Episode 71 - Diplopia

[Music] Hello and welcome to the Neurology Exam Prep Podcast. My name is Dr. William Senior ELA of PGI4 Neurology Resident at Yale University. And today we're joined by one of the incredible former residents here at Yale Neurology, now moving on to Emory for a fellowship in Neuroophthalmology. Dr. Kevin Yann. Hi, thanks for having me, Billy, and it's good to be back. So, Kevin, today we wanted to talk about double vision. You know, you hear this issue or chief complaint a lot of the times in the emergency department, usually when you first encounter it, especially as a Neurology resident. What is it? What's your thought process behind this? Yeah, so double vision is a very common complaint and I'll say that when the patient comes in with double vision, they don't actually always say I'm seeing double. Sometimes they'll come in as saying, I can't see clearly. Sometimes they'll say, I can't see. Sometimes they'll say, I have blurry vision. But what double vision means is it is essentially where the visual system is not able to generate one coherent image and the input gets split up into double vision is two, but it can actually be more than two. There are four important questions that everyone should remember when you ask about double vision and this will help you both figure out what the problem is and where it is. Number one is is it monocular or binocular? And by that I mean, does it go away when you cover either eye? You don't ask does it go away when you cover AI? Because if it's monocular double vision from that one eye that you just covered, it would go away. You ask does it go away when you cover the right eye and does it go away when you cover the left eye? If the answer to both is yes, then you know it's binocular double vision, which is a neurologic problem caused by misalignment of the two eyes. If it goes away when you cover one eye, but persists when you cover the other eye, that is a monocular diplopia, which is caused by something in the eye itself, which is more an often melodic issue. If anyone is curious, the most common cause of monocular diplopia is carado conjunctivitis, sicka, better known as trii. But that's an often melodic diagnosis, not a neurologic one. The second question you ask, once you've established that it's binocular double vision is are the two double objects purely horizontal or is their vertical component? And this will get into localization, which we'll talk about more later. The third question you ask is, does it get worse when you look in any particular direction? Left, right, up, down, and you can even parlay head tilt in that as well? And the last question, and this is one that a lot of people tend to forget to ask is does it get better with near or distance vision? Basically convergence or divergence? Yeah, excellent point, Kevin. When you bring up the initial question, establishing whether or not it's monocular versus binocular is quite important, especially for newly minted neurology residents in the emergency department trying to piece out a chief complaint of double vision and then ruling out ocular pathologies. But more so knowing that hey, this is a neurologic issue that we have to elaborate more on. Now that we've gone over very important questions on history, taking for a double vision complaint, let's go into a little bit more about the anatomy that you have just mentioned. So I think the important thing to think about is the entire visual system is quite lengthy and there's a lot of different parts that have to be balanced very well in order to produce a coherent set of images. For the purposes of double vision, we're really interested in the horizontal and vertical gaze pathways. As an overview, I'll give our listeners a summary of both the horizontal and the vertical gaze pathways and we'll describe these in a lot of detail later. And if you have a good understanding of the anatomy, then you'll be able to work through a lot of the disorders when it comes to double vision and figuring out exactly where the problem could be. So we'll start with the horizontal gaze pathway. I think this is probably the slightly simpler one. So the horizontal gaze pathway, we should think of it as beginning somewhere in the cortex. These are either going to be your frontal eye fields when it comes to generating saccades, which are fast movements of the eyes, or the parietal occipital temporal lobes, which are responsible for generating pursuit. But somewhere, cordically, your brain says, look in this direction. And then that travels down and it gets adjudicated in the superior colliculus and then it reaches the parametion pontine reticular formation, the PPRF. This is the horizontal gaze center and it's responsible for generating horizontal gaze outputs. The start of the final common pathway for horizontal gaze is the abducine nucleus, which is just adjacent to the parametion pontine reticular formations. This then has an output to the Ipsilateral abducine nerve as well as to the contralateral ocular motor nucleus via the medial longitudinal vesiculus. The other input that you can have to the final common pathway is from the vestibular system, which is where you get your ocular vestibular reflex. But that's the summary of the horizontal gaze pathway. Those are all the structures that are involved in generating horizontal gaze. Second, let's talk about the vertical gaze pathway. Similarly to horizontal gaze, you also have saccades and pursuit, which start in the frontal eye fields or the parietal temporal occipital lobes respectively. And those are just responsible for generating either fast or slower eye movements. This also travels to the superior colliculus and then it goes to the vertical gaze center. The vertical gaze center consists of several small nuclei in the thelamo-besence of allic junction, which is basically the junction between the phalamus and the midbrain. These include the rostral