Dysosmia is a disorder described as any qualitative alteration or distortion of the perception of smell. Qualitative alterations differ from quantitative alterations, which include

anosmia Anosmia, also known as smell blindness, is the loss of the ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells. Anosmia can be due to a num ...

and

hyposmia Hyposmia, or microsmia, is a reduced ability to smell and to detect odors. A related condition is anosmia, in which no odors can be detected. Some of the causes of olfaction problems are allergies, nasal polyps, viral infections and head trauma. ...

. Dysosmia can be classified as either

parosmia Parosmia (from the Greek παρά ''pará'' and ὀσμή ''osmḗ'' "smell") is a dysfunctional smell detection characterized by the inability of the brain to correctly identify an odor's "natural" smell. Instead, the natural odor is usually tr ...

(also called troposmia) or

phantosmia Phantosmia (phantom smell), also called an olfactory hallucination or a phantom odor, is smelling an odor that is not actually there. It can occur in one nostril or both. Unpleasant phantosmia, cacosmia, is more common and is often described as s ...

. Parosmia is a distortion in the perception of an odorant. Odorants smell different from what one remembers. Phantosmia is the perception of an odor when no odorant is present. The cause of dysosmia still remains a theory. It is typically considered a

neurological disorder A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakn ...

and clinical associations with the disorder have been made. Most cases are described as

idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...

and the main antecedents related to parosmia are URTIs,

head trauma A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inju ...

, and nasal and paranasal sinus disease. Dysosmia tends to go away on its own but there are options for treatment for patients that want immediate relief.

Signs and symptoms

Smell disorders can result in the inability to detect environmental dangers such as gas leaks, toxins, or smoke. In addition to safety, nutritional and eating habits can also be affected. There is a loss of appetite because of unpleasant flavor and fear of failing to recognize and consuming spoiled food. A decreased or distorted sense of smell therefore results in a decreased quality of life. Distortions are believed to have a greater negative impact on people than the complete loss of smell because they are constantly reminded of the disorder and the distortions have a greater effect on eating habits.

Classification and terminology

Olfactory dysfunction can be quantitative and/or qualitative. Quantitative smell disorders are disorders in which there is complete or partial loss of olfaction.

Anosmia Anosmia, also known as smell blindness, is the loss of the ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells. Anosmia can be due to a num ...

, the complete loss of olfaction, and

, the partial loss of olfaction are the two disorders classified as quantitative because they can be measured. Qualitative smell disorders cannot be measured and are disorders in which there is alternation or distortion in the perception of smell. Qualitative disorders include parosmia (also called troposmia) and phantosmia. Dysosmia is a qualitative olfaction disorder and includes both parosmia and phantosmia. Olfactory dysfunction including anosmia, hyposmia, and dysosmia can be either bilateral or unilateral on either nostril. Anosmia only on the left nostril would be termed unilateral left anosmia while bilateral anosmia would be termed total anosmia. If the distortion is unpleasant, the disorder can be referred to as cacosmia. Under an alternative definition, ''cacosmia'' is used for an unpleasant perception of an odorant due specifically to nasosinusal or pharyngeal infection. The rare term torquosmia can be used when the perceived smell is chemical, burning or metallic.

Parosmia

Parosmia Parosmia (from the Greek παρά ''pará'' and ὀσμή ''osmḗ'' "smell") is a dysfunctional smell detection characterized by the inability of the brain to correctly identify an odor's "natural" smell. Instead, the natural odor is usually tr ...

is a distortion in the perception of an odorant. Odorants smell different from what one remembers.

Phantosmia

Phantosmia is the perception of an odor when there is no odorant present. When a phantom smell lasts less than a few seconds, the term

olfactory hallucination Phantosmia (phantom smell), also called an olfactory hallucination or a phantom odor, is smelling an odor that is not actually there. It can occur in one nostril or both. Unpleasant phantosmia, cacosmia, is more common and is often described as s ...

can be used.

Cause

Even though the causes of dysosmia are not yet clear, there are two general theories that describe the etiology: the peripheral and central theories. In parosmia, the peripheral theory refers to the inability to form a complete picture of an odorant due to the loss of functioning olfactory receptor neurons. The central theory refers to integrative centers in the brain forming a distorted odor. In phantosmia, the peripheral theory refers to neurons emitting abnormal signals to the brain or the loss of inhibitory cells that are normally present in normal functioning. The central theory for phantosmia is described as an area of hyper-functioning brain cells that generate the order perception. Evidence to support these theories include findings that for the majority of individuals with distortions, there is a loss of sensitivity to smell that accompanies it and the distortions are worse at the time of the decreased sensitivity. It has been reported in parosmia cases that patients can identify triggering stimuli. Common triggers include gasoline, tobacco, coffee, perfume, fruits and chocolate. The cause of dysosmia has not been determined but there have been clinical associations with the neurological disorder: *

Upper respiratory tract infection An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the nose, sinuses, pharynx, larynx or trachea. This commonly includes nasal obstruction, sore throat, t ...

