Phantosmia

Animation: human left temporal lobe (right side similar).

Phantosmia is an olfactory hallucination. A hallucination is the sensory perception of something with no basis in reality, as opposed to an olfactory illusion, which is a misinterpretation of a physical stimulus; in the case of an odor it is known as parosmia. Phantosmia is the perception of a smell in the complete absence of any physical odor. The perceived odor can range from pleasant to disgusting. Although the causes of phantosmia are uncertain, it often occurs with neurological and psychological disorders such as schizophrenia, mood disorders, Parkinsons disease, epilepsy, neuroblastoma, and frequent migraines.

Galen also mentioned olfactory hallucinations in his work and stated that these hallucinations constitute the signs of an oncoming disease.

Different types of phantosmia include: Unirhinal (single nostril), episodic, and recurrent, where the activation of brain's GABAergic system seems to play a role in the inhibition of the unirhinal phantosmia.[1]

Treatments for phantosmia range from drug therapies (e.g., venlafaxine) and brain stimulation therapies to invasive surgical procedures involving removal of the olfactory bulbs or olfactory epithelium.

The word phantosmia is a noun of Greek origin. It is composed of two words: (1) phant- meaning "phantom" and (2) -osmia (from osme) meaning "smell".[2]

Olfactory system

The olfactory system is connected to the limbic system and gustatory system. An example of the relation between the systems is the common cold. When an individual suffers from a cold, the abilities to smell and taste are co-affected. Furthermore, the smells of food tell people if the food item is safe to consume or not; foods with unpleasant smells may be poisonous or harmful. So the sense of smell warns them away before they taste the food, or it cautions them to taste carefully, to confirm what the smell has already told us. Although this relationship exists, the olfactory system is not affected by the gustatory system. The two systems are independent and have different neuronal pathways to the brain. It is thought that the olfactory and gustatory systems were originally one and became defined and distinct over time.

Odors have a strong influence on the cerebrum where the emotions are seated; thus olfaction is also related to the limbic system. The olfactory system gave rise to the limbic system. It has also been found that the olfactory and limbic systems have evolved into two different structures known as the olfactory stratium and the corpus stratium. In a study done by Dr. Alan Hirsch, it was found that gamblers spent 33–55% more money and time gambling when they were exposed to a certain odor compared to those that were not exposed to the odor.[3]

The limbic system structures that are responsible for memory, the hippocampus and the amygdala, are part of the rhinencephalon. The nerve fibre that connects the olfactory mucosa to the olfactory bulb ends in this region of the brain.

The olfactory bulb is composed of several million neurons. All olfactory messages from the olfactory limbic system are received there and are carefully organised. After this the message or signal is transmitted to other regions of the brain. Insects do not have an olfactory bulb. The olfactory nerve is composed of nasal nerve cells. These nerves link the nose and the olfactory bulb together. Accidents, damage due to surgery, infections and brain tumors may damage or destroy the olfactory nerve; this will cause the patient to lose the ability to smell and taste. This can also occur if the olfactory bulb or olfactory tract is destroyed. The olfactory tract is composed of many axons that connect the olfactory bulb and other limbic brain regions as well as temporal lobe.[3]

Chemoreceptors

Chemoreceptors play a major role in the olfactory system, as they are responsible for signalling the nervous system that a change has occurred in the body. Chemoreceptors help organisms identify and distinguish between different odors due to their different distinct molecular structures. Two odorant molecules may seem to have the same shape and size, however they result in different sensations and they act on different parts of the neurons in the olfactory system. Examples of different types of common odors are benzaldehyde (Marzipan), vanillin (vanilla), and Anisole (Aniseed). Humans have the ability to distinguish more than five thousand different odorants because humans possess many unique olfactory receptor proteins (ORs).[4]

Pheromones

Pheromones play a critical role in determining the behaviour of humans and other animals. This is evident as airborne or waterborne pheromones can be used by one member of a species to affect the behaviour of their sexual partner. Pheromones have a different and fixed structure. Furthermore, they have specific receptors that are different from ORs. The vomeronasal organ (olfactory sense organ) is responsible for the sensing of pheromones in mammals. The structure of this organ is very similar to the olfactory system.[4]

