Chapters Transcript The Eyes Have It! Great Cases in Neuro-Ophthalmology Course: Neurology Updates 2023: Case by Case Good morning everyone. Thanks for being here with us. Thanks Doctor Howard for the set up on horizontal nystagmus. You knew what was coming. We won't quite discuss 100 causes of it, but we will discuss the top 5 causes of direction changing nystagmus. I have no financial interests or conflicts, so I'm going to share a patient with you who I've learned a tremendous amount amount from and about over the last year. She's a 38 year old woman. She came to the emergency department at NYU. She received a neurology consult. Her symptoms were headache, blurred vision, and dizziness. And we're gonna watch a couple of very brief video clips of her that are on loop. So here she is looking centrally fixating. And this nystagmus is very subtle, but I think you can appreciate that she has a little bit of left beat nystagmus in central position here. And when we have our look to the left. We see a a ramp up a little bit, but it's still quite a subtle taggmis, and when she looks off to the right, we see a little bit of larger amplitude, a little bit of faster right beat nystagmus. So let's just watch through that one more time. So she's got headaches, she's got dizziness. We're probably thinking something's going on in her posterior fossa, but some kind of vestibulo cerebellar disease, and so the team appropriately gets an MRI scan, brain and internal auditory canals with contrast, and that MRI is completely normal. So they treat her headache and discharge her, and we see her in neuro ophthalmology follow up. So we'll step away from her now and just take a step back and talk about nystagmus at a very basic level. The definition of nystagmus is a spontaneous repetitive to and fro oscillation of the eyes, and it's very important to remember that the very pathologic part of nystagmus is the slow drift of the eye from where it belongs, so. It's not the quick phases that are the pathology. It's that something in the brain is not holding the eye steady in fixation, be that in central fixation and eccentric fixation, and so the eye is slowly drifting from where it's supposed to be, and then that may be followed by quick resetting phases or it may be followed by additional slow phases. So in jerk we have. Quick resetting phases and there's types A, B, and C here in the diagrams and so the lines just represent the position of the eye. The red line is the slow drift away from where the eye belongs and the blue are the quick resetting phases so you can see in A, B and C that the difference here is the velocity or trajectory of. The velocity phase of the slow phase and so in a it's linear and B it's a decreasing velocity and in C it's increasing velocity and I'm not gonna emphasize the importance of these things too much, but suffice it to say that C is pretty typical for congenital nystagmus. So if we have a question about what. Type of nystagmus we're dealing with we can record the patient with eye tracking or VNG and see what those slow phases look like and then D here is pendular nystagmus where there's no quick resetting phases but just slow oscillations back to back in a repetitive nature that are pendular nystagmus which we're not going to talk about further today. And then in describing nystagmus for jerk nystagmus, even though the slow drift is the pathology, we name that nystagmus for its fast phases. It might be left beating as shown here in this video. This is a patient with MS who had a demyelinating lesion at the level of the vestibular nuclei. It might be right beat, downbeat, upbeat, or even a primary torsional jerk nystagmus. Similarly with pendular nystagmus, and you can see an example of a horizontal pendular nystagmus here, there's no quick phases. You have to train your eye a little bit, but it looks very different than jerk nystagmus, and it can have, it can be a purely horizontal pendular which is shown in the video. It might be a pure vertical pendular, it might be a pure torsional pendular, or it could have more components to it and look kind of elliptical. And of course the retina does not tolerate motion, so when patients have nystagmus, they typically get degraded vision and oscillopsia, which is a subjective sense of motion in the visual world, and this video that I made out of my old office shows probably a um a vertical jerk nystagmus and what the patient might experience with that. So today's concept is uni versus multidirectional or unidirectional non-direction changing nystagmus versus multidirectional or direction changing nystagmus. Couple little arrow diagrams we're gonna use this schematic as we go through the types so you can see when these eyes are looking centrally in the top one there's a left beat with a little bit of torsional component and then that ramps up when the eyes look all. The way to the left, that's Alexander's law so that nystagmus is ramping up in the direction of the quick phases so left beat ramping up in left gaze with a little bit of torsional component. The bottom one would be our direction changing example where you have some this is like our patient where you have some left beat some left beat and central and left beat and left gaze, but when she looks to the right you have right beat the stagmus and this concept of direction change. nystagmus really was popularized by the hints test to diagnose stroke in the acute vestibular syndrome, so we apply this all the time in the emergency room now the hints standing for head impulse test, nystagmus, and test of skew deviation and to really properly use the hints in the emergency room, there must be nystagmus