 I'm going to be talking this morning about a patient that was seen in neuro-ophthalmology clinic with Dr. Warner. Dr. Warner's here. Well, hopefully she'll be in at some point. So the patient had the diagnosis of ocular neuromitonia, which I'm giving it away kind of at the beginning, but the story is pretty straightforward. He's a 57-year-old bookstore manager. He came in as a referral. His chief complaint was that his eyes were not tracking well. And this happened three or four years prior where he noticed the left eye had infrequent episodes initially of crossing inward. They don't last very long, only 30 to 90 seconds. He has a sensation during these episodes that he can't close his left eye. He says it feels really tight. And he's noticed that it seems to happen when he's looking in the mirror either combing his hair or shaving his right sideburn, not his left sideburn. This is right. Oh, it's terrible. This is out here. They're pretty symmetric. But he was a really observant gentleman. So he took that to mean that it happened either when he looked up or looked to the right. And that's what he came in and told us. And then these episodes had occurred much more frequently since that time. So up to the point when we saw him there happening up to 15 times each day. In between episodes, this has been starting to occur where his left upper eyelid has been droopier and droopier over the years. He has also noticed that his left eye doesn't elevate well. That's just been in the last year, even when this is not going on. And even between episodes, he started to have vertical deplopia. And this is both in primary and up gaze. It goes away in down gaze. Someone put him in prisms and that didn't really seem to help. And he doesn't have any. The vision is good with each eye. So he doesn't have any complaints about that. Molecular history is just significant for my open astigmatism. His medical history is interesting. He's had a pituitary adenoma. This was diagnosed in 1985 on the basis of acromegaly symptoms. So he actually went in and had grown a shoe size and a half in about a month and thought that was strange and mentioned it to his doctor. And along with some other symptoms was diagnosed with pituitary adenoma. Never had any visual field abnormalities. He's had visual field tests in the past. So it wasn't a very big one causing any mass effect. It was just causing some hormonal effects. And because of that he had an initial transfenoidal resection which wasn't successful and they went back in a month later and just did a craniotomy and did a gross total resection. But because of a small recurrence he ended up having subsequent external beam radiation a year later. And then since that time has been fine he hasn't had any recurrences either on imaging or with surveillance hormonal lab work and he hasn't had any subsequent symptoms either until what's going on now. Other than the pituitary issues just depression and arthritis he takes medications including replacement pituitary hormones and then the rest of these are either just supplements or for the arthritis. On exams vision is good in each eye. He has a little bit of anisocorrhea where the left pupil is larger but no APD. Color vision is normal. Serovision is pretty good. Normal pressure, it's not proptotic. He does have left upper eyelid ptosis with a decreased levator function. 12 millimeters in the left compared to the normal on the right. And his muscle balance exam shows that he has a left 12 prism after left hypotropia and an 8 prism after exophoria. This is in primary gaze and we couldn't test it in different gaze directions because it would cause him to go into dysspasm which changes his measurements drastically so this was just in primary gaze. His motility was full in both eyes except for a minus 3 deficiency of elevation in the left eye and he had signs of aberrant regeneration because when he looked down his left upper eyelid retracted. We'll see that some on the video. So this is what happens on right gaze. I think this was... We started the video right after he went into dysspasm so he had a little exophoria normally but when this video starts he'll already have a little bit of an iso. And look to your right. And so you can see that now he has a little... That was there before the deficiency of up gaze but now that he's in the spasm he has a new deficiency of abduction in the eye and much more deficiency of elevation and also this left upper lid retraction which wasn't there before and that explains the sensation of him having difficulty closing his eye during these spasms and now he's a little isotropic. Ignore that handsome guy in the mirror. I'm going to show that one more time. So the main things here before he was exophoric now he's iso and before he had left upper lid ptosis and now he has left upper lid retraction and a deficiency of abduction which wasn't there before. So this is just kind of what I just showed. Left upper lid elevation, infraduction and adduction of left eye are kind of what composes this spasm. What it results in is an isotropia from what was an exophoria. Greater restriction of up gaze, restriction of abduction which wasn't present before and notably there was no change in his pupils when this spasm occurs. So we diagnosed him with partial left third nerve palsy even in between episodes with aberrant regeneration. That video didn't really show. He has some left upper lid retraction on down gaze and the differential diagnosis and then left ocular motor neuromyotonia which is a differential diagnosis of that or of the two in combination includes a cyclic isotropia ocular motor paralysis with cyclic spasm. Not superior to bleak my camera doesn't really look like this but I included it on there too in my senior grabbis. I'm going to go through each one of these and talk about why this is neuromyotonia that the features really fit best with neuromyotonia. This is an episodic condition. It's spontaneous or induced by various gaze positions and it can occur years after whatever injury or insult that causes it which we'll talk about. It only rarely involves the pupil as opposed to ocular motor paralysis with cyclic spasm which always involves the pupil and this really happens in the first year of life. You never have with this condition normal ocular motor function in between the spastic episodes whereas in neuromyotonia you could have totally normal function of that cranial nerve in between the tonic episodes. Superior bleak myocymia doesn't look like this but if you had a patient with a fourth nerve neuromyotonia there might be some overlap on the exam. The big difference there is that the patients with myocymia have symptoms of oscilopsia and microtrimor present on exam in addition to the vertical deviation in the plopia which may also be present with neuromyotonia. Cyclic isotropia also develops during childhood and consequently they don't usually have the plopia and they don't have signs of cranial neuropathy in between