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Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology.

OBJECTIVES: To assess olfactory function of patients with dementia. Odour detection ability is impaired in clinical Parkinson's disease. Evidence of impaired detection in patients with clinically diagnosed Alzheimer's disease is inconsistent. No studies of olfaction have been neuropathologically validated. METHODS: The olfactory function of 92 patients with dementia and 94 controls was assessed using a simple bedside test as part of the Oxford Project To Investigate Memory and Ageing (OPTIMA). Neuropathological assessment was made of cortical Lewy bodies and substantia nigra (SN) cell counts and of Alzheimer's disease in all 92 patients, 22 of whom had SN Lewy bodies and 43 of whom had only Alzheimer's disease. RESULTS: Patients with Lewy bodies were more likely to be anosmic than those with Alzheimer's disease or controls. Patients with Alzheimer's disease were not more likely to be anosmic than controls. Nor was anosmia associated with degree of neurofibrillary tangles, as assessed by Braak stage. Among subjects with Lewy bodies, overall cortical Lewy body scores and Lewy body density in the cingulate were higher in those who were anosmic. Consensus clinical criteria for dementia with Lewy bodies had a sensitivity of 64% and specificity of 89%. In the absence of definite Alzheimer's disease, the criteria had sensitivity of 100%. In patients with definite Alzheimer's disease, anosmia was slightly more sensitive (55%) than the consensus criteria (33%). However, the addition of anosmia to the consensus criteria did not improve their overall performance. CONCLUSION: Dementia with Lewy bodies is associated with impaired odour detection. Misdiagnosis may have accounted for some previous reports of impaired odour detection in Alzheimer's disease. Simple but more sensitive tests of anosmia are required if they are to be clinically useful in identifying patients with dementia with Lewy bodies.

Aged↗

Decreased trigeminal sensitivity in anosmia.

The present study aimed to investigate intranasal trigeminal sensitivity in a large sample of patients with anosmia due to different etiologies. We investigated the trigeminal detection threshold for formic acid in healthy controls (n = 96) and patients with anosmia due to head trauma (n = 18) or sinonasal disease (n = 54). Anosmics exhibited higher thresholds compared with normosmics (p < 0.001). In addition, thresholds were found to be higher in patients with posttraumatic anosmia compared to anosmics with sinonasal disease (p < 0.001). The data indicate that (1) loss of olfactory sensitivity in humans may be associated with a decreased sensitivity towards trigeminal stimuli and (2) alteration of intranasal trigeminal function is stronger in patients with posttraumatic anosmia compared to patients with sinonasal disease. This may have implications for the medicolegal investigation of anosmic patients where trigeminal stimuli are frequently used to assess the patient's response bias.

Adolescent↗

Influence of subcutaneous deposits of melatonin on the antigonadotrophic effects of blinding and anosmia in male rats. A dose-response study.

23-day-old male rats were left intact, rendered blind and anosmic, pinealectomized together with blinding and anosmia, or subcutaneously implanted with graded doses of melatonin in beeswax immediately following surgical blinding and anosmia. 5 weeks later, blind, anosmic animals were found to have significantly depressed anterior pituitary, testicular, and accessory sex organ weights. Both pituitary and plasma prolactin and luteinizing hormone (LH) concentrations were also significantly suppressed. Pinealectomy of blind, anosmic animals completely restored testicular and accessory organ weights. Likewise, pituitary LH and prolactin and plasma LH levels were also restored to intact control levels by pineal removal. Only the highest dose of melatonin (1 mg) restored the testicular and accessory sex organ weights to those of the intact controls. As little as 1 microgram melatonin restored plasma and pituitary LH concentrations to the levels of the intact controls. However, none of the dosages of melatonin reversed plasma prolactin concentrations to those of the untreated animals. The decrease in pituitary prolactin induced by blinding and anosmia was reversed by pinealectomy or by the lower doses (1, 50 or 100 micrograms) of melatonin. These results indicate that melatonin can reverse the antigonadotrophic effects of blinding and anosmia in male rats. The minimal dose of melatonin required to restore testicular and accessory sex organ weights in blind, anosmic rats is 1 mg implanted subcutaneously in beeswax.

Animals↗

Magnetic resonance imaging findings in the evaluation of traumatic anosmia.

