Multiple Sclerosis | Etiology, Pathophysiology, Types of MS, Clinical Features, Diagnosis, Treatment

what's up ninja nerds in this video we're going to be talking about multiple sclerosis before we get started the most absolute best way that you can support us here at ninja nerd is by subscribing hitting that like button and commenting down in the comment section that enables us to continue to make videos for you guys enjoyment all across the world so in engineers let's get into it all right ninja nurse so let's start talking about etiology and pathophysiology of multiple sclerosis so first thing when we talk about multiple sclerosis there's no completely like defined causes but what we do know is that it is a particular type of autoimmune disorder it's a type 4 hypersensitivity meaning it's a cell-mediated type of reaction now things that we've kind of traced back as potential etiological factors come down to environmental and genetic types of things so environmental these primarily involve infections so was there some viral infection in their history and the two viruses that i want you guys to remember is epstein-barr virus and human herpes virus type 6. i'll explain what their relationship will be in a second the other one and we don't know how this one is but we notice that people with multiple sclerosis there seems to be a higher kind of incidence rate farther away from the equator and what we know is that people with low vitamin d levels which are generally maybe having less sun exposure farther away from the equator have higher incidence rates of having multiple sclerosis again how that is we don't completely know the genetics that are behind this because when you have an autoimmune disease there has to be kind of two components involved an environmental component and a genetic component combined that genetic component is it's believed to be some type of susceptibility genes and the susceptibility genes that we've kind of traced this back to is hla dr2 so there's a particular type of mutation polymorphism within this gene that basically are present on antigen presenting cells okay which are dendritic cells macrophages b cells when they are exposed to a particular type of antigen like what maybe epstein bar virus maybe human herpes virus 6 they develop this immune reaction to it that is exaggerated it's beyond what the normal immune reaction is the other thing that we see with the genetic component here is that it seems to be more common in those with the xx chromosome so those who are biologically female and to add on to that an epidemiological aspect of this we see this primarily in younger females generally anywhere from 20 to 40 years of age okay so what do i want you to take away from this the things that we've traced back to is environmental and genetic and autoimmune type of reaction type 4 hypersensitivity big thing to take away two viruses have been seen epstein-barr human herpes virus six things that we don't know but we see a relationship or correlation is low vitamin d levels farther away from the equator and genetic susceptibility genes like hla dr2 and we see this more commonly in the xx chromosome genetically female and 20 to 40 years of age now how does all of these things come together is that's what we really should try to understand so let's say here we take an antigen presenting cell so here's an antigen presenting cell and this type is just a macrophage i could have picked any of them i'm just picking that one and this antigen presenting cell is exposed to a particular type of antigen let's say it's one of these one of these viral agents we're just going to for right now we're going to put antigen of some kind because it doesn't just have to be these things it could be things that we don't know about yet what happens is the macrophage will engulf the antigen and what's that called whenever you engulf an antigen it's called phagocytosis so from this process it'll take and engulf that antigen and express a piece of that antigen on its membrane surface on what's called mhc2 complexes now you know another name for these mhc2 complexes are the hlas right particularly the ones with the drdq and the dp types what happens is when it expresses this antigen on the mhc2 complex it then will take and present this antigen to a t cell a helper t cell of some kind and this helper t cell if we were to draw this bad boy up here here's our helper t cell this helper t cell has a particular type of t cell receptor that can recognize that antigen and when it recognizes that antigen it's then kind of primed for that antigen to recognize that anywhere else in the body if it ever experiences it again so now watch this type of reaction should occur here where you have this connection between the macrophage [Music] where it's exposing that antigen to interact with the t cell receptor and then there also has to be some molecules that connect between these right so you know there has to be like a c d four positive type of molecule present either way when this interaction occurs your t cells will start kind of releasing bunch of cytokines and start proliferating but now the big thing is is we have a t cell a t helper cell okay which has a tcr which can recognize a very particular type of blue antigen now here's what's weird these blue antigens may look like a particular protein that we'll talk about a little bit later a protein that's present within myelin so there may be a protein called some type of myelin basic type of protein or other types of myelin proteins that look like or almost have a very similar configuration to that antigen and so now your t cell receptors they're supposed to recognize that antigen but guess what they recognize proteins within our body that maybe mimic that antigen it's called molecular mimicry and that's the mechanism by which this can happen all right so let's take this t cell that we've pretty much primed and put it into our circulation right and track it as we track this t cell okay look what happens it gets to a point of the body where it enters into what's called the blood brain barrier what's the blood brain barrier made up of we're not going to write them all down but i want you guys to think about these two three components here within the blood brain barrier the first one is the endothelial lining right which has lots of nice tight junctions there then the second one is this green layer which is the basal lamina it's a nice little connective tissue layer and the third one is this like little weird-looking blue thing here looks like an octopus it's called the astrocytes so the foot process of the astrocytes are particularly