Smell

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Disorders of Smell and Taste : 

Disorders of Smell and Taste Shahram Anari June 2009

Topics : 

Topics Olfaction Gustation

Olfaction : 

Olfaction Prevalence (US study) Anosmia: 1.4% Dysosmia: 10% Age related <60: 1% of population 60-80: 50% of population >80: 75% of population

Ignored symptom? : 

Ignored symptom? Patient don’t complain Generally disregarded by physicians Not much we can do? Not interesting for physicians?!

Olfaction : 

Olfaction Nobel Prize 2004 Linda Buck and Richard Axel Smell receptors and gene coding

Outline : 

Outline Quiz Olfaction Anatomy Physiology Aetiology Management Gustation Quiz answers

Quiz 1 : 

Quiz 1 The primary olfactory neuron cell body lies in: Olfactory bulb Olfactory mucosa Frontal cortex Dura

Quiz 2 : 

Quiz 2 Smell of ammonia is detected through: Cranial nerve I Cranial nerve V Cranial nerve VII Cranial nerve IX

Quiz 3 : 

Quiz 3 Approximately, how many genes encode olfactory receptor proteins? 100 1000 10,000 1000,000

Quiz 4 : 

Quiz 4 An odourant specific anosmia is caused by mutation in a gene encoding: Olfactory G-protein Cyclic AMP Calcium/Sodium channel Olfactory receptor protein

Quiz 5 : 

Quiz 5 Which one would perform better in odourant identification tests? A 38-year-old man A 40 year-old woman A 5-year-old boy A 67-year-old woman

Quiz 6 : 

Quiz 6 A 40-year-old woman complains of total anosmia after a head cold for the past 6 years. There is no other symptoms (including nasal symptoms) and the cranial nerve and nasal examination is normal. What is the next step? MRI of brain High does steroids CT scan of nasal sinuses Counsel on hazards of anosmia

Quiz 7 : 

Quiz 7 Name four health risks associated with total anosmia (advice to patients)?

Quiz 8 : 

Quiz 8 How many choices are correct? The olfactory mucosa is present on the: Septum Cribriform plate Middle turbinate Inferior turbinate

Quiz 9 : 

Quiz 9 What kind of an olfaction test is an UPSIT regarded as? Threshold testing Quantitative test Identification test Discrimination test

Quiz 10 : 

Quiz 10 What does a score of 5 mean in an UPSIT score range? Normal sense of smell Mild anosmia Possible malingering UPSIT score is not a numerical one.

Quiz 11 : 

Quiz 11 Which one does not have taste buds: 1) fungiform papillae 2) circumvallate papillae 3) filliform papillae 4) foliate papillae

Quiz 12 : 

Quiz 12 Which is the central olfactory route from olfactory bulb? 1) directly to cortex 2) through thalamus 3) through hippocampus 4) through hypothalamus

Quiz 13 : 

Quiz 13 True or False? Olfactory epithelium can regenerate Vagus is involved in gustatory reception Greater superficial petrosal nerve innervates taste buds on the palate Central gustatory pathway is entirely ipsilateral Epilepsy could cause unilateral anosmia Olfactory receptor cells are the only CNS cells exposed to outside directly

Quiz 14 : 

Quiz 14 Where does the facial nerve afferent taste cell body lie? Submandibular ganglion Otic ganglion Pterygopalatine ganglion Geniculate ganglion

Quiz 15 : 

Quiz 15 How do you manage a 30 year-old referred by his solicitor complaining about anosmia after a car accident?

Outline : 

Outline Olfaction Anatomy Physiology Aetiology Management

Anatomy : 

Anatomy Olfactory epithelium Pseudostratified columnar epithelium Surface area 1 cm2 in each nostril Covers cribriform area, sup/mid turb, septum In foetus is a continuous sheet of cells. As the child grows, becomes irregular In elderly the proportion of non-olfactory epithelium increases

Anatomy : 

Anatomy Olfactory epithelium consists of two layers (separated by basal membrane) Mucosa Lamina propria

Anatomy : 

Anatomy Olfactory mucosa contains: Cell body of olfactory receptors neurons Sustentacular cells Basal cells Duct of Bowman’s glands Microvillar cells Olfactory lamina propria contains: Bowman’s glands Neurovascular bundles

Anatomy : 

Anatomy

Other Olfactory Cells : 

Other Olfactory Cells Sustentacular cells surround ORN and maintain ionic milieu Basal cells are the stem cells of the olfactory epithelium. Bowman’s glands secret olfactory mucus which is different to respiratory epithelium mucus

