Effects of head injury on olfaction and taste

Traumatic events such as motor vehicle accidents, falls, or assaults can lead to dysfunction in olfaction or gustation. Mechanisms of posttraumatic olfactory dysfunction include direct injury to the sinonasal tract or olfactory epithelium, shearing effect on olfactory fibers at the cribriform plate, or brain contusion or intraparenchymal hemorrhage. Posttraumatic gustatory dysfunction is rare, but may occur as a result of direct injury to the tongue, injury to cranial nerves VII or IX, or brain contusion or hemorrhage. Evaluation of head-injured patients presenting with olfactory or gustatory complaints should include a thorough history, including assessment for pre-and posttraumatic chemosensory dysfunction and potential mechanisms of injury, complete head and neck examination including nasal endoscopy and cranial nerve testing, and focused radiographic imaging, usually CT of the sinuses and skull base. Formal olfactory and gustatory testing may be performed using various techniques, although in cases potentially involving litigation, methodologies able to detect malingering should be used. Treatable causes of chemosensory disturbance, most notably conductive olfactory losses caused by chronic rhinosinusitis or nasal obstruction, should be ruled out. In the event of neurosensory deficits, recovery may occur up to 12 to 18 months after the traumatic event. All patients should be counseled regarding the risks of their chemosensory deficits, and given suggestions for appropriate compensatory strategies.     

Immunopathology of olfactory mucosa following injury to the olfactory bulb

Removal of the olfactory bulb was performed on rats in an attempt to elucidate the processes of olfactory dysfunction following head injury. Degeneration and regeneration of the olfactory mucosa were examined, histopathologically and immunohistochemically. We used antisera to olfactory marker protein (OMP) and neuron specific enolase (NSE) as a marker of the mature olfactory receptor neurons. Following rapid degeneration after bulbectomy, the olfactory receptor neurons regenerated. OMP and NSE containing cells re-appeared 49 days later. However, the cell population of the neuroepithelium did not revert to the numbers observed in the non-operated neuroepithelium, even three months later. The lack of a connection between regenerated axons and the olfactory bulb may result in immature neuronal replacement and reduce the number of olfactory receptor neurons.     

Pathogenetic mechanism of olfactory cell injury after exposure to sulfur dioxide in mice

OBJECTIVES: This study aimed to investigate the cellular pathogenetic mechanism involved in olfactory tissue injury and regeneration. STUDY DESIGN: Adult male mice were exposed to 40 ppm SO2 for 2 hours. METHODS: The mice were sacrificed immediately, 4 hours, and 1, 3, 5, 7, 10, 14, and 21 days after exposure to SO2. Olfactory neuroepithelium and bulbs were harvested at the time of sacrifice. Western blot and immunohistochemical staining were performed. RESULTS: Injuries of the olfactory neuroepithelium were found 24 hours after exposure to SO2. The number of total olfactory neuroepithelial cells decreased after SO2 exposure and recovered after 3 weeks. In contrast, the number of proliferating cell nuclear antigen (PCNA)-positive cells increased after SO2 injury and then decreased. In the neuroepithelium, where PCNA expression increased, olfactory marker protein (OMP)-positive cells were sparse. The expression of inducible nitric oxide synthase (iNOS) was localized in the lateral half of the turbinates. However, there was no expression of iNOS in the medial half of the turbinates, in which PCNA was strongly expressed. There was increased immunoreactivity of neuronal NOS (nNOS) in the surviving cells after SO2 exposure. Immediately after exposure to SO2, the immunoreactivity to phosphorylated fraction of extracellular signal-regulated kinases (phospho-ERK)-1/2 increased in the cytoplasm and nucleus of supporting cells. In Western blot analysis, nNOS expression increased 4 hours after SO2 exposure. CONCLUSIONS: These findings suggest that the regenerative activity of the neuroepithelium might be well demonstrated by PCNA immunoreactivity and that regeneration of the neuroepithelium can be activated several days after SO2 injury. The two NOS isoforms, iNOS and nNOS, might contribute to neuroprotection in the olfactory neuroepithelium.     

Immunohistopathology of human olfactory epithelium, nerve and bulb

The immunohistochemical characteristics of the human olfactory system were (OMP). OMP was detected in the olfactory receptor neurons and processes extending from the olfactory neuroepithelium to the olfactory bulb. The olfactory receptor cells located close to the epithelial surface also contained OMP. In severely degenerate regions, only a few OMP-containing cells were observed. Differences in OMP-staining intensity were noted among the olfactory receptor cells. The thick neuroepithelium. Proliferating olfactory neuroepithelium contained OMP reactive and nonreactive olfactory receptor cells. The presence of OMP reactive and nonreactive olfactory neurons indicates the coexistence of two functionally different phases of olfactory neurons. These findings suggest that continuous cell turnover is occurring in human olfactory neuroepithelium.     

