Smell loss is a much-discussed symptom of COVID, though it can be associated with other viral infections and even diseases such as Parkinson’s. Otolaryngologist Patricia A. Loftus, MD, discusses what’s known about smell loss in COVID patients as well as its general prevalence in our aging population. She presents the workup process for olfactory dysfunction, including objective tests for evaluating a patient’s sense of smell. Bonus: Learn about the treatment called olfactory training
Um, OK, so thanks for the great introduction. Yes, I'm a, um, assistant professor at UCSF in the division of Rhihnology and Skull-based Surgery in the Department of ENT, um, And I'll be talking about olfactory dysfunction with an emphasis on COVID, um, smell loss. I have no disclosures. Uh, so, quick overview, what we're going to talk about today is whyolfaction is important. We'll talk about its prevalence, um, some of the anatomy and physiology behind it, its relationship to taste. We'll go over some definitions and classifications and then talk about how, um, you evaluate it based on history, um, exam, and, and, in our clinic, we, we usually do a nasal endoscopy, so I'll show a video of that, um, objective smell testing and then question of whether imaging is, um, Uh, uh, something that you should get. Um, and then for the ideologies, we're gonna focus on COVID and then we're gonna end with some treatment options, um, specifically something called olfactory training, um, that some of you may be familiar with that I wanted to talk about a little bit more. Uh, so just to start, we're gonna, um, uh, mention why is olfaction important. So, uh, for starters, it helps us enjoy life. It helps determine, distinguish the flavors of the food we eat, with its relationship to taste, so we'll talk about a little bit more. Um, it plays a role in our memories, um, since the olfactory bulb has direct connections to the, um, amygdala and the hippocampus. Um, and, um, you know, nice scents such as flowers. and perfumes can make us feel happy. Um, it's important in terms of social interaction, going out to dinner, proper or improper hygiene, um, and even parent, um, child bond, and then also a lot of occupations, um, you know, most occupations, but some ones, uh, very important ones listed here. And also, um, safety concerns. So, you know, when I have a patient come in with, um, smell loss, I don't let leave until we discuss some of these things. I've I've definitely had patients um described having multiple bouts of food poisoning, um, because they, um, couldn't smell that the food was spoiled. Um, you know, our smell also helps us notice, notice pollute polluted air or toxins, um, helps us smell smoke from a fire or gas leak from a stove. So all these things are things that you need to talk about with the patient. Um, it can also be, um, an early sign of certain, um, diagnosis, um, most particularly Parkinson's disease, and we'll talk a little bit about this more. Um, you know, a lot of these listed will obviously have some other symptoms besides smell loss, but in Parkinson's, the smell loss can sometimes precede the diagnosis by many, many years. So, um, it's something that you, you know, would ask about in terms of the family history. Um, and brain tumors. You know, they, of course, usually will have some other symptoms associated as well, but um we'll talk about when you may consider um getting an MRI for um someone coming in with smell loss and worry and maybe worried about something like that going on. So, um, how prevalent is it? Uh, According to the National Institute on Aging, which is a division of the National Institute of Health, 15 million Americans over the age of 55 suffer from smell loss. So 25% of men in their sixth decade and then 11% of women in the same age range. And overall, 5% of the general, general properization is considered to be anosmic, um, which means complete loss of smell, and we'll go over some of these definitions. And then 15% considered hyposmic, which means decreased sense of smell. And then, um, this study of almost 2000 people ages 5 to 99, women outperformed men, um, and smell function across ages and non-smokers outperformed smokers, which makes sense. Um, this study also demonstrated that smell peaks in about the 3rd to 5th decade of life and then declines after that, um, and found that half of people aged 65 to 80, um, We were suffered from smell loss and then over three quarter of patients over 80. So, um, you know, it's also when patients come to see us, um, we wanna look for a reason, um, and we should do that, but we do also need to remember much like hearing loss, smell function can decline. With age and sometimes that is what's going on. Um, and then the question is what can we do for that, but um we'll talk about that in a bit. And then Lastly, in terms of prevalence, I just wanted to mention this study um that used objective smell testing rather than just like, um, subjectively patients saying that their smell was decreased, um, and we'll, we are gonna talk about the ways that you can test smell objectively. Um, but this, uh, the numbers were still pretty close. The prevalence was 12.4% on objective testing and, um, over 13 million adults in the United States. So it's, um, it's a pretty big number. All right. So, um, in terms of the anatomy and physiology of smell, um, we know that cranial nerve one is the olfactory nerve, and, um, one of its unique qualities as far as cranial nerves go, um, is that it is capable of some regeneration if damaged. And then the other, um, cranial nerve that should be mentioned as it relates to smell is the somatosensory portion of the trigeminal nerve. So the nasal ciliary and nasopalatine nerves bring the sensation of pain to the nasal epithelium and they respond to like chemical irritants such as ammonia. So, um, actually one way that you can test for malingering of loss if, if you need to test for that, um, is to actually have the patient sniff ammonia because um they should still have a reaction to it, um, and if they say they can't, that they don't have any type of reaction, you know, they may be, um, making that up. So, Um, some terminology when describing, um, the olfactory pathway, um, as well as when we describe kind of our our endoscopy findings when we, we look into the nose. So, um, is the difference between the olfactory cleft and the fossa. So the cleft is actually that space, um, within the nasal cavity where the neuroepithelium is. It's kind of the superior septum, um, and, um, the space like in between the, um, the middle turbinates there and the septum, the cribiform