Evaluation of a non-auditory neurocognitive test battery in hearing-impaired according to age.

PURPOSE: Due to the demographic shift, the number of older people suffering from hearing loss and from cognitive impairment increases. Both are closely related and hard to differentiate as most standard cognitive test batteries are auditory-based and hearing-impaired individuals perform worse also in non-auditory test batteries. Therefore, reference data for hearing-impaired are mandatory. METHODS: The computer-based battery ALAcog assesses multiple cognitive domains, such as attention, (delayed) memory, working memory, inhibition, processing speed, mental flexibility and verbal fluency. A data set of 201 bilaterally hearing-impaired subjects aged ≥ 50 (mean 66.6 (SD 9.07)) was analysed. The LMS method, estimated curves for the 10th, 25th, 50th, 75th and 90th percentile were calculated, and classified according to age, starting from the age of 50. RESULTS: Cognitive function shows a decline in all subtests as people age, except for verbal fluency, which remains almost stable over age. The greatest declines were seen in recall and delayed recall and in mental flexibility. Age and hearing ability did not correlate (p = 0.68). However, as people age, inter-subject variability of cognitive test results increases. This was especially the case for inhibition. Cognitive function was not correlated with hearing ability (each p ≥ 0.13). CONCLUSION: The present results make an approach to establish reference data for a comprehensive non-auditory test battery in a large sample of elderly hearing-impaired people which can be used as a simple tool to better contextualise cognitive performance beyond mean and median scores.

[O-DEM: a new cognitive screening in patients with hearing loss]. / O-DEM: ein neues kognitives Screening bei Schwerhörigkeit.

BACKGROUND: Hearing loss is a significant risk factor for dementia. To date, cognitive impairment and dementia in patients with hearing impairment (HI) cannot be adequately diagnosed by commonly administered cognitive screening tests due to sensory impairments. Therefore, an adapted screening is needed. The aim of the present study was to develop and evaluate a cognitive screening for people with HI. MATERIALS AND METHODS: The new cognitive screening, called O­DEM, entails a word fluency test, the Trail Making Test A (TMT-A), and a subtraction task. First, the O­DEM was tested in a large clinical sample (N = 2837) of people without subjective HI. In a second step, the O­DEM was evaluated in 213 patients with objectively assessed HI and compared with the Hearing-Impaired Montreal Cognitive Assessment (HI-MoCA). RESULTS: The results indicate that the O­DEM subtests significantly discriminate between participants with no, mild, and moderate to severe cognitive impairment. Based on the mean and standard deviation of the participants without cognitive impairment, a transformation of the raw scores was performed and a total score with a maximum value of 10 was determined. In the second part of the study, the O­DEM was shown to be as sensitive as the HI-MoCA in differentiating between people with and without cognitive impairment. CONCLUSION: Compared to other screenings, the O­DEM is a quickly administrable screening for the detection of mild and moderate cognitive impairment in people with HI.

Parameters assessing neurological status in malignant glioma patients: prognostic value for survival and relapse-free time.

Malignant gliomas are the commonest primary brain tumours in adults and harbour a dismal prognosis. So far, established parameters with predictive significance for prognosis do not include the neurological functional assessment of patients. The aim of this study was to investigate the prognostic value of parameters assessing neurological status in malignant glioma patients for outcome and survival. Evaluation of neurological status included the Sawaya Functional Grade (SFG) and the Neurological Performance Scale (NPS). Moreover, the Karnofsky Performance Status (KPS), medical risk factors, extension of resection, postoperative complications, and the predictive value of these variables for outcome and survival were studied. For this purpose, we have analysed 110 consecutive patients with malignant gliomas who were treated at our institution. As expected, age (p <0.001), KPS (p = 0.003) and extent of resection (p <0.001) were good predictors of survival. Strikingly, SFG and NPS showed the highest significant correlation with survival (both p <0.0001) and, furthermore, they were the only predictors of the relapse-free time (p = 0.035 and p = 0.004, respectively). Our data strongly suggests that SFG and NPS accurately predict both survival and relapse-free time, which may add a valuable tool for tailoring individual therapy strategies.

[Predictors of nodal metastasising in laryngeal squamous cell carcinomas as decision support for neck dissection: comprehensive analysis of literature]. / Prädiktoren der nodalen Metastasierung des Larynxkarzinoms als Entscheidungshilfe bei der Neck Dissection: Literaturanalyse zur Frage zuverlässiger Parameter.

