Postinfectious Olfactory Disorders

The common cold, while a minor inconvenience for most, remains a scourge of modern medicine, with treatments limited to over-the-counter remedies. All of us can probably recall having had a cold where our sense of smell and the pleasure of eating was lost for a few days. However, for an unfortunate minority, this disturbance in olfactory function persists long after the nasal congestion and rhinorrhea have abated. Estimates of the prevalence of olfactory disorders of any cause suggest that ~5% of the population is affected.1–4 Postinfectious olfactory disorders are believed to account for 11 to 40% of cases5,6 with the higher figures likely to represent the prevalence in specialist centers. Extrapolation of the lower figures suggests that an estimated 1.7 million people in the USA and 330,000 people in the UK are suffering from postinfectious olfactory disorder at any one time. Viruses that give rise to the common cold are thought to be the pathological agents responsible for postinfectious olfactory loss. These include rhinoviruses (30 to 50%), parainfluenza virus (5%), coronavirus (10 to 15%), influenza virus (5 to 15%), coxsackie virus (<5%), adenoviruses (<5%), and respiratory syncytial viruses (10%). However, there are over 200 viruses in total that can cause upper respiratory tract infections (URTIs).7 When Wang et al set out to study the most likely culprit of this disparate band of viruses, they found that parainfluenza virus was present in 88% of patients with postviral olfactory loss compared with 9% of controls8; Sugiura et al had similar findings.9,10 However, another study published the same year by Suzuki et al showed that at least four viruses were identified in biopsies from patients with post-viral olfactory loss and parainfluenza virus only accounted for 1 of the 24 cases examined. Other identified viruses included Epstein–Barr virus, rhinovirus, and coronavirus.11 The mechanism by which the virus wreaks its havoc usually involves hijacking of the cellular apparatus, but the exact details may depend on the actual virus implicated. Rhinovirus, for instance, causes a selective neutrophil and monocyte recruitment to occur. The ensuing inflammatory cascade includes an increase in bradykinin, cytokine, chemokine, and soluble intercellular adhesion molecule-1 concentrations.12 The response in an immunocompetent individual involves T-lymphocyte activation, allowing the viral pathogen to be eliminated.

With specific respect to the olfactory apparatus, these viruses appear to cause partial loss of receptors in the olfactory epithelium. Ultrastructurally, previous studies of olfactory epithelial biopsy specimens have revealed a decrease in the number of olfactory receptor cells and nerve bundles, with squamous metaplasia occurring in a few cases.13 This reduction in ciliated olfactory receptors means there is a lack of dendrites and vesicles at the epithelial surface and, therefore, a decrease in the area available for odor molecule detection.14 Studies of patients with congenital anosmia have shown that the number of olfactory receptors in the neuroepithelium is likely to reflect the severity of the loss.15 It is unclear why an individual may be susceptible to the viral agents, but, as the age range of affected patients is typically after the fourth decade of life, there is weight behind the argument of a cumulative effect of the virus(es) on the olfactory epithelium. This may explain why some patients do not recover their olfactory ability, especially as the regenerative ability of the olfactory epithelium denudes with advancing age.16

It is by virtue of this partial loss of receptors that patients typically complain of hyposmia rather than anosmia, but, more importantly, they frequently describe various forms of dysosmia.17 Decreased olfactory input to the OBs (1–3) down-regulates dopaminergic interneurons (arrows), which may affect transmission from the olfactory nerve to the bulb and subsequent processing of those signals from the bulb (solid/dotted lines) ( Fig. 8.1 ). As all inflammatory edema associated with the initial viral URTI should have dissipated after the initial event, postinfectious disorders are considered to be sensorineural olfactory disorders (SNODs) and are not caused by pathology in the nasal cavity, olfactory cleft, or the paranasal sinuses; that is to say, airflow into the olfactory cleft is normal both orthonasally and retronasally. That does not, of course, mean that postinfectious olfactory disorders are exclusive from those secondary to chronic rhinosinusitis; indeed the viral URTI may have been the precursor to acute bacterial rhinosinusitis that then fails to resolve; there may also be septal deviation. The physician assessing patients with postinfectious olfactory loss should bear in mind that these patients may have a multifactorial etiology implicated in their disorder.

