Ep 170: A 35-Year-Old with Changes in Vision

This episode is a discussion with Harrison’s editor, Dr. Andrew Josephson, about multiple sclerosis.

Read more on this topic in Harrison's.

Harrison's Principles of Internal Medicine, 22nd Edition

Transcript

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[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

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[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine. Welcome to Harrison's Podclass. Today's episode is a 35-year-old with vision changes. Cathy, once again, we're thrilled to welcome Dr. Josephson as our guest discussant for today's clinical case. 

[Dr. Handy] All right. Who are we seeing today? 

[Dr. Wiener] So your patient is a 35-year-old woman who reports a change in vision over the last two weeks. She first noticed that her left eye was mildly painful when she was moving it, but she attributed it to stress at work, since she started a new job about four months ago. She took acetaminophen, which helped the pain. However, over the last 10 days, she's had a noticeable decrease in the acuity of her left eye. If she covers her right eye, she notices objects at a moderate distance are blurry, and that's new for her. 

[Dr. Handy] Any prior eye problems or any redness in the eye? 

[Dr. Wiener] She has never worn glasses or contact lenses. She has no prior ocular history. And she's not noticed any redness of her eyes. 

[Dr. Handy] Any other symptoms? 

[Dr. Wiener] Yeah. On your review of systems, she does admit that over the last two to three weeks, she's had a strange pins-and-needles-like effect or feeling on her right lateral thigh and her upper left forearm. She notices when she touches these areas, there appears to be numbness despite the pins and needles. At first, she was worried she was developing shingles, but no skin lesions developed. She's also noticed increasing fatigue over the last two months. She's supervising more people at work, and during the day, has started drinking energy drinks to combat the fatigue. She also notes that when she gets home, she's exhausted. Resting over the weekend does help some, but she's doing less even on weekends because of the fatigue. 

[Dr. Handy] Has this or anything like this ever happened before? 

[Dr. Wiener] She did not spontaneously report this, but when asked the question, she reports to you that she recalls about 18 months ago, she developed severe pain in her lateral leg and in her right abdomen. She actually had an ultrasound that ruled out gallstones. At that time, she also developed numbness of her right foot and weakness after running. She was going to pursue further evaluations, but the symptoms abated over the next week. 

[Dr. Handy] Tell me about her physical exam. 

[Dr. Wiener] Her vital signs are normal, and the only abnormalities are in the neurologic examination. She does have moderate decreased visual acuity in her left eye and a left afferent pupillary defect. Fundoscopic examination is normal. There's no evidence of uveitis. She also has decreased sensation to light touch on her right lateral thigh and left forearm. She also has an upgoing toe on the right. 

[Dr. Handy] All right. I think we're beginning to narrow the differential. I do want to remind our listeners about afferent pupillary defects. This is elicited with a swinging flashlight test. That is, the pupillary response in both eyes is normal when a light is shined in the right eye, but is slowed in both eyes when the light is shined in the left. 

[Dr. Wiener] So what are you thinking? 

[Dr. Handy] I think she has optic neuritis. 

[Dr. Wiener] And how does that connect with the other symptoms? 

[Dr. Handy] It may be connected to multiple sclerosis, which would explain her other symptoms. 

[Dr. Wiener] Great. That gets us to our question, which asks, all of the following statements regarding this patient are true, except? A. Fatigue is an uncommon symptom of multiple sclerosis. B. Multiple sclerosis is most common in women between the ages of 20 and 40. C. Optic neuritis is a common initial symptom of multiple sclerosis. D. Relapsing remitting multiple sclerosis is the most common form of the disease. And E. Sensory loss and paresthesias are common initial symptoms of multiple sclerosis. 

[Dr. Handy] This is a great question and a perfect time to bring in our guest expert, Dr. Andrew Josephson. So welcome back to the Podclass. 

[Dr. Josephson] Thanks for having me back. 

[Dr. Handy] So today's case is about a young woman with ocular and sensory defects, in particular, optic neuritis. Can you tell us a little bit about that? 

