DISORDERS OF OLFACTION

BY

ABU SAYEEDJUNIOR RESIDENT, MS-ENT.

J.N.MEDICAL COLLEGE.ALIGARH MUSLIM UNIVERSITY, ALIGARH.

Characteristics of odorants- An odorant should be –• Volatile,• Organic substance,• Low molecular wt.

Pre requisites for smell-• 1) Odorants should enter the nasal cavity- actively or passively. (Actively by sniffing, and passively by diffusion.)• 2) should pass in the olfactory cleft.• 3) should be dissolved in largely aquous phase of the olfactory mucous.

Cross-sectional view of the olfactory epithelium showing the columnar supporting cells (S) that extend the full length of the epithelium. An olfactory neuron (O) with its dendrite and basal cell (B) can be seen among supporting cells (×1241). (From Morrison EE, Costanzo RM. Morphology of the human olfactory epithelium. J Comp Neurol 1990;297:1. From Wiley- Liss, a division of John Wiley & Sons.)

ABNORMALITIES OF SMELL

Anosmia refers to an inability to detect qualitative olfactory sensations (i.e. absence of smell function).Partial anosmia defines an ability to perceive some (but not all) odours.Hyposmia or microsmia refers to decreased sensitivity to odours.Hyperosmia reflects increased sensitivity to common odours. It reflects a patient’s heightened response to an odour, rather than an increased ability to smell. This problem has been reported in some conditions associated with a change in hormone balance, such as in pregnancy and Addison’s disease (adrenal-cortical insufficiency), as well as migraine, drug withdrawal, epilepsy (intericatal period), multiple chemical sensitivity and psychosis.

Dysosmia (sometimes termed cacosmia or parosmia) is distorted or perverted smell perception to odour stimulation.

Phantosmia is a dysosmic sensation perceived in the absence of an odour stimulus (also known as olfactory hallucination).

Olfactory agnosia refers to an inability to recognize an odour sensation, even though olfactory processing, language and general intellectual functions are essentially intact, as in some stroke patients.

Presbyosmia – a decline in smell sense with age.

Osmophobia – a dislike or fear of certain smells.

Loss of olfactory function can be subdivided into two classes:

(1)conductive or transport impairments result from obstruction of the nasal passages (for example, chronic nasal inflammation, polyposis, etc.)

(2) sensorineural impairments result from damage to the olfactory neuroepithelium, central tracts and connections (for example, viruses, airborne toxins, tumours, seizures, etc.).

In some circumstances, it is difficult to classify an olfactory disorder into one of these classes, (conductive or sensorineural) because of both blockage of airflow to the receptors and damage to the receptors or other elements of the olfactory neuroepithelium, can be present.

For example, Chronic rhinosinusitis, can produce damage to the olfactory membrane in addition to blocking airflow, and altered membrane function over time, can lead to degeneration within the olfactory bulb.

1. Conductive Olfactory DisordersThe conditions which can decrease the nasal airflow and block the access of odorants to the olfactory epithelium; however, patients may still have some retronasal airflow, allowing the ability to detect the flavor of food.Causes of decreased nasal airflow include nasal septal deformities, nasal polyposis, tracheostomy, or nasal cavity tumors, post op adhesions. Although rhinosinusitis may cause a conductive loss, and a change in the sense of smell is one of the most predictive symptoms of true rhinosinusitis, evidence also points to a sensorineural olfactory loss especially with long-standing inflammatory disease.

2. Sensorineural Olfactory Disorders

2.1. Upper Respiratory InfectionsLoss of olfaction after a URI is one of the most common causes of smell disorders, and occurs more commonly in women and the elderly. Olfactory dysfunction during a URI can initially be conductive, but persistence of loss of smell after resolution of other symptoms indicates sensorineural injury to the olfactory epithelium. In patients with post-viral olfactory dysfunction, the presence of rhinovirus, coronavirus, parainfluenza virus, and Epstein-Barr virus have been detected in the nasal discharge. Other infectious causes that have been reported include hepatitis, herpes simplex encephalitis, pneumonia and variant Creutzfeldt–Jacob disease.