BACKGROUND: A subset of advanced laryngeal squamous cell carcinomas (SCC) does not metastasize in regional lymph nodes (pN0). However, more than 30 % of tumors without signs of metastasizing in the clinical examination (cN0) show occult metastases. The guidelines of the German ENT-Society intend the extent of neck dissection (ND) depending on clinical stage of tumor and lymph nodes. If laryngeal surgery is followed by an adjuvant radiation/chemotherapy, ND is not always necessary. Histomorphological, immunohistochemical, or molecular parameters with predictive value for nodal metastasizing could support the planning for ND, especially in patients with cN0. METHODS: Within the last 20 years there were many publications concerning this problem. Herein, we analyzed the results of 455 publications. We have chosen studies regarding the predictive value of tumor stage, grading, peritumorous inflammation, invasion of lymphatic vessels, angioneogenesis, proliferation, overexpression of p53 or cyclin D1, inhibitors of cyclin-dependent kinases, growth factors, apoptosis, cell-adhesion, nm23, metalloproteinases, DNA/ploidy as well as tumor genetics. RESULTS: All examined parameters did not allow a fail-safe prediction of the risk for nodal metastasizing. CONCLUSIONS: Up to now, reliable predictors do not exist. The investigation of above mentioned parameters in pre-operative tumor biopsies is not helpful for the planning of ND in the stage cN0 (out of T1).

[Malignant paranasal sinus tumors. Diagnosis, therapy and results]. / Maligne Nasennebenhöhlentumoren. Diagnostik, Therapie und Ergebnisse.

BACKGROUND: Malignant neoplasmas of the paranasal sinuses are rare and present usually in advanced tumor stage due to the lack of early clinical symptoms. PATIENTS AND METHODS: In the last 10 years, 63 patients with paranasal malignancies were treated at the Department of Otolaryngology, Head and Neck Surgery of the University of Würzburg. 33% of the patients showed an occupational exposition (wood-processing or metal industry). At the time of the first visit to our institution 95% of the patients presented with an extensive disease, staged T3 and T4. Adenocarcinoma (24%), squamous cell carcinoma (22%) and malignant melanoma (19%) were the most common histologies. Surgery combined with radiotherapy was the treatment strategy in 55 patients (87%). RESULTS: Patients with a complete surgical resection showed a higher 5-year-survival rate (77%) than patients with an incomplete resection (56%). In 38% (n=21) of the patients treated with surgery and radiotherapy, a local recurrence of the tumor was observed. This recurrence localised in the skull base and/or the orbita/periorbita occurred most frequently in the first (46%) or the second year (31%). CONCLUSION: The prognosis of malignant paranasal tumors depends mainly on the control of the local tumor growth. Modern strategies of surgical treatment in combination with radiotherapy need to be implemented in an effort to achieve a continuous remission.

Frequent detection of Mycoplasma pneumoniae in Bell's palsy.

The cause of Bell's palsy (BP) remains unknown despite various hints to an infectious etiology. Mycoplasma pneumoniae is a common pathogen of the respiratory tract causing pharyngitis, tracheobronchitis or pneumonia. Neurological complications are the most frequent extrapulmonary manifestation. So far, only a few case reports suggested an association between cranial nerve palsy and M. pneumoniae infection. Patients with a BP who were admitted to the Department of Otorhinolaryngology or Neurology of the University of Wuerzburg between 2000 and 2002 were tested serologically for the presence of antibodies against Borrelia burgdorferi, herpes viruses (HSV-1/2, VZV) and M. pneumoniae. The diagnosis of mycoplasmal infection was made when at least one of the following criteria was met: a threefold rise or more in the titer of antibody of M. pneumoniae in paired sample or a microparticle agglutination assay (MAG) of > or =1:40 and the detection of IgA and/or IgM antibodies in the acute phase serum. Ninety-one consecutive patients could be included. Fifteen patients showed a reactivation of a VZV ( n=12) or of a HSV-1 ( n=3) infection. In six cases the immunoblot revealed specific antibody bands for B. burgdorferi. In 24 patients (26.4%) a seroconversion of M. pneumoniae could be detected. Only two patients complained of mild respiratory symptoms. According to our results, M. pneumoniae is frequently associated with Bell's palsy. Thus, a routine screening for this pathogen, even in the absence of respiratory symptoms, is necessary.