OBJECTIVES: Head trauma is a common cause of anosmia, but diagnosis is typically late, owing to more life-threatening sequelae of the injury. Herein, we describe our workup for a case of traumatic anosmia and the magnetic resonance imaging (MRI) findings both at the time of injury and at the 18-month follow-up. METHODS: We present a case report and a review of the literature. RESULTS: A 33-year-old woman presented to our institution with a chief complaint of loss of smell and taste following an occipital blow to her head that occurred when she was hit by a car while riding a bicycle. We present the findings of MRI performed at the time of the injury and at the 18-month follow-up. We describe the clinical progression of her disease, from symptoms of parosmic and phantosmic episodes accompanied by dysgeusia to total anosmia at the 18-month follow-up. CONCLUSIONS: We advocate the use of MRI, coupled with otolaryngology consultation and formal olfactory testing, in the diagnosis, management, and counseling of patients with anosmia sustained from head injury.

Accidents, Traffic↗

Brain perfusion single photon emission computed tomography findings in patients with posttraumatic anosmia and comparison with radiological imaging.

BACKGROUND: Different techniques in neuroimaging have been proposed for assessment of olfactory dysfunction but they are not without limitations. Recently, some studies showed the usefulness of single photon emission-computed tomography (SPECT) in evaluation of patients with posttraumatic anosmia. This study was designed to assess the possible diagnostic value of SPECT findings in patients with posttraumatic anosmia in comparison with magnetic resonance imaging (MRI)/CT imaging. METHODS: Sixteen patients who had head trauma and consequently anosmia, which was defined according to Cain's identification test, were included in this study. Two nonanosmic groups, traumatic patients and nontraumatic healthy individuals, were selected as control groups for this study. Qualitative and semiquantitative brain perfusion SPECT was performed by measuring the uptake ratio of the orbital frontal cortex to occipital pole in the sagittal projections (uptake index). All 16 target patients had a previous CT scan and/or MRI. Semiquantitative and qualitative brain perfusion SPECT were compared with radiological imaging. RESULTS: Semiquantitative assessment of brain perfusion SPECT revealed remarkable orbital frontal hypoperfusion as compared with two control groups. 87.5% of anosmic patients showed orbital frontal hypoperfusion (-2 SD below the lowest level in healthy controls). In addition, the semiquantitative SPECT method detected more orbitofrontal abnormality than the qualitative method or radiological imaging (MRI and/or CT). CONCLUSION: Findings suggest that by using SPECT, posttraumatic anosmia corresponds to the hypoperfusion in the orbital frontal cortex in a great number of patients. Because of its availability, rather low cost, technical ease, and possibility to obtain objective quantitative information, brain perfusion SPECT can be complementary to other diagnostic techniques in the evaluation of olfactory function, although additional neurophysiological and imaging studies are needed.

Adult↗

[Findings using magnetic resonance in a patient with non-traumatic anosmia].

INTRODUCTION: The presence of alterations in the neuroimaging in patients with anosmia without traumatic antecedents is not frequent. CASE REPORT: Male aged 38 who came to surgery after having suffered, 6 months earlier, for 1 week, a picture of intense, oppressive holocranial headache, accompanied by fever. Associated with this, an acute complete anosmia also began and persisted up to the moment the patient came for consultation. It was not associated with any infection of the respiratory tract, there was no history of cranial trauma, no ingestion of medicines nor toxins, nor had he been exposed to toxic products. The exploration to which he was submitted only showed an anosmia and was otherwise found to be normal. Cranial MRI showed signal alterations in both lower (orbitary) convolutions of the frontal lobes, in the anterior region of the right temporal lobe and in both olfactory nerves. Tests for HIV serology, parotiditis, hepatitis B and C virus, HSV, VZV, Mycoplasma pneumoniae and lues were negative. The acute onset of the anosmia in midst of a picture of febricula and headaches made us suspect the presence of an infectious aetiology, and the alterations found in the neuroimaging could be due to post encephalic lesions, with a special predilection for olfactory areas. CONCLUSIONS: 1. MRI plays a fundamental role in the topographic and aetiological evaluation of olfactory dysfunctions of a central origin; 2. Affectation of the central olfactory passages of an infectious aetiology in a non HIV patient and with neuroimaging findings is a rare complication.