Olfactory receptor proteins

Olfactory receptor proteins possess seven hydrophobic intermembrane domains. Furthermore, ORs are a part of the G protein coupled receptor family. This family of proteins further subdivides into categories. For example there are the third, fourth and fifth membrane spanning domains and they are known to bind to specific odor molecules. There are approximately one thousand different ORs that are translated from their own unique genes. This genetic material is approximately one percent of the genome of a vertebrate.[4]

Olfactory perception

Human olfactory system. 1: Olfactory bulb 2: Mitral cells 3: Bone 4: Nasal epithelium 5: Glomerulus (olfaction) 6: Olfactory receptor cells

Olfaction is the sense of smell. Humans and most other land mammals have receptors in the nasal chambers that detect molecules coming into the nose and send signals to the brain. The main component of the olfactory system is the olfactory cranial nerve, or CN I. CN I is responsible for interpreting typical odor sensations and has a large impact on our sense of taste. The upper portion of the nasal chambers contain the sensory receptors responsible for olfaction, and are situated in a neuroepithelium which lines the cribriform plate. Once the cells in the neuroepithelium detect a stimulus, a signal is sent up the cranial nerve and travels to the olfactory bulbs in the brain where the initial processing of olfactory information occurs. The rest of the olfactory processing is done in the rest of the olfactory cortex.[5]

Causes

The cause of phantosmia can either be peripheral or central, or a combination of the two. The peripheral explanation of this disorder is that rogue neurons malfunction and transmit incorrect signals to the brain or it may be due to the malfunction of the olfactory neurons.[6] The central explanation is that active or incorrectly functioning cells of the brain cause the perception of the disturbing odor. Another central cause is that the perception of the phantom odor usually follows after the occurrence of seizures. The time span of the symptoms usually lasts a few seconds [7]

Other studies on phantosmia patients have found that the perception of the odor initiates with a sneeze, thus they avoid any nasal activity. It has also been found that the perception of the odor is worse in the nostril that is weaker in olfaction ability. It has also been noted that about a quarter of patients suffering from phantosmia in one nostril will usually develop it in the other nostril as well over a time period of a few months or years.[8]

Several patients who have received surgical treatment have stated that they have a feeling or intuition that the phantom odor is about to occur, however it does not. This sensation has been supported by positron emission tomography, and it has been found that these patients have a high level of activity in their contralateral frontal, insular and temporal regions. The significance of the activity in these regions is not definitive as not a significant number of patients have been studied to conclude any relation of this activity with the symptoms. However the intensity of the activity in these regions was reduced by excising the olfactory epithelium from the associated nasal cavity.[7]

There are a few causes for phantosmia, but one of the most common and well-documented involves brain injury or seizures in the temporal lobe. During a temporal lobe seizure the victim rarely faints, but usually blacks out and cannot remember anything that happened during the seizure. Several people who have had these seizures did, however, recollect having phantosmia just prior to blacking out. Epilepsy is a disease characterized by seizures. In the case of phantosmia, if smelling and something else become so strongly linked, the action of "something else" occurring can induce activation of the olfactory bulb even though there was no stimulus for the bulb present. This is an example of plasticity gone awry. Those with lesions on the temporal lobe, often brought about by a stroke but also from trauma to the head, also experience these olfactory hallucinations.

Other leading causes of phantosmia include neurological disorders such as schizophrenia and Alzheimer's disease. Both of these disorders have well documented cases of hallucinations, most commonly visual and auditory. Both also, however, have instances of phantosmia too, although not as frequently. In both cases, incidences of olfactory delusions are more common, especially in Alzheimer's, where it is exceedingly difficult to convince the patient that these are in fact hallucinations and not real. Specifically in Alzheimer's disease, atrophy in the temporal lobe has been known to occur. As evidenced in trauma and seizures, phantosmia is strongly associated with this area; leading to its appearance in some Alzheimer's patients. Parkinson's disease patients can also experience phantosmia, as well as parosmia, however their appearance is less common than the muscle tremors the patients experience.[9]

