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The Glymphatic System, Glaucoma, and Outer Space

Brad Emde OD

Description

OBJECTIVES 1. Give an overview of the glymphatic system in the brain—the relatively recent findings of CSF (cerebral spinal fluid) exchange which occurs during sleep. 2. Explore how sleep deprivation can contribute to neurodegenerative disease such as Alzheimer’s, Parkinson’s, dementia, and possibly glaucoma. 3. Examine the recent theories of why astronauts are losing their vision during long-term space flight. 4. Show how the knowledge of the above topics can affect our medical decision making process as we treat glaucoma on a daily basis.

Presenter

Brad Emde OD

Optometrist practicing and Owner of East View Eye Care in Greeneville, TN

Conference

Recorded

  • November 1, 2019
    4:00 PM
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The a Heavenly Father thank you for making us so wonderfully complex and your workmanship is marvelous and now Lord as we ask that your Holy Spirit come into this place in our hearts and minds we ask that you speak to us as we discover new and exciting things about your creation in our wonderfully complex bodies so that we all know how to take care of them in share this information with others so we ask for your wisdom now and we ask that you give us clarity of thought and give me clarity of thought you know my brain so I have no disclosures except for a listening audience I'll be reading several quotes on the screen written by various authors of each study and for the sake of time I will just have the references listed on each slide. So they don't go in fabric system glaucoma and outer space how in the world are these related to eye care Well let's look at our learning objectives number one we want to provide and want to provide a general overview of the goal in phatic system in the brain Number 2 I want to examine the problem of blindness in astronauts occurring with prolong stay in outer space and number 3 to explore some of the latest theories of both topics above as it relates to glaucoma and other neurodegenerative diseases such as i l s and Alzheimer's disease I love will design things I love well design cars tools medical equipment and I love well designed scientific studies. In other things and I love designing things well even if it's just a shelf in the closet for my wife I love doing it in a way where she says no that's perfect that's that's exactly right whether it's an overseas vision clinic that we might set up the dentist would teach me how to do you know where it flows just right you know I love well design things I love designing things well and I love it when I do I've designed something in somebody studies it in appreciates the design in it and I think God does too and so today we're going to study some things about our created our mind our brain and. I think we're going to be before I go on I think we're going to be spending eternity learning about the design that God has put into our bodies into his creation and David himself will be more marveled yet again. So let's proceed and see if I designed this lecture to where you can understand it. Interesting fact about the brain the blood vessels are in our brain are organized in a very different way than they are in the peripheral organs in the peripheral organs often the arteries the veins in the lymph run parallel and next to each other into the organ surrounded by fibrous tissue but in the brain the arteries in the veins are always separated they don't run in parallel together they never do that the large vessels dive directly down into the tissue and they're separate the veins and arteries are separate. The brain is well designed it floats in c.s.f. the cerebral spinal fluid and that's 99 percent water approximately in our brains weigh about 3 pounds but in water they weigh 50 grams the brains weigh 50 grams or a 10th of a pound and that prevents the brain from collapsing in on itself which is a well designed feature in also the c.s.f. protects the brain from mild traumatic injury the total volume of c.s.f. is about an 8th of a leader at any one time and we produce about a half a liter per day and so it completely turns over $3.00 to $4.00 times a day it's mostly produced in the cord plexus of the latter lateral ventricles as at approximately $20.00 to $25.00 millimeters per hour but I want you to remember this part c s f production decreases by 50 percent normally as we age. C.s.f. production decreases 50 percent as we age so let's review the lymphatic system in the lymphatic system most of the body's organs remove dead cells and other waste using the Olympic system and these vessels run alongside the blood vessels and transport out lymph the colorless fluid containing infection fighting immune cells and waste lymph is filtered through the lymph nodes and then return back into the bloodstream. So right here you can see a picture of a limp vessel in the x. in the extracellular matrix right here these proteins are are basically washed in the lymph drains that and then it gets put back into the bloodstream here and. There are 3 leaders of length that is returned into the general circulation every day and 24 grams of protein every day are our washed out of our extras their matrix and our bodies the interesting thing is is how the brain clears waste and fights infections has been a mystery and although the human brain has blood vessels there's no evidence it has a lymphatic system so here's the lymphatic system and notice the brain is void of any lymphatic system and what was known was that the cerebral spinal fluid cleanse is the brain tissue but how the fluid moves through the brain and clears the waste wasn't well understood until now scientists could only study brain tissue in animals that were already dead they thought nutrients and waste were transported through the slow process of the fusion so let's really remind ourselves of fluid mechanics here a little bit diffusion is the transfer of particles along a concentration gradient convection refers to the refers to the motion of fluid and then we have thermal and thermal convection which is driven by temperature gradients and we have but in the brain convection refers to the fluid flow driven like a river caused by a pressure gradient such as an arterial pulse or gravity. So the problem with diffusion is that it's slow so this says diffusion right here and this is convection and this is a particle and that's how far it traveled and you can see how little it traveled over the same amount of time with convection that particle can travel much much further the other nice thing about convection is that other than it's fast if you're a small particle. Like beta amyloid or if you're a larger waste particle particle like a towel then which is 10 times larger both