 This is Blake Williams coming from Chicago and he's presenting a case of up gaze restriction. Hello everyone, I'm Blake Williams coming from the University of Chicago. Thank you for having me this morning. I'm gonna be talking about a case of up gaze restriction. So we have our patient, ZW. He's a 42 year old male who presented to the emergency department with a two month history of right sided, initially in then bilateral numbness and weakness and a three day history of difficulty ambulating and worsening numbness. His past medical history is significant for a developmental delay, it was unspecified but he had muscle tenacity in the neck and back as an infant, as well as congenital right sided ptosis. He's had a number of surgeries in the past. He had a right ptosis repair with frontal fixation in 79 followed shortly by a strabismus surgery for a right up gaze paralysis and he also had a negative cardiac cath which was part of the workup for his diffuse numbness. For social history, he has no smoking history, quit drinking shortly before presentation. He had been drinking a few beers a night. He's single and worse with his father. No family history of neurologic or ocular diseases and he has a history of coronary artery disease and MI in his father. He has no known allergies and has been taking aspirin 81 since the cardiac workup shortly before he presented. For his hospital course, he initially presented in June of 2015 at an outside hospital for this weakness and numbness. A head CT on June 1st showed ventriculomegaly, predominantly left sided. He got an MRI of the cervical spine without significant findings, CTA was normal and his diagnosis was congenital hydrocephalus and discharge on aspirin. He was admitted about two months later on July 31st with worsening numbness and recent instability. A RIPID MRI showed stable hydrocephalus similar to the outside imaging. Neurology and neurosurgery were consulted. No intervention was indicated but then the next day it was noticed that he had bilateral up gaze restriction that was new and so ophthalmology was consulted. On ocular examination, that visual acuity was 2070 corrected to 2020 pinhole on the right, 2020 on the left. Pupils were symmetric and equally reactive. Full visual fields, pressure was 13 in each eye. Then the interesting findings were on extroocular motility. He had a right exotropia with inability to look up or down. He adducted on up gaze and abducted on down gaze. While on the left eye he just had an up gaze restriction and he adducted on up gaze. And then the very interesting finding was that he had a convergence retraction nystagmus noted on up gaze and it took a second examination by ophthalmology to confirm this. This is not the patient that we saw we weren't able to get pictures of before he was discharged but this is pathenomonic for the condition that he had. Significantly you can see when he has an up gaze restriction as well as a few other findings which I'll go into. So I wanted to show a quick video of the convergence retraction nystagmus. Actually, what we are seeing is convergence retraction nystagmus but you can't really appreciate the fact that the eyes are actually retracting. But this is what convergence retraction nystagmus looks like from straight on in somebody being asked to look up. Now looking from the side as she's being asked to look up you can see the eyes actually retracting in the orbit in this example of retraction nystagmus. So I tried to get a video on my iPhone but it was not nearly as good as that. Okay, for the rest of the physical exam we had a portable float lamp and he had some minor poteosis in the right eye some blufferitis in the left eye but basically everything else was normal. Lenses were clear, he had cup to disc of 0.4 normal dysmaculin vessels in the retina. This is taken from the neurologist, their physical exam. No cranial nerve exam finding except for the eye exam and on the sensory exam he had decreased sensation bilaterally in the lower extremities and hands and then also he had a narrow-based slow gait. So to recap, we have a 42 year old male with a two month history of numbness and weakness who presents with gait instability, worsening numbness and up gaze restriction with convergence, retraction nystagmus. So we got a number of studies and everything was largely normal. CBC metabolic panel, ToxScreen, they did a myocene agravus panel, copper was normal, B12 normal, CRP was less than 0.1 and no abnormalities on the lumbar puncture either. So this is the MRI that he got just showing diffuse enlargement of the lateral ventricles. The ventricular megal is more pronounced on the left side than the right but this was stable compared to the outside imaging and then just another view showing the ventricular enlargement and there are no other abnormalities seen on those scans. So what is the differential diagnosis of an up gaze restriction? There's a long list but basically the top two or three will be seen in the vast majority of cases. The first is dorsal mid-brain syndrome or perinode syndrome. Also progressive super nuclear palsy which presents similarly to Parkinson's disease and then a few other rare ones which I could not find much information on. In terms of other imaging, a CT