Neuroblastoma

Neuroblastoma is a rare form of a malignant cancer that initiates in the olfactory nerve. The olfactory nerve is responsible for smell sensation. This cancer can become aggressive and progress into the ethmoid sinuses, brain cavity, surrounds the cribiform plate. The tumor can be tested by performing a surgical biopsy and the possible treatment options include surgical removal of the tumor, radiation therapy and chemotherapy. This can cause damage to the olfactory system and possibly result in phantosmia.[10]

Diagnosis

The most challenging task for the examiner is to determine and obtain the correct symptoms and associate them with one of the olfactory disorders, as there are several of them and they are related to each other.

The first step the examiner usually takes is to investigate if the problem is olfactory or gustatory related. As it may be that the patient releases certain bodily odors that are causing them to have this perception.[11]

If the examiner is able to confirm that the problem is olfactory related, the next step is to determine which olfactory disorder the patient suffers from. The following is a list of possible olfactory disorders:

The second step is very difficult for both the examiner and the patient as the patient has some difficulty describing their perception of the phantom odor. Furthermore, the patient is in a position of stress and anxiety thus it is crucial that the examiner be patient.

After determining the nature of the disorder, and confirming phantosmia, the examiner must then have the patient describe their perception of the phantom odor. In many cases, patients have described the odor to be that of something burning and rotten and have described it to be unpleasant and foul.

The third step for the examiner is to determine the past history of the patient in terms of if they have had any head trauma, accidents, upper respiratory infections, allergic rhinitis or chronic rhinitis.[12] Although these may be events that have resulted in the phantom odor, studies conducted by Zilstrof have found that the majority of phantosmia patients have no previous history of head trauma and upper respiratory infections.[13]

Development

The complaints of Phantosmia include unpleasant odors most commonly including "burnt", "foul", "rotten", "sewage", "metallic" or "chemical". These odors may be triggered by strong odorants, changes in nasal airflow or even loud sounds, whereas sometimes it occurs spontaneously. Patients having complaints of Phantosmia self-admit a poor quality of life, with each meal having the unpleasant odor as well. The disorder's first onset, usually spontaneous, lasts only a few minutes. Its recurrences are then gradually increased from monthly, then weekly, and then daily over a period of 6 months to a year. The duration of the perceived odor also increases over same time, often lasting most of a day after 1 year.[14] Some patients also state that the odor they smell is different from any known odor.

Symptoms

Other olfactory disorders such as hyposmia and anosmia have been found to be a symptom of mood disorders (depression). However, it is not known what olfactory disorders occur and if they are indeed a symptom of a depressive disorder.[15] It has been found that phantosmia may be an early sign of the neurodegenerative disease: Parkinson's disease.[16] It may also be a sign of an intracranial hemorrhage[17] (brain tumours or epilepsy).[18] Other studies have also found that the symptoms of phantosmia have been alleviated after the patient has been treated for depression.[19][20] Another case of a 70 year old male reported that his first abnormal symptoms were irregular bowel movements. After this the patient developed irregular eye movements and had developed a sleep and behavior disorder after this he developed phatosmia; which was described to be as "stinky and unpleasant". The patient did not display the following symptoms: loss of awareness, confusion, automatisms, convulsive seizures, auditory/visual hallucinations.[8]

Treatment

Due to the rareness of the disorder, there is no well-defined treatment yet. Sometimes the patients are just told to live with the disorder or the patients end up performing "stereotypical methods" that might help in reducing the severity of the odor. This might include forced crying, bending over holding knees while holding breath, rinsing the nose with saline water and gagging. All these behaviours at the end fail to resolve the hallucination. Various treatments like prophylactic have been suggested but more research is needed for its confirmation. Also, due to being a poorly understood disorder, and having analogies to some psychiatric conditions, some patients are told that they have a mental illness. It is also usual for these patients to have suicidal thoughts as they are not provided with much support or hope from many physicians.

