All right, thank you so much. Dr uh It's a pleasure to be here. An honor to be here to talk about. Uh huh. Topic that I'm extremely passionate about. So we're gonna we're gonna talk about Parkinson's disease and you know, what's what's the state of the art care? What do we mean by jeez if my mother had Parkinson's disease, you know, what do we have to do to get the best possible care set up for you know, for my mom, for my dad for you know, my family member, that's that's the way I think all of us want to be thinking about caring for for you know, each of the diseases that we that we um you know care for. So these are my disclosures. I have multiple um consulting uh relationships and research the educational grants for from multiple companies. So, movement disorders in the general community are highly prevalent prevalent and But they are substantially under recognized and therefore under treated. The prevalence for only the common categories of movement disorders is 28% in the general population so that they are extremely common. But as as you can see uh You know, if that number shocked you of 28% prevalence, it means that you agree with me that they are extremely under recognized and therefore what that means is that our patients are suffering without any need? Uh and our patients deserve the best possible care. Movement disorders are the third worst neurological disease in terms of quality of life after paying and spinal disease. Um so this is this is critical. We need to, we need to make the diagnosis so that we can help them. Um and that reminds me, you know, to we we are here to cure sometimes to relieve often and to comfort always. So help me think today, how do we cure Parkinson's disease? How can we best care for patients with Parkinson's disease? Um and there are many considerations in health care when we're when we're thinking about those questions? You know, it all starts with the patient and the caregiver and the disease, but then we have to think about the health care system and research and and medical and education, medical and patient education and costs and payers and you know, many, many factors. So today I'm going to tackle, I'm going to try to tackle some of these questions. So the first one is, what do we really mean by Parkinson's disease today? Right, because that concept has been changing over time. The next is how do we diagnose Parkinson's disease at this point? And what do we why do we say that Parkinson's care must be comprehensive and multidisciplinary. Uh what are the most common innovations in Parkinson's disease care. And lastly, what can we do right here right now to enhance the Parkinson's patient experience? Um So what do we really mean by Parkinson's disease? Well, this is the way, you know, people used to think about Parkinson's disease, and this is the way I think now about Parkinson's disease. You know, this is a boxing class for our Parkinson patients. You know, this is what we get now, a bunch of people exercising, being active, trying to do the best they can to improve their disease. Uh So, you know that the face of Parkinson's has changed dramatically. We used to think of very old people. Parkinson's disease affects patients that are extremely young as well. So we need to think about it in a different way as well. Parkinson's disease is extremely common. 1 to 2% of the population is a neurodegenerative disease that is widespread and and produces a myriad of modern and non motor symptoms. And, you know, it has multiple diagnostic criteria. But it all starts with the presence of braddock Indonesia plus either resting tremor or rigidity and radical amnesia, which is basically slowness of movement um is is required for, you know, for the presence of this disease? Um dr louis described uh you know, the what we now call the Lewy bodies, which, you know, are these cytoplasmic inclusions in Parkinson's disease, which primary structural component is an abnormal protein called alpha sina claims and the accumulation of this alpha sinew plane inside the Lewy bodies uh is uh seems to be essential uh in uh in the disease. And as you can see here this round uh cytoplasmic inclusion is the Lewy body in the substantia nigra, which is typical of Parkinson's disease. And when that occurs in the cerebral cortex, then we tend to have Lewy body dementia as uh as well. So this louis body diseases, that distribution started to be described how, how that distribution would happen in 1984. And uh and then brag and brag more recently in 2000 and two describe this ascending distribution of of the alpha sino plane and the Lewy bodies in Parkinson's meaning that, you know, that the disease is spreading from a particular location into the rest of the brain and implications for our path of physiological understanding of the disease um can be drawn from this. For sure. The common motor symptoms in Parkinson's disease are a resting tremor, braddock, amnesia and rigidity and discuss. But then later on, the patients can develop balance issues and false gait disturbance, including freezing and motor fluctuations. And I truly believe that one of the biggest problems in Parkinson's disease are the non motor symptoms and they are frequently unrecognized, not only by physicians, but also by the patients because they don't think that the non motor symptoms are, you know related to the disease and therefore they are untreated. And these are major determinants in the quality of life, you know, from the disease. So what are these non motor symptoms in in in Parkinson's disease? Well, you know, the first is the neuropsychological features uh some patients can develop dementia, some can develop psychosis, meaning hallucinations, which tends to be medication induced is a side effect, usually from the from the drugs that we use, depression, anxiety, uh impulse control disorder, which is a common side effect from the drugs that we use in Parkinson's disease. And