[Diagnosis, treatment and results of malignant skull base tumours]. / Diagnostik, Therapie und Ergebnisse in der Behandlung maligner Schädelbasistumoren1.

BACKGROUND: Malignant tumours of the cranial base are rare and present usually in advanced tumour stage due to the lack of early clinical symptoms. PATIENTS AND METHODS: Sixty patients with malignant tumours infiltrating the skull base were treated at the Department of Otorhinolaryngology Head and Neck Surgery, University of Würzburg between 1987 and 1999. Most of the tumours (n = 51) originated from the nose or paranasal sinuses, the epipharynx, the outer ear canal or the middle ear. Seven tumours were malignant brain tumours infiltrating the bony structures of the skull base or originated from the cranial base itself. Two patients suffered from metastases of an adenocarcinoma of the prostata. The histological diagnosis was confirmed in 53 patients preoperatively and in seven patients during tumour resection. Squamous cell carcinoma (n = 24), adenocarcinoma (n = 10) and sarcoma (n = 7) were the most common histologies found. RESULTS: A radical en bloc resection of the tumour was only possible in 26 out of 60 cases. A surgical tumour reduction with postoperative radiation therapy was performed in seven patients as a palliative approach. Eight patients underwent a combined radio- and chemotherapy according to the histological diagnosis. Primary radiotherapy was the treatment of choice in eleven patients, where the tumours were located in the central area of the cranial base. Palliative radiotherapy or solely medical pain control were applied to eight patients who presented either with distant metastases or an advanced tumour growth. The mean postoperative survival following radical surgery was 48 months and after primary radiotherapy 27 months. DISCUSSION: A statistical analysis of the results is not applicable due to the great variety of the disease concerning the histological diagnosis, the tumour size and the location as well as the small number of patients.

[Detection of loudness recruitment in patients with retrocochlear lesions using the "Würzburger Hörfeld" loudness scaling]. / Rekruitmentnachweis bei retrokochleären Raumforderungen mit der Lautheitsskalierung im "Würzburger Hörfeld".

BACKGROUND: The pathogenesis of hearing loss caused by cerebellopontine angle tumors such as acoustic neuromas is unknown. The lack of loudness recruitment is thought to be one of the features of retrocochlear hearing impairment. In contrast to conventional suprathreshold tests, the categorial loudness scaling using the "Würzburger Hörfeld" is a valuable tool to describe the individual perception of sound. The aim of the present study was to analyze the loudness growth rate in patients with acoustic neuroma. PATIENTS AND METHOD: Pure tone and speech audiometry as well as auditory brainstem response and bilateral categorial loudness scaling were performed preoperatively in 54 patients with acoustic neuroma. Loudness scaling was done in free field switching off the contralateral ear by using an ear-plug. RESULTS: An abnormal rapid loudness growth function was found in 38 of the 54 patients (70.4%) at least at one frequency on the tumor side. The contralateral side was effected only in 57.4% of the patients. The incidence of a recruitment depended on the frequency with a maximum at 4 kHz. The slope of the loudness function showed a tendency to increase with increasing hearing loss. CONCLUSIONS: Loudness recruitment is not a rare phenomenon in patients with acoustic neuroma. The underlying cause (a preexisting hair cell damage, hair cell changes resulting from an obstruction of the cochlear blood supply or a disruption of the cochlear efferents) still remains unclear.

[Inner ear depression after middle ear interventions]. / Innenohrdepression nach Mittelohreingriffen.

BACKGROUND: Any type of otosurgical procedure involves the risk of inner ear damage. As middle ear surgery is also performed for functional reasons this risk should be taken into consideration. The aim of this study was to analyse the frequency and the nature of sensorineural hearing loss following chronic ear surgery. PATIENTS: A total of 3989 middle ear cases operated on between 1991 and February 1999 at the Department of Otorhinolaryngology, Head and Neck Surgery, University of Würzburg, Germany were studied retrospectively: 781 type I tympanoplasties, 2408 type III tympanoplasties and 800 cases of stapes surgery. The pre- and the postoperative audiograms in the frequency range between 500 and 8000 Hz were analysed and correlated to the different intraoperative findings. RESULTS: Sensorineural hearing loss occurred in a total of 1.3% of 2224 patients with normal preoperative bone conduction thresholds: 0.2% became deaf, 0.8% acquired a high tone loss at 4 kHz and in 0.3% patients also 2 kHz was affected. None of the documented intraoperative complications such as bleeding, unexpected opening of a semicircular canal, extensive manipulation at the ossicular chain or a gusher phenoma showed a relevant effect on postoperative bone conduction thresholds. The incidence of high tone loss was not increased in cases of extensive drilling of the temporal bone. An unexpected opening of the vestibulum led to a small, but statistically significant change in postoperative bone conduction thresholds. CONCLUSIONS: Our results demonstrated that the risk for sensorineural hearing loss caused by middle ear surgery is low. None of the analysed factors seems to be a relevant prognostic risk factor for postoperative inner ear depression.