It is not clear what predisposes someone to virus- and bacteria-induced smell dysfunction, or the precise mechanisms behind it. Patients may present with hyposmia, anosmia, or dysosmia. There is a higher incidence of hyposmia (post URI), than is seen with other sensorineural causes of olfactory disorders.In a study of olfactory biopsies of 4 patients with anosmia and 11 patients with hyposmia due to a viral illness, ‘Jafek and colleagues’ noted that patients with anosmia had markedly reduced numbers of receptors and those receptors were abnormal compared with those patients with hyposmia.Given the ability of the olfactory receptor neurons to regenerate, spontaneous recovery of some smell function is theoretically possible over a prolonged period. However, complete recovery is less likely, the longer the patient has the loss, and is inversely related to the degree of dysfunction.

2.2. Head traumaHead trauma often results in smell loss, particularly where rapid acceleration/deceleration of the brain occurs (i.e. coup/contrecoup injury). • The prevalence of olfactory loss following head trauma is around 15

percent and is proportional to the severity of the injury.• Blunt trauma to the occiput has been found to produce greater

olfactory loss than trauma to the front of the head.• Following head trauma, the loss of smell is usually, but not always,

immediate. However, it may take a while for the patient to recognize the presence of the dysfunction.

• Fracturing of the cribriform plate is not a prerequisite for smell loss.

Common mechanisms include- • Disruption from shearing forces of the olfactory fila through the

sinonasal tract, and • Direct contusion and ischaemia to the olfactory bulb and frontal and temporal poles.

Animal research shows that intracranial haemorrhage and ischaemia can lead to degeneration of the olfactory epithelium without transection of the olfactory nerves. Iatrogenic trauma, such as surgery, can cause smell impairment and has been seen with such procedures as sinus surgery and craniotomy.

• Disruption of olfactory fila d/t shearing forces.

2.3. Tumours and mass lesions A number of tumours in and around the olfactory bulbs or tracts can cause olfactory disturbance. Examples include • olfactory groove meningiomas, • frontal lobe gliomas and • suprasellar ridge meningiomas arising from the dura of the cribriform

plate. • mesial temporal lobe tumours.

• Structural lesions affecting smell may also affect vision…..• Also, olfactory tumours may extend into the frontal lobes resulting

in symptoms of dementia and possibly the release of primitive reflexes (for example, grasping, snout and glabellar).

• Mass lesions around the olfactory region can result in a Foster-Kennedy syndrome, which consists of: (1) ipsilateral anosmia; (2) ipsilateral optic atrophy and (3) contralateral papilloedema (d/t raised intracranial pressure.)

Pseudo-Foster-Kennedy syndrome has been reported in patients with increased intracranial pressure, without any evidence of mass lesion on MRI.

Fig. showing Fundoscopic findings of papilloedema in one eye and optic atrophy in the other.

2.4. Congenital Loss• Accounts for about 3% of anosmia.• Usually an isolated finding. • Patients often present during their preteen or teenage years with an

inability to smell, often discovered by family members. Patients with a congenital lack of olfactory ability may not recognize their olfactory dysfunction and have no recollection of detecting odors. They may have distinct food preferences due to their inability to appreciate the flavor of food while retaining the ability to detect the fundamental taste sensations from the taste buds.

• Recent studies have demonstrated that genetic mutations in the gene SCN9A, which encodes the voltage-gated sodium channel Nav1.7, cause congenital anosmia.

• SCN9A loss of function mutations were originally studied in patients with congenital analgesia, although studies in both humans and mice have demonstrated patients with these mutations also have an inability to detect odors.

Associations exist between congenital anosmia and several abnormalities including • Kallmann syndrome, • de Morsier’s syndrome, • holoprosencephaly,• anterior neuropore anomalies.

Kallmann syndrome consists of anosmia and hypogonadotropic hypogonadism and has autosomal or X-linked forms. • Patients usually lack olfactory bulbs and the gonadotropin-releasing

hormone, resulting in hypogonadism. • The defects are due to a lack of migration of GnRH-releasing cells

from the olfactory placode to the hypothalamus and a lack of migration of the olfactory neurons to the olfactory bulb and hypothalamus.

• Magnetic resonance imaging (MRI) findings may reveal aplasia or hypoplasia of the olfactory bulb, or associated encephalocele or abnormality in the frontal lobe.

Lack of olfactory bulbs or tracts (arrows) in a 21year old woman with congenital anosmia on a T2weightedHigh resolution coronal magnetic resonance image.

