Lecture: Review of Cranial Nerves 3, 4, and 6

>> Good morning, everyone. Or wherever you are, whatever time it is, it’s morning here in Halifax, Canada where I’m assistant professor of neuro ophthalmology and adult strabismus. Today, is a basic review of cranial nerve 3, 4 and 6. Mostly anatomy focused and helping you localize the lesion. There will be a little bit of time for questions and I will go over some more common etiologies that I see. It will be very different from what you see probably where you are. But that doesn’t change the fact that the best way to figure out an etiology or determine what the next step for blood work or testing is going to be dependent on your history taking. So we will get started. I do not have any financial disclosures or conflicts of interest at all. Let alone related to this talk. So just out of curiosity, I just want to see who is in the audience. If you can let me know who I’m presenting to that would be great. Okay. So couple of others but mostly staff ophthalmologist and ophthalmology residents and a few medical students. Great. Now that we know the poll function works, of course, I cannot do a presentation without a pop quiz. Don’t worry about the answers, if you don’t know the answer, you can still answer in the poll. But we will be reviewing the answer at the very end. The answers to these questions will be part of the presentation as well. The oculomotor nerve or cranial nerve 3, innervates the medial rectus, superior rectus, inferior rectus, and inferior oblique. B is responsible for eyelid closure. C, innovates the levator palpebrae superioris and the pupillary sphincter. Or D, A and C are both true. Okay. Good. Next question. The trochlear nerve or cranial nerve 4 exits ventrally from the brain stem just like all the other cranial nerves. B, can cause a hypertropia if damaged. C, is hardly ever affected by head trauma. Or D, has a short segment that is unprotected in the subarachnoid space. Okay. Good. And last question, the abducens nerve or cranial nerve 6, the nucleus is located in the pons and surrounded by fibers of cranial nerve 8. B innervates the lateral rectus. C, B and D with both true. And D is communicates with cranial nerve 3 through the medial longitudinal fasciculus, otherwise known as the MLF. Okay. Good. So think about those questions and we will revisit them at the very end, okay. So I can’t talk about the cranial nerves without reviewing the anatomy. Let’s first review the anatomy of the extra ocular muscles which can cranial nerves innervate. To achieve extra ocular motility you have these six muscles. The easiest ones to start with are the horizontal, the medial and lateral rectus. They only have one function, the medial abducts the eye towards the nose and the lateral abducts the eye towards the temple. And then the inferior and superior muscles that do the vertical aspects of eye movement but they also have secondary and tertiary functions. So the secondary function is just a little bit more than the tertiary function but their main function, the inferior rectus depresses the eye and the superior rectus elevates the eye. They just have mild, very, very mild torsional components and the abduction and the adduction they both do is also very minimal. And then the inferior oblique and superior oblique. Inferior oblique, it excyclotorts the eye and then the superior is in the trochlea and intorts the eye when it contracts. They also have some role in the elevation and depression. So they are responsible a little for the vertical movements. And very, very mildly with abduction. The innervation for these muscles is fairly easy to remember if you have this mnemonic. Basically, LR6SO4 mean it is lateral rectus is innervated by the abducens nerve or cranial nerve. And the superior oblique is innervated by cranial nerve No. 4. Three does everything else including the eyelid and the pupil. This is a great anatomy diagram that overviews all the cranial nerves and their relationship to each other. So I always reference back to this diagram when I’m trying to think about where the cranial nerves are. It’s also important to think about where all the cranial nerves are all together if you have multiple cranial nerves. We’ll talk about that later in the talk. Not only that, I like this diagram because it shows the relationship between the cranial nerves in relation to other structures in the brain such as the blood vessels. You see in this diagram here you have all of the cranial nerves coming out. It has the orbit and the eye there but it’s also got the bones and importantly, the blood vessels that can cause problems sometimes. So this is a nice overview. You can see where everything originates. I’m going to put a laser pointer here. So you have cranial nerve 3 and 4 up in the midbrain and cranial nerve 6 in the pons along with the trigeminal nerve and such. We won’t talk about the other cranial nerves, we will briefly mention them. But the main cranial nerves will be 3, 4, and 6. So to jump into the anatomy, the oculomotor nerve or cranial nerve 3 has a fairly large nucleus in the midbrain and each section of the nucleus is responsible for a different function. Generally speaking, as it exits the midbrain, it will pass between the SCA which will be below it and the PCA which is above it. And then it will run obliquely to the tentorial edge and parallel and lateral to the posterior communicating artery. This becomes important because the pupillary fibers are usually on the dorsomedial side of the nerve which means that if there was any issue with the posterior communicating artery here, like it had an aneurysm, for example, you would be pushing on these pupillary fibers and these pupillary fibers end up with a large pupil. So I like this diagram it shows cranial nerve 3 just as it exits. It