Laryngeal electromyography: electrode guidance based on 3-dimensional magnetic resonance tomography images of the larynx.

OBJECTIVES/HYPOTHESIS: Laryngeal electromyography (LEMG) is an important tool for the assessment of laryngeal nerve and muscle functioning. The purpose of the study was to determine electrode insertion angle and insertion depth for the various laryngeal muscles. METHODS: Twenty-three cadaver larynges were examined with magnetic resonance tomography (MRT) and Materialize Interactive Medical Image Control System (Leuven, Belgium) 3-dimensional (3D) imaging software. Geometrical analysis was used to calculate the electrode insertion angles. RESULTS: All laryngeal muscles could be identified and 3D visualized on MRT scans. Although the insertion angles were the same in male and female larynges, the insertion depth was significantly larger in male than in female larynges (P<0.05). Of particular clinical importance is the fact that the electrode has to be directed lateral and upward for the thyroarytenoid muscle but lateral and downward for the lateral cricoarytenoid muscle (insertion point=midline lower border of the thyroid). CONCLUSIONS: This is the first study that analyzes electrode insertion angles and insertion depths for each laryngeal muscle using 3D imaging. We hope that the information gained from this study will help clinicians performing LEMG to localize the individual laryngeal muscles.

A study about the frequency of taste disorders.

Although 5% of the general population exhibit a functional anosmia, little is known about the frequency of gustatory disorders. Whenever taste function has been tested within large sociodemographic studies, so far only short test versions were applied making the interpretation difficult. Using two psychophysical taste tests, the validated "taste strips" and suprathreshold taste solutions of the four basic tastes sweet, sour, salty and bitter we investigated 761 healthy subjects within the age range of 5-89 years. Prior to testing, all subjects rated their taste function. According to testing with the taste strips, 5.3% scored below the result considered as hypogeusia. All four taste sprays were correctly identified by 82.3% of all subjects. Results of the two taste tests correlated positively (r = 0.33, p < 0.001), and there was a significant negative correlation between age and test results. However, we never observed complete ageusia. Misinterpretations of tastes were surprisingly common. In summary, hypogeusia was present in 5% while complete ageusia seems to be very rare, in contrast to misinterpretations of tastes.

Co-overexpression of p21 and Ki-67 in head and neck squamous cell carcinoma relative to a significantly poor prognosis.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are treated by surgery or radiotherapy. Tumor cell death-related markers, such as p21 and Ki-67, may predict response to therapy and improve treatment choice. We evaluated and compared the effect of their coexpression between patients treated by surgery or radiotherapy. METHODS: Immunohistochemistry for p21 and Ki-67 expression in 144 pharyngeal and laryngeal HNSCC samples was analyzed and correlated with follow-up parameters. RESULTS: p21 expression correlated significantly with positive cN classification (p < .001), locoregional relapse (p = .031), and poor overall survival (p = .016), and Ki-67 positivity with poor survival only (p = .025). Coexpressing tumor phenotypes showed the worst survival (p = .009), observed primarily in patients treated by radiotherapy (p = .077). CONCLUSIONS: Coexpression of p21/Ki-67 is a strong negative prognostic factor in HNSCC and could be of particular relevance in tumors treated by primary radiotherapy.

Biomechanics of the cricoarytenoid joint: three-dimensional imaging and vector analysis.

OBJECTIVES/HYPOTHESIS: Laryngeal framework surgery requires a good understanding of the biomechanics of the cricoarytenoid (CA) joint, the precise function of which is still only poorly understood. The aim of the study was (1) to show that, by superimposing two or more three-dimensional (3D) images, we can visualize the exact position of the arytenoid cartilages within the larynx at different phases of their movement; and (2) to demonstrate that it is possible to analyze the arytenoid cartilage movements mathematically with the help of vector analysis. STUDY DESIGN: In vitro cadaver study. METHODS: Twenty fresh and intact cadaver larynges were scanned by high-resolution computerized tomography with the arytenoid cartilages in "respiratory" position and in "phonatory" position. The two positions were superimposed and rendered in 3D with MIMICS (Materialise Interactive Medical Image Control System, Leuven, Belgium). The spatial trajectory of the arytenoid cartilage movements was calculated with vector analysis. RESULTS: The movement from the "respiratory" to the "phonatory" position has three components: (1) an inward rocking action around the longitudinal CA joint; (2) a forward sliding movement along the longitudinal axis of the CA joint; and (3) an inward rotation around a virtual axis that runs perpendicular to the CA joint axis. CONCLUSIONS: Superimposing 3D images of the larynx with the help of the software package MIMICS allows us to visualize and to analyze mathematically the trajectory of the arytenoid cartilage. The arytenoid cartilages rock inward, slide forward, and rotate inward when they move from the "respiratory" to the "phonatory" position.

