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 Okay so thanks for the great introduction. Yes I'm a assistant professor at UCSF in the division of rhinology and skull base surgery in the department of E. N. T. Um And I'll be talking about olfactory dysfunction with a emphasis on covid smell loss. I have no disclosures. Uh So quick overview what we're going to talk about today is while factions 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 you evaluate it based on history um exam And in our clinic we usually do a nasal endoscopy. So I'll show a video of that um objective smell testing and then the question of whether imaging is um 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. So just to start we're gonna mention wise olfaction important. So for starters it helps us enjoy life. It helps determine distinguish the flavors of the food we eat it with its relationship to taste. It will talk about a little bit more um it plays a role in our memories. Um Since the olfactory bulb has direct connections to the amygdala and hippocampus. Um And uh you know nice sense 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 child bond and then also a lot of occupations um You know, most occupations with some 1's 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 them leave until we discussed some of these things, I've definitely had patients describe having multiple bouts of food poisoning because they couldn't smell that the food was spoiled. Um You know, our smell also helps us notice notice polluted polluted air toxins helps to 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 diagnoses, 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 would ask about in terms of 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 getting an M. R. I. For um someone coming in with smell lost and worried and maybe worried about something like that going on. So um how prevalent is it 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 six decade and then 11% of women in the same age range. And overall 5% of the general general crop fertilization is considered to be an orgasmic um which means complete loss of smell. And we'll go over some of these definitions and then 15 considered hypothermic, which means decreased sense of Smell. And then um this study of almost 2000 people ages 5-99 women outperformed men um and smell function across ages and nonsmokers performed smokers which makes sense. Um This study also demonstrated that smell peaks and about the third to fifth decade of life and then declines after that Um and found that half of people aged 65-80. Um We're suffered from smell loss and then over three quarters of patients over 80. So um you know it's also when patients come to see us um We want to 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 that 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 well we are going to talk about the ways that you can test smell objectively. Um but this the numbers were still pretty close. The prevalence was 12.4% on objective testing and over 13 million adults in the United States. So it's um it's a pretty big number alright so um in terms of the anatomy and physiology of smell um we know that cranial nerve, one Z. 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 cranial nerve that should be mentioned as it relates to smell is the somatic sensory portion of the trigeminal nerve. So the nasal Salieri and nasal palatine 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 smell 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 neuro epithelium is, it's kind of the superior septum. Um And um the space like in between the the middle turbine, it's there in the septum the crib reform area um that contains the olfactory receptor neurons. And then the olfactory fossil also called because the group called the grouper recess. And I'll show a picture of this um is the area of the ETh Boyd 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 olfactory cleft go through those depressions within the portion of the f droid 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 going to be the um the neuropathy liam in this area houses um uh Inspector receptor neurons and then here's the the groove or the fossil or the recess where those neurons will then come through to synapse at the olfactory bulb. So the neural epithelium in the cleft. So within the nose um is made up of pseudo stratified cells. The cover again the superior septum in the superior middle turbinate area um And they contain about 12 million receptor neurons and put that into perspective, rabbits have about 100 million. Um and bloodhounds actually have four 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 many, many um receptor neurons here and then um again they will then travel through the crib form plate of the bone here and you can see that um they synapse with the second order neurons and the glamorous ally of the olfactory bulb. Um And then once um that happens they can then leave and go to the olfactory tract and and to the olfactory cortex. So to just run through this one more time the odorant bind to the olfactory receptor neurons and the neural epithelium, they become activated and they send electric signals to the glamorous lie in the olfactory bulb. And then after that this relays the signals to the olfactory tract and higher brain regions. And then um I did just mention this quickly about cranial nerve, one that um Basil sales in the neural epithelium can regenerate every 4-8 weeks to form new olfactory receptor neurons uh and that's just something that is important in terms of you know, talking about potentially you know, your smell coming back um And um if you lose it from a cold or something like that um And the problem is that this ability will decrease with age or injury. So um that's uh something to talk about with patients who 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 malnutrition but most I would say taste dysfunction is related to smell dysfunction. So um The the taste buds coordinate with the olfactory receptor neurons to be processed in the brain and recognize and distinguish certain tastes. So um actually about 80% of food flavor comes from olfactory input. Um So this is why a patient who comes in with a cold and you know swollen um inter nasal 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 odorant are not getting to the neural epithelium. So since they can't smell um it's going to affect their taste. And here are the definitions that I just want to quickly go over that we may use when we're evaluating some someone with smell loss. Um So the first three are quantitative um ways to