the part that make up your blood-brain barrier now the blood-brain barrier is very selectively permeable but only allows for certain things to come in so you have to either have particular channels or proteins that allow for things to move from the blood and enter into the tissue where the neurons and other different glial cells are so the t cells granted access in certain times where it says okay i'm going to come over and just kind of take and peruse around the actual neural tissue because the blood-brain barrier is going to allow for me it's going to provide specific types of means for me to get into the blood pass the blood brain barrier once this actual t cell gets in to where the neural tissues are it migrates its way to the neuron where it comes into contact with a very particular structure that it notices you see this little guy here this little pink eye this is called your oligodendrocytes they're called the oligo dendrocytes these are the ones that myelinate the axons in the central nervous system well guess what this is myelin myelin has particular proteins that can resemble some of those antigens that we were exposed to in the past and what it'll do is it'll say hey i recognize you i've seen you before you're not normal you're an antigen i've seen before and it starts to adhere and interact with that once it interacts with some of the myelin basic proteins that are associated with the myelin or the oligodendrocytes it becomes activated and says hey this something is not normal in here guys i need to let everybody else in the immune system know so then it starts releasing very very particular types of molecules what are these molecules i'm so glad you asked it releases molecules like interleukin-1 interleukin-6 and tumor necrotic factor alpha i feel like you guys if you guys have watched our videos before you've heard of these these cytokines like a million times right what these guys do is they do a couple things one is they go up and act on the particular endothelial cells within the blood-brain barrier and says hey i need more white blood cells to come to this area so what i want you to do is i want you endothelial cells to increase the expression of little types of like adhesion markers so that way whenever white blood cells are coming past they can stick to you and come to the area of where i want them to come so that's the first thing is that we have to express some cell adhesion molecules there okay second thing that it does it also says hey why don't you blood vessels also undergo some vaso dilation mechanism so it triggers what's called vasodilation why is that important well if you vasodilate a blood vessel you make it bigger and more blood can flow through there if more blood can flow through there more white blood cells can flow through there to come to this area guess what else it does so not only does it stimulate this process called vasodilation so this would be the second thing i want you to remember but it also increases the permeability between these actual endothelial cells so what's that called it's going to allow for things to leak through and so it's going to not only cause vasodilation but increase the capillary permeability and if you increase capillary permeability which is the third thing that i want you to remember more white blood cells can leak out of that blood vessel come to this area where this actual problem is so we've increased expression markers we've caused the death vessel to dilate and we increase cap permeability the other things these can do is that they can actually get into the bloodstream and if these little cytokines will represent them with these kind of like dots here get into the bloodstream imagine here there's other types of lymphocytes so there's more types of lymphocytes here so here let's say here's another lymphocyte it's like hey there's some cytokines over here i'm going to start moving to wherever this injury is or wherever this type of problem is so it can also stimulate another thing here the fourth thing which can kind of create kind of like a chemotaxis type of mechanism it also releases one more cytokine another cytokine that i want you to remember is called interferon gamma and this interferon gamma will actually also work out here it'll actually get out into the bloodstream and you know there's very specific types of white blood cells that it wants to trigger and cause to come to this area you know there's macrophages and macrophages love to be stimulated by interferon gamma so interferon gamma will also do what let's represent interferon gamma it'll stimulate these macrophages activate them and cause them to migrate to wherever this area is so that would be the fifth thing is that you activate macrophages so to recap before we kind of come into this area and start damaging this neuron what were the things that happened exposed to the myelin release cytokines cytokines that were released trigger increased expression of these casal adhesion molecules vasodilation increased capillary permeability chemotaxis of lymphocytes as well as interferon ganon cause macrophages to come to the area now these things come to the area then let's bring in here more lymphocytes and let's bring more macrophages once these let's represent the lymphocytes here and blue so we're going to switch the color of these lymphocytes just so that we don't confuse them because either these are a different type of lymphocytes okay different type of lymphocytes so we're going to bring over here the lymphocytes and then we're going to bring over here our macrophages okay guess what the macrophages do macrophages now that they've been activated they're going to come to the area and what do macrophages do they eat it's going to want to start coming and eating and engulfing these oligodendrocytes but guess what you know what macrophages love you take a piece of toast and you spread some jam on it they love it when you make things a little bit tastier so these b cells when they're stimulated by all these cytokines that come to the area they also convert into a special type of cell you know what kind of cell they specialize into an antibody producing factory baby it converts into what's called plasma cells and these plasma cells start popping out antibodies that are specific to the proteins present on the oligodendrocyte or on the myelin sheaths and so it'll tag this oligodendrocyte or the different components of it guess what macrophages love that and they come in they're like i'm gonna engulf you and it comes and engulfs or phagocytoses parts of these oligodendrocytes so what i want you to remember is plasma cells will produce