先天性失嗅患者的临床研究

目的总结先天性失嗅的分类、临床表现以及影像学特点。方法回顾性分析2004年8月-2006年9月收治的8例先天性失嗅病例的临床资料。4例为伴有其他异常的先天性失嗅患者，其中卡尔曼综合征（Kallmann syndrome）3例，鼻腔鼻窦发育异常1例；另外4例为孤立性失嗅。8例患者均行详细的病史采集、全面体检、T＆T嗅觉检查、嗅觉事件相关电位测试、鼻内镜检查和鼻窦CT检查。7例行嗅觉通路MRI和性激素检测，2例行嗅黏膜活组织检查。结果8例患者自幼均未闻到过任何气味。除1例鼻腔鼻窦发育异常外，其余7例耳鼻咽喉科常规检查以及鼻内镜检查未见异常。主观嗅觉测试均为完全失嗅。嗅觉事件相关电位测试显示最大嗅刺激引不出嗅觉事件相关电位。CT检查显示1例鼻腔鼻窦未发育，其余7例未见异常。MRI检查：6例均为嗅球、嗅束缺失，嗅沟缺失或部分变浅；1例双侧嗅球发育差。内分泌检查：3例青春期后外生殖器以及男性第二性征发育不良，血清睾酮、雌二醇、促黄体生成素以及促卵泡生成素水平低于正常。其余4例性激素检测正常。嗅黏膜活检：1例未见嗅上皮典型结构；另1例为鳞状上皮组织伴慢性炎性病变。结论先天性失嗅诊断应依据病史、专科体检、嗅觉测试、鼻窦cT以及嗅路MRI检查结果。嗅路MRI对诊断有重要价值。     

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.     

外伤后失嗅患者的嗅觉事件相关电位和MRI评估

目的 探讨嗅觉事件相关电位(olfactory event related potentials,OERP)和嗅觉通路MRI对外伤后失嗅的评估价值.方法 回顾性分析24例外伤后失嗅患者的临床资料.所有患者均行详细的病史采集、全面体检、T&T嗅觉检查、鼻内镜检查、OERP测试、颅脑CT和嗅觉通路MRI检查.结果 主观嗅觉测试:双侧完全失嗅20例;单侧完全失嗅,对侧嗅觉减退2例;单侧完全失嗅,对侧嗅觉正常2例.OERP测试:双侧最大嗅刺激均不能引出OERP者20例,单侧最大嗅刺激不能引出OERP者4例;单侧能引出OERP者4例,其中2例能正常引出,另2例OERP幅值下降且潜伏期延长.氨气刺激均能引出鼻内三叉神经化学感受事件相关电位.嗅路MRI检查:嗅球损伤24例次(100%),额叶直回损伤22例次(91.7%),额叶眶回损伤16例次(67%),远端嗅束和颞叶损伤各2例次(8%).结论 OERP能对外伤后嗅觉进行定性和定量的客观整体评估;嗅路MRI能对外伤后失嗅的损伤部位、程度进行客观、精确的评估.两者结合能对嗅觉功能进行全面、客观评价.     

Is imaging necessary in the evaluation of the patient with an isolated complaint of anosmia?

Imaging studies are often obtained during the evaluation of the patient with an olfactory deficit. The purpose of this article is to describe an investigation that was conducted to assess the effectiveness of imaging studies in determining the etiology of olfactory loss in the patient with an isolated complaint of anosmia and no relevant findings on physical examination, including nasal endoscopy. The author conducted a retrospective review of the records of 20 women and eight men, aged 22 to 71 years (mean: 45), whose duration of anosmia had ranged from 1 month to 2 years (median: 3 mo). Twenty of these patients had undergone contrast-enhanced magnetic resonance imaging of the paranasal sinuses and brain, and the other eight had undergone enhanced computed tomography. The author found that these imaging studies did not add to the information obtained by the clinical history and endoscopic nasal examination and were thus not useful in determining the cause of anosmia. Based on these findings, the author does not recommend that imaging studies be included as part of the evaluation of these patients.     

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.     

Surgery for nasal obstruction — Evaluation by rhinomanometry

Nasal obstruction is predominantly a subjective patient complaint. The physical examination of the nose for nasal obstruction is a subjective evaluation as well. While the history and physical examination are reasonable diagnostic indicators, an objective means of evaluation is needed. Rhinomanometry measures nasal obstruction objectively and reliably. Thirty-six patients with nasal obstruction were evaluated by rhinomanometry before and after nasal surgery. The results are reported here. Rhinomanometry confirms the effectiveness of intranasal surgery. Using rhinomanometry, various techniques of intranasal surgery are evaluated, and several interesting observations are made.     

Congenital lack of olfactory ability.