area. Um, that contains the olfactory receptor neurons. And then the olfactory fossa also called, cause the groo, called the groo or recess and I'll show a picture of this, um, is the area of the ethmoid bone in the anterior cranial fossa that contains the olfactory bulb and nerve. So the axons of the olfactory receptor neurons, um, that are within the, um, olfactory cleft go through those depressions within the portion of the ethmoid bone to then reach the olfactory bulb. So here is um a picture of that, the olfactory cleft, again, here's the superior septum, um, so that's gonna be the um the neuroepithelium in this area houses um uh olfactory receptor neurons and then here's the um the groove or the fossa or the recess where those neurons will then, um, come through to synapse at the olfactory bulb. So the neuroepithelium in the cleft, so within the nose, um, is made up of pseudostratified cells, uh, that cover again the superior septum, um, and the superior middle turbinate area. Um, And they contain about 12 million receptor neurons and to put that into perspective, rabbits have about 100 million, um, and bloodhounds actually have 4 billion, so we don't, it's, we actually don't have that much as compared to, to some of the other mammals, but still, um, many, many, um, receptor neurons here. And then, um, again, they will then travel through the cribform plate of the ethmoid bone here and you can see that, um, they synapse with the second-order neurons in the glomeruli of the olfactory bulb. Um, and then once um that um happens, they can then leave um and go to the olfactory tract and, and to the olfactory cortex. So to just run through this, uh, one more time, the odorants, um, bind to the olfactory receptor neurons in the neuroepithelium. They become activated and they send electric signals to the glomeruli in the olfactory bulb, and then after that, this relays the signals to the olfactory tract and higher, um, brain regions. And then, um, I did just mention this quickly about cranial nerve one that, um, basal cells in the neuroepithelium can regenerate every 4 to 8 weeks to form new olfactory receptor neurons, uh, and that's just something that is, um, important in terms of, you know, talking about potentially, you know, your smell coming back, um. And um if, if you lose it from a cold or something like that, um, and the problem is that this ability will decrease with um age or injury, so um that's uh something to talk about with patients who uh we decide that their smell loss is happening because of aging. And then, um, in terms of the relationship to taste, um, there are primary taste disorders. They could be related to, um, issues with salivation or potentially, um, malnutrition, but most, uh, uh, I would say taste dysfunction is related to smell dysfunction. So, um, They, the taste buds coordinate with the olfactory receptor neurons to be processed in the brain and um recognize and and distinguish certain tastes. So, um, actually about 80% of food flavor comes from olfactory input. Um, so this is why it a patient who comes in with a cold and, you know, swollen, um, intranasal, um, mucosa and mucus, they will, um, complain of loss of taste as well, but likely nothing is really going on with their actual taste buds. It's just that the odorants are not getting to the neuroepithelium, so since they can't smell, um, it's going to affect their taste. And here are the um definitions that I just want to quickly go over that um we may use when we're evaluating someone with smell loss. Um, so the first three are uh quantitative um ways to describe smell disorders. So hyposmia is a decreased ability to smell. You can still smell but it's just decreased and we will, um, We also kind of put it into a category of, um, you know, mild, moderate, or severe, um, based on objective testing that we'll talk about. And then anosmia is the absence of smell. Um, hyperromia is an increased olfactory acuity or a heightened sense of smell. Um, and causes for this, obviously we don't see this as much as we see hyposmia and anosmia, um, but there are some like environmental reasons, um, uh, or like amphetamines or, um, results of benzo withdrawal. Um, and sometimes in pregnancy for hor hormonal issues. And then the, um, these other definitions are more, um, qualitative, so dysosmia means a distorted, uh, distorted identification of smell and, um, Under this falls um perrosmia and phantasmia. So for peromias, this is when an odor is present, but the smell is distorted, so people will say like normal food that they like tastes, uh, smells like smoke or, or something like that. Um, whereas, um, phantasmia or uh olfactory hallucinations is when there's a perception of smell, when, when a smell is not around. And then these two are the difference between if the smell they're perceiving is, is good or bad. So to just talk about this, um, These qualitative smell disorders a little bit more. So perrosmias can be linked to um cancer, um, traumas, URIs, toxins, neurodegenerative disorders. Um, it's hypothesized that the, that URI's result in prosmias because of damage to the actual, um, olfactory receptor neurons and then trauma can affect the olfactory bulb because of the, the shearing factors. Um, and then the perrosmias in Parkinson's are thought to be caused by potentially a lack of dopamine. Um, however, there are some idiopathic cases, um, but usually, um, this, this tends to lessen over time with, um, even without treatment, um, although it can last for a while in some patients, and we actually do see perrosmias in, um, COVID patients, um, especially as their smell, uh, COVID patients who have lost their smell. So especially as their, their smell has, um, sort of started to return, um, we think that overall, it's a good prognostic sign that their synapses are, you know, trying to regenerate. They may just be, um, you know, go from no smell to at least like smelling something even if it smells distorted, and we'll, we'll talk about that a little bit, um, more later. So, um, olfactory hallucinations, um, they can be caused, um, by, um, common medical conditions such as polyps or dental problems like if there, um, is, uh, um, swelling or, um, mucus in the nose, patients may say that they're, um, that they're just constantly smelling like weird smells even if it's not like related to the mucus. Also, um, neurologic conditions such as migraines or head injuries, um, strokes, um, also can be a symptom of certain, um, disorders such as, uh, depression or bipolar disorder or intoxication, um. Or withdrawal from drugs and alcohol and um environmental exposures sometimes as