Psychophysiological and electrophysiological testing of olfactory and gustatory function in patients with multiple sclerosis.

The olfactory (OF) and gustatory function in multiple sclerosis (MS) patients and possible influencing variables of the disease, such as depression or fatigue, were determined. In an open prospective controlled clinical study 30 patients with MS and 30 healthy controls matched for age, sex and smoking-habits were investigated. With Mini Mental State Examination cognitive dysfunction was excluded, with Expanded Disability Status Scale the patient's ability to accomplish the tests was ensured. The severity of depression was measured with the self-reported Beck Depression Inventory. The orthonasal olfactory function was derived with olfactory event related potentials (OERP) and TDI-score (Threshold, Discrimination and Identification, Sniffin' Sticks). Retronasal olfactory function was tested with Taste-Powder-score, gustatory function with Taste-strip-score. There was a significant loss of olfactory function measured with TDI-score [12/30 (40%), p = 0.002] and gustatory function [5/23 (21.7%), p < 0.001] in MS-patients, 23.8% (5/21) of MS-patients showed hyposmia with OERPs, significantly correlating with the TDI-score (p = 0.03). The Expanded Disability Status scale score inversely correlated with the TDI-score (p = 0.002). This study confirms the incidence of olfactory disorder in MS-patients and reveals a frequent gustatory deficit. The Identification subtest can be proposed as a marker of the OF in MS-patients: it includes complex cognitive tasks and may be influenced by depression and fatigue, which are common symptoms of MS. It inversely correlates with the disability status.

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.

Reporting of rejection after renal transplantation in large immunosuppressive trials: biopsy-proven, clinical, presumed, or treated rejection?

BACKGROUND: Prevention of acute rejection still is an important endpoint in randomized controlled trials. Poor study reporting may create confusion and render decision-making difficult. The present study thoroughly analyses the presentation and definition of rejection in reports on large multicenter immunosuppressive trials published in the field of renal transplantation. METHODS: Publications of large immunosuppression trials in kidney transplantation were identified by a predefined search strategy. The reported acute and biopsy-proven acute rejection (BPAR) episodes and additional information on number of patients recruited, publication year, impact factor, definition of acute rejection and the reporting of efficacy analyses were extracted. All reports were scanned for (a) at what point and (b) for which signs or reasons a biopsy was performed. RESULTS: Eight of 41 (19.5%) papers investigating rejection rates reported a sufficient definition of acute rejection. Twenty-eight of 41 (68.3%) presented more than one rejection rate and were published in significantly higher impact journals. The absolute difference between clinical rejection and BPAR had a median of 6.5% and a wide range (0-16.9%). Efficacy analysis was presented in all but four (90.2%) reports. Thirteen of 35 (37.1%) papers did report the timing of the biopsies and 25 of 35 (71.4%) publications gave specifications of when a biopsy sample should be taken. CONCLUSIONS: The requirements of proper reporting of rejection episodes are not fulfilled in most of the publications and the use of many different terms for the description of rejection rates is confusing at present. Our comprehensive review clearly demonstrates the need for improved and standardized reporting of rejection episodes and we suggest to report both acute rejection and BPAR.

Effect of laser treatment on olfactory dysfunction.

Olfactory disorders are not rare and affect quality of life in patients. The purpose of our study was to evaluate the outcomes of an outpatient-based diode laser inferior turbinate reduction (ITR) in otherwise therapy-refractory olfactory disorder. In a prospective clinical investigation, 20 patients (7 male, 13 female, mean age 53.2 ± 15.34) with olfactory disorder and 10 patients (8 male, 2 female, mean age 52.5 ± 17.55) without olfactory disorder underwent ITR under videoendoscopic control with a continuous diode laser in "contact" mode after topical anesthetic preparation. Treatment efficiency was assessed before and 2 months after surgery. Subjective nasal airflow (NA) and the olfactory function were rated by means of visual analogue scales (VAS). Olfactory function was assessed using the "Sniffin' Sticks" test battery. VAS showed very low median values for intraoperative pain (0) [0-1.20] and high postoperative patient satisfaction (8) [5-9]. After 2 months there was no significant improvement of objective olfactory function as measured by the TDI score (threshold, discrimination and identification). The VAS displayed a slight significant improvement in the group of patients with olfactory disorder from 2.95 to 3.65 (P = 0.04). After 2 months, NA data revealed a statistically significant improvement of subjective VAS from 5.05 to 6.25 (P < 0.0005) and of objective NA from 353.77 to 443.50 (P = 0.007) as measured by rhinomanometry in both groups. Outpatient diode laser ITR represents an effective option providing recovery by NA improvement but not a significant improvement of the olfactory function.

