Gil Y Melmed, MD, on Neurologic Complication in IBD

Dr Melmed discusses neurological complications that may arise among patients being treated for inflammatory bowel disease--and what clinicians should watch for to prevent or mitigate them.

Gil Y Melmed, MD, is director of Inflammatory Bowel Disease Clinical Research and codirector of the Clinical Inflammatory Bowel Disease program at Cedars-Sinai Medical Center in Los Angeles, California.

TRANSCRIPT

Hi. I'm Dr Gil Melmed from Cedars Sinai in Los Angeles, and it's been a terrific Advances in IBD. I had the opportunity to speak about neurological complications in inflammatory bowel disease, which is a topic that we don't spend enough time really talking about or thinking about that our patients certainly can experience and present to us with neurological complications. And the question really laid out by the topic of the talk is when we see neurologic complications in patients with inflammatory bowel disease, is it the IBD? Is it the medication? Or perhaps it's a consequence of chronic inflammation.

For example, when we think about neurologic complications that may arise from the IBD itself, there are actually some variants of Crohn's disease that have been described with respect to associations with cranial nerve facial nerve palsy called Melkersson Rosenthal syndrome, which is maybe a topic on board exams, but also, patients have but there have been case reports about patients with Melkersson Rosenthal syndrome that perhaps is a genetically driven autosomal dominant condition associated with Crohn's disease and perhaps some other autoimmune or immune mediated conditions. It may need to be treated a little bit differently, perhaps with higher dose steroids to keep the cranial nerve palsy is under control. Also, it's been associated with plicated tongue, glossitis, and other such manifestations.

Perhaps a more common IBD-associated neurologic complication is an incidental finding of white matter changes on an imaging of the brain. These white matter changes have been described over decades. Nobody really knows what are they about, and that association perhaps with what white matter changes that may be seen in patients with multiple sclerosis and or in patients with Crohn's disease. What is that association? And what is that perhaps combined genetic influence that may predispose to having both, because we have seen an increased incidence of MS in people with IBD and an increased incidence of IBD in people with MS, suggesting some underlying shared pathophysiology.

When it comes to thinking about complications associated with medications, those of us that have been practicing for more than 10 years or so may be familiar with PML and the PML issue that really was driven to the fore of us as gastroenterologists with the introduction of natalizumab. because it was associated and has been associated with PML, progressive multifocal leukoencephalopathy, which is a condition of demyelination in white matter in the brain associated with JC virus and perhaps that immune surveillance that's so important to keep viruses under control was somehow particularly triggered by this medication. PML has also been described with other medications, not just natalizumab, but is seen more so in that particular medication, but we do need to be aware where if our patients present with blurry vision, ataxia, stumbling gait, we need to be thinking about what could be going on here and pay attention to the medications our patients are on because they may be immunosuppressive in a way that may be associating with, that immune surveillance drop in the CNS, the central nervous system that may be underlying perhaps some very, very serious neurological condition. And finally, complications associated with chronic inflammation. A patient perhaps presenting with a stroke might be somebody who is at risk for developing thrombin, for developing blood clots associated with inflammation. And this has been certainly well described that our patients with IBD are at increased risk for venous and arterial thromboembolic events, but the presentation of such may actually be with the neurologic condition such as a stroke.

There are also other complications that have been associated with chronic inflammation and particularly related to nutritional deficiencies that they themselves also present with neurologic complications. For example, vitamin B12 deficiency, certainly well described to, in anybody with Crohn's but certainly those with ileal disease, ileal recession, and if vitamin B12 is not checked and not repleted, a significant B12 deficiency can associate with neurologic complications, including memory loss, brain fog, and associated with ataxia and other such neurological conditions. So we need to be mindful as gastroenterologists that there are neurological issues that our patients may present with. They may be associated with the disease. They may be associated with the medications, or they may be simply associated with having chronic underlying inflammation.

