Seizures | Etiology, Pathophysiology, Clinical Features, Treatment, Complications/Status Epilepticus

what's up ninja nerds in this video we're going to be talking about seizures and epilepsy as well as taking a discussion down the road of status epilepticus before we get started it's so important for you guys to continue to support us and the best way that you guys can do that is by hitting that like button commenting down in the comment section and most importantly subscribe subscribe alright ninja nerds let's get into it all right ninja nerd so what the heck is a seizure a seizure is basically this abnormal excessive synchronous electrical activity that occurs

within the central nervous system that can lead to outward manifestations which we'll talk about in the clinical features like focal and generalized seizures now what are the potential causes the triggers the reasons why people develop seizures and then how does the pathophysiological mechanisms occur that trigger these seizures the easiest way to remember the causes of seizures is through the mnemonic vitamin d and e and we'll go through each part systematically the first one is your vascular causes so these are very common for focal kind of structural causes leading to focal types of seizures usually but

they can cause generalized this includes acute ischemic strokes intracerebral hemorrhage and subarachnoid hemorrhage another common cause is whenever you have very very high blood pressure that causes some vasogenic edema to occur with inside of the posterior cerebral territories that is visible on mri you see the vasogenic edema they have hypertension it's visible on the mri sequences we call this posterior reversible encephalopathy syndrome this is basically hypertensive encephalitis encephalopathy basically the next one is whenever you have severely low oxygen levels in the blood so low that there's almost no oxygen being delivered to the brain and

a very large area of the brain suffers from that severe hypoxia anoxia and then can develop seizures this is called anoxic brain injury to summate the vascular causes so that you guys don't forget them it includes acute ischemic stroke intracerebral hemorrhage subarachnoid hemorrhage hypertensive encephalopathy but if it presents with vasogenic edema on the mri it's called pres posterior reversal encephalopathy syndrome and then severe anoxic brain injuries boom roasted let's move on to the next part the next thing i want you to remember is infectious causes so vi infectious causes include meningitis that's very close to

the cortex and so that irritation of the meninges can also irritate the nearby cortex the next one is if you irritate the actual brain tissue itself and that is called encephalitis okay encephalitis the next one is when you have a big loculated accumulation of pus and bacteria or other types of microorganisms that are accumulating near the cortex and this is called a brain abscess okay brain abscess so three particular infectious causes that i want you to remember either inflammation of the meninges meningitis inflammation of the brain tissue encephalitis or a big loculated accumulation of infectious

material caused and called an abscess these things need to be near the cortex though in order to trigger seizures the next one so we got the first part of our vitamin d and e mnemonic the next one is traumatic causes so traumatic causes that i want you to think about here is if you form kind of a lens shaped bleed that is called an epidural hematoma or if you form this crescent-shaped bleed so epidurals are usually rupture of the middle meningeal artery subdurals are usually venous bleeds and so this is called a subdural hematoma these

are near the cortex can agitate the cortex and trigger seizures the next one i want you to remember is autoimmune causes so there's some type of antibody mediated activity on the actual brain tissue causing some type of autoimmune type of encephalitis to be present and so one of the big big triggers to remember is there is a very common autoimmune disease that can trigger antibodies to attack the brain tissue and this is called systemic lupus erythromatosis so please remember that one the other thing to remember is that sometimes people can develop what's called perineoplastic syndromes

you're like what in the heck does that mean so perineoplastic syndromes is you have some type of neoplasia and then what happens is that cancer leads to the production of antibodies that'll go and attack other tissues in this case the brain tissue and so this also can cause an encephalitis so again big thing to remember for autoimmune causes it can either be due to an autoimmune disease like systemic lupus erythematosus or perineoplastic syndrome where somebody has like a small cell lung cancer and they develop antibodies that attack the brain tissue particular receptors of the brain

tissue either way they're attacking the cortex and leading to an autoimmune type of encephalitis so usually this may present as an auto immune encephalitis that can lead to seizures okay so we have these parts of the vitamin d and enomonic let's move on to the other parts all right so we talked about the first part of our vitamin d mnemonic the next part here begins with m metabolic causes now metabolic causes usually cause more like diffuse types of seizures and the particular ways i'd like to remember these is let's think about some of the nutrients

and electrolytes that are inside of the blood and even vitamins one of the big ones is vitamin b1 thymine thymine is a very important vitamin and it's very important with a lot of electrical activity so sometimes whenever there is a thymine deficiency a decrease in vitamin b1 that can occur in things like wernicke's encephalopathy and alcoholism that could be a potential cause for a seizure the other thing is glucose whenever you lower those glucose levels hypoglycemia is a very intense trigger for someone developing a seizure weirdly enough though in some situations it's also important not

as common but sometimes even high glucose levels less common let's actually put here an abbreviation less common high glucose levels can also cause seizures the next one is sodium sodium regulates a lot of that movement of water to and from the actual cerebral tissue and blood and so whenever there is low sodium so hyponatremia or high sodium but more particularly low sodium is a little bit more common of a trigger so hypo or hypernatremia can also be triggers for seizures calcium whenever you have low calcium that is really going to cause a lot of seizures

to occur another one magnesium magnesium really stabilizes a lot of membranes and regulates the activity of calcium channels so low magnesium can also trigger seizures and last but not least low phosphate level hypophosphatemia can also trigger seizures so what again metabolic nutrient kind of molecules are important remember a deficiency in thymine low glucose hypoglycemia less common hyperglycemia hyponatremia more common hypernatremia a little bit less and then hypocalcemia hypomagnesemia hypophosphatemia these are the potential triggers with this aspect of the metabolic causes the next thing think about the kidney the kidney if someone accumulates a lot of

urea so if there is an increased accumulation of urea this also can cause some type of trigger of seizures so increasing urea increasing kind of metabolic waste let's put increase in waste metabolic waste okay the other one is the liver so think about that good old beautiful liver if the liver decides hey i'm gonna start making i'm gonna have less ammonia that's actually being converted into urea and so now because of my liver failing and i'm not able to take and perform the urea cycle as appropriately i'm going to build up a lot of ammonia

and that ammonia also has the ability to trigger seizures next one is the thyroid gland and someone who has think about it hyperthyroid everything's sped up that could be causing seizures as well so when someone has an elevation and their t3 t4 levels that can also trigger seizures so to quickly recap metabolic causes uh thymine deficiency hypoglycemia less common hyper hypo hypernatremia hypocalcemia magnesemia hypophosphatemia uremia liver failure and hyperthyroidism let's move on to the next one idiopathic causes now idiopathic causes is actually what we term epilepsy okay we really could define this more as epilepsy

so epilepsy is a little bit different from seizures in a way that epilepsy is where you have two unprovoked seizures greater than 24 hours apart that's how we kind of define epilepsy another newer definition in 2014 was that you have an unprovoked seizure with at least a 60 reoccurrence rate so either way it's whenever someone has multiple seizures is that they're more likely to have epilepsy and these could be due to a couple things and we'll talk about these one is if that person has epilepsy okay and they're being treated with anti-epileptic medications what if

they are either on that anti-epileptic and they're either not taking it because of side effects or they just don't want to or the level of the aed is sub-therapeutic they're not in a nice therapeutic range and they just their dose wasn't increased appropriately for whatever reason that's a potential trigger the other one is epilepsy syndromes and there are so many different types of these and this is more pertaining to like pediatrics but this can include things like west syndrome which usually presents with like these infantile spasms this can present with a very sad case called

lenox gestate syndrome and then another one is called a juvenile myoclonic epilepsy and again this is just some of many different types of epilepsy syndromes okay so idiopathic causes when we really say idiopathic we're talking about people with epilepsy who either have an epileptic syndrome of some kind or they're just either not complying with their aed or it's not at the therapeutic dose so think about that as another potential cause so so far we're up to i of vitamin d and e what's the next one neoplasia so this is another structural type of cause that