Beyond the peripheral theory described above, central theories have also been mooted for the qualitative disorders that encompass parosmias. However, in the presence of the postinfectious disorder, viral receptor damage is strongly believed to be the key culprit. In fact, it is largely due to the fact that postinfectious and post-traumatic disorders account for most parosmia, and that some degree of olfactory function is preserved, that the peripheral theory is the most popular. Certainly OB volume has been shown to be decreased in parosmic versus nonparosmic patients, indicating possible decreased and incorrect rewiring between the neuroepithelium and the OB.18,19 Functional magnetic resonance imaging studies have shown the impact that the addition of parosmia to hyposmia can have upon central olfactory processing.20 The anterior cingulate gyrus, thalamus, and orbitofrontal cortex showed more activation in patients with only hyposmia, adding further weight to the theory of decreased signal traffic between the neuroepithelium and the OB. It should be remembered, when discussing the mechanism of viral impact on the olfactory epithelium, that the olfactory system is a portal of entry for viruses to invade the central nervous system and so central effects of viruses cannot be discounted.21,22

Post-traumatic Olfactory Disorders

The clinical term post-traumatic anosmia (PTA) is commonly used to describe olfactory impairment following a head injury. The injury can include direct injury to the face and nasal structures or any part of the skull. The reported incidence varies from 5%23 to 66%,24 but this extreme difference is because of the inclusion of specialized smell centers that have a high incidence of referrals. The important point is that PTA is not an uncommon cause of olfactory impairment and it should be clinically pursued as a cause in any patient presenting with olfactory loss or taste impairment. Of cases of olfactory loss presenting to a physician, 17 to 24%3 are due to head or facial trauma.25,26 Olfactory loss due to head trauma can be divided into four mechanisms as discussed below, and can be the result of any combinations of these.

Direct Injury to the Nose and Face with or without Nasal and Facial Fractures

Head trauma associated with direct facial and nasal injuries, with or without fractures, often results in edema and mucosal hematoma of the nasal passages, which can lead to olfactory impairment by preventing odors from reaching the olfactory cleft and olfactory receptors (conductive disorder) ( Fig. 8.2 ). This same trauma can cause injury to the olfactory receptors directly, or later on by scarring of the olfactory epithelium and possible development of rhinosinusitis.24 With time, as the edema and possible hematoma subside, the conductive block improves, with possible recovery of olfactory function. However, injury to the olfactory receptors at the onset or secondary to scar tissue, or presence of rhinosinusitis, can lead to longer term olfactory loss. The incidence of olfactory loss in facial and nasal fractures varies from 11 to 60%.27,28 It is hard at times to isolate the pathophysiology of olfactory loss specifically, because injuries to the face and nose (e.g., fracture of the nasal skeleton) may not only cause a blockage of the nose, but also produce direct impairment of the olfactory organ and indirect injury to olfactory nerves owing to the acceleration and deceleration of the head when the nasal trauma occurs.

Direct Injury to Any Part of the Skull without Contusion or Hemorrhage into the Brain

In direct skull injury, acceleration and deceleration forces shift the brain forward and backward very rapidly, and the olfactory nerves, passing through the cribriform plate of the anterior cranial fossa en route to the OB, get sheared or stretched ( Fig. 8.3 ). Some studies have suggested that occipital head trauma is more likely to cause olfactory injury than trauma to other areas.29 In a series of 168 post-traumatic anosmia cases, it was found that injury to the occiput and the sides of the head was more likely to cause greater olfactory nerve damage than frontal head injuries.24 It is believed that the frontal sinus may be somewhat protective in helping to decrease the force of the blow. Fractures of the cribriform plate were relatively rare. In this mechanism of olfactory loss, biopsy of the neuroepithelium in the olfactory cleft has found degeneration of the olfactory vesicles and cilia.30 Other studies of the histopathology of post-traumatic anosmia have confirmed similar findings to postinfectious changes, with disorganization of the olfactory epithelium as well as damage to olfactory nerve fibers and changes in the OB.14,31

Injuries to the occipital and temporal regions of the head are more likely to cause smell impairment than frontal injuries.

Direct Injury to Any Part of the Skull with Contusion or Hemorrhage into the Brain

PTA can occur in mild, moderate, or severe head injury because of contusions to the OB and the brain, or intraparenchymal brain hemorrhage. Contusions of the OB and the orbitofrontal pole of the brain are the most common injuries associated with olfactory loss in this category ( Fig. 8.4 ).32 Injuries to other areas of the brain (e.g., the anterior piriform cortex, amygdala, and temporal lobe regions) lead to loss of olfactory discrimination and odor identification because olfactory nerve fibers leave the OB and synapse in all these areas.33 The reason that head trauma particularly affects the frontal and temporal lobe is that, during acceleration and deceleration, the brain slides over the rough base of the anterior and middle cranial fossae as it hits the front part of the inside of the skull ( Fig. 8.5 ). The clue to involvement of these cerebral regions is that memory and other areas of cognitive function, including behavior, are often impaired.

The frontal and temporal lobes are the most commonly injured regions of the brain in head and facial trauma, because the brain slides over the rough bone of the anterior and middle cranial fossae.