Adult↗

[Post-traumatic anosmia: description of a clinical case, proposal of a standardized protocol and medico-legal comments].

Man's olfactory perception is considerably limited compared to that of other animals; this sense is, however, extremely important in our social lives: it helps us to "savour" our food, it enables us to appreciate perfumes and, even more important, to pick up smells that signal a danger, such as a gas leak or a fire. We describe the clinical case of a patient with anosmia and hypogeusia that appeared immediately after suffering a concussive head injury. We go through the diagnostic protocol for medico-legal assessment of hypoanosmias previously described in the literature, which includes a clinical and an imaging section. In 9% of all anosmic patients, a traumatic event precedes the onset of the disorder, with repercussions on the olfactory channels and centres of the peripherical and/or central nervous system. The overall rate of anosmia following head injury is estimated to be around 7.5%. Among the principal causes of anosmia, those of medico-legal interest constitute 35% of the total. On the basis of our personal experience and of clinical studies conducted by other Authors, we propose that a bioptic investigation of the olfactory mucosa be added to the existing protocol. The olfactory neuroepithelium of patients suffering from post-traumatic anosmia, in fact, evidences some characteristic degenerative aspects. In conclusion, we report several comments regarding the quantification of the reduction of the olfactory function in different areas of medico-legal interest.

Adult↗

Anosmia after intranasal zinc gluconate use.

BACKGROUND: Zinc is an essential mineral. Beneficial zinc absorption takes place via enteral, parenteral, or cutaneous routes. However, direct application to the olfactory epithelium has been reported to cause loss of smell. Recently, intranasal zinc gluconate has been recommended as a treatment for the common cold. Severe posttreatment hyposmia and anosmia have been observed. METHODS: The case report of a typical patient is presented and analyzed in detail, followed by a series of patients with severe hyposmia or anosmia after the use of intranasal zinc gluconate. RESULTS: Although interindividual variation in drug response and drug effect is apparent, the severe hyposmia or anosmia appears to be long lasting or permanent in some cases. The mechanism of olfactory loss is thought to be the direct action of the divalent zinc ion on the olfactory receptor cell. CONCLUSIONS: Zinc ions are toxic to olfactory epithelium. Reports of severe hyposmia with parosmia or anosmia have occurred after intranasal use of zinc gluconate.

Administration, Intranasal↗

Congenital anosmia.

Seven patients with congenital anosmia underwent detailed chemosensory evaluation, followed by the performance of biopsies of the olfactory region. Olfactory epithelium was not found in any of the biopsy specimens. It appears therefore that patients with congenital anosmia lack any olfactory epithelium. Several possible explanations for this finding are discussed. The most attractive hypothesis is that the olfactory placode forms either normally or abnormally during development but later degenerates and is replaced with respiratory epithelium. Only one patient in our series had congenital anosmia in association with a syndrome (Kallmann's syndrome), indicating that congenital anosmia is found more often as an isolated symptom.

Adolescent↗

NeuroSPECT findings in patients with posttraumatic anosmia: a quantitative analysis.

OBJECTIVE: To investigate quantitative neuroSPECT findings, particularly from orbital frontal cortex, in patients rendered totally anosmic from head injury. SETTING: Veterans Administration (VA) Medical Center. SUBJECTS: Eighteen patients with head injury resulting in severe anosmia and five normal controls. All 18 patients had sustained their head injuries at least 5 years prior to involvement in the study. MEASURES: Quantitative neuroSPECT (count density) from sagittal regions of interest (ROIs) ranging circumferentially from orbital frontal cortex to occipital pole. RESULTS: Quantitative evaluation of neuroSPECT findings for anosmic patients as a group showed substantial orbital frontal hypoperfusion compared with controls, with 67% of individual anosmic patients showing orbital frontal hypoperfusion at a level two or more standard deviations below that of the worst control subject. By contrast, there were no between-group differences for five other ROIs (inferior frontal pole, superior frontal pole, posterior superior frontal lobe, the parasagittal region, and occipital pole), and individual abnormalities were infrequent in these areas. In addition, orbital frontal count was significantly correlated with ratings of outcome, the only ROI to have such a relationship. CONCLUSIONS: Findings strongly suggest that posttraumatic anosmia and the neuropsychological deficits typically associated with posttraumatic anosmia are closely and specifically associated with hypoperfusion in orbital frontal cortex. The results also underscore the importance of posttraumatic anosmia as a clinical sign of orbital frontal damage, which is particularly important in patients with mild head injury who have normal computed tomography and magnetic resonance imaging scans.

