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Bilateral participation of the hippocampus in familiar landmark navigation by homing pigeons.

Recent findings indicate a different role of the left and right hippocampal formation (RHF) in homing pigeon navigational map learning. However, it remains uncertain whether the left or the RHF may play a more important role in navigation based on familiar landmarks. In the present study, we attempted to answer this question by experimentally releasing control and left and right hippocampal ablated pigeons from familiar training sites under anosmia, to render their navigational map dysfunctional, and after a phase-shift of the light-dark cycle, to place into conflict a pilotage-like landmark navigational strategy and a site-specific compass orientation landmark navigational strategy. Both left and right hippocampal ablated birds succeeded in learning to navigate by familiar landmarks, and both preferentially relied on sun-compass based, site-specific compass orientation to home. Like bilateral hippocampal lesioned birds, and in contrast to intact controls, neither ablation group adopted a pilotage-like strategy. We conclude that both the left and RHF are necessary if pilotage-like, familiar landmark navigation is to be learned or preferentially used for navigation.

Animals↗

Parental behavior in the mouse: effects of lesions in the entorhinal/piriform cortex.

The effects of bilateral radiofrequency lesions in the region of the entorhinal and piriform cortex (ENT/PIR cortex) on pup-retrieving and ultrasound-elicited pup-searching behavior were investigated in ovariectomized estrogen-treated female mice, which were sensitized to pups by co-caring for a litter for 5 days together with the mother (FoEBex), as well as in primiparous lactating females (Flact). A further group of FoEBex were rendered anosmic by an intranasal treatment with zinc sulfate-solution before the sensitization period and tests for parental motivation. Both pup-retrieving and pup-searching behavior were disturbed to the same extent by ENT/PIR lesions and ZnSO4-induced anosmia in FoEBex. In Flact, however, pup-retrieving was not affected by the lesion, while ultrasound-recognition leading to pup-searching was disrupted. The present data suggest sensitization to pups as a case of olfactory learning and thus, the effects of the ENT/PIR lesions are regarded as anterograde olfactory amnesia. From the present data and results reported in the literature, it is suggested to differentiate between the neural substrates processing stimuli relevant for the appetitive component (pup-searching) of parental behavior (among others, the region of the entorhinal and piriform cortex), and the mechanisms regulating the consummatory component (pup-retrieving).

Animals↗

Olfaction and peripheral olfactory connections in methimazole-treated rats.

Methimazole has been reported to produce extensive degenerative changes in olfactory epithelium and a severe deficit in odor detection [Genter BM, Owens DM, Carlone HB, Crofton KM. Fundam. Appl. Toxicol. 1996;29:71-77; Genter BM, Owens DM, Deamer NJ, Blake BL, Wesley DS, Levi PE. Toxicol. Pathol. 1995;23:477-486.]. To examine this further, rats were tested on olfactory detection and discrimination problems before and after intraperitoneal injection of 300 mg/kg methimazole. In the first 2 days after treatment, experimental rats had nasal congestion and a modest decrement on odor detection and odor mixture discrimination tasks. They performed almost as well as control rats on the third post injection day. In a separate group of rats, anterograde transport of horseradish peroxidase from olfactory epithelium to the bulb was examined 1, 2, 3, and 5 days after administration of methimazole. The treatment produced a modest but progressive disruption of bulbar input: 2 days after administration only approximately 10% of bulbar glomeruli had reduced levels of reaction product while 30-40% of glomeruli had little or no reaction product in 3-5 day survival rats. These results indicate that methimazole is not a particularly effective olfactotoxin and does not produce anosmia or even a severe hyposmia.

Animals↗

Mutations of the GnRH receptor gene: a new cause of autosomal-recessive hypogonadotropic hypogonadism.

Mutations in a few genes have been identified in hypogonadotropic hypogonadism (HH): the gene KAL-1 is involved in X-linked Kallmann syndrome associated with anosmia and mutations in transcription factors, namely, DAX-1 and Prop-1 were also evidenced when associated with other pituitary or endocrine defects. Recently, compound heterozygote mutations in the GnRH receptor gene were described both in males and females and hormonal resistance was confirmed in vitro. There is a wide spectrum of phenotype, ranging from complete HH with lack of pubertal development and cryptorchidism to partial hypogonadism with an arrest of pubertal development. In complete GnRH resistance, endogenous LH secretory patterns were abnormal, either apulsatile or characterized by a low-normal pulse frequency with small pulses or erratic pulses of low amplitude. In patients with partial resistance, basal LH plasma concentration was low, but FSH level was in the normal range. LH pulse analysis revealed normal frequency with decreased amplitude. Mutations are distributed along the coding sequence, as reported for other GPCRs. However, two hot-spots, Q106R and the R262Q, were observed, regardless of the geographic origin of the patients. In most cases, patients responded to GnRH administration, making the GnRH test inappropriate for screening GnRH resistance in IHH.