then sleep disorders are common in parkinsonism, insomnia, restless leg syndrome, Rem sleep behavior disorder and excessive sleepiness during the day. This oughta know mia is almost uh you know, universal in patients with Parkinson's disease. Constipation, disfigured, drooling, bladder dysfunction, Ortho, static hypertension and sexual dysfunction. And as you can see, all of these things can induce extreme changes in the quality of life of the patients. So, and then lastly, our sensory issues that we need to be considering as well, what causes Parkinson's disease. Well, you know, at this point, we're thinking that Parkinson's, it's not just the one disease is multiple diseases, you know, it has um has been associated with multiple gene mutations? Um over 15 genes have been associated with Parkinson's, I think more than 20 genes right now and then environmental factors, pesticides, solvents, occupational exposures, um rural exposure now, urban exposure. So go figure that one um If you have more than uh 14 years of education that increases your risk of having Parkinson's disease. So, you know, multiple environmental factors, drinking more milk in comparison with the general population? I mean, it's just so many factors that have been linked with this disease, none of them truly causal, just an association with the disease. Um Now G. B. A. Uh gene mutations, the the the gene that encodes for glucose cerebro SIDS and the one that has been associated with those mutations are the most common genetic risk factor for Parkinson's disease and both by Allele IQ. And single mutation mutations have been associated with the disease. And as you can see in this slide, um it also has been associated with Lewy body dementia, rem sleep behavior disorders uh and uh you know, can be seen in many different uh communities and ancestries. Um Probably one of the most important messages that I can share with one of my patients is the physical activity prolongs the life in Parkinson's disease. I truly believe this. I believe that exercise can make a huge difference in their quality of life long term. And you know, this this study from Korea In more than 10,000 patients show that physical activity, regardless of intensity, is associated with reduced all cause mortality among patients with Parkinson's disease. So this is an important thing that we need to continue to remind all of our patients about? Um So in summary for this question, what do we really mean by Parkinson's disease. This is a common neurodegenerative disease, uh maybe the second most common uh neurodegenerative disorder. Both motor and non motor symptoms are affecting quality of life and therefore we need to address both. Um It is associated with accumulation of alpha sinew playing in Lewy bodies and it's a syndrome with many diseases with genetic and environmental risk factor. The next question that we wanted to think about today is how do we diagnose Parkinson's today? And and I think about these three questions. First, does the patient have parkinsonism? Which type of parkinsonism? And is this genetic or not? So and and proper management and quality of life of the patient depends on these questions. So we must address them with our patients for sure. So, you know, we have said tremor rigidity and slowness, braddock, amnesia. Make up the diagnosis of parkinsonism. And then, you know, parkinsonism can be either primary or secondary when you have primary. Then we divide that between idiopathic Parkinson's disease and the Parkinson's plus syndromes and idiopathic Parkinson's disease, as we said, has many genetics, types and variations. But Parkinson's plus syndromes are multiple different diseases, including multiple systems, atrophy, M. S. A PSP progressive, super nuclear policy, cortical, basal ganglia, nick degeneration and many others. And then you have the secondary parkinsonism vascular drug induced infections, trauma. When the patient comes to your office, you don't know which of all of these they have? Right, they come with symptoms that look like Parkinson's disease. So our first job is to this is to figure out which of these the patient is actually having because all parkinsonism patients must be assessed for curable or treatable causes of parkinsonism including you know some lab work and imaging testing to reasonably rule out treatable conditions. So all Parkinson patients and all parkinsonism patients share these three features of radical amnesia, rigidity and about 60% of them have resting tremor. But Parkinson's plus syndromes then have something else that's why we call them plus how clever. Um And we must differentiate them because the life expectancy for Parkinson's is basically normal. Um But for Parkinson's plus the the prognosis is is different is much much poorer. So we must know they don't respond to oral treatments or the brain stimulation surgeries. So we we must make that differentiation so that the patients can plan and we can work with them accordingly. Um So if you have a taxi opera modern neuroscience severe disorder. No mia. Then we start thinking about another type of disease like multiple systems atrophy and that is an alpha sino klein opened the just like Parkinson's but the accumulation of the alpha sinew plane is in glia rather than in neuron. And if you have abnormal extra ocular movements then we think about progressive super nuclear policy. And if you have a hemi syndrome of hemi dystonia and a proxy a and other symptoms then we think of cortical basal ganglia, nick degeneration and other diseases. And these two are how or parties accumulation of tau another protein and imaging can help us dramatically. And we were learning a lot about the imaging of these diseases and you can see here how in PSP we have what we call the penguins sign or hummingbird side. Uh we have the mickey mouse ears in the midbrain uh in cortical basal syndrome, we have significant asymmetry between the