One of the Surgical treatments proposed has included olfactory bulb ablation through a bifrontal craniotomy approach.[21][22] But a counter-argument by Leopold, Loehrl and Schwob (2002) has stated that this ablation process results in a bilateral permanent anosmia and includes risks associated with a craniotomy. According to them, the use of transnasal endoscopic exhibition of olfactory epithelium is a safe and effective treatment for patients with unremitting Phantosmia with the olfactory function being potentially spared. It is also cautioned that the surgery is challenging one and is associated with major risks, and that it should be restricted to expertise centres.[14]

On the other hand, many cases have also reported that the strength of their symptoms have decreased with time. (Duncan and Seidan, 1995) A case involving long term phantosmia has been treated with the use of an anti depressive medication by the common name Venlafaxine. The brand name of the drug is Effexor. The relation between mood disorders and phantosmia is unknown, and is a widely researched area. In many cases, the symptoms of phantosmia have been reduced by the use of anti seizure and anti depressants that act on the central and peripheral neurons.

The most commonly used treatment method is the removal of the olfactory epithelium or the bulb by means of surgery to alleviate the patient from the symptoms. Other traditional methods include the use of topical anesthetics (Zilstorff-Pederson, 1995) and use of sedatives [8]

Nasal spray

Many patients seeking a quick form of relief achieved it by rinsing the nose with a saline solution. This treatment option is easily available and can be repeated several times throughout the day to obtain relief. An example of a nasal spray that can be used to alleviate symptoms is Oxymetazoline HCl, which seems to provide relief for a longer time period. The relief achieved by the use of nasal sprays seems to be because it results in the blockage of the nostril that does not allow any air to enter the olfactory cleft.[8]

Topical solutions

Another treatment option is the topical solution of cocaine HCl which also provides relief for a short time period by acting as an anesthetic and desensitizes the nasal neurons. The topical solution is applied on the nostril. This topical solution can have several side effects as it has been found that some patients suffering from troposmia started to show symptoms of phantosmia after its use. Other patients have lost complete function of the nostril where the drug was applied.[8]

Venlafaxine

Structure of Venlafaxine

This anti depressant medication is a serotonin norepinephrine reuptake inhibiter (SNRI). In the case study of a 52-year old female suffering from phantosmia since the past 27 years, a dose of 75 mg/ a day relieved and eliminated her symptoms. The drug was prescribed initially in order to treat her depression.[15]

Gender and occurrence

Phantosmia is most likely to occur in women between the ages of 15 and 30 years. The time of the first hallucination(s) lasts from anywhere from five to twenty minutes. It has also been found that the second hallucination will occur approximately a month later in the same manner as the first. Over time, the length of the hallucination will begin to increase.[7]

Pregnancy

A longitudinal study on pregnant females found that 76% of pregnant females experienced significant changes in gustation and olfaction perception. This was found to be caused and linked to their pregnancy. The study concluded that 67% of the pregnant females had reported a higher level of sensitivity to smell, 17% suffered from an olfactory distortion and 14% suffered from phantosmia; these distortions were very minimal towards the last stages of pregnancy and in the majority were not present post partum. Furthermore, 26% of these participants also claimed that they also experienced an increased sensitivity to foods that were bitter and a decreased sensitivity to salt. These findings suggest that pregnant females experience distorted smell and taste perception during pregnancy.[23] It has also been found that 75% of women alter their diets during pregnancy. Further research is being conducted to determine the mechanism behind food cravings during pregnancy.[24]

Co-occurrence with other disorders

Phantosmia has been found to co-exist in patients with other disorders such as: schizophrenia, epilepsy, alcoholic psychosis, and depression. It has also been found that many patients may began to suffer from depression after the occurrence of phantosmia and have looked towards committing suicide. The occurrence of depression resulted from the severe symptoms of phantosmia as everything even food smelled spoilt, rotten and burnt for these patients.[8] By the age of 80, 80% of individuals develop an olfactory disorder. As well 50% of these individuals suffer from anosmia.[25]

Parkinson's disease

Earlier studies suggested that Phantosmia might be one of the late complications of Parkinson's disease.[26]

However recent studies have suggested that Phantosmia occurs early in the development of the disease and usually precedes the motor symptoms by several years.[27] In the event where later suggestion is correct, then according to some researchers, Phantosmia can be used as a premotor biomarker of Parkinson's disease, for the prediction of the development of Parkinson's of in risk populations.[28][29] There are however contradictions to this argument present as well.