Non-olfactory Smell : 

Non-olfactory Smell Common chemical sense Ophthalmic and maxillary branches of trigeminal contribute to: somatosensory innervations irritants (eg ammonia), cooling sensation, tickling Nasal reflexes V and I interact in Thalamus V perceives pungent odour (ammonia, hot pepper) Most odourants stimulate V at high concentration

Physiology : 

Physiology Odourant: volatile substance molecule Odourant molecules reach the olfactory epithelium via nose or mouth 15% of inspired air goes towards cribriform area (sniffing increases the rate)

Physiology : 

Physiology Olfactory receptor neurons Bipolar neuron Projects a single dendrite to the epithelium Connecting to outside world Conduits for viruses? Zinc Sulphate! Sends a single axon to the olfactory bulb There are 10-20 million ORN in the nose The cilia are of “9 plus 2” pattern The cilia are non-motile (lack of dynein arms) Cilia increase surface area to 22 cm2

Physiology : 

Physiology OR are expressed on mature ORN 1000 different genes encode OR Each ORN expresses only one type OR One gene, one receptor cell Pattern of ORN stimulation encodes for perceived odour

Physiology : 

Physiology Each olfactory receptor cell expresses only one type of odourant receptor, and each receptor can detect a limited number of odorant substances

Physiology : 

Physiology One single olfactory receptor can recognise multiple odourants. One single odourant can stimulate multiple olfactory receptors. Odourant molecules interact with odourant-binding proteins (OBP) to bind to OR OBP-odourant complex results G-protein initiation (depolarization)

Physiology : 

Physiology Receptor cells carrying the same type of receptor, converge their processes on the same glomerulus.

Physiology : 

Physiology Axon of ORN synapse with second-order neuron in olfactory bulb Neurotransmitter: Glutamate Axons from the bulb directly go to cortex (unique feature) There is no topographic distribution in cortex From cortex there are links to other areas (hippocampus; smell evokes memories)

Smell Disorder Classification : 

Smell Disorder Classification Normosmia Anosmia: inability to smell Complete: all odourants Partial: some odourants Hyposmia/Microsmia: Decreased sensitivity to odours Dysosmia: altered perception Parosmia: with stimuli Phantosmia: without stimuli Hallucination: temporal lobe seizure Cacosmia: bad smell with no external stimuli

Smell Disorder Classification : 

Smell Disorder Classification Heterosmia All odours smell the same Presbyosmia Age-declining smell sense Hyperosmia Increased sensitivity/heightened response to common odours Hormone imbalance: pregnancy, migraine, epilepsy Olfactory agnosia Inability to recognise an olfactory sensation Generally olfactory processing is intact Eg Stroke patients, temporal lobe lesions

Aetiology : 

Aetiology Sensorineural Sensory Neural Conductive (obstructive) Proportion 30% Nasal disease (CRS, polyps) 30% Post-URTI/Viral 30% undetermined 10% others

Aetiology : 

Aetiology Sensorineural Sensory: URTI, head trauma, iatrogenic, tumour, congenital Neural: MS, Parkinson, Alzheimer, Schizophrenia Tumour Epilepsy

Aetiology : 

Aetiology Sensorineural Causes Parkinson, Alzheimer, Multiple sclerosis Schizophrenia, epilepsy Olfactory dysfunction can be an early sign of dementia Tumour: frontal, temporal lobe tumours Epilepsy: Temporal lobe epilepsy: unilateral nostril

Aetiology : 

Aetiology Conductive Obstructive Polyps, tumours Transport problems Mucus secretion

Aetiology : 

Aetiology Conductive Rhinitis, polyps, CRS CRS conductive and sensorineural Local inflammatory toxicity Impaired ciliary motility Biopsy shows early apoptosis of olfactory epithelium in CRS

Aetiology : 

Aetiology Tumours Olfactory neuroblastoma Granulomatous disease Wegener’s, syphilis, sarcoidosis Laryngectomy Retronasal stimulation? Nasal mucosa dryness Sjogren syndrome, atrophic rhinitis Side effects of medications anticholinergics

Aetiology : 

Aetiology Congenital Kallmann’s syndrome anosmia + hypogonadism MRI: absent olfactory bulbs Familial anosmia Absent olfactory bulb Bilateral frontonasal menegocele

Aetiology : 

Aetiology URTI (viral) 30% of causes of smell dysfunction 80% in females More common in over 65 30% improve after 6/12 60% improve on long term follow-up The longer the anosmia, the poorer the outcome.

