Antoinette am Zehnhoff-Dinnesen

Organic cation transporter 2 mediates cisplatin-induced oto- and nephrotoxicity and is a target for protective interventions.

The use of the effective antineoplastic agent cisplatin is limited by its serious side effects, such as oto- and nephrotoxicity. Ototoxicity is a problem of special importance in children, because deafness hampers their language and psychosocial development. Recently, organic cation transporters (OCTs) were identified in vitro as cellular uptake mechanisms for cisplatin. In the present study, we investigated in an in vivo model the role of OCTs in the development of cisplatin oto- and nephrotoxicity. The functional effects of cisplatin treatment on kidney (24 hours excretion of glucose, water, and protein) and hearing (auditory brainstem response) were studied in wild-type and OCT1/2 double-knockout (KO) mice. No sign of ototoxicity and only mild nephrotoxicity were observed after cisplatin treatment of knockout mice. Comedication of wild-type mice with cisplatin and the organic cation cimetidine protected from ototoxicity and partly from nephrotoxicity. For the first time we showed that OCT2 is expressed in hair cells of the cochlea. Furthermore, cisplatin-sensitive cell lines from pediatric tumors showed no expression of mRNA for OCTs, indicating the feasibility of therapeutic approaches aimed to reduce cisplatin toxicities by competing OCT2-mediated cisplatin uptake in renal proximal tubular and cochlear hair cells. These findings are very important to establish chemotherapeutical protocols aimed to maximize the antineoplastic effect of cisplatin while reducing the risk of toxicities.

A systematic review of the mismatch negativity as an index for auditory sensory memory: From basic research to clinical and developmental perspectives

Auditory sensory memory is an important ability for successful language acquisition and processing. The mismatch negativity (MMN) in response to auditory stimuli has been proposed as an objective tool to measure the existence of auditory sensory memory traces. By increasing interstimulus intervals, attenuation of MMN peak amplitude and increased MMN peak latency have been suggested to reflect duration and decay of sensory memory traces. The aim of the present study is to conduct a systematic review of studies investigating sensory memory duration with MMN. Searches of electronic databases yielded 743 articles. Of these, 37 studies met final eligibility criteria. Results point to maturational changes in the time span of auditory sensory memory from birth on with a peak in young adulthood, as well as to a decrease of sensory memory duration in healthy aging. Furthermore, this review suggests that sensory memory decline is related to diverse neurological, psychiatric, and pediatric diseases, including Alzheimers disease, alcohol abuse, schizophrenia, and language disorders. This review underlines that the MMN provides a unique window to the cognitive processes of auditory sensory memory. However, further studies combining electrophysiological and behavioral data, and further studies in clinical populations are needed, also on individual levels, to validate the MMN as a clinical tool for the assessment of sensory memory duration.

Left-right asymmetry in hearing loss following cisplatin therapy in children--the left ear is slightly but significantly more affected.

Objectives: Bilateral symmetric high frequency hearing loss is regarded as one of the main characteristics of cisplatin-induced ototoxicity. Hair-cell damage because of cisplatin is discussed as the leading cause of hearing loss. Our observations in long-term audiological follow-up of children treated with cisplatin did not always show the anticipated symmetry of hearing loss. Design: Pure-tone audiograms of 55 (34 m, 21 f) children receiving chemotherapy with cisplatin at Muenster university hospital were analyzed. We compared pure tone hearing thresholds, transient evoked otoacoustic emissions levels and distortion product otoacoustic emissions levels before and after chemotherapy with cisplatin. Results: After therapy, the 55 children showed slightly higher average hearing levels in the range 2000 to 8000 Hz in the left ear. The side difference was significant at 4000, 6000, and 8000 Hz. In girls, the effect was less pronounced than in boys. Conclusions: This result, on the one hand, indicates that the auditory system is already responding asymetrically at the cochlear level, on the other hand it underscores the need for further research into the pathophysiology of platinum ototoxicity. There are parallels with stronger effects to the left ear in oiseinduced hearing loss as described in literature. Special attention should be given to possible supracochlear pathways of damage. Clinicians should consider that cisplatin associated hearing loss is not necessarily symmetric.

