 Our last and final speaker today is Devin West. He's a fourth year medical student visiting us from St. Louis University School of Medicine. And he's gonna be talking about CPEO. Okay, good morning everyone. My name's Devin West, as he said, I'm from St. Louis University. And I spent the first two weeks here at the Moran. This is my third week. So I spent the first two weeks in neuro-othemology clinic. And so today I have a case to present to you. So I will first present the case, talk about the diagnosis, and then thirdly talk about just kind of the take-home points for us to have in practice. So the patient was a 57-year-old Caucasian female without a chief complaint. She was referred to us by her neurologist. And her story started in May of last year. She went to her optometrist for complaints of blurry vision. It was her routine checkup. And her optometrist noted some bilateral limitation of extracular movements and referred her to an ophthalmologist. The ophthalmologist confirmed that she had cataracts, visually significant in both eyes. And confirmed that she did indeed have some extracular limitations in all directions, both eyes, and also had some bilateral ptosis with the right eye being greater than the left eye. Which per her history was present for many, many years. And so this ophthalmologist then, prior to taking any action with the cataracts, referred her to a neurologist for a workup. Now speaking with her, her past medical history is significant for diabetes type two. Her last A1C was 9.7 in December of last year. Asbestosis and abnormal thyroid, which had been detected several years prior and she had had an ultrasound and it was determined to be normal and just kind of benign, multinodular type picture. Depression. And following the workup, she did have cataract extraction bilaterally in April and June of this year, which resolved the blurry vision. And her surgical histories there as well, some C-sections, cholecystectomy and tonsils and adenoids. So her family history, she has no family history of any muscle issues, no progressive weakness, no history of miastinia or any autoimmunity specifically, we asked about thyroid disease. She does have a fairly strong family history of Alzheimer's disease in both her parents and several aunts and uncles. Coronary artery disease and coincidentally, she has an aunt who is a non-blood relative that has a mirf. And her daughter, when she came to clinic to see us, her daughter was there with her and her daughter said that she from time to time has diplopia, has some double vision and has been told before that her movements are not completely normal. So I mentioned she was referred first to her neurologist and this was the workup that he had done. He did first some blood work. He obviously checked her thyroid, which was normal. She was negative for any anti-acetylcholinestrates or acetylcholine receptor antibodies, but she did interestingly have an elevated lactate and pyruvate. MRI was normal, bilateral carotid ultrasound was normal, swallow study was normal and he also did send her for some genetic tests. ANT1 opal 1, POLG, twinkle and milis, which were all negative. And then referred her to us for confirmation of the diagnosis, which of course is CPEO, Chronic Progressive External Ophthalmoplegia. So on exam, this is what we found, fairly normal except for stereo. We noted that she had limitation or poor stereo vision and facial, in terms of cranial nerves, she was normal except for a few noted weaknesses that are here. Bilateral, orbicular, succulite weakness and an incomplete blink in the right. And we'll look at the doll's eyes, movements in a second. Her thyroid was non-palpable and on slit lamp and fundus exam it was unremarkable, except for some peripapillary pigment changes. So I'm gonna play this video. This is Dr. DeGree doing her extracular movement exam and there's audio. Can you follow my finger with just your eyes? And you can see that she has limitation of gaze to the right and to the left. And her dog gaze is slightly better, but it's still limited in her dog gaze. I'm gonna check her saccades. Look at my thumb, finger, over here. Over here, can you look over that? There you go, thumb, finger, and there's slow, thumb, down here, finger, finger. And slow there as well. Now close your eyes as tightly as you can, tight, tight, tight, tight, tight. And I can easily overcome it. And as you can see, she has tighter. She has very little bells phenomena. Her eyes don't roll up when I have her. Close her eyes really, really tight. Yet she has really good facial musculature. Keep your mouth closed now as I try to open it. Very good strength of her mouth closure. Can you focus on your finger here? And I'm gonna turn your head, and I just want you to, let's get it up a little bit higher. Just try to keep focusing, focus, focus, focus, focus, focus, focus, focus, focus. And maybe she can overcome it a little bit. Now I'm gonna have your head go down, down, down, down, down, but not very much. She can get down further, keep looking down, but we're not able to really overcome