exits between two blood vessels, two arteries and courses along the side another artery before going to the dural canal. The other thing that is interesting about cranial nerve 3 in this position is it’s vulnerable to compression by uncal herniation. That means the most medial aspect of the temporal lobe which is not shown in this diagram, but basically as the medial aspect of the temporal lobe is forced through the tentorial notch to push on the cranial nerve 3, because there’s a mass above it supra tentorially causing that downward pressure. This again, would also cause a blown pupil because the pupillary fibers are dorsomedial in this area. After it enters the dural canal at the back edge here in the dura of the clivus, right above cranial nerve 4, it runs in the superior lateral wall of the cavernous sinus before it separates into the superior and inferior divisions and enters the orbit to innervate everything but the lateral rectus and the superior oblique. This is a good diagram to summarize in a schematic form the course of the cranial nerve 3 and all the different locations that you can have a lesion that would cause a problem with cranial nerve 3. So you have either a nuclear lesion which we will not go into. Just know the anatomy is a very important fundamental basic knowledge that you need to know when you think about cranial nerve 3 to see where all the possible locations of the lesion can be. Moving on from cranial nerve 3, we’ll touch on cranial nerve 4 now. So cranial nerve 4 is unique because its nucleus is in the midbrain just below the aqua duct. But it decussates, it crosses before it exits. The other interesting thing is it’s the only cranial nerve that exits on the dorsal surface of the brain stem where others will exit ventrally, like you saw in cranial nerve 3. The other thing about it is that it is the longest and thinnest and also got the longest unprotected intracranial course that makes it vulnerable to closed head trauma. As it exits here, it’s in free subarachnoid space and not protected by any other surrounding structures which is why you end up getting a cranial nerve 4 palsy most commonly when you have closed head trauma. It doesn’t have to be massive trauma, it can be something that can cause a concussion and some people end up with a cranial nerve 4 palsy. After this, it swings around the midbrain and it will parallel the tentorium just under the tentorial ridge or the edge, sorry. If you see from this diagram when I was focusing on cranial nerve 3, cranial nerve 4 is right, where is it, right here. This thin tiny small one as it keeps going. And because of that, it’s just under the tentorial edge. So any neuro surgical procedure that involves the tentorium can potentially damage the cranial nerve 4. So in that case you would get an iatrogenic cause of cranial nerve 4 palsy if they dinged the tentorium and hit cranial nerve 4. After that, it then enters in the posterolateral aspect of the cavernous sinus underneath cranial nerve 3. And then goes into the orbit after that. And again, this is a good diagram to summarize basically all the possible places that you can get a cranial nerve 4 palsy where the lesion could be, with the subarachnoid space being probably the most common one because it’s unprotected there. Okay. Last but not least, the abducens nerve, cranial nerve No. 6. Its nucleus is in the dorsal caudal pons and it is surrounded, like literally hugged by the looping fibers of cranial nerve 7. Which is the facial nerve. So the seventh cranial nerve has its nucleus just around where cranial nerve 6 is, the nucleus as well. The fibers wrap around before they exit. Cranial nerve 6 runs within the subarachnoid space along the clivus and enters the dura 1 cm below the petrous apex and travels beneath the petroclinoid ligament, also known as Gruber’s ligament. It’s a ligament that connects the petrous pyramid to the posterior clinoid. After that, it then goes into the inferior petrosal sinus and exits the dura into the cavernous sinus. The only cranial nerve that is in the stuff of the cavernous sinus. If you remember in the cavernous sinus most of the cranial nerves are off to the side. Cranial nerve 6 is the only one inside. It’s beside the internal carotid artery. And enters the orbit through the superior orbital fissure. Why is it cranial nerve 6 that is most vulnerable and you get a cranial nerve 6 palsy when you have elevated intracranial pressure? That has to do with its anatomy. You see here it’s vulnerable in this area right between the brain stem and the clivus in the subarachnoid space. As it enters the canal, it gets tethered there. What happens in elevated ICP, you have high pressure in the brain for whatever reason, is sometimes the brain stem is pushed downwards. When it’s pushed downwards, there is stretching of the cranial nerve 6 which is why you get cranial nerve 6 palsy when you have high pressure in the brain. So that’s the review of the anatomy. I can show you this again if there are questions at the end asking for it to be shown again. But the anatomy is very important and always go back to basics to your anatomy if you’re confronted with a nerve palsy and you don’t know where to localize. Now, we’ve talked about the nerves, what happens when there is a nerve palsy. A lesion somewhere in the nerve that is causing a problem. How does that present clinically? The things you need to ask about are to screen for all of these possible etiologies. I’m not going to go in detail because I assume with the audience being mostly staffed ophthalmologist or neurologists you know how to take a history. You know how to ask about associated symptoms. You know how to examine that if there is more than one cranial nerve involved you know where that would localize to. But generally speaking, fall back on these