antibodies so let's kind of put here uh let's kind of add on here the sixth thing to happen here is antibody production which is important for tagging these oligo ninja sites and myelin sheaths and the seventh thing is i want you to remember for this last part here is that these macrophages will undergo phagocytosis of what thing particularly these oligodendrocytes so now as you start breaking down these oligodendrocytes look what happens as a result of this if we were to put an arrow to represent the actual end result look at this look at this poor little oligodendrocyte it got all jacked up now that it got all jacked up and we ripped off pieces of myelin some astrocytes and other types of cells will come to the area and start putting on actual like scar tissue and as you start causing scar tissue to form this leads to these things called plaques okay so you start forming these things called plaques on the axon you know what another name for this plaque is sclera and this happens to multiple neurons and so over time you cause plaques or sclera to develop on multiple neurons which is called multiple sclerosis dang we good man so that is the process by which this thing can occur now here's the nice thing our body in certain types of multiple sclerosis primarily relapsing remitting multiple sclerosis there's another immune system cell that we should just be so thankful for that it says hey i realize that the immune system is having a rough day let me come out here and let people know to chill and calm the heck down this cell here is another type of t cell but it's called a t regulatory cell okay regulatory t cell it secretes a lot of cytokines that try to kind of really shut down a lot of this inflammatory reaction so it releases things called interleukin-10 transforming growth factor beta which says hey stop all of this madness that's going over here let's calm down let the nervous system calm down and allow for these oligodendrocytes to try to remyelinate and try to heal and sometimes there will be a little bit of healing there may be here we'll just but right here during that time period where these kick in there may be some minimal kind of healing or remyelination that will occur but then guess what that doesn't last long another immune reaction will occur start damaging more neurons leading to this consistent damage over time okay now that we got that let's talk about the different types of multiple sclerosis all right so what i want us to do is talk about the different types of multiple sclerosis this is extremely important and the first one that i really want you guys to spend the most time remembering out of all of these is relapsing remitting multiple sclerosis abbreviated rrms this accounts for 90 percent of the ms types it is the most common by far now what happens in this is what we described in the pathophysiology and that's why it's so important so let's say that we take time here on the x-axis and disability which is presenting as neurodeficits in a particular graphical representation on the y-axis so what happens is let's say that here we have a time where a patient is having no types of uh bouts or you know flare-ups of their ms and then all of a sudden they have a bout where they experience some type of neurodeficit maybe it's a visual change maybe it's weakness maybe it's sensory loss but whatever it is they experience that bout where they have a flare-up then they have a pretty much a remission where they'll have some time to heal a little bit but then what will happen is after that time period they'll have another bout that'll occur and they'll have again more injury maybe more visual changes maybe more weakness and then after that they'll have some time to heal but they won't completely heal and they'll have another bout and this will just keep happening and happening here's something that you should notice with this there will be every single time this was their initial disability right so let's say that this was their initial state of neurological function every time look at how much neurological function you knock out consistently with every bout so this is measuring the disability the neurodeficits are getting worse as time goes on there may be after that about a little bit of time of healing remyelination but you never get back to that complete baseline okay this is the most important one that i want you to remember the next one is called secondary progressive multiple sclerosis now this one is usually someone starts off with relapsing remitting multiple sclerosis and then what happens is it kind of progresses in a particular way it secondarily generalizes into this progressive ms so they may have that same kind of thing where they have about and then they go into this remission and then they have about and then they go into this remission and then after that they just have this constant steady state of demyelination neurological deficits and disability okay so that's secondary progressive ms now these are the two big ones i want you to remember these other ones down here are less common but they're very severe okay this next one that i want you to remember is called primary progressive multiple sclerosis so we had relapse remit this one has relapse remit and then constant this one's just constant constant demyelination and disability the entire time it'll look like this okay so consistent disability the entire time no time for remission healing remyelination the last one is by far the most severe because it's kind of like progressive and having a relapse on top of that but with no remission so watch this you have this time where you're going you're having a constant demyelination then that constant demyelination you develop an acute flare but it never goes back to at least the baseline on top of that you just go back into a constant state of demyelination and disability then you'll have this next state where you'll have acute flare-up as it tries to come back down boom you'll have another demyelination event so it's this constant demyelination with relapses that are built on top of that pretty snasty scary stuff all right so quick recap so we remember all this stuff because we got to remember it right relapsing remitting you're going to have these relapses with a period of remission but you never gain true function there's a time period of a little bit of remyelination but you have this kind of bouts flare-ups with remission between okay secondary progressive you have these relapses these bouts where you have a little bit of remission but then it progressively gets worse at a constant rate primary progressive constant demyelination