Septo-optic dysplasia (SOD), (de Morsier syndrome) is a rare congenital malformation syndrome featuring- 1) optic nerve hypoplasia, 2) pituitary gland dysfunction, and 3) absence of the septum pellucidum (a midline part of the brain).

Two of these features need to be present for a clinical diagnosis — only 30% of patients have all three.

Patients with septo-optic dysplasia (de Morsier’s syndrome) can have hyposmia, visual symptoms and precocious puberty.

Holoprosencephaly (HPE, once known as arhinencephaly) is a  cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres.• The condition can be mild or severe. According to the 

National Institute of Neurological Disorders and Stroke(NINDS), "in most cases of holo- prosencephaly, the malformations are so severe that babies die before birth."

• When the embryo's forebrain does not divide to form bilateral cerebral hemispheres (the left and right halves of the brain), it causes defects in the development of the face and in brain structure and function.

• In less severe cases, babies are born with normal or near-normal brain development and facial deformities that may affect the eyes, nose, and upper lip.

Holoprosencephaly

2.5. ToxinsOlfactory dysfunction attributed to toxin exposure is relatively low (2%), but a large number of toxins are associated with olfactory loss.

These include-• Environmental pollutants.• Specific metal fumes (Cadmium, Chromium, Nickel, Mercury, Lead etc).• Gas exposure from industrial plants (formaldehyde, methyl bromide).• Solvents including toluene and paint solvents.• Tobacco smoke.

Mechanism of injury• The olfactory receptor neurons are in direct contact with the

environment, leaving them vulnerable to inhaled toxins.• By-products of metabolism of the odorants by ‘Cytochrome P450 mono

oxygenase system’ in the supporting cells.

Damage to the olfactory epithelium can occur with • 1)acute, high levels of toxin exposure or with • 2)chronic low level exposure, causing more gradual olfactory decline.

• If the regenerating cells (Basal Cells) are spared, the olfactory neurons may regenerate after acute toxic injury, but with more severe injury to the olfactory epithelium or with chronic injury and increasing age, the regenerative potential may decrease, causing noticeable olfactory loss.

• Within the supporting cells and Bowman’s glands are high levels of xenobiotic enzymes, including cytochrome P450 monooxygenases and other biotransformation enzymes. These enzymes detoxify inhaled or systemic substances, presumably to protect the olfactory neurons and CNS, or to process odorant molecules for receptor activation. Byproducts of these enzymes may include toxic metabolites, which themselves may damage the olfactory epithelium.

Metals, in the form of dust or fumes, can be toxic to the olfactory system. The most well-known is Cadmium, used in the production of batteries, semiconductors, and electroplating.

Factory workers exposed to Chromium, which is often used with nickel in industrial manufacturing and steel production, can have increased olfactory thresholds.

Other metals linked to olfactory loss include manganese, mercury, aluminum, and lead.

• Tobacco smoke exposure is associated with hyposmia in active smokers. Studies find increased olfactory receptor neuron apoptosis with tobacco smoke exposure.

• In one study, the olfactory scores of former smokers were not significantly different than the scores in lifelong nonsmokers, suggesting that the olfactory ability can return with cessation of smoking.

2.6. Age

• Under the age of 65 years, approximately 1% of the population has major difficulty in smelling.

• Between 65 and 80 years, this increases remarkably, with about half of the population experiencing a demonstrable decrement in the ability to smell.

• Over the age of 80, this figure rises to nearly 75%.

There is accumulation of damage over the years, and a single event, such as a bad cold, can be the precipitating factor.

The age-related changes in smell function are due to-• Damage to the olfactory receptors.• Decreased activity of Basal cell to regenerate.• Replacement of olfactory epithelium by respiratory epithelium.• Occlusion of the foramina of the cribiform plate, pinching off the

axons of the olfactory receptor cells as they enter the brain cavity.• Decreases in number of glomeruli within the olfactory bulb.

Low magnification of the surface of the nasal cavity taken from a transition region. Patches of respiratory epithelium (R; dark areas) can be seen within the olfactory (O) region (×28). (From Morrison EE, Costanzo RM. Morphology of the human olfactory epithelium. J Comp Neurol 1990;297:1. From Wiley-Liss, a division of John Wiley & Sons.)

2.7. Neurodegenerative disorders

• In patients with Alzheimer and Parkinson diseases, 90% exhibit olfactory dysfunction in the early stages of the diseases.