possible etiologies. Some people use the mnemonic vitamin C and D to go through the V stands for vitamin, I is ischemic and they go through all the possible etiologies like that. That is a great fall back as well if you’re trying to think about what is causing this patient’s cranial nerve palsy. The other thing that is important is while you’re taking history, don’t forget about the patient’s general health and their medications and if they ever had any trauma or neuro surgical procedures or anything like that. History is very important. In terms of infectious causes, they vary from place to place. But neigh can hit the brain can potentially affect a cranial nerve. And any history of neoplasm in the body, potentially can metastasize to the brain and also don’t forget that we can cause problems especially if you’re tinkering around in the brain and causing — neuro surgery usually, causing problems. And sometimes you can’t help that. Sometimes cranial nerves need to be sacrificed during surgery. Don’t forget that a good history will usually point to the most likely etiology that will then guide your investigations. Cranial nerve 3 palsy. So we talked about how cranial nerve 3 basically innervates everything except for the lateral rectus and the superior oblique. Which means that when it is not working, your eyelid comes down because you have no more innervation for something to keep the eyelid up. And you get exotropia because the lateral rectus is functioning just fine and it’s pulling because that is innervated by cranial nerve 6. You get a hypotropia because the superior oblique has a small vertical component and keeps the eye a little bit up. If you don’t have cranial nerve 3 working, everything else doesn’t work. You will get a ptosis, an exotropia, a hypotropia, the eye is down and out. And you may or may not get pupil involvement if the pupillary fibers are involved. This is a good diagram with the gaze showing this. In primary, there is a left ptosis. There is a positive thumb sign in the photograph meaning the eyelid has to be held up by the examiner. Abduction of the eye is no problem. No adduction, no elevation, and not a lot of inferior down gaze depression either. So classic presentation of a cranial nerve 3 palsy. You can’t see the pupils in this diagram. So a good pupil examination is important. If there is major anisocoria, a big pupil on the left side compared to the right side, you suspect there is pupil involving cranial nerve 3 palsy. That is important. Why is it important? It helps you make your decision for whether or not you do imaging. This is a very basic and for me, I like to think about cranial nerve 3 palsy and when I need to get neural imaging with this diagram. I first think, is the cranial nerve 3 palsy complete or sit partial? If it’s partial, I’m getting imaging. I’m getting a CT, CTA or MR, MRA or if you need to get angiography, you get angiography for this. You’re screening for the Pcom aneurysm or a blood vessel abnormality. Remember where cranial nerve 3 exits in the brain. Is there aberrant regeneration? Yes. I’m getting imaging. I don’t care, it’s compressive until proven otherwise. These are the two situations where it’s compressive until proven otherwise. If it’s complete, you can have some time. If it’s complete and involves the pupil, the pupillary fibers are vulnerable to either uncal herniation or aneurysm, you’re getting imaging right away. If it spares the pupil, you have time to observe. In my experience, everyone gets imaging for cranial nerve 3 palsy anyway. The difference is if it’s pupil sparing you have time. You have time to schedule the imaging. It doesn’t have to be urgent or semi-urgent like in these cases. Pupil sparing complete, the eyelid is completely down, completely down and out, the pupil is not involved, you can observe. If eventually, it’s pupil sparing at first, you still need to follow these people. It becomes pupil involving, you’re getting imaging right away. If it never involves the pupil you’re okay to observe and wait to get imaging when either the pupil gets involved or it’s not resolving. This is an example of a nine-gaze photograph of someone who has a cranial nerve 3 palsy but has aberrant regeneration. You need to get urgent CTA or MRA head to screen for either the posterior communicating aneurysm, a compressive lesion or if there is any history of major trauma. The reason being is, there is now evidence that cranial nerve 3 has been affected by likely a compressive or a traumatic etiology. And has already regrown to the wrong targets. So in this case, you see there isn’t a ton of ptosis. So you won’t even suspect it’s a cranial nerve 3 palsy until they look down. What is your eyelid supposed to do when you look downwards? The eyelid is supposed to come down with your eye when you look downwards. If you look at someone looking down, you notice their eyelids come down. In this case there is a left nerve cranial nerve that has aberrant regeneration because there are fibers that are innervating, when you look down, the eyelid comes um instead. There is aberrant regeneration to the eyelid. And I think there is also aberrant regeneration, yes, there is aberrant regeneration in elevation here in this photo. The medial rectus is also involved. We have muscle to muscle and muscle to eyelid aberrant regeneration here. This is concerning. If there is no history that you know of of trauma and you don’t know whether or not there is compressive etiology, you need to image to rule those out. Okay. I would encourage you to please sign up and register for this upcoming webinar in December which will go into more detail about cranial nerve 3 palsy and its treatments with Dr. Sriram at the Moran eye center in Utah. Because of this webinar, I won’t go into more details about cranial nerve 3 