well, such as smoking or exposure to certain types of chemicals or radiation treatment um to the head and neck. There, these are most common in um women age 15 to 30 and they can be intermittent or persistent. Uh, potential treatment options, and again this is not a very common thing, but just wanted to, um, to bring it up, but potential treatment options, um, include intranasal, um, anesthetics or decongestants. Um, but luckily, Over 50% of these patients improve spontaneously by a year, so it's similar to the Prosa is that there's a lot of spontaneous um resolution. But there, there are some, uh, patients that do not improve and this really affects their quality of life and there have been Um, there has been a procedure described where you actually go in and ablate the, um, the neuroepithelium on both sides, uh, but the problem with this is that it can result in complete smell loss, um, and potentially a CSF like so it's not something that's commonly done, but that is something that has been described to treat this if it's really bothering people. So, um, for, in terms of classification, much like hearing loss, um, smell loss can also be classified as conductive or sensorineural. So, um, conductive losses are, um, When the odorants cannot reach the olfactory epithelium because of obstruction. Um, so this is, you know, inflammation from URIs or allergies, nasal polyps, sinonasal tumors, and then on the other hand, um, sensor neuro losses result from damage to the processing center itself, um, such as the olfactory neurons or the olfactory bulb. Um, and then the, this is a list of, um, some of those that we've actually already talked about a little bit, post viral smell loss, um, trauma, aging, medications, neurodegenerative disorders, and then if the, um, loss doesn't fit into either of these, uh, it's determined to be, um, uh, idiopathic. And then, um, so the question now is, uh, what type of smell loss is COVID? And, um, let's kind of sidetrack a little bit and now focus on COVID smell loss. Um, it's, it's definitely, I think, very interesting and, and pertinent to many of our practices right now. So, um, to talk about COVID smell loss, we'll, we'll talk about post viral olfactory dysfunction in general, since, um, this was already a thing prior to COVID. Um, we know that that's, that viruses can cause smell loss. We already knew that and we knew the coronaviruses could cause smell loss. So in, um, Post viral olfactory dysfunction, PVOD, um, in general, um, hyposmias and perrosmias tend to be more common than with other, um, reasons to, to lose your smell like the other things I was talking about like head trauma and stuff like that. Um, and it's also the most common cause of smell loss in adults when, um, a cause can be identified. So, it, it occurs more commonly in women and in the middle um to older age range. Um, the mechanism is believed to be direct injury to the neuroepithelium which reduces the number of um olfactory receptor neurons, um, and then also limits their ability to regenerate. So with Post-viral, um, smell loss in general, um, not, not just focusing on COVID right now. Um, recovery usually happens within weeks to months, but we tend to see it be more months rather than weeks, um, which is, uh, something to mention in terms of COVID because COVID recovery is a little bit different. Um, And, and we'll discuss that, but a lot of these patients, um, will, will recover within um a year or so. So, um, then which is COVID? We know that people with COVID-19 smell loss do recover relatively quickly. Um, the numbers are around 75 to 80% of people will have resolution of their, um, smell within the first month, within the 1st 3 to 4 weeks, um, which suggests that Damage is to non-neuronal cells since those cells, um, can regenerate faster than neuronal cells. So if other types of post-viral smell loss we think are related to um the actual nerves being damaged, that may be why they take a little bit longer to resolve, but we're finding that COVID in general, the smell loss does come back relatively quickly with an average of about, um, 3 weeks. So, so why does this happen? Um, we know that the virus enters cells via attachment, uh, of the spike protein to ACE2 receptors and that these receptors are abundant on the supporting cells of the neuronal cells and not actually as abundant on the neuronal cells themselves. Um, and, um, another reason that points to a non-conductive type of smell loss, um, is that a lot of COVID Smell loss patients will report losing their smell without associated symptoms of like nasal congestion and nasal obstruction, which would be expected if, if the loss was conductive and is usually in non-COVID viral smell loss, people with smell loss will usually also, um, during the cold, um, will say that they also have some congestion and obstruction. So, um, that's an interesting thing about COVID. So, um, obviously, ACE2 receptors are important, um, for COVID smell loss. So some data to, um, back up their important role includes that 2, there's a 200 to 700-fold increase of their expression on the olfactory versus the respiratory epithelium. So that's why smell loss is such a common symptom of COVID-19. Um, and also the fact that, uh, their increased expression can correlate to outcomes. Um, for example, more severe infections in young obese patients who express higher levels of ACE2 in their lung epithelium. Therefore, the most likely mechanism of COVID smell loss is disruption of the olfactory neuronal supporting cells. So if the neurons are not receiving the support they need, um, such as nutrition from the supporting cells which we call sustennacular cells, then they won't function properly and, um, won't be able to regenerate. But when the sustennacular cells regenerate, um, smell should technically return. Um, So that, this is why we think maybe the smell loss happens, um, the recovery happens a little bit quicker because it's not damaged to the actual nerves themselves, which is interesting. And then another um interesting thought is obviously we do have this, um, population of patients who are not recovering their smell, so why do most people recover it, but some people do not. Um, and there's a thought that if it's the stem cells in those patients that are being affected, um, it's harder for regeneration to occur and then the smell loss, um, is like has a longer course or perhaps is even permanent. And then this is um just a slide about other um important facts, I think, um, about COVID smell loss, so. It's a very common symptom of COVID-19 infection. I think everybody um can agree on that. It's