usually can present more with focal seizures but if you have a neoplasia that's again near the cortex it has to be near the cortex to really trigger seizures or it has to be something really diffuse like metabolic in nature if that's the case then when these are having these neoplastic things like someone has for example a big old nasty mask one of the scariest ones that you can develop within the brain is like a glioblastoma multiforme right that could be a potential one or you have a mass that develops within the meninges compressing onto the

cortex of the brain what could that be due to that could be due to a meningioma and sometimes there even could be you have a mass somewhere that spread to the actual brain from another primary location and it metastasized so this could also be some type of malignancy that's secondary to metastatic type of activity there okay so that's the next thing to be thinking about all right the next cause within our vitamin d and e mnemonic is drug causes now drug causes similar to like metabolic causes as we mentioned above these things lower your seizure

threshold so they just kind of lower the threshold to which a seizure could be triggered there's a bunch of different medications i don't want you to remember every single medication but some of the important ones to remember can be remembered by this mnemonic otis campbell and so the first one is opioids and this includes drugs like maperidine and tramadol they seem to be very strong triggers tricyclic antidepressants like amitriptyline or triptyline even anticholinergic drugs isoniazid which is used to treat tuberculosis remember that in a clinical vignette as well as salicylate toxicity so taking maybe too

much aspirin another one is a double whammy cocaine for sea as well as cefepime which is a type of cephalosporin antibiotic a for amphetamines which includes things like ritalin and adderall m for metronidazole which is a type of antibiotic p for penicillins which are types of antibiotics b for benzo withdrawal as well as don't forget the medication buproprion which is wellbutrin okay another one is ethanol withdrawal and last but not least lithium these are all common drugs that you guys need to remember that it could be potential causes of someone developing a seizure by lowering

that seizure threshold if you want to be really really extra smart ninja nerds you guys can add into the d of drug causes to other types i'm not too concerned if you don't really want to remember them but they can be added on into the drug like the d part of the mnemonic and this includes degenerative diseases things like alzheimer's and the other one that you could add into this is demyelinating diseases including multiple sclerosis okay so if you guys want to be extra engineered you can add these into that d part of the vitamin

d mnemonic the last part of our mnemonic here is e for eclampsia and kind of everything else that you can kind of think of eclampsia is a very strong trigger of this so eclampsia would be again when someone's pregnant they have uh they're pregnant they also have high blood pressure so pregnant we'll put prego high blood pressure and they also have seizures it's kind of the classic things with eclampsia so that could be one thing everything else just mentioning a couple extra things to remember here is fevers fevers can be a pretty strong trigger especially

in children so whenever they have a very particular viral infection called rosiola which is a human herpes virus infection that can cause febrile seizures as well as a rash and then the last one we are not going to go through all of these but there is particular genetic causes that predispose someone to seizure things like fiddle canoe neuria things like a lot of mitochondrial diseases and lysosomal disorders and peroxisomal disorders so many different types but these are the big causes that i want you guys to remember as potential triggers of seizures now that we know

the causes invasive hunter vitamin d mnemonic the next thing i want us to talk about is how these things really lead to pathophysiologically neurologically at the cellular level seizures all right so we have our causes now how do these particular causes at the cellular level generate seizures let's have a big kind of like general overallized understanding of it the basic pathophysiological mechanism is that there is a decrease in the inhibitory pathway which is primarily the gaba pathway and there is an increase in the stimulatory pathway which is primarily the glutamate pathway let's start with glutamate

now for whatever reason in these individuals who develop seizures there is an increase in glutamate production or an increase in the glutamate activity on the particular receptors that are on this postsynaptic neuron and there's two different types of receptors to remember one is called the nmda and the other one is called the ampa receptors either way whenever glutamate binds onto these little channels it allows for cations like calcium and cations like sodium to enter and even magnesium to enter into the cell whenever cations enter into a neuron what do they do to the inside of

the cell they make the inside of the cell super positive when you make the inside of the cell super positive that creates just enough positive charge to activate voltage-gated channels that are present on this axon and lead to a propagation of depolarization down this axon what is that called an action potential so this could lead to a depolarizing depolarization and then therefore action potentials if you have increased glutamate because of this whole theory of increased positive activity pathway there'll be more glutamate more activity on the ampa are in in mda more calcium more magnesium more

sodium influx more positive charges more depolarization more action potentials and that's where you get that abnormal excessive synchronous electrical activity that can occur within the central nervous system the other pathway is very interesting so the basics basis of this pathway is that there is a problem with these channels here these channels here are called your gaba a receptors and what's believed to be wrong in these patients is by any of these causes that we discussed these are dysfunctional and they don't respond as well to gaba so for example if gaba is released when gaba acts

on this type of channel normally what would you want to happen normally what would happen is these channels would open and this would allow for ions like chloride to enter into the cell if chloride were to enter into the cell what does chloride it's kind of charges it's negatively charged that negative charge would be enough to inhibit the activity of action potentials down what down the axon and if you decrease the the actual voltage inside the cell and decrease the action potentials this can lead to hyper polarization okay so what is this called again this

activity where you make the inside of the cell extra negative because of bringing chloride ions is called hyper polarization then if you have hyperpolarization you make the inside of the cell set negative it's unlikely that action potentials will be triggered so you'll have decreased action potentials right now think about this if there's a decrease in the gaba pathway or that inhibitory pathway even though gaba may be present at normal levels there's decreased reaction of these gaba receptors to gaba that means decreased chloride ions are coming into the cell that means decreased negative ions are accumulating

into the cell that means that there is decreased hyperpolarization of the cell if there's decreased hyperpolarization that means the cell's not becoming as negative it's not as inhibitory and instead it'll cause an increase in action potentials so you lead to an increase in action potential which leads to an abnormal excessive electrical activity that is synchronous with inside of the central nervous system whether it be due to a decrease in the inhibitory pathway due to gaba receptor dysfunction or an increase in the glutamate pathway via the increase in glutamate or increased sensitivity of those receptors to

glutamate that is the method or the pathophysiology now here's where it gets even cooler if these abnormal electrical activities occur within the brain our central nervous system if you will how can it actually present and that's the good question to think about so whenever this abnormal electrical excessive synchronous activity is occurring by the causes and the mechanisms that we discussed let's say that there's a particular focus where this electrical activity is occurring right here and now that is going to spread that abnormal electrical activity is going to spread to other parts of the brain but

it's going to stay in this one cerebral hemisphere that is called a focal seizure so a focal seizure is occurring at one point usually involving kind of one hemisphere of the actual cerebral cortex but let's say that you have a focus some focus here and what happens is this electrical activity is occurring throughout all parts of the cerebrum and the bilateral cerebral hemispheres holy crap what is that called that is a generalized seizure so big thing to remember here focal seizure usually as it's occurring in one point stays within that one hemisphere due to this

mechanism we talked about above or that abnormal electrical excessive synchronous activity is occurring in bilateral cerebral hemispheres which is a generalized seizure this leads us into our next discussion which is clinical features all right ninja nerds so now let's talk about the clinical features with seizures we already kind of introduced that there can be focal seizures and generalized seizures so we have here focal seizures we're going to talk about them and then down here we'll talk about generalized seizures so first thing with focal seizure just to quickly recap there is a focal location where this

abnormal electrical activity is occurring and spreading throughout that one cerebral hemisphere right and staying within that cerebral hemisphere when that happens you want to think about this whenever there's abnormal excessive electrical activity within a per a particular part of the brain think about your anatomy and physiology of the brain so first thing frontal lobe what are the big big things to think about that are controlled within the frontal lobe there's a lot of motor activity that occurs within the frontal lobe your primary motor cortex your supplementary motor cortex your frontal eye fields broca's area a

