 She's a fellow co-resident of mine, and her second year is an awesome co-resident to have. She's very thoughtful. She's really good. She's awesome. Some fun facts, something that you guys don't know. So before she chose a career in optimization, she's been an actress. Wow. Been used before. You can actually YouTube her. She's in the movie Bloodsport 2, and she was about 10 years old or something. Yeah, but it's actually pretty cool. Without further ado, deliver. So I'm going to be talking about a case this morning that we saw at the VA when I was there recently. So the patient first kind of started having some problems in October, October 5th. And at this time, he didn't see ophthalmology, but he presented to the emergency department with complaints of a rash. So he was a 75-year-old man, fairly healthy, had five days of eyelid swelling and rash. He felt like at first, when this first started, the left ear kind of felt a little bit achy, felt like it might be an ear infection, and he had some kind of rash symptoms in that left side. And then this rash spread over the left side of his forehead and progressed up to his scalp. He really complained. I mean, this is all according to the ER notes of some itchiness, not really pain, but also maybe some achiness. He had some, endorsed some recent chills. He didn't have any fevers or other systemic problems that he had noticed with all of this. So his past medical history, he's had hyperlipidemia, COPD, coronary arteriosclerosis with a triple bypass in the past. He had prostate cancer, but he had a prostatectomy, and that was all under control. He's not on chemotherapy, not immunosuppressed from that at this time. Hypertension, and then a previous history of a traumatic brain injury. His medications are listed up there. And really, the only review of systems thing that was positive, according to the ER, was this kind of recent chills, without any fever. So they noted a rash on the left forehead and right brow along the hairline that extended over the midline of his scalp. They didn't note any lesions on his nose. They did note some edema of his left lower eyelid. They didn't really describe the rash or the lesions very well in their record. And it looked like they had consulted dermatology, although there wasn't clear documentation from that either. So this is kind of what we have to work on regarding the rash. But given the distribution and kind of clinical presentation, this was the differential diagnosis that they came up with. So like in planus, psoriasis, contact dermatitis, I guess he had started using a new hair dye. They thought that might be causing this or some manifestation of skin cancer. I'm not sure about that one. So they started him on trance and alone, and just told him to come back if he had any changes and definitely come back soon if he had any vision changes. So he did. Came to the ER again on the 21st. So about two weeks later, and they of course referred him up to the VA ophthalmology intern clinic. And at that time he was complaining of a new onset of a vertical binocular dyplopia. Again, nothing really else on his review of systems. And at this time the rash was almost completely resolved. I mean there wasn't really documented any signs of it on his exam. Note his pupil exam was normal. Eye movements looked full. His alignment exam with alternate cover we can see here. And he had a left hypertropia. It was fairly comatant. No ptosis. And then anterior segment in a dilated exam was normal. Optic nerves looked healthy. So this is kind of a list of differential diagnoses to think about with a vertical dyplopia. But some of these don't fit his presentation. But of course the skewed deviation would fit myasthenia, thyroid eye disease. You always think about if you have a unilateral or bilateral third or fourth near palsy. You really didn't measure torsion in him. So that could be something that we missed. Stricted ophthalmopathy. Giant cell arthritis. Gamberay. Miller Fisher. Trauma. Paranod syndrome. Superior bleak myasthenia. Again, that might be more of a torsional dyplopia. Disseminated zoster could cause a presentation like this. But given his kind of presentation and clinical exam, I thought that he had a new skew deviation. And so the plan was to look for causes of the new skew and rule out an ischemic attack or artery insufficiency. And then also evaluate him for myasthenia. So the plan was to get an MRI of the brain within without contrast. An MRI of the head and neck in a myasthenia panel. So only two out of three were done for unknown reasons. But the results were pretty, were normal. He had some chronic microvascular disease, kind of as expected, given his history of hypertension and atherosclerosis. But no other findings to explain this. And then the myasthenia panel just wasn't done. But he comes back on the 30th. So now he initially presented with his rash on the 5th. And then the first time he kind of noted double vision was around the 20th of October. And now we're at the 30th. And now he's complaining that his double vision is still getting worse. And on exam, the, you know, extracular movements, it looked like someone noted about a half, a minus, a half restriction of left abduction. So pretty minor that it was there. But alternate cover showed still the left hypertropia. But that was worse than left gaze now. And then a new esotropia. Again, worse than left gaze. So a pretty big change from just the left hypertropia, too. That was commentant. That was noted about a week before. The remainder of his eye exam still remained fairly normal. No new ptosis, no Cogan-Lind twitch. Interior segment looked normal. No signs of any cornea disease. And again, the dilated exam looked normal. So at this point, kind of seeing this changing picture and progression of his diplopia, Mycenae kind of rose to the top of the differential. And that was kind of the