that up gaze parruses. Okay. So very typical findings of CPEO, which we'll go over in a minute. So Chronic Progressive External Thalmoplegia first described in, as early as 1856, by Dr. Von Graf, who was instrumental in glaucoma and also pictured there designed the Von Graf knife, which I believe was used for cataract surgery for several years in the past. So the main symptoms for CPEO are progressive bilateral limitation of vision with progressive ptosis. And one study showed that the most common symptoms were difficulty with small print and difficulty with driving, so almost a convergence, divergence, insufficiency type of picture. But most patients are asymptomatic and often do not complain of dyplopia. You look at their movements and you think, wow, this person should have dyplopia. And actually, I didn't show up, but on exam she also had about 12 exophoria, which was similar in lateral gazes. But again, she did not have any dyplopia. So etiology for CPEO, it's not specific for any single disease. However, it is the most frequent manifestation of mitochondrial myopathies, hence the genetic workup that the neurologist performed initially. Now the history of etiology initially, it was just sort of thought to be a neurologic process. And then an early biopsy showed myopathy and so then people said, okay, well it's myopathic. But then brain biopsies from patients with CPEO showed some spongiform changes. So then it kind of swung back to the neuropathic side. And it wasn't until Olsen and others in 1972 did biopsies that showed the prominent ragged red fibers that we know from mitochondrial myopathies. And the consensus today is that it is a myopathic disorder. However, it is multi-system and may involve the nerves as well. And interestingly, there's no genotype or phenotype correlation. There may be, people may have CPEO with none of the non-genetic defects. And specific defects are not associated with any worse prognosis. So there's a list there at the bottom of some of the other differential diagnosis considerations when you find CPEO. But again, the number one or most frequent, it is the most frequent manifestation of mitochondrial disease. And so that's what we should think of first. Now, most important with CPEO are the associations which are listed there. Most we can observe on exam. A couple require that we take more action to get more objective data. That would be pigmentary retinopathy and the cardiac conduction abnormalities. So in terms of the evaluation, again, we've sort of already touched on all these blood work to rule out myosthenia and thyroid. Muscle biopsy which can show in the top right there the ragged red fibers on Gamori trichrome staining. And ECG, which is kind of the most important. And these patients are prone to heart block, syncope and sudden cardiac death. And so when CPEO is found on exam, that is one of the most important, if not the most important thing that we do. Fundus exam, ERG, MRI to rule out any mass or cerebellar involvement. Oculofaryngeal dystrophy is on the differential and so that would be the reason for a swallow study. And plus or minus Tensilon test for myosthenia. However, the Tensilon test, as you know, increases the acetylcholine which can slow the heart and in these patients that are susceptible to heart issues can be a dangerous thing. And then as always the genetic assays. Treatment, there's not too much treatment. We can divide it between mechanical and medical. You can use as pictured above the ptosis crutches added to glasses or tape to help the lids stay open. Strabismus surgery is sometimes performed but with a little bit of hesitancy because these patients obviously are myopathic and the muscles do not react to surgery or adapt from surgery as normal muscles do. And then some medical treatment. One study showed that coenzyme Q supplementation improved neurologic function and decreased the lab values of lactate and pyruvate but did not improve the CPE or the ptosis. So and others, other supplements are sort of anecdotal. So back to our patient. She, we did a full field ERG which was normal. We recommended that she have an annual EKG. We did a Humphrey visual field which was also normal and her daughter reported some of the similar symptoms that I mentioned in the family history so we counseled her daughter has never sought a work up for this and so we thought that she might be interested in that in the future. But these are the kind of the take home points. It's progressive extracular muscle restriction or limitation with weakness and ptosis. It's the most frequent manifestation of mitochondrial disease. No proven treatment exists. However, some anecdotal evidence is there for some supplements. And the serious complications include cardiac conduction, defects, retinopathy, endocrine abnormalities if you'll remember she was diabetic and dysphagia. So I wanna thank the neuro team that I worked with for the first two weeks for their teaching and help with this case and everyone else I've met I've had a great experience thus far, thank you. Any comments, questions? Okay, thank you.