bunch of different things so whenever you have for example let's say that the right frontal lobe there's a lot of this abnormal excessive electrical activity you may start developing movements abnormal movements on the contralateral side and we'll talk about that the different ways that those movements can present the other thing is think about sensory symptoms so think about the other lobes so think about for example this blue one here that's right behind the central sulcus so think about parietal that's where a lot of your sensations somatic sensations occur think about hearing purple think about the

occipital that's where a lot of the visual sensations occur and then think here in green think temporal and you can even include in the insula a little bit and that's where a lot of auditory sensations as well those other kind of primitive sensations also occur so for example what i want you to remember here is again sensory symptoms so for example as an example we'll give you more examples if you have a seizure that is going on within the right parietal lobe you may have abnormal sensations of the arm and the leg on the contra

lateral side maybe pain paresthesia so on and so forth okay the last one i want you to think about here is again kind of tucked deep within this again temporal lobe and then even add on to this the insula these can lead to very interesting types of symptoms whenever you involve the temporal of the deep temporal lobes the ensulolymbic structures there it can lead to autonomic symptoms as well as psychological symptoms and we will discuss what the heck i mean with that as well okay so whenever someone talks about again focal seizures it's abnormal electrical

activity that is excessive its synchronous within one area staying within that cerebral hemisphere if it affects particular parts of the brain it can lead to what kind of main symptoms abnormal motor symptoms abnormal sensory symptoms abnormal autonomic symptoms and abnormal psychological symptoms and that is particularly with focal seizures before we start talking about the basics of generalized seizures i want us to talk about the anatomy the basic kind of process of seizures since we're getting ready to introduce this whenever someone is having a seizure there's a stage or phase kind of process that they go

through so what is that so let's say that we first start off with the trigger we already talked about them all the different vitamin d and e causes so we can talk about there is a trigger right and that trigger could be any of the vitamin e and d causes it also can include other simple ones that could be superimposed on those what's very common things that most people know stress severe stress sleep deprivation very bright lights and bright sounds on top of superimposed on any of these issues we just discussed can trigger a seizure

activity now once you have that trigger this can lead to in some patients if it's a focal seizure it can lead to something called an aura what the heck is an aura a aura consists of a couple different things so let's describe what an aura is and aura is you usually feel a couple different things one is deja vu okay this kind of impending sense of fear this impending sense of doom in some way shape or form you may have some nausea this kind of feeling of like nausea that kind of moves throughout the abdomen

up into like the chest you may exhibit what's called auto matisse what the heck is automatisms automatisms is when someone's like doing this rapid blinking of the eyes so maybe if they're doing rapid blinking if they're chewing and lip smacking that could also be kind of an automatism so chewing like abnormal chewing even have any food or gum in their mouth so they're just kind of like an abnormal chewing or they're smacking their lips these are common kind of automatisms that you can see with these patients so if someone comes they have a trigger bright

lights bright sounds stress sleep deprivation superimposed on all the vitamin d and e causes boom they feel this impending sense of doom they feel this nausea they start rapidly eye blinking they start having these lip smacking and chewing type of symptoms then what can happen this is kind of a premonition letting them know hey seizure common baby and then what will happen they will start to seize and so we call this the ichthyl event and that's where we're really going to discuss a lot of the different characteristics of if it's a focal or generalized seizure

and that's where you kind of see this is where sometimes if someone's coming into the emergency department or you see in a movie someone's thrashing around that's their ichthyl event but maybe previously they may have had some type of aura or trigger that we're just unaware of after the ichthyl event they have what's called a post-ictal phase and the post-ictal phase is very important the post-active phase after the person sees whether it's a a visible seizure like a focal seizure or whether it's a non-convulsive seizure whether it's a generalized seizure whatever it may be after

that actual event occurs they can show certain types of symptoms that they had a seizure and usually the post-dictal phase occurs usually in two types of seizures so focal with impairment or a full on generalized seizure so if you have focal seizures with impairment a generalized seizure and then one more which is a focal that's secondarily generalized and will describe what the heck i mean by that so it's either you had a focal seizure where you lost consciousness or you were impaired you had a generalized seizure where you lost consciousness or you started off with

a focal seizure with impairment that became generalized secondarily and these po these issues these types of situations their post-dictal state the symptoms that they usually show include usually they're confused they're lethargic or really drowsy they have amnesia they don't even remember what the heck happened you could they could go up and say hey do you remember what happened like no i just kind of blacked out and also here's a common one that they love to ask on the boards is especially in focal seizures with impairment they can develop what's called todd's paralysis and that's basically

where they have weakness on one side of the body okay and that's usually common after a focal seizure with impairment so quick quick anatomy of a seizure you have a trigger lead to potentially if it's a focal seizure especially with impairment you can develop an aura aura deja vu impending sense of fear nausea automatism leading to an actual event the actual visible scene scene of a seizure focal seizures generalized seizures or focal that becomes generalized or even sometimes you might even see it it could be a non-convulsive seizure and then after the actual event occurs

you have a post-ictal phase and that post-ictal phase is usually only common in seizures that are focal with impairment focal that secondarily generalizes or a generalized seizure and is classified as having afterwards being confused lethargic fatigued forgetting having amnesia of what happened and especially don't forget for your boards and focal seizures with impairment they also have weakness or paralysis on one side of the body that usually goes away over time called todd's paralysis okay now that we hit kind of the anatomy and pathway of a seizure let's start talking about these ictal phases here focal

and generalized seizures in more detail all right cool focal seizures with the motor type so again this is primarily a seizure being generated within the frontal lobe this can present in a couple types of ways the first one that i want you guys to remember here is a tonic so basically a tonic is their muscles just become super relaxed and weak and they can collapse actually another one is the exact opposite of a tonic it's tonic they're stiffening of the muscles clonic is there's quick jerking of the muscles myoclonic is there is a asynchronous very

rapid jerking movement and then last but not least is you can have these movements that we just talked about in a very very weird way that is very common in situations where a patient especially you need to remember this for your exams called a jacksonian march what the heck is a jacksonian march let's say that you have a clonic seizure it starts in the hand then it moves up into the forearm then it moves up into your upper arm and then your entire arm is involved a jacksonian march is it usually starts at a distal

limb and works its way proximally this is common in motor seizures and one of these types of you know forms usually clonic okay so that's a big thing to remember so here we'll write distal to proximal kind of spread okay so don't forget that jacksonian march distal to proximal spread of these types of motor movements all right that describes that now one quick thing here is that if people present with these kind of focal motor seizures there's a couple classic ways that they can show up we talked about the different types of contractions that they'll

exhibit but how will it visibly look i think is an important thing and so some of the ways that that may present is they may have like we already kind of showed you a unilateral shaking of a limb another thing that could be not as obvious is their eyes could be hardly deviated to one side so maybe you look and if they have a seizure going on in like the left frontal lobe they may actually have their eyes deviated to the contralateral side so that's important and the last thing is they may have their head

cocked or turned to one side so head turning to one side hard eye deviation as well as unilateral shaking can be signs of focal motor seizures now focal sensory it's really straightforward i want to go through the cortex and we'll kind of try to color code these things accordingly so first one blue somatosensory cortex if you're having abnormal electrical activity you can feel abnormal sensations so feeling pain and or paresthesias so kind of a pins and needles feeling and you know what's interesting about this this can also occur in a jacksonian march type of fashion

so where you feel abnormal pain and tingling and numbness in the hands that then spreads up to the forearm that then spreads up into the upper part of the arm that then spreads up into the shoulder so you can still have jacksonian marches with focal sensory and focal motor anyway the next one we picked purple so if there is a kind of abnormal electro activity within the occipital lobe this may lead to visual hallucinations so you maybe see things that aren't actually present so visual hallucinations okay the other one now move on to the green