because there will be an excellent webinar about it later this year. With that, I’m going to move on from cranial nerve 3. Cranial nerve 4 palsy. It’s always the tough one with the park’s 3-step test. This is to review how you find a cranial nerve 4 palsy using park’s 3 step test. If there is a cranial nerve 4 palsy, it usually causes the eye to be higher. So the first step is which eye is the higher one in primary position? Okay. The impacted muscle will either be the depressor of the higher eye or the elevator of the lower eye. In your diagram, those are the things that you circle. I will get to that in a second. Once you determined which eye is the higher one, you need to see does it get worse in right or left gaze. Does the higher eye get higher in left gaze or in right gaze. If it’s in left gaze, then it’s the superior oblique in the right eye or the superior rectus in the left eye that is affected. So you circle over there in the left side. Okay. If it’s the right side that is affected when it’s worse looking to the right, you circle the superior oblique in the left eye or the superior rectus in the right eye. Circle those ones. And finally, is the hypertropia worse in the left head tilted or a right head tilt? If it’s worse in right head tilt, the right eye intorters, the superior oblique or the superior rectus, or the left eye extorters, inferior oblique and inferior rectus, are affected. You circle this way. And if it’s worse in left head tilt, it’s the left eye intorters or the right eye extorters. I think this diagram does a good job of it. You will end up with the superior oblique or if you don’t, you end up with another muscle that is circled three times but that is how you find out where the problem is when dealing with vertical deviations. I encourage you to look at this website and go through it again. Eye wiki. Really go through it and try to understand it. I know for beginning learners, the first step that is important is figuring out which eye is higher and circling the correct ones for these ones. And then the cheat after that is if it’s worse in left gaze, you circle the ones on the left side. If it’s worse in right tilt, then you just circle the ones tilting to the right this way. But, it’s better to also understand the concept. But if you’re in a pinch for time, make sure you get the first step right and then the other steps are a little easier. If it’s worse in right gaze, you circle the right ones. If it’s worse in left, you circle the left. If it’s worse in right tilt, you circle the tilt to the right. And if it’s worse left, you circle to the left. Don’t tell anyone that I told you that. Like I said before, it’s the longest and thinnest of the cranial nerves and most susceptible to trauma. It doesn’t have to be major trauma. But it’s one of the ones that are more commonly congenital. So you can have a congenital cranial nerve palsy and not notice until later in life when it decompensates. People don’t get double vision for most of their life from their congenital cranial nerve palsy and they have an illness or it decompensates over time. Clues to telling you it’s long standing or congenital, look at their old photographs. Ask them to bring in photo albums from when they’re children or teenagers and you can almost see when they get the palsy. Children that have cranial nerve palsy and grow up with it don’t have double vision because they compensate well. The vertical fusional amplitudes are large. I see people that have double vision but when you check the vertical fusional amplitudes they’re like 6 which is not normal. The only way that can be is if they had it for a very long time, usually within childhood. Because of the long standing head tilt to one side, gravity causes changes to that size of the face that is down. When you finally straighten them out, they have a little facial asymmetry. So these are the three clues that can tell you it’s probably long standing, and you don’t need to do any neural imaging urgently for them. However, if it suddenly becomes acute and there is no documented history of trauma to the head, I would get an MRI brain with contrast. It’s best when you are talking to neuro radiology that you’re ordering this test because you’re looking specifically at cranial nerve 4 so they know which sequences to get the best to image the cranial nerve 4. Cranial nerve 6 palsy. So this one is fairly easy. You get an abduction deficit. In this diagram here, the left eye is not abducting and it doesn’t matter if it’s up or down, it doesn’t abduct. Where the abduction towards the right is normal. So generally speaking, neural imaging is recommended if the patient is younger than 50. If there is associated pain or other neurologic symptoms. If there is a history of cancer. If it’s bilateral. If any of the other cranial nerves are involved. Or if it doesn’t go away after 3 month, you’re thinking about getting imaging. If they have papilledema on examination or they are complaining of symptoms of elevated intracranial pressure. Things like headache, nausea and vomiting, pulsatile tinnitus, transient visual — diplopia from the cranial nerve 6 palsy, all those together indicate maybe there is high pressure in the brain and you should get an urgent CT, CT gram or MR, MR venogram. The reason for the venogram is you’re also screening for a venous sinus thrombosis that can cause elevated brain pressure. You need to image these people if there is something unusual about it or any of these criteria come up. Okay. I know this is not a cranial nerve but it relates to two cranial nerves that need to talk to each other. So have you ever wondered when you look to the right or when you look to the left, you are utilizing one lateral rectus to move one eye the other way and one medial rectus to move the eye in the same