 I'm going to move on to Dr. Byrd. All right. I'm going to be presenting a case today that I saw while I was on the pediatric rotation. All right, so this is a case of a six-year-old female who initially presented to clinic with a complaint. Well, her parents' chief complaint was an abnormal head position. And this was July 2015, but her parents and teachers have noticed kind of her starting to turn her head around October of 2014. So it had been going on for quite a while. And really the only other thing they had noted was some frequent tripping, which they weren't sure if that was just because of this head turn or really what was going on. But otherwise, she was healthy, no other past medical history. She had, because of this head turn, and she saw an outside optometrist who thought that she had some amblyopia and Dwayne syndrome and referred her to the pediatric ophthalmology clinic. So when she was seen, her visual acuity was 2060. Hers to business exam was significant for a large left head turn. She had impaired abduction in the right eye and impaired abduction in the left eye, so kind of a left conjugate gaze palsy. But the rest of her extracurricular motility was full. She was ortho and primary gaze. No large refractive error. And the remainder of her dilated exam and slant-lamp exam was normal. So I'm just going to talk a little bit about a horizontal conjugate gaze palsy and what kind of go over some anatomy and differential. So it can localize to a few different locations. A lesion in the contralateral frontal eye fields can cause it. An ipsilateral peramine, pontine, reticular formation lesion, or an ipsilateral abducens nucleus lesion. So if we review the abducens nerve nucleus, we can remember that the nucleus not only innervates the ips lateral rectus, but it also sends neurons to the medial rectus of the contralateral eye. So if you get a lesion of the nucleus, you do get a conjugate gaze palsy. And then just kind of similarly, or a few things that are related to this anatomy, we can remember that the seventh cranial nerve in the facial nerve here is in close proximity. And so a lot of times, we do see lesions that can cause a conjugate gaze palsy or a cranial nerve sixth palsy in association with a cranial nerve seventh palsy. And then also, just as a reminder, that one and a half syndrome is another thing you can get with lesions in this area, where you have damage to abducens nucleus and the ipsilateral MLF, which can cause essentially you have a conjugate gaze palsy and an ips lateral I&O, where you have only preserved contralateral abduction. So that's just something to keep in mind. So if we think about a differential diagnosis for a conjugate gaze palsy, I wanted to break it down into adult and pediatric differentials, but realizing that you can have these in the pediatric population. So we can think about brainstem ischemia, infiltration, trauma, inflammation, compression, demyelination, or any key Corsipov syndrome, which is a reminder is metabolic insult. And it can insult the cranial nerve sixth nucleus. We can see it in a lot of different things, including pancreatitis, anything where you have kind of abnormal electrolytes, but also most commonly in alcoholism, and then ALS. There are rare complications of listeria meningoencephalitis, where you can get cranial nerve palsies, so infectious causes as well. In the pediatric population, we have more congenital problems that are on the differential. That I'll kind of review some of these that are a little more rare. And we probably haven't gone over too much before. But a brainstem AV malformation could certainly cause a conjugate gaze palsy. Neoplasms, such as a pontine glioma, is on the differential. And we'll go through the rest of these. And in this patient, this is a new onset, kind of a cute presentation. So these don't necessarily all fit with her, but we'll go over them. So if you have a bilateral Duane's retraction syndrome, it could have some characteristics that look like a horizontal gaze palsy. But you wouldn't really see a unilateral gaze palsy. This and Duane's retraction syndrome is really a disinheritation syndrome, where you have varying degrees of abduction, abduction, or both deficits in one eye. But the classic hallmark of the disease is this co-contraction in the eye, where it is the medial rectus and the lateral rectus are firing at the same time. And you have this contraction, which causes the palphebral fissure narrowing that we see. These images are of an ipsilateral or unilateral Duane's. But if you had a bilateral Duane's, it could be, I guess you could think that it was a horizontal gaze palsy. But you do see other potential abnormalities with the eyes in up-shoot and down-shoot changes, or up-shoot in certain gazes. So that is probably not really what, you know, in our patient, she doesn't really fit that criteria. There's another disease called Wildervanx cervical ocular acoustic syndrome, which is a triad of Duane's retraction syndrome, Clipple fiel anomaly, where you have congenital fusion of your cervical vertebrae and sensory neural deafness. These are pretty rare. Another disease that's in the spectrum of the disinherbation syndrome is the Mobius syndrome, that we also know as congenital bulbar paralysis. These patients can have an abduction or absent horizontal gaze bilaterally. So they can basically no horizontal gaze. But they do have, or they can have preserved vertical gaze. These are congenital problems with the cranial nerve nuclei, so they have cranial nerve seven palsy. So these kind of masked faces, no facial expressions. And multiple cranial nerves can be involved. So this is image demonstrating an atrophic tongue. And