It should be noted that not all patients of Parkinson's disease exhibit Phantosmia. Only one half of the patients suffering from anosmia and hyposmia perceive their deficit, even when they are specifically asked to do so.[16] According to a study by Doty et all, 72% of the patients with olfactory disorders are not aware of their deficit,[27] hence making it harder for physicians and specialists to truly rely on the reliability of Phantosmia as a biomarker.

Migraines

In 2011 Coleman, Grosberg and Robbins did a case study on patients with olfactory hallucinations and other primary headache disorders. In their 30 months long study, the prevalence rates for Phantosmia turned out to be a low as 0.66%.

In their findings, it was observed that a typical hallucination period was of 5–60 minutes, occurred either before or with the onset of head pain, and typically consisted of an unpleasant odor. It was also noted that Phantosmia occurs most commonly among women having a migraine complaint.[30] In their study, prophylactic therapy for headaches helped cure Phantosmia in most of the patients.

This finding is consistent with the findings of Schreiber and Calvert in 1986 which also mentioned the olfactory hallucinations before the occurrence of a migraine attack in four of their subjects.[31]

Case studies

Surgical treatment with the preservation of olfactory ability

A 26-year-old woman was diagnosed with mononucleosis at the age of 18. After this diagnosis she began to experience headaches on the right side of her head, and phantosmia in her left nostril that would often occur together. The olfactory hallucination reported by the woman was an unpleasant mixture of vinegar, fecal material, and rotten eggs. This would happen every day beginning in the morning, and the symptoms would worsen during the few days before her menstrual period. If the symptoms did not occur in the morning, they would be triggered by strong olfactory stimuli or by loud noises. Occasionally she could avoid the phantosmia symptoms by forcing herself to sneeze.

The woman consulted many medical practitioners but could not receive a reliable diagnosis. She was prescribed medications including nasal steroid sprays and other drugs, but they would not relieve her of her headaches and phantosmia symptoms. Through chemosensory evaluation, it was found that her senses of smell and taste were working normally. Due to some phantosmias believed to be caused by a blockage causing the odor molecules to not reach the olfactory receptors, doctors surgically widened the olfactory cleft. Unfortunately, the phantosmia symptoms remained. Further unsuccessful treatment included a long-term disruption of the axonal projections from the primary olfactory sensory neurons onto the olfactory bulb. This was accomplished by intranasal irrigation with zinc sulfate.

The patient was successfully treated with a surgical procedure involving permanent disruption of the olfactory epithelium. This was accomplished with the surgical excision of a "plug" of olfactory epithelium from the area of the cribriform plate. This excision was meant to sever all the fila olfactoria entering the central nervous system from her left nostril. 5 weeks after surgery, the woman reported a complete absence of her phantosmia symptoms, and her olfactory ability was maintained (Hornung et al. 1991).[12]

Drug treatment

For a 52-year-old woman, phantosmia occurring as fluctuating episodes occurred for a period of 27 years, and there was no discernible reason for the onset of symptoms. She could weaken the symptoms by rinsing her nose with a saline solution, and by going to sleep. The smells she would encounter often were very unpleasant, resembling a burnt and rotten fruity odor. When her family doctor prescribed her the antidepressant venlafaxine, she noticed that the drug resulted in the complete elimination of her phantosmia symptoms. This discovery has caused scientists and doctors to research if a link between phantosmia and mild depressive disorders exists, and this idea is supported by the reported improvement of phantosmia after repeated transcranial stimulation used to treat depression.[32]

Co-morbidity with Parkinson's disease

Phantosmia symptoms are often seen in patients with Parkinson disease. Sometimes, a patient will report an impaired sense of smell before the onset of the motor symptoms of Parkinson disease. Therefore, phantosmia is often used as a potential marker for the diagnosis of Parkinson disease.