Olfactory dysfunction in Parkinson's disease

An olfactory function test in 18 patients with Parkinson's disease (PD) and 10 age-matched control subjects was performed. Both detection and recognition thresholds were measured with five kinds of synthesized odorants (T & T olfactometry). Before each test, rhinoscopic inspections were performed to exclude subjects who could have respiratory hyposmia. Both detection and recognition thresholds in patients with PD were significantly elevated in comparison with those of control subjects. Auditory acuity of PD patients, however, was well preserved and there was no significant correlation between auditory and olfactory threshold. On the basis of the present study, the authors conclude that olfactory dysfunction is one of the characteristic symptoms of PD and it may be attributed to lesions in the olfactory neural pathway including olfactory neuroepithelium.     

Olfactory dysfunction: a sequela of pediatric blunt head trauma

OBJECTIVE: To evaluate olfactory function in children with blunt head trauma. METHODS: Eligible subjects were consecutive children presenting at San Diego Children's Hospital Emergency Department or Trauma Service with blunt head trauma. Thirty-seven head injured children mean age 10.11+/-2.74 were evaluated; 36 healthy age and gender matched community children, mean age 10.08+/-2.99, served as controls. The medical record was reviewed for clinical measures related to head injury (HI). All children underwent olfactory assessment with the San Diego Children's Odor Identification Test (SDOIT). Olfactory event-related potentials were recorded on a subset of head injured and control children. RESULTS: Three of 37 head injured children had olfactory dysfunction. The head injured hyposmics had signs of more severe head injury represented by lower Glasgow Coma Scores (GCS), 10.33+/-5.51, when compared to their normosmic counterparts with mean GCS of 14.06+/-2.82. When stratifying the head injured children by clinical measures, lower Glasgow Coma Score, and abnormalities on head CT scan were associated with poorer olfactory performance. CONCLUSION: Children with blunt head injury may suffer post-traumatic olfactory impairment. More severe head injuries are more likely to produce olfactory deficits. In cases of significant head injury, cranial nerve I evaluation is imperative.     

Histopathology of the olfactory pathway due to ischemia

Various agents, such as trauma, viral infections and neoplasms cause olfactory dysfunction. However, little is understood concerning the role of ischemia. An experimental model of brain ischemia was developed in the Mongolian gerbil, and the olfactory pathway was studied. This animal was chosen because of its incomplete circle of Willis, since poor patency of the circle of Willis is not an uncommon finding in the aging human. Ischemia was induced by unilateral ligation of one common carotid artery or temporary occlusion of both common carotid arteries. Under both circumstances, ischemic changes occurred in the lateral olfactory tract, the olfactory ventricle, and the olfactory tubercle. Damage is more severe with bilateral temporary occlusion than unilateral ligation. The olfactory bulbs and neuroepithelium, however, are resistant to ischemia.     

Numerical modeling of nasal obstruction and endoscopic surgical intervention: outcome to airflow and olfaction

BACKGROUND: Mechanical obstruction of odorant flow to the olfactory neuroepithelium may be a primary cause of olfactory loss in nasal-sinus disease patients. Surgical removal of nasal obstruction may facilitate the recovery of olfactory ability. Unfortunately, quantifying the functional impact of nasal obstruction and subsequent surgical outcomes using acoustic rhinometry, rhinomanometry, or CT scans is inadequate. METHODS: Using computational fluid dynamics (CFD) techniques, we can convert patient CT scans into anatomically accurate 3D numerical nasal models that can be used to predict nasal airflow and odorant delivery rates. These models also can be rapidly modified to reflect anatomic changes, e.g., surgical removal of polyps. RESULTS: CFD modeling of one patient's nose pre- and postsurgery showed significant improvement in postsurgical ortho- and retronasal airflow and odorant delivery rate to olfactory neuroepithelium (> 1000 times), which correlated well with olfactory recovery. CONCLUSION: This study has introduced a novel technique (CFD) to calculate nasal airflow dynamics and its effects on olfaction, nasal obstruction, and sinus disease. In the future, such techniques may provide a quantitative evaluation of surgical outcome and an important preoperative guide to optimize nasal airflow and odorant delivery.     