interstitial nucleus of the medial longitudinal vesiculus, the interstitial nucleus of cahal, and the nucleus of dark shavits. And I want to apologize to any of our Russian listeners because I'm pretty sure I mispronounced Dr. Darkshavist's name. These then spread to the ocular motor and trochlear nuclei as the start of the final common pathway for vertical gaze, which then project to the ocular motor and trochlear nerves. It's notable that up gaze fibers are bilateral and will cross or decasate at the posterior comasher, whereas down gaze fibers are not crossed. And that's the vertical gaze pathways. Those are the components of the horizontal and vertical gaze pathways, both of them of course will end in the muscles and the neuromuscular junction as the final output. So if you understand the horizontal and vertical gaze pathways and all of the intricacies that go into it, you'll be able to localize whatever problem comes at you. Excellent summary, Kevin. Good discussion regarding the horizontal and vertical gaze pathways. Now that we're talking about the anatomy, let's delve in a little bit deeper and talk about the nuclei and the nerves themselves. Which one do you want to start with? Let's talk about the ocular motor nerve. Okay, so the ocular motor nerve and the ocular motor nucleus, this is probably one of the more complex nuclei in the brain. So the ocular motor nerve, it controls the levator, palpipray superior or is muscle, which elevates the eyelid. It controls the medial rectus, which adducts adducts the eye. It controls the inferior oblique, which superducts the eye. It controls the superior rectus, which also superducts the eye, and the inferior rectus, which infroducts the eye. And the rectus and obliques also do other things that we'll talk about later. The ocular motor nucleus is located in the median midbrae. It consists of several subnucleus that are just coddled to the edinter, best fall nucleus, each controlling one of the muscles that I just talked about. The two things that are interesting about the ocular motor nucleus is that the levator palpipray subnucleus is midline and it's shared between the two sides. So it's not actually possible to have a central lesion that causes unilateral toses. The levator palpipray subnucleus does not delineate which side it goes to. It just projects to both equally. Secondly, for whatever reason, all of these nuclei other than the levator palpipray subnucleus, which is bilateral, but all the ones that are lateralized are epsilon lateral with the exception of the superior rectus subnucleus. That is the only one that projects to the contralateral side. This is mostly a trivia question, but ever so often you might see a central ocular motor nucleus problem that will present with contralateral superior rectus palsy instead of epsilon lateral. These fibers then project out from the nucleus and become the ocular motor nerve. We have motor fibers from each of the subnucleus that I mentioned and the eddinger vestvol nucleus contributes parasympathetic fibers to the outside of the nerve that come from the ciliary ganglion. The ocular motor nerve emerges from the medial aspect of the cerebral peduncle and enters the inter-poduncular system at that location. It then travels anteriorly and it passes between the posterior cerebral artery and superior cerebellar artery, which is where it might be compressed by the classic posterior communicating artery aneurysm, and it pierces the duramotor at this place to enter the cavernous sinus. In the cavernous sinus, the ocular motor nerve is one of the more superior nerves, and here it gets the last input, which is where sympathetic fibers from the carotid plexus join with the ocular motor nerve. It passes through the orbital apex and through the superior orbital fissure where it splits into the superior and inferior divisions. The superior division travels to the levator palpibre superior osmuscle and the superior rectus muscle, as well as muir osmuscle, which is innervated by the sympathetic fibers that I mentioned earlier. The inferior division contributes to the innervation of the inferior oblique inferior rectus and medial rectus, as well as the parasympathetic fibers. Actually, discussion regarding the ocular motor nerve there, Kevin. Let's talk about another nerve next. How about the trochlear nerve? Okay, so we'll go in numerical order here. So the trochlear nerve and nucleus are responsible for the superior oblique muscle. This is the only thing that it does, which contributes to the introduction of the eye. The trochlear nucleus is located midline of the midbrain just below the ocular motor nucleus at approximately the level of the inferior colliculus. This is interestingly the only nucleus that decasates after the nucleus. And by that I mean the right trochlear nucleus will generate the left trochlear nerve and control the left superior oblique muscle, whereas every other cranial nerve nucleus controls the Ipsilateral nerve and will have Ipsilateral function. So the axons from the nerve will run dorsally and decasate at the trochlear decazation before they emerge from the brain's dimpt dorsally. And again, this is the only nerve that actually does that every other nerve will exit the brain stem eventually. So the trochlear nerve is the smallest nerve and also the longest intracranial nerve. It exits the midbrain just inferior to the inferior colliculus and of course is laterally and anteriorly along the ponds. And then it passes between the posterior cerebral artery and superior cerebellar arteries before piercing the dura just under the tentory cerebelli and entering the cavernous sinus. It follows a similar course as the other cranial nerves that go to the eye, the ocular motor nerve and the abducine's nerve. And it will travel through the cavernous sinus, through the orbital apex, through the superior orbital fissure and finally reaches the superior