direction. The reason it can do that is because there is a connection. There is an internuclear connection, a connection between the nucleus of cranial nerve 6 and 3. That coordinates this movement so you can look to the left or look to the right, you can look side to side at the same time. And this connection happens through the medial longitudinal fasciculus, the MLF. Right here. You have cranial nerve 6 here, cranial nerve 3 here and they talk to each other through this bundle, the highway. So when you need to look to the left, there is a connection here so the eyes both move together. What happens if you get a lesion in the MLF? They can’t move together anymore and that is when you get an internuclear ophthalmoplegia. There is a communication between them that is not good and the ophthalmoplegia, because of this it’s not moving together. Classically on examination, you have an adduction deficit. The medial rectus doesn’t go when you’re trying to go this way. And you get a contralateral abducting nystagmus. There is beating nystagmus and the eye cannot adduct. One can’t adduct and the other is beating with nystagmus. The most common etiologies, generally speaking, is a younger patient, usually demyelination in my part of the world. And stroke is more likely in older patients in my part of the world. When I see an internuclear ophthalmoplegia, if they’re young or old, I get an MRI. If they’re old, I get a CT or CTA or angiography, I need a blood vessel testing because stroke is most likely. I’m looking for a stroke in the blood vessels, is there an occlusion somewhere. So the MRI brain with contrast achieves that. But in a pinch, the MRI brain is good for demyelination because you find the white matter lesions. And the CT scan in a pinch is you can’t get MRI urgently is okay for stroke because can get a CT, CTA head and neck for that. I said I would talk about multiple cranial nerves. This is back to anatomy. Think about where the cranial nerves all come together and if they have other symptoms. If more than one is involved, you have to think about where it localized: Anatomically you know that 3, 4, 5, and 6, if all of them are somehow involved, it’s either going to be at the cavernous sinus or the orbital apex if cranial nerve 2 is involved. If they have vision loss and these other things you think the orbital apex or the cranial nerves and it’s probably cavernous sinus. Remember 6 and 7, if you have an abduction deficit and facial palsy, that can only be in the pons and the cerebral pontine angle. That’s the only place the two are together. It’s more likely for one thing to hit two things together if they’re close together. Don’t think about where they’re anatomically separate, but where are they the closest together. And so this will help your radiologist localize the lesion better if you tell them exactly where you’re looking for a lesion. Okay. So most of this was focusing on the anatomy because it was mostly looking at compressive etiologies. Where I am, I also see a lot of ischemic micro vascular cranial nerve palsy. And because of where I am also, I see a lot of vasculitic. That doesn’t mean that any of these are not possible but these are found out by history. And so for infectious, here in Canada, I tend to order a lot of Lyme serology because Lyme is endemic here. This can be very different for someone else in another part of the world. TB for example is a common cause potentially somewhere else. I do also test for TB here because we have a lot of newcomers coming to the country as well. Lyme, TB, or any of the viral infections sometimes I will think about as well. But again, history. And the examination, are they febrile. Do they have other issues. So there’s that. Traumatic is pretty obvious, they’re usually in the ICU with a big trauma. And demyelinating, infiltrative, neoplasmic, iatrogenic, again, history, history, history. I’m going to touch on ischemic and vasculitic because for me they’re most common. Micro vascular ischemic nerve palsy tends to happen in patients with poorly controlled vascular risk factors: They have diabetes, they have high blood pressure. They have high cholesterol. They have an unhealthy lifestyle. They’re obese. You know what this person looks like. If they come in with a cranial nerve palsy, most likely than not it’s probably this. You still need to do your exam. Do your due diligence and make sure if there are more cranial nerves involved. Sometimes vascular nerve palsies can be painful. It’s an aching pain. And classically they should resolve in two to three months. If they’re not resolving in two or three months and they’re not starting to get better, then you worry it’s not micro vascular. You need to think all the other etiologies, review the history, did I get neuro imaging. You should if it doesn’t resolve in two to three months. And you need to collaborate with the patient’s general practitioner, their family physician to make sure you get the help they need. They need vascular risk factor modification. They need to control diabetes. They need to bring down cholesterol. They need to stop smoking. You need help for this. It’s a collaboration with the patient’s other health providers as well. When the microvascular nerve palsy happen, it’s a sign they’re having trouble with one of these things and you need to talk to their family physician to help with that. I see giant cell arteritis a lot. In Nova Scotia, our population is older and mostly white. Giant cell arteritis, if you don’t see it much if your part of the world, that’s goods. But in my part of the world I see it quite a lot. It’s the most common primary vasculitis in the older pop lakes. The median age is 75. I think about this in anyone older than 60. On pathology, it’s a granulomatous inflammation of the medium to large sized vessels and