two hemispheres and in M. S. A. We have multiple signs including um the lateral linear T. To hyper intensity in the attainment due to um the atrophy there and the hot cross bond sign and uh pointing atrophies, Arabella, atrophy and many more. Specked dopamine transporter. Uh imaging is also very useful in patients with Parkinson's disease and Parkinson's and disorders because it helps us differentiate between the generative Parkinson ian syndromes and the nun the generative causes and this is sort of the interpretation of the results of the dat scan. So you know if it's positive we're thinking about Parkinson's disease and any of these the degenerative diseases that cause strata, negro degeneration but if it's negative then we're thinking more of document responsive Estonians and vascular parkinsonism medication induced parkinsonism which is one of the most important uses of this particular technology, essential tremor functional movement disorders and many other conditions should patients with Parkinson's disease. Get a biopsy. Well the short answer to that is many patients will need to consider it now, but not a biopsy where you're thinking this is this is different. We're not trying we're not trying to get a biopsy in the brain anymore. Um although that's where alpha sinew plane is going to be right, the red dots here is alpha sinew plane inside the neurons. But remember that we also have neurons in other places in the body. In fact, we have more neurons in the abdomen than we have in the brain. So accumulation of abnormal phosphor related alpha Sino claim is associated with five different disorders. Parkinson's disease, dementia, Lewy bodies, multiple systems, atrophy, pure or economic failure and rem sleep behavior disorder. So if we find this alpha signed mclean accumulated in, you know somewhere, then we need to be thinking about these conditions. So, the search for for ways of confirming this, this presence of phosphor related alpha sign a plane has been ongoing for a long time. And you know, we have used multiple options like brain imaging, including functional imaging is not specific. The use of of CSF, you know from, from a lumbar puncture and measuring false seeing is not sensitive colonic and sub mandibular uh okay, okay, colonic or sub mandibular gland biopsy um is harder to do than skin for sure. And this is a true could biopsy of the sub mandibular gland that was uh has been described because you can find alpha sinew claim there as well. So, uh these are options that we have currently on trying to find alpha sino claim and helping us know if the parkinsonism that the patient has is caused by an alpha site nuclear no empathy or not. Um But now we have basically a very very simple option uh and it's the the scheme biopsies uh which allow the visualization of the nerves and these nerves have been demonstrated to contain phosphor related scene Uh in Parkinson patients and accurately diagnosed Parkinson's disease with more than 95% sensitivity and a specificity higher than 99%. So these are this is a great option that has been around for a while and we need to be expanding its use because it's so simple to do. It helps us answer a very important question. Is there alpha sinew plane in in the nerves of this of this patient? And then uh more research is being done that is helping us understand if you know differentiate between Parkinson's disease and other P. D. Plus syndromes. So in summary for this question of how do we diagnose Parkinson's disease? You know we used to just examine the patient and say you've got Parkinson's now it's different. You know we we must rule out treatable conditions. Parkinson's disease patients need to be differentiated from P. D. Plus syndromes. And we continue to do that through a comprehensive history taking and a thorough neurological exam. Yes. But we also have to do lab work on all patients and an M. R. I. Of the brain and spying in most patients consider at that scan in some patients. And then the skin biopsy um skin nerve biopsy is going to have a growing role in the future. Next question that we wanted to talk about is why do we say that Parkinson's care must be comprehensive and multidisciplinary? Well, you know, the the short answer to that is is basically well because Parkinson's care has become very complex and and because Parkinson's disease is a multi systems disease, so, you know, a single person cannot care for Parkinson's anymore. Um You know, the management team uh starts off worse with the patient in the center and and we have a lot of people occupational therapy, speech therapy, uh physical therapy, the family and the caregivers the community. Um and and the physicians and and then you know the physicians Who are leading the team, um you know, we only have about four or 5000 movement disorder specialists in the United States. So we cannot lead, we cannot care for all patients with Parkinson's disease. So the care for Parkinson's is handled by neurologists by primary care physicians, internal medicine. Um and that is how you know how things are done. Currently, levodopa is the most effective treatment in Parkinson's disease. Hands down. But we have many, many more options. And I'm going to just show you a few in historical order of the medications that have been developed over the year and over the years and each year there are there are a few more you know each of these medications has a different mechanism of action, has a different side effect profile, has a different place in the treatment of patients with Parkinson's disease. And you know it is critical to know which of these medications I can use for my patients for the particular symptom that the patient is having because you know each of them each of these drugs um is not for every patient. Every patient cannot get all of the drugs at the same time. So understanding okay what's you know all of them is extremely complex learning about them