there's a couple different things within the green that temporal lobe so first one is primary auditory cortex so you hear abnormal sounds maybe you hear kind of an abnormal ringing in the ears that actually is not even present or the primary olfactory cortex so you smell things intensely or abnormal that isn't really there maybe you smell some type of abnormal smell maybe you smell burnt toast for whatever reason and then inside of the temporal lobe tucked in there is all the also the gustatory cortex kind of within the insula a little bit and that is

responsible for taste and so there may be abnormal tastes in your mouth even though you're not actually chewing or eating or drinking anything maybe you have this weird like metallic taste in your mouth as well so to recap again focal sensory seizures they can present if it's somatosensory kind of pain and paresthesias they can present visual hallucinations if it's auditory they can hear abnormal sounds like ringing if it's olfactory they can smell abnormal intense smells like burnt toast or if it's abnormal if it's the gustatory cortex abnormal weird tastes like maybe a metallic taste in

the mouth okay the last part for the focal seizures for the particular lobes that are involved here especially again temporal lobes is those autonomic symptoms so this is really particularly when you get to the insula the insulin can actually regulate a lot of your autonomic activity and so whenever there's autonomic involvement that can also lead to some interesting symptoms which include what it can really increase your cardiac activity so it can increase your heart rate leading to tachycardia and it can also increase your blood pressure leading to hypertension it can also act on the actual

bladder system okay and it can lead to urinary incontinence and it can actually affect salivation as well okay and sweating so it can even lead to salivation and sweating okay so whenever there's abnormal firing of areas within the temporal lobe particularly tucked near the insula it can lead to autonomic symptoms like high blood pressure tachycardia urinary incontinence as well as increased salivation and sweating now if you start getting into that temporal lobe as well a temporal lobe a lot of the structures within there are the limbic system right which control a lot of our emotions

our behaviors and so one of the big things to think about is emotions right so sometimes people can exhibit like emotional uh behavior okay and so maybe they can present like really angry or maybe not only can they present really angry maybe they present like hypersexual so sometimes hypersexual behavior is another thing to think about as well and the last thing to think about here within this list is particularly some other kinds of psychological symptoms such as we already talked about this one deja vu where you kind of have this sense of impending kind of

doom or fear depersonalization where you have kind of this disassociation uh from kind of yourself or the environment or derealization okay which is again kind of a disconnect from your environment as well so these are particular symptoms that you can exhibit so again we talked about focal motor focal sensory focal autonomic and psychological symptoms that you can see with focal seizures a couple more things that we have to talk about before we go into generalized seizures is if these focal seizures that we can see presenting in any of these ways are in causing impairment potentially

loss of consciousness or no impairment there's no loss of consciousness and so in those situations it's important to understand some of the things that can maybe clue you into that and what are those things here first before we talk about that it's important to remember your anatomy so when we say with impairment it may be meaning that these seizures are involving some particular areas of the brain and brain stem so let's say that here you're having your focus of seizure activity and that focus of seizure activity that's causing with impairment is involving some particular structures

here maybe it's involving the reticular formation which you know is the seed of consciousness uh well particularly helps with the not the seed of consciousness but more particularly with our arousal what we decide it sifts through all sensory information and decides what we need to be alerted about or aroused about so it's kind of our arousal system if you will and the other structure here is the thalamus which is kind of the relay station for all sensory information going into the central nervous system so whenever focal seizures involve the thalamus and they involve the reticular

formation it can lead to impairment loss of consciousness in a way and so because of that there may be a loss of consciousness that's one thing that can help with focal seizures the second thing is that usually focal seizures with impairment also present with auras right so they present with automatisms nausea deja vu some of those kinds of things and on top of that usually they have a post-ictal state so a post-ictal state means that they actually either have some amnesia they have some confusion and guess what else they could have if there is impairment

todd's paralysis okay so important to remember that so if you have a focal seizure that is with impairment it means it's involving the reticular formation the thalamus there's a loss of consciousness they also can have auras automatisms deja vu all of that stuff and they have a post-ictal state with confusion amnesia lethargy as well as potential todd's paralysis if there is a focal seizure without impairment there is no thalamic involvement and there is no reticular formation involvement so there is no impairment with respect to loss of consciousness so it's just a focal seizure that's firing

and involving one half of the cerebral hemisphere without involving the thalamus and the reticular formation so there should be no loss of consciousness there's usually no auras and there's usually no post-ictal state okay that's the big things to remember for that the last thing that i want to talk about before we go on to generalized seizures is that there's something interesting and this kind of it's a nice prelude into generalized seizures is focal seizures with impairment can lead to generalized seizures because we said it can secondarily generalize how does it do that so here's what's

really interesting let's say here you have a focus of epileptogenic kind of potential it's firing leading to that abnormal electrical activity that's spreading throughout that hemisphere even comes down and involves the thalamus and involves the reticular formation so now you get impairment but then enough electrical activity can pass from one cerebral hemisphere over into this cerebral hemisphere and now you get this abnormal electrical activity that is in both cerebral hemispheres because it passed through the corpus callosum so the corpus callosum is a commercial fiber connecting both cerebral hemispheres so if these focal seizures are powerful

enough that they cause impairment spread through the corpus callosum enough to involve the other cerebral hemisphere now you have bilateral hemispheric involvement what is bilateral hemispheric involvement that is also involving the thalamus and the reticular formation called a generalized seizure so this was a focal seizure that became generalized so this is very very important what you really want to remember with these is that usually this presents as a type of seizure that we're going to talk about within the generalized topic called a tonic clonic seizure now how do i know if a person had a

generalized seizure or they had a focal seizure with impairment and it became generalized usually if there was a history afterwards or you could find there in some way they had a history of aura they had automatisms they had some type of focal seizure symptoms so in other words maybe they had some unilateral shaking their eyes deviating their head turned to one side and then on top of that postictal they have todd's paralysis that may clue you in that this was never really a generalized seizure from the get-go it was a focal seizure that secondarily generalized

ninja nerds we went through focal seizures talking about the different types the width impairment without impairment and then on top of that secondary generalization now let's move into the beast and generalize seizures now generalized seizures usually again involve bilateral hemispheric involvement so bilateral hemispheric involvement that involve the thalamus and involve the reticular formation so there is definite loss of consciousness and there is definitely a post it state but that's a postdictal state in the motor type of generalized seizures because there's actually two types and we'll talk about these the obvious one is the generalized motor

and then the second type is the non-motor which we also call absence seizures okay the big overall theme here generalized seizures bilateral hemispheric involvement with impairment because of involvement of the thalamus and the reticular formation has a post-dictal phase especially in that generalized motor but there is two types motor non-motor let's talk about the generalized motor how can a generalized motor seizure present they can present like we talked just above they can present as a generalized a tonic a generalized clonic a generalized tonic a generalized myoclonic all with impairment and all bilateral or the classic

type the tonic clonic a mixture of tonic and clonic we also give this the name grand mal seizure this is the classic convulsive type stiffening as well as jerking movement of bilateral aspects of the body trunk everything whenever there is this tonic clonic seizure because of generalized bilateral hemispheric involvement it leads to insane muscle contractions of various parts of the body not only do you see it of the limbs so upper limbs lower limbs trunk but guess what else you see the exams love to ask you this it also involves the muscles of the respiratory

system and those suckers contract so hard they let out a big burst of air and so when it hits the respiratory system it can lead to a kind of a cry or like an involuntary screen okay if it involves the extra ocular muscles it loves to pull those eyeballs up and lead to an up gaze or an uprolling of the eyes if it involves the oropharyngeal muscles it loves to clench down on those so hard so that all your oral secretions pull up in the oral cavity so it causes pooling of oral secretions that's why

sometimes in the movies or things like that they like to show you like oh they're foaming out of the mouth it's probably seizures that's kind of the the view of that the other thing is it causes intense contraction of the mastication muscles your chewing muscles what does that do you clench down unfortunately what could come between that teeth the tongue and so that whenever these contract this can cause tongue biting oh man this making sense isn't it baby all right what else we got it also can involve those good old sphincter muscles so if it