Twenty-two patients, all of whom reported never having been able to smell anything, were studied to determine the particular features that distinguish individuals with congenital anosmia. The clinical evaluation on these patients included a thorough medical and chemosensory history, physical examination, nasal endoscopy, chemosensory testing, olfactory biopsies, and imaging studies. There was no evidence to indicate that these patients ever had a sense of smell. The results of olfactory testing suggested that these patients had an inability to detect both olfactory and trigeminal odorants; however, many of the patients in the group seemed to have a slight ability to perceive at least some component of trigeminal odorants. The olfactory epithelium, if it was present at all on biopsy, was abnormal in appearance.     

Placebo-controlled,randomized, double-blind study evaluating the efficacy of fluticasone propionate nasal spray for the treatment of patients with hyposmia/anosmia

OBJECTIVE: To compare the effect on olfaction of topical glucocorticoid treatment versus placebo given for an extended period in addition to oral short-term glucocorticoids in patients with anosmia/hyposmia. MATERIAL AND METHODS: This was a randomized, double-blind, placebo-controlled study. The criterion for inclusion in the blinded phase was an improvement of at least 2 steps in the butanol odor threshold test following open treatment for 10 days with oral and nasal corticosteroids. Forty patients were included: 20 were randomized to treatment with fluticasone propionate, 10 to placebo and 10 others as controls. The topical treatment was continued for 6 months. RESULTS: The 3 groups showed similar improvements in their sense of smell after the initial 10-day treatment with combined oral and nasal corticosteroids. Patients who continued the local treatment maintained the same level of improvement throughout the study, whether or not they had been given nasal corticosteroids or placebo. We found no significant differences between the treatment groups. CONCLUSIONS: In patients with anosmia/hyposmia partly caused by local inflammation, no further improvement in the olfactory threshold is achieved by continuing with a topical intranasal glucocorticoid after an initial combined topical and systemic glucocorticoid treatment.     

Steroid-dependent anosmia

In steroid-dependent anosmia (nasal polyps, inhalant allergy, anosmia), high doses of steroids will temporarily restore the sense of smell, a diagnostic test. Appropriate surgery can then be carried out, followed by low-dose, long-term steroid therapy to maintain the sense of smell. Olfactory biopsy specimens taken during the course of evaluation and treatment show electron-optically normal olfactory receptors, meaning that the probable pathogenesis of the sensory deficit is an obstruction, mechanical and possibly biochemical. Two cases of steroid-dependent anosmia are presented to detail a fully reversible anosmia using state-of-the-art techniques.     

Steroid-dependent anosmia

OBJECTIVE: To document the response to steroids in patients remaining anosmic following endoscopic nasal and sinus polypectomy. STUDY DESIGN: A prospective study of 24 patients with nasal and sinus polyps who were anosmic prior to endoscopic nasal and sinus surgery. Those who remained anosmic after surgery were treated with steroids. Most patients had asthma, allergic rhinitis, or both. A few had aspirin sensitivity. METHODS: All 24 patients had testing of their sense of smell before and after surgery. Those who remained anosmic postoperatively were first treated with topical nasal and then oral steroids and then tested again. RESULTS: Twelve of the 24 remained anosmic after surgery and were found to be unresponsive to nasal steroids, but oral steroids were found to restore the sense of smell to normal in most patients. Few patients continued to take the medication for long periods of time mainly because of a fear of side effects. Recent studies have suggested the role of systemic steroids in olfactory secretion, which may explain the mechanism for this response. CONCLUSION: Patients who remain anosmic after the removal of nasal and sinus polyps can be treated with oral steroids resulting in improvement of their sense of smell. Further research is needed on a molecular level to determine the reason for this and also why oral but not nasal steroids are helpful in these patients.     

Olfaction and olfactory epithelium in mice treated with zinc gluconate

OBJECTIVE: We assessed whether a nasal spray containing zinc gluconate (ZG) compromises the integrity of olfactory epithelium and olfactory function. METHODS: Axonal transport of horseradish peroxidase from olfactory epithelium to the olfactory bulb was studied in 2- to 21-day survival mice given intranasal injections of 2, 8, or 50 microL of ZG (approximately 4, 15, and 94 times the equivalent recommended human dose). Other similarly treated mice were tested using precision olfactometry to detect and discriminate odors. RESULTS: Anatomic changes were graded as a function of dose and survival time. Two microliter injections had no discernable effect. while the 50 microL volume produced substantial deafferentation of input to the olfactory bulb in short-survival cases. Nearly complete restitution of input occurred within 3 weeks. At each volume and survival time, zinc sulfate (ZS) had a greater effect. Behaviorally, 2 microL and 8 microL ZG-treated mice and those given multiple injections of 2 microL ZG performed as well as controls, whereas those given 50 microL were hyposmic but not anosmic. ZS-treated mice performed more poorly, and those injected with 50 microL were anosmic for the first 8 to 10 test days. CONCLUSIONS: A massive dose of a ZG nasal spray did cause a transient disruption of the olfactory epithelium and compromised olfaction. More moderate volumes, even those far in excess of a recommended dose, were largely without effect on odor detection and discrimination tasks. These outcomes fail to support the claims from recent clinical case reports that use of a ZG-containing nasal spray can produce anosmia.     