proteins essentially move at the same speed as the fluid is moving so convection can move larger molecules just as fast as the smaller melt molecules. This is an m.r.i. of the brain and through m.r.i. eyes we know that c.s.f. is in motion all of the time and this is just simply a image taken off of Wikipedia but it's fascinating to me because that's your you can see the arterial pulse in the c.s.f. and how it's moving all the time so let's consider sleep a little bit here and we have a there's a few facts about sleep in number one sleep is helpful we all know that and we all know that we have to have sleep if we don't have sleep we eventually would die. It refreshes us as we sleep and studies have shown that the dendritic complexity within the brain decreases with sleep deprivation basically the connections in the brain are lost when we lose sleep it helps our bodies fight infections as we sleep and it calms inflammation the anti inflammatory process actually is much more efficient while we're asleep than while we're awake and we all know that if you ever take a red eye flight the reason that your eyes are red is because of the inflammation you you were supposed to sleep 8 hours to London but instead you slept 2 and so everybody's eyes are red and inflamed and that's because sleep is anti-inflammatory. Sleep also improves cognition and memory and we're more alert and less drowsy and it helps us retain the things that we learn and we could go on and on about other things about the benefits of sleep but Fact number 2 about sleep is that we do not sleep to preserve energy only a little bit of energy is saved during sleep the brain consumes nearly the same amount of energy while our sleep than while we're awake why it's because the brain is still active quite active while we're asleep so what's the brain doing during sleep that takes all this energy well they found out in August of 2012 and in a new study and I'm going to quote this from the and I each website and a new study a research team led by Dr easy doctors Jeffrey eyelift and make a Netter guard at the University of Rochester Medical Center used a method called 2 photon laser scanning microscopy to analyze the flow of serial spinal fluid in the living mouse brains this new technology allowed scientists to study the intact brain in real time they injected tracer molecules into the sub or acknowledge space in a cerebral spinal fluid cavity between the membranes that cover the brain in the spinal cord. Why did they pick mice the reason is because the Scole of a mouse is very transparent and they could literally peel back the skin of the of the mouse the skull in the photons would actually penetrate the Scole and they could look inside the mouse brains alive all the mouse was alive and they could see the distribute distribution of these tracer molecules. And you're looking at a molecule a 594 that they did they injected this into the space and within 30 minutes the entire brain had this tracer molecule in it within 30 minutes Ok. And this was not accomplished by extra lymphatic vessels in the brain remember there are no lymphatic vessels in there so this is all through the c.s.f. and what they found was that Astro sites which is this is a picture of an Astro site here with the in feet there a little in feet right here form a barrier around the blood vessels in the brain that covers 98.4 percent of all the vasculature in the brain. And when they when they cover the blood vessel it makes a space a gap around the blood vessels. And so here is the blood vessel diving down into the brain and so you're looking right here at one of these blood vessels so here come there's the artery the artery dives down deep in the brain here is here is an Astro site here's the in feet it's picturing it surrounding this blood vessel is also known as the Is that how are her Virchow work our Robin's face so the pair of asking her space basically around the blood vessel there. And there's there's these Aqua porn for channels that are these little dots right here these are water channels that literally the c.s.f. can flow into the ext in the extracellular space. And this channel so so the white gap right here would be the space that the c.s.f. can access quickly piggybacking the blood vessel into the brain in so talk about well designed inefficient you've already got the blood vessels you've already got them in the brain you're taking the blood there let's just bring the cleaning fluid on the outside of it and take that right into the brain within 30 minutes and so this picture depicts an artery and a van and now you know why God designed us with separated blood vessels in the brain because the c.s.f. comes on the outside of the artery and because this pressure is higher there's a convective book flow through the extracellular space that washes away the Sol Utes and the metabolic waste that builds up during the day and it comes over to vis bass which is surrounding the veins and it leaves clever very clever so this Gill Eagle sell the Astra sites are all cells and this is very similar to the lymphatic system what it does and so they call it the good legal lymphatic system. And that was the term that Dr neder guard coined for this process because these are not typical lymph vessels but they do the same thing that limb festivals would do that's why it's called the Glen phatic system this it would this was not taught. Before 2012 nobody knew this really existed and I shouldn't say that because there was some evidence of it but some of the researchers were that originally kind of saw this they didn't have the technology that Dr Aneta Guard has in her lab but but they were kind of made fun of and the researchers that originally found this I think it was and ninety's eighty's or ninety's actually stopped doing research because they were made fun of so much and so. She went on to. I think directed a nursing program or something acumen or she went but anyhow that's an aside so pretty amazing stuff and pretty amazing design element and because of the pressure gradient it's unidirectional and this is another picture of this so you can kind of see the artist here has the artery and there's the space the pier vascular space with the 4.4 channels these water channels and then washing out draining over on to the Venus side the waste. Interestingly. The pair vascular space in mice is a lot larger than was previously thought so they thought originally that the space was very tiny very little maybe a few microns thick but in reality what you're seeing here is that with this Dexter on tracer molecule here you can see that how wide this space actually is almost as wide as the blood vessel itself when they inserted these microspheres and each one was had a different tracer molecule you can see how thick the actual channel that the tracer