Active olfactory training for the treatment of smelling disorders.

Olfactory function appears to be influenced by repeated odor stimulation. We conducted a nonrandomized, nonblinded, retrospective study of the impact of an 8-month period of olfactory training in patients with olfactory dysfunction. Our study population was made up of 46 adults-14 men and 32 women (mean age: 59.17 ± 13.25 yr)-with olfactory dysfunction of different etiologies (sinonasal: n = 15; post-upper-respiratory-tract infection [URTI]: n = 16; post-traumatic: n = 7; and idiopathic: n = 8). All patients had been previously treated without success with systemic or topical corticosteroids. For their training, patients exposed themselves to four different odors twice a day. Olfactory function was evaluated at baseline and again at 4 and 8 months, and results were quantified in the form of each patient's TDI (threshold, discrimination, and identification) score. Of the 46 patients, 28 had undergone olfactory training only, while the remaining 18 had received topical corticosteroids in addition to training. At study's end, the mean overall TDI score in the entire group increased by 4.09 points over baseline--a statistically significant increase (p = 0.01); this increase was mainly attributable to improvement in the identification component of the TDI, which increased by 2.51 points (p = 0.02). Among the 18 patients who received a topical corticosteroid in addition to training, the mean TDI increased by 6.83 points (p = 0.001), primarily because of improvements in the discrimination and identification components. The 28 patients who underwent olfactory training alone experienced a mean increase in the identification component of only 2.20 points (p = 0.14) after 8 months. Olfactory function in the post-URTI patients increased significantly at 4 months. We conclude that olfactory discrimination and identification can be enhanced by the addition of a topical corticosteroid to a program of defined, daily, short-term exposure to olfactory training.

Olfactory function in patients with multiple sclerosis: a diffusion tensor imaging study.

BACKGROUND: Previous research has shown that multiple sclerosis (MS) patients can develop olfactory disturbances. OBJECTIVE: The purpose of our study was to investigate how olfactory function in MS patients correlates with cerebral magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI). METHODS: Olfactory performance was tested in 30 MS patients and 30 controls to determine odour threshold (T), odour discrimination (D), and odour identification (I) summarised in the TDI score. The lesion load (number and total volume of lesions) was measured on proton-density (PD)- and T2-weighted images of the olfactory brain and the total brain. Fractional anisotropy (FA) of the lesions and the surrounding normal-appearing brain tissue (NABT) was quantified using DTI. RESULTS: The median FA of white matter lesions was 0.29 and was on average 11.1% lower than in the surrounding NABT. The normalised TDI score and the normalised I subscore were significantly poorer in the MS group compared to controls (p<0.0001), while the T and D subscores were similar in both groups. The median FA of lesions in the olfactory brain correlated inversely with the decreased I subscore (p=0.001). There was also a strong correlation between the TDI score and the Expanded Disability Status Scale (EDSS) (p=0.001). CONCLUSION: A strong inverse relationship between decreased odour identification ability of MS patients and FA values in the olfactory brain indicates that the reduction in I is more strongly affected by lesions in areas with high FA values, i.e., with an increased amount of affected white matter tracts.

Topical beclomethasone in the therapy of smelling disorders-a new application technique.