causes the release of the sphincter muscle around the urethra the release of the sphincter muscle around the uh the anal sphincter area what can this lead to it can lead to poopoo it can lead to incontinence so they can have urinary incontinence or fecal incontinence what else there's also autonomic involvement so a generalized motor seizure we're seeing a lot of the kind of somatic type of involvement here but you also get the autonomic involvement okay and this can even you know exacerbate the incontinence as well but it can also increase the activity of your heart

so it can increase the the the beating activity or the action potentials throughout the heart leading to an increased heart rate or increasing the contractility of the heart leading to an increase in blood pressure so it can also lead to hypertension and tachycardia so again generalized motor like particularly tonic clonic of that type grand mal seizures which lead to loss of the consciousness they lead to tonic chronic movement of the upper extremities lower extremities trunk head neck as well as involuntary scream cry up gaze pooling of oral secretions tongue biting incontinence and tachycardia and hypertension

and then afterwards they have a postdictal state where they have amnesia confusion lethargy and that can last for a decent amount of time until they return back to their baseline okay the last type of seizure here that i want you guys to remember that are part of the generalized type are called generalized non-motor seizures and these are classified as what's called absence seizures so absence seizures now epsilon seizures are also uh kind of defined as petite mall so petite mall seizures now epsilon seizures are very interesting what can happen with absent seizures is they can

have like everything can kind of black out on them and it can they can kind of look like they're staring out um in our daydreaming as we can kind of say it here so there's kind of like staring out into the abyss or or they're daydreaming then that can occur so again absent seizures do what they can cause this staring out they can cause this daydreaming effect all right engineers what the heck happened you guys just had an absence seizure everything kind of blacked out for you and then you guys came back and this is

what happened so where did we leave off here we talked about absent seizures leading to staring out daydreaming but here's what's really interesting it's non-motor usually there is no loss of muscle tone so they don't actually collapse in any way shape or form they just sit there and stare out like their daydream sometimes can actually be misdiagnosed as adhd very interestingly sometimes in the atypical types of generalized non-motor absence seizures that this can present with automatisms so again sometimes they may stare out daydream no loss of muscle or postural tone but they have that rapid

blinking of the eyes they have the lip smacking and chewing sad thing with these is they can happen up to a hundred times a day what's interesting about this is that there is no post-ictal state for this okay one other thing that i want you guys to remember we'll talk about it with diagnostics but i want to briefly talk about it absent seizures are a very classic thing here and what happens with these is that whenever people get eegs whenever you obtain an eeg of these patients and we'll talk about it with diagnostics where that's

why you get eegs and electroencephalograms this shows a very classic pattern that you guys need to remember for your exams and it presents as a three hert spike and wave pattern so i just wanted to kind of make sure that we preface this within the diagnosis on the eeg with absence seizures you can use eeg to see this classic three hertz spike in wave pattern as well okay so that kind of finishes up our clinical features discussion now let's start going into the diagnostics all right nigerians we're at the diagnosis the person came in they

were seizing based upon the features that we talked about whether it was a focal or generalized seizure we got to figure out why did they seize so what if the person comes in and upon chart review or per the patient or per the family this person has a history of seizures well maybe this isn't kind of a seizure from an underlying thing that we have to evaluate here maybe they just truly have epilepsy so if they have history of caesar's how do we define epilepsy so it's two or more unprovoked seizures greater than 24 hours

apart or a unprovoked seizure with a 60 recurrence rate according to the epilepsy foundation definition so if they fit that definition and they have epilepsy what do you do about going to elucidate the problem here the next thing you do is if they have epilepsy it's most likely that they're on an anti-epileptic medication so we need to assess the adequacy of that anti-epileptic so what do we need to do we need to assess adequacy of the anti-epileptic that they are taking how do we do that check a level if they're on a particular drug that

you can check a level for check the aed level if you check the aed level and it is low they have a low aed level so let's say that for example they're on phenytoin you get an aed level of the phenotone you get a phenytoin level and it's sub-therapeutic what do you do you increase the dose to get it into the therapeutic range so increase the dose and maybe that was the reason that they seized it they just weren't actually within the appropriate therapeutic range of their aed what if you take an aed level and

you have a normal aed level okay well then guess what you can do if you have a normal aed level let's say they check the phenytoin level it's in the normal range but you still have some wiggle room you can get up to the maximum point of the dose before it becomes supra therapeutic what can i do if i have some wiggle room then increase the dose if you have some wiggle room if you're at a normal aed level and maybe you're close to the maximum dose and there's no point of increasing the dose of

the aed what would you do switch the anti-epileptic drug so switch to another anti-epileptic drug okay that is the important thing to remember the next thing that you guys need to remember here is what else could we be thinking about here if we have a patient who has a normal aed level we switch them to another anti-epileptic drug another thing to be thinking about is is there an underlying c other algorithm and that's what we're going to go into the next part okay so to briefly recap this part patient comes in with a seizure has

a history of a seizure you suspect epilepsy you you want to assess the adequacy of the anti-epileptic if they're on that one if they're on it check a level if it's low increase the dose if it's normal but you still have wiggle room to keep it to the max therapeutic range increase the dose if it's in the normal range but you don't have a lot of wiggle room switch it to another anti-epileptic drug and consider an underlying cause from the other algorithm okay now the next thing here is they have a first time seizure so

there's no history of seizures this is the first time that they've ever seized you have no history of it on chart review from the patient from the family whatever you need to go through these causes and figure out which one of these is the reason that this person seized first one is vascular what were the causes of vascular acute ischemic stroke subarachnoid hemorrhage intracerebral hemorrhage anoxic brain injury and prez posterior reversal encephalopathy syndrome what could i do i could get a ct i could get an mri and if i really wanted to especially for subarachnoid

hemorrhage what else could i do i could get a lumbar puncture for subarachnoid hemorrhage right good enough okay infectious etiology what were the causes meningitis encephalitis brain abscess what do i do get a ct get an mri get a lumbar puncture okay so ct mri maybe get a lumbar puncture you could also obtain blood cultures you could also attain a cbc why a cbc maybe they have an elevated white count that clues you in there's an infection blood cultures see if there was an infection that was in the blood and that spread to the brain

or if they have sepsis lumbar puncture because maybe there'll be infectious pathogens within that cerebral spinal fluid if they have meningitis or encephalitis so on top of a ct and mri to help to see if there was any brain abscess you can further evaluate that how do we further evaluate it i can actually go the next step which is doing what's called a stereo tactic aspiration where you actually go in and suck some of the fluid or kind of biopsy some of that fluid or abscess out to see what kind of pathogens are there so

you know what types of antibiotics antifungals antiparasitics whatever it needs to be to treat that patient okay so we got so far vascular infections what about trauma well if they come in with a history of trauma and you obtain a ct scan that shows either a epidural hematoma or a subdural hematoma i'd say that you're pretty darn good there okay what else autoimmune autoimmune's a little bit different if someone has autoimmune encephalitis this is usually a little bit lower what if they have a history of lupus or systemic lupus erythematosus or some other autoimmune disease

you can further evaluate that with an autoimmune panel and so sometimes an autoimmune panel starts off with just kind of like an a a so an antinuclear antibody with reflex and that will just send off a bunch of other other antibodies that may be related to different types of autoimmune disorders the other thing is what if you suspect a para neoplastic type of syndrome so maybe there is a cancer somewhere and that cancer is what's actually leading to antibodies being produced well how do i find the cancer maybe i need to do a full ct

scan so maybe i need to obtain a ct scan of the chest abdomen and pelvis also when you get into these autoimmune kind of like panels you can also check very specific antibodies that are present with kind of autoimmune encephalitis like anti-nmda anti-who anti-gaba anti-ampa antibodies there's so many different types but that can be included within that panel all right so we got our autoimmune types okay metabolic what do i do here well think about it what was the first one we said thymine so check a b1 level that could be low they have hypoglycemia