describe smell disorders. So hypothermia 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 based on objective testing that we'll talk about. And then anatomy is the absence of smell um hyper as me as 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 hypoglycemia and and as mia. Um But there are some like environmental reasons um or like amphetamines or result of benzo withdrawal. Um And sometimes in pregnancy hormonal issues. And then the these other definitions are more qualitative. So dysosmia means a distorted distorted identification of smell. And um under this falls um Perata's mian fantasma to so for Perot's mia's this is when an odor is present but the smell is distorted. So people will say like normal food that they like tastes smells like smoke or or something like that. Um Whereas um fantasma or 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 of their perceiving is is good or bad. So to just talk about this um these qualitative smell disorders a little bit more. So para Bosnia's can be linked to cancer. Um traumas Ur eyes toxins neurodegenerative disorders. Um It's hypothesized that the that U. R. I. S result in prod me is because of damage to the actual um olfactory receptor neurons and then trauma can affect the olfactory bulb because of the sharing factors. Um And then the process MIA's in Parkinson's are thought to be caused by potentially a lack of dopamine. However there are some idiopathic cases um but usually um this this tends to lessen over time with even without treatment. Um Although it can last for a while in some patients. And we actually do see para as mia's in um covid patients 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 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 their 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 disorders such as depression or bipolar disorder or intoxication 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 to the head and neck. There these are most common in women age 15-30 and they can be intermittent or persistent 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 inter nasal um anesthetics or decongestants. Um But luckily over 50% of these patients improve spontaneously by a year. So it's similar to the problem is that there's a lot of spontaneous resolution, but there there are some patients that do not improve in this really affects the quality of life. And there have been um there has been a procedure described where you actually go in and a plate, the the neural epithelium on both sides. But the problem with this is that it can result in complete smell loss um and potentially a CSF leak. 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 sensor and neural, so um conductive losses are um when the utterance cannot reach the olfactory epithelium because of obstruction. Um So this is you know inflammation from UR. Eyes or allergies, nasal polyps, sino, nasal 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 in the olfactory bulb. Um And then this is a list of some of those that we've actually already talked about a little bit. Post viral smell loss, trauma, aging medications, neurodegenerative disorders. And then if the loss doesn't fit into either of these it's determined to be um idiopathic and then um so the question now is uh what type of smell loss is covid? And um let's kind of sidetracked a little bit and now focus on covid smell loss. Um It's it's definitely I think very interesting and pertinent to many of our practices right now. So um to talk about covid smell loss will will talk about post viral olfactory dysfunction in general. Since this was already a thing prior to covid, um we know that that's the viruses can cause smell loss. We already knew that and we knew that corona viruses could cause smell loss. So in um post viral olfactory dysfunction. P. B. O. D. Um in general. Um Hi paz Mia's and Sarah's Mia's 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 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 neural epithelium which reduces the number of 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 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 first 3 to 4 weeks um which suggests that damage is to non neuronal cells. Since those cells 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 the covid in general The Smell loss does come back relatively quickly with an average of about three weeks. So why does this happen? Um We know that the virus enters cells via attachment of the spike protein to ace two 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 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 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 obstructions. So um that's an interesting thing about covid. So obviously is to receptors are important for covid smell loss. So some data to back up their important role includes that too. There's a 200-700 fold increase of their expression on the old factory versus the respiratory epithelium. So that's why I smell loss is such a common symptom of covid 19 And also the fact that their increased expression can correlate to outcomes. Um for example more severe infections in young obese patients who express higher levels of ace two 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 sustain ocular cells then they won't function properly and um won't be able to regenerate but when the sustenance ocular 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 damage 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 smells. 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 and those patients that are being affected um it's harder for regeneration to occur. And then I lost 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 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 inpatient outpatient part of the country. Um So they're not not the most reliable but there is a systematic review that reported an average of about 52% of 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 half. 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 patients are under reporting this 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 Ryan area 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 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 I. C. U. But there is a study to show that norma osmium meaning normal smell was shown to be an independent predictor for hospital admission with covid 19 which supports the thought that maybe there is more smell loss um is small. This is more common in mild infection. And I just think that that's like an interesting thing to know because um no younger people 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 us. 