oblique muscle. Very interesting. Thank you Kevin. Definitely a superior orbital fissure in area of many nerves, quite the junction in the cranium. Let's keep it going and talk about six. Everyone's favorite abducins here. Yeah, so the abducins nerve and nucleus, this nucleus actually does more things than some of the other nuclei do. But the nerve is actually quite simple when it comes to localization. So the abducins nerve and nucleus are responsible for the lateral rectus, which controls AB duction, abduction of the eye. So the abducins nucleus is located in the caudal portion of the ponds and is beneath the fourth ventricle. It's really split into two portions functionally. One portion has direct control of the Ipsilateral abducins nerve and the other portion directly projects to the contralateral ocular motor nucleus via the medial longitude and obfaciculus. And this is part of the lateral gaze center of the brain, which is why it has to have this contralateral output because to look to one side, you have to both tell your Ipsilateral lateral rectus to fire, but you need the contralateral medial rectus to fire. The abducins nerve will exit the brainstem at the ponto medallary junction to enter the pontean cistern. It runs superiorly between the ponds and the clivus and will pierce the dura-moder to enter the derellos canal. It sharply turns up the apex of the petrous part of the temporal bone to run anteriorly to be able to enter the cavernous sinus and then it follows a similar course through the orbital apex in the superior orbital fissure before eventually reaching its muscle. I mentioned some parasympathetic and sympathetic function with the ocular motor nerve. I'll mention here that for both the troclear and abducins nerve, they are purely motor nerves without any other sensory or sympathetic or parasympathetic function. Yeah, it's very interesting how some of the nerves spare the use of sympathetic parasympathetic function. Others are just purely motor, kind of cool how we got to that point and got to be a big fan of the word derellos canal. I just feel like there's hidden treasure hidden there somewhere. But wonderful. So now that we've talked about the nerves in there at the nuclei responsible for vision, let's talk a little bit about the muscles that they intervene. So the six muscles are the metorectus, lateral rectus, superior oblique, inferior oblique, superior rectus and inferior rectus. This is a basic medical student question that I hope all of our listeners know at this point, but the superior oblique is integrated by cranonore for the troclear nerve. The lateral rectus is integrated by the cranonore of six, the abducins nerve and everything else is integrated by cranonore of three. There is a mnemonic out there. I believe called SO4 and LR6, which might be helpful to some people if you need to remember which one does what. So to run over the function of each of these muscles, the two horizontal eye movement muscles are quite simple. They only do one thing. So the metorectus and the lateral rectus only AD duct or AB duct, that's it. The metorectus AD ducts and the lateral rectus AB ducts. The two muscles involved in superduction of the eye are going to be the superior rectus and the inferior oblique. The way to remember this is that oblique is basically telling you that the muscles essentially coming at an odd angle with the oblique angle. So it essentially does the opposite of what its positioning might suggest. So the superior rectus directly pulls the eye up while the inferior oblique comes at an oblique angle. Even though it's pulling from below, it's also actually lifting the eye. The two muscles that are responsible for infreduction then, going on the same principle, are the inferior rectus and the superior oblique. Now those are the direct actions that these muscles have when it comes to eye movements. But there's also further activity that they do. When it comes to twisting the eyeball or torsions of the eyeball, which might be relevant if people start to tilt their head, for example. Those are performed by the superior rectus, inferior rectus, superior oblique and inferior oblique. The way to remember this is the superior muscles, the superior rectus and superior oblique will perform in torsion of the eye. That's twisting the eye in if you're looking at the patient. The inferior muscles, which are the inferior rectus and inferior oblique, will extort, or twist the eye out. And an amonic can be extortion, which is technically what this is called, though it's spelled exto-rs-i-o-n, is an inferior thing to do because it's a homonym of extortion, exto-r-t-i-o-n. Lastly, the four muscles that are involved in superduction or infreduction all have a tertiary action as well. I don't think our listeners are going to need to worry too much about these, but just to put it out there, if anyone is curious, the muscles with oblique in the name, the inferior and superior obliques are responsible for ABduction as their tertiary action while the muscles with rectus, the superior or inferior recti, are responsible for ADduction as their tertiary action. Another thing to keep in mind is that the obliques tend to do most of the superduction or infreduction work when they are ADducted. So if you want to test the function of the superior oblique, for example, you want to have the eye move in and then down. Well, the recti do most of the vertical movement when the eye is ABducted. So that's an overview of the exact function of each of the six muscles of extroctory movement. I think that was a very comprehensive review on both the anatomy of the nerves, muscles and nuclei that I'll contribute to our gaze. Now let's go in and discuss how we can use that to our advantage to localize some of these common complaints of dyplopia. Let's start with localization of the binocular gaze paulses. Yeah, so these are ones where you have a clear deficit in eye