Neural Correlates of Speech Processing in Prelingually Deafened Children and Adolescents with Cochlear Implants

Prelingually deafened children with cochlear implants stand a good chance of developing satisfactory speech performance. Nevertheless, their eventual language performance is highly variable and not fully explainable by the duration of deafness and hearing experience. In this study, two groups of cochlear implant users (CI groups) with very good basic hearing abilities but non-overlapping speech performance (very good or very bad speech performance) were matched according to hearing age and age at implantation. We assessed whether these CI groups differed with regard to their phoneme discrimination ability and auditory sensory memory capacity, as suggested by earlier studies. These functions were measured behaviorally and with the Mismatch Negativity (MMN). Phoneme discrimination ability was comparable in the CI group of good performers and matched healthy controls, which were both better than the bad performers. Source analyses revealed larger MMN activity (155–225 ms) in good than in bad performers, which was generated in the frontal cortex and positively correlated with measures of working memory. For the bad performers, this was followed by an increased activation of left temporal regions from 225 to 250 ms with a focus on the auditory cortex. These results indicate that the two CI groups developed different auditory speech processing strategies and stress the role of phonological functions of auditory sensory memory and the prefrontal cortex in positively developing speech perception and production.

Responsive parenting intervention after identification of hearing loss by Universal Newborn Hearing Screening: The concept of the Muenster Parental Programme

BACKGROUND Parents of newborns with hearing loss (HL) identified by Universal Newborn Hearing Screening (UNHS) programmes wish for educational support soon after confirmation and for contact with other affected families. Besides pedaudiological care, a high level of family involvement and an early start of educational intervention are the best predictors for successful oral language development in children with HL. The implementation of UNHS has made it necessary to adapt existing intervention concepts for families of children with HL to the needs of preverbal infants. In particular, responsiveness has proven to be a crucial skill of intuitive parental behaviour in early communication between parents and their child. Since infants with HL are being fitted earlier with hearing devices, their chances of learning oral language naturally in daily communication with family members have noticeably improved. OBJECTIVES The Muenster Parental Programme (MPP) aims at empowering parents in communicating with their preverbal child with HL and in (re-)building confidence in their own parental resources. Additionally, it supplies specific information about auditory and language development and enables exchange with other affected parents shortly after the diagnosis. CONCEPT The MPP is a responsive parenting intervention specific to the needs of parents of infants with HL identified by UNHS or through other indices and testing within the first 18 months of life. It is based on the communication-oriented Natural Auditory Oral Approach and trains parental responsiveness to preverbal (3-18 months) infants with HL. The MPP has been developed for groups of 4-6 families and comprises six group sessions (without infants), two single training sessions with video feedback, and two individual counselling sessions. At the age of 24-30 months, an individual refresher training session is offered to the parents for adapting their responsiveness to the current verbal level of the child via dialogic book reading. The programme also benefits parents of paediatric cochlear implant (CI) candidates preimplantation and postimplantation. CONCLUSIONS The MPP is evidence-based (see Glanemann et al., this volume) and meets the current need for effective family-centred educational intervention after UNHS.

Spontaneous Otoacoustic Emission Enhancement in Children with Reduced Speech-in-Noise Intelligibility

Reduced speech-in-noise intelligibility is one of the main difficulties experienced by children with auditory processing disorder (APD). Previous studies have established a relationship between the function of the medial olivocochlear system (MOCS) and reduced inhibition of otoacoustic emissions (OAE) in children with APD. This study measured spontaneous OAE (SOAE) in 27 children with reduced speech-in-noise intelligibility, and those of a control group matched by gender and age. A significantly higher prevalence of SOAE was found: 85% of the study group presented SOAE, 44% in the control group. An abnormally functioning MOCS with reduced inhibition could lead to an increase in SOAE. Identifying a higher prevalence and number of SOAE may be a helpful objective mean to include in an APD diagnosis test battery.