or hyperglycemia check a point of care glucose they have some type of electrolyte abnormality like sodium calcium magnesium phosphorus i can get a bmp and add on magnesium and phosphate levels because a bmp is going to give me what it's going to give me their sodium it's going to give me their calcium as well okay and it can even give me a glucose what else is good about the bmp it'll give us their renal function so if there's any elevation in urea elevation and creatinine which is a cause for uremic encephalopathy if i want to

let's actually take this a step further we could you know what a bmp you can add a bmp plus lfts when you had a bmp plus lfts what is that actually called it's a cmp so if i really wanted to save money instead of ordering two tests what i really could do is i could get a cmp adding on magnesium and adding on phosphate why a bmp will tell me the sodium it will tell me the calcium i'll get the mag and foss separately and then the cmp also gives me their lfts so it'll tell

me if there's an increase in ast alt out phos maybe telling me that there's a liver problem also it'll tell me their renal function their bun and creatinine telling me if there's a renal function there as well so it'll help me with hepatic encephalopathy uremic encephalopathy or any other electrolyte derangements what was the other molecule that i told you though to add on because it could be the trigger for the seizure besides the lfts for the liver what else can i add on an ammonia level okay look to see if there's an elevation in their

ammonia one more cause for the metabolic that i want you guys to remember is thyroid hyperthyroid so get a thyroid function test and the way that we check this preferably is tsh with a reflex so if the tsh comes back low they'll send in to check for a t3 and t4 to see if that is high okay alrighty so these are the big things to think about here the next one that i want you guys to think about as a potential cause and how we're going to evaluate that is idiopathic c epilepsy we already talked

about that you're assessing the anti-epileptic drug level and adequacy and why is that important he's anti-epileptics they're not always perfect they come with side effects which we'll discuss in a separate video on anti-seizure medications and so sometimes people can be on an anti-epileptic and just stop taking it because of the side effects or because they're taking it and it's just not at that therapeutic level or it's just not the right epileptic for them and they need to try another one what's the next one to evaluate neoplasia so they have a glioblastoma they have a meningioma

they have a metastatic type of cause from a malignancy how do i figure that out a ct can start off with that maybe find some type of abnormal mass and then i want to get an mri with contrast okay that's another big thing to think about when we talked about abscesses we said mri mri with contrast you should add that on for abscesses because it enhances the rim showing that ring-enhancing lesion when you add contrast you want contrast for cancers as well because it again it will enhance that mass okay so mri with contrast a

ct scan to start which may lead to an mri with contrast to follow up and then sometimes to figure out the true like ethiology of it you may even need to do kind of a resection or biopsy to figure out what the actual pathology of that mass is what the cause is if you really are interested the other thing is when we say ct there's actually two of them you get the ct of the head and also if you suspect a malignancy like a metastatic cause get a ct chest abdomen pelvis okay drugs so drugs

there's so many different types of drugs that we got to think about so go through and evaluate their med list so you really need to look at their medication list what are they taking and figure out is that one of those otis campbell things that we talked about if it is then what do i need to do discontinue that medication but the other thing is what if it was something else like it was ethanol it was cocaine it was like amphetamine it was a benzo it was an opioid something like that that i may be

able to pick up on a toxicology screen so what i may do is a toxicology screen okay and usually that's a urinary drug screen is what we'll kind of start off with okay now remember we added into the list there demyelination and degenerative diseases you can also do imaging for that as well the next part is eclampsia and everything else eclampsia what did we say was the primary thing is you needed high blood pressure seizures and got to be pregnant so what am i going to order i'm going to order a urine um and also

maybe even a serum beta hcg okay to see if it's elevated because maybe they're pregnant and that's the reason why this person is seizing okay the other thing is are they fibril so check a temperature so if they have a fever that could be a potential cause and then genetics that may require more kind of like in-depth tests so you may have to do more genetic testing okay and we're not going to go down that rabbit hole the only other thing that i want you guys to add on to this is some additional labs to

think about whenever you're trying to work up a patient with who's seizing other things to add on because it can help if you're trying to really determine if the patient's seized is you can add on a ck level so a creatinine kinase level a ck level sometimes in these patients who have pretty bad seizures this will be increased and the reason why is you're causing those muscles to contract and contract and contract and they end up rupturing and spilling out some of that creatine creatinine kinase into the blood the other thing is whenever your muscles

are just constantly burning through that like actual oxygen and consuming and consuming and consuming so much oxygen to break down glucose make atp so that your muscles can keep contracting when they're in the seizure state is it can increase the lactate and it can lead to an acidosis what type of acidosis a lactic acidosis type b lactic acidosis and so sometimes you may even add on maybe an abg to help with that process but getting a lactate level getting a ck can also be important another thing to add on is prolactin you're probably like what

the heck i'm not spilling milk out what the heck what does this have to do with anything sometimes prolactin levels if they're elevated and a patient comes in with seizures but you're not sure is this a real seizure or is this a pseudo seizure a psychogenic non-epileptic seizure prolactin levels if they're elevated they more suggest seizure versus peroxis so the psychogenic non-epileptic seizures also called pseudoseizures the other thing that you can check is a troponin troponins usually whenever muscles are damaged muscles contain troponin so also you can have troponin leaks and again this could be

indicative of skeletal muscles rupturing open and releasing that troponin because they're seizing and you're trying to cause your muscles to go into this rhabdo type of state so you may be able to pick up rhabdomyolysis but i got increase of ck a lactic acidosis by an increase in lactate and abg suggesting metabolic acidosis elevated prolactin more suggestive of seizure versus a pseudo seizure and the troponins you can add that one on as well to look to see if there's a troponin leak okay and if you get troponins you should add on an ekg just to

make sure that you rule out any arrhythmias as well because you know what another type of differential for seizures is syncope and so sometimes syncope can also present what looks like it is actually a seizure but it's actually an underlying arrhythmia a cardiogenic cause that caused them to pass out and look like an actual seizure so add-on and ekg so we talked about the additional labs but there's one more thing that we need to add on that definitely aids in the diagnosis of seizures now just because it's not present on this type of test does

not mean that the person doesn't have seizures we just might not have picked up on it but another test that definitely needs to be done to kind of evaluate if their seizures present is you need an e e g an electroencephalogram determining the electrical activity within different parts of the brains to seeing if there's any weird epileptic activity that is occurring there so very very important another test that you need to add on is an eeg looking for abnormal electrical activity within the central nervous system all right now let's talk about treatment all right engineers

now we need to talk about the treatment of seizures or epilepsy so go back a person seized okay when they seized you need to treat them with anti-epileptics depending upon if they've been seizing for a long period of time we'll talk about the status epilepticus you can treat them with anti-epileptic medications while you try to stabilize them with these anti-epileptic medications you should be searching for an underlying cause as you search for them that underlying cause based upon the diagnostics we talked about if it's a reversible cause that's causing the seizure you treat that underlying

cause and then maybe you can discontinue the anti-epileptic if it is a cause that is not easily reversible you may have to continue the anti-epileptic until that cause has resolved but it's important to remember that seizure is a symptom of an underlying disorder that we talked about with the vitamin d causes if you can reverse it it could potentially stop the seizure if you can't and they have epilepsy or a non-reversible cause you may need to keep them on an anti-epileptic okay what are these anti-epileptics before we talk about all these dang anti-epileptics we need

to have a basic remembrance and understanding of that pathophys for seizures right what was the basic concept behind seizures there was two things there was an increase there was a a decrease in the inhibitory gaba pathway right so a decrease in the inhibitory gaba pathway that was one cause the other one is there is an increase in the glutamate or stimulatory pathway so it's two causes here that are really kind of hidden here glutamate or stimulatory pathway so increase in the glutamate or stimulatory pathway or a decrease in the gaba inhibitory pathway either of these