molecule molecules went through another interesting feature is that it's not like a donut like this like the artist it's actually triangular shaped so where it's flowing these 2 channels right here on cross-section right there of that artery it's actually a triangular shaped space it's not a donut like they originally thought so they wondered how in the world would you transport half of the leader out of the c.s.f. I mean out of the brain of every day and Anton love oh at the University of Virginia in 2015 so this is just 4 years ago they actually did find actual lymphatic vessels in the brain and he basically says we discovered functional lymphatic vessels lining the Dural sinuses and these structures express all the hallmarks of lymphatic into feel cells and are able to carry both fluid and immune cells from the c.s.f. in are connected to the c. deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date thereby contributing to the long held concept of the absence of lymphatic vasculature in the CNS and there's risk of really of CNS lymphatic system a call for a reassessment of basic assumptions in neuro immunology and shed new light on the etiology of neuro inflammatory and neurodegenerative diseases associated with immune system dysfunction now it made sense how the brain to process so much fluid to take to the liver to be processed and they wondered well how can the brain act almost like a kidney and pump all of this fluid around while it's awake because if you're awake and you have neural activity cognition cognitive activity requires a lot of energy and pumping fluid also requires a tremendous amount of energy and how could this happen. How could both be going on at the same time in they realize that all these mice that they were checking they were all anesthetized and so they were basically asleep during all their research to date these mice were asleep and so they said well does this happen in real awake mice so this is a little video that they're showing in this on the left is an awake mouse brain and on the right is a mouse brain that's asleep and this is over a 30 minute period and you can see it's only during sleep that c.s.f. starts going in like that. So the doctor never guard she. It is the one that's kind of speaking right here and that's that was a picture of her so this extra that they found that the extracellular volume within the brain cortex increased by 60 percent when the mice were asleep or or anesthetized So in the skull you only have so much room and if the extracellular matrix increases by 60 percent that means that the brain cells would have to shrink while you're asleep to allow for this extras and that's in fact what they're suggesting and they found that beta amyloid which is important in many diseases including Alzheimer's disappeared twice as quickly wall mice were asleep than while they were awake. So the understanding of how and when the brain activates the goal in phatic system and clears waste is a critical 1st step in efforts to potentially modulator the system and make it work more efficiently cording to doctor now to govern the how in is driven and at least in part by the arterial pull 70 that we mentioned about earlier and explains why the c.s.f. enters the brain around the pulsating arteries and not the veins the when is during sleep and the same modulators that wake us up turn off the Glenn phatic system mainly norepinephrine an erection and when they're decreased. The Glen phatic system is turned on so then they wonder does body position matter during sleep and we know that body position matters for the lymphatic system. For the rest of our body and most animals sleep with their head down as do humans and you know this if you've ever taken the red eye and you're trying to sleep in your seat upright and how much you would pay for 1st class tickets just to lay down and people pay thousands just to lay down so it's very hard to sleep sitting up. In So yes the answer is yes body position does affect the glue in phatic system and if you happen to be a rat sleeping on your right side allows 30 percent more inflow of the c.s.f. into the brain to wash away the metabolic waste if you happen to be a human Yes body position affects the glow in phatic system too they found this in humans and other species as well and why they think this is because of the heart on the left side as we sleep on the right side it's able to beat more efficiently in the norepinephrine and stress levels and everything would be lower and so that would turn on Morgan phatic activity if you're pregnant a New Zealand study just in April of this year provides the strongest evidence to date that women can more than half their risk of stillbirth by going to sleep on either side during the last 3 months of pregnancy Now this is nothing new but this is interesting because they estimate that just this knowledge could save $153000.00 babies a year. So in humans so forget mice for a 2nd let's go to humans they go in phatic system in humans inspiration is the major regular regulator of human c.s.f. flow so remember how I showed you the picture of the m.r.i. zone we know that arterial pulse a to Vittie is contributing some to that but this study shows that inspiration in this There researchers say we observed significant c.s.f. flow exclusively with inspiration in particular during the forced breathing high c.s.f. flow was elicited during every inspiration whereas breath holding suppressed it only a minor flow component could be ascribed to the cardiac pulsation the present results on ambiguously identify inspiration is the most important driving force for c.s.f. flow in humans if you happen to have sleep apnea and you have patients that are worried or scared about using their mask. You might want to tell them why they should wear it if nothing else just for they go in Vatican system and then you have to give this a lecture. Or if you don't have at least maybe a breather right strip or maybe sleeping on your right side so Dr Net a guard says these findings have significant implications for ter treating dirty brain diseases like Alzheimer's and the reason is because protein accumulation is a general feature of all neurodegenerative diseases so in Alzheimer's you have the. Beta amyloid plaques. In Parkinson's you have the Lewy Bodies right here in Huntington's you have the enter nucular inclusions in prion disease. You have the amyloid plaques and then last you have the aggregates as well so in my niece they go in phatic system gets less active as they got older so in my niece if you're a mouse you're glim phatic system gets less active by 80 to 90 percent as you get older why because in mice they also have a decrease in c.s.f. production by 66 percent in over 2 they have a decrease in c s f pressure by 27 percent but what about humans or what did you member