movement in some direction. So first, it's really important to figure out what actions and what muscles are affected. And I would encourage people to just forget about the nerve and the pattern of innovation and just test each muscle individually and just have a checklist. Is this muscle working? Yes or no? And the best way to do this, I think, is to test each eye individually. Cover one eye and just have the patient follow your finger and look in all four cardinal directions plus all four ordinal directions. So eight total directions. And this will really help you figure out which of the muscles is working and which one is not working. Sometimes if someone has subtler deficits, you can use alternate cover testing. If someone has an isolated one muscle deficit, then there is a test called the Parks Beals Gavoski, three step test. And I would like to apologize to any of our German listeners because I probably mispronounced Beals Sikovsky. I'm not going to get into the details here for the purposes of the podcast because I think it's a little beyond the scope of a neurology examination preparation podcast. But if anyone is curious, it's a really good clinical pearl that you can use to figure out what is going on with your patients. Another thing I will say is you should probably check convergence, especially if someone has an adduction deficit. Convergence is from the philamo mesosvalic junction, so it's an alternate way to activate to the medial rectus that does not involve the lateral gaze pathway. So as an example, if a patient came in to me and I wanted to do a good examination to figure out what particular muscles are affected, I would start recovering the left eye and then I would have the right eye look to the left, adduction to test the medial rectus. I would have the right eye look in and up to test the inferior bleak. I would have it look straight up just to test superduction in general, but that's less helpful in localizing. I would have it look up and out, which is going to be primarily the superior rectus. I would have it look to the right or abduction to test the lateral rectus. I would have it look right and down to test the inferior rectus. I would have it look straight down to test in production in general and I would have it look down and in to test the function of the superior bleak. If you check each of these eight directions in both eyes, you can very quickly figure out which action is not working and what muscles are not working. And based on this, you can figure out is this in a cranial nerve pattern is this in a super nuclear pattern, what's the pattern? But localization at a very basic level to figure out exactly what functions are missing is I think really important in this process. And the other thing to remember is if you have both eyes that are having the same deficit, this is where you should think about a central process. If you have just one eye that can't do something, then it's more likely though not guaranteed to be a peripheral thing, either something of the nerve neuromuscular juncture muscle itself. But if both eyes are not able to do the same action, then this raises our index of suspicion for a central process, either something of the frontal eye field for saccades or something of the horizontal or vertical gaze centers that I mentioned above. Cannot be understated enough that doing testing for each eye individually is very important and essential in finding those subtle deficits, I think you would agree. Yeah, definitely. And the reason really is sometimes when the eyes are looking together a fusion can actually mask some of these deficits, especially the more subtle ones. Wonderful. Now we've talked about localization of binocular gaze palsies. Let's try and think about localization from the outside in and really look at some of the common ideologies or things on our differential that could be causing such types of double vision. I do this in a very structured fashion. I go through this way with all of my medical students because I think it's important that you think about all these possibilities to make sure that you don't miss anything. And I would also encourage our listeners when they see someone with a gaze policy to say, okay, this patient has, for example, an isolated abduction deficit of the right eye. I would encourage you not to say this patient has a right cranial nerve six policy because when you do that, you kind of pigeonhole yourself in to thinking that it's a nerve problem. Statistically, it probably is, but as you'll see shortly, there's a lot more possibilities that we might miss if you think that this is a nerve problem too quickly. So from the outside in first, the very outside is what I call the structural problems. These are things like a mass in the orbit, dehisses of a muscle, basically something that causes the eye to structurally not be able to move in that direction. Usually these aren't too hard to figure out. You know, if there's a mass, it'll be pretty obvious either on just your gross physical examination or on whatever initial imaging study you get. And these are definitely not neurologic. If you see something like this, then ophthalmology is usually the team that has to be involved. So I'm not going to talk too much more about them. The outer most part of the nervous system, as people might say, would be the muscle. So these are the six extroachular muscles that we talked about earlier. Some people might include the muscles of eyelid elevation as well. So the etiologies to think about include my cytos. It's certainly as possible to have inflammation of one of the extroachular muscles. Myopathy, this can include both acquired and hereditary myopathy. And I'll point out that a lot of mitochondrial myopathy especially can be associated with extroachular movement disorders like current serideses or chronic external progressive pharmaclegia to mention a few that are listeners will