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.     

Biofeedback training of nasal muscles using internal and external surface electromyography of the nose

BACKGROUND: The purpose of this paper is to describe the outcome of biofeedback training of nasal muscles in cases of nasal valve stenosis and collapse. The present study was performed to investigate the best way of using surface electromyography (sEMG) in biofeedback training of muscles involved in nasal valve function. In the present study, we present the way of biofeedback training of these muscles introducing the intranasal placement of sEMG electrodes and a home exercise program. METHODS: A nonrandomized pilot study of patients presenting with symptoms of obstructed nasal breathing was conducted. All selected patients (n = 15) demonstrated nasal valve stenosis with a positive Cottle maneuver and clinically evident nasal valve collapse. Follow-up ranged from 9 to 12 months. Treatment included surface and intranasal EMG biofeedback-assisted specific strategies for nasal muscle education and a home exercise program of specific nasal movements. RESULTS: All patients exhibited variable subjective improvement. In 86.66% (n = 13), the improvement was proved objectively and there was no need for operation. In 13.33% (n = 2), an endonasal operation was recommended. CONCLUSION: Relieve of obstructed nasal breathing after nasal valve stenosis and/or collapse can be achieved with biofeedback training of nasal muscles and a home exercise program as described. It helps a significant cohort of patients with symptoms of obstructed nasal breathing to avoid surgical intervention.     

The diagnosis of a conductive olfactory loss

OBJECTIVES/HYPOTHESIS: Two of the most common causes of olfactory loss include upper respiratory infection (URI) and nasal or sinus disease. The etiology of most URI-related losses is thought to be viral and, as yet, there is no available treatment. In contrast, nasal or sinus disease produces an obstructive or conductive loss that often responds dramatically to appropriate therapy. Therefore, the distinction is important but in many cases may be difficult because such patients often present with no other nasal symptoms, and routine physical findings may be nonspecific. The purpose of this report is to characterize those aspects of the history and physical examination that will help to substantiate the diagnosis of a conductive olfactory loss. STUDY DESIGN: A retrospective, nonrandomized study of consecutive patients presenting with a primary complaint of olfactory loss. METHODS: This study reviewed 428 patients seen at a university-based taste and smell clinic from July 1987 through December 1998. Of this total, 60 patients were determined to have a conductive olfactory loss. All patients were referred specifically because of a primary chemosensory complaint. The University of Pennsylvania Smell Identification Test (UPSIT; Sensonics, Inc., Haddon Heights, NJ) was administered in all cases. RESULTS: The most commonly diagnosed etiologies of olfactory loss were head injury (18%), upper respiratory infection (18%), and nasal or sinus disease (14%). Of the 60 patients with a conductive loss, only 30% complained of nasal obstruction, whereas 58% described a history of chronic sinusitis. Only 45% reported that their olfactory loss at times seemed to fluctuate in severity. Anterior rhinoscopy failed to diagnose pathology in 51% of cases, whereas nasal endoscopy missed the diagnosis in 9%. Systemic steroids elicited a temporary reversal of conductive olfactory loss in 83% of patients who received them, offering a useful diagnostic maneuver, whereas topical steroids did so in only 25%. CONCLUSIONS: The etiology for olfactory loss can in many cases be difficult to determine, but it is important to establish prognosis and to predict response to therapy. Diagnosis requires a thorough history, appropriate chemosensory testing, and a physical examination that should include nasal endoscopy. A trial of systemic steroids may serve to verify that the loss is indeed conductive.     

Chemosensory function in Wegener’s granulomatosis: a preliminary report

Despite the fact that Wegener’s granulomatosis affects the nasal and paranasal cavities and the cranial nerves regularly, chemosensory impairments have not been reported. The objective of this study is to test the three chemosensory systems, olfaction, taste, and intranasal trigeminal function in Wegener disease patients. We tested olfactory, gustatory, and intranasal trigeminal function in nine patients (5 women, 4 men, mean age 57 years) with confirmed Wegener’s granulomatosis. Olfaction was tested with the Sniffin’Sticks, gustatory function with the “Taste strips” and intranasal trigeminal function with a lateralization task. One patient had anosmia (11%), four patients had hyposmia (44%) and four patients were normosmic (45%). Gustatory testing function showed pathological taste strip results in five patients (55%) and normal results in three patients (33%). One patient did not undergo taste testing. Intranasal trigeminal function was lowered in five patients (56%) and normal in four patients (44%). Neither previous nasal surgery status nor endoscopic status was associated to a higher frequency in pathological scores for any of the three chemical senses. In conclusion, these preliminary results suggest a consistent affection in chemosensory functions in Wegener’s granulomatosis patients.     