what we said humans c.s.f. production decreases by 50 percent Ok And so as we age less waste is cleared like beta amyloid which could potentially lead to increased risk of neurodegenerative diseases such as Alzheimer's so then the question is are there other factors in addition to age that can affect the going phatic system what about other diseases maybe diabetes or hypertension Well sure enough in July of 2016 this study shows clearance of cerebral spinal fluid contrast agent from the interest of space was slowed by a factor of 3 if you're a type 2 diabetic rat. In August of this year which is basically 2 months ago going phatic transport is compromised both in early and advanced stages of hypertension so we know that hypertension leads to what hardening your arteries right and so you're going to have less arterial pulsation with that. And we all know too that patients with hypertension are much more at higher risk for developing dementia and Alzheimer's as well and it makes sense when you look at the the going Fanuc system and what how much it compromises is compromised in 2018 the study came out and that was a this is a hot topic for the National Football League and traumatic brain injury is an increasingly important issue among veterans and athletes and the general public difficulties with sleep onset and maintenance are among the most commonly reported symptoms following injury and sleep debt is associated with increased accumulation of beta amyloid in fossil phosphor related Tao in the interstitial space in part due to relocalization of awkward for Aqua porn for channels away from the asteroid static in feet What does that mean that means when you hurt your brain those little channels those water channels that are supposed to be out here they go in other places in the astro sites and they're moved in so you don't get the glowing phatic flow that convective flow is missing after 2 or bad traumatic brain injury especially repeated over and over and over that's a big issue for. Football. And then again this year. Interesting is when is the Glen phatic system most active we're going phatic system they found just this year the study of this study which appears in the journal Science advances indicate that the slow and steady brain and cardio cardio pulmonary activity associated with deep non r.e.m. sleep are optimal for the function of the Golan phatic system as we age it becomes more difficult to consistently achieve deep non r.e.m. sleep and the study enforces the importance of deep sleep to the proper function of the glim phatic system so you've got to know the stages of sleep and the stages basically you know there's 2 stages non r.e.m. rapid eye movement sleep and rapid eye movement sleep r.e.m. and so memory consolidation requires both of these stages. But. The key is right here it's Stage 3 before right before r.e.m. sleep this deep stage 3 non r.e.m. sleep is the period of deep sleep that you need to feel refreshed in the morning it occurs in longer periods during the 1st half of the night the 1st half of the night we just said this study showed that it's the deep non r.e.m. sleep that are optimal for the function of the glen phatic system so if you put $2.00 and $2.00 together that means the Glen phatic system is more effective during these longer periods the 1st half of the night does that ring a bell over 100 years. Sorry. Well we'll get to that slide over 100 years ago the quote that I'll show you later by Ellen White says that an hour of sleep before midnight is worth 2 hours after midnight Ok so don't be staying up late at night go to bed early and this study this year confirms that now that wasn't a statement that she was shown that it was in her own research in talking with brain workers as she puts it so brain workers are those that might be sitting in this room you know that use their brain all that all day long instead of there there are other other muscles that. Build up more waste maybe and so they need to go in phatic system extra So it's really important for brain workers to go to bed early Ok So Brad simple summary so far there has been a relatively new discovery of how the brain clears it's metabolic waste that has built up during the day called the Glen phatic system it's active during sleep especially the dirt during the 1st half of the night it decreases with age potentially due to overall less c c s f production and lower c s f pressure as we age and problems with the glim phatic system may be a very significant factor in neurodegenerative diseases possibly exacerbated by other systemic diseases like diabetes and hypertension everybody follow me so far I know this is heavy Ok here's the famous quote I know from the testimonies given me from time to time for brain workers that sleep is worth far more before midnight than after midnight 2 hours good sleep before 12 o'clock is worth more than 4 hours after 12 o'clock that's 2nd I mean that's many skip releases number 7 page to 24. So as I learned about this several years ago when I started thinking about this I started to wonder is if you have a critical and phatic system affect our eyes especially the neurodegenerative disease that we deal with every day that causes a loss of neurons in the brain that has exponentially higher risk as we age that might be asleep so she was sleep disorders such as sleep apnea and is associated with other systemic diseases such as diabetes and hypertension glaucoma ring a bell it's the neurodegenerative disease that we deal with every day causes a loss of neurons in the brain higher risk as we age some studies have shown associate with sleep apnea some haven't is associate with other systemic diseases such as diabetes and hypertension huge risk factors for glaucoma so I wasn't the only one in the world that thought this Peter Wilson and his team in Belgium wondered the same thing and they wondered what about an ocular going Fanuc system and he's published over 60 studies on this topic covering the c.s.f. going phatic disease Alzheimer's and glaucoma in 2 years ago he published a study called the gloom phatic hypothesis of glaucoma and he says intriguingly recent reports presented at arvo 2016 No this is not our of O'Connor who goes to church with us but it is the association of research for research and vision and ophthalmology annual meeting together with preliminary data from our own post-mortem study show that a similar pair of vascular clearance system is present in the human optic nerve and retina now I'm going to say that again for the eye doctors and I surgeons that are in this room. A para vascular clearance system is present in the optic nerve and in the retina. That means every blood vessel and every. Artery and nerve artery and vein have this pair of vascular clearance system retinas were examined using multum marker immuno