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 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 if our publication out of R. E. N. T. 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 maybe 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 the way that covid smell loss um can sort of be differentiated from other types of 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 a quarter of people admitted to the hospital um in this study had complete loss of smell on objective testing, but the most common was um the most common severity was severe, my Krahz mia or hypothermia. 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 a 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 caused less of a severe loss and then here's a different study kind of showing the same thing um severe Microsemi slash hypothermia 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 and a few slides. So then um we talked a little bit about tasting this relationship to smell. But in covid, how is how does taste sort of fall into all of this? And we know that many covid 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 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 due to the impaired retro retro nasal olfaction. So maybe the the the true prevalence of taste loss is actually over reported and they're more if they're more just talking about a flavor loss. Um But still there is um some published case series about taste dysfunction in covid um And taste in sometimes taste disturbance can be more common than um olfactory disturbances and sometimes can be present alone and even 10 to 20% of the time. So um we also know that there's a cell 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's not just being completely related to smell but we do think that a lot of the covid taste losses related um to covid smell loss. Um But the mechanism by which the ace two inhibitors can cause taste disturbance um is unclear which is a little bit different than how we were able to sort of explain how they can cause smell loss. Um But um they don't think that it's related to any alteration in um like serum or salivary zinc levels. Um And one thought is that the virus could occupy the binding sites of the silex 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 had touched on a little bit already. Obviously our patients are extremely interested in this um information so We do have pretty good data by now to show that the number falls around 75-80% of people recovering their smell in about a month which with the mean recovery being around three weeks and then longer term About 95% of people will recover their smell by six months and um yeah that seems pretty good and it is but with the amount of covid patient 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 six months after a year. Um And um including having continued parra's mia's but like we mentioned we do think plasmas 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. 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 pros meus and over 50% of those cases lasted over three 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 the baseline severity of loss um is 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 from what you know from 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 currently have, there does not seem to be a difference between recovery between genders. Aside from one study that did show later recovery in women Um and younger patients under 40 um do have a higher chance of. Okay, so those are some good prognostic factors and then um in terms of the work up, if the timing makes sense with a covid infection, we really don't need to do further um work up for that. Like you know, get any imaging or I will still scope these patients just to see if they have some like lasting inflammation or something going on that could potentially um b 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, headache, facial numbness, tempest axis. Um you know that could be concerning that um that something else is going on and then the these are the objective measurements that I was talking about um that 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 I will the the two main ones are the ups at the University of pennsylvania smell identification test and then sniffin sticks um that are shown here and I'm gonna I'm gonna talk about both of them in a little bit more detail in a second. Um However, if uh if there's no history of covid, so we're kind of going back to um presentation of smell loss in general. Um The work up can be much more extensive to try to figure out what's going on. Um So it's very important to discuss the onset and the duration of the smell loss and really press the patient on any events that could have occurred around from the time of smell loss. Especially because it may take patience awhile to sort of realize that their smell is gone or that 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, they don't tend to forget if it was happened because of a head trauma or if it happened because of a certain medication but um sometimes like you are i history really needs to be pulled out of them and it is one of the most common reasons. So it is something that you want to try to pick up just to have a reason for what's going on um should also um elicit any type of um sino nasal history. Um That could mean that the smell loss is just from you know some nasal inflammation or maybe a tumor 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 neurologic disease um especially like we mentioned before parkinsons um and that that should be like a personal or family history because it may be, you know, if there's a family history of something that's genetic, you may even if the patient is not diagnosed with it and maybe something that you want to 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 less 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 Auto immune disorders, put potential exposure to certain pesticides or metals and then um psychiatric disorders have been linked to smell dysfunction in particular the um Olfactory hallucinations. Which we discussed a little bit before. Also a history of chemo radiation can affect salivary function and have caused can cause atrophy or scarring in the nose. Um bad reflux can cause an unpleasant smell for the patient. Um Also inter nasal drug use is something that you should talk about. Uh Inter nasal 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 you know patients say that they haven't had smell for over a decade and then got out of them that they had used inter nasal 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 