Mechanism of olfactory deficit in neurotrauma and its related affective distress: A narrative review

Traumatic brain injury (TBI) is among the leading causes of death and disability all over the globe. TBI is also commonly associated with clinical sequelae of posttraumatic depression, and reports of other subsequent affective distress are common. Similarly, posttraumatic changes in chemoreceptive sensory functions, primarily due to coup-contrecoup injury induced shearing of the olfactory nerve fibers, leading to anosmia and ageusia are also well documented in the literature. However, the current literature is limited in addressing the intersections between said variables. The aim of this study was to provide a focused narrative review of the literature, to address these intersections found in clinical sequelae of TBI. As chemoreceptive sensory deficits are also linked to significant affective distress of their own, this review addresses the bidirectionality between sensory deficit and affective distress. Prevalence, demographics, mechanisms, and clinical implications are presented. Previous research is presented and discussed, in an effort to highlight the importance of consideration for all factors in TBI patient care and future research.     

CORRELATIONS AMONG BEHAVIORAL MEASURES OF ORBITOFRONTAL FUNCTION

Orbitofrontal cortex plays an important role in guiding behavior based on emotional input and rewards. It receives multimodal higher order sensory information and mediates reinforcement for primary as well as secondary or conditioned forms of reinforcement (e.g., monetary rewards). Several behavioral measures have demonstrated putative sensitivity to orbitofrontal function: smell identification, delayed alternation, and response inhibition (go/no-go and antisaccades). A correlational study of performances on these tasks by healthy controls demonstrated some interrelationships: go/no-go correlated with antisaccades, left nostril smell correlated with go/no-go, and right nostril smell correlated with delayed alternation. Further analysis showed that certain smells correlated with tasks more strongly than others. Given the diversity of these tasks, it is suggested that these intercorrelations result from at least the partial overlap of the neural substrates for olfactory identification and tasks requiring response modification based on reinforcement contingencies.     

卡尔曼综合征-家系报道

患者,男,18岁,主因智力低下、性腺发育迟缓18年来诊。患者出生时窒息(评分不详),哭声异常,外生殖器较同龄儿童小。2岁走路,4岁会讲话。智力差,频繁上感、顽固呕吐,生长无减慢。曾在北京解放军总医院、北京宣武医院小儿科及神经内科就诊,拟“智力发育迟缓,胃肠道功能紊乱”,给予营养脑细胞,止吐治疗,效果欠佳。12岁和14岁时,因“外生殖器不发育”,分别在北京空军总医院和山东省人民医院泌尿外科注射绒毛膜促性腺激素治疗,每次连续约1个月,均因出现乳腺发育自行停药。今为进一步诊治入院。既往史:母亲妊娠期间无重要病史及服药史、精神创伤史…     

内镜鼻窦手术前后鼻气道阻力和嗅觉功能的测试结果

目的　定量分析内镜鼻窦手术前后患者鼻气道阻力和嗅觉功能的变化。方法　采用前鼻测压法和T&T标准试嗅法对 12 7例慢性鼻窦炎、鼻息肉患者鼻气道阻力和嗅觉功能进行测试。结果　①患者鼻气道阻力的增加和嗅觉障碍的程度基本上随临床分期的增高而呈加重的趋势 ;②内镜鼻窦手术后 ,患者的鼻腔通气状况及嗅觉功能得到明显改善 ,总有效率分别为 93 4 % (85 / 91)和71 9% (6 4 / 89) ;③变应性因素是影响术后鼻功能改善的主要原因之一。结论　鼻气道阻力和嗅觉功能测试作为鼻功能的检测手段 ,可广泛的应用于内镜鼻窦手术前后。     

Changes of pressure and humidity affect olfactory function

The present study aimed at investigating the question whether olfactory function changes in relation to barometric pressure and humidity. Using climate chambers, odor threshold and discrimination for butanol were tested in 75 healthy volunteers under hypobaric and hyperbaric, and different humidity conditions. Among other effects, olfactory sensitivity at threshold level, but not suprathreshold odor discrimination, was impaired in a hypobaric compared to a hyperbaric milieu, and thresholds were lower in humid, compared to relatively dry conditions. In conclusion, environmental conditions modulate the sense of smell, and may, consecutively, influence results from olfactory tests.     

Sex differences in odor identification ability: a cross-cultural analysis

To ascertain the generality of a sex difference noted in odor identification ability, the University of Pennsylvania Smell Identification Test (UPSIT) was administered to four groups of subjects: Black Americans (n = 438), White Americans (n = 1559), Korean Americans (n = 106), and Native Japanese (n = 308). The women of all four groups outperformed the men to the same relative degree. The Korean American group performed better than the Black and White American groups, which, in turn, outperformed the Native Japanese. Analyses of the proportions of subjects correctly answering each of the test items revealed considerable similarity of relative item difficulty among the subject groups. Taken together, these data suggest that sex differences in odor identification ability are probably not due to ethnic or cultural factors, per se.     