difficult to give an exact percentage of how many people it affects. The early publications kind of report the number all over the place as you can see here, but a lot of these studies were subjective questionnaires, um, sort of varied by location in terms of, um, inpatient, outpatient part of the country. Um, so they're not the most reliable, but there is a, um, systematic review. They reported an average of about 52%, um, of Uh, patients with COVID will have, um, smell loss, and I think this number makes, um, makes sense based on the people I know who have had COVID, maybe about half or so of them are like more than 50%. Um, it's also interesting that in one study, um, smell loss was more common on objective testing than with subjective reporting. So maybe the number is actually higher than 52% um if the patients are underreporting the symptom, but also if it's not clinically relevant, if it's not bothering them, then maybe it doesn't necessarily matter. Um, but that was, that was an interesting fact. And then, um, something we, we discussed earlier, um, is that a lot of the smell loss um can happen without nasal congestion. Um, and rhinorrhea, meaning that, um, in many cases, smell loss occurs during the acute infection without other cold symptoms. Um, and we discussed how that could happen, um, based on the mechanism that it affects the supporting cells of the neurons instead of being like inflammation and causing a conductive loss. And then, um, lastly, smell loss and COVID, uh, seems to be more common and mild as compared to moderate or severe infection. So one thought is that, you know, very sick people are not as aware of this symptom, um, since they have more worrisome things to think about and you can't necessarily Um, properly ask them about their smell when they're in the ICU. But there is a study to show that normasmia, meaning normal smell, was shown to be an independent predictor for, um, hospital admission with COVID-19, which supports the thought that maybe there is more, um, smell loss. Um, is smell loss is more common in mild infection. And I just think that that's like an interesting thing to know because, um, You know, younger patients may say, you know, I'll just have a mild infection like, you know, who cares, but, and it's probably true, their infection will, will be mild, but they may end up with smell loss, they may end up with a case that doesn't improve and then that is a, I mean, that's just a horrible thing to have long-term smell loss from a mild cold. So, um, this is like something that I try to use, um, when, when younger people are talking about whether, you know, to be vaccinated or not and, and that kind of thing. So then, um, looking at the data a little more closely, this is an IFAR, um, publication out of, um, our ENT department at UCSF that demonstrated that the presence of smell loss, fevers, and body aches, um, without shortness of breath or throat, or sore throat. Gave an 82% chance of discriminating between COVID and non-COVID illness. So, um, basically what, what this sort of means is that smell loss, the symptom of smell loss is a little bit more important in making a COVID diagnosis than it may be with other types of viral illnesses. And then similarly, in this study, you can see that um loss of taste and loss of smell and body aches were much more common in COVID versus non-COVID illness and sore throat was more common in non-COVID illness. Um, and it also here, um, Again, demonstrated that in non-COVID illness, nasal obstruction is more common than smell loss, but the opposite is true in um COVID illness. So just kind of interesting facts that um in, in the way that COVID smell loss um can sort of be differentiated from other types of um viral illness and um The symptoms that, that you have from other types of viral illness. And then in terms of severity um of the smell loss in COVID, about 25% of people admitted to the hospital um in this study had complete loss of smell on objective testing, um, but the most common was, um, the most common severity was severe microsmia or hyposmia, so severe, um, decreased smell, not complete loss of smell. Um, so the other thought about this is that, um, maybe the severity of smell loss in COVID-19 is what makes it such a prominent symptom. You know, most of the patients had either complete loss of smell or severe loss of smell rather than more of like a mild loss. So, um, potentially that's why it has become a prominent symptom. Maybe other viral illnesses cause less of a severe loss. And then here's a, uh, a different study kind of showing the same thing. Um, severe microsmia slash hyposmia was again the most common, um, severity of loss, but you can see everything improved relatively quickly, um, like we discussed, and, um, we'll talk more about recovery in a few slides. So then, um, We talked a little bit about taste and its relationship to um smell, but in COVID, how is, um, how does taste sort of fall into all of this. And we know that many COVID uh smell loss patients will also report taste loss, but some won't, and, uh, some actually will report taste loss even without smell loss. So we're still sort of trying to figure out, um, what's going on in this area, but Due to the functional correlation between these two senses that we discussed, it does make sense that taste loss could simply be present due to smell loss. Um, and we do see that these two things sort of resolve and recover together. Um, Some people actually suggest that COVID, um, smell loss patients might confuse taste lost with flavor loss, uh, due to the impaired, um, retro retronasal olfaction. So maybe the, the, the true prevalence of taste loss is actually overreported and they're more, they're more just talking about a flavor loss. Um, but still there is, um, some published case theories about taste dysfunction in COVID, um, and taste, and sometimes taste disturbance can be more common than, um, olfactory disturbances and sometimes can be present alone and, in 10 to 20% of the time. So, um, we also know that there's ACE receptors prevalent in the oral cavity, especially on the tongue. Um, so there might be something more to They're actually being damaged to, um, you know, the salivary glands as well and it not just being completely related to smell, but we do think that a lot of the COVID taste loss is related, um, to COVID smell loss. Um. But the, the mechanism by which the ACE2 inhibitors can cause taste disturbance um is unclear, um, which is a little bit different than how we uh we're able to sort of explain how they can cause smell loss, um, but, uh, um, they don't think that it's