histo chemistry and remember this aqua porn for channel the network and sheath the entire retinal vascular system including between the blood vessels in the authors concluded that this may be the end of tunnel correlate of a retinal lymphatic system he continues the lamina corrosive might play a critical role in the pair of ask flow between the optic nerve in the retina they can cause a blockage of this flow with the creased elimination of neuro toxic substances such as beta amyloid or analog beta and subsequent glaucoma n'est optic atrophy. Yeah atrophy neuropathy so the discovery of this ocular going phatic system may be particular importance for the understanding of the pathophysiology of glaucoma given that studies back in 2007 so I was 12 years ago in glaucoma us animal models have shown that beta amyloid is likely. A mediator of pressure induced retinal gangly and cell death I have never heard that before but they knew this 12 years ago and I haven't sat in any lectures that were anybody brought this up but it makes sense because of beta amyloid is being collected and found in the optic nerve and in the retina because of the lack of the pair of asking her flow it could lead to this. And then 2009 said We have hypothesized that there may be a causal relationship between Alzheimer's and glaucoma that they may be explained by decreased c.s.f. pressure in patients with Alzheimer's disease a very recent study showed or reported now this is 2009 when this is coming out reported the intriguing new observation that mean c.s.f. was 30. Was 33 percent lower in subjects with with primary opening Oklahoma than that of nor known glaucoma as controls it was noted that this observation supports the concept of an abnormal high trans laminate pressure difference whether the result of elevated into ocular pressure or reduced c.s.f. or both plays an important role in Glasgow. And interestingly it was also reported that a substantial proportion of Alzheimer's patients have very low c.s.f. pressure so I'll summarize this here and 2nd Therefore we have authorized than abnormal high trans laminate both the pressure difference makes plain why patients with Alzheimer's have a greater risk for developing glaucoma so basically what he's saying is that here comes the c.s.f. around the central retinal artery into the back of the eye and here in the central retinal vein as it leaves with the waste around it from the retina draining from the retina could be impinged based on the difference between the eye pressure and the c.s.f. pressure this is this is the laminate Crow Bosa So the trans lamina Kryptos a pressure difference is what he's keen on with this. Jonas in 2011 his he says recent clinical studies reported that patients with normal pressure glaucoma had significantly lower c.s.f. pressure in a high trans lamina pressure difference so more so in normal tension or low tension glaucoma. So then. Could go in fact disruption contribute to other eye diseases to other than just glaucoma and the answer is they think so so this was researchers in Rio de Janeiro Brazil and they published this in the front tears in their ology and this little sentence right here says we propose that diffuse retention of interstitial fluid or extracellular fluid there is a direct consequence of imbalance of Glen phatic flow and this is in pseudo tumor cerebral I. So you get that pinching of the optic nerve from the high c s f pressure and they think that the actual cause of that is not so when I was an optometrist cool this is I know in the dark ages 22 years ago 23 years ago but they were telling us that it was interruption of the acts on all flow within the axons of the retina ganglion cells in the impingement there might be causing the. Neurodegeneration of the optic nerve the neurons Well this is another theory in so it's not even called pseudo tumor cerebral anymore or benign intercranial hypertension those are misnomers if you're supposed to call this idiopathic intracranial hypertension. It's also known as primary intracranial hypertension. But they called it this in their study a year ago and so I'm going to read you this sentence right here in this is the rationale for the hypothesis springs from m.r.i. studies which have shown many signs related to intercranial hypertension without evidence of over production of c.s.f. In other words so that heis c.s.f. pressure that's in the brain in sort of in sort of tumor is because not because the c.s.s. c.s.f. is overproduced but probably a direct consequence of imbalance of going phatic flow Ok within the brain so in other words in the brain again the influx of the c.s.f. might be the inflow might be affected or the outflow of the c f a c s f could be impaired in some and maybe it's the water channels that causes this retention of interstitial fluid and then creates the swelling of the optic nerve. Ok so all this talk about c.s.f. pressure and what it does to the I would not be complete without talking about our last topic and that's vision loss in outer space so John Phillips back in 2005 was the 1st astronaut he was on board the International Space Station. And he was the 1st one that noticed a change in his vision and what they found is that 80 percent of astronauts that spend more than 30 days in outer space come back with vision loss and it's so important that the number one concern of space travel right now is getting blown up getting blown up Ok explosion the number 2 concern of space travel right now is blindness Ok it's high on the list for NASA. And it was so this this was called the visual impairment intercranial pressure v.i.p. but now they call it the spaceflight associated neuro ocular syndrome or sans So in 2005 John Phillips had 2020 vision when he left for the International Space Station he comes back 6 months later and his vision dropped to $2100.00 and what they found is that after 6 months on the International Space Station he ended up getting basically a Papel edema or pseudo Papel edema here in microgravity the. Venus system has been put into minimal outflow and maximal obstruction and that causes the cranial venous hypertension Ok so the pressure builds up in a anti or microgravity environment and impinges the optic nerve Now this isn't like Papel edema that we see you know with the with the baseball sized brain tumor it's subtle but it's definitely elevated so if you had a slit lamp and how do you know lens you could see that elevation on these disks and it's in it's concerning because it's affecting their vision and sometimes it's permanent so I have a quiz now for you all right so wake up a 10 year old child presents to your office for her 1st I am she's 2020 vision normal pupils normal visual field normal no nor a logical signs or symptoms no headaches. Upon dilated fundus exam you find significantly elevated disks