Assessment of the Sniff Magnitude Test as a clinical test of olfactory function

Olfactory threshold and odor identification tasks currently serve as the standard approaches to the clinical assessment of olfactory function. Although these methods can be used effectively with the average patient, they suffer from some limitations when used to evaluate children, people with cognitive impairment, or people from diverse cultural backgrounds. A novel approach to the clinical evaluation of olfactory function, the Sniff Magnitude Test, attempts to minimize the cognitive demands of an olfactory test and thereby overcome some of the limitations of alternative tests. This is achieved by measuring the reflex-like reduction in sniffing that occurs when a malodor is encountered. The reliability and the validity of the Sniff Magnitude Test were assessed by testing people on two occasions using the University of Pennsylvania Smell Identification Test (UPSIT), a butanol threshold task, the Alcohol Sniff Test, and the Sniff Magnitude Test. The test-retest reliability of the Sniff Magnitude Test was r=.80, higher than the butanol thresholds and Alcohol Sniff Test but somewhat lower than the UPSIT. Performance on the Sniff Magnitude Test (the sniff magnitude to a malodor relative to nonodorized air) was correlated between r=-.61 and r=-.66 with the other measures of olfactory function. This range of correlations was comparable to that observed between the butanol threshold, the UPSIT, and the Alcohol Sniff Test. Finally, evidence for the advantages of the Sniff Magnitude Test, as compared to the UPSIT, was provided by a study with young children. It is concluded that the Sniff Magnitude Test has significant potential as a clinical measure of olfactory function, and that further testing and development of this method are warranted.     

嗅觉功能检查在帕金森病诊断中的应用

目的 探讨帕金森病(Parkinson's disease,PD)患者的嗅觉功能改变特点.方法 对37例临床确诊的50岁以上PD患者和95名年龄匹配的健康中老年人进行T&T主观嗅觉识别阈测试和嗅觉事件相关电位(olfactory event related potentials,OERP)检查,比较其主观嗅觉识别阈和嗅觉事件相关电位P2潜伏期的差异.结果 ≥70岁的PD患者左、右侧鼻腔主观嗅觉识别阈分别为4.6±1.1、4.4±1.2,<70岁PD患者左、右侧鼻腔主观嗅觉识别阈分别为3.9±1.7、4.0±1.7;≥70岁的对照组左、右侧鼻腔主观嗅觉识别阈分别为0.4±0.9、0.4±0.9,<70岁对照组左、右侧鼻腔主观嗅觉识别阈分别为0.5±0.8、0.5±0.8;PD患者组的主观嗅觉识别阈明显高于对照组(t=15.246、15.378、8.664、8.776,P<0.01);≥70岁的PD患者左、右侧鼻腔OERP P2潜伏期分别为(734.9±143.2)、(696.1±165.9)ms,<70岁的PD患者左、右侧鼻腔OERP P2潜伏期分别为(730.5±159.4)、(719.5±159.2)ms;≥70岁的对照组左、右侧鼻腔OERP P2潜伏期分别为(547.9±65.0)、(558.5±56.3)ms,<70岁的对照组左、右侧鼻腔OERP P2潜伏期分别为(523.3±61.9)、(526.8±62.0)ms,OERP P2潜伏期则明显长于对照组(t=-3.940、-3.750、-7.514、-8.205,P<0.01);同时PD患者组的主观嗅觉识别阈和OERP的异常率明显高于对照组.结论 PD患者主观嗅觉识别阈测试和OERP P2潜伏期结果 明显比对照组差,提示嗅觉功能减退是PD的重要临床表现;嗅觉功能检查可以作为PD筛查、诊断的参考指标.     

Transplantation of Neural Stem Cells in Anosmic Mice

Objectives

Treating olfactory dysfunction is a challenge for physicians. One of the therapeutic options could be transplantation of stem cells. In this study, neural stem cells were transplanted into anosmic mice.

Methods

Neural stem cells were generated from the olfactory bulb of green fluorescent protein (GFP)-transgenic C57BL6 mice. Anosmia were induced by injection of intraperitoneal 3-methylindole. The neural stem cells were transplanted transnasally on the next day. The olfactory function was evaluated by a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis at 4 weeks.

Results

Twenty-five percent (6/24) of the control mice that were not transplanted with neural stem cells survived at 4 weeks while 67% (8/12) of the transplanted mice survived (P=0.029). The food finding test showed that the transplanted mice resumed finding food at 3 weeks while the control mice resumed finding food at 4 weeks. GFP-positive cells were observed in the olfactory neuroepithelium of the transplanted mice. Western blotting revealed that the olfactory marker protein expression was significantly lower in the control mice than that in the transplanted mice.

Conclusion

This study demonstrated that improvement of mouse survival was achieved and recovery of olfactory function was promoted by transnasal transplantation of neural stem cells in the anosmic mouse model. These results indicate that stem cells might be one of the future modalities for treating olfactory impairment.