related to any alteration in, um, zinc uh like serum or salivary zinc levels. Um, and one thought is that the virus could occupy the binding sites of the, um, sylic acid on the taste buds which accelerates the degradation of gustatory particles, but again, um, more research needs to be done in this area. So then recovery I touched on a little bit already. Um, obviously, our patients are extremely interested in this, um, uh, information. So, We do have pretty good data by now to show that um the number falls around 75 to 80% of people recovering their smell in about a month, which with the mean recovery being around um 3 weeks, and then longer term, um, about 95% of people will recover their smell by 6 months. And um, You know, that seems pretty good and it is, but with the amount of COVID patient, uh, cases and the amount of patients who suffer from COVID smell loss, um, it still leaves a large percentage of patients out there, um, who continue to have smell loss after 6 months, after a year. Um. And, um, including having continued perrosmias. But uh like we mentioned, we do think perrosmias are a good prognostic factor because it means there is some underlying neural function still there, um, and the nerves are actively trying to regenerate, uh, but this can obviously be very distressing for patients to, um, not have their smell fully back and just be smelling like weird smells all the time and not really knowing like what the natural history of this is going to be. And um in, in one study, 11% of patients with COVID smell loss reported perrosmias and over 50% of those cases lasted over 3 months. Um, so again, that can be very distressing to patients. And, um, you know, in terms of recovery, you can also discuss with your patients how a Um, baseline severity, uh, the baseline severity of loss, um, is, uh, can be a prognostic factor, meaning that obviously the worst the smell loss, um, when it happens, you know, the worse the prognosis and obviously that's hard to tell. Um, we usually can need to do some objective testing to tell them just how severe it is. Um, but, uh, from What, uh, you know, from. Uh, talking to patients, you can kind of get a sense of like just how bad their smell loss is and um, Let them, can let them know that, you know, the worse it is, then that might be a bad prognostic factor, but not always. Um, but that, this is true of any type of smell loss after a viral illness. Um, and then from the data that we, um, currently have, there does not seem to be, um, a difference between, uh, recovery between genders, um, aside from one study that did show later recovery in women. Um, and, uh, younger patients, uh, under 40, um, do have a higher chance of recovery, so those are some good prognostic factors. And then, um, In terms of the workup, if the timing makes sense with a COVID infection, we, we really don't need to do further, um, workup for that, like, you know, get any imaging or I, I will still scope these patients just to see if they have some like lasting inflammation or, or something going on that could potentially Um, be, um, improved, but, um, you know, you don't really have to like delve into other, other reasons this might be going on if the, if the COVID infection makes sense. But if there's something that doesn't add up like, um, other red flag symptoms, um, headache, facial numbness, epistaxis, um, you know, that could be concerning that, um, that something else is going on. And then the, these are the objective um measurements that I was talking about, um, that, uh, they're important because they can kind of guide the discussion about prognosis like I, I just mentioned that based on Um, the severity, you know, how, how good is their prognosis, and it's also nice to be able to monitor their progress, uh, especially if you've tried some type of treatment, so have them come back after trying and see if there's been any improvement on, um, these, these tests. And, um, I will, the, the two main ones are the upset, the University of Pennsylvania smell identification test and then sniffing sticks, um, that are shown here, and I'm gonna, I'm gonna talk about both of them in a little bit, um, more detail in a second. Um, However, if, uh, if there's no history of COVID, so we're kinda going back to, um, uh, presentation of smell loss in general, um, the workup can be much more extensive to try to figure out what's going on. Um, so it's very important to, uh, discuss the onset and the duration of the smell loss and really press the patient on any events that could have occurred around. Um, the time of smell loss, uh, especially because it may take patients a while to sort of realize that their smell is gone or they realize that there's, that something is going on with their smell, and they may not, um, remember that they had a bad cold around that time. Um, you know, uh, they don't tend to forget if it was happened, uh, because of a head trauma or if it happened because of a certain medication. But, um, sometimes like a URI history really needs to be pulled out of them and it is one of the um most common reasons, so it is something that you wanna try, um, to pick up just to have a reason for what's going on. Um, should also um elicit any type of um sinonasal history. Um, that could mean that the smell loss is just from, you know, some nasal inflammation or maybe a tumor or polyps. Um, thyroid disease or diabetes, um, should be discussed, um, and, uh, as those can sometimes, um, endocrine disorders can sometimes be the cause. Um, also, uh, neurologic disease, um, especially like we mentioned before, Parkinson's. Um, and that, that should be like a personal or family history cause it may be, you know, if, if there's a family history of something that's genetic, you may, you know if the patient's not diagnosed with it, it may be something that you wanna think about. So you can really, you know, get into a lot of questions and it can obviously be hard to know whether this is actually what is causing the smell loss or not, but Um, but it's good to just kind of hit on all these things and, and sort of get a sense of what could actually be going on, um, autoimmune disorders, potential, um, exposure to, to certain, um, pesticides or metals, and then, um, psychiatric disorders have been linked to smell dysfunction, particularly the, uh, um, olfactory hallucinations which we discussed a little bit before. Also, a, um, history of chemo or radiation can affect, uh, salivary function and have caused, um, can cause atrophy or scarring in the nose, um, bad reflux can cause an unpleasant smell for the patient. Um, also intranasal