Systemic corticosteroid is the first-line-treatment for olfactory dysfunction of sinonasal origin but is afflicted with many side-effects. Topic corticosteroid does not reach the same efficacy but has a remarkable safety profile. In this trial we investigated the efficacy of topic therapy with beclomethasone (BDP) -spray. The drug was applied precisely to the olfactory cleft by a special spraying top-part. In addition we determined extinction and volume of a gelaspon sponge placed in the olfactory cleft to show the difference of the topical spray application. 18 patients with anosmia or hyposmia of different genesis and duration applied BDP-spray twice daily for four weeks. The olfactory function was determined using the TDI score ('Sniffin'-Sticks test battery'). Factors correlated with therapy efficacy were assessed. The median TDI score increased from 13.5 (0-25) at the beginning to 18.5 (1-26) after therapy of four weeks (P = 0.005). The extinction and volume in the moistened sponge was more than two times greater with the top-part than without. The direct application of BDP-spray to the olfactory cleft attained superior therapeutic effects than a usual applied mometasone spray, but did not perform as good as systemic corticosteroid treatment.

Structural correlates of taste and smell loss in encephalitis disseminata.

BACKGROUND: Olfactory dysfunction in MS patients is reported in the literature. MRI of the olfactory bulb (OB) is discussed as a promising new testing method for measuring olfactory function (OF). Aim of this study was to explore reasons for and optimize the detection of olfactory dysfunction in MS patients with MRI. MATERIALS AND METHODS: OB and olfactory brain volume was assessed within 34 MS patients by manual segmentation. Olfactory function was tested using the Threshold-Discrimination-Identification-Test (TDI), gustatory function was tested using Taste Strips (TST). RESULTS: 41% of the MS patients displayed olfactory dysfunction (8% of the control group), 16% displayed gustatory dysfunction (5% of the control group). There was a correlation between the OB volume and the number and volume of MS lesions in the olfactory brain. Olfactory brain volume correlated with the volume of lesions in the olfactory brain and the EDSS score. The TST score correlated with the number and volume of lesions in the olfactory brain. CONCLUSION: The correlation between a higher number and volume of MS lesions with a decreased OB and olfactory brain volume could help to explain olfactory dysfunction.

Olfactory and gustatory function in patients with multiple sclerosis.

BACKGROUND: The olfactory function (OF) and gustatory function in patients with multiple sclerosis (MS) can be limited. METHODS: We performed the testing of orthonasal (Threshold Discrimination Identification [TDI] score with Sniffin' Sticks) and retronasal (Taste Powder) OF and gustatory function (Taste Strips; Burghart, Wedel, Germany) in patients diagnosed with MS and healthy controls matching in age, sex, and smoking habits. RESULTS: Eight of 16 MS patients (50%) displayed hyposmia (TDI score, 28.75 ± 1.28; p = 0.06); the identification subtest significantly was restricted (12.63 ± 1.67; p = 0.001). Four of 16 MS patients (25%) had limited retronasal OF with a Taste Powder score of 4.5 ± 1.29. The gustatory function in 19% of MS patients was significantly limited (Taste Strip score, 5.33 ± 2.52; p = 0.02). Patients who estimated their ability to smell as diminished performed more poorly on retronasal OF testing (r =0.657; p = 0.046). CONCLUSION: This study confirms the incidence of olfactory disorder in MS patients that has been reported in the literature. Interestingly, a significant correlation between orthonasal and retronasal OF testing was not shown. A higher incidence of gustatory dysfunction was shown and might serve as another potential marker for this disease.

Cancer of the external auditory canal-diagnostic and treatment.

BACKGROUND: Ear squamous cell carcinoma (SCC) is a tumor with a poor prognosis, due to a late initial diagnosis because of a concealment by primarily benign symptoms and due to the unfavorable localization including the infiltration of important structures such as the middle ear, mandibular joint or dura. PATIENTS AND METHODS: We retrospectively examined 10 patients, medium age: 63.8 ± 9.3 years between 2002 and 2008 with a histological confirmed SCC of the external auditory canal. The median follow-up period was 20.5 months (range 7-60 months). RESULTS: The treatment involving surgery, radiotherapy and/or chemotherapy yielded a survival rate of 38.3 ± 11.3 months for T1 and a survival rate of 17.0 ± 3.0 months for T2-T4 tumors. 3/10 patients at T1 stage are under follow-up, all 7/10 (70%) patients at T2 and T4 stage did not survive 5 years. CONCLUSION: The prognosis for ear SCC primarily depends on early clinical and histopathological diagnostics and requires a sufficient and standardized staging to determine the therapy involving surgery and radiochemotherapy.