Adult↗

Reversible anosmia after amikacin therapy.

Olfactory disorders are among the rare adverse effects of antibiotic therapy. To date, olfactory losses or distortions have been reported after the use of doxycycline, amoxicillin, clarithromycin, roxithromycin, kanamycin sulfate, and streptomycin sulfate. We describe what we believe to be the first case of transient anosmia associated with the use of intravenous amikacin sulfate. The appearance of the disorder and its subsequent resolution were demonstrated by psychometric testing as well as by chemosensory evoked potentials. Based on the well-documented temporal course of the anosmia, there is a probable causal correlation between the administration of amikacin and the appearance of the olfactory disturbance. However, the exact pathogenesis of the anosmia is still a matter of conjecture.

Amikacin↗

Posttraumatic anosmia.

Two hundred twelve patients with traumatic anosmia had been seen at a clinic during the past 16 years. Sequelae of olfactory disorders were observed in 212 (4.2%) of the 5,000 cases seen that involved head and face injuries. The two most severe olfactory disorders were anosmia in 154 (72.6%) cases and hyposmia in 58 (27.4%) cases. The most frequent trauma site was the occipital region followed by the facial and frontal regions. Follow-up investigative results revealed olfactory improvement in eight (14%) of 56 cases. Six (10%) of the 56 cases prompted an aggravation of the olfactory problem. The fragmentation of olfactory nerve fibers appeared to be the most frequent cause of the anosmia after head injury.

Adolescent↗

Isolated congenital anosmia with morphologically normal olfactory bulb in two Iranian families: a new clinical entity?

Congenital total loss of the sense of smell occurs as a part of a syndrome or isolated anosmia. Kallmann syndrome is the most well known congenital anosmia associated with hypogonadotropic hypogonadism. Isolated congenital anosmia (ICA) is a very rare condition and appears to be due to changes in the olfactory epithelium or to aplasia of the olfactory nerve, bulb, and tract. Here we report two unrelated Iranian families with ICA. One family consisted of nine affected members, and the other family contained three affected members. Clinical history, physical examination, and smell testing by intravenous injection of combined vitamins (Alinamin trade mark, Takeda Pharmaceutical Co. Ltd., Japan) confirmed the disease in each affected member. No signs of hypogonadism or other neurological disorders were observed in any affected members. Family analysis with the complete ascertainment method under assumption of the same condition in the two families suggested that the disease is not inconsistent with an autosomal dominant mode with incomplete penetrance. The inheritance in one family appears unusual, i.e., there were no affected individuals in the third generation. When only two upper generations in the family are concerned, the segregation ratio was 0.39 +/- 0.11. Male-to-male transmissions were observed and both sexes were affected in both families. Magnetic resonance imaging (MRI) of the olfactory bulb and sulcus revealed no evidence of morphological changes in all affected members, suggesting that these patients have either a defect in the olfactory epithelium or a functional defect in the olfactory cortex.

Female↗

On the trigeminal percept of androstenone and its implications on the rate of specific anosmia.

Specific anosmia is a term that describes an inability to perceive a particular odorant in the context of an otherwise normal olfactory acuity. The most common example, for the odor of androstenone, has been ascribed a prevalence ranging from 2 to 45%. In two experiments we sought to determine whether this wide range could be explained by the difference in steroid concentrations used, and by the degree to which the trigeminal system contributes to perception of androstenone. Experiment 1 demonstrated that high concentrations of androstenone stimulated the trigeminal system, as indicated by electrophysiological recordings. Experiment 2 demonstrated that conscious detection of androstenone is possible based solely on the trigeminal system. Interestingly, detection seems to interact with olfactory acuity in that subjects with a low olfactory sensitivity to androstenone were better able to detect its trigeminal component. The agreement between conscious experience and behavioral discrimination was not well calibrated, in that subjects demonstrated a clear overconfidence in their abilities. Altogether, the current study suggests that androstenone is an odorant that produces a concentration-dependent degree of trigeminal stimulation. This trigeminal component explains the diversity of the reported prevalence of specific anosmia for androstenone and might have implications on future use of specific anosmia as a tool to understand odor processing.