Aetiology : 

Aetiology Toxins Usually permamanet Common toxins Formaldehyde Cyanoacrylates Herbicieds Pesticieds Solvents Cigarette smoke

Aetiology : 

Aetiology Iatrogenic Nasal surgery Superior meatus polypectomy Over-resection of sup/middle turbinates

Aetiology : 

Aetiology Trauma Head trauma induced smell loss 10-15% in adults 1-3% in paeds Pathophysiology Shearing of the olfactory axons Brain contusion Onset Mostly immediate Delayed (months after injury)

Aetiology : 

Aetiology Trauma Recovery after trauma 10% smell returns but diminished Regenerates but cannot find the cribriform perforations to reach the bulb

Aetiology : 

Aetiology Vitamin deficiency Vitamin B deficiency Vit B1 (Thiamine): Korsakoff’s psychosis Vit B3 (Niacin): Pellagra Vit B12: Pernicious anaemia Vitamin A deficiency Zinc deficiency

Aetiology : 

Aetiology Ageing olfactory degeneration after 60 Damage to olfactory receptors Decrease in glomeruli Occlusion of cribriform plate foramina Medication Antibiotics Anti-inflammatory Anti-hypertensive Anti-metabolite Anti-depressant Anti-convulsant

Aetiology : 

Aetiology Medication Mostly the underlying condition for which the medication was given is the the culprit. Antibiotics Ampicillin Azithromycin Ciprofloxacin Clarithromycin Metronidazole Tetracycline

Aetiology : 

Aetiology Anticonvulsant Carbamazepaine Phenytoin Antidepressant Amitriptyline Imipramine Antimanic Lithium

Aetiology : 

Aetiology Cardiac/Blood pressure medication Amidarone Captopril Diltiazem Enalapril Nifedipne Propranalol Sprinolactone

Aetiology : 

Aetiology Anti-inflammatory Beclomethasone Dudesonide Colchicine Fluticasone Hydrocortisone Penicillamine

Aetiology : 

Aetiology Others: Anti-migraine Anti-neoplastic Cisplatin Methotrexate Anti-psychotic Anti-thyroid Methimazole

Aetiology : 

Aetiology Endocrine Hypothyroidism Addison’s disease Cushing’s disease Diabetes

Management : 

Management History Examination Investigation Smell tests Imaging Blood tests Treatment Counselling

History : 

History Detailed history Taste or smell? Degree of loss Anosmia? Hyposmia? Length of problem Sudden onset or gradual? Constant or fluctuating Fluctuation common in rhinitis/nasal cycle Any initiating factor? Head trauma, URTI, start of a new medication

History : 

History Any other nasal symptoms Nasal blockage, epistaxis What was the smell like before? Congenital/familial causes PMH: Surgery, CRF, hypothyroidism, diabetes, seizure List of medication Family history Social history Jobs: fire-fighter, cooks Hobby: wine taster

Clinical Examination : 

Clinical Examination ENT Nasendoscopy Mini-Mental state examination Olfactory testing

Olfactory Tests : 

Olfactory Tests Olfactory tests to Threshold test Identification test Discrimination test

Olfactory Tests : 

Olfactory Tests Two general types Psychophysical testing: clincial Electrophysiologic testing: research The above tests do not differentiate between central and peripheral causes

Olfactory testing : 

Olfactory testing Psychophysical testing Quantitative tests: Olfactory threshold test Finding the threshold Odour identification/discrimination test Supra-threshold test

Olfactory threshold testing : 

Olfactory threshold testing Lowest concentration of odourant detected Phenyl ethyl alcohol (PEA) as stimulant Two common ways to present the stimulus Ascending method of limits Increasing concentration of PEA presented with bottle of water until stimulus detected Single staircase More reliable and more often used Increasing dose to detection and reducing afterwards

Identification - Discrimination : 

Identification - Discrimination Supra-threshold forced test UPSIT CCSIT Sniffin’ Sticks Alcohol Sniff Test

UPSIT : 

UPSIT Identification test Doty 1984 Suprathreshold test Forced response 4-99 year olds 4 scratch and sniff booklets Each booklet has 10 micro-encapsulated odourants Normal data based on 4000 people UPSIT score =< 6: probably malingering

CCSIT : 

CCSIT Cross-cultural smell identification tests Variant of UPSIT 12 items Contains internationally known odourants

UPSIT v CCSIT : 

UPSIT v CCSIT

Sniffin’ Sticks : 