Vomeronasal organs and nerves of Jacobson in the human fetus

The vomeronasal organs and nerves of Jacobson were found on both sides of the nasal septum in a 28-week human fetus. The vomeronasal organ in the human is a tubular structure with an opening into the nasal cavity anteriorly and closed posterior end. The vomeronasal nerve is distributed equally to the medial and lateral aspects of the organ, courses along the nasal septum and goes through the cartilaginous cribriform plate with the olfactory nerve. The cellular configuration of the vomeronasal organ is similar to the olfactory neuroepithelium. No areas of receptor-free epithelium were found in the vomeronasal organs. Intraepithelial blood vessels and mitotic figures were not observed in the epithelium of the vomeronasal organs at 28 weeks. The lack of intraepithelial blood vessels and mitoses may suggest that the vomeronasal organs are undergoing degeneration at 28 weeks of gestation.     

Steroid treatment of posttraumatic anosmia

The objective of this study was to treat posttraumatic anosmia with oral steroid and evaluate its effect. One-hundred sixteen posttraumatic patients whose olfactory thresholds were –1.0 by the phenyl ethyl alcohol threshold test assembled in our department. They were treated with a course of high-dose steroid, and followed up for at least 3 months. During the latter period of this study, magnetic resonance imaging was performed to measure the volumes of olfactory bulbs and to detect subfrontal lobe damage. Among them, 19 (16.4%) patients’ olfactory thresholds improved after steroid treatment, but the other 97 patients’ thresholds did not change. The incidences of loss of consciousness and intracranial hemorrhage after head injury, the ratios of admission and craniotomy, the intervals between head injury and steroid treatment, the volumes of olfactory bulbs, and the incidences of subfrontal lobe damage were not significantly different between patients whose thresholds improved and those whose thresholds did not improve. However, patients with olfactory improvement were significantly younger than those who remained unchanged. Our study showed that oral steroid treatment might improve olfactory acuity in some patients with posttraumatic anosmia, but the possibility of spontaneous recovery cannot be ruled out.     

Cortical Magnetic Resonance Imaging Findings in Patients With Posttraumatic Olfactory Dysfunction: Comparison According to the Interval Between Trauma and Evaluation

Objectives

Patients with smell loss after craniocerebral trauma are known to have some brain abnormalities, but there was no study to analyze the findings according to the time interval between injury and evaluation. We aimed to identify whether the time interval may influence on the findings in the brain.

Methods

Medical records of 19 patients with posttraumatic olfactory dysfunction were reviewed. All of them underwent a magnetic resonance imaging and olfactory function tests. The patients were divided into early (n=10) and delayed (n=9) groups according to the time interval.

Results

Magnetic resonance imaging was taken at a mean time of 2.2 and 59.6 months after trauma in the early and delayed groups, respectively. Abnormal findings in the brain were found in 6 and 8 patients in the early and delayed groups, respectively. The olfactory bulb and orbitofrontal cortex were commonly affected olfactory pathways in both groups. In the early group, the abnormalities were brain tissue defect, hemorrhage, and focal edema whereas tissue defect was the only finding in the delayed group. In the early group, 5 of 6 patients with severe olfactory dysfunction showed brain abnormality while 1 of 4 patients with mild dysfunction had abnormality. In the delayed group, all the patients had severe dysfunction and 8 of 9 patients showed brain abnormality.

Conclusion

Most patients with traumatic olfactory dysfunction had abnormality in the brain, and brain abnormality might be different according to the timing of evaluation. Furthermore, there might be an association between the severity of olfactory dysfunction and radiological abnormalities.     

Post-traumatic olfactory dysfunction

OBJECTIVES: This study demonstrates histopathologic and immunocytochemical changes in the olfactory bulb of a patient with post-traumatic olfactory dysfunction. These results are analyzed in light of current understanding of the pathophysiology of anosmia and dysosmia following head trauma. Emphasis is placed on potential mechanisms of human regeneration and recovery. STUDY DESIGN: The current study documents the history of a patient with the initial complaint of complete anosmia following minor head trauma. Two months after the injury the patient developed persistent, severe dysosmia with debilitating weight loss. Neurosurgical treatment, including removal of the olfactory bulbs and tracts, resulted in permanent resolution of dysosmia. METHODS: Histopathologic and immunocytochemical analysis of the olfactory bulbs was undertaken and compared with age-matched control tissue. RESULTS: Pathological analysis of the olfactory bulb revealed a marked reduction in the number of nerve processes with few intact olfactory glomeruli compared with an age-matched control. Specific immunohistochemical staining for the olfactory neuron-specific protein OMP, however, demonstrated the presence of intact axonal projections between the olfactory mucosa and the bulb. CONCLUSIONS: These results support the hypothesis that post-traumatic anosmia involves, at least in part, damage to peripheral olfactory nerve fibers with histological changes in the olfactory bulb. Potential mechanisms for the development of post-traumatic dysosmia are also discussed.     