two things or compounded on one another leads to increased depolarization of these postsynaptic neurons increased action potentials increase abnormal excessive synchronous electrical activity seizures so what do we need to do we need to give drugs that either shut down the stimulatory glutamate pathway or give drugs that are going to stimulate the inhibitory gaba pathway so let's briefly talk about some of the pathways here with the glutamate first thing is let's say here's a glutaminergic neuron if action potentials are moving down this glutaminergic neuron it'll open up voltage-gated sodium channels that are present on the axon

when these voltage-gated sodium channels are open sodium will rush into the cell cause the inside of the cell to become positive and then again depolarize the next segment so really these voltage-gated sodium channels on the glutaminergic neurons are very very important because what do they do they allow for depolarization of that glutaminergic neuron very very important voltage-gated sodium channels on the actual glutaminergic neurons are important because they allow for depolarization of this neuron if this neuron depolarizes and triggers action potentials that move down this axon to the synaptic bulb guess what it'll do it'll lead

to the release of neurotransmitters from this neuron like glutamate and glutamate will then act on this postsynaptic neuron stimulating it and triggering action potentials so what if i give drugs that inhibit or block these voltage-gated sodium channels if i block these sodium channels can positive ions come into the cell no so i am decreasing or inhibiting these positive charges from coming in if i decrease positive charges from coming in am i going to be able to trigger action potentials no i'll decrease action potentials if i decrease action potentials am i going to be able to

release glutamate from these neurons no decreased glutamate leads to decreased action potentials being carried down this axon less seizures right so the good thing to ask ourselves is what are the name of these drugs that block the sodium channels you can remember them by very problematic to let phosphonatoin cuddle so v is valproate so valproate or valproic acid p is phosphenetoin t is topiramate l is lamotrigine f is phosphonatoin and c is carbamazepine carbamazepine okay so basic concept there sodium channel blockers inhibit the sodium channels on the glutaminergic neurons decreases action potentials down those glutaminergic

neurons decreases glutamate release if there's less glutamate what happens that means less glutamate binds on to the nmda receptors and ampa receptors that means less cations enter into the cell less cations decreases depolarization and if you decrease the depolarization you decrease action potentials decreasing seizures all right what else all right well the other thing that you want to add on here is that we didn't explain how these action potentials lead to glutamate release let's explain these action potentials right that are propagating down the axon this flow of positive charge can also activate these specialized channels

only located on the axon terminal called voltage-gated calcium channels if these positive charges stimulate these voltage-gated calcium channels guess who starts flowing on in calcium guess what calcium does calcium binds on to special types of receptors called sv2a receptors that are present on these vesicles binds onto them and engages this synaptic protein with the cell membrane to induce glutamate release glutamate acts on ampa nmda receptors causes cation influx causes depolarization causes action potentials if i give a drug like a calcium channel blocker which will inhibit calcium entry calcium can't enter decrease calcium enters decrease binding

to the sv2a receptor decreased fusion to the cell membrane decreased glutamate release decrease activation of nmda ampa decrease cation influx decrease depolarization and decrease action potentials you guys get the point what are the drugs to remember for this class this one i want you to remember what's called gabapentin which is kind of an old school one and one more called etho soxamide ethosoxamide i want you to remember a very specific type of seizure we treat this one with and this is absence seizures so absent seizures respond best to what kind of drug calcium channel blocker

which type etho sucks my very important very high yield okay we got the sodium channel blockers calcium channel blockers we got another one these sv2a blockers so this is a drug we already kind of a little bit discussed it is this is where calcium will bind on right so calcium will bind on to this actual sv2a receptor when calcium binds onto the sv2a receptor what will happen this membrane this vesicle will fuse with the membrane induce glutamate release what if i give a drug that blocks calcium from binding to the sv2 receptor or binds the

blocking of that synaptic protein to fuse with the cell membrane either way whether it's not interacting with calcium or not fusing with the cell membrane what's the end result think about it less of this sv2a binding with calcium are fusing with the cell membrane results in decreased glutamate release because you're having less fusion with the cell membrane less nmda ampa activity less cation influx less depolarization less action potentials what is the name of the drug that inhibits this sv2a protein leva teracetam uh an easier way to remember this one is by the brand name kepra

okay that's why it's easier to remember that one but either way sv2a blockers like levitarazetam inhibits the binding of calcium to the sv2a or inhibits the fusion to the synaptic membrane decreasing glutamate decreasing action potentials decreasing seizures okay there's one more drug that i want to add on to inhibiting this glutamate pathway what is that there's actually drugs that can target the nmda receptors and this one's a very interesting one and this is called ketamine ketamine is a very interesting drug and what it has the ability to do here is block glutamate from binding to

the nmda receptors if you block glutamate from binding to the nmda receptors what happens there's less positive charges coming into the cell like cations less cations less depolarization less action potentials so to summarize the decreasing stimulatory pathway what do we have sodium channel blockers calcium channel blockers sv2a blockers and nmda receptor blockers so we blocked that part of the seizures we can also affect this part which is increasing the inhibitory pathway the gaba pathway what drugs can we use here let's remember what the gaba pathway is involved in first thing you need to remember is

gaba is actually formed from a molecule called glutamate so glutamate is actually converted into gaba and then it's incorporated into these vesicles and then what happens is when these actual vesicles fuse with the cell membrane and they release gaba gabo will bind onto these little pockets here of these very special receptors and these receptors are called gaba a receptors when it binds onto the gaba a receptors the channels open and allow for anions like chloride to enter into the cell making the cell extra negative it becomes super super negative and this causes hyper polarization now

hyperpolarization is where you make the cell extra negative like we did the problem with that is that hyper polarization affects your action potentials and decreases your action potentials but you're like wait if i'm decreasing the action potentials then i'm not having seizures right remember what was the problem with seizures the problem with someone having a seizure is that these gaba a receptors were in some way shape or form either dysfunctional or not responsive as well as they should be and so because of that there was actually kind of decreased chloride ions coming in there was

actually decreased hyperpolarization and if your cell's not as negative what does that mean by by that process it's actually positive and if that's the case you can actually depolarize these cells and lead to increased action potentials okay so i need to give drugs in some way shape or form to try to increase this gaba pathway or overcome these dysfunctional gaba a receptors in some possible process so what we can do here is another thing that you want to remember a part of this pathway we got to add on it's not over right once gap was

done exerting its effect on these gaba a receptors it shouldn't sit in the synapses it should get brought back up into these channels here brought back into the terminal bulbs once the gaba is brought back into the terminal bulbs it can get converted into a molecule called succenic semialdehyde you're probably like what the heck what do i need to know this well there's an enzyme that helps to mediate this process and basically kind of renders gaba ineffective and being formed at that process there so this protein and we're going to draw this in blue here

we kind of have this like little dude here look at this guy look at this cute little dude a little nose got a little eye got some hair some leggies and then he's got his arms involved into this reaction what is this enzyme here called gaba transaminase okay we'll put transaminase okay so this is your gaba transaminase which is converting gaba into what's called succinate semialdehyde and that basically renders gaba ineffective from being able to be recycled okay so that's our basic pathway gaba is released axon gaba a receptors causes anion influx hyperpolarizes decreases action

potentials but in seizures you actually have dysfunctional gaba a receptors they don't respond to the gaba as well they don't allow for anions to come in they don't hyperpolarize instead they depolarize and cause increased action potentials also gaba gets reuptaken back into the neurons via the gaba reuptake proteins and then convert it into an inactive molecule called succinic semialdehyde via the gaba transaminase now we have drugs that can target this pathway to increase the gaba pathway let's talk about them the first thing is where was the first part of the path when we released gaba