Postinfectious Olfactory Disorders

As outlined above, patients with postinfectious olfactory disorders experience, in the first instance, the usual symptoms of the common cold, including nasal congestion, rhinorrhea, coryza, pyrexia, and general malaise. Symptoms of olfactory disturbance will become apparent as the illness progresses. Other symptoms may also develop, such as facial pressure, otalgia, dental pain, and postnasal drip, indicating a wider picture of acute viral rhinosinusitis. A duration of 10 days or more is currently accepted as the demarcation between a viral and a bacterial etiology for acute rhinosinusitis. Unfortunately, it is only when all the other symptoms have subsided, and the loss of olfactory perception persists, that the problem becomes apparent. Patients will initially assume that the symptom will eventually disappear and hence there is often a delay in presentation to a physician (closing the ideal window of opportunity for early intervention, if this does indeed exist). However, a sense of apathy and lack of knowledge or interest among many physicians encountering patients with olfactory disorders means that patients are often dismissed, and, even among those who make it to secondary care, a further level of apathy prevents many from receiving a satisfactory assessment of their problem.

Along with hyposmia/anosmia, it is likely that about two-thirds of patients will suffer from parosmia (a distorted olfactory sensation; usually unpleasant). Conversely, of patients suffering from parosmia, 40 to 80% have a viral URTI as the preceding cause.17,34 This symptom in itself can become more disabling than the actual loss of olfactory ability, with over half of patients saying that it has a negative impact on their quality of life.17

A history for a patient presenting with olfactory loss following the presence of other upper respiratory tract symptoms should clarify whether the onset of the olfactory disturbance coincided with that of the other symptoms. If there is any doubt that the URTI was associated with the onset of olfactory disturbances, consideration should be given to other potential causes, which may modify subsequent investigations. Obviously, if other symptoms of rhinological origin are still present, then it is likely that active and continuing sinonasal disease is present and needs to be thoroughly evaluated as indicated in Chapter 7. A significant problem with the delay between development of the disorder and presentation to a physician with an interest in olfaction is that patients often find it difficult to remember the onset of symptoms. Some patients may, however, remember the cold as being “more severe” than previous URTIs. Typically, patients are aged between 40 and 70 years old, and women appear to be afflicted more often than men. The highest incidence occurs in March and May, following peaks of URTI bouts in the community.

The duration of olfactory disturbances after a viral URTI can vary widely, although approximately one-third of patients is expected to spontaneously recover normal function within 3 years. The disturbing symptoms of parosmia have been separately reported to disappear in 29% of affected patients after a mean duration of about a year. Interestingly, the presence of parosmia from the outset of the disturbance has been shown in a recent study to be less likely to lead to an anosmic outcome in the long term than parosmia that develops later.35

Post-traumatic Olfactory Disorders

In mild-to-moderate head injuries without facial or nasal fractures or cerebral complications, complaints of altered smell or taste are usually noticed early after the injury (2 days to 1 week). In one study, 25 patients with post-traumatic anosmia presented within 7 days of the head injury.36 In another study, it was reported that 83% of patients presented with smell loss immediately (1 to 5 days) after trauma, while 17% noted deficits 3 weeks to 4 months after injury.37 The reason for these differences is that traumatic anosmia can be associated with hospitalization, memory and cognitive impairment, and behavior problems, if cerebral hemorrhage or contusions occur. In addition, hospitalization for fractured bones and other organ complications can prolong recovery and recognition of smell loss. The nature and severity of smell impairment in traumatic olfactory loss shows strong similarities in many studies. The incidence of anosmia varies from 60 to 80%, with hyposmia occurring in 20 to 25%.24,38–40

Parosmia is not uncommon in post-traumatic olfactory loss. The incidence of post-traumatic parosmia varies from 14 to 35%.23,24,41 These differences are probably due to history taking and the fact that many patients recover early and may be missed. Does the occurrence of parosmia correlate with olfactory loss? One study found that it was more common in hyposmia than anosmia.24 It appears to be more common with frontal and temporal lobe injury than injuries to other brain areas, occurring in 45 to 50% of such cases.42 Fortunately from a prognostic perspective, parosmia shows gradual spontaneous improvement in the majority of cases. In an 8-year study, it improved or disappeared in 15 to 42% of cases.24

Related posts:

The Human Vomeronasal System Clinical Disorders of the Trigeminal System Sinonasal Olfactory Disorders Assessment of Olfaction and Gustation Functional Anatomy of the Olfactory System II: Central Relays, Pathways, and their Function Functional Anatomy of the Olfactory System I: From the Nasal Cavity to the Olfactory Bulb

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