with blurred margins and you can't see any buried optic nerve had risen and as a clinician you have to decide if the patient has true Papel of Emma or is this just physiological elevated discs. If you're like me I have lots and lots of each kids that come in and if you dilate them and look at their optic nerves you have a lot of this nasal elevation there on the nasal aspect many many times it's not uncommon well what other signs should you look for Upon examination. And I'm going to tell you the hint is the vessels at the margin are just slightly obscured so kind of halfway in between so you can't really tell if the swelling is that the red on a fire layer or if it's actually the r.p. layer which is the distinguishing factor of the you know the optic neuritis or the I o. n. scheme adopting about. Neuropathy versus the true popular Bhima So what should you look for what So all you have now you don't have any other equipment except your slit lamp and a prick or no lens there's something very very simple that should come to your mind to look for what you say very good a spontaneous Venus pulls in why is that because if the spontaneous Venus pulse is present in other words if you can see the the vane the central retinal vein pulsating then you know that the intracranial pressure at that moment is normal so that relieves you from an acute situation where immediate m.r.i. right and why they found this actually from this in 1978 material that I'm telling you about so that covers a lot of us in the room the presence of spontaneous being as pulsations as a reliable indicator of an intra cranial pressure below 182190 millimeter millimeters of water on opening pressure so there's lots of different theories and I'm not going to go into all of these why. The vein actually pulses so there's initial theories where the heartbeat I think might have caused a spike in the i.o.p. and enter ocular pressure compressing the vein and there's the theory of the difference in pulse pressure between enter ocular space in the cerebral spinal fluid. And we can get into all of these but the key here is why does the bunting is Venus pull stop if the c.s.f. is high Ok so what happens is is the is the cranial pressure increases above the eye pressure then you won't see that and that's a red flag Ok so if you don't see a spontaneous Venus pulls then you'd be more likely to order the m.r.i. if you see that pulsating or you know the c.s.f. it's not 100 percent but it's close to that this c.s.f. pressure is going to be normal you know they're not going to have a huge. Brain tumor in there and so usually on opening pressure when you do a spinal tap it's going to be higher when the patient sitting up than when Lang down so normal high pressure is what 2121 so if you convert the opening pressure to millimeters of mercury the high norm c.s.f. would be like 13 or 14 so you see that the normally the eye pressure is higher than the brain pressure that makes sense Ok if the brain pressure goes high then you lose that spontaneous Venus pulse and more likely to have a brain tumor that's that's the clinical Pearl here that say it saves me all the time in clinic and. So when I pressure is high or normal but it's still above the cranial pressure you're going to see the pulse spontaneous Venus pulls. That least at that moment you know the c.s.i. pressures normal if that i pressure the brain pressure goes higher than the eye pressure then it will not be seen and that could be a bad finding if you're worried about a brain tumor so back to the quiz question that happen to be one of my patients she was 10 years old I saw elevation without a spontaneous Venus polls Ok so I can't rule out high intracranial pressure in soft since I can't rule out the pressure I'm going to order an m.r.i. 1st and then if that's clear I'm going to order the Spinal Tap or have my neurologist locally ordered the Spinal Tap So if if this in fact I was kind of quizzing this patient a little bit though before I made that decision and I asked her any headaches dizziness she didn't admit any headaches I remember but Disney a she says yeah you know during the normal times and I said normal to I said Would you like if I spent spun you around in a chair you know or something really fast you get dizzy and she goes yeah batten like you know if you hold your breath right she goes that happens everybody doesn't and I looked at her and I said show me and she's like this and she got dizzy within 2 seconds and I said no that's not normal. You know the m.r.i. go on in the radiologist you know an m.r.i. with and without contrast by the way and the card comes back as Carrie type one brain malformation that she's had since she was a baby and nobody knew it and. The radiologist called me and said Brad you've got to get this girl she needs surgery now because every time she took a breath a deep breath this sort cerebellum was going down into the frame and Magnum which is way too big and pinching and in squeezing the the spinal cord there and there was a concern and to me it sounded like a splitting of the spinal cord or something that they're like if it goes one more centimeter down it's going to affect her lung innervation and breathing and she will die so now it's 15 years later she's graduated from college and is now a nurse and because we got her seen and other little aside to this she came up to your own mountain in Tennessee there and when we were camping and the family just came up for the day and I happened to look across the valley there the in the road and there was this like waterfall coming down these rocks and here's this girl about 6 months after she had surgery or so and I seen I look and she's coming down on her rear end don't don't don't don't don't like that on the on the rocks you know like kids do you know riding the you know I thought to myself you know that might have killed her if she would have done that 8 months ago and nobody would have known why until the autopsy came back so it's a it's a valuable thing and you know this doesn't happen very often but when it does we want to be we want to know what we're doing in and be the best we can be and so she's special to me and always will be. The clinical Perl is 90 percent of normal patients that you see 90 percent of them are going to have a spontaneous Venus pulse if you take the time to look 10 percent of normal patients will not. But if you can see it breathe a little easier it doesn't always rule out high c.s.f. pressure there was a study actually in India in the Indian Journal of Ophthalmology that showed that when the patient actually laid down this this particular patient the pressure went up which is opposite of what should happen but it's not 100 percent but. Now spontaneous means pulse the study here showed that significantly fewer glaucoma patients were observed