Sniffin’ Sticks Kobal and Hummel 1996 Mostly used in Europe Needs medical assistance Contains: One threshold test Stimulant: n-butanol Two supra-threshold tests Discrimination Identification

Combined Olfactory Test : 

Combined Olfactory Test Robson 1996 Odour recognition of 9 odours Forced choice (1:4) Followed by threshold testing Series of three-fold dilutions of butanol Validated for UK

Alcohol Sniff Test : 

Alcohol Sniff Test Davidson1997 Distance from the nose when the alcohol pad can be detected Normal > 20cm Hyposmia 2-20cm

Miscellaneous tests : 

Miscellaneous tests UPSIT modifications Pocket Smell Test (PST) Quick Smell Identification Test (Q-SIT) Zurich Test Smell Diskette Olfaction Test CCCRC Connecticut chemosensory clinical Research centre

Electrophysiologic testing : 

Electrophysiologic testing Electro-olfactogram Electrodes on olfactory mucosa Odour event-related potentials Electrodes on scalp Good for detecting malingering Functional MRI Areas of brain activity in response to odour

Imaging : 

Imaging CT Sinus MRI brain Central lesion: frontal/temporal lobe Absence of olfactory bulb (Kallmann) Ordinary MRI protocol will not detect olfactory bulb abnormalities UK survey 73% use CT 37% use MRI

Blood tests : 

Blood tests Vitamin B B12 Zinc FBC anaemia

Treatment : 

Treatment Treat the cause Most conductive causes are treatable Vitamin deficiency Traumatic Allow regeneration (15-40%) Unknown aetiology Vit A, B and Zinc supplement? No benefit in Zinc therapy Most treatment studies are case reports with no control

Treatment : 

Treatment Systemic steroids possibly work as long as given for: Nasal polyps/CRS URTI Idiopathic Trial as a diagnostic tool Stop the offending factor Medication Exposure to toxins Prevent iatrogenic causes Conservative surgery

Health Warning/Counselling : 

Health Warning/Counselling Smoke Fire safety Gas Food Spoiled food Decrease in consumption (elderly) Flavour enhancer/food colouring Salt Adding salt for taste; hypertension Psychological/OCD Bathing too much! Emotional/Sexual behaviour

Sense of Taste : 

Sense of Taste Gustatory deficit Aetiology Anatomy Physiology Management

Gustatory System : 

Gustatory System Of smell disorder presentations only 5% are proved to have gustatory deficit Degrees of impairment Ageusia: no tatse Hypogeusia: reduced taste Dysgeusia: altered Parageusia: with stimulus Phantgeusia: without stimulus

Taste and Smell : 

Taste and Smell 80% of food taste is perceived by olfaction Flavour is combined taste and smell Flavour: retronasal stimulation of olfaction

Aetilogy : 

Aetilogy Oral pathology Viral, Bacterial, fungal infections Mucositis Poor oral hygiene Ageing Central, middle ear and infra-temporal lesions/pathology involving the corda tympani and glossopharyngeal nerve

Aetiology : 

Aetiology Iatrogenic Damage to corda tympani Middle ear surgery Damage to IX Tonsillectomy Tumours Glomus tumour

Aetiology : 

Aetiology Systemic disease Diabetes neuropathy Renal failure Uremic toxins: improves after dialysis

Anatomy : 

Anatomy Taste buds are on tongue, pharynx, larynx and soft palate Taste buds contain three types of cells: Receptor cells Basal cells Edge cells

Anatomy : 

Anatomy There are three types of taste buds: Fungiform (anteiror 2/3) Foliate (lateral edges) Circumvallate (border of posterior 1/3) Filliform papillae do not have taste buds

Physiology : 

Physiology Taste molecules transport through saliva to reach taste receptor cells Main taste qualities: Salt Sweet Bitter Acid Umami (elicited by glutamate)

Physiology : 

Physiology All taste buds can perceive all tastes. There is no taste-specific locations on tongue

Gustatory Innervation : 

Gustatory Innervation Taste receptors are innervated by: VII, IX, X GSPN innervates taste buds on soft palate IX fibres are more responsive to sour and bitter VII fibres are more responsive to sweet and salty

Gustatory Innervation : 

Gustatory Innervation VII nerve Anterior tongue taste buds > lingual nerve > petrotympanic suture > middle ear > corda tympani > VII > Geniculate ganglion (cell body)> nervus intermedius > solitary tract (superior salivary nucleus)

Gustatory Innervation : 

