 So this is a 10-year-old previously healthy female who had failed her school vision screening exam for fourth grade. Two years prior she had had a school vision screening exam which she passed without any difficulty. So the school recommended that she go get an eye exam and she was referred to an optometrist. Her right eye was 2020 and her left eye was 2200 and he noted a pale optic nerve. The patient denied any decreased visual acuity that she was aware of. She had had no problems in school or seeing the board. So she came into neuro-ophthalmology clinic. Her past medical history, she had had a tumor in her index finger on her right hand. This was removed in Mexico. She had a post-operative infection and there was some concern about the surgeon, so mom wasn't sure what, if any, studies had been done on that tumor. She had an unremarkable birth history, she was developmentally normal. There was no unexplained vision loss in the family. She was not in any medications and she had no allergies. So on exam her visual acuity in the right eye was 2010-20 and the left eye was 2200. She had decreased stereo vision and in the left eye her color vision was decreased. Her pupils in light were 3 millimeters bilaterally and in dark were 5 millimeters. She had a .9 log APD on the left. Her visual fields on the left were constricted to confrontation. She had some mild proptosis. Her extracular movements were full and on her fundoscopic exam her left optic nerve was very pale. So she was sent for an MRI and this is the MRI of her brain. This is an axial T2 lip contrast and this was read as bilateral vestibular schwannomas. They're most easily seen at the cerebellar plantain angle and they're described as porous here. And this is the most recent of her MRIs and at this point this is her actual second MRI. There was involvement of not just the eithner but the facial nerve as well. And then also in her brain MRI responsible for her proptosis and her loss of visual acuity she has a left optic nerve she's meningioma. So this constellation of findings is consistent with neurofibromatosis type 2. This is caused by a mutation in the NF2 tumor suppressor gene which is on 22Q12. There approximately occurs 1 in 25,000 births so Utah has about 60,000 births a year. So there should be about 2 to 3 cases a year. It's autosomal dominant. The most common finding is the bilateral vestibular nerve schwannomas. You can also have meningiomas, epindemomas, astrocytomas, and neurofibromatosis 2 are quite rare. And then the ocular findings which we'll be talking about include cataracts, epiretinal membranes, and then retinal hammeratomas. NF type 1 is a phenotypically and genetically distinct disorder and that's on 17Q11. I'm in the gene. And that is class, does have cafe au lais spots, many more neurofibromas. So in diagnosis approximately 50% do not have a family history. The Manchester criteria is used for diagnosis so if a patient has bilateral vestibular schwannoma you don't need additional findings for diagnosis. And then if they have a positive family history you need either a unilateral vestibular schwannoma or two NF2 associated lesions. So meningioma, glioma, a neurofibroma, a schwannoma, or a cataract. If they have a unilateral vestibular schwannoma then you need two other NF2 associated lesions. And if you have a patient with multiple meningiomas you need either a unilateral vestibular schwannoma or two other associated lesions. The average age of diagnosis is 20 years of age but the delay in diagnosis is approximately seven years. There is a childhood onset form and those patients more often present with visual disturbances so the cataracts, hamartomas, or intracranial tumors. They can also present with skin tumors which likely was the earliest manifestation that our patient had. Also mono neuropathy so they can present with facial peresis or foot drop. 30% will present with hearing loss. There's a study done by Bosch and Zurich and she's an ophthalmologist. It was published in the American Journal of Ophthalmology in 2006 and she did a retrospective observational study and had 30 patients that had come to their clinic. And she found that 10 years after the first symptoms all of these patients had at least two CNS tumors. Then for the later onset NF2 these patients are more likely to present with hearing loss from the vestibular schwannoma so 92% will have hearing loss. They also can complain of tinnitus, dizziness, or imbalance. And then Bosch found that only 11% of these patients at 10 years after their symptom onset had two or more CNS tumors. So the frequency of the lesions that are associated with NF2, bilateral vestibular schwannomas you'll see in 90 to 95%. The cataracts you'll see in 60 to 81% which was similar to what Dr. Bosch had found. Epi-retinal membranes you'll see in 12 to 40% and then retinal hematomas in 6 to 22%. So here I'm gonna go through just the neurological manifestations of the other tumors and then we'll talk a little bit more in detail about the ocular findings. This is an axial T1 image with contrast of the brain which shows the bilateral vestibular schwannomas with the aeroplane here and then you have extension of the schwannoma. And then here you have a dumbbell shaped schwannoma which is actually pressing on the spinal cord here. This is a schwannoma which is involving the intercostal nerve. And then here is the H&E staining which you see spindle cells. And you also see Antoni A and B cells. The meningioma is the second most common tumor found at NF2. 