their episodes and their cycles are more on the order of hours to days whereas neuromyotonia is like seconds to minutes. Myocinic grabs don't look like anything but the important thing here is that there's no pupil involvement which with some of these other things there can be. So ocular neuromyotonia fits best with what this patient has. It's previously been reported in only 45 patients since 1966 and we already talked about it's characterized by periods of sustained involuntary contraction of one or more, usually one, extracular muscles caused by spontaneous excitation of the nerves that control those muscles. The definitions here are important because neuromyotonia is a pretty specific entity. So myotonia is described as just a delay in muscle relaxation after a voluntary contraction and that's from a muscle membrane disorder. Neurotonia is the same thing except that's from an actual nerve disorder so you have repetitive neural discharges and then neuromyotonia is neurotonia but just accompanied by instead of just delayed relaxation it's accompanied by actual excessive contraction either small contractions, fibrillations and fasciculations or an entire muscle group or an entire extracular muscle. A recent review of all the reported cases in the literature showed that in terms of ocular neuromyotonia the most commonly affected cranial nerve is the third nerve followed by the sixth and the fourth and then the most commonly reported association or causes depending on how you want to look at it are prior cranial irradiation in almost half of the cases which our patient had and then a lot of other things that could potentially cause injury but not complete death of that cranial nerve and then rarely there have been reported patients who have neuromyotonia without any identifiable prior cause and then our patient's cause we thought was prior cranial irradiation and this is just a couple of representative images from his MRI scan which he had done just a several months prior to our exam this is an axial T2 just showing the course the subarachnoid course of the third nerves here there wasn't any tumor or mass effect on the nerves visible on the scans and then post contrast axial and chronal images showing enhancement of the third nerves on both sides and that enhancement was just thought to be due to the prior irradiation he didn't have any other signs of an active meningio process going on pathophysiology we don't really know but the prior electromyographic studies point toward this being a neurogenic disorder rather than a myogenic disorder the theories are based on either this being a peripheral nerve origin or a central or nuclear origin and I'm going to focus on the peripheral nerve origin based on the fact that I think it makes a little more sense this paper down here described a possible mechanism of how this may occur based on theories of what happens in peripheral nerves after an injury there's three things that have been described to happen in peripheral nerves after an injury this emphatic transmission is crosstalked between adjacent axons so instead of the impulse going this way it actually into another neuron it actually can crosstalk between adjacent axons and nerves that have been damaged reflection or antidromic conduction is just the impulse traveling the wrong way up the nerve after injury and then proximal sprouting or branching of axons describes just what it sounds like you have in the process of re-growing the axon they can come off more proximal and you end up with multiple axons coming off in parallel and what that can cause is it can set up this so if you have the ability to have the impulse travel the opposite direction and you have multiple axons crosstalk with each other then you can set up this reverberating circuit that's similar to what's seen in cardiac re-entry tachycardia like in Wolf-Parkinson white and that can just cause a really amplified intense signal that when it is transmitted to the muscle can cause a sustained contraction and delayed relaxation and this is I think supported a little bit by the fact that in a lot of these patients who have had cranial nerve injury they can have aberrant regeneration which can also be explained by this proximal axon sprouting going to a different location and there's been a lot of patients who including our patient with neuromyotonia who have been described to have aberrant regeneration also so that supports I think this possible mechanism treatment, carbamazepine has worked well on a lot of patients as well as other anti-epileptic drugs the membrane carbamazepine is a sodium channel blocker and most other anti-epileptic medications are membrane stabilizing medications and that also supports the pathophysiology that we talked about there was one patient that was reported in the British Medical Journal last year who actually had ocular neuromyotonia and found relief from no medications and the only thing that ever helped her was wearing these goggles which she stole from her grandson these are Bob the Builder goggles which Bob the Builder actually doesn't wear goggles I don't know where that came from but they were described as Bob the Builder goggles and the authors thought that so she had the her neuromyotonia was induced by lateral gaze and they thought that because she tried other goggles she tried swimming goggles and you know goggles and this was the only thing that worked and so she just wore this around so they thought that it blocked enough of her peripheral vision that she didn't have the impulse to look to the side and then she didn't go into the spasm so she just walked around wearing these all the time so in conclusion and so our patient we started on I think we recommended starting gabapentin and I don't know if he's been seen in follow up yet or not but Dr. Warner says no so in conclusion it's a particular neuromyotonia it's an uncommon but pretty unmistakable condition when you see it it doesn't really look like anything else occasionally I think maybe if you had a fourth nerve neuromyotonia it could overlap a little bit with myokimia but the features of this are pretty different than a lot of other things that you might mistake it for the associations are usually with things that injure or irritate cranial nerves and therefore these patients deserve neuroimaging most commonly inspired or radiation and they can be successfully treated with anti-epileptic medications or goggles or builder goggles so I'd like to thank the patient for letting me video him external beam radiation for making this possible and the neuro-ophthalmology faculty both for helping with this presentation and for everything this is my last neuro-ophthalmology presentation and I also just wanted to yeah it's terrible and it happens yeah can you see impaired abduction with that also I mean if there is a spasm any other questions or comments no just you know for your information only September 3rd in Missouri State Younger, Handsomer President, Governor Clinton