Gustatory Innervation IX nerve Posterior tongue taste buds > inferior IX ganglion > IX > solitary tract (inferior salivary nucleus) X nerve Hypopharynx taste buds > internal branch of superior laryngeal nerve > inferior vagal (nodose) ganglion > solitary tract nucleus

Taste Physiology : 

Taste Physiology Stimulant > taste receptor > influx of Ca++ > release of neurotransmitter (unknown) > primary afferent neuron Different transduction methods for different tastes (unclear in human)

Central Taste Pathway : 

Central Taste Pathway Nerve fibres > Parabrachial nucleus in pons (other links) > thalamus > cortex Gustatory pathway is entirely ipsilateral

Taste Evaluation : 

Taste Evaluation Do smell test first! Taste tests Quality NaCl, Sucrose, Citric acid and quinine/coffee Intensity Differences between right and left of the tongue assessed for different concentrations

Taste Evaluation : 

Taste Evaluation Magnitude matching Comparing magnitude of hearing stimulus to concentration of the taste stimulant Patient should have normal hearing Hypogeusic patients perceive the noise louder Spatial testing Different taste applicators applied on tongue Patient should identify the quality and rate the intensity (1-10) Taste Sticks/tablets

Taste Evaluation : 

Taste Evaluation Electrogustometry Weak electrical stimulus Resembling sour taste Provides qualitative control of the stimulus Not suitable to assess the quality of non-sour taste

Treatment : 

Treatment Treat smell deficiency Nasal pathology Oral hygiene Improve saliva Treat any cause found Tumours? Mucositis Dehydration

Quiz Answers : 

Quiz Answers

Quiz 1 : 

Quiz 1 The primary olfactory neuron cell body lies in: Olfactory bulb Olfactory mucosa Frontal cortex Dura

Quiz 2 : 

Quiz 2 Smell of ammonia is detected through: Cranial nerve I Cranial nerve V Cranial nerve VII Cranial nerve IX

Quiz 3 : 

Quiz 3 Approximately, how many genes encode olfactory receptor proteins? 100 1000 10,000 1000,000

Quiz 4 : 

Quiz 4 An odourant specific anosmia is caused by mutation in a gene encoding: Olfactory G-protein Cyclic AMP Calcium/Sodium channel Olfactory receptor protein

Quiz 5 : 

Quiz 5 Which one would perform better in odorant identification tests? A 38-year-old man A 40 year-old woman A 5-year-old boy A 67-year-old woman

Quiz 6 : 

Quiz 6 A 40-year-old woman complains of total anosmia after a head cold for the past 6 years. There is no other symptoms (including nasal symptoms) and the cranial nerve and nasal examination is normal. What is the next step? MRI of brain High does steroids CT scan of nasal sinuses Counsel on hazards of anosmia

Quiz 7 : 

Quiz 7 Name four health risks associated with total anosmia (advice to patients)? Fire smoke Gas alarm Spoiled food Adding salt to food OCD (washing)

Quiz 8 : 

Quiz 8 How many choices are correct? The olfactory mucosa is present on the: Septum Cribriform plate Middle turbinate Inferior turbinate

Quiz 9 : 

Quiz 9 What kind of an olfaction test is an UPSIT regarded as? Threshold testing Quantification test Identification test Discrimination test

Quiz 10 : 

Quiz 10 What does a score of 5 mean in an UPSIT score range? Normal sense of smell Mild anosmia Possible malingering UPSIT score is not a numerical one.

Quiz 11 : 

Quiz 11 Which one does not have taste buds: 1) fungiform papillae 2) circumvallate papillae 3) filliform papillae 4) foliate papillae

Quiz 12 : 

Quiz 12 Which is the central olfactory route from olfactory bulb? 1) directly to cortex 2) through thalamus 3) through hippocampus 4) through hypothalamus

Quiz 13 : 

Quiz 13 True or False? Olfactory epithelium can regenerate Vagus is involved in gustatory reception Greater superficial petrosal nerve innervates taste buds on the palate Central gustatory pathway is entirely ipsilateral Epilepsy could cause unilateral anosmia Olfactory receptor cells are the only CNS cells exposed to outside directly

Quiz 14 : 

Quiz 14 Where does the facial nerve afferent taste cell body lie? Submandibular ganglion Otic ganglion Pterygopalatine ganglion Geniculate ganglion

Quiz 15 : 

Quiz 15 How do you manage a 30 year-old referred by his solicitor complaining about anosmia after a car accident? History Examination Validate the claim Quantitative assessment Investigation Treatment Counselling

Questions? : 

Questions?

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