have to be aware of for the boards. Thyroid eye disease is a very common entity that can cause double vision and it's usually associated with things like proptosis and pain and infiltrative lesions. These include infiltration by malignancy, infiltration by other cells, even infiltration by priods as in the case of crutzwood yacchup disease. I think the most common thing in the infiltrative category would be something like a lymphoma that infiltrates into one of the extroachular muscles. And lastly, there's ischemia of the muscle itself. This can be caused by usually inadequate blood supplies sometimes due to vasculitis or sometimes just due to inadequate perfusion. The causes ischemia of one of these extroachular muscles and affects their ability to properly perform their action. The classic one that we really try not to miss is Hortens syndrome, also known as temporal arteritis or giant cell arteritis. And this is something that definitely should not be missed. You have to check a C-reactive protein or erythrocyte sedimentation rate and refer them for temporal artery biopsy and high dose intravenous corticosteroid therapy. If you have an index of suspicion because if you miss this then the ischemia is going to progress and they might actually go blind once the ischemia reaches the retina. So that's definitely something to remember. Elderly patients with double vision do not forget about Hortens syndrome. Make sure you send that Rithroidcyte sedimentation rate or other inflammatory markers. So next moving in from the muscle we have the neuro muscular junction. This is something that I think everyone is very familiar with from medical school. The classic condition is going to be the post-synaptic acetylcholine receptor blockade resulting in myocene agrabis. Don't be fooled by whatever you see in textbooks because it really can cause any kind of extra ocular movement abnormality. It can cause an isolated abduction deficit. It can cause an superduction deficit. It can be bilateral. It can really mimic any of the other things. We'll talk more about ocular myocene later in some clinical purls. Another neuro muscular junction process is Lambert-Eaten Myethinic syndrome. Classically associated with a small cell lung cancer though this tends to affect the extra ocular muscles less. It's a presynaptic process rather than post-synaptic as in the case with myocene agrabis. Other common things include Botox or Botalism. Spread of injected Botox for Cosmetic purposes or for example for Blepharous Basin does happen. It tends to not affect the extra ocular muscles as much as the levator palpribrim muscle for example. But it does happen. And Botalism is certainly one of the things that can cause a pretty rapid onset of Thalmplej if you're seeing a baby or if you're seeing someone who does their own canning. And next we move on to the nerves. And this is going to be the bulk of the differentials that you have to worry about because there's so many different things that can affect the nerves. So first we have to worry about micro-vascular nerve paulses. This is essentially where the nerve suffers ischemic injury due to damage of the small blood vessels that perfuse the nerve. Because of the prevision distribution the nerve tends to die from the inside out when it suffers a micro-vascular pattern of injury and we'll get to the clinical person a little bit. Other things to worry about include inflammation or demyelination. There's a lot of things in this category. Direct inflammation or inflammation of the nerve sheaths. There are certain inflammatory disorders such as the Miller Fisher variant of Guillain-Barracin room that can do this. And you have trauma that can cause traumatic nerve paulses. Usually these are more subtle. And you have compression. And this is where anatomy comes into place so much because there are so many different places that each of the nerves can get compressed. So for example, because all three of these nerves pass through the cavernous sinus, the superior orbital fissure, the orbital apex, lesions in any of those places can cause compressive nerve paulses. So you have to be worried about things like lymphoma, metastatic lesions, infectious lesions, especially fungi when it comes to the cavernous sinus. You can be worried about nerve sheathment in geomas. You can be worried about squamous cell carcinomas. There's a ton of things that can affect this. Vascular lesions can also be at play. This include the classic posterior communicating artery aneurysm for the cranial nerve free paulsi, but really any of these infracranial vessels that run near the nerves can have an aneurysm that will compress one or more of these nerves. You can also have fistulas. For example, the carodid cavernous fistula can cause issues. The cranial nerve six because it starts in the ponds because it exits the brainstem at the level of apontometricary junction. It has to run up quite a bit and it runs adjacent to the bazzle artery for a good distance. So if you have a particularly severe case of bazzle artery doule actasia, which means the artery is not straight and kind of squiggly to use a technical term, that can also push the cranial nerve six. And something that's relatively unique about cranial nerve six is that high or low pressure can also cause issues. And we call this a falsely localizing cranial nerve six because the pressure can cause the brain to kind of sit on the nerve as it interests the relus canal and can cause what we call falsely localizing cranial nerve six paulsi. So this is where thinking about the entire anatomy of the nerve is so important in figuring out exactly what you have to watch out for. And lastly, after the nerve, we think about central causes. So if you have a unilateral nerve paulsi, then it's relatively unlikely to be a central lesion. It's usually going to be peripheral. But there are a few central things that you have to worry about. One