Amino Acid Sequence↗

Diffuse nasal polyposis: postoperative long-term results after endoscopic sinus surgery and frontal irrigation.

Diffuse nasal polyposis remains a challenge despite recent improvements in endonasal surgery. The purpose of this study is to evaluate the results after a radical complete sphenoethmoidectomy with peroperative and postoperative frontal irrigation in cases of diffuse nasal polyposis. In this prospective study, we include 50 consecutive patients with diffuse nasal polyposis suffering from nasal obstruction, anosmia, and other symptoms of chronic sinusitis. All patients were refractory to medical therapy. In each patient an endoscopic complete sphenoethmoidectomy including total excision of all diseased ethmoid mucosa was performed. Preoperative and postoperative frontal irrigation was performed systematically. The patients were followed closely with serial endoscopic examination, and CT scanning was performed between 2 and 3 years after surgery. There were no complications. Thirty-nine of the 50 patients regained satisfactory olfaction. Partial nasal obstruction persisted in four of the 50 patients. Endoscopically, polyp recurrence was noted in 3% of posterior ethmoids, 23% of anterior ethmoids, and 50% of frontal recesses. We conclude that in cases of refractory and extensive nasal polyposis, a total sphenoethmoidectomy with perioperative frontal irrigation followed by long-term postoperative topical steroid therapy provides excellent improvement or cure with safety and reliability.

Adult↗

Outcome analysis of the transglabellar/subcranial approach for lesions of the anterior cranial fossa: a comparison with the classic craniotomy approach.

The classic approach to anterior skull base lesions uses bifrontal craniotomies together with lateral rhinotomies. This approach requires frontal lobe retraction and is associated with postoperative anosmia and the development of frontal lobe encephalomalacia. The transglabellar/subcranial approach permits removal of anterior skull base lesions without frontal lobe retraction and avoids facial scars. No studies to date, however, have directly compared the two approaches in terms of patient morbidity. The present retrospective study compares the two approaches when used for the removal of anterior skull base lesions in terms of estimated blood loss, number of transfusions, number of days in the hospital and intensive care unit, and postoperative complications. Twenty patients with anterior skull base lesions were examined. The classic approach was used on 10, and the transglabellar/subcranial route was used on 10. When compared with the classic approach, the transglabellar/subcranial approach resulted in a lower estimated blood loss and subsequent transfusion rate, fewer days in the hospital and intensive care unit, and lower numbers and less severe types of complications. Furthermore, visualization of the tumors before resection with the transglabellar/subcranial approach allowed preservation of olfaction in virtually all of these patients. Although this study represents a small sample population, the results are sufficiently impressive to favor the transglabellar/subcranial approach for the removal of a variety of anterior skull base lesions.

Adult↗

Subjective improvement of olfactory function after endoscopic sinus surgery for chronic rhinosinusitis.

OBJECTIVE: The purpose of this study was to determine the effect of functional endoscopic sinus surgery (FESS) on subjective olfactory dysfunction in patients with chronic rhinosinusitis. Materials and methods Prospective collection of data on consecutive patients undergoing FESS after failing prolonged medical therapy for chronic rhinosinusitis at a tertiary institution. Patients were asked to grade their olfactory dysfunction from 0 to 10, with 0 representing normal function and 10 complete anosmia. In addition, data such as computed tomography scores, presence or absence of nasal polyps, and the presence or absence of asthma were recorded and analyzed. Patients were followed up to 1 year after surgery. RESULTS: Data were collected on 178 patients who had sinus surgery over a 2-year period. The average olfactory dysfunction score before surgery was 4.9. This improved to 0.9 at 1 year after surgery (P =.00). Higher computed tomography scores as per Lund and MacKay correlated with higher olfactory dysfunction scores (r = 0.62, P <.01) and greater improvement after surgery (r = 0.82, P <.01). Asthmatics and patients with polyps had higher subjective olfactory dysfunction scores than nonasthmatics and patients without polyps (6.8 and 7.2 v 4.4 and 4.1, respectively). All groups had subjective improvement at 1 year (2.3 and 1.5 v 0.6 and 0.7, respectively; P =.00). CONCLUSION: Patients with subjective olfactory dysfunction despite appropriate medical management for rhinosinusitis benefit from FESS.