The role of the cricothyroid joint anatomy in cricothyroid approximation surgery.

OBJECTIVES/HYPOTHESIS: Cricothyroid approximation (CTA) surgery aims at raising the voice pitch in male-to-female transsexuals. However, 30% of the patients are not satisfied with the result. The purpose of our study was to examine the cricothyroid joint (CTJ) biomechanics and to analyze if (and how) the CTJ anatomy influences the movement of the cricoid and, consequently, the elongation of the vocal fold and the voice pitch after CTA. METHODS: Twenty-four cadaver larynges were examined with high-resolution computerized tomography and MIMICS three-dimensional imaging software (Materialise Interactive Medical Image Control System, Leuven, Belgium). After superimposing the two scans taken in "neutral" and in "CTA" positions, vector geometrical analysis was used to determine the effective rotation axis of the CTJ and to calculate the elongation of the vocal folds after CTA. RESULTS: Our results showed that the cricoid rotates around an axis, the position of which depends on the anatomical structure of the CTJ. Based on the location of this effective rotation axis, we could distinguish three groups. In group I (N=13), the rotation axis was located in the lower third; in group II (N=5), it was located in the middle third; and in group III (N=6), it was located in the upper third of the cricoid. The elongations of the vocal fold were 12%, 8%, and 3%, in groups I, II, and III, respectively. CONCLUSIONS: The anatomical structure of the CTJ influences directly (1) the position of the effective rotation axis and (2) the elongation of the vocal folds.

Olfactory testing in clinical settings - is there additional benefit from unilateral testing?

In clinical settings, olfactory testing is usually performed bilaterally; thus, unilateral olfactory loss may go unnoticed. The aims of this study were to evaluate 1) whether patients presenting with self-reported olfactory disorders demonstrate significant side differences in odour perception, depending on the prevalance of measured unilateral disorder, and 2) to evaluate the existing testing procedure. In 518 patients presenting with olfactory disorders, olfactory testing was performed using the "Sniffin' Sticks" test battery (consisting of a threshold, discrimination, and odour identification test) examining each nostril separately. According to the history and results from the clinical examination, olfactory disorders were classified as related to trauma, sinunasal disease, upper respiratory tract infection (URTI), tumour, congenital, idiopathic, and other. A difference of three or more points in one of the subtests or six or more points in the composite olfactory test score was considered a side difference. In almost one quarter of all presenting patients (23.4%), a side difference was detected. To not to miss lateralized disorders, we recommend testing each nostril separately. Depending on the presence or absence of a significant difference, testing then can be continued birhinally or separately for each nostril.

Hydroxyapatite versus titanium implant: Comparison of the functional outcome after vocal fold medialization in unilateral recurrent nerve paralysis.

BACKGROUND: Results of medialization thyroplasty for treatment of unilateral vocal fold paralysis are often unsatisfactory. This study compares glottal closure and voice quality after use of 2 different medialization implant types: VoCoM and TVFMI. METHODS: In all, 26 patients with unilateral vocal fold paralysis following thoracic surgery underwent medialization thyroplasty. In 11 patients (group I), a hydroxyapatite implant (VoCoM) was used. In 15 patients (group II), a titanium implant (TVFMI) was used. Preoperative and postoperative glottal closure and voice function were assessed with videostroboscopy, perceptual and objective voice measures, and the Voice Dysfunction Index (VDI). RESULTS: Group II showed a higher rate of complete glottal closure and greater improvement in perceived hoarseness, maximal phonation time, and maximal voice intensity than those in group I. CONCLUSIONS: With the individually adjustable titanium implant, better glottal closure and better functional outcome (phonation time and voice quality) were achieved.