Adult↗

Permanent postoperative anosmia: a serious complication of neurovascular decompression in the sitting position.

In posterior fossa surgery, the sitting position offers a number of advantages believed to outweigh complications such as air embolism and pneumatocephalus. For this reason, the sitting position is frequently used in neurovascular decompression for trigeminal neuralgia. Two years ago we reported on a previously undescribed complication: permanent postoperative anosmia. Following the recent occurrence of a second case, we conducted a nationwide survey to determine the frequency of this complication. Permanent postoperative anosmia following surgical procedures in the sitting position has been observed in 3 other institutions. In addition, the survey revealed that only 40% of German neurosurgeons still favor the sitting position for surgery of the posterior cranial fossa. Considering that permanent anosmia severely reduces quality of life, and that it can be avoided by using another position, the sitting position for surgical procedures in the posterior fossa should be restricted to special cases (e.g., brain stem tumors).

Decompression, Surgical↗

Peripheral anosmia affects puberty-influencing chemosignals in mice: donors and recipients.

A series of five experiments tested the effects of peripheral anosmia on both donors and recipients of urinary chemosignals that accelerate and delay puberty in female mice. Control tests determined that the manipulations, in and of themselves, did not bring about any changes in release or reception of the chemosignals. Rendering mice peripherally anosmic using a solution of zinc sulfate did result in effects on both donors and recipients. For donors, release of the substances in male urine, urine from females in estrus, or urine from pregnant or lactating females, all of which accelerate female puberty, were not influenced by peripheral anosmia. Peripheral anosmia did, however, bring about the cessation of release of the substance in the urine of grouped adult females that delays sexual maturation in conspecific females. Peripherally anosmic young female recipients of the chemosignals were accelerated in their sexual development when the treatment applied involved urine from pregnant or lactating females. However, the acceleratory effects normally produced by male urine or urine from females in estrus did not occur in peripherally anosmic young females. The substance in the urine of grouped adult females did not produce delays in puberty when the recipient females were rendered peripherally anosmic prior to urine treatment.

Animals↗

Quantitative EEG analysis in post-traumatic anosmia.

Many objective and quantitative methods have been developed to create a procedure or a device to prove, describe and quantify olfactory deficit and anosmia, especially after a head trauma. Electrophysiological testing throughout olfactoelectroencephalography (olfactoEEG) is based on brain activity desynchronisation, and on the subsequent disappearance of alpha activity on the posterior regions after an olfactory stimulus. Yet traditional evaluation of EEG can be difficult, because of little or hardly detectable alpha activity on the posterior regions ('alpha rare'). The aim of this study was to evaluate the Olfactory Stop Reaction (OSR) by means of frequency band power calculation and subsequent topographical mapping in patients with post-traumatic anosmia, who presented 'alpha rare' EEG. Twenty-five consecutive patients, affected by anosmia caused by head trauma, were submitted to an EEG recording with olfactory stimulation. After signal processing and analysis, an Olfactory Stop Reaction was detected in 17 out of 25 patients; moreover, in these patients we detected a significant decrease in alpha band power in the occipital regions and an increase in theta band power on midline frontal and central regions after olfactory stimulation. In the remaining eight patients, no significant variation in band power was observed. In conclusion, an objective evaluation of the olfactory function with this method of automatic EEG signal analysis allows the limits given by psychophysical methods and traditional EEG to be overcome and attempts to fulfil the requirements for standardization of olfactory function evalution.

Adult↗

Antibodies to dorsal root ganglia and olfactory cells in a patient with chronic sensory neuropathy and anosmia.

We report the case of a 51-year-old woman with anosmia and chronic sensory ataxic neuropathy. Olfactory tests suggested neurosensory anosmia. Immunocytochemical analysis showed serum antibodies against dorsal root ganglion (DRG) cells and olfactory neurons, in the absence of other known causes of anosmia and sensory neuropathy. Clinical and laboratory data suggested a slow autoimmune process affecting dorsal root ganglion and olfactory cells.

Antibodies↗