focus, was to try to evaluate him for this. And, you know, at this time, he still wasn't placed on any acyclovir or anything. So he hasn't really been treated for anything at this point. His lab results for Mycenae were normal. He did get an ESR. And this high sensitivity CRP is the only thing they have at the VA. So not extremely helpful. But it was definitely reassuring that his ESRs, too. But because of the high suspicion for Mycenae, a single fiber EMG was ordered. And then just for further evaluation, an MRI of the orbits was ordered as well. So single fiber EMG was normal. No sign of Mycenae. And then his MRI of the orbits was basically normal, at least no evidence of anything to explain this double vision. So he comes back to the neuro-ophthalmology clinic on the 12th of November. This is now, we're about a month or more like five weeks after his onset of double vision. And at this point, he's saying his double vision is actually almost completely resolved. And you can see by his alignment examination that it is much improved. And again, the rest of his examination looks really quite normal. So kind of looking at what we had there, we've ruled out Mycenae with a single fiber EMG. And it's gotten better. There's no other systemic signs or other kind of clinical findings to point us in that direction. He had this rash, which does fit with disseminated zoster, but was kind of in a different pattern in the ophthalmology. I mean, as an ophthalmology team, we didn't get to actually see the rash. But NGCA was also kind of excluded with his workup. So the plan with this diagnosis was to treat him with acyclovir, five times a day for six to eight weeks and refer him to neurology for them to manage the kind of long-term treatment with acyclovir and decide how long he needs to be on it. And if there were secondary problems from this disseminated zoster. So this case, although it is zoster, which we care about a lot and we talk about a lot, I think that in this case we all kind of missed the diagnosis because the rash didn't quite fit into what we were thinking and we are so focused on Mycenae. So I wanted to review disseminated zoster and kind of the presentation with cranial neuropathies. And then the reason that it is so important not to miss it because of some of the neurologic complications that we really need to identify and treat. And then kind of along the lines of the scary diagnoses that we shouldn't miss talk about giant cell arteritis presenting as diplopia and that also is something we need to really, again, I know we talk about it all the time but keep on our differential. So I'm going to talk a little bit about the history of varicella zoster. It's fairly kind of interesting when you look back because the route to discovering that this is kind of a latent infection that presents itself over time wasn't something that was obvious but there's reports of the segmental zoster rash, you know, dating back to at least 1831 and people is kind of thinking, well, what does this mean? Why is it segmental? How can we explain this? And so, you know, back in 1862 even there was autopsy or verified that there was damage to the sensory nerves in the ganglion caused by zoster. And then in 1900, Head and Campbell did a fairly detailed post-mortem study of 20 patients with zoster and they were able to map out dermatomes related to how the rash had presented and this was kind of one of the things that really helped people understand what the sensory dermatomes actually were and what their distribution was so kind of a, you know, helpful historically for us to have a little bit more understanding but then once they did that the question was how varicella or how and if varicella and this zoster rash were actually linked or related and it wasn't until the 50s that people were able to grow the varicella virus from tissue culture and then also to prove that this was the same virus from both, you know, an active chicken pox varicella presentation and then the zoster. And I was kind of surprised that, you know, in 1965 this was still kind of a controversy but one of the larger studies is an epidemiologic study of 192 cases of zoster over 16 years to try to evaluate and prove or disprove some of the hypotheses for how this infection was transmitted and how it came to be so, you know, kind of at that time they were competing explanations that this was alternative acute infection so these were kind of unrelated and they just happened to have this association and there was also the thought that it was, zoster was actually just caught and from a case of acute varicella infection from someone who was actively infected with chicken pox then there was this theory of this reactivation of a latent virus which, you know, in this epidemiologic study they were kind of saying that this is most likely because there weren't any endemics of zoster and there weren't really clear links between the people that they had noted that had this infection and transmitting it. So it's kind of one of the times that the idea of how this virus actually presents was that the thought was shifted. So this is, you know, we all kind of know this but zoster occurs in people who've had chicken pox or some clinical infection of varicella but it is important to note that in rare infants who develop zoster they can develop zoster as their primary clinical manifestation of a latent varicella zoster that was acquired transposentially so this is kind of the exception to the rule. Epidemiologic data, there's variations in the numbers and with the vaccine out and everything there this number could change but kind of as an estimate about 10% of the population will have an attack of herpes zoster about 4% will have a second attack and it's fairly rare to have a third attack. And then again this is stuff we all know but just the classic presentation is this unilateral vesicular eruption