having enough experience for you know with each of them um is um is hard. It's a lot um These medications don't come without without a price. They have side effects. The most common one is this garnishes moral fluctuations and other complications like loss of appetite and difficulty sleeping. Or too much sleepiness like headedness upon standing including cinco p loss of control issues. Um O. C. D. Like behaviors, hallucinations as I discussed and somnolence. So it's not easy. Um A lot of people ask me Diego give me the short answer. What you know what what do you do, what's the what's the fix? And I wish I could I could give you a short answer. Um I'm gonna give you some general thoughts uh and and and it is a generalization that does not do justice to the complexity of the disease for sure. But you know, I'm going to start with some general principles of of what do we do with the presence of of when the patients are not feeling well continuously. The first is to always consider and treat the non modern symptoms. That's important as as we discussed because they drive quality of life. The second is to always treat the patients must bother some symptoms, not yours. You might see the patients shaking like a leaf, but that might not be the problem that that they that that is driving their, you know, their quality of life for them, it might be a different problem like walking difficulty. So you must address the problem that they are most bothered. Um uh about always do general management of Parkinson's before trying pharmacological treatment for each of the problems that you're dealing with. So exercise, physical, occupational and speech therapy, skin care. Remember that patients with Parkinson's disease are at a much higher risk for melanoma. Uh so, you know, the patients will not die from Parkinson's but they can die from melanoma. So you must make sure that this is taken care of and a lot of people don't know about this association and then think about social determinants of health for sure in the presence of always consider to do on demand therapies and maintenance treatment changes because that is the best uh course of action and introduced the concept of surgery early, the patients need to hear about options uh because it's not you making the decision is them. So they need to be educated properly about what their options are. Um What are the first drugs to start? This is another question that I'm I'm always asked. And again, you know, this is a horrible oversimplification. But Uh if you're older than 60 I would I would think Levodopa is the first choice. If you're younger than 60 and strong, Mild symptoms, wrestling and or a dopamine agonists are options. If you're younger than 60 and strong and you have moderate symptoms, then leave it up as a choice and dopamine agonists as well. But if you are young and strong and you have severe symptoms, then levodopa is the first drug to start, no matter what, no matter how young you are. I have patients who are 20 and are using Levodopa. Um I think that we have been worrying too much about the early use of levodopa for many years and I don't believe that that is grant in the presence of off. If the off time between doses is more than an hour uh then um I usually add one more dose of levodopa for example going from T I. D. Two Q. I. D. Or exchange the patient. Uh you know, from cinema carbon levodopa to right harry. Uh If the off time between doses is less than than one hour then we can add any of these options and tack up on recycling. Safina might or pick up on east road in a field and then as needed options that on demand treatment um if symptoms are mild, I usually failure in bridge, if symptoms are beyond mild, I usually failure up of morphine sublingual, so what do we mean by this on and off? When the medications are working, we call it on and when the medications are not working, we call it off, right, when the symptoms are back, we call it off. So at the beginning of the disease, the patients take their medications and their own all the time. But as the disease progresses then they start developing these off periods in between doses and sometimes they develop the the, you know, periods of side effects. Uh this guy knishes as well um at the peak doses and some other times. So basically they are either on off or over with their, you know, with their disease and their treatments Of episodes are highly prevalent. Approximately 50% of people with Parkinson's disease develop off as early as 2-5 years in the majority By 10 years. In a survey by the Michael J. Fox Foundation with 3000 patients, 92% of patients on that survey had at least one of episode per day, 20% experience four or more off episodes per day and 64% of patients spent two or more hours in the off state. Now this I think is a calamity. I mean think about this for a second. We have more than 30 drugs, we have, you know, surgeries, we have so many options available in the market. And yet our patients are undertreated suffering from the disease. Um and the question is, what are we doing to fix all of these symptoms? Um so how, how can we detect? Excuse me? How can we detect these off states better? Right. I mean, clearly we need to, we must so how can we detect this off states? Well, we can use the patient report during the visit. We can, you know, have the physicians detect these off states during the visit. We can use surveys and scales. We can use patient diaries. We can use wearable devices. Um Let me tell you this with the current environment that physicians live in, where we are being asked to see a patient in 15 minutes. Uh I'm not sure how we can do all of the things that we must do for a patient with, you know, with a complex disease like this. Um, so let's think about our options. The patient reporting is not accurate. Uh that is clear and well known physician detection is definitely not perfect. You know, about 50 other scales are not as