old factory area. So uh like I mentioned smell testing can be performed to both um document and quantify um document that the smell loss is present and quantify how severe it is. So the university of pennsylvania smell identification test. It's a 40 question scratch and sniff test um that has scored on gender and age norms. Um And you know it they technically the smells that used our cross culture 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 a certain language but um it's a validated test um that does um you know work very well. So for instance this graft is the female age norms. So Anosmia is considered 18 or lower out of 40 and then malingering would be five or lower. Um because just guessing you should get more than that. And then um normal, mild, moderate and mild moderate to severe um smell loss uh are are different numbers based on the age norms. Uh And then like I mentioned, it's also good to do this because besides besides documenting the loss um it's also useful to monitor for improvement and smell. Um And you can kind 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 sniffin sticks um In our clinic we have the opposite. It's it's definitely a lot easier um to do sniffin sticks are nice because they test some other um parts of olfaction like threshold discrimination and identification. And these tend to be the test that's used more in um um like research setting because it has these different things that it can look at. Um So they're basically just these pens that you open and smell. Um But uh the thresholds uh is tested by using and beautiful and also pens with no smell and evaluating when the patient can detect the odor. And then odor discrimination. You present three pens too with the same odor. And the other is the lupin. And you try to have the patient sort of discriminate between those odors. And then lastly is the identification um that you have uh the patient's smelled a specific deodorant and then have them choose between four answers sort of like a force multiple choice similar to the upset. 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 neurologic exam. Um You want to look in the mouth and perform an intra oral exam to look for um dental disease or um you know tonsils, stones that may be causing halitosis and affecting the patient's perceived sense of smell. Vitamin deficiencies may cause papillary hypertrophy or flattening of the tongue. But obviously overall vitamin deficiencies are not are not that common um With with the diet um that we eat here unless you see that there's obvious malnutrition in these patients and then um anterior rhine Oscar p. Should be performed um before um without any d congestion. Um Just to see if there is any inter nasal 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 cleft region. And this is a video here of that. So I am 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 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 is that uh we will examine um internationally 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 in the middle turbinate here. Um And this patient does have some um polyps in the uh in the middle mediators here. This is the insanity and this is the drain the drainage area of the maxillary 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 uh I see that. Let me show that again. I see this um kind of lesion here so that was you know a positive finding on endoscopy. Um So then lab work up 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. 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 if you are suspecting this could be related to um sino nasal disorders like chronic sinus disease or something like that. A. A. C. T. Is better. And then for M. R. I. This is when the exam is normal maybe there's no sino nasal symptoms and um you can't um you know really explain what's going on. So you're sort of looking for intracranial pathology like around the whole factory cleft and a foster 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 is a finding here this is the crystal golly. So obviously this is where I was showing you where the olfactory cleft in 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 a video up a thick loss. Um The question is um when do you 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 there's if the patient is relatively young it really can't be explained by anything um even aging. Um And I've really delved into it and they have a normal exam and we just really can't find a cause. Um I may have them get an M. R. I. Just to make sure that I am not missing something. Um But I don't have really a great um answer for that because there's really no guidelines about it. So it's something that we can look at is um the utility in terms of I guess like cost effectiveness for MRI's with video idiopathic smell loss. So um here this study evaluated the cost for correct diagnosis of idiopathic um olfactory loss. Um And so it basically included um a group of patients who underwent M. R. I. As part of the work up and a group of patients who did not undergo M. R. I. As part of the work up for their idiopathic olfactory loss. And the main cost from my M. R. I work up 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 quote effective. So The incremental cost effectiveness ratio for em reverse no imaging was over $100,000. Which is higher than most acceptable willingness to pay through thresholds. And the conclusion here was that it's of course more cost effective to not routinely obtain memories for idiopathic olfactory loss. Uh So we can understand that. Getting it getting an M. R. I. Is more expensive but does it improve patient outcomes so that the cost is worth it. And this study included about 100 and 4 840 patients Um with old idiopathic olfactory loss 247 or 29% of them. Um we're um 29% of those. Uh this was all a factory last sorry and 29% of those had idiopathic And then M. R. I. was obtained in 55% of these patients um with the Idiopathic loss. Um within these they found abnormalities and 4.6% but only .8% of these um were an abnormal finding that could potentially explain um the reasons for the small loss. So the estimated cost for for attributable um abnormal finding was over $300,000. Um so the authors concluded that the rate of abnormal findings was actually similar to that seen in the normal population. So based on this data. Um the use of routine M. R. I. And patients presenting with idiopathic um olfactory loss without other concerning symptoms of course. Um Maybe 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 M. R. E. S. That I have gotten for smell loss. I have yet to pick up something important