 Okay, I think that's eight o'clock. So our first speaker this morning is Dr. Vinolevich from the Pediatric Neurology Service. She'll be giving us a great talk and then that will be followed by Dr. DeGree who will be talking about some projects that we have going around here at the Moran, mainly the library. So without further ado, Dr. Vinolevich. Hi there. Can you hear me all right? Great. So as your colleague mentioned, I'm from Pediatric Neurology, but did have a recent neuroophthalmology rotation in which I saw a patient I'll be discussing today with Dr. Judith Warner. I have very few disclosures. This patient was a 51-year-old woman who had been referred by neurology to neuroophthalmology because of some abnormal eye movements that they had observed and also developing double vision. She did develop dizziness first in August of 2013. And since then had been diagnosed with migraines because of having some light sensitivity, sound sensitivity, and nausea with these. No medications that she had tried had been very effective, neither had violence and hearing therapy. Then she started to have some double vision. This developed in the fall of 2015 and kind of came on to her gradually. The two images were always separated vertically, but sometimes there was a lesser horizontal component in their separation. It was binocular and improved with patching of one eye. She was having frequent falls by the time that we saw her and did require a walking stick and found going downstairs particularly difficult. More alarmingly, for about a one month period in April of this year, she had difficulty talking. She could express herself by writing and her husband had noted that she had some intermittent left arm shaking during this period as well. She had already had some work up through neurology. So first when she developed her persistent dizziness was seen by audiology, diagnosed with just some mild hearing loss, was seen by an otolaryngologist as well when her symptoms started and they did note down beating nystagmus indicated a possible central contribution to her pathology. So she was referred to neurology. They performed a lumbar puncture and MRI which were reassuring as well as some other serum tests. And the abnormality they noted was slightly elevated thyroid studies. Her past medical history is notable for some psychiatric disease including quite serious depression with a history of suicide attempt. She has used glasses for driving for the last two years and has had perhaps a concussion. She did have headaches prior to 2013 which were non-migratous in character. And then family history is significant for some headache history as well as some cancer and autoimmune. So her exam, she did have normal corrected visual acuity, no afferent pupillary defect. Her visual fields were subjectively a little decreased. I think it was on the left but they were full to finger counting and her motility was full in range but this is where her exam was the most abnormal. She had an alternating skew, also psychotic downward pursuit, downbeat nystagmus in right gaze and down gaze, and left-beat nystagmus in left gaze and up-beat and up-gaze. Interior segments slightly abnormal with regularity of the left pupil margin and intraocular pressures and dilated of fundus examination were fine. So for those of you who haven't encountered skew deviation before provided a kind of image of what it looks like, essentially when patients look to the right, they have a right eye hypertropia. In primary gaze, they look fairly normal. And then in left gaze, they have a left eye hypertropia. And they kind of refer to it here as a vertical misalignment caused by damage to pre-nuclear vestibular input. But don't get fixated on this idea that it has something to do with the inner ear because that word vestibular can be resulting from the lesion in the cerebellum, brainstem, superior colliculi, those sorts of areas. It can be differentiated on exam from a bilateral fourth nerve palsy. In that, you have a right eye hypertropia in left gaze and a left eye hypertropia in right gaze. So after examining this patient, Dr. Warner, who I was working with, was most concerned for cerebellar pathology. But as I noted, the MRI was normal. This can occur in certain antibody mediated diseases, especially early on in the disease before there's cerebellar atrophy. So she was tested for perineoplastic antibodies, GAD65, and gliadin antibodies. Episodic ataxia was considered, but her symptoms hadn't really been that episodic. We did suggest that a trial of dialogues could be considered by her primary care doctor. And then this subjective visual field deficit she had was difficult to evaluate because she didn't have her glasses with her. So we asked her to fill a new prescription for her myopia and return in six weeks to test her visual fields, and perhaps to make a trial of prisms as well, and then prescribe vestibulotherapy. She'd been having a great number of falls. And then her results came back, very positive for GAD65 antibodies. Her gliadin antibodies and myopia or neoplastic panel were negative. So GAD65 antibodies can present in a number of ways. They've been associated quite strongly with stiff person syndrome, probably the initial disorder in which they were reported to be associated. Insulin-dependent diabetes, though in lower titers typically. Progressive encephalomyelitis with rigidity and myoclonus or perm. Cerebellar ataxia, which this patient certainly was exhibiting. Encephalitis, questionably also present in this patient. Epilepsy, and some patients have elements of multiple of these. It is an ophthalmologic disease with reported associations, including the cerebellar signs found in this patient, hypo-metrics accords. And then I've also seen a patient with perm who had terrible ophthalmoplegia as well. The epidemiology of GAD-related cerebellar ataxia in particular is highly female predominant. The average age of onset is somewhere in the middle years. And half of these patients have type 1 diabetes as well. The antibodies can be sent out to Mayo or here to Arup. And typically the titers will be higher than those found in type 1 diabetes. And often these patients have antibodies to other endocrine tissues. Occasionally the etiology can be perineoplastic. The pathophysiology is that these antibodies attack the presynaptic nerve terminals around the cerebellar prokinzy cells. And GAD is an enzyme that synthesizes GABA from glutamate. Patient symptoms that can be a clue when you're interviewing folks for which you're considering this diagnosis include double vision, difficulty walking, stiffness, personality changes, diabetes, and other rheumatologic diagnoses. The treatment, there haven't been a huge number of cases reported of this. And response has been quite variable, but generally immunosuppression is the main treatment for the underlying disorder. There is one case report of periodic alternating nystagmus responding to baclofen. And again, if you think about a disorder of GABA production, a GABA-ergic drug such as baclofen ideologically makes some sense. So the patient was referred on to neuroimmunology once this diagnosis was made. And their impression was that her condition was highly consistent with GAD-65-related progressive cerebellar dysfunction. They invoked some other things like her increased anxiety and startle response as well and recommended treatment. And in fact, when I spoke to this attending who had seen her yesterday in clinic, she mentioned that they were planning to proceed very aggressively with plasmapheresis. Her anxiety, they recommended treating with volume. So for the results, they sent out for GAD-65 to get a precise tighter to track over time in response to immunotherapy to Mayo. And then she also had an elevated hemoglobin A1C, so perhaps working her way towards type 1 diabetes. And then her thyroid is much more elevated now than it was a few years ago. They also sent for glycine receptor antibodies because these can present in a very similar fashion, particularly with respect to the cerebellar findings. So these are my references for the presentation, and I will welcome any questions at this time. When should we order antibodies for GAD-65? I think if you have, as in this case, some abnormalities of eye movement that could be best characterized as cerebellar, rather than being attributable to any of the cranial nerves. And certainly either just isolated cerebellar atrophy or a normal cerebellum on MR imaging that antibodies should be considered, especially if you have any clues such as these associated symptoms like the maybe stiffness in the back or already diagnosed diabetes. Other questions? All right, thank you.