In the case of a 57-year-old woman, strong olfactory sensations were reported, ranging from odors of perfume to slightly unpleasant odors of "wet dog". The episodes experienced would last between seconds and hours and would occur multiple times per day. The patient would report phantosmia symptoms, but would correctly identify known odors and would claim to have no symptoms of smell loss. She had no history of epilepsy, and her electroencephalographic results were normal. Later on, while the symptoms of phantosmia were decreasing, she developed severe symptoms of Parkinson disease. While the patient was treated for her tremors with pramipexole, amantadine hydrochloride, levodopa, carbidopa and entacapone, the phantosmia symptoms disappeared completely.

In the case of a 52-year-old woman, the first symptoms of phantosmia reported appeared to the woman as an increased sense of smell. She believed to have the ability to detect odors before other people, and with better accuracy. She later began to experience the typical symptoms of phantosmia and would smell things that she could recognize in the absence of any odor producing molecules. The reported smells were of perfumes, candles, and fruits, however the woman could not accurately identify what type of perfume or fruit she was smelling. Her phantosmia episodes would occur abruptly and would last from minutes to half an hour. A rhinologic examination came back with normal results. When her phantosmia symptoms began to dissipate, she began to complain of clumsiness, slowness, and problems with her left hand that would alternate between tremors and rigidity. A neurologic examination revealed symptoms of Parkinson's disease.[16]