is all these nerves before they exit the brainstem run in fascicles, which is essentially just the nerve before it exits the brainstem. So if you have a stroke or other lesion affecting the that happens to pick off the fascicle of the nerve, you're going to have symptoms that are consistent with a peripheral nerve paulsi. Lesions of the cranial nerve nuclei can also cause these kinds of symptoms ocular motor and trochlear nuclei lesions will cause symptoms very similar to ocular motor nerve or trochlear nerve paulsi with the exception of the contralaterally innervated superior rectus that I mentioned earlier. It's important to keep in mind that an abducine nucleus paulsi will cause a lateral gaze paulsi because it's the lateral gaze center of the brain. So that will not cause an unilateral abduction deficit. There are also some interneuclear of thalmapleaches that we should be worried about. There's a classic interneuclear of thalmaplegia affecting the medial longitudinal fasciculus that I'll talk about in a little more detail. But there's also something called the posterior interneuclear of thalmaplegia of luts, which affects the interneuron that runs between the paramedian pontine reticular formation and the abducine nucleus. That is actually one way that you can cause a central isolated abduction deficit. It is very rare. I have never seen one and most of the people I've asked have not seen one either. just because of how small a lesion you have to have in such a specific spot. I think that was a very inclusive discussion of common differentials for Diplopia that we have just discussed. Let's talk about maybe some clinical pearls, some high-yield clinical syndromes in particular to kind of bring everything home. Yeah, that sounds good. And just to our listeners, these are going to be some of the syndromes that I think you're probably likely to see on certification examinations. I think these are some of a high-yield clinical pearls or patterns that I think you should be able to recognize. Let's start off with everyone's favorite cranial of three palsy. Yeah, so the cranial of three palsy classically if it's a complete palsy where you'll have the down and out eye due to the unopposed action of the superior bleak and lateral rectus. But for partial palsies it might not actually be all that far down or out. On examination you're going to see deficits in the four muscles that are innervated by cranial nerve three. So the medirectus, superior rectus, inferior oblique and inferior rectus with preserved function of the superior oblique and lateral rectus. Oftentimes you're also going to see a pretty complete toses or pretty severe toses on the Ipsilateral side from involvement of the levator palpipyrase superioris muscle. The key thing to remember is that because the parasympathetic fibers run on the outside of cranial nerve three, then if the parasympathetic fibers are involved then you're going to have a big pupil. So we have the pupil sparing cranial nerve three palsy if the pupil is reactive like normal and the pupil involved cranial nerve three palsy. The pupil involved palsies because they affect the outside of the nerve or much much more worrisome because that suggests that the etiology is a compressive etiology. And the most acute thing is going to be the posterior communicating artery aneurysm that I mentioned before. The other mass lesions can also do it. If the pupil is spared then that suggests that the nerve is affected from the inside out and the pattern is most suggestive of a microvascular palsy. There are other things of course like nerve sheath spread of primary tumor or some kind of infiltrative process or some kind of inflammatory or demyelinating thing but inflammatory slash demyelinating process but compressive or microvascular tends to be the most common. Clinically what this means is you definitely need to have vessel imaging for any patient that comes in with a pupil involved cranial nerve three palsy. And honestly we get them for anyone with a cranial nerve three palsy regardless of whether or not the pupil is involved because you really don't want to miss an aneurysm because of how morbid that can be if it is missed. But our indexes suspicion is much much higher if it's a pupil involved cranial nerve three palsy. The microvascular palsies tend to be painful and they tend to be associated with vascular risk factors things like hypertension diabetes hyperliplidemia so you need a pretty good vascular workup and I usually send their primary care physician the message that I'm worried about a microvascular cranial nerve palsy and that they really should have better control of their vascular risk factors. The microvascular nerve palsies for cranial nerve three especially tend to be pretty painful so that's another thing that you can watch out for in the question stem. Usually microvascular nerve palsies will get better on their own within a few months but not always. That's an important point Kevin should always check pupillary response to light when anyone comes in with visual complaints. Now we talked about cranial nerve three. Let's go up one in the cranial nerve chart and talk about the ever rare cranial nerve four palsy. cranial nerve four palsy will manifest as a deficit of the superior oblique muscle which deals with infroduction and intortion of the eye. So what you oftentimes see is that patients will have double vision when they look down and there's excessive exterction of the eye from unexposed action of the inferior oblique. So patients will actually just compensatorily tilt their head away from the side of the palsy. So a right cranial nerve four palsy will cause a left head tilt for example. Sometimes we'll see people who always have a particular direction of head tilt and one of the possibilities is that they might just have a congenital cranial nerve four palsy and they're just slightly compensating for it. Because