45 to 58% of patients will present with this. Often there'll be at least more, there'll be more than one. And if they have a meningioma this will increase their mortality. It also increases the morbidity if it originates from the optic nerve sheath. And 20% of children who are presenting with the meningioma will actually have NF2. So if you have a patient that has a meningioma this should certain NF2 should be on your differential. For the appendemoma, here you see the C7 that's kind of swelling here. And then this is post-contrast. And something that's distinctive of this is this kind of string of pearls appearance. This accounts for 75% of inter medullary spinal cord tumors. It's present in 18 to 53% of patients but it's symptomatic in less than 20%. And for those patients that are symptomatic, they'll have back pain weakness or parasthesias. The cutaneous manifestations. So skin tumors will be seen about 59 to 68% of patients. These often are plaques, so you can have hyperpigmentation and hypertrichosis. These are usually small plaques, less than about two centimeters. You can also have subcutaneous tumors, allowing the peripheral nerves and intradermal tumors, which are most often schwannomas. Caffeolay, though, it's much more common in the neurofibromatosis type one, you can have this in neurofibromatosis type two, except it's often singular. So in neurofibromatosis type one, for the diagnosis, you have to have more than six lesions and they have to be greater than 15 millimeters depending on the age group. But in neurofibromatosis, you can still have a Caffeolay spot. It's usually just one. And this was true of our patient. She had a Caffeolay spot. The ocular findings. So you'll find cataracts in 60 to 81% of patients. They usually found in the posterior subcapsular or regions or you can have cortical and ticular opacities. Only cataracts in patients that are less than 50 years old can be considered part of the constellation of NF2. And they interfere with vision in approximately 10 to 25% of patients. The second common finding is epiretinal membranes. These usually are not the cause of loss of visual acuity in patients. You can also find retinal hamartomas. Frequently, these do reduce visual acuity. You can also see disc gliomas or as in our patient an optic nerve sheathment in geoma. So here's some photos of the ocular findings. So here's the cataract in the post subcapsular and capsule region. And then this picture is actually a magnification here of the wedge cataract in the peripheral. And then this picture is an epiretinal membrane. And then this picture is a retinal hamart. Again, here are a couple of pictures. So here, the first picture you see posterior and anterior subcapsular lens opacity. And then the peripheral cortical cataract is right here. And then I think it's a little bit difficult to see the epiretinal membrane in this picture, but they're pointing it out here. And then in the last picture, the patient has an epithelial. And then here are just a couple other pictures of the epiretinal membrane. This patient had an optic disc glioma. Her onset was at a very young age and the course of her disease was very severe, which is most of the early presenting cases are more severe. This is a patient who had had several surgeries for tumor devulking. She has an optic nerve sheathment in geoma here. She had a multi-lobular vestibular schwannoma, which you can see here. And then she also had bilateral meningiomas here. This chart is from the study done by Bosch. So she had 30 patients and there were ocular findings and 25% of the 30 patients on their initial exam. And for the childhood onset cases, 94% of these patients had visual symptoms. This probably is a little bit elevated because of a referral bias for her. And also that the childhood onset are more often very present with visual symptoms early. So these patients had, as is typical of NF2, cataracts, epiretinal membranes and optic meningioma. And then on the adult onset patients, only 67% of those patients had initial ocular findings on there. So the first line here are the number of eyes that were involved. And this is the number of patients in the associated findings. So for discodema, seven patients with 12 eyes had discodema. All of their discodema resolved, but these two patients right here were new onset discodema at their follow-up visit. The exoptalamus was due to intracranial tumors and the lid dysfunction was often related to tumor resection that might have involved the facial nerve or corner syndrome for those patients. So our patient had a six-month follow-up and at that time her vision and her left eye was still 2,200. Her affilarant pupillary defect was a little more severe. It was logged at 1.2 and she still had a pale optic nerve. Her Goldman visual fields, which I think are over here, are constricted and depressed in the left eye. She had an audiology evaluation, which was normal. She saw genetics, who ordered an MRI for spine and genetic testing. So when you see a patient with neurofibromatosis in particular a child, they get to refer to the neurofibromatosis center at Primary Children, which is nationally renowned. They found the gene for NF1 and they will see the patient. So unless the patient is having seizures or headaches or weakness, they don't usually get referred to neurology, but they go to the NF clinic. And for this patient, they wanted an MRI of the spine because she had these cafe-olay spots and she also had some axillary freckling. They wanted to look for ependymomas in our patient, which she actually did have. And at that point in time, they were gonna pursue genetic testing and then test the rest of her family. The patient was also evaluated by ENT in neurooncology. So the recommended screening intervals, these screening intervals are actually for a patient who has a family history of NF2. So for a child, they recommend at least an ophthalmological evaluation yearly, a neurological exam yearly, which doesn't have to be done by a neurologist. There's an audiology evaluation with brainstem evoked potentials and then a brain MRI at 10 years of age and a spinal MRI at the same. So again, the average age of the onset is 20 years old, but the diagnosis is delayed on average approximately seven years. Bosh found that through follow-up with her patients that 30% became completely deaf. 63% had marked hearing impairment and only 7% of the patients had normal hearing. Markers for increased risk of mortality include an early age of onset and the presence of an intracranial meningioma. Yes, it does, yeah. So it's particularly important because so many patients will become deaf to preserve as much of their vision as possible. So these patients should be referred very early and one of the major problems with removing the meningiomas intracranial is that they can't have a lot of facial weakness and there's just a lot of morbidity associated with those surgeries. Questions? So unfortunately our patient probably has a pretty, and then she has a penicillin. So likely if that needs to be resected, she'll have lower extremities.