classically they have headaches, PMR symptoms or joint pain getting worse. Scalp tenderness, jaw claudication. They are losing weight. They don’t look good: They don’t feel good. I know we think about the giant cell arteritis when there is an arteritic anterior ischemic optic neuropathy. But don’t forget, the cranial nerves also need to be supplied by some of these medium size blood vessels. You can get cranial nerve palsies with giant cell arteritis. So I have a low threshold of suspicion in someone who is 70 and doesn’t have much in the way of vascular risk factors. They have been healthy most of their life and all of a sudden, they get cranial nerve 6 palsy or cranial nerve 4 palsy. I have a low threshold of asking about these symptoms and if they have a few of them, I test for ESR, PSC, look for platelets for inflammatory markers and I get a biopsy and manage with corticosteroids if that’s needed. You can get nerve palsies if giant cell arteritis is something you see commonly in your side of the world. If you don’t see giant cell arteritis ever, keep it in the back of mind and screen the more common things but for me, it’s one that I cannot forgot about. The worst that I think can happen is you think it’s micro vascular and they lose vision from an arteritic ischemic optic neuropathy. Prevent the vision loss from happening and treat the giant cell arteritis sooner rather than later. So here we are back at the quiz questions. I think the majority of you guys did really well even before the presentation. So they were fairly easy questions. But the oculomotor nerve, A and C are true. It innervates all of these muscles and also all of this. It’s not responsible for the closure, a cranial nerve 3 palsy results in eyelid ptosis because it innervates the eyelid in terms of opening it. And then cranial nerve No. 4 can cause a hypotropia if damaged. Remember the park’s 3-step test. Which eye is higher. We talked about how it’s one of the unique cranial nerves that exits dorsally from the brain stem. Unlike the other cranial nerves. It’s easily affected by head trauma because it has the longest unprotected course of all the cranial nerves. It’s a long segment which is why it’s prone to trauma. That was the answer for this question. And then the abducens nerve, cranial nerve 6, yes, it innervates the lateral rectus. The nucleus is located in the pons and surrounded by fibers of cranial nerve 7. That is cranial nerve 7. You have to think about this with a facial palsy and abduction deficit. Think of something happening in the pons. As you awe before the cranial nerve 6 nucleus is wrapped around by the cranial nerve 7 fibers and then, yes, it needs to communicate to cranial nerve 3 with the nucleus of cranial nerve 3 through the MLF in order for you to do a horizontal gaze properly. Because you are, whenever you do a horizontal eye movement, you are activating a lateral rectus and medial rectus in order to look in that direction. In order to do that properly and together, there needs to be communication and that’s the MLF. If you have a lesion in the MLF, you cannot do that communication properly and you get an intranuclear ophthalmoplegia. So B and D are true in this question here. Okay. That was a lot and it was a basic review. I didn’t touch hard on some of the clinical aspects of it because this was meant to be a beginners review of the anatomy and just to think about basics again. But I guess we will move onto questions now. So I’ve got the Q&A open. Okay. I’ll just start going in order and I guess I’ll answer them. A question, have you noticed an increase in cranial nerve palsies post COVID? If yes, was it temporary or permanent palsy? I don’t know I did notice an increase in cranial nerve palsies post COVID. I’m also fairly new to practice. I did my fellowship during COVID. As I came into practice, I still see the most common things are micro vascular and giant cell arteritis is the most common causes of nerve palsies. There have been a few cases where it resolved on its own and they didn’t have vascular risk factors even though I looked for them. But they weren’t immediately after a COVID infection. Some of these are idiopathic and maybe post viral and I don’t know. I can’t speak to it because of my lack of experience. And so that’s the answer to that question for you. I’m sorry, I can’t answer for you. But I don’t think there’s been an increase in cranial nerve palsies post COVID but I would have to ask my more experienced colleagues for that. Next question, how long can you delay imaging for pupil sparing cranial nerve 3 palsy? Is there a specific algorithm you utilize? What I do, if there is a complete pupil sparing cranial nerve 3 palsy, I actually observe them. So I will actually still order the CT, CTA and send it to radiology. But I don’t put on it it’s urgent or anything like that. At least they have the requisition. Because there’s a delay for us here in getting things done sometimes for imaging. So I put in the requisition anyway. I observe them once weekly. If they’re a very reliable patient, I tell them to check their pupil every day and call my office if it changes. For the unreliable patient, I check them once a week. Bring them back to make sure the pupil is okay. If the pupil is okay after three weeks, I’m like, okay, you’re probably micro vascular. Normally I only feel comfortable doing that if I see their medical history and it’s diabetes, poorly controlled hypertension, sleep apnea. The whole thing. That’s the only time that I’m like, okay, you’re probably micro vascular. Most of the time I’m sending a requisition anyway and if they improve, I cancel the requisition. If the pupil is changing, I call them and say I need this done urgently. That’s how I do things. It might be different at your institution but that is how I do it. Seems