Developing a 3D model of the laryngeal cartilages using HRCT data and MIMICS's segmentation software.

Discussions relating to the biomechanics of the larynx are still generally controversial. The purpose of this study is to develop a 3D model of the larynx based on high-resolution computer tomography (HRCT) data identifying and visualizing anatomical landmarks and structures of the larynx. We examined four fresh cadaver larynges with HRCT. The DICOM (Digital Imaging and Communication in Medicine) data were post-processed with the software package MIMICS for three-dimensional visualization. All relevant structures of the laryngeal cartilages could be identified on HRCT and visualized in a 3D model. We conclude that 1) HRCT provides excellent data for three-dimensional visualization of the laryngeal anatomy, and 2) the combined technology of HRCT and MIMICS is useful to study the biomechanics on 3D images and for preoperative planning of laryngeal framework surgery.

Three-dimensional imaging of the larynx for pre-operative planning of laryngeal framework surgery.

Modern laryngeal framework surgery (LFS) requires an exact understanding of the laryngeal biomechanics and precise pre-operative planning, for which bi-planar imaging is not sufficient. The aim of the study was to test whether MIMICS, a commercially available software package for three-dimensional (3D) rendering of high-resolution computerised tomography (HRCT), is suitable for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning. We examined four cadaver larynx and one patient larynx. In the five larynges, all relevant structures and landmarks could be 3D visualised. Superimposing of two HRCT scans shows that when the arytenoids move from 'respiration' to 'phonation', they perform a rotating, translating and tilting motion. Moreover, we could demonstrate that the vocal fold elongates by 7% with cricothyroid approximation. We conclude that MIMCS is well suited for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning of LFS procedures.

Is the improved prognosis of p16 positive oropharyngeal squamous cell carcinoma dependent of the treatment modality?

The incidence of human papilloma virus (HPV) induced oropharyngeal squamous cell carcinoma (OPSCC) increases in the western countries. These OPSCC show distinct molecular characteristics and are characterized by an overexpression of p16, considered a surrogate marker for HPV infection. When compared to patients with p16 negative OPSCC, patients with HPV induced p16 positive OPSCC show a significantly better prognosis, which is reported to be caused by increased radiosensitivity. The objective of the present study was to analyze the impact of p16 expression status on the prognosis of OPSCC treated by either radiotherapy (RT) or primary surgery. Results are based upon a tissue microarray (TMA) of 365 head neck squamous cell carcinomas (HNSCC) including 85 OPSCC with clinico-pathological and follow-up data. p16 positivity correlated significantly with oropharyngeal tumor localization (p < 0.001). Patients with p16 positive OPSCC exhibited a significantly better overall survival than those with p16 negative tumors (p = 0.007). In a multivariate analysis, survival benefit of patients with p16 positive OPSCC was independent of clinico-pathological parameters such as cT and cN classification and treatment modality. The improved prognosis of p16 positive OPSCC is found after RT as well as after surgery.

Olfactory impairment predicts brain atrophy in Parkinson's disease.

Olfactory dysfunction is a frequent nonmotor symptom in idiopathic Parkinson's disease (PD) and may be considered as an early clinical feature of the disease preceding motor symptoms by years. According to recent neuropathological staging concepts, impaired olfaction is assumed to indicate an early pathological process and might be associated with structural changes in the brain. A morphometric analysis of magnetic resonance images [voxel-based morphometry (VBM)] was used to investigate gray matter atrophy related to psychophysically measured scores of olfactory function in early PD patients (n = 15, median Hoehn and Yahr stage 1.5), moderately advanced PD patients (n = 12, median Hoehn and Yahr stage 2.5), and age-matched healthy controls (n = 17). In PD patients, but not in controls, cortical atrophy in olfactory-related brain regions correlated specifically with olfactory dysfunction. Positive correlations between olfactory performance and gray matter volume were observed in the right piriform cortex in early PD patients and in the right amygdala in moderately advanced patients. The results provided first evidence that olfactory dysfunction in PD is related to atrophy in olfactory-eloquent regions of the limbic and paralimbic cortex. In addition, olfactory-correlated atrophy in these brain regions is consistent with the assumption that olfactory impairment as an early symptom of PD is likely to be associated with extranigral pathology.

