The olfactory system is not of major importance in neurologic diagnosis, however certain clinical information would be useful, and therefore a basic knowledge of the anatomy of the olfactory pathways, and especially their relationship with the surrounding neural structures is required.
The olfactory nerves or nerves of smell are distributed to the mucous membrane of the olfactory region of the nasal cavity: this region comprises the superior nasal concha, and the corresponding part of the nasal septum. The nerves originate from the central or deep processes of the olfactory cells of the nasal mucous membrane. They form a plexiform net-work in the mucous membrane, and are then collected into about twenty branches, which pierce the cribriform plate of the ethmoid bone in two groups, a lateral and a medial group, and end in the glomeruli of the olfactory bulb. Each branch receives tubular sheaths from the dura mater and pia mater, the former being lost in the periosteum of the nose, the latter in the neurolemma of the nerve.
The olfactory nerves are non-medullated, and consist of axis-cylinders surrounded by nucleated sheaths, in which, however, there are fewer nuclei than are found in the sheaths of ordinary non-medullated nerve fibers.
The olfactory center in the cortex is generally associated with the rhinencephalon.
The olfactary nerves are developed from the cells of the ectoderm which lines the olfactory pits; these cells undergo proliferation and give rise to what are termed the olfactory cells of the nose. The axons of the olfactory cells grow into the overlying olfactory bulb and form the olfactory nerves.
The axons of the mitral and tufted cells leave the olfactory bulb and course posteriorly, as the olfactory tract, in the olfactory sulcus on the orbital surfaces of the frontal lobe. The olfactory tract divides into a median and a lateral olfactory stria on either side of the anterior perforated substance (the triangular area formed by the two striae is called the olfactory trigone). Some of these strial fibers decussate in the anterior commissure and join the fibers from the opposite olfactory pathways, terminating in the contralateral cerebral hemisphere.
Other strial fibers, especially those of the lateral stria, supply the ipsilateral piriform lobe of the cerebral (temporal) cortex (the primary olfactory cortex) and terminate in the amygdaloid nucleus, septal nuclei, and hypothalamus.
There are quantitative methods to test olfaction, such as tests of the minimal perceptible odor or measurements of olfactory fatigue), the sense of smell is usually tested by asking the patient to sniff various nonirritating substances (each nostril is tested separately) and then attempt to identify the odor (perception of the smell is of more value than identification of the specific substance). Irritating substances (e.g., ammonia) are to be avoided because they stimulate the trigeminal nerve fibers in the nasal mucosa as well as the olfactory fibers.
Disturbance of olfaction
Lesions Causing Anosmia
Anosmia (loss of smell) or hyposmia (diminished olfactory functioning) may or may not be apparent to the patient. They may, in parallel have disturbance to the sense of taste because the identification of tasted substances depends in part on the olfactory system.
Age-related decreased smell function is usually normal, and is mainly more severe to males than females. Approximately 25 of the population younger than 65 years has a chronic impairment of smelling, and between 65 and 80 years, this rises dramatically with half the population experiencing significant decrements in the smell ability.
The pathophysiology of age-related changes in smell includes ossification and closure of the foramina of the cribriform plate, development of early neurodegenerative disease pathology, and cumulative damage to the olfactory receptors from repeated viral and other insults throughout life.
Local nasal disease such as allergic rhinitis, nasal obstruction, and polyposis must first be sought as the cause of anosmia, especially if the olfactory difficulty is bilateral. The most common cause of transient and bilateral anosmia is the common cold.
Exposure to airborne toxins, including herbicides, pesticides, solvents, and heavy metals can alter the ability to smell, especially when exposure has been chronic. Among the heavy metals, the best documented cases are for cadmium, chromium, nickel, and manganese.
After local nasal disease has been ruled out, anosmia, especially unilateral anosmia, should raise the suspicion of a lesion affecting the olfactory nerve, bulb, tract, or stria.
The cortical representation for smell in the piriform cortex is bilateral, therefore a unilateral lesion distal to the decussation of the olfactory fibers causes no olfactory impairment.
Head injury is the most common cause of disruption of the olfactory fibers prior to their decussation, and frontal impact produces less dysfunction than back or side impacts.