(URTIs) * Nasal and paranasal sinus disease * Toxic chemical exposure * Neurological abnormalities *

Head trauma A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inju ...

* Nasal surgery * Tumors on the frontal lobe or olfactory bulb *

Epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

Most of cases are described as idiopathic and the main antecedents related to parosmia are URTIs, head trauma, and nasal and paranasal sinus disease. Psychiatric causes for smell distortion can exist in

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

, alcoholic psychosis, depression, and

olfactory reference syndrome Olfactory reference syndrome (ORS) is a psychiatric condition in which there is a persistent false belief and preoccupation with the idea of emitting abnormal body odors which the patient thinks are foul and offensive to other individuals. People w ...

Pathophysiology

Anatomy and physiology

Olfactory receptors

The olfactory neuroepithelium, located in the roof of the nasal chambers, comprises bipolar receptor cells, supporting cells, basal cells, and brush cells. There are approximately 6 million bipolar sensory receptor neurons whose

cell bodies The soma (pl. ''somata'' or ''somas''), perikaryon (pl. ''perikarya''), neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. The word 'soma' comes from the Greek '' σῶ� ...

and

dendrites Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...

are in the epithelium. The axons of these cells aggregate into 30-40 fascicles, called the olfactory fila, which project through the cribriform plate and pia matter. These axons collectively make up the

olfactory nerve The olfactory nerve, also known as the first cranial nerve, cranial nerve I, or simply CN I, is a cranial nerve that contains sensory nerve fibers relating to the sense of smell. The afferent nerve fibers of the olfactory receptor neurons tr ...

(

CN I The olfactory nerve, also known as the first cranial nerve, cranial nerve I, or simply CN I, is a cranial nerve that contains sensory nerve fibers relating to olfaction, the sense of smell. The afferent nerve fibers of the olfactory receptor ...

) and serve the purpose of mediating the sense of smell. Characteristics of the bipolar receptor neurons include

cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

on the dendritic ends which project into the mucus, regeneration from basal cells after damage, and each receptor neuron is also a first order neuron. The first order neurons project axons directly from the nasal chamber to the brain. Its first neuron characteristic allows direct exposure to the environment, which makes the brain vulnerable to infection and invasion of

xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

agents. Supporting cells, called

sustentacular cell A sustentacular cell is a type of cell primarily associated with structural support, they can be found in various tissues. * Sustentacular cells of the olfactory epithelium (also called supporting cells) have been shown to be involved in the phag ...

s, provide metabolic and physical support to the receptors by insulating the cell and regulating the composition of the mucus. Basal stem cells give rise to both neurons and non-neuronal cells and allow for constant regeneration of receptor cells and its surrounding cell.

Olfactory transduction

Olfactory transduction The olfactory system, or sense of smell, is the sensory system used for smelling ( olfaction). Olfaction is one of the special senses, that have directly associated specific organs. Most mammals and reptiles have a main olfactory system and an a ...

begins with the movement of odorants from the air phase to the aqueous phase in the olfactory mucus. Odorants are transported by odorant binding proteins or diffuse through the mucus and reach the cilia on the dendritic ends of bipolar receptor neurons. Stimulation causes

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

s to be initiated and the signals are sent to the brain via the olfactory fila.

Olfactory bulb

Olfactory receptor neuron axons project through the

cribriform plate In mammalian anatomy, the cribriform plate (Latin for lit. ''sieve-shaped''), horizontal lamina or lamina cribrosa is part of the ethmoid bone. It is received into the ethmoidal notch of the frontal bone and roofs in the nasal cavities. It supp ...

to the

olfactory bulb The olfactory bulb (Latin: ''bulbus olfactorius'') is a grey matter, neural structure of the vertebrate forebrain involved in olfaction, the sense of odor, smell. It sends olfactory information to be further processed in the amygdala, the orbitof ...

. The olfactory bulb is a structure at the base of the frontal lobe. It comprises neurons, nerve fibers,

interneurons Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. In ...

microglia Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for about 7% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune de ...

astrocytes Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...

, and

blood vessels The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...

. It is made up of 6 layers: olfactory nerve layer, glomerular layer, external plexiform layer, mitral cell layer, internal plexiform layer, and granule layer. The terminals of the receptor axons synapse with the dendrites of mitral and tufts cells within the

glomeruli ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...

of the olfactory bulb. The axons of the mitral and tufts cells send signals to the olfactory cortex.

Olfactory cortex

Signals from odor sensation are sent from the olfactory bulb through

mitral The mitral valve (), also known as the bicuspid valve or left atrioventricular valve, is one of the four heart valves. It has two cusps or flaps and lies between the left atrium and the left ventricle of the heart. The heart valves are all one-w ...

and tufts cell axons via the lateral olfactory tract and synapse at the primary olfactory cortex. The

primary olfactory cortex The primary olfactory cortex (POC) is a portion of the cerebral cortex. It is found in the inferior part of the temporal lobe of the brain. It receives input from the olfactory tract. It is involved in the sense of smell (olfaction). Structure ...

includes the anterior olfactory nucleus, the piriform cortex, the anterior cortical nucleus of the

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...