throughout the entire time period and then progressive relap progressive relapsing multiple sclerosis is it is continuous demyelination with these bouts or flare-ups that are built on top of that okay now let's talk about clinical features all right so now let's talk about the clinical features of multiple sclerosis this is a very very high yield component of the lecture that we got to talk about so first things first one of the first earliest manifestations of multiple sclerosis is demyelination right because that's what this is a demyelinating disorder but affecting the oligodendrocytes what is the only cranial nerve that is actually containing all the good energy sites that myelinate it cranial nerve two the optic nerve so if we demyelinate the optic nerve we're gonna lead to optic neuritis this is called what is this called optic neuritis and so with optic neuritis what does the optic nerve do is involved in vision if we demyelinate we destroy these actual oligodendrocytes that myelinate the axons of cranial nerve two we're going to alter the electrical potentials that are being sent via the optic nerve to your cerebral cortex and so this can lead to manifestations such as decreased visual acuity and you know what else you know there's this particular particular photoreceptors that are present within the retina that pick up color and that's carry via the optic nerve you also develop color vision abnormalities so there could be particular color blindness or abnormalities that are present there okay so color blindness or abnormalities okay the last thing that i want you guys to remember here is that a very important physical exam finding if you're taking a pen light and shining it into their eyes and you're going back and forth from one to the other one to the other when you shine it into their pupils instead of them actually constricting they'll dilate what is that called we talked about in our cranial nerve video it is a marcus gum pupil but also known as a relative afferent pupillary defect so what do we call this we're going to write it as a relative afferent pupillary defect but on your exams remember a marcus gun pupil okay these are the big things so again remember optic neuritis decreased visual acuity maybe some color of vision loss they have a very important thing called the marcus gun people you shine a light into both eyes when you go from one to the other they dilate okay rather than constricting okay beautiful the next manifestation there is a structure in our brain stem you know here we have the vestibular nuclei and they receive information from the vestibular nerve that comes from our inner ear right well these vestibular nuclei will tell information to our six nerve nucleus what's the sixth nerve the abducens it'll say hey abducens i want you to go ahead and stimulate the lateral rectus of that same eye so these will go to the lateral rectus of the same eye ipsilateral but then what else it'll do is it'll send this kind of tract upwards that'll stimulate on these two nerves here what is this tract here that goes up and stimulates these two nerves that are located within the midbrain let's write these down this first one here in red i'm just going to write down here the roman numeral is three so what is this this is the oculomotor nerve and then in blue here which one is this one this is the trochlear nerve the main one that i want you to focus on is the oculomotor nerve and so just to be consistent here the pink one here is going to be the sixth cranial nerve so we have six four three they're connected via this little tube this pink tube here called the medial longitudinal fasciculus this thing right there and there's two of them right this would be on the right and this would be the medial longitudinal fasciculus on the left it's connecting these three structures together guess what an ms there's a love this this structure loves to get damaged and so you lose a connection between the six nerve nucleus and the third nerve nucleus what does the third nerve nucleus do it'll send via the oculomotor nerve to go to the medial rectus on the ipc lateral side okay so now here's what happens with this if you damage let's represent this here in black so that we're completely clear of what structure is being damaged this structure here is being damaged the connection between the six nerve and the third nerve what will happen as a result of that when you have a patient look right look left follow your fingers inward or have them just look straight that's what i want you to remember because the condition that you see with this when you damage both of these is called bilateral we're going to abbreviate it enter internuclear ophthalmoplegia what does this look like let's talk about that all right so this is a very very important thing so that when you get out in the clinical field you know what this is supposed to look like in a perfect world so let's say that i have i'm going to kind of represent here have the patient look to the right or follow your fingers in this case to their right when you do that remember what is the structure that's being damaged if you're knocking out both bilateral medial longitudinal fasciculus the sixth nerve is firing because the sixth nerve its fibers are going up straight to the lateral rectus okay that's not being hit it's the connection to the third nerve that's being hit so if you have them look to the right their right abducens is going to fire and it's going to cause them to abduct their eye but it's going to be so intense that when it abducts because it has no kind of like opposition by the oculomotor nerve it's going to do it so fast that it creates kind of like a little nystagmus if you will so you'll have them look to the right that lateral rectus will pull the eye to the right nicely but it'll have a little nystagmus now if this was let's say the right lateral rectus that was firing it should send signals to the left third nerve the left third nerve will then go to the medial rectus on the left eye it should cause it to go and move this way as well but it's damaged so it can't do that so this action will not occur the adduction and so it just stays kind of in that midline boom we good all right next one you have them look to the left the left six nerve is firing there's nothing wrong with that so it's again going to move to the side but it's going to have no opposition by that medial rectus because the oculomotor nerve is not connected so when it does this it looks to the left it creates a nystagmus in that direction now if the left sixth nerve is firing it should send signals to the right third nerve nucleus to go to