on their pathologic findings, they've found atrophy and necrosis of cranial nerve nuclei. One theory for this is potential vascular insult in the prenatal period, but it's not completely clear. Another rare disease that could, congenital disease, that could present with the horizontal gaze palsy is this congenital horizontal gaze palsy with progressive scoliosis. It's again in the spectrum of a cranial disinherbation syndrome. And these kids can have horizontal gaze palsy. They don't have a horizontal vestibular ocular reflex. They can have esotropia, but they usually have preservation in their convergence, normal vertical gaze. And they can't initiate saccades, so they have head saccades. And then goucher disease is in the metabolic spectrum. So you don't have glucosuribrosidease, so you can't break down your glucosuribroside. And these, they could have just a horizontal gaze palsy, but they can also just have ocular motory proxy and anything that falls into the super nuclear gaze palsy. They have a lot of other systemic problems and varying. There's different types, so they might not present. There's some infantile types that are more kind of severe. And there's other types that present later in life and are more mild. And there's Leigh syndrome, which is basically an infantile or neurodegenerative condition. You can get a thumb oplegia with this. And again, kind of super nuclear problems could be horizontal gaze palsy and that, but they have a lot of other neurologic problems that are kind of degenerative over time. So with our patients, I mean, we have an acute onset of a new gaze palsy. Looking at the differential, really the concerning things are a neoplasm. So she did get an MRI. And unfortunately, these are the results. So this is a T1 image. And you can see this large hypo intense lesion here. We see it again on T2 imaging and hyper intense here, kind of heterogeneous. And then again here. And you can notice that it's really isolated to the ponds and you have this distinction between the ponds medullary junction. This is, this imaging is characteristic of a diffuse intrinsic pontine glioma. And if we go back, we can also see that this lesion is causing mass effect in obstructive hydrocephalus as well. So unfortunately, this is a really kind of sad diagnosis and a hard one to give patients. I think in this case, I was around when she got the MRI. And it kind of reminds you that as ophthalmologists, we do sometimes have to deliver really bad news and hard news. I think you don't have that experience a lot. But when you do, it's a good learning experience. So this is the, this neoplasm is usually diagnosed between five and nine. So it presents in childhood that it can be diagnosed at other ages. But many times the first symptom is a cranial nerve palsy. And typically, you see six cranial nerve palsy as the presenting sign. You can have facial paralysis so patients may come in or parents may come in and say they have, you know, they noted their child has an asymmetric smile. And then clumsiness, difficulty walking, loss of balance, weakness are all things that can be presenting signs. So our patient had some, you know, tripping that was noted. It's unclear if that was, you know, I think the parents maybe thought that was from the head turn, but a lot of patients, about a third of patients that diagnosis do have symptoms and increased intracranial pressure because a lot of times these lesions do cause a obstructive hydrocephalus, just given their location. And it's a really rapidly progressing disease. So usually once the patient starts having symptoms it's diagnosed within three months and the symptoms progress pretty rapidly. The prognosis is quite poor, and it's the main cause of brain tumor-related deaths in children at this time. Without radiation the median survival is about four months. Overall survival is 30% at one year, less than 10% at two years. There's rare cases where the patients have had longer-term survival, but these have been associated with atypical features clinically and in the imaging. So at the moment, the treatment that we have is radiation, it's not curative, it only prolongs survival by a mean of three months. A lot of times patients are started on steroids just to try to help some edema, but again, nothing curative. There's, of course, research being done into alternative treatment methods and they've identified this mutant histone K27M in about 80% of cases that is a potential target, but they're starting some clinical trials, nothing that's imminently gonna be available. And then immunotherapy as well as another kind of target. There are a few clinical trials with some vaccines against various, or targeted against the Ponting glioma, but again, nothing that's imminently gonna be out. So going back to our patient, she was seen again in clinic. This is kind of a month or a few weeks after her MRI. She had gotten hooked up. When she got the MRI, she did get admitted, had oncology, see her, they did more imaging, did a spine imaging, and got hooked in. So she ended up getting radiation therapy. Prior to getting, starting her radiation therapy, again, no disc edema was seen. She still had her left gaze paralysis and her left face turn. In a few months later, she progressed and had left facial paralysis and leg ophthalmos. And then in this timeframe, she started getting radiation therapy and she did have some improvement on her imaging of the brain stem glioma. When she was seen again in February, she actually had improved abduction of the right eye. So really kind of more of a picture of a isolated left cranial nerve six palsy and now in clinical esotropia. And she still had a really, really significant