drug use is something that you should talk about. Uh, intranasal zinc actually has been shown to cause smell loss. It's been off the market, um, I think for like over 10 years now, so unlikely to be the cause, but I have had, um, You know, patients say that they've haven't had smell for over a decade and then got out of them that they had used intranasal zinc in the past. Um, and then we should ask about any prior, you know, surgeries here that, um, could have, could have damaged the olfactory area. So, uh, like I mentioned, smell testing, um, can be performed to both, um, document and quantify, um, document that the smell loss is present and quantify how severe it is. So, uh, the University of Pennsylvania smell identification test, it's a 40 questions scratch and sniff test, um, that is scored on gender and age norms. Um, and You know, it, they, technically the smells they used are cross-cultural and they do have this in different languages, but that, that can be a little bit of a downside to this that um not everyone is familiar with all the smells, um, or, you know, we may not have it in a, in Um, a certain language, but, um, it's a validated test, um, that does, um, you know, work very well. So, um, for instance, this, uh, graph is the, of the female age norms. So anosmia is considered 18 or lower out of 40, and then malingering would be 5 or lower, um, cause just guessing, you should get, um, more than that, and then, um, Normal, mild, moderate to mild, moderate to severe um smell loss, uh, are, are different numbers based on, on the age norms. Uh, and then, uh, like I mentioned, it's also good to do this because beside, besides documenting the loss, um, it's also useful to monitor for improvement in smell. Um, And you can, if the, if the smell loss is not too horrible, you may say, oh, that's a good prognostic factor that hopefully, um, your smell will continue to, to return. And then sniffing sticks, um, in our clinic, we have the opposite. It's, it's definitely a lot easier um to do. Sniffing sticks are nice because they test some other, um, parts of olfaction like threshold discrimination and identification, and these tend to be the, the test that's used more in, um, Um, like research setting because it um has these different um things that it can look at. Um, so they're, uh, basically just these pens that you open and smell. Um, but, uh, the threshold Uh, is tested by using and butanol and also pens with no smell and evaluating when the patient can detect the odor. And then odor discrimination, uh, you present three pens, two with the same odor, and the other is the, um, clue pen, and you, uh, try to have the patient sort of discriminate between, uh, those odors. And then lastly is the identification, um, that you have, um, Uh, the patients smell the specific odorant and then have them choose between four answers, sort of like a forced multiple choice, similar to the opposite. And then for um the physical examination, um, complete head and neck exam, looking for any lumps or bumps or signs of underlying malignancy that could affect smell. This includes a full cranial nerve and neurologic exam. Um, you wanna look in the, uh, mouth and perform an intern oral exam to look for, um, Dental disease or, um, you know, tonsil stones that may be causing halitosis and affecting the patient's perceived sense of smell. Uh, vitamin deficiencies may cause papillary hypertrophy or flattening of the tongue, but obviously, overall vitamin deficiencies are, are not that common, um, with, with the diet, um, that we eat here. Um, unless you see that there's obvious malnutrition in these patients. And then, um, anterior rhinoscopy should be performed, um, uh, before, um, Without any decongestion, um, just to see if there is, um, any intranasal inflammation and then in our office, we will Um, then decongest these patients and um look in their nose, um, look for signs of reflux but also specifically look along the olfactory, um, cleft region and this is, um, a video here of that. So I am, um, in the left nasal cavity. So this is gonna be the septum here in the middle turbinate. And basically, I'm looking high up on the septum. This is where the middle turbinate is attaching up to the skull base, and this again is the septum here. So I'm looking into this cleft space that I showed on the uh imaging before and I'm looking all around here and this area obviously looks normal. Um, so that would be, so yeah, again, left nasal cavity, septum, inferior turbinate, middle turbinate, and I was just looking up towards the uh superior septum. And I've said I don't see any polyps or really inflammation or anything here to explain um the smell loss, but this is a, is it, uh, we will examine um uh intranasally um with endoscopy when these patients come to our clinic. And then actually this I wanted to show because it was a positive finding. Um, still the left nasal cavity, so the, um, the septum here, the inferior turbinate here, and the middle turbinate here. Um, and this patient does have some, um, polyps in the, uh, in the middle meatus here. This is the, this is the drain, the drainage area of the maxillary and ethmoid sinuses. But then when you look up, this is the space that I was looking at before that was clear. But when I look up here now, I see a I see that, uh, let me show that again. I see this, um, kind of lesion here. So that was, um, you know, a positive finding on, uh, endoscopy. Um, so then lab workup, um, It's kind of based on history, um, such as, you know, a history of toxin exposure. Um, so that's kind of just as needed. I usually don't pick much up on that, but, um, imaging is something that I wanted to talk about. Um, you don't always need it, but, um, If you are suspecting this could be related to um sinonasal disorders like chronic sinus disease or something like that, a um a CT is better, and then for MRI this is when the exam is normal, maybe there's no sinonasal symptoms and um you can't um You know, really explain, uh, what's going on. So you're sort of looking for intracranial pathology like around the, um, olfactory, uh, cleft and, um, uh, fossa region where the olfactory bulb will be. So here is the, um, This is the CT scan of the prior patient that I just showed, and you see that there um is a finding here. This is the crystogali, so obviously this is where I was showing you where the olfactory cleft and the olfactory fossa are. Um, there's obviously a lesion here. Um, so this is, this is a time where, you know, imaging was indicated and, and picked something up. Uh, and then, um, You know, the For idiopathic loss, um, the question