the right medial rectus but because that right medial rectus is not going to receive signals is it going to be able to beat and toward the adduction side no so we'll not be able to add ducts so they'll be able to look to the left with the left eye but that right eye will just stay in the center okay if you have them follow your finger inward they'll be able to do that why because when you have to look to the right it's based upon like the vestibular ocular reflexes right which has to go through the sixth nerve but if you have them just follow your finger that's in primarily your third nerve you're not depending upon the medial longitudinal fasciculus for this so the medial longitudinal particulus is not involved in this action so it's just your third nerve nuclei that are firing without the medial longitudinal fasciculus so they'll be able to do that so if you have them bring your finger inwards towards them they'll be able to converge okay so having uh the accommodation kind of reflex or bringing your finger closer to them they'll be able to converge okay they'll have a positive convergence on that the last thing is if you have them kind of just look straight at you and this is usually if it's really severe if the six nerves are firing okay and sometimes a little bit too much and there's not much opposition by that third nerve they can kind of the lateral recti can actually pull the eyeballs a little bit out more towards that lateral side and so you might even develop kind of an exotropia bilaterally so there may even be a little bit of a bilateral exotropia that's present at rest when you're just having them look straight at you okay usually this is as you get a little bit more severe but these are the things i want you to look out for with bilateral internuclear abdomiplasia let's move on to the next manifestation all right so what's the next clinical manifestation the next one is that okay we talked about the eyes we talked about kind of the brain stem that is connecting to the eyes the other thing i want you to remember is another aspect so i'm just kind of moving down right so we have the eyes we got the brain stem there's some other aspects that are involved within the brainstem so you know there's these fibers that come from the cortex from like your primary motor cortex premotor cortex all of those cord cortices and send these fibers down from the cortex and come and give innervation to particular cranial nerve within the brain stem such as which nerves this is what i want you to remember okay first one is cranial nerve five the next one is cranial nerve seven which is the facial nerve cranial nerve would be the trigeminal nerve the next one is the blue one which is actually going to be a bunch of them this is actually cranial nerve 9 cranial nerve 10 and a little bit of cranial nerve 11. and then the last one here in pink is going to be cranial nerve 12. so you have these purple fibers that are coming from the cortex coming to this aspect of your brain stem and giving innervation to these cranial nerves these fibers here in this purple color is actually representing what's called the corticobulbar tracks now these are myelinated by oligodendrocytes so when a person who develops multiple sclerosis we're going to demyelinate these bad boys and so then you lose proper innervation 2 cranial nerve 5 cranial nerve 7 cranial nerves 9 10 11 and 12. this condition is an upper motor neuron type of lesion called bulbar palsy what is this called again guys say it out loud pseudo bull bar palsy now with this how would it present we're not going to go crazy i just want you guys to think about this logically don't let's not have to write down tons of stuff what does trigeminal nerve 5 do the motor component chewing muscles if that's affected you're going to have decreased chewing simple as that let's not make it too complicated right there is another aspect of this where it is involved in the jaw jerk reflex and because this is an upper motor neuron lesion what would happen if you tapped on their their jaw it would create a brisk type of jaw drip reflex so they would have a hyperactive jaw jerk reflex if you really went the distance of that okay but let's not focus too much just decrease chewing the next thing is facial nerve what does it do facial expressions so that's effective what's going to happen to the facial expressions they'll have absent facial expressions boom done let's move on to the next thing these two combined actually okay cranial nerve nine creatine nerve 10 cranial nerve 11. okay the motor components of those are involved in the muscles of speech and the muscles of swallowing so if you jack those up what's going to happen dysphagia for difficulty swallowing and dysphonia for difficulty with speech so they can develop dysphagia and they can develop dysphonia with the speech production the other thing it's an upper motor in our lesion when you do things like reflexes there's a reflex where you tap the back of the tonsils and it's supposed to trigger a a gag reflex because it's an upper motor neuron lesion they'll have a hyperactive gag reflex again not super big that you know that but it's just taking into consideration upper motor neuron lesion type cranial nerve 12 is involved in your tongue movements but it's also involved in speech particularly the articulation of speech if you jack up 12th cranial nerve not only will you develop what's called a type of tongue it can affect speech in a particular way that it leads to maybe some dysarthria okay so think about that as well all right but that's the suitable of our palsy that's the big thing okay done so we got optic neuritis bilateral instant nuclear ophthalmoplasia pseudobulbar palsy what's the other thing that i want you to remember it demyelinates a lot of other tracts within the nervous system in our higher order brain centers and if you involve some of the higher order centers like your limbic system like the cortex you start really leading to some involvement of memory centers like your papay circuit and so they can develop maybe some decreased memory and you may also alter some of the neurons that are involved in serotonin release and lead to depression so these are some of the higher order level types of symptoms that you would see in these individuals okay potentially maybe demyelination of some of the components within paper circuit or involvement of serotonin neurons the other thing is there's lots of white matter tracks that are present within the cerebellum coming from the cerebellum or to the cerebellum you demonate those bad boys you alter a lot of the things that are involved in