to have a spontaneous Venus' pulls thing glaucoma suspects in other words glaucoma suspects had spontaneous Venus pulls more then patients with glaucoma Now this didn't make sense to me and I've been in practice 22 years and one of the things that I have noted just personally is that when I have somebody that is a low tension glaucoma suspect if I look in they and they have a very very prominent spontaneous Venus polls and when I say prominent the ones that are just boom boom and you can just see it there those patients were the ones that went on to develop glaucoma damage Ok And so when I saw this. First I'm like This doesn't make sense with what my personal findings are now I've never heard anybody speak on that Ok And I've talked to several glaucoma specialists and speakers that you know I've sat in their classes but that was just my personal experience and it. So basically right here a normal glaucoma suspect is when Let's just assume that the patient's brain pressure is normal but they have a high i pressure Ok a low tension glaucoma suspect is when they have a normal high pressure but we just read that in those patients the c.s.f. is low Ok And so if you had a very low c.s.f. then you would have a more prominent spontaneous Venus pulls right Ok and that's my finding and so the spontaneous Vinas pulse would be present in both of these actually now you put the same patients on drops so now what you have you done you've lowered the eye pressure you've lowered the eye pressure now below the brain pressure the brain pressure is high now in both of these so what's going to be missing the spontaneous Venus' polls so my point is is that when it said that glaucoma suspects have more spontaneous Venus pulls then glaucoma patients well of course because we put them on drops and lowered the press I pressured and then it made sense to me. And it wasn't Intel I listened Saeco in 2016 John Birdsall is a glaucoma specialist in Sioux Falls South Dakota and he is now on the vision for Mars team at NASA and why he's a vision from Art Why is he on the vision for Mars team because he thinks that glaucoma is. A 2 pressure problem not a one pressure problem it's not I pressure problem it's the c.s.f. pressure we've got to consider as well Ok so it's that difference that shearing the optic nerve basically if you want to think of it that way and so in his theory is that these astronauts when they go to outer space if their c.s.f. pressure in their brain increases then why not wear special goggles that increase the eye pressure high to counteract the high c.s.f. in take away the shearing of the at the limit of OSA and so he's actually on their team and they're like just might work so we'll find out yeah swimmers glaucoma Ok the like scuba diving deep or oh I have no oh you mean because they're pressing on there you know what I do I swim every week and that does get to be careful here. It I haven't actually thought about no I have not heard of that so thank you there is a reason that I wear a looser tie no joke because the tie wearing was associate with glaucoma as well and so when I saw that study every single one of my shirts went back there you know and I increased my neck size by half yes. You will look as professional if you don't wear tie right so it's very interesting what John Birt all found because when he was a resident at Duke he did this study in found that c.s.f. pressure here is a normal patient Now these are think glaucoma here a normal patient with normal intracranial pressure. If you have an ocular hypertensive patient where the eye pressure is high Ok look at that. The intercranial pressure on those patients these are patients that do not get glaucoma their pressures may be 28 so high Norma's 21 they might have high entered. But they're intracranial pressure is also high and they don't get glaucoma there's no sharing of that optic nerve that makes sense whereas glaucoma and especially normal tension glaucoma or low tension glaucoma they have lower c.s.f. which the other studies confirmed as well which is fascinating to me and that's my my point about this so many of my low tension or normal tension glaucoma suspects have the spontaneous Venus pulls not a faint one but a significant one and perhaps they don't have the high i.o.p. they probably have just really low c.s.f. pressure and again here you know one at age 65 the pressure decreases Now earlier in the lecture when you talk about the gloom fabrics we said c.s.f. pressure I mean production decreased by 50 percent in humans right now you know that age 65 the actual pressure c.s.f. pressure also decreases Ok Which means that potentially you might see a more prominent Venus pulls because that c.s.f. is going to lower and lower and lower and why wouldn't you know that about that same age the risk of glaucoma starts to skyrocket as well as dementia and Alzheimer's and Parkinson's and other things potentially And so Dr Bergdahl who's like. We know a couple of things and this is what puzzles him we know that most people with high I pressured do not get glaucoma and we know that so much is is only 10 percent potentially go on to get glaucoma you've got to treat all 100 the same to catch those 10 that could go blind from it and we also know that only about 30 or 40 percent or 30 or 40 percent of all the people that get glaucoma there pressure is never high Ok but if you're an Asian 70 percent of those glaucoma patients don't have high pressure Ok so they're much more likely to get low pressure glaucoma and so this puzzled him and this is where he came up with his glaucoma is a 2 pressure disease not one pressure to disease so yet I think about the i.o.p. but you also have to think about the intracranial pressure as well so this is a cross-section of the optic nerve so there's your intra ocular pressure this black areas the lamina Kryptos are right here kind of the skeleton right there in the c.s.f. So if this is high or if this is high these neurons right here are clipped or basically damaged and prob a bully now that you know about lymphatic flow probably maybe if they're going phatic have something to do with this as well so this is a schematic here that if you raise this it's going to create the cupping that we see in glaucoma and when this pressure is higher than this pressure so he's actually so convinced of this as a glaucoma specialist that he's actually start of a company called equinox and this is a treatment that they're doing trials on right now. In this mask right here you hook up to this device and it creates a vacuum in a pair of goggles opposite of his idea for outer space but this is for. Terrestrial beings so what you can do is you can actually dial in on the front of the eye a decrease pressure of 25 percent 50 percent 75 percent lower pressure. For sleep so you put this on while you're