is, um, when do you, uh, decide to do some type of, um, Imaging for that, and I think for me there's obviously no good like algorithm for this, but um, If the, if the, there's, if the patient's relatively young, it really can't be explained by anything, um, even aging, um, and I've really delved into it and I have a normal exam and then we just really can't find the cause. Um, I may have them get an MRI just to make sure that I am not missing something, um, but I don't have really uh A great um answer for that, uh, cause there's really no guidelines about it, so something that you, we can look at is, um, the utility in terms of I guess like cost effectiveness, um, for MRI's with idiopath idiopathic smell loss. So, um, here, this study, um, evaluated the cost for correct diagnosis of idiopathic, um, olfactory loss. Um, And so it basically included um a group of patients who underwent MRI as part of the workup and a group of patients who did not undergo MRI as part of the workup for their idiopathic olfactory loss. And um the mean cost for my MRI workup was $2400 as compared to $86 for the group that did not have imaging, which makes sense. Um, and they found that both were very effective, quote unquote, effective, so The incremental cost-effectiveness ratio for MRI versus no imaging was over $100,000 which is higher than most acceptable willingness to pay thresholds, and the conclusion here was that, um, it, it's of course, more cost-effective to not routinely obtain MRI's for idiopathic olfactory loss. Uh, so we can understand that getting it, getting an MRI is more expensive, but does it improve patient outcome so that the cost is worth it. And, um, this study included about 104 840 patients um with idiopathic olfactory loss and 247 or 29% of them, um, were, um, 29% of those, uh, this is all olfactory loss, sorry, and 29% of those had idiopathic. And then MRI was obtained in 55% of these patients um with the idiopathic loss. Um, within these, they found abnormalities in 4.6%, but only 0.8% of these um were an abnormal finding that could potentially explain. Um, the reasons for the smell loss. So the estimated cost for, for attributable, um, abnormal finding was, um, over $300,000. Um, so the authors concluded that the rate of abnormal findings was actually similar um to that seen in the normal population. So based on this data, um, the use of routine MRI in patients presenting with idiopathic, um, olfactory loss without other concerning symptoms, of course, um, may be unwarranted. So again, maybe you can get it if it's a young patient, if there's other concerning symptoms, um, but I don't have like a great answer for that, but it's definitely, um, I will say that all the MRI's that I have gotten for smell loss, I have yet to pick up something important like, like this. OK, so, um, we already talked a bit about the most common reason for smell loss in adults, which is the post viral. Um, so just quickly, I'll mention a few other types, um, head trauma. Um, so the lower the presenting GCS, um, the higher the percentage of patients who will experience olfactory loss, which Um, makes sense and the, the more severe the loss, the less likely it is to improve like we discussed. Um, although improvement can, um, happen even sometimes, uh, a few years after the trauma, although it's, um, it's pretty rare for that to happen, and the mechanism here is the shearing of the axons, but also, um, edema of the neuroepithelium, um, and, um, like a fracture through the, the cribriform area or brain contusion or hemorrhage. And then in terms of um aging, about the number of fibers in the olfactory bulb as well as the um olfactory receptors uh will decrease with age and the bulb losses may be secondary to sensory cell loss in the olfactory mucosa along with a general um deterioration in the central nervous system, cognitive processing functions that happens with aging, aging. Um, and even in the absence of disease, olfactory receptor neurons do undergo apoptosis at a baseline, um, rate in each person, but the regenerative process of this, um, apoptosis that is happening is going to decrease with age, which is another reason that, um, that patients will start to experience smell loss as they age. Um, an increase in receptor cell death also may occur with aging, and, um, This just results in a reduction in the surface area of the olfactory epithelium along with reduced numbers of the receptor neurons in general. Um, and then lastly, um, in some cases, this, the olfactory, um, uh, function can decline, um, due to age-related, um, bone growth resulting in pinching off of the olfactory neurons as they, uh, transverse the ethmoid bones. There are a lot of reasons for, uh, smell loss to happen with aging. And then, um, for neurogenerative diseases, specifically Parkinson's disease, um, this slide is actually taken from the Michael J. Fox Foundation. Um, but it, uh, it shows how smell loss can precede a Parkinson's diagnosis by up to 10 years, and that 96% of newly diagnosed Parkinson's patients have smell loss. And then, um, You know, some odors that Parkinson's patients have difficulty recognizing are listed here, banana, licorice, pineapple, um, and, um, pickles, and a possible theory or reason for early olfactory loss in Parkinson's, um, is also talked about a little bit on, uh, this website, but, uh, potentially a misfolded alpha synucleon protein. Which is the major constituent of Lewy bodies, um, and the, the protein clumps that are the pathological ha hallmark of Parkinson's disease, they can first take up position, um, in the olfactory bulb, and then after this, the, the protein may go to the substantia nigra in the region of the brain, um, that's the region of the, the brain that when affected results in a, a dopamine deficit. So, um, you know, with, without other signs of Parkinson's, you don't necessarily like prophylactically treat, but it's just if, if a patient has, you know, this, uh, family history or something like that, I may just say, you know, it's a thought, maybe, you know, sort of be on the lookout as um time goes on that, uh, um, if you start to notice any other, you know, um, abnormal symptoms. And then for um conductive um disorders, we look for things like polyps, inflammation, infection, um, but also for sinonasal disorders, there can potentially be a sensor neural part of it too, like if the neuroepithelium has been damaged, um, but this usually sinonasal disorders are traditionally, um, conductive. And then, uh, what I, I put some of these under the, uh, the category of other, um, although they, they do affect the neurosensory, sensory