like like this. Okay so um we I already talked a bit about the most common reason for smell us in adults which is the post viral. So just quickly I'll mention a few other types of head trauma. Um So the lower the presenting GCS um the higher the percentage of patients who will experience olfactory loss which makes sense. And the more severe the loss the less likely it is to improve. Like we discussed. Um Although improvement can happen even sometimes a few years after the trauma although it's um it's pretty rare for that to happen. And the mechanism here is the sharing of the axons but also a demon of the neuropathy liam um And um like a fracture through the crib reform area or brain contusion or hemorrhage. And then in terms of um aging both the number of fibers in the olfactory bulb as well as the um olfactory receptors 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 rate in each person. But the regenerative process of this um a apoptosis that is happening is going to decrease with age which is another reason that that patients will start to experience smell loss as the age. Um An increase in receptor cell death also may occur with aging and this just results in a reduction in the surface area. 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 due to age related bone growth, resulting in pinching off of the olfactory neurons as they transfers the f droid bones. There are a lot of reasons for smell loss to happen with aging and then um for neurodegenerative diseases, specifically Parkinson's disease. This slide is actually taken from the Michael J. Fox foundation. Um But it shows how Smell loss can proceed 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 pickles and a possible theory or reason for early olfactory loss in Parkinson's um is also talked about a little bit on this website but potentially a misfolded alpha. So nuclear protein which is the major constituent of Lewy bodies. Um and the protein clumps that are the pathological harmony Harlem mark of Parkinson's disease. They can first take up position in the olfactory bulb and then after this, the protein may go to the substantial Niagara in the region of the brain. Um That's the region of the brain that when affected results in 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 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 time goes on that. Um If you start to notice any other, you know, um abnormal symptoms. And then for um conductive disorders we look for things like polyps, inflammation infection. Um But also for sino nasal disorders, there can potentially be a sensor neural part of it too, like if the neural epithelium has been damaged. Um But this usually sino nasal disorders are traditionally um conductive and then uh what I put some of these under the the category of other um although they do affect the neuro sensory sensory pathway rather than being conductive. So the first uh the there's some congenital causes like common syndrome um where there is 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 familiar in Bosnia 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 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 co morbid condition. 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 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 smell us as something that can happen. Um And then um I I spoke about this a little bit, but preventative measures that we do need to talk to our patients about to check and recheck um that they're smoking. Their alarms are working. Their gas stove is turned off that they labeled 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 prognosis 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 aged nonsmoker, pros mia and absence of a left or right side preference in the smell function. And then just put the last thing I want to talk about a little bit was treatment. Um So then then we'll have some time for any questions. Uh So there is a surgical treatment can be offered for some of these conductive losses like polyps and um tumors um uh In anything to kind of treat on the mucosal inflammation. So inferior turbinate surgery may improve olfaction by improving nasal airflow and the ability of odorant to enter the nasal cavity. Um And same thing with septa plasticity. Of course we can't guarantee our patients that straighten 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 septa placidity anywhere from 10 to 70%. 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 thing that I mentioned here in italics is that um there um if patients are having smell loss due to inflammation from allergens or something like that, you can you can treat with saline and topical, inter cortical topical um cortical steroids and you know, anti histamines, energy congestions and that kind of but now we're going to focus on um what to potentially do for patients who have like these um uh center neural reasons for smell loss that their exam is normal. Um So you you may or may not be um familiar with something called a factory training. Um This is where different like flavors of scents are used to try and stimulate the natural regenerative capacity of the olfactory epithelium, epithelium and the central processing center, although the true mechanism of action is not fully known. So essentially um each of the four, we usually start with four 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 a few think about the smell or think about a memory regarding the smell while you're doing it. That could potentially um 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 sense to for 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 demonstrated a significant improvement in the T. D. I. Or the threshold discrimination and identification score um in the olfactory training group First the control group with a mean T. D. I. Improvement in um of 10.3 um which is um meaningful. And I was going to talk about steroids that there's conflicting data about oral steroids and um also 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 destiny could have 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 old factory is a function is common um It's the the the post viral is the most common type of aside from sino nasal disease. But many times a 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 lots. Um It's a little bit different than um P. V. O. D. 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. The recovery right here is about 95%. At six months. We're going to have further data about that. And for this again I give I have offered olfactory training and steroid rinses um and then repeat the smell um testing after that, mm hmm.