the cranial nerve four has the longest intracranial course it's also the one that's most susceptible to traumatic injury. So the question stem might mention that your patient was in a car accident or had some kind of head trauma and if you're seeing these patients on examination the other clinical pearl is that cranial nerve one and four are the ones that are most susceptible to trauma. So I think it's generally good practice if you check their sense of smell as well especially on the Ipsilateral side. And cranial nerve four palsies are similarly susceptible to the other things that we talked about particularly micro vascular nerve palsies. You heard it here folks. Ulfaction does matter. Now let's talk about the next nerve cranial nerve six. Yeah so cranial nerve six palsy or the isolated abduction deficit as I prefer to call it because I really want to make sure that you don't forget about the other things that will cause an abduction deficit. The abducine's nerve has a pretty long course because it has to run up from the pontometalliary junction. So I mentioned the bazzle artery douletectasia earlier. I mentioned that it can get caught in the clivus at the levels canal. It can get caught in the cavernous sinus either by a math or corroded cavernous fistula or an aneurysm. It can get caught in the orbital apex it can get caught at the superior orbital fissure. There can be something that goes on at the neuromuscular junction or something that goes on at the lateral rectus muscle itself. And one thing that actually is important to keep in mind is when you're looking at the images don't just look at the lateral rectus muscle. Sometimes you'll see that it's really atrophied in cases of myopathy but you should also look at the medial rectus because sometimes an abduction deficit is caused by inability of the medial rectus to relax because those muscles are yoked. And that can be common in thyroid eye disease for example. And there's a clinical pearl. The way to distinguish between myocytus and thyroid eye disease on imaging is that one will involve the tendon in addition to the muscle. That's myocytus. While thyroid eye disease will not it will really only just affect the muscle belly but spare of the tendon. And always remember about the possibility of a falsely localizing cranial nerve six palsy. So whenever you have patients with especially subtle cranial nerve six palsies especially if they have headaches make sure you get out your trustee of thomascope and take a look at their optic discs because if they have papillodema or optic dyskidema that will really change your differential diagnosis management. And similarly cranial nerve six is susceptible to compression and micro vascular lesions like we mentioned earlier. Always important to keep that fundoscope handy. You never know what it's going to be needed especially for complaints about double vision. Let's keep it going with some of these clinical pearls and talk about the peripheral ones like ocular myastenia. Yeah so myocytocrabis like I mentioned earlier is a post-synaptic disorder affecting the post-synaptic aceticoline receptors. Ocular myazine in particular can cause deficits in any of the six muscles. It can cause deficits in multiple muscles. It can mimic super nuclear deficits. It can mimic infernuclear deficits. It sits if it mimics nuclear deficits. It can really do anything. The things to keep in mind are that a) the symptoms really should be fatigable. So if there's double vision involved and you have them do sustained updates for two minutes or so then usually that will make symptoms worse. Another thing that you can do is do an ice pack test. This only really works for toses. It doesn't really work for the extroocular muscle movements but what you do is you place something cold over the eyelid for about two minutes and the purpose of this is to essentially decrease the kinetic action of acetycholinescerase which will break down the acetycholine. You want the acetycholine to stay in the snyptic junction for a little longer. If that improves the toses then that's pretty suggestive of a post-synaptic neuromuscular junction problem. Back in the day though this might still be seen on tests you can do the tensilon test or etrophonium test which is a pharmacologic acetycholinesterase inhibitor that's got very quick onset and very quick offset. The problem is it tends to cause arrhythmias so we don't do that anymore and most pharmaceutical companies don't even produce tensilon anymore but that is something that you might see on tests where they'll ask you about what diagnostic procedure can you do to diagnose my scenegravice and they might say etrophonium or tensilon. Wonderful and let's finish it up peripherally with the other similar disorder, guion-brae miller-fisher variant. Yeah so this is a variant of guion-brae syndrome that was first described by Dr. Charles miller-fisher. Back I believe in the 1950s or 1960s. I don't need to apologize to our Canadian listeners because I'm pretty sure I pronounced miller-fisher correctly. This is associated with the classic triad of a phalliplegia etaxia and areflexia. Though if you look at the literature most patients don't actually have all three components of the triad but it's something that you know you should keep in mind especially if someone has areflexia and there's a pretty prominent vision complaint either blurry vision or double vision. This was caused by antibodies specific to GQ1B and I believe back when I was the host of this podcast I did an episode with Dr. Roy on neuro-muscular quick facts where we went into these in a lot more details. I'll refer our listeners back to that episode if you want to hear a little more. The miller-fisher variant of guion-brae syndrome is something that can be somewhat easily treated with a typical treatments for guion-brae syndrome. So intravenous immunoglobulin therapy or plasma frecis. The important