• Olfactory loss may be the first clinical sign of these neurodegenerative diseases, preceding signs of dementia in Alzheimer disease (AD) or motor symptoms in Parkinson disease (PD) by several years.

• Neurofibrillary tangles and neuritic plaques appear in the olfactory bulb, anterior olfactory nucleus, and olfactory cortex in patients with AD.

• First degree family members of patients with AD were found to have significantly reduced smell identification scores, pointing to genetic predisposition in the development of the disease.

• Smell deficits are more common in PD than in other diseases with parkinsonian symptoms, and may help to differentiate PD from other diseases such as essential tremor.

• Smell identification is the most accurate predictor of the presence of PD compared with healthy controls in motor and nonmotor diagnostic tests for PD.

• Because of the implication of viruses and environmental toxins in the development of AD and PD with the finding of early olfactory loss, some theorize that these diseases may be caused by agents entering the brain through an olfactory route.

Huntington disease is also characterized by olfactory deficits and findings of degeneration of central olfactory degeneration.

Multiple Sclerosis: a recent study suggested that hyposmia was present in almost 50% of patients within a known MS group.

2.8. Epilepsy and migraine• Olfactory auras, also described as hallucinations, are rare.• When present, they are often associated with seizures and headaches.

Olfactory auras consist of sudden unexplained sensations of smell that are usually, but not always, unpleasant and are rarely isolated events.

• In epilepsy, mesial temporal lobe structures involved in the usual processing of odour information – such as the amygdala and hippocampus – have been implicated as the generators of ictal olfactory sensations (simple or complex partial seizures) that often evolve into secondarily generalized seizures.

• Common aetiologies include mesial temporal sclerosis and tumours.

CLINICAL EVALUATION OF SMELL FUNCTION

Proper assessment of a patient’s smell function requires (1) a detailed clinical history.(2) quantitative olfactory testing, and (3) a thorough physical examination emphasizing the head and neck with

appropriate brain and rhinosinus imaging.

HISTORY TAKING

• Does the patient have a problem with smell, taste or both?• Mode of onset, duration of impairment and pattern of occurrence?

Sudden olfactory loss can be consistent with possible head trauma, ischaemia, infection or a psychiatric condition.

Gradual loss may indicate a progressive and obstructive lesion in or around the naso sinus region, particularly if the loss is unilateral. Intermittent loss may suggest an inflammatory process in association with nasal and sinus disease.

Seasonal variation ? (Allergic rhinitis)

Any history of precipitating antecedent events, such as head trauma, viral upper respiratory infections, chemical or toxin exposures and nasosinus surgeries?

Does the patient have any nasal discharge that is mucous-appearing (for example, allergy), purulent (for example, infection), or clear (CSF rhinorrhoea after trauma)?

History of headache suggests sinusitis, migraine or intracranial tumour. Comorbidities such as renal failure, liver disease, hypothyroidism, diabetes or dementia?

Are smells present without an obvious stimulus?A simple partial seizure or aura may not be obvious and other signs of ictal activity should be explored (for example, limb shaking, difficulties with speech, unresponsiveness, automatisms, loss of consciousness).

Given the strong relationship of Alzheimer’s disease and idiopathic Parkinson’s disease to smell impairment, one should also look for memory- and parkinsonism related complaints in older patients.

Personal History: Appetite may decrease owing to decreased/altered flavour. Addiction to alcohol, cigarette smoking, drug abuse- intranasal cocaine.

Menstrual history: Delayed puberty in association with anosmia (with or without midline craniofacial abnormalities, deafness and renal anomalies) suggests the possibility of Kallmann’s syndrome or some variant thereof.

Physical examination and evaluation

Patients complaining of smell disturbance typically require a general assessment of the head and neck and more detailed otolaryngological and neurological examinations.Any signs of trauma such as healing wounds, scarring or distorted nasal or skull architecture?Inspection of the nasal passages to view the peripheral nasal cavity for signs of polyps, congestion, deviation of septum or inflammation. Nasal endoscopy, employing both flexible and rigid scopes, is needed to ensure thorough assessment of the olfactory meatal area.

The additional presence of polyps, masses and adhesions of the turbinates to the septum may adequately obstruct airflow.The presence of mucopus above the Eustachian tube orifice suggests posterior ethmoid and/or sphenoid sinus disease.