Correlation of olfactory dysfunction of different etiologies in MRI and comparison with subjective and objective olfactometry.

BACKGROUND: The clinical diagnosis of olfactory dysfunction of different etiologies has been standardized by the German Working Group of Olfactology and Gustology, but there is no agreement about the most suitable imaging modality for diagnosing this disorder. MATERIAL AND METHODS: A total of 24 patients (13 women, 11 men; mean age 52 years) with different types of olfactory dysfunction (anosmia, hyposmia) were examined by objective and subjective olfactometry and magnetic resonance imaging (MRI) of the olfactory bulb. RESULTS: There was a positive correlation between objective olfactometry and volumetry of the olfactory bulb but no correlation between subjective olfactometry and MRI. CONCLUSION: MRI allows an evaluation of the olfactory bulb and appears to be superior to other modalities such as computed tomography (CT). Objective olfactometry remains the gold standard for reliable diagnosis of olfactory dysfunction.

The scent-diffusing ventilator for rehabilitation of olfactory function after laryngectomy.

BACKGROUND: The larynx bypass (LB) is the only device capable of providing laryngectomy patients with the ability to smell. Our findings regarding one-time and long-term use did reveal an improved olfactory function in these patients. Because the LB is difficult to use, however, it is not appropriate for everyday use. Therefore, we devised a new instrument: the scent-diffusing ventilator (SV). METHODS: Between January 2006 and February 2007, we researched the olfactory function of 16 patients who had undergone a laryngectomy (13 men/3 women; median age, 63 years) by using the LB and the SV. Their olfactory function was measured with the Sniffin' Sticks test battery. Further practicability of both methods was determined through a visual analog scale (1-10). RESULTS: The patients' olfactory function significantly improved (SV median 8 versus LB median 7; p < 0.002). In addition, the SV was much easier to use than the LB (median, 6 versus 5; p < 0.001). CONCLUSION: Further technical improvements are necessary to make the SV an established part of the rehabilitation of the olfactory function after laryngectomy.

Rehabilitation of the olfactory sense after laryngectomy: long-term use of the larynx bypass.

Patients who undergo laryngectomy typically lose their sense of smell. One device that has been used to rehabilitate olfactory function in these patients is the larynx bypass. We conducted a long-term study of the larynx bypass in 16 laryngectomized patients. After undergoing objective and subjective baseline evaluations, patients were asked to use the device at home for at least 30 minutes each day for 3 months. They were also asked to record in a diary subjective ratings of their sense of smell and the practicability of using the device every day. At study's end, patients experienced a statistically significant improvement (p < 0.001) in olfactory function on objective measurement (Sniffin' Sticks testing). Subjective improvement was seen after 1 week (p < 0.001) and maintained throughout the study. Practicability scores improved statistically (p = 0.003), but the device remained difficult to use. The long-term use of the larynx bypass has not been studied previously, and we hope that our findings will serve as a basis for further investigation.

Reports of large immunosuppression trials in kidney transplantation: room for improvement.

The reporting quality of publications of clinical trials can affect the quality of clinical decision-making. We systematically assessed the quality of publications of large multicenter trials evaluating immunosuppressive regimens in de novo kidney transplantation. Study quality, reporting quality and accessibility of the results of 63 publications were assessed independently by three blinded investigators using an instrument combining the Jadad scale with a list of reporting quality items. Study quality was rated with an average of only 2.3 (range 1-5) on the Jadad scale. Unblinded studies were reported in 68.3% of publications and follow-up longer than 12 months was reported for only 13 out of 50 studies. The reviewed publications fulfilled an average of 69.1% of the reporting quality criteria. Fifty-four percent of publications did not report both treated and biopsy-proven rejections. Whether reported graft survival was censored for death could not be determined for 27% of publications. Only a few publications gave confidence intervals (CIs) or stated whether additional analyses were pre-specified. Even the largest trials of immunosuppression in kidney transplantation show considerable quality deficits in their design and publication. Additional efforts are required of investigators, editors and sponsors to achieve maximum study and reporting quality.