good either. So, new wearable devices are more accurate on detecting off. Um and and therefore I really prefer this choice. So continuous objective measurement devices are having such a slow practice inc and I don't understand why. Well I do but we must do we must change these. Um They are more sensitive than patients and physicians. Um and uh you know they are more accurate at measuring tremor and a cagney Jha fluctuations on a on a on this paper that we did would just publish um evaluating the morning morning braddock amnesia in patients with Parkinson's disease. In the United States, we studied more than 3000 patients using the P. K. G. The personal kinetic graph which is um you know uh a um device that is able to measure uh most Parkinson's signs and symptoms and it's just like a little watch that the patients carry day in and day out Using that device in in more than 3000 patients we detected morning braddock amnesia in 85% of us individuals. And after this is this is the worst. The worst piece of the of the of the data is that after the first levodopa does so after they treated their disease in the morning, Still 64% of them had continued morning radical amnesia. Many didn't even know because they had taken their medication, they had started their day. They they had not even realized that the medication was not working fully or properly. So this is tragic in my eyes. Um Parkinson's disease also carries a great risk for another movement disorder called dystonia. Dystonia is excessive muscle contraction that can cause tremors and can cause abnormal postures and it can be extremely disabling to our patients with Parkinson's disease. And what causes dystonia in Parkinson's is the disease itself, but it's also uh it can also be a medication side effect. Um and we have multiple treatment options for dystonia is extremely treatable conditions, physical therapy and occupational therapy, oral medications. Uh and there are many options. Many of the drugs that we use for Parkinson's can help with some of the dystonia symptoms unless the Estonia is medication induced. Bottom line on toxic injections are extremely helpful for Estonia and are the mainstay of the treatment. And then surgery can be very beneficial. And I was just uh speaking earlier today with Doctor speech about how you know, we do so much for the estonian patients with deep brain stimulation in particular in Parkinson's disease. Popular non toxic injections for patients with referees, possum can be lifesaving. So Blefary possum is is a Dystonia of the eyes of the orbit carries ocular and what the patients get is that they cannot open their eyes and they're trying but they cannot and you can see on the right side, the patient is really trying to open their eyes on week one and two after Botox injections and then on the right side of the screen. You see weeks six and seven after the medication actually started to work. So the this can save the patients from being functionally blind. Which is, you know, a dramatic improvement of their quality of life. Patients with Parkinson's disease can have also severe Antero calls a neck Estonia. Look at these extreme postures. This is an extreme case in particular. But you can help the patients with bottom line on toxic injections. And this is the after injection picture. You also can have camp decor mia which is the bending of the entire spine. So here notice that the neck is actually aligned properly with the spine. So there is no anti oracles. There is no change in the neck. But what you see is a bending of the spine. I'm sure that ah you're seeing how dramatic this can, how dramatically this can affect the patient's quality of life. But with injections with botulinum toxin, you can actually improve these easily. Mhm. Autonomic dysfunction in Parkinson's disease. Yes. Ah widespread, extremely significant. It drives quality of life uh And it's a very, very important situation to get ahold of um It affects the cardiovascular system causing Ortho static hypertension, gastrointestinal disturbances, urinary impairment, sexual dysfunction and sweating. So we must address each of these problems. Uh If we hope to help the patient's quality of life in neurogenesis Ortho static hypertension. Which is this change in the blood pressure upon changes on posture um is present in about 30 to 40% of people with Parkinson's disease. And it can be made worse by the use of the medications to fix Parkinson's. So imagine this you have this which is caused by the disease and the drugs that we use to fix the disease make it worse. Um There are many symptoms of this condition and some of the patients don't present with just the lightheadedness. They can present with cognitive impairment. They can present with changes in their gait. They can present with falling, they can present with many symptoms and uh it is terribly under recognized and therefore undertreated. The standard of care is early detection, recognition of the uncommon signs of neurogenesis, Ortho static hypertension. The use of autonomic lab testing is key for the diagnosis and of course the use of appropriate medications. But you know we cannot fix it if we cannot diagnose it. So this is why we must include this multidisciplinary team to be able to help diagnose this condition. So I hope I have been able to answer this particular question as to why we must include a multidisciplinary comprehensive uh team so that we can care for this extremely complex disease with new diagnostics, many innovative devices, many new drugs, specialty procedures and surgeries and I'm you know for a disease that is multi system with this autonomy, a psychiatric gastrointestinal genital urinary symptoms we wanted to talk about then what are the most important innovations in P. D. Care and uh you know there are many I really was fighting to decide okay what do I include here. And uh you know I'm I'm I'm in general a very optimistic guy. I