in a dermatomal distribution and you can have pain, itching or a pair of seizures in the affected dermatome and then usually 48 to 72 hours after the onset of the sensory symptoms you get the skin lesions and then you can also have some other systemic manifestations with headache, fever, malaise and then of course immunocompetent patients they are more likely to follow the rules although they don't have to and the lesions will kind of form over a period of 10 days and then start to regress and then of course in immunocompromised patients it's more of anything's kind of fair game. So herpes zoster pathogenesis, we know that the virus establishes latency in the dorsal root ganglia and the cranial root ganglia, the question kind of up for debate at least from what I saw is how the virus actually gets there. There is a theory that it's the actual intradermal or intraepidermal projections of the sensory neurons carry the virus and it goes retrograde through the axons and reaches the cell body versus bare cell being carried in the T cells which happens in an episode of acute viremia and the primary infection and then the T cells will kind of fuse with the infected neuronal cell bodies and apoptosis in those situations is prevented and then the virus establishes latency. So we know there's a lot of different presentations that zoster can have in the ocular system in ophthalmology but I want to focus on cranial neuropathies. So one of the kind of syndromic or associated syndromes that we should talk about is Ramsey Hunt syndrome and this is also called herpes zoster oedicus so you have peripheral facial nerve precess with pain in that ips lateral ear and then you can see the classic vesicles on the pinin external auditory canal. Also get loss of taste in the anterior two-thirds of the tongue and then dysfunction of the ips lateral vestibulococlear nerve which then can result in deafness, tinnitus, vertigo and unsteadiness. Of course because nothing is so straightforward rare patients there's reports of people who've developed this without having a rash which would make this diagnosis more difficult but something to keep in mind. At least in Walsh and Hoyt they were saying that the facial nerve is really commonly affected and it's definitely possible that a lot of these people who are kind of categorized as idiopathic bells palsy patients this might actually be a manifestation of zoster so we might be under diagnosing it. The trigeminal nerve as we know is definitely can be affected and it can affect one, two or all three divisions. The ophthalmic division is affected in 7 to 15 percent of cases usually unilateral but if you're immunocompromised it can be bilateral lacrimal, branch is the least common then the nasociliary branch is the characteristic Hutchinson sign where you have the vesicles on the nose. So in reviewing the literature and looking at how these commonly present and what we might be looking for you know there are actually case series going back again fairly far back into the 1909 was the first one I saw. So out of 158 patients 15 percent presented with cranial neuropathy. Third nerve was the most common, fourth is least common, sixth is kind of in the middle and that holds true kind of for all these other series. This most recent series this was a review retrospective review of the literature of 21 patients with a known cranial nerve palsy and after zoster or with zoster and so the sixth nerve was a little more affected in that series but in general third is the most common followed by sixth and then fourth but you can have any combination you can have multiple you can have all ocular motor nerves involved also it can be contralateral to the side of the rash and it can be bilateral so it doesn't necessarily follow any rules. This is a case series of trochlear nerve palsies from zoster, Mike Grimson a few things to point out in this series the interval between zoster and the fourth nerve palsy usually it's about one to two weeks from the time of the rash to any nerve neuropathy but you know these patients even up to I'm not sure exactly why there was such a big range in this patient from four to eight weeks but it can be up to four weeks and there's reports of it being even longer of course if you had a patient that presented after that much time who had a rash they do need to work up but this is something to keep in the mind and always ask again on our review of systems have you had recent rashes any recent zoster shingles anything like that and then you know in this series of only six but these patients did improve but a few of them still had their diplopia and in these series it looks like most patients do have pretty good resolution of the diplopia some still have some misalignment and extreme gazes but most people recover in primary gaze over variable amounts of time. Here's just an example of 63 year old female with isolated trochlear nerve palsy one month after she had a left zoster outbreak so you can just see the left trochlear nerve and superior oblique muscle not working properly and then a 69 year old with generalized ophthalmoplegia with herpes zoster so like I said you don't have to have just one or two and you can have complete ophthalmoplegia and in this patient we see the rash and then we also see complete ptosis and really complete ophthalmoplegia and this is just as a side note we know where I'm talking about varicella zoster as it's reactivation but chickenpox is a primary infection can also cause neurologic sequelae which is a whole different talk but just you know this virus can do this in kids after their primary infection so this was a two year old that developed a left ocular motor nerve priestess two weeks after a mild attack of chickenpox so something to keep in mind. The mechanisms of how this is actually happening isn't necessarily completely clear and there's been a lot of theories over