cisternogram was recommended by neurosurgery but they actually didn't do it at Loyola which is the hospital I was at. They did an MR sign, showed no CSF flow, was appreciated in the third and fourth ventricles or the cerebral aqueduct was a minor flow at the foramen magnum but since this hydrocephalus was stable compared to before they didn't think it was a huge problem. So he was diagnosed with dorsal mid-brain syndrome, likely secondary to hydrocephalus and I already kind of went through his work up. So dorsal mid-brain syndrome is also known as perinode syndrome, sylvan aqueduct syndrome, pre-tectal syndrome or corbosalus L. schnig syndrome. There are five main criteria for diagnosing this syndrome. Basically clinical syndrome characterized by a cluster of eye findings and with movement abnormalities and pupillary dysfunction. The first of which is paralysis of up gaze which was kind of alerted us to his condition. Vertical palsy super nuclear, so the doll's head maneuver which is more of a reflex is preserved early on but eventually all upward gaze mechanisms fail. Second is pseudo-argyllarobbertson pupils. As you know, Argyllarobbertson is seen with syphilis but the difference between this finding and actual Argyllarobbertson is that in perinodes the pupils are mid-dialated and in syphilis they're very small. Third is convergence retraction nystagmus which is virtually pathodendemonic for perinode syndrome. Fourth is eyelid retraction also known as Kalei sign which we see a lot in thyroid eye disease. And finally conjugate down gaze in the primary position, the setting sun sign which gets its name from seeing the sclera and the patient is looking down when they're trying to look straight ahead. The main, main cause of perinode syndrome is pinealoma that's the correct board answer. This shows a large pineal gland tumor pressing on the dorsal midbrain but some other causes include other brain tumors really any compression of the tectum. Hydrocephalus especially after shunt failures it was thought that this patient's hydrocephalus caused his perinode syndrome. Other cause of multiple sclerosis, vascular lesions, myasthenia can mimic a vertical gaze palsy and uncle herniation. So in terms of epidemiology there are three main groups of patients who present with perinode syndrome the first of which is a young patient with a brain tumor of the pineal gland or pinealoma which is most common. Also women in their 20s to 30s with multiple sclerosis can present with this and finally older patients following a stroke to the upper brainstem. For pathophysiology, perinodes results from an injury to the dorsal midbrain or the tectum specifically compression or a scheming damage to the mesencephalic tectum and it includes the superior colliculus which is adjacent to the ocular motor and edginger lesion nuclei. I wanted to show some anatomy just to highlight the proximity of the pineal gland to the superior colliculi and obviously if you get enlargement of the pineal gland through a tumor you'll get compression of the area and dysfunction of the superior colliculi. And then this is just to show the control centers for horizontal gaze which is the PPRF or Pontine Paramedic Articular Formation as well as vertical gaze which is the Rostral Interstitial Nucleus of the MLF and you can see the horizontal gaze center is very close to the Abusin's Nucleus and the vertical gaze center is very close to the ocular motor nucleus and it just helps, if you help visualize that you can remember the association between the two. Treatment and Resolution. Treatment is primarily directed towards the etiology of the dorsal midbrain syndrome through a workup including neuroimaging is essential. He got the MR sign to evaluate his flow. The eye findings generally improve over the first three to six months and if they don't improve after that time it's unlikely that they will. And if the cause is from acute hydrocephalus especially shunt failure, if you correct the shunt failure and correct the hydrocephalus they should get rapid resolution of symptoms. So back to our patient. Given his stable hydrocephalus and the crinicity of this condition no further intervention was recommended at this time by neurosurgery and he was planning to follow up with ophthalmology and neurology and clinic in a few weeks and hopefully he would have improved. Then I did a quick literature search. It's very difficult to find anything on dorsal midbrain syndrome since it is so rare. I was only able to find this paper from 1990. This author kind of put together 206 patients with the syndrome and the most common sign is pupillary abnormalities. 96% of the patients had that. I just think it's interesting that only 34% had the classic convergence retraction nystagmus which is quite rare to see but if you do see it you can nail the diagnosis. Then for etiology it's most commonly hydrocephalus 39% but also stroke and turmeric can cause it as well. And it had mentioned in this paper that there was a large amount of sister circuses going around with these patients so that might have made the hydrocephalus more common than pinealoma because more recently I've read that pinealoma is the most common cause. Here are my references. Thanks for having me and any questions?