I'm always uh staying on the bright side and there are many many bright ideas about this condition. So let's talk about some of them. One uh you know is the recognition that carbon levodopa absorption is extremely variable because of the presence of gastro paris's. So the one of the G. I. Symptoms from this aura no mia is that the stomach doesn't move the castro paralysis. And here in this picture you can see during endoscopy a peel of cinema sitting in the stomach after an hour and a half of the patient taking the drug. So but the pill is still sitting in the stomach. Cinema is not absorbed in the stomach. It has to be absorbed in the in the small bowel. So if if the drug doesn't pass the stomach you're not getting the benefit. And and in here in the on the right side you can see the oral carbon levodopa absorption in a number of pd patients. Each of these lines is a P. D. Patient. And you can see that for example this patient in blue had an immediate absorption within you know 10 minutes and a peak within 15 minutes. But this particular patient in yellow for example started to have absorption you know and peaking at about 60 minutes. And this patient here in purple Didn't have any absorption whatsoever for 90 minutes. And then all of a sudden started to have absorption and the peak was at 120 minutes. The variability between patients is incredible. And the variability inside the same patient is also extremely high. So imagine if you cannot. The most important treatment for Parkinson's uh is levodopa and most of the drugs that we give our given orally. But if you as a patient cannot rely on the onset of this treatment, how, you know much can that affect your quality of life, your planning of your day? Right. It's like, well I take it now, it should be starting to work in the next whatever, but then it doesn't. Right. So so this drives quality of life dramatically. So we must address that with our patients. And that's why I believe that we must empower them with the use of on demand therapy options. And we have now three options. We have levodopa inhaled in the form of Enbridge. A and we also have sublingual um apple morphine and I have consulted for both of these companies And we have a third option which is Apple morphine uh injectables, you know, which has been around for many years. These drugs are powerful. They're effective. They start working within 10 to 15 minutes With a peak benefit within 30-60 minutes. They can use them up to five times a day and they bypass the G. I. track. So it can be extremely helpful to set to salvage those patients who are in the off state so that they don't have to suffer those off states. So this is important to incorporate another great innovation. I think in the in the Parkinson scare is estrogen. A field feeling is the first uh Dennis ng a two, a receptor antagonist that has been used in Parkinson's disease. Why is this important? And then using a two receptor stimulation in the indirect pathway reduces the motor activity. It works when you stimulate these receptors, it works like a brake pedal on your movements and then dopamine. That's the opposite right? So you stimulate dopamine receptors actually uh increases motor activity. It works like the accelerator pedal. But in Parkinson's disease, the A two A receptors are increased while the dopamine receptors are decreased. So basically you are not only not pushing on the accelerator but you are also pushing on the brakes. So these two issues are making the patients move slower. Um So the use of estrada feeling can has been proven to improve symptoms in Parkinson's disease. And and the good news that you know that the importance of this is that this is a drug that is not addressing the top um Inside is finally addressing something that we have never been able to address before, which is the uh Dennis inside in Parkinson's care is given once daily and that it has some side effects as I have written there but is in general well tolerated. Um the next advancement for sure is P. K. G. Uh And the the continuous objective monitoring. This is one of the eight pages uh of data that I get from each patient. And I'm gonna show you an example of those failure. This patient was telling me doc I get so sleepy after after my lunch. And I said well me too. Uh But he said no but it's it's just it's weird but it's too much. And I said okay let's look at it. And here in the bottom you can see in black each day you can see tremor. Uh The red lines are the doses of the medication. Okay so there is tremor around the doses tremor around the doses and then when the when the medication kicks in there is no tremor that's great. But then after two p.m. Look at what happens there is a lot of tremor after two p.m. So it's like huh That's interesting. This does doesn't seem to be working. Let's look at the at the charts here is the measurement of braddock amnesia and as you going up means is less radical initial here. So you take your dose the radical goes away and then comes back. You take your dose radical goes away and then comes back And you take the dose at two PM and radical in Asia. Oh nothing happens to Braddock in Asia. So with this with P. K. E. I was able to prove that the patient was having a dose failure at two p.m. You know uh some days and I was able to address the patient's symptoms so it can be extremely helpful. Um And then with the motor fluctuations in Parkinson's disease, which are many different subtypes, we need to consider advanced options including surgery when you have you know, motor fluctuations or dyskinesia is for sure. And surgeries continue to be one of the most important innovations that we have. They have they help you stay on longer with less disk finishes and less medication. Side effects. Um So what are the surgical options we have to open pump which delivers levodopa continuously beyond the stomach into the uh and by doing that, you know, into the small