Chronic Disease↗

Clinical evaluation of olfaction.

An odor identification test and an odor threshold test offered satisfactory quantitative information on olfactory function in patients with chemosensory complaints. The threshold test used various concentrations of butanol presented in an ascending sequence. On each trial, the participant had to choose between stimulus and blank (two-alternative forced-choice procedure). The identification test used common odorous items (e.g., baby powder and ground coffee) and pungent items (e.g., ammonia) to test trigeminal function. A list of odor names and use of corrective feedback during testing overcame word-finding difficulty in odor identification. Each test readily distinguished between patients and control subjects. At present, a score that reflects the combined outcome of the tests is used to indicate five categories of functioning: normal osmesis, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia.

Chemoreceptor Cells↗

Intracranial complications of submucous resection of the nasal septum.

Submucous resection of the nasal septum (SMR) is a relatively simple and frequently performed operation. Yet, its intracranial complications, although rare, can be very serious and include anosmia, visual disturbances, cavernous sinus thrombosis, meningitis, cerebrospinal fluid rhinorrhea, pneumocephalus, subarachnoid hemorrhage, subdural empyema, and brain abscess. This article reviews intracranial complications of SMR, and the pathogenesis and prevention of such complications are discussed.

Adult↗

Kallmann syndrome: towards molecular pathogenesis.

Gonadotropin Releasing Hormone (GnRH) is a key regulator of reproduction and sexual behaviour. During the last decade, embryological studies have clarified the question of the early development of GnRH-synthesising neurones before the onset of neurosecretion. These studies have revealed the existence of a topographical link between GnRH-synthesising neurones and the embryonic olfactory system, thereby shedding new light on Kallmann syndrome, a developmental disease characterised by the association of hypogonadotropic hypogonadism and anosmia (or hyposmia). Although Kallmann syndrome was identified as an inherited disease in the forties, familial cases of the disease are infrequent. However, the identification, by positional cloning strategies, of the gene underlying the X-chromosome linked form of the disease (KAL-1) has opened the way to molecular pathophysiology. KAL-1 encodes an extracellular glycoprotein of compound modular structure. The protein, named anosmin-1, has been produced in a transfected mammalian cell line and purified. Polyclonal and monoclonal antibodies have been generated, which allowed us to study the distribution of the protein during the period of human organogenesis (4--10 embryonic weeks), by immunohistofluorescence. During this developmental period, anosmin-1 is a locally restricted component of various extracellular matrices (interstitial matrices and basement membranes). Later in embryonic life, KAL-1 expression apparently becomes restricted to definite neuronal populations. Based on the distribution of anosmin-1 in the early olfactory system, the pathogenesis of the olfactory loss and GnRH deficiency in X-linked Kallmann syndrome is discussed.

Cell Adhesion Molecules↗

Olfaction in rats with extensive lesions of the olfactory bulbs: implications for odor coding.

Rats were initially trained on a series of odor detection tasks and then received a unilateral olfactory bulbectomy and removal of different parts of the contralateral bulb. After postoperative recovery they were tested for detection of different concentrations of four odors, on a series of odor discrimination tasks and for their ability to acquire a relatively easy and a more difficult odor mixture discrimination task. Groups were formed based on which region of the bulb was intact (regional savings score) and on amount of bulb intact (bulbar savings score). In general, only rats with bulbar savings scores of less than 21% had deficits in detection or discrimination tasks but most performed as well as controls in most tasks. Correlations between bulbar savings scores and error scores were relatively low across all rats but, within the subgroup with the largest lesions (bulbar savings scores <21%), high correlations between these variables were obtained. There was no evidence for a specific anosmia in any group or individual rat and, except for the more difficult odor mixture discrimination, no one task proved difficult for any subgroup. The present results demonstrate that rats with relatively small remnants of one olfactory bulb can perform a variety of odor detection and discrimination tasks as well or nearly as well as controls. These outcomes provide no support for localization of function within the olfactory bulb but are in accord with recent proposals that odors may be coded by a highly distributed pattern of bulbar input.

Animals↗

Effects of olfactory bulbectomy on neuropeptide gene expression in the rat olfactory/limbic system.