coordination and this can lead to ataxia okay and one of the big things i can't stress this enough how they can present with this is when you're doing a test called the finger to nose test as they bring their finger to their nose into the clinician's finger as they get closer towards that person's finger the tremor will increase what is that called it's called an intention trimmer that is extremely high yield i want you guys to remember that please okay all right the next thing that i want you guys to remember this is a sign that whenever they present this it's going to be on the exam because it has someone's name on it it does not mean that you're going to see this all the time in clinical practice because guess what there's a lot of other diseases that do this but when a person flexes their neck it creates this electric sensation or pain that runs down the neck down the spine and even can run into the extremities you not only see this in ms but you can see it in like any kind of cervical myelopathy cervical spondylysis but it is a very common thing that they'll ask on the boards with multiple sclerosis and this is called meets sign okay and again it's this we have that little a little electric or like you know a sensation that you can feel in the back of the neck down the spine and into the extremities another sign that you need to remember because it's going to be asked on your exam they'd love to throw in people's names it's a very specific type of sign okay or phenomenon if you will it's called utops phenomenon now what happens with this and people with multiple sclerosis they're going to have a lot of these deficits that we've already talked about and even more but whenever you increase the temperature and usually in a vignette it'll be like the person's in a hot tub they got a hot shower something like that they got a bath their symptoms of weakness visual disturbances sensory changes anything like that is worse at higher temperatures the thought behind this is that higher temperatures in particular neurons and some cells that doesn't do this but in particular neurons that have been demyelinated it's generally going to higher temperatures already decrease the action potentials down these neurons now if a person already has a demyelinating disorder where the action potential is being conducted down it is already lower and you increase their temperature now the action potentials will be even lower than it was before that's going to worsen their weakness worsen their sensory changes worsen their visual abnormalities but what's important about this is that usually it'll kind of be reversible after they start to cool their body down they'll go back to whatever their baseline was before that okay it's not a permanent type of thing big thing to remember there okay all right so we've talked a lot about how multiple sclerosis demyelinates a lot of particular cranial nerves like cranial nerve two how it affects the brain stem the cortical bulbar tracts we talked about other aspects of the brain stem we've even hit uh the cerebellum and higher order centers but we got to talk about the spinal cord and that's a big one to think about because it does demyelinate a lot of axons within the spinal cord so you have to remember your tracks i'm not going to go through all of them we're going to hit the biggest things now this track here in pink is your dorsal column now what is the dorsal column sensations do you guys remember because what we're going to do is we are going to demyelinate these axons and so whatever sensations are carried by these is going to be diminished to the point where it could even be absent so what are these you're going to decrease your dorsal column sensations i just want you guys to tell me which dorsal column sensations we could be dropping think about them this could be dropping proprioception fine touch discriminative touch vibration sense any of those could be potentially diminished in that worst case scenario absent the next one that i want you guys to be thinking about here you see this tract here which is on the lateral white column so we hit the dorsal column but here in the lateral white column there's this red tract it comes from the cortex down through the spinal cord and eventually it'll give axons that'll stimulate here these lower motor neurons near anterior horn and cause it to go out to those muscles this is your corticospinal tract if you knock out a corticospinal tract what type of lesion is that upper motor or lower motor neuron lesion upper motor neuron lesion really quickly how do upper motor neuron lesions present what are the classic highlights you will have weakness what about tone increased tone so we call that hypertonia what about reflexes hyperreflexia what about particular pathological types of reflexes you can have a particular one where you scrape the bottom of the foot and it causes a dorsiflexion and fanning of the toes it causes the positive babinskis these are some of the big things i want you to see that you can see with this condition all right next one here you know uh this here particularly within the thoracic spinal cord and the thoracic spinal cord you can demyelinate some of the preganglionic motor neurons of the sympathetic nervous system and in the sacral aspect of the spinal cord you have parasympathetic if we have decreased autonomic nervous system innervation to particular organs like which ones to the bladder and to the last part of the gi tract around the rectum and the sigmoid colon what can happen as a result you can develop two things with the actual sympathetic nervous system remember it controls the sphincter muscle right because it has the alpha-1 receptors present on if you damage that you may cause that to do what you may lead to them having that relax and then they can have incontinence but if the parasympathetic is affected that causes contractions of the bladder and causes contraction of the large intestine if that's damaged you can't contract those so you could also develop retention so in some ways you can develop a little bit of urine incontinence but you may also have potential for retention and then same thing with the fecal cyst system you may have the same kind of concept here where you can have incontinence and then in some ways retention as well okay all right beautiful move on to the next one we have another tract here these tracks are conveying particular types of sensation from the extremities that are carrying what type of sensations it's carrying pain temperature crude touch pressures this is our anterior and lateral spinal thalamic tract if you damage these you could cause