The olfactory nerve may be damaged by fractures involving the cribriform plate of the ethmoid bone, but closed head injury without fracture may also disrupt the olfactory pathways unilaterally or bilaterally. Closed head injury can produce impairment of olfactory recognition despite relatively preserved olfactory detection.
Olfactory naming and recognition may be impaired by traumatic injuries affecting the orbitofrontal and temporal lobes, and the degree of olfactory disturbances is directly related to the severity of the injury.
Disturbances of complex olfactory function regardless of the relatively preserved detection of odors have been reported with alcoholic Korsakoff syndrome and following thalamic or prefrontal cortical lesions. Significant olfactory dysfunction has also been described with neurodegenerative disorders such as Alzheimer disease, Lewy body disease, Huntington chorea, corticobasal ganglionic degeneration, Creutzfeldt–Jakob disease, frontotemporal dementia, multiple sclerosis, Parkinson disease, Refsum disease, spinocerebellar ataxias (including Friedreich ataxia), Wilson disease, narcolepsy, pure autonomic failure, and in adults with Down syndrome.
Impaired olfaction may predate clinical PD by at least 4 years and may be a useful screening tool to detect those at high risk for development of PD in later life. Patients with PD have decreased performance on odour discrimination tests in addition to deficits of odour detection and identification. REM sleep disorder and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular, PD.
Olfactory loss in patients with multiple sclerosis has been associated with plaque formation in the central olfactory (i.e., inferior frontal and temporal) brain regions.
Hawkes in his comprehensive review  noted that there has been an increase of interest in olfactory dysfunction because it was realized that anosmia was a common feature of idiopathic PD and Alzheimer dementia (AD). In his review of PD, parkinsonian syndromes, essential tremor, AD, motor neuron disease, and HC, the following observations are made :
- Olfactory dysfunction is frequent and often severe in PD and AD.
- Normal smell identification in PD is rare and should prompt the review of diagnosis unless the patient is a female with a tremor-dominant disease.
- Anosmia in suspected progressive supranuclear palsy and corticobasal degeneration is atypical and should likewise provoke diagnostic review.
- Hyposmia is an early feature of PD and AD and may precede motor and cognitive signs, respectively.
- Subjects with anosmia and one apoE4 allele have an approximate fivefold increased risk of later AD.
- Impaired sense of smell is seen in some patients at 50% risk of parkinsonism.
- Smell testing in HC and motor neuron disease, where abnormality may be found, is not likely to be of clinical value.
- Biopsy of olfactory nasal neurons shows nonspecific changes in PD and AD and, at present, will not aid diagnosis.
Incidental Lewy Bodies
The presence of Lewy bodies in the brains of deceased individuals without a history of PD or dementia during life, are thought to represent a presymptomatic stage of PD, and is associated with olfactory dysfunction.
Congenital anosmia or hyposmia
Congenital anosmia or hyposmia may occur owing to cleft palate in men, absent or hypoplastic olfactory bulbs or tracts, familial dysautonomia, and Turner syndrome. A familial syndrome of permanent anosmia with hypogonadotropic hypogonadism (Kallmann syndrome) has also been described; patients with this syndrome may also have cerebellar ataxia and mirror movements of the hands.
Olfactory discrimination and detection may be abnormal after unilateral frontal or temporal lobectomy. After temporal lobectomy, deficits in olfactory discrimination are confined to the nostril ipsilateral to the lesion. After frontal lobectomy, discrimination is also impaired; however, in patients with right frontal lesions including the orbital cortex, the impairment is found in both nostrils. Therefore, the orbitofrontal cortex is important in olfactory discrimination, and the nostril difference found in healthy subjects, together with the birhinal impairment in patients with right orbitofrontal damage, suggests a relative advantage of the right orbital region in olfactory processing. Anosmia may also complicate rhinoplasty, ethmoidectomy, laryngectomy, submucous resection of the nasal septum, radiotherapy, and surgery for anterior communicating artery aneurysms owing to the olfactory nerve dysfunction. Olfactory damage is much more common after an anterior interhemispheric surgical approach rather than after a basal interhemispheric approach.