, the periamygdaloid complex, and the rostral entorhinal cortex. A unique characteristic of olfaction is its independence from the

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...

. The odor signals are sent directly from the sensory receptor neuron to the primary cortex. However, communication between the primary and secondary olfactory cortex requires connections with the thalamus.

Odor perception

Odor identity, quality, and familiarity are mainly deciphered by the

piriform cortex The piriform cortex, or pyriform cortex, is a region in the brain, part of the rhinencephalon situated in the cerebrum. The function of the piriform cortex relates to the sense of smell. Structure The piriform cortex is part of the rhinencephalo ...

. Consciousness of smell is achieved by projections from the piriform cortex to the medial dorsal nucleus of the thalamus and to the orbitofrontal cortex, which the secondary olfactory cortex is part of. There are approximately 1,000 olfactory receptors coded for in the

human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...

. Less than 500 receptors are functional in the nasal epithelium. Each receptor neuron is a single type of olfactory receptor and is not specific to any one odorant. An odorant is recognized by more than one type of receptor and thus odorants are recognized by a combination of receptors. The olfactory system relies on different excitation patterns to obtain different codes for different odorants. Nobel prize recipient

Linda B. Buck Linda Brown Buck (born January 29, 1947) is an American biologist best known for her work on the olfactory system. She was awarded the 2004 Nobel Prize in Physiology or Medicine, along with Richard Axel, for their work on olfactory receptors. She ...

compared this system to combining different letters of the alphabet to produce different words. In this case, each word represents an odor. This coding explains why we can detect more odors than there are receptors in the nasal epithelium.

Olfaction and flavor

Flavor is perceived by the combination of the sense of taste, sense of smell, and the

trigeminal nerve In neuroanatomy, the trigeminal nerve ( lit. ''triplet'' nerve), also known as the fifth cranial nerve, cranial nerve V, or simply CN V, is a cranial nerve responsible for sensation in the face and motor functions such as biting and chewin ...

(CN V). The

gustatory system The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...

is responsible for differentiation between sweet, sour, salty, bitter, and

umami Umami ( from ja, 旨味 ), or savoriness, is one of the five basic tastes. It has been described as savory and is characteristic of broths and cooked meats. People taste umami through taste receptors that typically respond to glutamates and ...

. The olfactory system recognizes the odorants as they pass to the olfactory epithelium via a retronasal pathway. This explains why we can identify a variety of flavors in spite of only having five types of taste receptors. The

senses texture, pain, and temperature of food, and related qualities such as the cooling effect of menthol or the burning sensation of spicy food.

Diagnosis

Diagnosing dysosmia precisely can be difficult due to the variety of causes and symptoms. Often, patients may be unsure whether or not they are having issues with smell or taste specifically. It is important to identify whether the distortion applies to an inhaled odorant or if an odor exists without the stimulus. Distortion of an odorant is presented in two types: when the stimuli are different from what one remembers, and when everything has a similar smell. A clinical history can also help determine what kind of dysosmia one has, as events such as respiratory infection and head trauma are usually indications of parosmia. Phantosmia often occurs spontaneously. Unfortunately, there are no wholly accurate diagnostic tests or methods for dysosmia.; evaluation must be done through questionnaires and medical history.

Treatment

Even though dysosmia often goes away on its own over time, there are both medical and surgical treatments for dysosmia for patients who want immediate relief. Medical treatments include the use of topical nasal drops and oxymetazoline HCL, which give an upper nasal block so that the air flow can't reach the olfactory cleft. Other medications suggested include sedatives, anti-depressants, and anti-epileptic drugs. The medications may or may not work and for some patients, and

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s may not be tolerable. Most patients benefit from medical treatment, but for some, surgical treatment is required. Options include a bifrontal craniotomy and excision of the olfactory epithelium, which cuts all of the fila olfactoria. According to some studies, transnasal endoscopic excision of the olfactory epithelium has been described as a safe and effective phantosmia treatment. The Bifrontal craniotomy results in permanent anosmia, and both surgeries are accompanied with the risks associated with general surgery.

Epidemiology

The frequency of phantosmia is rare in comparison with the frequency of parosmia. Parosmia has been estimated to be in 10-60% of patients with olfactory dysfunction and from studies, it has been shown that it can last anywhere from 3 months to 22 years. Smell and taste problems result in over 200,000 visits to physicians annually in the US. Lately, it has been thought that phantosmia might co-occur with

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

. However, its potential to be a premotor biomarker for Parkinson's is still up for debate as not all patients with Parkinson's disease have olfactory disorders

References

External links

{{Medical resources , ICD10 = {{ICD10, Xxx.x , ICD9 = {{ICD9, xxx , ICDO = , OMIM = , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = Symptoms and signs: Nervous system Olfactory system