Feasibility of 1000 Hz tympanometry in infants: Tympanometric trace classification and choice of probe tone in relation to age

OBJECTIVES Universal newborn hearing screening (UNHS) has significantly reduced the age of children undergoing audiological examinations. Middle ear function is usually evaluated with tympanometry using a probe tone of 226 Hz, although higher frequencies are recommended in infants. The aim of this study was to compare the feasibility of 226 and 1000 Hz tympanometry for different trace classification systems in relation to age, risk factors for hearing loss and ear canal volume. METHODS Data from 577 infants (915 ears) <1 year were analyzed. Tympanograms were classified according to the classification systems of Jerger, Marchant et al. and Kei et al. and correlated with ear microscopy as the gold standard. Test quality parameters of tympanometry with probe tones of 226 and 1000 Hz were compared in four different age groups. RESULTS The trace classification following Kei et al. presented the best correlation to ear microscopy and reduced the number of unclassified tympanograms. The use of probe tones of 226 Hz in infants below the age of nine months showed a poor level of sensitivity. CONCLUSIONS We recommend the use of a 1000 Hz probe tone in infants at least up to the age of nine months. In this age group, 226 Hz tympanometry is inappropriate. In children with craniofacial abnormalities and smaller ear canal volumes, 1000 Hz tympanometry could be taken into consideration, even for older children. High-frequency tympanograms should be evaluated according to the classification system of Kei et al., which differentiates between peaked (normal) and flat (abnormal) curves.

Progressive hearing loss after completion of cisplatin chemotherapy is common and more pronounced in children without spontaneous otoacoustic emissions before chemotherapy

OBJECTIVE High frequency hearing loss following cisplatin chemotherapy is frequent in children and often necessitates the fitting of hearing aids. During therapy, hearing is usually monitored. Post-therapeutic follow-up does not routinely include monitoring of hearing, although there are indications that hearing thresholds can decline after therapy. METHODS Pure-tone audiograms taken from 27 children (17 males, 10 females) treated with cisplatin at Muenster university hospital (mean age 9.84 years, standard deviation 3.67 years) including an audiological follow-up at least 6 months after therapy, were analyzed retrospectively. RESULTS In follow-up tests after completion of therapy, 24.1% of all ears showed an increase in mean high frequency hearing thresholds (4-8 kHz). Post-therapeutic hearing deterioration was significant at 4 kHz and significantly more pronounced in children without measurable spontaneous otoacoustic emissions (SOAE) before therapy. Post-therapeutic hearing deterioration did not occur in ears with normal pure tone thresholds (≤ 10dB at all frequencies) after cisplatin therapy. No correlation was found between post-therapeutic hearing deterioration and cranial irradiation. CONCLUSIONS Cisplatin chemotherapy follow-up should include audiological monitoring in all children with elevated pure tone thresholds after therapy. Routine SOAE measurements taken as part of baseline audiometry before the start of chemotherapy can be taken into consideration.

Communication disorders in the elderly

Abstract The percentage of elderly individuals in the general population is increasing because of rising average life expectancy. Elderly people today enjoy much more active and more communicative lives than previous generations. However, due to age related changes and the increasing prevalence of diseases affecting phonation, articulation, respiration, speech, deglutition and their neurological regulation mechanisms – dysphonia, dysarthria, aphasia/dysphasia and dysphagia, they are becoming more frequent in this population group. These communication disorders can cause social isolation, anxiety and depression. Patients and family members alike suffer from the negative impact these disorders have on communication and quality of life. The prevalence of age related voice problems in the elderly is reported to be as high as 20–47%, for speech and/or language problems 70–75%, and up to 40% for dysphagia. There is a growing need for effective therapeutic approaches to communication disorders in the elderly. Physiological age related changes, the causes of communication disorders in the elderly, their impact on daily life, and rehabilitative options are presented.

Development and evaluation of the new module ‘communication disorders’ in medical education

Background: Communication disorders are not taught as a self-contained topic in medical education, despite their high incidence and the similarities in the way in which they present clinically. Aims: This article describes the development of an elective subject ‘Phoniatrics and Pediatric Audiology’ covering five topics: hearing, language, and voice as well as psychometric tests and swallowing, with the objective of teaching a basic knowledge of the anatomy, physiology, and pathophysiology of the hearing and language system as well as symptoms, diagnostics, examination, and therapy of communication disorders. It contains theoretical background, practical exercises, and demonstrations of patient examinations. Methods: After initial modifications to the course, a statistical evaluation of the last two half-years in 2006 was performed. Results: The majority of students believe that the subject will be useful in their subsequent studies (94.2%) and medical practice (51.9%). All students affirmed that their expectations had been met by the course and they would choose it again. Conclusions: Uniting several communication disorders within a self-contained topic provides the opportunity to understand pathophysiological principles, similarities, and differences between normal and impaired function of the hearing and language system and voice production. In the authors’ opinion, it is a reasonable inclusion in medical training recognizing the importance of communication in todays service society.