the gaba a receptors right so the gaba-a receptors can we use drugs to make these gaba-a receptors either more sensitive or we just stimulate the living crap out of it enough that we cause anions to rush in yeah we can give drugs that are agonists to gaba what are those drugs benzodiazepines so this is a big one to remember okay so what are some of these benzodiazepines i'm not going to list them all because there's so many we'll have to have a separate lecture on just those but i want you to remember lorazepam as a

very very important one diazepam is another important one and finally midazolam these are very important drugs okay the next one i want you to remember is propofol so propofol another one is pheno barbitol and there's also other ones in there as well but these are the real big ones that i want you guys to remember okay so gaba a agonist how will they work is the good question here what will they do the gaba a agonist will come and stimulate these gaba a receptors if you stimulate the gaba a receptors what do you do you

increase the chloride ions if you increase the chloride ions you increase the hyperpolarization because you make the cell super negative if you make the cell super negative it's unlikely that it'll depolarize instead it'll have decreased action potentials and decrease your seizures okay all right that's that one now what else the other part of the pathway here is gaba gets re-uptaken back into these neurons what if i keep gaba in the synapses and i actually prevent it from getting re-uptaken into these actual synaptic bulbs son of a gun if i do that and i inhibit this

uptake then gabo will stay in the synapses longer if it stays in the synapses longer it will stimulate these gaba a receptors more increase chloride ions increase hyperpolarization and decrease the action potentials what is the name of the drug that can do that tiaga bean the next thing not only can i actually prevent gaba from getting re-uptaken but what if i try to prevent gaba from being converted into this inactive form and instead try to inhibit this process and allow gaba to be recycled put back into the vesicles and excrete it again so i inhibit

this enzyme from doing this activity what is the name of those drugs that are gaba transaminase inhibitors like i did that inhibitors these are vigabatrin and valproate and that would cover our seizure medications our anti-epileptics if you will son of a gun right okay we've stabilized these patients by doing what reversing their underlying cause if it was reversible put them on anti-epileptics and if they still had a cause that we couldn't reverse we should keep them on these epileptics consistently now there's one more scenario an extremely emergent complication that can arise from seizures and that

complication is known as status epilepticus status epilepticus is when a person is two definitions if you will a seizure that's lasting greater than or equal to five minutes that's a long time for that brain to be on fire baby we don't want that another definition is you have a seizure followed by another seizure without a return to baseline you have a seizure after another seizure after another seizure with no return to baseline in between that is status epilepticus this is a neurological emergency what do we do while you're going to be doing the same diagnostic

work up we just talked about figuring out the underlying causes vitamin d and e workup you need to stabilize these patients how do we treat them first and foremost initial treatment should always in any emergent situation begin with what a b c's airway breathing circulation are they protecting their airway if not intubate if they're hypoxic so are they hypoxic i think this is a good question to ask if they are intubate them and protect their airway also again control their hypertension because most likely they're going to be hypertensive and control their tachycardia and we can

do that in other ways as well so that's our abcs the second thing is you need to reverse the actual causes so easily reversible causes let's put easy once so ones that it wouldn't take a lot of investigation things that we can quickly figure out so what if the person comes in you get a quick point of care glucose and they have hypoglycemia what do i give for hypoglycemia i give them d50 what if i come they come in and they say oh this person has a history of alcoholism so they have a history of

alcoholism which leads me to think vitamin b1 deficiency i give them thymine i give them a thymine infusion or a bolus if you will okay what if the person is pregnant if they're prego or you get a beta hcg but obviously if they come in with a big old bump a baby bump what are you going to do suspect eclampsia and if it is eclampsia it's not really going to respond great to all of these anti-epileptics guess what you give them magnesium you give them magnesium four to six grams of magnesium okay the other one

is if they come in with maybe a history of tuberculosis and they've been on isoniazid you need to give them something to reverse the ionizing is a toxicity and you give them vitamin b6 these are the quick things that you can do based upon the clinical vignette and in real life to reverse these seizures quickly okay the third thing that you'll do after you try this stuff is you'll start getting a benzodiazepine to shut down or actually to stimulate those gaba a receptors increasing the gaba activity shutting down those seizures and so that's the third

thing that you'll do is you'll get on board with your benzo diazepines benzodiazepines okay what are the benzodiazepines that you will start the preferable one if you have iv access is lorazepam and you can give this one as kind of like a four milligrams iv push okay the other one is if you don't have iv access you can give a drug called midazolam okay and sometimes they give this 10 milligrams im but either way you give a benzodiazepine to increase the gaba a activity and cause to shut down those seizures okay so quick thing right

away abcs reverse easy causes start a benzodiazepine okay you've done that they're still seizing what do you do next the next thing you do is you load them up with an anti-epileptic drug we already talked about tons and tons of anti-epileptic drugs which is the best one for status epileptic because when a person is coming in with a generalized tonic clonic seizure the best ones for generalized tonic chronic seizures include levatoracetam phenytoin phosphinetoen valproate these are just some of them but these are kind of one of the more common ones another one that we can

talk about a little bit later in a future video is leucosamide as well we'll talk about that one again later locosamide i'm not going to talk about it just yet but these are some of the drugs that you can load them up with so how should you be doing this patient comes in you stabilize the airway breathing you control their circulation you search for any reversible easy causes reverse them still seizing give them a benzodiazepine after you give them the benzodiazepine and they're still seizing load them up with an aed just after you give them

the benzodiazepine so again what do you do reassess okay after you've done all of this to this point if they're still seizing you need to intubate and start pairing preparing for some more heavy-duty iv anti-epileptic drugs okay so now we go to the next part so what have we done abcs reverse easy causes give them a benzodiazepine load them up with an anti-epileptic if they're still seizing we're going to intubate them and if after we've done that so let's kind of just continue this process they're still seizing we've intubated and now we're going to start

iv anti-epileptic drugs these are the heavy duty bad boys okay so we've loaded the anti-epileptic as we've discussed with these the next thing that we're going to do iv anti-epileptics these include a couple the first one is going to be propofol so propofol is going to be a very important one this one is going to try to shut down that gaba a activity the next one that you could give is iv midazolam okay so midazolam another option includes ketamine so these are three of the big ones here and then one more option that you have

if you really need it is what's called pentobarbital which will also help to shut down those gap increase the gaba a activity and shut down those seizures so these are some of the hardcore iv infusions that you can give to shut down the seizures the other thing you should do in the interim is you should also add on the maintenance maintenance [Music] doses of the selected anti-epileptic drugs so for example if you started them on levotyrazetam you load them up with 60 migs per keg after you've loaded them up then you give them a maintenance

dose maybe you give them 1 000 milligrams bid on top of giving them propofol or midazolam or ketamine or pentobarbital okay if these still haven't worked then sometimes you may even start exploring other options such as like the ketogenic diet and other kind of like downstream options as well okay and so once you get into this part if you still have the person seizing again search for underlying cause and if that is the case if you still have them seizing after putting them on maybe propofol midazolam ketamine pentobarbitol you also have maintenance doses of anti-epileptic

drugs and he tried the ketogenic diet still not working search for other underlying causes because there must be something that's hidden there and you just have to treat that and that will ablate the seizures sometimes what may even happen is you add things sometimes you may put something on maybe you might have propofol and versed or midazolam maybe you'll have propofol and ketamine and maybe you'll have propofol and ketamine and have another maintenance dose of some anti-epileptic or maybe you're adding multiple anti-epileptic medications the point is what is this step-by-step very important remember ready abcs

reverse the easy causes benzodiazepines after they've done that still seizing load them up with an anti-epileptic one of these if they're still seizing after that and you reassess them and they're still seizing intubate after you've intubated them put them on iv anti-epileptics like propofol midazolam ketamine pentobarbital or a combination of those two and then give them maintenance doses of their anti-epileptics that you've picked if they're still seizing you can try a ketogenic diet but you should really figure out why they're still seizing from an underlying cause if you reverse that you may stop the seizures

ninja nerds we've covered seizures epilepsy and status epilepticus [Music]