bowel. Then we're avoiding the whole issue of the gastro paris's which is great. It's a continuous infusion and it helps many of our patients and uh we have seen a reduction of off time. That is very significant with the use of this medication and the side effect profile is very acceptable. Most of the side effects as you can see in this light occur during the first week of of the insertion and after that the side effect uh numbers um go down significantly. And another important innovation is deeper in stimulation as you heard from uh dr spore before. Uh is a great choice for Parkinson's disease. And we have an extensive evaluation protocol at our center that starts with the movement disorder evaluation and a multidisciplinary team discussion including neuropsychologist uh neurosurgery and uh and the movement team together thinking about uh the candidacy for each of the patients and after that they come back for programming. But the risks of the procedure are listed here uh you know, stroke bleeding basically and infections are important to consider. Uh and we discussed that with the patients including death, but the benefits outweigh the risk for many of the patients. And as you can see here, this patient is extremely happy in the are having absolutely no tremor. I'm sure you can see no tremor here right now. Right alright. Um and then we just talked about foss, what's the fuss about uh foss in Parkinson's disease? Well, it's now in additional but its regional um we have to think about single side implications. We don't have long term data. There is a relative high complication rate in comparison with what we get from dBS currently, but it definitely has a place in the care of Parkinson's patients. And we're excited to have that new technology. So with so many treatment options, patients should not have to adapt to the disease treatments and physicians must adapt to the patient's needs to maintain dignity, lifestyle and quality of life intact. Uh you know, we have so many options uh you know, for example, uh an important innovation now is the detection for the cardiac disorder No mia in Parkinson's disease. Using continuous noninvasive arterial pressure monitors which are you know are able to pick things up when the autonomic lab fails to do it. So I think that the you know the future is bright in Parkinson's care. We have so much so many innovations and so much help. The next question that we were going to review is what can we do right here right now to enhance the patient experience the Parkinson's disease experience. And I I asked a question earlier during my visit um which is you know how many unique patients about this health Has inside the system. And and that's the number that I was given 700,000 people. Um uh If you if we use this number to calculate the expected minimum expected number of parking Sony in patients, You know the minimum expected number would be 14,500 patients with parkinsonism, 7000 or so of Parkinson's disease and 7000 or so of p. d. plus syndromes. So if we calculate the number of visits that this is that this you know would need to provide proper care for these patients including uh Estonia visits, deep brain stimulation visits and regular Parkinson's care. We're talking about more than 16 100 visits per week to care for the patients that are already inside our system with Parkinson's disease. Um So I think that the first thing that we need to do is to recognize that we are doing a poor job inside every system in the United States. Uh you know, for the care that we provide for Parkinson's. We we must recognize that we're failing so that we can do better and we can we can do what we must do what we what we did to win into medicine to do which is to help our patients. So I'm going to finish uh my chat uh to summarize some of the thoughts. Um We must provide a patient center. Comprehensive multidisciplinary um care in Parkinson's disease, neuropsychology, physical therapy, occupational speech nutrition is so important. We did a study collaboration with Harvard Where we found 35% of our patients have nutritional deficiencies, remember G. I. Problems. We must provide the collaboration of many specialists in Parkinson's disease. Um you know, neurologist, movement disorder experts, neurosurgeons, psychiatrists, primary care physicians, radiologists, neurologists. We need advanced imaging M. R. I. That scans cardiac andra energetic imaging. We need an autonomic lab, continual objective monitoring has to be part of what we do. Alpha sino, clean skin nerve biopsy. Deep brain stimulation program. All targets all systems are key for comprehensive Parkinson scare you up. A pump program has a place uh you know, so that we can provide the best care for our patients. Focus ultrasound procedure program, genetic counseling For the 15% of patients who have a genetic basis for this disease patient and caregiver education and advocacy is key and I'm extremely passionate about that local training in Parkinson's disease for the next generation of healthcare workers. We movement disorder experts cannot do it all for sure. We must train everybody in detecting and helping us with this disease. And then for sure clinical trial research availability has to be expanded so that our patients can have access to that and also we can enhance our future and find a cure for this disease. And with that, I'm going to finish and I'm open for questions. Thank you so much for inviting me to speak. It has been a real honor. Thank you. Any questions. Any questions? Yeah. Hi dr Torres. It's Ron Tolchin. Um, great lecture. Great talk appreciated all your insight into this very uh significant disease. Um, I wanted to ask you brought up a slide earlier on the boxing program. You have and and I do feel as a psychiatrist that sending people to um uh, general physical therapy is not always the answer for these patients. You need a more comprehensive program. The question is, there