detected in the patient and then you identify it as either. Non-direction changing or direction changing. So high risk for stroke is if the head impulse test is normal. If it's abnormal, suggest peripheral. nystagmus being direction changing and the SKU deviation being present, but the hints is not what I'm going to talk about today. There's other forms of direction changing nystagmus that have other implications for our patients beyond stroke, and that's the focus for today. So peripheral vestibular nystagmus is what we're after in the emergency department to make sure that we're not gonna miss a stroke in that patient and that's a unidirectional nystagmus. It beats away from the affected side of the lesion. So in our example here in the schematic of left beat nystagmus that ramps up in left gaze, that would be a right right peripheral vestibular lesion. And it's typically a mixed horizontal and torsional, so central forms of horizontal and nystagmus tend to be more pure without mixed horizontal torsional, and you might just see this in in this example in left gaze. So if you just see left beat nystagmus in left gaze and nothing in right gaze, you may need to. Eliminate fixation in the patient in order to be able to detect the nystagmus in central position. So here a tool called friends with goggles is being used and when the patient is without the goggles, there's not much. nystagmus visible, but when the patient puts the goggles on, you can see this right beat torsional nystagmus that's unmasked that signifies a left peripheral vestibular lesion. So I'll just let you watch that once more. So you won't have friends or goggles in your practice necessarily. You don't need them. You can pull out your ophthalmoscope and look in one eye while the patient covers the other eye, and you may unmask some nystagmus that you can see in the back of the eye with your ophthalmoscope. So we're gonna move on now to the top 5 causes, at least in my book, of direction changing nystagmus. The first is gaze evoke nystagmus, so this would be nystagmus that is absent in central position, right beat and right gaze, left beat and left gaze, and this is due to either. Disease at the level of the medulla in the structures that are called neural integrators for gaze holding. These are the medial vestibular nucleus and the nucleus propositous hypoglossi or cerebellar connections to those nuclei. So this is very medullary and or cerebellar in localization. It's can be completely physiologic. The features of it, when it's physiologic, the patients here is pathologic, but the physiologic features are it's only present in far lateral gaze. It's very poorly sustained. It's got a very small amplitude and it's only horizontal. When it's pathologic, it is more easily seen in a less eccentric gaze position tends to be sustained, it doesn't fatigue, it has a larger amplitude and it can be present in up gaze as well. So in this. Patient of Doctor Balser's who had imbalance and a cerebellar problem, you can see when he looks to the right that he has right beat in a stagmus, when he looks to the left, it's left beat it's fairly large amplitude. He doesn't have an upbeat, but in this pathologic case they might. The second direction changing nystagmus is rebound nystagmus, and then some of our patients with gaze voke nystagmus from cerebellar disease usually they might have a little bit of nystagmus when they come back to central position. So here he's got right beat and right gaze, and when he comes back to central position, you can see some left beat and left gaze. Let me play that again. I may have to. Go back. It's subtle, but it's there, and if you had any question as to whether that gaze evoke nystagmus was physiologic or pathologic when you have them look back to central position, if you even see a couple tiny little beats of nystagmus in central, that's rebound and that's gonna be pathologic nystagmus. So the third direction changing nystagmus for today is Brune's nystagmus, and I'll just point out that our patients nystagmus favored this a little bit. So it looked like a Bruins type of pattern. So in central position there's some left beat here when the patient looks to the left, there's more left beat it ramps up and when the patient looks to the right, there's right beat the stagmus. So that's what Brunes is, is this combination of. A peripheral vestibular nystagmus, so when the patient is in the schematic looking straight ahead, getting left beat that ramps up in left gaze, that's a right peripheral vestibular process in Bruun's nystagmus, and then in right gaze those neural integrators down in the medulla and at the cerebellum are affected and they get gaze evoked nystagmus, so it's a combined mechanism nystagmus. And I'll show you an example. Then the sagis is a little bit subtle in this video. You can see that right beat and right gaze. She has some left beaten central, and then that ramps up when she looks to the left and the classic pathology that causes this combined mechanism, nystagmus. Is a CP angle lesion because there you can easily get the peripheral vestibular nerve being compressed by this mass lesion as well as some cerebellar and some medullary compression that are gonna cause the gaze evoked nystagmus in the ipsilateral direction. So they have the vestibular nystagmus and the contralateral direction from the lesion and the gaze of oak nystagmus in the ipsilateral direction. The 4th direction changing nystagmus is always a very interesting one that you have to really watch for or you will miss it, which is periodic alternating nystagmus. I most frequently see this in patients with multiple sclerosis, but it