decrease pain temperature and so pain temperature crude touch and one last one pressure sensations okay boom roasted move on to the next and the last one here is you have these tracks here in orange so you have your ventral spinal cerebellar tract and your dorsal spinal cerebellar tracts which are carrying information from proprioceptors to the cerebellum that are involved in telling us position sense if you knock these out you lose the position sense and become uncoordinated what is that called ataxia so they can also develop if you damage these bad boys they can develop ataxia all right so the last thing i want to make sure that you guys know before we move on to diagnosis there is a common triad that gets asked in your exams and it helps you to also kind of like a brief review of everything and so this is kind of the big triad that you see in patients with multiple sclerosis it's called shark hots or shark hose triad and the particular things that you need to remember is that these patients will present with nystagmus via that kind of thing we talked about with the internuclear ophthalmoplasia they can also present with dysarthria sometimes this is written as what's called a scanning speech okay and we talked about that before and then the last one is they also have those intention tremors which we see with the ataxia so again please don't forget this this is extremely high yield you might see this on your exams it's kind of a nice quick review of what we talked about all right let's talk about diagnosis all right so now let's talk about the diagnosis of ms and i want us to focus on the big stuff so what is the first line if so where they ask you on an exam what is the first line diagnostic test and for multiple sclerosis you'll see an mri but let's be a little bit more specific let's say an mri of the brain and you should also obtain the spinal cord because this involves both of them and you should say with and without contrast so we're going to get an mri of the brain and spinal cord with and without contrast now i want us to briefly remember what were some of the areas that you needed to remember the first one that i want you to remember is it affects the peri ventricular white matter this is an extremely important one it's actually one of the first ones to get affected that you'll see on imaging the second one that it loves to hit the brain stem so you're also going to get your brain stem involvement so you have to watch out for that on the mri you're also going to hit the spinal cord so we'll look for lesions of that on the mri and then the last thing is we also know that it can hit the cerebellum so you're seeing these white matter lesions are going to show up all over man it can be very very nasty stuff okay so this is the big things that i want you to realize now when we get an mri there's two particular sequences that i want us to notice t2 and t1 particularly the t2 flare t1 is your anatomy image and when you look at this usually the lesions will show up as dark okay or we call them hypo intense for t2 they'll show up bright or white and we call this hyper intense the last thing that i want you to do is sometimes in people who have ms and they have an acute flare up if you give them contrast it will actually enhance the acute lesions rather than the ones that were already occurring in the past when you've had damage okay so these will highlight big things that i want you to take away from this okay so now let's take a look at an image of an mri all right and before we move on to this second line test just remember we talked about the mri but we actually use mri and other particular types of qualification criteria and a very specific name called mcdonald's criteria there's actually a revised mcdonald's criteria but that's used to enhance and aid in the actual true diagnosis of ms all right so what is our second line test they say on the exam what's the second line test that you can do to determine if someone has ms the second line test that you can have is called visual evoked potentials and this one's actually really cool because it should make sense to us what was one of the first types of structures to be damaged in ms the optic nerve if you apply a visual stimulus to them a very particular types of visual stimulus and it's supposed to hit the retina and then travel down the optic nerve if the optic nerve is damaged what's going to happen to the conduction potentials down the optic nerve to show up on the screen in a graphical representation the action potentials will be reduced so the conduction velocity will be reduced so they'll read this as what's called a low conduction velocity based upon the graphical representation when you do these visual evoked potentials because the optic nerve is demyelinated man we're smart guys all right what's some extra tests they're not like definitively diagnostic but they just aid in the diagnosis this is where you can go as far as saying let's get a lumbar puncture why would we get a lumbar puncture well we're smart in engineers let's think about this what were the particular things that were produced i remember i told you there were some antibodies that our plasma cells produced i didn't say what kind but generally the one that those uh plasma cells if we were to go ahead and draw them again remember the plasma cells infiltrated into the brain tissue and when those plasma cells infiltrate into the brain tissue they produced antibodies well these antibodies are actually i g g antibodies and they can kind of get deposited into around the cerebral spinal fluid so they can show up so one of the things that we can see is lots of i g g antibodies now when they put this on an electrophoresis it has this banding type of pattern that we see to it and we call that this is high yield oligoclonal banding so this might show up on the exam it's just a lot of these igg antibodies that are being produced by the plasma cells in that pathophysiological reaction and when you put on the electrophoresis it creates that banding type of process the other thing is what were there were so many cells that were infiltrating into the tissue right there were not only these b cells and plasma cells but there were also t cells and what were the other type of cell that was actually infiltrating into there the macrophages what do you call it when you have lots of cells kind of just infiltrating into this particular area when they infiltrate it's called pleocytosis an increase in the number of cells so we have a pleocytosis primarily it's going to be consisting of lymphocytes and macrophages man we're good okay so again what was all of this called