head turn that was difficult for her. So the decision was made to do surgery and she was taken to the operating room because of basically no function and forced sections in the OR. Vertical rectus transposition with a foster suture modification was done and a Botox and Melachmedial rectus. Or sorry, oh yeah, that's correct. And the foster modification is basically doing a fixation suture to attach the transposed superior rectus and the transposed inferior rectus to the lateral rectus to try to give it more power. And on her five week follow-up, she did have an improved face turn and a little bit of near-intermen-hypertropia and a little bit of exotropia in primary position but overall they were very, you know, her parents felt like this was a great improvement. But unfortunately, around February, she did have increased tumor size on her MRI and then she was put on hospice and then couldn't pass away. So she, you know, it's a really sad case. I think for me the things that stood out for the case is just kind of the, first of all, delivering really hard news more than just, you know, you won't be seeing again but that this is kind of a lethal malignancy in a child. And then also, you know, it is hard to do at times a pediatric eye exam but knowing that this is the potential when you have to know that that's an option before you call something a Dwayne's or a Mobius or saying it's a congenital thing because these do need to be picked up and where some, you know, many times the ophthalmologist might be the first person seeing it and the doctor that has to actually order the MRI and diagnose it before it, you know, before time goes on. So that is my case. Does anyone have any questions or comments? Dr. Kapps? So not to cast any esperses of why operate on a little girl whose life expectancy is less than? Well, I'm, I don't, yeah, I, it's a quality of life thing. And so I think just based on the difficulty and the parents feeling like the head turn was a, you know, was a problem that that was enough of a thing. And in February, her, I mean, her scan had gotten better and then it got worse. So I don't think, I mean, the life expectancy thing we know overall of the statistics, but I don't think for her at that time, you know, if the parents, yeah, you never know. And it was basically quality of life operation. I think, and it's Dr. Dries's, I mean, if you have anything, I think that was the rationale, which is very reasonable. Whatever you can do, I mean, if the parents and the patient are having, you know, head turn and neck pain and everything from this head turn, then, you know, she's on hospice, but it is a quality of life intervention at that point. Yeah. That's a great presentation. Do you, you know, we're now treating a lot of other gliomas with carbonyl flat and other chemotherapy aids. Did you find anything? Because we've got actually in comparative when we use radiation treatment for, you know, visual pathway, for optic pathway gliomas in NF1. Yeah. And even the non-NF1 tumors, they respond wonderfully. Yeah. They're causing troubles. It's, I mean, these appear to grow much more rapidly, more aggressively, exactly. They've done studies and they hadn't shown, you know, in the studies that they did with other chemotherapy agents, there wasn't any improvement and just kind of caused more toxicity. So there had, I mean, at this point, the focus is really on kind of the more novel mechanisms, but the chemotherapy agents that are tried haven't worked. And I think, you know, the location and the rapidly, the rapid progression, I think just put it in a little bit of a different category. But yeah. Dr. Werner. I think the other thing with optic pathway gliomas is that they're such a different tumor. Some people even wonder if, there was a huge debate at NANOS the other year about, are they really gliomas or are they just tomatomas? And should they be treated with chemotherapy ever? Sometimes, not at all, because there's a pretty high spontaneous regression, right? Even with vision and with imaging. So I think it's been very difficult to show unequivocally that whatever we do to treat optic pathway gliomas is actually better than the natural history, which is so good anyway in children. Right. That's a relief. Whereas these guys, these diffuse pontine gliomas are just so uniformly fatal. Yes. I think that might even argue for ongoing and more aggressive trials of chemotherapy. That's cute, right? Like you don't have very much to lose, whereas in a tumor that's going to potentially regret on its own, then you have to be pretty sure you're actually doing something beneficial. That it's also going to grow and cause harm. But the kids have worked for you. I mean, what this reminds me of, as far as the collateral damage of radiation that we induce in kids with the optic pathway gliomas for that F1. Right, yeah. It's for friends. Yeah, yeah. And it's such a night and day difference. So it'd be very cool if they could find something that would go up. I mean, at this point, the radiation therapy is, I mean, it's, they don't have any, yeah, I mean, and kind of, it doesn't, you know, it's like prolonging things by not very long, but you don't even see the downstream consequences because unfortunately the survival rate is so low. But that's kind of like the option we have and they're using, there's a lot of clinical trials and I mean, hopefully there are things that as they're setting genetics in more of the mutations, but down the line, yeah. Yeah, there wasn't, you know, it looks like there had been some studies done and nothing really panned out. And now the focus is more on the kind of alternative newer methods of treatment from what I've seen.