A broad spectrum PCR method for the detection of polyomaviruses and avoidance of contamination by cloning vectors.

Polyomaviruses induce tumours of different histological types when inoculated into experimental animals, but their aetiological role in the development of malignant tumours in humans remains questionable. We developed a degenerate PCR assay in an attempt to identify additional, presently unknown human polyomavirus types which may be involved in the malignant transformation of human tissues. Degenerate oligonucleotide primers were deduced from four different conserved amino acid motifs in the highly conserved viral capsid protein, VP1. Three different sets of primers were included for the each test. Bladder carcinomas, Hodgkin's lymphomas, meningiomas, Kaposi-tumours and -cell lines were analysed. No polyomavirus DNA sequences could be detected. A comparative analysis led to the recognition of the presence of SV40 DNA sequences in more than 200 vectors available in the EMBL and Genbank Databanks and commonly used in laboratories worldwide. The majority of primers used to detect polyomavirus sequences in human tumours are distributed throughout these regions also present in the vectors. Only a small stretch of 286bp in the overlapping region of the VP1, VP2 and VP3 genes is not present in the vector sequences. We propose to use this region for the design of additional non-contamination primers.

Screening human tumor samples with a broad-spectrum polymerase chain reaction method for the detection of polyomaviruses.

Polyomaviruses induce tumors of different histological types when inoculated into experimental animals. An etiological role for this virus group in the development of malignant tumors in humans remains questionable, despite several reports demonstrating the presence of SV40, JCV, and BKV DNA in human cancers. Only two human polyomavirus types are known to date: JCV, causing progressive multifocal leukoencephalopathy (PML) under severe immunosuppression, and BKV, first isolated from the urine of a renal transplant recipient and associated with hemorrhagic cystitis. We developed a degenerate polymerase chain reaction assay in an attempt to identify additional, presently unknown human polyomavirus types that may be involved in the malignant transformation of human tissues. A large part of the gene coding for the viral capsid protein VP1 is highly conserved in nine polyomavirus types (and their strains) and was therefore selected as most suitable for the primer design. Degenerate oligonucleotide primers were deduced from four different conserved amino acid motifs in this region. Three different sets of primers were included in each test to obtain the highest sensitivity in combination with primers with the lowest degeneracy numbers. The sensitivity obtained ranged from 1 copy/cell for bovine polyomavirus to 100 copies/cell for LPV after ethidium bromide staining and was increased at least 10-fold after hybridization with a radiolabeled probe. A subsequent seminested amplification allowed for the detection of 1 copy/cell for LPV. These degenerate primers were applied to analyze bladder carcinomas, Hodgkin lymphomas, meningiomas, Kaposi tumors, and Kaposi-derived cell lines. No polyomavirus DNA sequences could be detected.

Novel HPV types present in oral papillomatous lesions from patients with HIV infection.

Patients infected with the human immunodeficiency virus (HIV) often develop multiple papillomatous lesions of the oral cavity. In the present study, a total of 67 biopsies from benign oral lesions were analyzed for the presence of human papillomavirus (HPV) DNA using Southern-blot hybridization in combination with a polymerase chain reaction designed to detect all known HPV types, as well as unidentified types. These samples, collected at random from a high-risk population, were subsequently divided into 57 biopsies originating from patients with confirmed HIV infection and 10 biopsies from patients with unknown HIV status. Each sample was amplified with 7 different combinations of degenerate primers. All amplified products were sequenced. HPV DNA sequences were detected in 67% (45/67) of the samples. HPV 7 (19%) and HPV 32 (28%) were the predominant HPV types. HPV 32 was present in 2/4 fibromas tested. Two new HPV types, HPV 72 and HPV 73, were identified in oral warts with atypia. The complete genomes of these viruses were cloned and sequenced. Other HPV types detected were HPV 2a, HPV 6b, HPV 13, HPV 16, HPV 18, HPV 55, HPV 59 and HPV 69.