asleep and you can lower the patient's pressure and this is going to be more effective I mean the hardest ones to treat are the ones that are low pressure to begin with Ok so if they're 14 to get them down to 9 or something is very difficult with medication and stuff and so this is very effective so the this is some studies that were done where they did it on one on not the other eye and it just shows that they can get a very good going from fs 161516 down 299910 then after they take it off it goes back up but there they've still have to obviously do a long term. Evaluation of this but I opiate night is the most vulnerable time you know when your pressure is the highest it midnight in so this makes sense to counter act of that that's why we use and approach than all of the other welcoming medicines so equalizing this pressure difference is in creating this balance is. What we want and then raising i.o.p. for the astronauts might help their vision loss problem as well so let's put this all together. I believe that all neurodegenerative diseases like ls Alzheimer's and even glaucoma are multifactorial and could it be that if we see a very prominent spontaneous Venus' pulls in our patients with significant cupping that it could be another risk factor for low tension or normal tension glaucoma because the c.s.f. might be very very low something we may not have thought about and could it be that this very very low c.s.f. pressure which creates less bill in phatic clearance could also be contributing to go coma and these are things that I found interesting and I want to give my one of my professors was Dr Leo Sam's a u.a.b. he was one of my favorite professors and I had him several times in clinic and what I liked about him is that he had a vast knowledge of the literature and this summer at the a.o. a meeting in St Louis he spoke on. Retina some nutrition and retina and and what not and so I want to pick his brain like I used to do in the locker room and stuff as well and I said Dr Simms I said you know this is my theory I haven't had time to research it or anything like that but I've talked to you know I usually have time after a lecture or whatever go up talk to the glaucoma specialist or whatever that speaking on glaucoma and nobody they'll just look at me like I'm an idiot and nobody's ever heard of this I said Have you hit do you know of any studies. That have ever been done on this he's like you know a lot he says yeah he says Give me a couple of weeks and I'll get him to you and sure enough he actually followed up with this in sent me for some studies some of which I showed you. And so he hit that encourage me I'm like Ok I'm going to dig deeper on this and and that's about the time that I was working started to work on this lecture and so I want to give him a shout out because his vast knowledge of the literature sparked my interest to dig a little deeper personally so I. Hope that we are learning objectives were covered where we covered the lymphatic system. Well the question is have they done anything yet to reduce this issue maybe with film fabrics or the c.s.f. and all that that's the whole front here so that's one reason I went ahead and did this lecture because I'm hoping that somebody out there hears this and it sparks their interest to do research in this because this opens up a whole new field and they're already doing it for Alzheimer's they're already looking at these are poor and for. Water channels and trying to figure out how to make those more efficient or how to open them up if they get clogged on the drainage side on the venous side so there's all kind of issues that they're hoping that they can solve with this it's exciting actually but number 2 we owe sorry Argo. So what he's saying is if I can repeat that is. There should be a correlation between low pressure glaucoma and some of the other diseases that cause very low c.s.f. pressure is that what I'm Is that right with college and disorders and things I didn't even mention this actually but if Does it make sense why sleep apnea so we always think of sleep apnea affecting glaucoma because of well no oxygen no no life right so I kind of as a no brainer no pun intended but it's actually possibly more glim phatic disruption in a sleep cycle with sleep apnea so if you have sleep apnea and you're not getting that good non r.e.m. stage 3 sleep you're not getting the clearance that you need and I know that's college some some. Of what expert in that field at all but. That's right you know although it is a convective flow unidirectional from the high pressure from the artery to the vein so low veins side. Is a good thing for some of that I would think if the prep if the arterial pressure side was high again. Oh higher Venus I thought you said lower Venus pressure so that makes sense so if you so like an obesity what he's saying is that if the if the Venus pressure was high then yeah there's going to be less pressure difference there in. Exactly they can't drain the c.s.f. out that's that's exactly right I would think so. Right. Well they've been Yeah they've been talking about neural protection for years and glaucoma but but never never because that not knowing what it's protecting. That's exactly right and so I would expect that over the next 5 years maybe that you're going to hear more lectures on the Glen phatic system and I disease and there's a lot more out there that I did not have time in the 60 Minutes to cover you know I've gone over that so let's go ahead and read our text again and says I'm fearfully and wonderfully made and now as you read this and David Oh I can't wait to maybe be the one to show him or somebody you made all the delicate inner parts of my body in it me together in my mother's womb thank you for making me so wonderfully complex your workmanship is marvelous and how well I know it and it is marvelous So with that let's let's pray the Holy Father thank you again for making him so wonderfully complex and again your workmanship is marvelous thank you for this opportunity to learn more about how you created us He reminds us how only you can recreate in us the image you originally intended for us to have. We ask that you bless the rest of our meetings together we ask that you bless each person in this room as they come in contact with people and patients and. As we introduce them to Jesus We ask that you live your life through us and give us the tact and wisdom to know how to do it as if you were in the room doing it yourself and yes this Jesus. This media was brought to you by audio verse a website dedicated to spreading God's word through free sermon audio and much more if you would like to know more about audio verse or if you would like to listen to more service later visit w w w dot audio verse or.

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