The effect of human olfactory biopsy on olfaction: A preliminary report

Normal human olfactory function is subject to a wide variety of factors. Although biopsy of human olfactory neuroepithelium has been reported by several researchers, there are no studies which have evaluated the effect of this procedure on olfactory function. In this retrospective study, we sought to determine if tissue removal from the olfactory cleft has an adverse influence on the sense of smell. Nineteen subjects underwent bilateral olfactory testing and subsequent endoscopic olfactory mucosal biopsy. All subjects were retested 6 weeks to 1 year after olfactory neuroepithelial biopsy. No statistical difference was found between olfactory tests performed before or after biopsy. These data suggest that biopsy of human olfactory neuroepithelium has no discernible adverse effect on the ability to smell.     

The risk of olfactory disturbance from conchal plate injury during ethmoidectomy

BACKGROUND: Even though the olfactory function usually is improved or unchanged after ethmoidectomy, some patients complain of olfactory disturbance, which may be caused by direct injury to the olfactory nerves. However, the detailed anatomic pathway of the olfactory nerves that leave the olfactory mucosa and after going through the cribriform plate insert into the olfactory bulb is uncertain. In the studies of lateral nasal wall, we referred to the thin bone that connects the middle, superior, and supreme turbinates to the skull base as the "conchal plate." We undertook this study to determine the anatomic relation between the conchal plate and the olfactory nerve. METHODS: Ten midsagittal sections from adult cadaver head specimens were used for gross anatomy and the midportion of the conchal plate was taken and fixed in 10% formalin. The microscopic structures of the conchal plate were observed after hematoxylin and eosin staining. RESULTS: The olfactory nerves originated from the olfactory mucosa lining the middle and superior turbinates and ran upward within the bone of the conchal plate. These results suggest that the olfactory nerve may be injured inadvertently in the conchal plate during ethmoidectomy and that this injury is likely to be one of the possible causes of olfactory disturbance. CONCLUSION: We propose a possibility that injury to the conchal plate can affect olfactory function. Therefore, care should be taken to avoid damage to the conchal plate during ethmoidectomy.     

Olfactory and sensory attributes of the nose

The human nasal cavity contains multiple sensory and olfactory structures. The nasal mucosa with its complex innervation detects the danger substances in the air and stimulates the protective reflexes. Healthy olfactory mucosa allows for appreciation of pleasant aromas and food flavors.The olfactory nerve, in concert with the trigeminal nerve, serves as a main interpreter and modulator of chemosensory information. The anatomy of the olfactory neuroepithelium, which occupies only a small portion of the nasal mucosa, is generally well understood, while the presence and distribution of the sensory/tactile receptors in the mucosa of the nasal cavity is still a subject of controversy. The nasal vestibule, lined with skin, contains receptors that can sense noxious stimuli and air-flow. The sensitivity of the nasal mucosa to air-flow still needs further research. Understanding the distribution of the air-flow receptors could help to guide nasal surgery for obstruction.     

Head trauma and olfactory function

Olfactory impairment is a well-established sequela of head injury. The presence and degree of olfactory dysfunction is dependent on severity of head trauma, duration of posttraumatic amnesia, injuries obtained, and as more recently established, age. Deficits in smell can be conductive or neurosensory, contingent on location of injury. The former may be amenable to medical or surgical treatment, whereas the majority of patients with neurosensory deficits will not recover. Many patients will not seek treatment for such deficits until days, weeks, or even months after the traumatic event due to focus on more pressing injuries. Evaluation should start with a comprehensive history and physical exam. Determination of the site of injury can be aided by CT and MRI scanning. Verification of the presence of olfactory deficit, and assessment of its severity requires objective olfactory testing, which can be accomplished with a number of methods. The prognosis of posttraumatic olfactory dysfunction is unfortunate, with approximately only one third improving. Emphasis must be placed on identification of reversible causes, such as nasal bone fractures, septal deviation, or mucosal edema/hematoma. Olfactory loss is often discounted as an annoyance, rather than a major health concern by both patients and many healthcare providers. Patients with olfactory impairment have diminished quality of life, decreased satisfaction with life, and increased risk for personal injury. Paramount to the management of these patients is counseling with regard to adoption of compensatory strategies to avoid safety risks and maximize quality of life. Practicing otolaryngologists should have a thorough understanding of the mechanisms of traumatic olfactory dysfunction in order to effectively diagnose, manage, and counsel affected patients.     