A case report on congenital anosmia

We report 2 cases of congenital anosmia, in a 13-year-old girl and the other in a 10-year-old boy. They reported having no concept of "smell". The girl has no complications but the boy has congenital microphthalmia and is completely blind. They showed scale-out results on both T & T olfactometry and intravenous Alinamin test. Brain MRI detected hypoplasia or lack of the olfactory bulbs, tracts, and olfactory sulci in the frontal lobe of the brain in both patients. Neither had endocrinal dysfunction. In the boy, we biopsied the nasal mucosa in the olfactory cleft and found it had no olfactory epithelial cells at all. We found MRI to be the most useful imaging for diagnosing congenital olfactory disturbance.     

Nasal polyposis: long term functional results in 203 patients treated by ethmoidectomy combined with intranasal corticotherapy

OBJECTIVE: Evaluate the long term quality of life in patients after ethmoidectomy associated with intranasal corticotherapy for nasal polyposis on the appreciation of the intensity of nasal symptoms. MATERIAL ET METHOD: The authors report their experience about 203 patients treated by endonasal endoscopic ethmo?dectomy intranasal followed by a long term intransal corticotherapy, with a mean follow up of six years. In this prospective study, each symptom was evaluated using an analogic visual scale and a questionnaire. The evolution of asthma after surgery and the patients global satisfactory rate were noted. RESULTS: There is a global improvement of the nasal symptoms with a mean postoperative individual scores calculated at 32% for nasal obstruction, at 34% for rhinorrhea and at 51% for anosmia. No impact on asthma or improvement of asthma was encountered in 92% of the patients. The patients global satisfactory rate of this medico-surgical approach of the disease is 93.6%. A positive correlation was found between the severity of the olfactory disorders and the oral corticosteroid therapy. CONCLUSION: Endoscopic endonasal ethmo?dectomy followed by intranasal corticotherapy represents a valuable protocol in treating patients with severe nasal polyposis.     

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.     

Muscle-building therapy in treatment of nasal valve collapse

OBJECTIVES: The purpose of this paper is to describe the outcome of muscle-building therapy for nasal muscles in cases of nasal valve stenosis or collapse. The present study was performed to investigate the best way to combine transcutaneous and intranasal surface electromyography (sEMG) biofeedback training of muscles involved in nasal valve function with a home exercise program and electric stimulation of nasal muscles. METHODS: A randomized pilot study of 3 groups of patients (n1=12, n2=12, n3=10; total 34 patients) presenting with symptoms of obstructed nasal breathing was conducted. All selected patients demonstrated nasal valve stenosis with a positive Cottler maneuver and clinically evident nasal valve collapse. Follow-up ranged from 8 to 12 months. Treatment for Group 1 included transcutaneous and intranasal electric stimulation of nasal muscles only. Treatment for Group 2 included biofeedback training and home exercise program of specific nasal movements, and treatment for Group 3 included surface and intranasal EMG biofeedback assisted specific strategies for nasal muscle education, home exercises and electric stimulation. RESULTS: All patients in these groups exhibited subjective improvement. For Group 3, in 80% the improvement was proved objectively; for Group 2, in 75% the improvement was proved objectively; for Group 1, in 58,33% the improvement was proved objectively. We found no significant difference between the results in Groups 3 and 2 and poorer results in Group 1. CONCLUSION: Relieve of nasal valve stenosis and collapse can be achieved with a complex muscle-building therapy as described. It helps a significant cohort of patients with symptoms of obstructed nasal breathing to avoid surgical intervention. Electric stimulation of the muscles does not contribute significantly in achieving of good results.     

Circadian anosmia: A rare clinical presentation

We report the case of a 27‐year‐old female who presented with a peculiar story of anosmia fluctuating in a circadian manner. Olfactory function appeared an hour after breakfast, was normal during daytime, and disappeared in the early evening. Imaging confirmed chronic rhinosinusitis (CRS). Initial systemic, followed by topical steroid treatment, rapidly and sustainably reversed this condition. The olfactory fluctuation paralleled the endogenous steroid production. This suggests that slight congestion changes in a chronically inflamed nasal mucosa may have been sufficient to induce this circadian anosmia. The importance of identifying fluctuation of olfactory function as a sign of CRS is emphasized and discussed. Laryngoscope, 128:1537–1539, 2018