Bilateral olfactory bulbectomy in the rat produces a well-characterized syndrome that is independent of anosmia. This syndrome is reversed by chronic antidepressant administration, which provides the basis for the olfactory bulbectomy model of depression. The present experiments focused on neuropeptide plasticity in central olfactory/limbic structures following olfactory bulbectomy in rats. Male Sprague-Dawley rats received bilateral surgical ablation of the olfactory bulbs, sham surgery, or no surgery and were killed either three, seven, 14 or 28 days later. Relative levels of messenger RNA encoding neuropeptide Y, somatostatin, thyrotropin-releasing hormone, and corticotropin-releasing factor precursors in the forebrain were measured by quantitative in situ hybridization histochemistry using oligonucleotide probes. Prepro-neuropeptide Y messenger RNA levels in the piriform cortex and dentate gyrus were significantly elevated in bulbectomized rats 14 and 28 days after surgery compared to sham-operated and surgically naive rats. Prepro-somatostatin messenger RNA levels in the piriform cortex were marginally increased in bulbectomized rats at these time-points. Thyrotropin-releasing hormone and corticotropin-releasing factor precursor messenger RNA levels were not altered in the brain regions studied. The results indicate that olfactory bulbectomy causes long-term increases in the expression of the neuropeptide Y gene. These findings suggest that neuropeptide Y plasticity in the olfactory/limbic system may contribute to the olfactory bulbectomy syndrome in rats, and they provide further evidence of a role for neuropeptide Y in the pathophysiology of depression.

Animals↗

Effects of olfactory function, age, and gender on trigeminally mediated sensations: a study based on the lateralization of chemosensory stimuli.

The present investigation aimed to compare trigeminal nasal function of anosmic and hyposmic patients to healthy controls. Further, we aimed to study effects of age and gender on trigeminally mediated sensations following intranasal chemosensory stimulation. Participants were 35 patients with olfactory dysfunction (n=13: functional anosmia; n=22: hyposmia; age 28-69 years, mean age 56 years). Their results were compared with 17 normosmic subjects (28-82 years, mean 52 years). To analyze effects of age and gender in healthy subjects, an additional 24 healthy subjects were included (19-27 years; mean 24 years). Olfactory function was assessed using the 'Sniffin' Sticks' test kit (butanol odor threshold, odor discrimination, odor identification). The subjects' ability to lateralize odors was investigated for benzaldehyde and eucalyptol. Patients with olfactory dysfunction had lower scores in the lateralization task than controls (P<0.001) indicating decreased trigeminal sensitivity. Among anosmic patients scores were not different in relation to different causes of olfactory dysfunction (P>0.29). There was a weak, but significant, correlation between localization of eucalyptol and duration of olfactory dysfunction (P=0.017). When investigating normosmic subjects only, no gender-related difference was apparent for lateralization scores. However, older subjects had lower scores than younger ones (P<0.01). Results of partial correlational analyses controlling for age suggested a relation between the trigeminal and the olfactory systems. In conclusion, results of the present study indicate that patients with olfactory dysfunction have lower trigeminal sensitivity compared with normosmic controls. This seems to be independent of the cause of olfactory loss. The deficit appears to improve with duration of the olfactory dysfunction, possibly indicating adaptive mechanisms. Further, the data suggest an age-related decrease of intranasal trigeminal sensitivity in healthy subjects. Analyses additionally indicate a correlation between olfactory and trigeminal sensitivity.

Adult↗

Olfactory dysfunction in patients with head trauma.

OBJECTIVE: There are few reports about following up olfactory acuity of the patients who have post-traumatic olfactory dysfunction. In this study, we studied about patients with post-traumatic olfactory dysfunction for a short period under a treatment. METHODS: The olfactory function of 27 patients with head trauma was studied. The olfactory acuities of all the patients were examined using olfactory tests before the treatment, and 18 patients were examined again after the treatment. Olfactory functions were evaluated in 26 patients by T&T olfactometry and in 27 patients by Alinamin test. All of the patients were treated with a local injection of suspended steroid solution into the nasal mucosa [J Otolaryngol Jpn 102 (1999) 1175]. RESULTS: Before the treatment, 16 patients (61.5%) presented anosmia, five patients (19.2%) presented severe hyposmia, three patients (11.5%) presented moderate hyposmia, and two patients (7.7%) presented mild hyposmia. Eighteen cases (69.2%) were negative for the Alinamin test and eight cases (30.8%) were positive. The improvement rates of recognition and detection thresholds by T&T olfactometry were 35.3 and 23.5%, respectively. CONCLUSION: Olfactory dysfunction caused by head trauma can be recovered to a limited degree in some cases by the local injection of steroid within the relatively short period from the start of the therapy.

Adolescent↗

Cementifying fibroma in the ethmoidal sinus extending to the anterior cranial base in an 11-year-old girl: a case report.