[Dr. Josephson] Sure. Well, optic neuritis is an inflammation of the optic nerve, and it has a broad differential diagnosis. And there are certainly some cases of optic neuritis that have nothing to do with multiple sclerosis, they involve infections or other autoimmune diseases, but we must always remember the association of optic neuritis and multiple sclerosis. And in a patient like this, where there is additional history that there are other neurologic deficits, not only now, but in the past, when we carefully take a past medical history and hear about these episodes, you've got to think about multiple sclerosis. And in fact, if we think about the initial symptom of multiple sclerosis, optic neuritis is one of the things high on the list, in addition to people who present with sensory loss, or weakness, or paresthesia. So, I would try to tie those two together and really think about multiple sclerosis in this patient. 

[Dr. Wiener] Dr. Josephson, from what you told us, we know that options C. and E. are true. Can you tell us a little bit about the epidemiology of multiple sclerosis? 

[Dr. Josephson] Sure. Well, it is true that MS is more common in women than men, probably at least three times the prevalence. And it does occur most commonly between the ages of 20 and 40, so that choice is correct. In addition, at least 90% of patients begin with a relapsing, remitting form of MS, where there are episodes of inflammation in the central nervous system that then resolve, and it goes up and down like that, whereas only 10% have a more slowly, primary progressive course. The one that's false is the idea that fatigue is an uncommon symptom in MS. Interestingly, fatigue is a very common symptom in MS, affecting at least 50% of our patients with multiple sclerosis, and probably higher, if we ask careful questioning. While this is a little unclear, but something that we observe all the time. And in surveys of patients with multiple sclerosis, fatigue is often a very debilitating symptom that they wish to have addressed by their physicians. 

[Dr. Handy] How do we establish a definitive diagnosis for this patient and in general? 

[Dr. Josephson] Well, this is an area of continued change, with new criteria coming out later in 2025. And the bottom line is we can do this in many different ways. Classically, the MRI scan is very, very helpful. And MRI with gadolinium shows lesions that are scattered in different areas and are different time-based, in other words, some are enhancing, meaning they're recent, some are non-enhancing, meaning they are older. So, the classic used to be a dissemination across time and space on an MRI, but there's other things that we can do. We can use visual evoked potentials or what we call an OCT test to look for evidence of old optic neuritis. We can do spinal taps, looking for evidence of inflammation in the spinal fluid. And we can look not just at the brain with an MRI scan, but the spinal cord as well. And so, all of these put together, and they're often not all necessary in every patient, allow us to figure out which patients have multiple sclerosis, and therefore, should be thinking about beginning treatment. 

[Dr. Wiener] Along those lines, Dr. Josephson, much of our audience are primary care internal medicine folks. How do we decide when to involve the neurologists in these types of cases? 

[Dr. Josephson] Well, I'll tell you, it's become more and more complicated for one important reason, which is the incredibly increasing prevalence of people getting brain MRI scans. So in this case, it's very straightforward. Here's a woman with optic neuritis who's got symptoms. They probably should get an MRI scan to try to explain those other symptoms, and then should be referred to a neurologist to help make this diagnosis and think about treatment. A more common problem that our primary care colleagues encounter is that somebody gets an MRI for whatever reason, a headache, maybe a neurologic deficit. Maybe they got one because they chose to get an MRI scan commercially, and the read says something about, there's white matter lesions or T2 hyperintensities, and, quote, "can't rule out demyelinating disease." This has become more and more common, and neurologists are around to answer these questions, but an MRI alone, particularly in someone who doesn't fit that demographic or hasn't had classic attacks, really puts us in a difficult position. And many of us in neurology then see these patients, think about whether or not other testing is needed to exclude the possibility of multiple sclerosis. 

[Dr. Wiener] Those are great points. Before we close, anything else you'd like to talk about? The stages of the disease or any other final teaching points? 

[Dr. Josephson] Well, I would just say that we are very lucky in the world of multiple sclerosis in that there has been an explosion of new therapies in the last decade. Many of them focus on B-cell depletion. And these therapies are so effective that in patients who have the more common, relapsing, remitting form, if they can be treated with some of these highly effective therapies early in the disease, we have the potential to prevent, in the vast majority of patients, an accumulation of disability and more relapses. So, a disease that used to be very challenging to treat now is something where we have effective therapies if we can catch people early on in the course. 

[Dr. Handy] Thank you so much. That's great. And it was so great to have you on our episode today. For our listeners, you can find this question and other questions like it in Harrison's Self-Review, and you can learn more about this topic on the Harrison's chapter on multiple sclerosis. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's, available exclusively on AccessMedicine. If you enjoyed this episode, please leave us a review, so we can reach more listeners just like you. Thanks so much for listening. 

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