time starting back to 1845 back that you know Ederchin thought that there was inflammation in the cavernous sinus or superior orbital fissure that was related to the trigeminal nerve and kind of transmitted to the ocular motor cranial nerves thrombophlebitis has been proposed histologic evidence has shown the virus in the ocular motor nerves and then people have you know back good body thought that it was related to the close relationship of the peripheral end of the ocular motor nerve related to the ophthalmic nerve myositis has been seen neuritis and vasculitis and kind of I think the take home message from this is that when they're doing the histologic studies there's evidence of inflammation and vasculitis in some cases and virus activity kind of spread throughout and so it is really a disseminated process and so that's why this is so important that we don't miss it because of the other complications from disseminated disaster so from a neurologic standpoint some of the things that can happen as a secondary result is muscle weakness, encephalitis, ischemic stroke which is really from a vasculitis and usually granulomanias angiitis something we can't miss acute cerebellary tuxia, Guillain-Barre, Ray syndrome, myelitis optic neuritis and then vasculopathy which is kind of like granulomanias angiitis and post-traudic neurology so the vasculitis that can happen, it can be an infection in large, small, or both of the cerebral arteries patients can have systemic symptoms of headache, fever, mental status changes, transient ischemic attacks and strokes, can occur without rash and then granulomanias angiitis is the most, so kind of is the subset of this vasculitis most commonly people have an uncomplicated attack of zoster and then a delayed onset of a contralateral hemiplegia that's caused by the cerebral vasculitis also with this kind of presentation a lot of patients will have or they can have visual field defect and hamonomous hemianopia so again keep it on the differential for pretty much everything usually occurs in people over 50, again just the kind of characteristic zoster presentation and then it can be delayed up to three to seven weeks after an episode on cerebral angiography you might be able to see some signs of segmental narrowing of the internal crowded artery, middle cerebral artery, anterior cerebellar or a combination and then of course it would be on the side opposite of where they were having hemiparesis CSF findings are variable in terms of the cell counts and everything but of course getting PCR and looking for the virus activity is important so shifting gears to giant cell arthritis we again it's drilled into us the classic presentation and vision loss, headaches, jaw claudication but 30% of patients can have neurologic manifestation which can be peripheral neuropathies, TIAs or strokes and I found numbers about 10 to 15% of people might have a presentation with diplopia and really this is another arthritis, vasculitis so you can get any portion of the ocular motor system can be affected so you can get cranial neuropathies but it can also cause brainstem ocular motor problems so you can have a presentation with an INO, one and a half syndrome, skewed deviation and it doesn't have to be just a single cranial neuropathy from giant cell this is an example of an 80 year old with a right superior division of ocular motor nerve precess, secondary to giant cell arthritis and you can see that here the ptosis and restriction of movement in that right eye and then here's another example of a 63 year old who had a two month history of scalp tenderness and a new onset of an acute horizontal diplopia and you can see on exam he's having difficulty adducting bullfie so he actually had a bilateral INO and that improved after steroids after he had a biopsy proven giant cell arthritis and then here's another example, a 78 year old woman had a one month history of neck and shoulder pain and a 12 day history of horizontal diplopia and you can see she's actually having difficulty abducting and she had bilateral six nerve palsies from giant cell so you know the case is Zoster and we talk about Zoster all the time but the important thing we just can't forget that it can be disseminated and we can't miss it because it can cause vasculitis, it can cause strokes if it is disseminated and I think this is another good example of when you really want to try to put all pieces of the history together you know that rash was kind of discarded in our busy clinics as not being related but it was and it didn't quite fit this dermatomal distribution but that's why it was disseminated and why this patient had multiple cranial nerves involved so this is a good learning case in these scary diagnoses that we need to keep in our minds and always look for. Does anyone have questions, comments yet? Very good Julia. Any thoughts on the role of steroids with herpes or Zoster I didn't look into that, I mean I just know there's debate and I don't know that there's any evidence one way or the other but I would probably defer to the audience for that if anyone has. I didn't review that, literature. There was a review at Academy and the consensus there was the evidence for steroids is much weaker than the evidence for it. And then you know there's a lot going on with Zoster between the actual chicken pox vaccine and what that will eventually be for Zoster and then also the Zoster vaccine and what that could mean. So there's a number of people who are really looking at that and one of the things also from this review at Academy is the likelihood of the age dropping down even lower for recommendations for the Zoster vaccine because you can have it in your 30s, 40s, 50s and it seems like the numbers justify even dropping down to an age of 50. So that's a potential change. Alright so short, I thought that there was another presenter today until yesterday.