can be due to other things as well. So in this schematic, you have the patient having left beating nystagmus to start off, and this is what you're gonna see in the video, left beat nystagmus for maybe 60, 90 seconds and then it's gonna reverse direction and beat the other way and then reverse direction and beat the other way and on and on and on and on and it just keeps reversing direction in a very periodic manner. And you'll miss this because we'll, we'll, we're quick in clinic we're looking once we oh we see some of the stagmus, it's left beat move on next patient, but you have to really sit and watch these patients for 2 or 3 minutes to confirm that it's periodic alternating nystagmus. So I'll show you the best video which is from the 1970s that is um from Doctor Robert Daroff. And you can see this left beat nystagmus that she has. This is a patient with multiple sclerosis. When it transitions, sometimes you'll see just a little bit of downbeat nystagmus, which she has in her transition phase, and then it ramps up and starts to beat to the right. And so it's also good to notice in the schematic that when it's in that left beat phase, it's going to be left beat no matter whether the patient looks straight ahead to the left or to the right and then it's gonna transition to right beat. So periodic alternating nystagmus is interesting. It's really the only nystagmus for which there is an animal model, and this was Bernie Cohen, one of my mentors up at Mount Sinai who did in primates some research where. The nodulus and uvula of the cerebellum were ablated and they caused periodic alternating nystagmus with that. There's acute case report in neurology of a patient with acute onset PAN who had a nodule stroke. So let's go back to our patients. So there's one more cause of direction changing nystagmus that we haven't discussed. So this is our 5th cause which I would venture to say at the end is probably pretty rare, but is the focus of our our case today and very interesting. So remind you she's our 38 year old woman who came to the emergency room with headaches, blurred vision, dizziness, had this nystagmus that had a bruises like pattern. Had her MRI scan that was negative, and she did report she had headaches before she got intermittent headaches with nausea, photophobia, occasionally a little dizziness, so you guessed it, she just has migraines and that headache that brought her to the emergency room was a migraine. But we also did send off some autoimmune studies looking for any underlying neuropathic cause for her nystagmus, GAD antibodies, DPPX, and the encephalitis panel, perineoplastic. Those were all negative. But I'm gonna let you watch her video again. So she's got that left beat and left gaze. It has a little left beat in central, you don't really see it clearly there. Now there's no right beat and right gaze. Watch when we test pursuit. Left beat and left gaze, and she's gonna get some right beat and right gaze here, but then it's gonna go away. When she looks all the way to the right, so it's kind of funny for acquired nystagmus. We don't usually see this sort of intermittent nature to it, and she tells us by history some things that enlighten us that she had nystagmus diagnosed at age 12. That was her first time she saw an eye doctor. She had no oscillopsia. She turned her head to the left for better vision, and her father and nephew have nystagmus since birth, so probably congenital. The most common congenital that we see is a horizontal pendular, which is what's in this video that I showed you before, but they can have some jerk components. They tend to have a null zone, which is a position of gaze where there's not much nystagmus, so that's why they will have a head turn to put their eyes in that position, and they tend not to have oscillopsia, which is really our biggest clue. So the first thing I did after she told me this history was I went to the literature and looked up. Has pseudo Brune's nystagmus been reported as congenital nystagmus pattern before, and in fact it has by Lou Deloso, who was one of the big researchers in congenital nystagmus for decades, but just this single report. And then my patient tells me, so my nephew who has nystagmus is coming for a visit. Would you like to see him while he's here? I said, Absolutely, bring him in. So her sister and the nephew come, and the nephew has a more typical pattern of congenital nystagmus. He has this horizontal pendular nystagmus, a little bit of jerk nystagmus when he looked off to the sides. And then the sister says, and I have nystagmus too. Do you wanna? Take a look at me I said of course I do. So I recorded all of these patients and she has nystagmus that's similar to her sister but is lower amplitude so even more subtle to see but you can see just a touch of right beat and right gaze here, little bit of left beat and left gaze. And then she says, oh, and the eye doctor got a genetic test on my son. This is literally how this unfolded so he had a confirmed mutation in FRMD7 just to summarize here, it's a firm domain containing protein 7. It's important in mid and hind brain development with regards to eye movement pathways, so it makes sense, and these patients can have nystagmus that can. Mimic cerebellar patterns of nystagmus and different wave forms and different family members. So top five direction changing nystagmus gaze evoked, rebound, ruins, periodic alternating, and occasionally congenital where no oscillopsia is your clue. Thank you very much for your attention. Published December 15, 2023 Created by Related Presenters Janet Rucker, MD View full profile
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