And it behooves us to recognize when there is a neurological issue going on with our patient to try to clarify further because some of these can be progressive and even fatal. Involving a neurologist early to help us think through some of these issues, because we are not experts in this condition, but we may be the first line, to whom our patients present so that we need to be aware of what these conditions are so we can appropriately get that patient on the right treatment path. Thank you very much for your attention.

Hi. I'm Dr Gil Melmed from Cedars Sinai in Los Angeles, and it's been a terrific Advances in IBD. I had the opportunity to speak about neurological complications in inflammatory bowel disease, which is a topic that we don't spend enough time really talking about or thinking about that our patients certainly can experience and present to us with neurological complications. And the question really laid out by the topic of the talk is when we see neurologic complications in patients with inflammatory bowel disease, is it the IBD? Is it the medication? Or perhaps it's a consequence of chronic inflammation.

For example, when we think about neurologic complications that may arise from the IBD itself, there are actually some variants of Crohn's disease that have been described with respect to associations with cranial nerve facial nerve palsy called Melkersson Rosenthal syndrome, which is maybe a topic on board exams, but also, patients have but there have been case reports about patients with Melkersson Rosenthal syndrome that perhaps is a genetically driven autosomal dominant condition associated with Crohn's disease and perhaps some other autoimmune or immune mediated conditions. It may need to be treated a little bit differently, perhaps with higher dose steroids to keep the cranial nerve palsy is under control. Also, it's been associated with plicated tongue, glossitis, and other such manifestations.

Perhaps a more common IBD-associated neurologic complication is an incidental finding of white matter changes on an imaging of the brain. These white matter changes have been described over decades. Nobody really knows what are they about, and that association perhaps with what white matter changes that may be seen in patients with multiple sclerosis and or in patients with Crohn's disease. What is that association? And what is that perhaps combined genetic influence that may predispose to having both, because we have seen an increased incidence of MS in people with IBD and an increased incidence of IBD in people with MS, suggesting some underlying shared pathophysiology.

When it comes to thinking about complications associated with medications, those of us that have been practicing for more than 10 years or so may be familiar with PML and the PML issue that really was driven to the fore of us as gastroenterologists with the introduction of natalizumab. because it was associated and has been associated with PML, progressive multifocal leukoencephalopathy, which is a condition of demyelination in white matter in the brain associated with JC virus and perhaps that immune surveillance that's so important to keep viruses under control was somehow particularly triggered by this medication. PML has also been described with other medications, not just natalizumab, but is seen more so in that particular medication, but we do need to be aware where if our patients present with blurry vision, ataxia, stumbling gait, we need to be thinking about what could be going on here and pay attention to the medications our patients are on because they may be immunosuppressive in a way that may be associating with, that immune surveillance drop in the CNS, the central nervous system that may be underlying perhaps some very, very serious neurological condition. And finally, complications associated with chronic inflammation. A patient perhaps presenting with a stroke might be somebody who is at risk for developing thrombin, for developing blood clots associated with inflammation. And this has been certainly well described that our patients with IBD are at increased risk for venous and arterial thromboembolic events, but the presentation of such may actually be with the neurologic condition such as a stroke.

There are also other complications that have been associated with chronic inflammation and particularly related to nutritional deficiencies that they themselves also present with neurologic complications. For example, vitamin B12 deficiency, certainly well described to, in anybody with Crohn's but certainly those with ileal disease, ileal recession, and if vitamin B12 is not checked and not repleted, a significant B12 deficiency can associate with neurologic complications, including memory loss, brain fog, and associated with ataxia and other such neurological conditions. So we need to be mindful as gastroenterologists that there are neurological issues that our patients may present with. They may be associated with the disease. They may be associated with the medications, or they may be simply associated with having chronic underlying inflammation.

And it behooves us to recognize when there is a neurological issue going on with our patient to try to clarify further because some of these can be progressive and even fatal. Involving a neurologist early to help us think through some of these issues, because we are not experts in this condition, but we may be the first line, to whom our patients present so that we need to be aware of what these conditions are so we can appropriately get that patient on the right treatment path. Thank you very much for your attention.