thing is just to make the diagnosis early and make sure you send the antibody for GQ1B early before you give the patients any IVIG because that would destroy your diagnostic utility. Great discussion on the peripheral causes there and some of the clinical pearls associated with them. Now let's go ahead. and talk a little bit more centrally and discuss mainly things like Ionaut. There's a lot of central disorders that will cause vision issues or a phantom pleija. I think this is one of the ones that our listeners will definitely need to know of the classic inter-nuclear of phantom pleija. Drawing out the horizontal gaze pathway, I'm just going to summarize the final column pathway. The abducence nucleus when you want to look to the right, let's say the right abducence nucleus has to tell the right lateral rectus, which it can do directly via the abducence nerve to activate, but it also needs to activate the left medial rectus for gaze to be yoked. It does that via a white matter track called the medial longitudinal vesiculus. It's medial, as the name suggests, it's longitudinal as its name suggests and it is a bundle of nerves, which is what the vesiculus is. The name is actually pretty descriptive. Elysian here and the most common causes are going to be either ischemia or demyelination, depending on the age of a patient and the other risk factors involved. Let's say you have a left inter-nuclear of phantom pleija. We'll cause an inability for the left eye to adduct when you're trying to look to the right. We always name these inter-nuclear phantom pleija based on the side of the adduction deficit. So what happens is when you're looking to the left, everything's normal, when you're looking to the right, the right eye will abduct as normal, but the left eye will stay midline because the medial longitudinal vesiculus is not able to get that message from the right abduceless nucleus to the left ocular motor nucleus. If you read the textbook, the right eye will also have some nistakmas. I've seen it pretty frequently, but it's not something that you're always going to see and it's not something that everyone checks for. A key thing for the inter-nuclear of phantom pleija syndrome is because there's not actually anything wrong with the ocular motor nucleus or the ocular motor nerve or the medial rectus muscle. The eye is still able to adduct if you're able to activate that pathway from a different input. And the way to do that is you check convergence because this comes from the thalamobesis and phallic junction. So it bypasses the medial longitudinal vesiculus and both eyes actually will converge appropriately. So that's your test to show that the medial rectus, the ocular motor nerve and the ocular motor nucleus are all functioning well. The one caveat is that a mid-brain inter-nuclear of phantom pleija might have impaired convergence just because it can affect the ocular motor nucleus itself. But most of these are caused by pontine lesions and pontine lesions classically will have preserved convergence. While we're on the same page, let's talk about some other super-newular palsies. I'll apologize in advance to our Polish listeners. One such example is steel Richardson-Aus-Zuski syndrome, also called progressive super-nuclear palsy, which typically presents with an up-case palsy as one of the complaints. There are other things that can also cause an up-case palsy. For example, paranode syndrome or dorsal midbrain syndrome. And just going back to the anatomy, if you remember that the up-case fibers are bilateral and the deca-state. So any kind of dorsal or central mid-brain lesion can very easily knock out the up-case fibers. Whereas down-case fibers because they're not bilaterally innervated and they do not deca-state, in order to have a bilateral down-case palsy, you actually have to have two separate lesions that will knock out both down-case pathways independently. So that's why a lot of these syndromes will have up-case palsy, but not down-case palsy. And other things to think about are the central-case palsies or case preferences to one side. So if you have, for example, a stroke or a seizure that either deactivates or hyper-activates one part of the frontal eye fields, then you can have gaze palsies towards or away from that side. A good rule of thumb is that you look towards a stroke and away from a seizure because the stroke causes hypofunction of the affected side of the frontal eye field will not be pushing as much. A seizure will cause hyper-function, so you're pushing farther away from that side. Not ironclad, there are things called wrong way eyes and strokes in rooms, but that's typically a good rule of thumb when you're dealing with frontal eye field lesions. And other things like mass effect, infiltrative lesions were really anything that affects the frontal eye fields can cause these central gaze palsies. It's also good to keep in mind that the vestibular systems will also cause inputs to the phytonocomment pathway, so you can certainly have things like vestibular lightest that will also cause some gaze dysfunction. But those are a lot less likely to cause double vision, so we won't get into those as much in this double vision episode. Very good. That was quite the comprehensive thorough discussion on double vision. Today we discussed the anatomy, looking at the nerves, particularly cranial nerve 3, 4, and 6, and then delving into their nuclei and associated innervated muscles. You can probably agree that there's a lot that can go wrong that could be the cause of double vision, but today I think we did an excellent job discussing everything as much as we could. Well, thank you Kevin for coming in and talking us today as the neuroophthalmology fellow from Emory. Yeah, thank you for having me Billy, and it's good to see that the podcast is doing so well. Pleasure to have you. Good luck on your certification examinations everyone. [Music]