Therapy of olfactory loss

BACKGROUND: Apart from olfactory loss due to sino-nasal disease therapy of olfactory dysfunction is a difficult task. METHODS: Own investigations were carried out using alpha-lipoic acid (Hummel et al. 2002) and caroverine (Quint et al. 2002) in both patients with posttraumatic olfactory dysfunction and patients with olfactory loss following viral infections. Both studies were designed as unblinded trials; the study using caroverine contained an arm where patients received zinc. RESULTS: While data from these investigations are preliminary both studies indicated a beneficial effect of the medication on olfactory loss. Therapeutic principles may involve the release of nerve growth factors through alpha-lipoic acid and the NMDA-antagonistic action of caroverine which might act at higher order centers of olfactory processing. CONCLUSIONS: These studies and other work indicate that olfactory loss may be treated through different pharmacological approaches. However, only double-blind, randomized, controlled trials will tell whether these effects are due to the potential pharmacological activity of these drugs, or, whether they merely reflect spontaneous recovery as it is seen in a relatively large percentage of patients suffering from olfactory dysfunction.     

The risk to olfaction from nasal surgery

Implicit in all types of nasal surgery is the potential for worsening of olfactory function. Not only can injury occur to the delicate olfactory neuroepithelium itself, but also more indirect disturbances are engendered by pharmacologic agents, distortions of intranasal anatomy, persistent mucosal edema or crusts, and other processes. This study examined 93 patients undergoing various types of nasal surgery, including ethmoidectomy, polypectomy, Caldwell-Luc procedure, open reduction of nasal fracture, closed reduction of nasal fracture, rhinoplasty, and septoplasty. Factors considered as contributing to loss of olfactory acuity were age, gender, use of general anesthesia, and type of operation. The University of Pennsylvania Smell Identification Test (UPSIT), a 40-item, microencapsulated scratch-and-sniff procedure, was used to ascertain olfactory ability. Sixty-one patients (66%) had either improved or unchanged UPSIT scores after surgery; the remaining 32 patients (34%) had a decline in score. One patient (1%) became anosmic. Statistical treatment of outcome data using analysis of covariance with repeated measures showed no effect of age, gender, type of operation, or anesthetic.     

Intermediate filament expression in human fetal olfactory epithelium

Antibodies to intermediate filaments and to desmoplakin were used to investigate the histogenetic origin of the olfactory neuroepithelium. Intermediate-filaments are tissue-specific molecular cytoskeletal markers; desmoplakin is the major desmosomal protein. The olfactory epithelia of eight human fetuses, aged 7 to 10 weeks (fertilization age) were immunofluorescently labeled with antibodies to the five classes of intermediate-filament proteins and to desmoplakin. Positive immunoreactivity to keratin and to desmoplakin was observed; both results indicate the epithelial nature of this tissue. The absence of neurofilaments and glial-fibrillary acidic protein in the tissue containing sensory neurons and gliallike supporting cells is a unique feature, and may be related to the fact that olfactory neuroepithelium, like other epithelia, undergoes continuous turnover.     

Effect of ginkgo biloba and dexamethasone in the treatment of 3-methylindole-induced anosmia mouse model

BACKGROUND: Olfactory loss is a challenging disease. Although glucocorticoid is sometimes used for the treatment of anosmia, it has been reported that it potentiated neural damage in the early phase of treatment. This study is designed to identify the effect of ginkgo biloba, an antioxidant that acts as a free radical scavenger, in the treatment of olfactory injury aggravated by dexamethasone. METHODS: Anosmia mouse model was induced by i.p. injection of 3-methylindole (3-MI). Twenty-five mice were divided into one control group without anosmia and four anosmia treatment groups (given treatments of dexamethasone and/or ginkgo biloba). The effects of treatment were evaluated by behavioral test, Western blot, and immunohistochemistry 2 weeks after 3-MI injection. RESULTS: Induction of anosmia was confirmed by behavioral tests. The thickness and cell number of olfactory neuroepithelium were decreased more significantly in the dexamethasone treatment group than in the combination treatment group. The expression of olfactory marker protein (OMP) in olfactory epithelium was more decreased also in the dexamethasone treatment group than in the combination treatment group. The expression of OMP was decreased significantly in the olfactory bulbs of anosmia groups but there were no differences between the anosmia treatment groups. CONCLUSION: Dexamethasone treatment was associated with further deterioration of olfactory injury by 3-MI and it was recovered by combination treatment of dexamethasone and ginkgo biloba. The antioxidant effect of ginkgo biloba might play a role in restoration of olfactory loss and it was effective only when oxidative stress is maximized by dexamethasone.