are not as many of them, you know around. They become costly. And I wanted to see if you've been able to uh, you know, navigate the system in such a way that these patients can have several hours, several days a week of therapy services and get it covered in some way. Yeah. Uh, well, that's that's a great, that's a great um you know, comment. We must enhance physical activity on every patient and and it's physical activity. Right? And there are studies on yoga that are studies on Pilates. There are studies on on dancing uh you know tango that our studies on salsa that are, you know, all of the studies are showing that the the more active the patients are the better their quality of life. So uh there is nothing magical about it. We must enhance their physical activity overall. Um and um sometimes uh you know what they need really is is a more guided approach and there are so many options in the community that are even free for the patients. So, understanding those options and providing advocacy for the patients is really key. The question is there no way to thank you. Yes. Hi, this is Kevin Abrams know radiology outstanding. Talk. The question I have for you is I wasn't aware about this biopsy um technique that's so sensitive and specific. So I guess the question is why is it not used more? I mean we do a lot of dat scans which a lot of times can't even get approved by insurance. It's not as you know, specific. Uh It sounds like the biopsy sounds even better. Is there a reason it's not putting done more. Yeah, that that's a please answer the question for me. I would love to know why I don't understand. There is significant research about it. Of course it's a new thing and every change, you know, find some resistance. Medicare covers it. But many people don't even know that it exists, right? So until we don't expand its use um it will continue to be. So I I believe that we just have to fight the fight and you know, continue to expand education and knowledge about it. So the we can provide you know, the best possible care well which physicians are doing the biopsy. So if you want to refer somebody who are you going to refer them to to do those biopsies? Yeah. So anybody you know who this is? A punch biopsy? A skin punch biopsy. So uh it is best to it has to be shipped immediately back to the lab that is going to be reviewing it. So we so we do it in in the movement disorder clinic. Uh and uh you know in neurology, usually the the experts that do skin biopsy are the neuro muscular experts because they do a lot of small fiber diseases or the movement disorder experts who are trained in skin biopsy. So at our center I have nine movement disorder experts and all of them are you know in the process of being certified to do the skin biopsies. So currently I'm the one that is doing them. Great. Thank you. Excellent. This is this is a fantastic presentation as well. I agree with um the rest of my colleagues. It was great having you and meeting you yesterday as well and regarding the skin biopsy. I agree. I mean this this is you know, this would be very helpful if we had more access to it. You would use the interpretation of the skin biopsy very similar to interpretation of that scan, meaning he wouldn't tell you or differentiate between any Parkinson's plus syndrome, but just generally Parkinson's disease or syndrome versus some mimics. Would that be how you would be looking at the interpretation of those biopsy results? So, you see a patient. Thank you Felipe you see a patient with parkinsonism. Right? So the question is which type if you find alpha Sino claim? Now, you know in the biopsy now, you know that it is an alpha sinew clean apathy. So now you have shrank the differential diagnosis uh to just Alpha Sino clean open these and you have only five Right out of those five that are only, you know, a handful. Right? So these are really very few. But there are only three that cause parkinsonism. So, you know, you have been able to really reduce your options by by doing that. So nothing is perfect. But the specificity in the right patient was extremely high in some of the studies. So it's just one more tool in our, you know, in our way to the diagnosis of Parkinson's, wow, yes, thank you for that question. Great question. And I see a lot of questions in the chat as well. Um Let's see but please if there are more questions uh Go ahead. Thank you so much. Dr Torres. This is Justin spore. Um That was awesome. Fantastic talk very thorough. My question is the do opa um who does those? And are the patients, how open are they to that when you mentioned that procedure to them? Yeah. Great question. Thanks. Justin the uh procedure is done by uh train G. I. Specialist or interventional radiologist. And uh it is patients have significant resistance to that particular procedure because they have to now have a tube hanging out of their abdomen continuously and and deal every morning with the exchange of the cassettes to you know, be able to get the medication. There are a number of patients who cannot qualify that they just cannot get deep brain stimulation surgery and they're having significant motor fluctuations. Uh and you know, they definitely will consider do opa. Um And then there are patients who are very scared of brain surgery and they would prefer for sure that route. Now with the use of uh you know ultrasound. Uh the use of do up is probably going to go down even further. But that's another option. I think we're running out of time, I'm I'm being told so let let me have the boss back here with you. Well thank you dr Torres. That was a very comprehensive discussion about the current status of treatment of Parkinson's. I think we'd all agree. Really. Thank dr Torres for coming. He's going off to a national meeting to present again on a slightly different topic today, but we thank him for making the trip. Thank you and have a good day, everybody and good weekend.