Swallowing is differentially influenced by retronasal compared with orthonasal stimulation in combination with gustatory stimuli.

Identical stimuli are processed differently when presented ortho- or retronasally. In contrast to orthonasal olfaction, retronasal odorant perception is strongly associated with flavor and food intake, which is usually followed by swallowing. Along with other stimuli, gustatory stimuli are known to influence the swallowing reflex. It was therefore the aim of present study to examine whether retronasal olfaction, in combination with simultaneous gustatory stimuli, influences swallowing in a manner different from that of orthonasal olfaction. Fifty normosmic and normogeusic subjects took part in the study. A sweet taste (glucose, delivered via an intraoral taste dispenser) was presented simultaneously with vanillin, a food-like odor, either ortho- or retronasally at random using a computer-controlled olfactometer. Ultrasound imaging of the mouth floor was recorded on videotape to continuously monitor swallowing activity. After retronasal stimulation, swallowing occurred significantly faster (7.49 vs. 9.42 s; P < 0.001) and also took place more frequently compared with swallowing after orthonasal stimulation (1.38 times vs. 1.14 times; P < 0.001). These results show that a food-like odorant presented retronasally in combination with a congruent taste stimulus can influence swallowing. Whether these results can be assigned to other, unfamiliar, unpleasant nonfood-like odors has yet to be determined.

Influence of simultaneous gustatory stimuli on orthonasal and retronasal olfaction.

Orthonasal and retronasal olfaction processes differ. The aim of this study was to examine whether congruent and incongruent simultaneous gustatory stimuli influence orthonasal and retronasal odorant perception, using olfactory event-related potentials as a measure. Thirty-two young, healthy subjects (16 men, 16 women) took part in two test sessions. Olfactory event-related potentials were recorded in response to a food-like odor, vanillin, and to an odor usually not associated with foods, the rose-like phenylethylalcohol. Each session consisted of four randomized blocks of 15 stimuli each which were applied either orthonasally or retronasally. Simultaneously, sweet or sour gustatory stimuli were applied. In response to retronasal vanillin, stimuli latencies P2 of the event-related potentials were significantly shorter in the congruent "sweet condition" than the incongruent "sour condition". In contrast, with orthonasal stimulation, shorter P2 latencies were seen for both odorants in the incongruent condition. Intensity of both odorants was perceived as less pronounced after retronasal stimulation than after orthonasal stimulation. In conclusion, application of a sweet taste significantly enhanced the processing of a congruent olfactory stimulus when presented through the retronasal route. Incongruent simultaneous gustatory stimulation applied during orthonasal olfaction seemed to induce conflict priming, also resulting in faster processing.

Is immunohistochemical epidermal growth factor receptor expression overestimated as a prognostic factor in head-neck squamous cell carcinoma? A retrospective analysis based on a tissue microarray of 365 carcinomas.

Epidermal growth factor receptor is overexpressed in more than 80% of head-neck squamous cell carcinoma. Its role as an independent prognostic marker is discussed controversially. No standardized evaluation methods are reported. The aim of our study was to analyze the prognostic relevance of epidermal growth factor receptor expression, using a tissue microarray with more than 300 tumor samples. Epidermal growth factor receptor expression was analyzed by immunohistochemistry and fluorescence in situ hybridization based on a tissue microarray of 365 head-neck squamous cell carcinomas with complete clinicopathologic and follow-up data. Multiple independent observers blinded for clinical data evaluated epidermal growth factor receptor immunostaining semiquantitatively. Cut-off scores for positivity were determined systematically by receiver operating characteristic curve analysis and validated by resampling of the data. Epidermal growth factor receptor expression cut-off scores for loco-regional relapse and overall survival were determined to be 60%. No significant correlation with clinicopathologic data was found. Independent significant differences in loco-regional control and overall survival could not be distinguished by epidermal growth factor receptor expression. Epidermal growth factor receptor expression could not be confirmed as a significant independent prognostic marker in head-neck squamous cell carcinoma using a large tissue microarray with 365 head-neck squamous cell carcinomas with complete clinical data, an evaluation based on immunohistochemistry and fluorescence in situ hybridization by multiple independent observers and systematic determination of cut-off scores.