See also

Related disorders

Other

References

  1. ↑ Levy, L., & Henkin, R. (2000). Physiologically initiated and inhibited phantosmia: cyclic unirhinal, episodic, recurrent phantosmia revealed by brain fmri. Journal of computer assisted tomography, 24(4), 501-520.
  2. ↑ "English Word Information". Word Info. Retrieved July 15, 2012.
  3. ↑ 3.0 3.1 {(Rhawn J.). The naked neuron:evolution and the languages of the body and brain. New York : Plenum Press.
  4. ↑ 4.0 4.1 4.2 Levitan, I. B., & Kaczmarek, L. K. (2002). The neuron cell and molecular biology. (3 ed., pp. 362–370). New York: Oxford University Press.ISBN 0-19-514522-4
  5. ↑ Doty, R. (2001). Olfaction. Annual Review of Psychology,52(1), 423-452. doi: 10.1146/annurev.psych.52.1.423
  6. ↑ Leopold, D.A., Schwob, J.E., Youngentob, S.L., Hornung, D.E., Wright, H.N. and Mozell, M.M (1991) Successful treatment of phantosmia with preservation of olfaction. Arch. Otolaryngol. Head and Neck Surg., 117, 1402-1406.
  7. ↑ 7.0 7.1 7.2 Leopold, D.A. and Myerrose, G. (1994) Diagnosis and treatment of distorted olfactory perception. In Kuriha, K., Suzuki, N. and Ogawa, H. (eds), Olfaction and Taste XI. Springer-Verlag, Tokyo, Japan, pp. 618-622.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Leopold D.A., (2002). Distortion of Olfactory Perception: Diagnosis and Treatment Chem. Senses 27:611-615 2002
  9. ↑ Hirsch, Alan R. (April 2009). "Parkinsonism: The Hyposmia and Phantosmia Connection". Archives of Neurology (PDF) 66 (4): 538–9. doi:10.1001/archneurol.2009.38.
  10. ↑ "Side effects of radiation for olfactory neuroblastoma". Livestrong.com. Retrieved July 3, 2012.
  11. ↑ Leopold, D.A., Preti, G., Mozell, M.M., Youngentob, S.L. and Wright, H.N (1990) Fish-odor syndrome presenting as dysosmia. Arch. Otolaryngol. Head Neck Surg., 116, 345-355.
  12. ↑ 12.0 12.1 Leopold, D.A., Schwob, J.E., Youngentob, S.L., Hornung, D.E., Wright, H.N. and Mozell, M.M. (1991) Successful treatment of phantomia with preservation of olfactoin. Arch. Otolaryngol. Head Neck Surg., 117,1402-1406.
  13. ↑ Zilstorff, K. (1966) Parosmia. J. Larynogol. Otol., 80,1102-1104
  14. ↑ 14.0 14.1 Leopold, D. A., Loehrl, T. A., & Schwob, J. E. (2002). Long-term follow-up of surgically treated phantosmia. Arch Otolaryngol Head Neck Surg.,128(6), 642-647
  15. ↑ 15.0 15.1 Basile N. Landis, Ilona Croy & Antje Haehner (2012): Long lasting phantosmia treated with venlafaxine, Neurocase: The Neural Basis of Cognition, 18:2, 112-114
  16. ↑ 16.0 16.1 16.2 Landis, B. N., & Burkhard, P. R. (2008). Phantosmias and parkinson disease. Archives of Neurology, 65(9), 1237-1239
  17. ↑ Nye, E., & Arendts, G. (2002). Intracerebral haemorrhage presenting as olfactory hallucinations. Emergency Medicine (Fremantle), 14(4), 447–449.
  18. ↑ Paskind, H. A. (1935). Parosmia in tumorous involvement of olfactory bulbs and nerves. Archives of Neurology and Psychiatry (Chicago), 33, 835–838.
  19. ↑ Muffatti, R., Scarone, S., & Gambini, O. (2008). An olfactory reference syndrome successfully treated by aripiprazole augmentation of antidepressant therapy. Cognitive and Behavioral Neurology, 21(4),258–260.
  20. ↑ Prazeres, A.M., Fontenelle, L. F., Mendlowicz, M. V., de Mathis, M. A., Ferrao, Y. A., de Brito, N. F., Diniz, J. B., Gonzalez, C. H., Quarantini, L. C., Marrocos, R. P., & Miguel, E. C. (2010). Olfactory reference syndrome as a subtype of body dysmorphic disorder. Journal of Clinical Psychiatry, 71(1), 87–89.
  21. ↑ Kaufman MD, Lassiter KRL, Shenoy BV. Paroxysmal unilateral dysosmia: a cured patient. Ann Neurol. 1988;;24:450-- 451.
  22. ↑ Markert JM, Hartshorn DO, Farhat SM. Paroxysmal bilateral dysosmia treated by resection of the olfactory bulbs. Surg Neurol. 1993;;40:160—163
  23. ↑ Nordin S. et al. (2004) A Longitudinal Descriptive Study of Self-reported Abnormal Smell and Taste Perception in Pregnant Women; Chem. Senses (2004) 29(5): 391-402 doi:10.1093/chemse
  24. ↑ Cantoni, P., Hudson, R., Distel, H. and Laska, M. (1999) Changes in olfactory perception and dietary habits in the course of pregnancy: a questionnaire study. Chem. Senses, 24, 58.
  25. ↑ "Phantosmia". Prospect. Retrieved July 15, 2012.
  26. ↑ Tousi, B., & Frankel, M. (June 2004). Olfactory and visual hallucinations in Parkinson's disease. Parkinsonism and Related Disorders, 10(4), 253-254 .
  27. ↑ 27.0 27.1 Doty RL, Deems D, Steller S. Olfactory dysfunction in Parkinson's disease: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 1988;38 (8) 1237- 1244
  28. ↑ Ponsen MM, Stoffers D, Booij J, van Eck-Smit BL, Wolters EC, Berendse HW. Idiopathic hyposmia as a preclinical sign of Parkinson's disease. Ann Neurol 2004;56 (2) 173- 181
  29. ↑ Haehner A, Hummel T, Hummel C, Sommer U, Junghanns S, Reichmann H. Olfactory loss may be a first sign of idiopathic Parkinson's disease. Mov Disord 2007;22 (6) 839- 842
  30. ↑ Coleman, E. R., Grosberg, B. M., & Robbins, M. S. (2011). Olfactory hallucinations in primary headache disorders: Case series and literature review. Cephalalgia, 31(14), 1477-1489.
  31. ↑ Schrieber, A. O., & Calvert, P. C. (1986). Migrainous olfactory hallucinations. Headache: The Journal of Head and Face Pain, 26(10), 513-514
  32. ↑ Landis, B., Croy, I., & Haehner, A. (2012). Long lasting phantosmia treated with venlafaxine. Neurocase,18(2), 112-114. doi: 10.1080/13554794.2011.568497

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