like the next question is very similar. How long does it take to have aberrant regeneration occur? I’m not sure but I think it’s within months. So in trauma and in compressive, you start to get aberrant regeneration within months. The scary thing is when you see a patient for the first time and there is no history of trauma and they have aberrant regeneration already, you send them for imaging right away. If you know there’s trauma, so there’s a neuro surgical procedure and they cut cranial nerve 3, you sometimes will see aberrant regeneration within a few months. Around the same timeline as when a micro vascular resolves I would say. I noticed it within two to three months when I see these patients in follow up. Okay. Next question, how do I know whether the cranial nerve 3 palsy is partial or complete? I had the exact same question when I was in fellowship. Partial is when you have only some eye movements involved. Say they can still adduct but they can’t elevate or depress well and the eyelid is only partially down. When I think of complete, complete ptosis, you only have a little bit on the bottom left. And the eye is completely down and out. That’s to me complete. So any time that it’s partial and it is early or hasn’t gone to complete yet, but I don’t care. If I see them at that point, I get neuro imaging because it’s partial. I hope that answers your question. How long do you observe or follow up a pupil sparing cranial nerve 3 palsy? I see them weekly to make sure the pupil is not becoming involved. I do that for three or four weeks and after that I’m okay, it should be fine. I still tell them to look at the pupil every day and call me if it gets bigger or changes. Usually by a month, I feel better about this. Next question. If the patient had acute cranial nerve 6 palsy and decided to give Botox, can we give bilateral Botox or only ipsilateral and why? I don’t have a lot of experience giving Botox but I know that a lot of people do just so you don’t get the contraction of the medial rectus while you’re waiting for it to resolve. From what I’ve seen, it’s only giving it to the medial rectus muscle. Because you don’t want to cause more paralysis of the lateral rectus muscle. Okay. How’s aberrant — Dr. Ahmed, how is aberrant regeneration caused. I may answer this question a little differently, it will still answer your question though. The reason you don’t get aberrant regeneration in a micro vascular nerve palsy is because all these structures of the cranial nerve, all the scaffolding for the nerve is intact. It was just ischemic, the nerves had ischemia and died and regenerate. They regenerate and have all the scaffolding that is normal for them. They all go to the correct targets after a micro vascular palsy. Takes 2 to 3 months for this to happen. That is for micro vascular. The scaffolding and all the micro vasculature is intact. The reason you get aberrants regeneration in cases of trauma or compression of the nerve is because you get destruction of the scaffolding and architecture for the nerve. When the nerve is regrowing, it doesn’t have scaffolding or architecture to follow to go to the correct target and it just grows and grows to abnormal targets in the same area. That is why you get muscle to muscle. You get co-contraction of the medial rectus when you’re trying to elevate. Or you get eyelid retraction, there is muscle to lid. And sometimes you get muscle to pupil as well. That’s why sometimes if you adduct the eye, you see aberrant regeneration and the pupil gets small. That is aberrant regeneration and that’s why. It’s because those specific causes the trauma and the compression causes destruction of the supporting surrounding scaffolding and architecture for the nerve itself. So because of that destruction, it doesn’t regrow in the correct direction because it doesn’t have anything to grow with, if that makes sense. Okay. I don’t know, I think I lost my place. How can you differentiate aberrant regenerations from complete cranial nerve 3 palsy? Complete cranial nerve 3 palsy will not move. The eye is down and out. Aberrant regeneration will become confusing for you at first. I remember the first time I saw aberrant regeneration, I was very confused as well. But you differentiate it by examination, basically. So you have to look closely, you get the patient to move the eyes in all the directions again and look very closely. If there is aberrant regeneration, the eye moves in an unexpected direction from what it’s supposed to do. So rather than being down and out and completely down for the eyelid, if you get them to move and they’re trying to adduct the eye and they can’t but the eyelid suddenly comes up, you’re suspicious for aberrant regeneration. Physical examination, if you have to get them to look multiple times over and over again for you to see et, that is okay. What is important is the patient is getting proper care. Don’t be worried about annoying them. Get them to move the eye over and over. And the eyelid comes down when you look downwards: If you see eyelid retraction when you look downwards, that is aberrant regeneration. Someone ask, can you have a mixed partial third, fourth, and sixth nerve palsy and how do you check for fourth nerve function in this case? If you have a mixed third, fourth, and sixth you’re thinking about the cavernous sinus because those three nerves are together in the cavernous sinus. If you notice those three all together, I don’t think you need to clinically try to distinguish how to check for cranial nerve 4. I don’t think. What will happen is if you have a partial third and sixth but four is spared you have cyclotorsion. That will, that will be all you see. Because three and six, so there’s no horizontal movement, no real vertical movement and then if four is intact for some reason, you