pathway rather than being, uh, conductive. So the first, uh, the, uh, there's some congenital causes like common syndrome. Um, where there is, um, congenital absence of the olfactory bulbs. Um, and then congenital anosmia is a condition in which people are born with a lifelong inability to smell, and, um, it's usually sporadic, but there are some familial cases. Um, and these patients actually present, usually present a little bit later in life because it takes some time for them to realize that they can't smell, they've never been able to smell before. And then there's this um condition term familianosmia that's associated with smell loss, baldness, and vascular headaches. These are not super common but just, um, you know, something that could be on the differential. And medications as well. Obviously, this is a very like huge list of um medications and I think it's really hard to know what to do with all this information. So, um, you know, should we discontinue a medication, um, that's helping treat a comorbid condition, uh, if we're not sure whether it's causing the smell loss or not. Um, and we might not even know if it's gonna help improve the smell loss if you come off the medication. So I think that if the timing works out, the medication was started around the time the smell loss occurred and you, you know, you can use a different medication. Um, you can think about, um, changing it, but, uh, this tends to, tends to obviously be a difficult thing to, um, you know, take patients off medications when you're not sure that that's really what's going on because there's a lot of medications that potentially list this as some, as smell loss as something that can happen. Um, And then, um, I, I spoke about this a little bit about preventative measures that we do need to talk to our patients about to check and recheck, um, that their smoking, their, uh, alarms are working, their gas stove is turned off, that they label perishable foods, um, just to make sure that they do not get sick from Um, food that has gone bad, and then, um, some favorable, uh, prognosis, uh, factors listed here. Again, the biggest one is the degree of initial smell loss, um, and then, um, also important are a shorter duration of smell loss, female gender, younger age, non-smoker, prosmia, and absence of a left or right side, um, preference in the smell function. And then, um, just quick, the last thing I want to talk about a little bit was um treatment. Um, so then, then we'll have some time, um, for any questions. Uh, so there is a surgical treatment can be offered for some of these conductive losses like polyps and, uh, Um, tumors, um, uh, and anything to kind of treat, um, the mucosal inflammation. So inferior turbinate surgery may improve olfaction by improving nasal airflow and the ability of, um, odorants to enter the nasal cavity. Um, and same thing with septoplasty, of course, we can't guarantee our patients that straightening their septum will, um, improve their ability to smell, but, um, There are some studies that demonstrate um patients uh improving their sense of smell after a septoplasty anywhere from 10 to 70%. Um, but again, it's not, it's not something that we would ever um tell our patients is a, is a guarantee from the surgery. Um, and then the last, uh, thing that I mentioned here in italics is that, um, There, um, if patients are having smell loss due to uh inflammation from allergens or something like that, you can, you can treat with saline and topical intercortical, uh, topical, um, uh, corticosteroids and, you know, antihistamines and decongestants and that kind of thing. But, um, now we're gonna focus on, um, what to potentially do for patients who have like these um Uh, sensor neural reasons for smell loss that their exam is normal. Um, so you, you may or may not be, um, uh, familiar with something called olfactory training. Um, this is where different like flavors of scents, um, are used to Try and stimulate the natural regenerative capacity of the olfactory epithelium and the um central processing center, although the true um mechanism of action is not fully known. So essentially, um, each of the four, we usually start with 4 essential oils from different, um, smell types, so flowery, fruity, spicy, are sniffed for 15 seconds twice a day. Um, some people also think that maybe if you think about the smell or think about a memory regarding the smell while you're doing it, that could potentially, um, uh, help with the processing of it. So this is done for 12 weeks and then we can repeat the objective testing, the upset, um, to see if there's been any improvement and then following this, um, there's some recent thought that switching up the scents to 4 new ones and then going for another 12 weeks can be helpful. And what's the data behind this? So actually, this is not new with COVID. We are definitely recommending this for COVID smell loss, but um this has, is something that's been around for um a bit. So, um, publishing as far back as 2009. Uh, so this study demonstrated, this is one of the first studies about, um, olfactory training that, uh, demonstrated a significant improvement in the TDI or the Threshold Discrimination and Identification Score. Um, in the olfactory training group versus the control group with a mean TDI improvement in, um, of 10.3, um, which is, um, Uh, meaningful, and I was going to talk about, um, steroids that, um, there's conflicting data about oral steroids and, um, also, uh, so we don't really recommend those for, um, treatment for smell dysfunction and then, um, topical sprays have shown no benefit but topical rinses with budesonide have um potentially shown improvement because they may get up to the olfactory cleft better. Um, and then, um, some, there is some data about acupuncture, but obviously not great data behind that. So my, um, conclusions were that olfactory dysfunction is common. Um, it's the, uh, the postviral is the most common type aside from sinonasal disease, but many times, uh, Uh, cause cannot be found. We recommend, um, olfactory training that I discussed and steroid rinses, and you need to discuss safety issues with your patients. And then for COVID smell loss, um, it's a little bit different than, um, a PVOD in terms of there's a higher prevalence of smell loss in this type of viral infection. There's a faster recovery rate and it can occur without other nasal symptoms. Uh, the recovery rate here is about 95% at 6 months. We're gonna have further data about that. And for this, again, I give, I offer olfactory training and steroid rinses, um, and then repeat the smell, um, testing after that.