where we actually had to tap in and pull some of that csf and collect it into tubes to find all this stuff this is called a lumbar puncture and so this would tell us this particular type of information okay let's talk about treatment all right so treatment there's two big things that i want you to remember we have acute treatment when they have these acute exacerbation what do i mean by acute exacerbation so let's just say they come in with a very significant like uh like visual deficit okay so they're decreased visual deficits or they have extreme weakness or paralysis of some type when they come up with an acute type of deficit of this kind you have to have an acute therapy and so the first line treatment in this that you have to remember is high dose corticosteroids so high dose cortico steroids and so we can use things like methylprednisolone prednisone anything like that but what i want you to remember is why do we give this corticosteroids are great anti-inflammatory types of agents so you remember when that t cell was releasing all those cytokines like interleukin-1 interleukin-6 tnf alpha all of those dang things even the interferon gamma these glucocorticoids are designed to be able to inhibit that process to inhibit a lot of these cytokines and their effects on the vascular system which is to induce vasodilation increase capillary permeability increase the expression of molecules cause chemotaxis all that stuff that we talked about it's trying to really shut that down all right so let's say that the iv corticosteroids and high dose don't work what's the next option what's the second line option they ask you this on the exam you say plasmapheresis baby i'm gonna clean that blood so how do we do that it's a very cool system now we're trying to clear out particular pathogens from the plasma so in this case we'll say there's some antibodies that we're trying to clear out that are causing some problems which they are we're going to have this like let's say the blood's flowing this way right as it's flowing it'll get sucked into this like tubing right get pulled through this kind of like chamber this sifting chamber that'll yank out some of those nasty like molecules antibodies and put them into this container then it'll run through the chamber and then through this other system as it runs through this other system or tubing that we're going to put back into the blood we get kind of this like plasma from a particular donor or some type of like thing like that saline solution with other types of molecules that we put back into this tubing to run back to the patient and we give them back the plasma that we kind of took away which was trying to clear away some of these problematic molecules pretty cool right so that's this that's the second line so if they say first line you say high dose corticosteroids because it's shutting down the inflammatory action if they say second line you say plasmapheresis now there's also supportive therapies sometimes remember with uh the upper motor neuron lesions they get spasticity the high tone a lot of that we know that we think that we talked about there you can give them anti-spasmodic agents there's things like dantrolene there's things like baclofen so on and so forth they also get paresthesias because of you hitting the dorsal column and spinal thalamic tracts so you're going to give them maybe gabapentin progabalin try tricyclic antidepressants of some kind and they're also going to suffer from depression which we talked about so antidepressants are very helpful in this scenario so giving supportive treatment on top of the acute exacerbating treatment is important but what's the final thing that we got to do we got to try to prevent let's kind of suppress their immune system a little bit to prevent them from developing these flare-ups in the future so how do we do that let's talk about that all right so prevention is primarily geared at like immunosuppression in a way now we're not going to go through all of these types of immunosuppressants i'm going to give you some of the most important ones that you should remember for the immunosuppression occurring in the prevention of acute flare-ups and ms and the big ones to remember here that i really want you to remember is interferon beta interferon beta is designed to be able to inhibit those t helper cells when they release all of those cytokines and all of those inflammatory molecules that's what they're designed to do okay so an interferon beta is designed to inhibit the t cells from triggering that entire inflammatory cascade another drug that's also important is called gluteramir acetate and gluteumir acetate does the same thing it also inhibits the t cells from that cytokine release but it does something else really interesting imagine glutaramire i'm going to draw like a g here it has little proteins on it that kind of resemble some of the proteins on myelin and so whenever the t cells try to come and interact with the oligodendrocytes guess what they actually interact with the glutaramir acetate and glutaminer acetate will inhibit those t cells so it kind of acts as a decoy in a way so that's pretty cool so you inhibit the t source from cytokine release but also glutamine acetate acts as a t cell decoy because it has proteins that mimic the myelin the next one here is actually a drug it's an it's an antibody the last two are antibodies it's called acrylism one heck of a name here but what it's designed to do is to inhibit the activity of these different types of b cells remember the b cells that came to the area it's trying to inhibit the activation of these b cells it's also trying to inhibit the activation of the plasma cells so basically the end result is to decrease the antibody production that is occurring by these cells pretty cool right and the last one is called another antibody monoclonal antibody and it's called natalizumab natalizumab and this one works by inhibiting lymphocytes right so your b lymphocytes and your t lymphocytes from invading and crossing the blood-brain barrier and coming to that area where they trigger that massive inflammatory cascade and demyelinating process pretty cool so there's so many other ones but these are the most important preventive ones of prevention meds that i want you guys to take away that covers multiple sclerosis all right ninja nerds in this video we talk about multiple sclerosis i hope it made sense i hope that you guys enjoyed it as always ninja nerds until next time [Music] you

Channel: Ninja Nerd

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Length: 54min 15sec (3255 seconds)

Published: Tue Aug 10 2021