see incyclotorsion in that eye. If all of them are involved, then there will be no movement. They have complete ophthalmoplegia. Why is cranial nerve 3 the most affected in diabetic patients? That is not my observation. I’ve seen a variety of cranial nerve 6, 3, and 4 for diabetic patients. So I’m not sure why. It does get confusing when a diabetic patient has a micro vascular cranial nerve 3 palsy because it’s quite painful for them and that can prompt neuro imaging. Okay. I’m sorry, I don’t speak Spanish. So I — I will get someone to try to translate, something about park’s versus Bielvschowsky. Someone asked, I had a case of acute third nerve palsy with severe headache in a young patient with normal MRI and normal MRA, how to proceed further. Go back to history, history, history and then get blood work based on the history. Acute third nerve palsy, are you certain the MRI and MRA is normal. Review the images with radiology. My only advice for you there is that is how I would proceed if all my investigations have been normal so far. And then I would still follow up with the patient with the acute third nerve palsy to make sure nothing else has changed. But history, do you blood work, screen for all the other causes and make sure the normal MRI and normal MRA are actually normal. In my experience, if someone had an acute third nerve palsy with severe headache, I’m not sure the reported normal MRI and MRA are actually normal. Always review the images you’re or with a radiologist and comb through them again. Next question, how are palsies cured? It depends on the etiology. I would say micro vascular nerve palsies just resolve on their own. But the cure for a nerve palsy would be determining what the etiology is and treating the etiology. Another question here, how do you distinguish congenital ptosis from pupil sparing third nerve palsy. Congenital ptosis you know from birth. They would have, I think a congenital ptosis would have the classic, there’s fat infiltration. You don’t have an eyelid crease. I don’t fully understand the question. Are you asking how you distinguish from congenital toe surfactants versus a third nerve palsy. Congenital ptosis has a distinct clinical examination. And clinical features. And pupil sharing third nerve palsy has a very classic examination. So pupil sparing you have the eye down and out. The extra ocular motility issues and it’s not just ptosis. In fourth cranial nerve palsy, patients would have discomfort, would patients have discomfort when reading a book? What are discomforts that patients have with other palsies? Yes, they would have discomfort if they had a fourth nerve palsy trying to read because your eyes need to incyclotort a little when you’re reading at this level, near. If they have a nerve palsy and the eye is excyclotorting, they have discomfort reading. They usually have double vision at that level. In other patients, other cranial nerve palsies, basically, in abduction deficits they have discomfort or more diplopia looking in that specific direction. So for my patients, usually, if they have a left cranial nerve palsy, they find it very difficult trying to drive. If they need to shoulder check, they see double vision. I advise them not to drive anyway. But for some people, if they’re trying to drive, that is how they notice the nerve palsy, they notice double vision when shoulder checking. Cranial nerve 3 palsy, normally, you don’t get double vision because the eyelid is down. Unless the eyelid comes up, if the eyelid is down, it’s covering the eye and they don’t have double vision or a ton of discomfort. I hope that answers your question. Please kindly explain once more best test neuro imaging for 3, 4 and nerve palsy. I believe my slides will be available and this talk will be available by video. So you can review that on your own time and review the slides again. What are the cranial nerves affected by GCA, the answer to that is basically any cranial nerve. The cranial nerves have to be supplied by a blood supply and for a GCA, it’s a vasculitis. It can affect any of them. What is your protocol for infectious etiology test, serology or CSF testing? That depends on the history. I start mostly with serology. I will start with serology and go from there. CSF testing, I will usually consider if we’re not getting anything on serology or there is a suggestion in the blood work there is something going on or if they have symptoms like meningitis symptoms. Then I would consider CSF testing because you need to do a spinal tap on that case anyway. What kind of refractive error is caused by cranial nerve 3 palsy? I don’t think there is any kind of refractive error caused by cranial nerve 3 palsy. Most of the time we’re concerned about double vision and the ptosis and making sure it’s not compressive etiology. Dr. Rahman asks, single tests which determines fourth cranial adduction downward, any specific name? Okay. I think you’re asking about how to check for cranial nerve 4 in adduction. So usually, when we see someone with a cranial nerve 3 palsy, what we’ll get them to do, we will lift the eyelid and everything. And to make sure that cranial nerve 4 is not involved, is we get them to abduct the eye. Lateral gaze. And then look down. You should see incyclotorsion of the eye if cranial nerve 4 is intact in that position. Incyclotorsion can sometimes be difficult to see. The trick there is to look at the blood vessels of the eye and make sure they’re horizontal and they move. So you might need to do it a few times but it will be there, I promise you. I think this is all the time I have for questions, actually, unfortunately. Thank you for all the good questions. I have somewhere to be right now. So I will stop here. Thank you for participating and listening to my lecture and I will maybe see you next time.