A case of an 11-year-old female with cementifying fibroma in the ethmoidal sinus extending to the anterior cranial base was presented. She complained of slowly progressive nasal obstruction and anosmia. Magnetic resonance imaging (MRI) revealed a tumor in both ethmoidal and sphenoidal sinuses and nasal cavity. Although a tumor reduction surgery was attempted through a transnasal approach, tumor size increased gradually and right exophthalmos subsequently appeared. The pathological diagnosis was cementifying fibroma of the nose. Total tumor removal was consequently accomplished through the intracranial anterior transbasal approach. The surgical approach should be selected according to the site and expansion of the lesion in individual patients.

Child↗

Importance of unilateral examination in olfactometry.

Hyposmia, the decreased sense of smell, and anosmia, the loss of sense of smell, may be unilateral or bilateral. If the olfactory acuity examined by means of bilateral test is normal, olfactory disorders are not found; unilateral examination is therefore necessary for definite evaluation of olfactory acuity. As evidence, 7 cases out of 94 patients with chronic rhinosinusitis and 6 cases out of 12 patients who received the surgery of anterior cranial fossa showed definite different olfactory threshold between nasal cavities, and there were no patients who recognized the diminished sense of smell in spite of unilateral high olfactory threshold. Additionally, we have experienced that a patient with brain tumor was diagnosed by the help of unilateral olfactory test. We thus strongly recommend the unilateral olfactometry as a method for simple and reliable test in clinical measurement of the sense of smell.

Chronic Disease↗

Unilateral examination of olfactory threshold using the Jet Stream Olfactometer.

OBJECTIVE: The Jet Stream Olfactometer, a modification by the T&T olfactometer, has been recently developed and is now commercially available. This Jet Stream Olfactometer can routinely measure the unilateral sense of smell. Clinical usefulness of the Jet Stream Olfactometer was evaluated. METHODS: Twenty-three patients with sinus-related symptoms were examined. Unilateral olfactory acuity was examined using the Jet Stream Olfactometer and compared it with the anatomy of the olfactory cleft by computed tomographic (CT) scans. RESULTS: In 13 of the 23 patients examined the right olfactory threshold was similar to that of the left. Of these 13, in seven patients there was transport damage of the odorants and in the other six there was sensorineural damage. Ten patients showed an apparent difference between the right and left smell thresholds. Anosmia in seven of these ten patients was due to a conductive olfactory disturbance resulting from rhinosinusitis, whereas sensorineural damage was recognized in the other three patients. The difference in the detection threshold between the right and left nasal cavities was well correlated to that of the opacity between the right and left olfactory clefts. CONCLUSION: Jet Stream Olfactometer provides a convenient and reliable means for assessing the ability of unilateral smell.

Adult↗

A molecular approach to the pathophysiology of the X chromosome-linked Kallmann's syndrome.

The human KAL gene is responsible for the X chromosome-linked Kallmann's syndrome, which consists of an association between hypogonadotropic hypogonadism and anosmia (or hyposmia). Additional symptoms are occasionally observed. The olfactory defect is associated with hypoplasia of the olfactory bulbs and tracts. The hypogonadism may be due to a defect in the embryonic migratory process of GnRH-synthesizing neurones from the olfactory pits up to the brain. The human and chicken KAL genes have been isolated. From the amino acid sequences deduced, it has been postulated that the KAL protein is an extracellular matrix component, with putative antiprotease activity and adhesion function. Various point mutations and, in a few cases, deletions of KAL have been detected in patients. By in situ hybridization, KAL expression has been studied during embryonic development in the chick. From embryonic day 2 (ED2) to ED8, the KAL gene is expressed in various endodermal, mesodermal and ectodermal derivatives, whereas the expression from ED8 is almost entirely restricted to definite neuronal populations in the central nervous system, most of which still express the gene after hatching. According to such a spatiotemporal pattern of expression, we suggest that the KAL gene is involved both in morphogenetic events and in late neuronal differentiation and/or neuronal trophicity. With respect to the olfactory system, the KAL gene is expressed in the mitral cells of the olfactory bulbs from ED8 onwards. In contrast, no expression of the KAL gene is detected at any stage in either the embryonic olfactory epithelium or the surrounding nasal mesenchyme. Therefore, assuming that similar conditions are found in the human embryo, we suggest that the olfactory anomaly in X-linked Kallmann's syndrome results from a central target cell defect. Current hypotheses regarding the pathophysiology of the GnRH deficiency are also discussed. In situ hybridization experiments in the human embryo, as well as characterization of the KAL protein, are in progress.

Animals↗