Olfactory disorders following upper respiratory tract infections.

Postviral olfactory disorders usually occur after an upper respiratory tract infection (URTI) associated with a common cold or influenza. With a prevalence between 11 and 40% they are among the common causes of olfactory disorders. Women are more often affected than men and post-URTI disorders usually occur between the fourth and eighth decade of life. The exact location of the damage in post-URTI is not yet known even though from biopsies a direct damage of the olfactory receptor cells is very likely. Nevertheless, central mechanisms cannot completely be ruled out. The diagnosis is made according to the history, clinical examination and olfactory testing. Affected patients usually recall the acute URTI and a close temporal connection should be present to establish the diagnosis. Spontaneous recovery might occur within 2 years. So far, no effective therapy exists even though specific olfactory training might be promising.

Gustatory stimulation influences the processing of intranasal stimuli.

OBJECTIVES: Taste and smell interact. The aim of this study was to examine this interaction using gustatory and olfactory stimuli applied at the same time, which exhibited perceptual compatibility and incompatibility. METHODS: Thirty-two, young, healthy normosmic subjects (16 men, 16 women) took part in two randomized sessions. Event-related potentials (ERP) were recorded in response to vanillin, or gaseous CO2. These two conditions were combined with three "taste conditions" including sweet taste, sour taste, and the intraoral presentation of an empty taste dispenser. RESULTS: Vanillin responses were largest for the "sweet" condition, while they were smaller for the "sour condition". In contrast, responses to CO2 were largest under the "sour" condition, and smallest under the "sweet" condition. Moreover, during the "sweet" condition the latencies of P1 and N1 were shorter than in the "sour" condition, which was the other way around for CO2. CONCLUSIONS: Results of the present investigation suggested that (1) the early processing of intranasal chemosensory stimuli is modulated through concomitant gustatory stimulation, and that (2) this modulation may depend, at least in part, on the contextual compatibility between intranasal and intraoral stimuli.

What is the correlation between ratings and measures of olfactory function in patients with olfactory loss?

BACKGROUND: Major complaints of many patients with olfactory dysfunction relate to the impairment of quality of life. Nevertheless, it is unclear to what extent there is a correlation between ratings of olfactory abilities/impairment and olfactory function. METHODS: Patients with olfactory dysfunction (n = 152) were examined psychometrically using the "Sniffin' Sticks" test battery. Ratings of olfactory function and ratings of impairment were recorded using visual analog scales. RESULTS: Following standardized olfactory testing, 78 of the 152 patients were categorized as functionally anosmic, 64 as hyposmic, and 10 as normosmic. Groups differed significantly with regard to ratings of olfactory function. Functionally anosmic patients rated impairment to be significantly higher compared with hyposmic and normosmic patients. Ratings of olfactory function correlated significantly with measured olfactory function (r = +0.57) and ratings of impairment (r = -0.30). CONCLUSION: There was a moderate correlation between ratings and measures of olfactory function. On average, functionally anosmic patients recognized their olfactory loss, although, on an individual basis, there were striking differences between measures and ratings of olfactory function.

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.

Anti-inflammatory and surgical therapy of olfactory disorders related to sino-nasal disease.

Olfactory loss may be caused by mechanical obstruction or inflammation of the olfactory epithelium due to allergic/non-allergic rhinitis and chronic sinusitis with or without polyps. Treatment of olfactory loss related to sino-nasal disease is possible. Apart from surgical approaches and/or treatment with antibiotics, both systemic and topical steroids are effectively used in the therapy of olfactory loss related to sino-nasal disease. In most cases improvement of olfactory function appears to relate to the anti-inflammatory actions of the steroids used. While some details of therapeutic effect and dose regimen are not clear, systemic steroids are often helpful even in patients without nasal obstruction due to polyps or obvious inflammatory changes.