The olfactory bulb and tract are frequently affected by tumors of the olfactory groove and especially meningiomas, which may cause the Foster Kennedy syndrome. Tumors of the sphenoid or frontal bone, pituitary tumors with suprasellar extension, nasopharyngeal carcinoma, and saccular aneurysms of the anterior portion of the circle of Willis (e.g., a giant anterior communicating artery aneurysm) may also compress the olfactory bulb or tract. Any diffuse meningeal process (e.g., meningitis) may involve the olfactory pathways. The anatomic relationship of the frontal lobe to the olfactory bulb and tract is especially important. Mass lesions of the frontal lobe (e.g., glioma or abscess) often exert pressure on the olfactory system and may lead to anosmia even before clear-cut frontal lobe signs and symptoms are noted. Therefore, in any patient with personality changes or subtle signs of frontal lobe involvement, olfaction should be carefully tested.
Esthesioneuroblastomas (olfactory neuroblastomas) are tumors that arise in the upper nasal cavity, often superior and lateral near the ethmoid sinus. These tumors may present with anosmia as well as persistent nasal obstruction and epistaxis. They may occasionally involve the orbit and cause periorbital swelling, proptosis, diplopia, and visual loss.
The Foster Kennedy Syndrome
The Foster Kennedy syndrome is occasionally noted with olfactory groove or sphenoid ridge masses (especially meningiomas) or space-occupying lesions of the frontal lobe. This syndrome consists of the following three signs:
- Ipsilateral anosmia due to direct pressure on the olfactory bulb or tract.
- Ipsilateral optic atrophy due to direct injury of the ipsilateral optic nerve.
- Contralateral papilledema due to raised intracranial pressure secondary to the mass lesion.
Many cases of Foster Kennedy syndrome may actually be due to direct bilateral optic nerve compression; even increased intracranial pressure without optic nerve compression may cause the syndrome.
A pseudo–Foster Kennedy syndrome may rarely be noted when increased intracranial pressure of any cause occurs in a patient who has previous unilateral optic atrophy. Because the atrophic disc cannot become swollen, only the previously normal fundus demonstrates papilledema. Olfactory nerve involvement varies depending on the etiology of the increased intracranial pressure, but increased intracranial pressure per se may impair olfaction without any evidence
of local olfactory pathway damage. A pseudo–Foster Kennedy syndrome is most often due to sequential anterior ischemic optic neuropathy (arteritic or nonarteritic) or optic neuritis in which optic disc edema on one side is associated with optic disc atrophy on the other side.
Lesions Causing Parosmia and Cacosmia
Parosmia or dysosmia (perversion of smell) and cacosmia (experiencing unpleasant odors) are rare phenomena that are usually seen after a head injury or with a psychiatric disease (e.g., depression).
Various scents are interpreted as “abnormal” and, often, unpleasant. Occasionally, these unpleasant odors may persist or occur spontaneously as an olfactory hallucination. It is not clear whether these phenomena are of cortical origin (due to primary olfactory cortex injury), and therefore possibly ictal in nature, or are due to direct irritation of the olfactory pathways.
Unilateral paroxysmal olfactory hallucinations (paroxysmal unilateral dysosmia) have been cured by resection of the homolateral olfactory bulb suggesting that, in at least some patients, olfactory hallucinations may be due to structural nerve damage. Olfactory hallucinations (especially foul odours) may occur with partial seizures with complex symptomatology or with migraine.
Olfactory epileptic auras are not necessarily unpleasant. In patients with olfactory epileptic auras, tumors are the most common etiology of the seizures, and mesial temporal sclerosis is relatively rare; the amygdala is the most likely symptomatogenic zone in these patients.
Hyperosmia (increased sensitivity to smell) may occur with migraine or hyperemesis gravidarum; phantosmia refers to the perception of an odor when none is present.
Hyposmia and parosmia have been associated with hypogeusia (diminished taste acuity) and dysgeusia (distorted taste perception) and have been correlated with zinc and vitamin A deficiencies.
Other conditions associated with altered olfaction include adrenal insufficiency, diabetes mellitus, hypothyroidism, pseudohypoparathyroidism, cystic fibrosis, and sarcoidosis.
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