A pale mucous membrane suggests allergy, usually as a result of oedema within the lamina propria.

Atrophy of the lamina propria is suggested by unusual spaciousness, dryness and crusting, as is seen in atrophic rhinitis.

Visual acuity, visual field and optic disc examinations aid in the detection of possible intracranial mass lesions resulting in increased intracranial pressure (papilloedema) and optic atrophy, especially when considering Foster Kennedy syndrome.

Quantitative olfactory testing

Several standardized and practical psychophysical tests have been developed over the last several years, including a number of brief self-administered tests ranging from the three-item Pocket Smell TestTM to the 40-item Universityof Pennsylvania Smell Identification Test (UPSIT).

The UPSIT is commercially known as the Smell Identification TestTM and is the most widely used olfactory test, having been administered to an estimated 400,000 patients since its development.

The UPSIT can be self administered in 10–15 minutes by most patients in the waiting room, and scored in less than a minute by nonmedical personnel.

This test consists of four booklets containing ten microencapsulated (‘scratch and sniff ’) odourants apiece. Test results are in terms of a percentile score of a patient’s performance relative to age- and sex-matched controls, and olfactory function can be classified on an absolute basis into one of six categories:1. normosmia, 2. mild microsmia,3. moderate microsmia, 4. severe microsmia, 5. anosmia and 6. probable malingering.

The four booklets of the40-odourant University of Pennsylvania Smell Identification Test (UPSIT; commercially known as the Smell Identification TestTM ). Each page contains a microencapsulated odourant that is released by means of a pencil tip.

Since chance performance is 10 out of 40, very low UPSIT scores reflect avoidance, and hence recognition of the correct answer, allowing for determination of malingering. The reliability of this test is very high (test–retest, r = 0.94).

Smell threshold test using Phenyl ethyl alcochol.

The recording of olfactory event-related potentials (OERP) is available in some specialized medical centres as an additional means of assessing the integrity of the olfactory system.Using brain electroencephalography (EEG), the test consists of discerning synchronized brain activity recorded from overall EEG activity following brief presentations of odourants.

TREATMENT OF SMELL DISORDERSThe most effective treatments available are those for conductive anosmia, where there is an obstruction of airflow through the nose to the olfactory neuroepithelium.

After diagnosis is confirmed using tools such as nasal endoscopy and CT scanning of the sinuses, the next appropriate course of action may include topical or systemic steroids. Conductive and sensorineural olfactory losses are often distinguishable using a brief course of systemic steroid therapy, since patients with conductive impairment frequency respond positively to the treatment, although long-term systemic steroid therapy is not advised.

Proper allergy management is essential and may require the use of an antihistamine.

When a bacterial infection is suspected (for example, infectious rhinosinusitis), a course of antibiotics should be used.

Surgery should be considered for: (1) very large and medically refractory polyps, or (2) situations where a malignant neoplasm is suspected.

Sensorineural impairment of olfaction is typically more difficult to manage and the prognosis for patients suffering from long-standing total loss due to upper respiratory illness or head trauma is poor.

The majority of patients who recover smell function subsequent to trauma do so within 12 weeks of injury.

Patients who give up smoking typically have dose-related improvement in olfactory function and flavour sensation over time.

Central lesions, such as CNS tumours that impinge on olfactory bulbs and tracts can often be resected with significant improvement in olfactory function.

When epilepsy or migraine is suspected, a course of antiepileptic or antimigraine medications may prove beneficial.

Medically refractory epilepsy resulting in olfactory disturbance can be successfully treated with surgery

In patients with multiple sclerosis, immunomodulatory therapies, including interferon-beta and occasional steroids, is the mainstay of treatment.

When depression or psychosis is suspected, a course of an antidepressant and appropriate psychiatric referral may be necessary.

In patients with complete anosmia, supportive measures are necessary to protect them from further harm. Thus,1. Smoke and carbon monoxide detectors need to be installed and properly working.2. When possible, electrical appliances should be used instead of gas appliances.3. Expiration dates for food products should be scrutinized and old food items checked by someone with normal smell function or discarded.4. A balanced diet, particularly in the elderly, must be kept to prevent weight loss and malnutrition.

Adding flavour enhancers (for example, monosodium glutamate, food colouring, chicken or beef stock) to foods can also help with their appeal.

THANK YOU…