Christian Desloovere

Treatment of Severe Laryngeal Papillomatosis With Intralesional Injections of Cidofovir ((S)-1-(3-Hydroxy-2-Phosphonylmethoxypropyl) Cytosine)

Respiratory papillomatosis is a rare and often severe disease, usually localized in the larynx. It may cause respiratory distress and even life‐threatening obstruction of the airways. Treatment is generally based on the evaporation of the lesions with a CO2 laser, but microsurgery, cytotoxic and/or cytostatic drugs, interferons, and vaccines are also used. Cidofovir [(S)‐1‐(3‐hydroxy‐2‐phosphonylmethoxypropyl)cytosine] (HPMPC) was shown to suppress the growth of tumors induced by rabbit papillomavirus as well as human papillomavirus (HPV). The efficacy of cidofovir was assessed in 17 patients with severe respiratory papillomatosis. Cidofovir at a concentration of 2.5 mg/ml was injected directly in the different laryngeal papillomatous lesions during microlaryngoscopy under general anesthesia. Biopsies were taken before the treatment was started both for anatomopathology and viral typing. HPMPC kinetics in serum was monitored in three patients, the drug levels being determined by high‐performance liquid chromatography. Complete disappearance of the papillomatosis was observed in 14 patients. Four patients relapsed and were successfully treated again with cidofovir. Of the three remaining patients, one progressed while under treatment with cidofovir, after an initial marked response. One patient had a partial remission and remained stable for more than 1 year after the last injection. He had a very aggressive and extensive disease originally. Finally, one patient was lost to follow‐up after four injections. Intratumoral injections of cidofovir for the treatment of severe laryngeal papillomatosis is a powerful new therapeutic approach for this disease. Treatment was well tolerated, and no significant side effects were noted. J. Med. Virol. 54:219– 225, 1998.

Earlier intervention leads to better sound localization in children with bilateral cochlear implants.

We present sound localization results from 30 children with bilateral cochlear implants. All children received their implants sequentially, at ages from 6 months to 9 years for the first implant and 1.5–12 years for the second implant, with delays of 10 months to 9 years. Localization was measured in the sound field, with a broadband bell-ring presented from 1 of 9 loudspeakers positioned in the frontal horizontal plane. The majority of the children (63%) were able to localize this signal significantly better than chance level. Mean absolute error scores varied from 9 to 51° (root mean square error scores from 13 to 63°). The best scores were obtained by children who received their first implant before the age of 2 years and by children who used hearing aids prior to implantation for a period of 18 months or longer. Age at second implantation was important in the group of children who did not use a contralateral hearing aid during the unilateral implant period. Additionally, children who attended a mainstream school had significantly better localization scores than children who attended a school for the deaf. No other child or implantation variables were related to localization performance. Data of parent questionnaires derived from the Speech, Spatial and Qualities of Hearing Scale were significantly correlated with localization performance. This study shows that the sound localization ability of children with bilateral cochlear implants varies across subjects, from near-normal to chance performance, and that stimulation early in life, acoustically or electrically, is important for the development of this capacity.

Clinical application of dichotic multiple-stimulus auditory steady-state responses in high-risk newborns and young children

Experience with dichotic multiple-stimulus auditory steady-state responses (ASSRs) in clinical practice is described. ASSR thresholds were assessed in a sample of 60 high-risk newborns and young children between birth and 4 years of age. Amplitudes and signal-to-noise ratios (SNRs) of the ASSR were compared between normal-hearing infants and adults. Age-related changes within a group of infants younger than 3 months of age were investigated. A comparison was made between ASSR, the click-evoked auditory brainstem response and behavioral hearing thresholds in infants with a wide range of hearing threshold levels. Mean ASSR thresholds for normal-hearing infants at an average corrected age of 12 days were 42 ± 10, 35 ± 10, 32 ± 10 and 36 ± 9 dB SPL for 0.5, 1, 2 and 4 kHz, respectively. Compared to adults, these thresholds were elevated by on average 11 dB and SNRs were 1.7 times smaller. However, based on ASSRs, reasonably accurate estimations could be made of behavioral hearing thresholds obtained at a later age (median delay of 7 months). The predicted thresholds were in 61% of the cases within 10 dB of the corresponding behavioral thresholds, and in 83% of the cases within 15 dB. In less than 1 h, thresholds at four frequencies per ear could be obtained. The optimal age of testing is between 1 week and 3 months corrected age. The dichotic multiple-stimulus ASSR technique is a valuable extension of the clinical test battery for hearing-impaired children, as a follow-up diagnostic after the neonatal hearing screening.

Sound localization, sound lateralization, and binaural masking level differences in young children with normal hearing.

Objectives: In this study, procedures for measuring sound localization, sound lateralization, and binaural masking level differences (BMLDs) in young children were developed. Sensitivity for these tasks was assessed in large groups of children between 4 and 9 yr of age to investigate potential developmental trends. Design: Sound localization was measured in the sound field, with a broadband bell-ring presented from one of nine loudspeakers positioned in the frontal horizontal field. A group of 33 children between 4 and 6 yr of age and 5 adults took part in this experiment. Sound lateralization based on interaural time differences was measured with headphones in 49 children between 4 and 9 yr of age and 10 adults. A low-frequency stimulus containing harmonics 2 to 5 from a click train with a rate of 160 Hz was used. In the BMLD test, the same filtered click train was presented diotically or dichotically (phase reversed or time delayed) in a broadband (200 to 1000 Hz) frozen noise to 23 children between 4 and 6 yr of age and 10 adults. For comparison with literature, additional measurements with a 500-Hz sinusoid were administered to adults. All tasks were adapted to the interest and attention span of young children. Results: Children of 5 yr of age did not perform significantly different from adults on the sound localization task, but mean absolute errors were larger for the 4-yr-olds. Also on the BMLD task, 5-yr-old children performed at the adult level, whereas the 4-yr-old children obtained significantly less binaural unmasking compared with the adults. Concerning sound lateralization, a small but significant difference between adults and children existed, but no age effects were apparent in the 4- to 9-yr-old group. Overall, the variation was relatively large in the 4-yr-old group, with some of the children performing at adult level, in all three tasks. Conclusions: The results of this study show that the modified procedures are suitable for testing children from the age of 4 to 5 yr. Furthermore, it seems that binaural hearing capacities of the 5-yr-olds are similar to those of adults. Several observations led to the hypothesis that the observed age differences between 4-yr-olds and older subjects on localization and BMLD or between those 4- to 9-yr old and adults on lateralization, were attributable to both a development in binaural hearing and to nonauditory factors, such as task comprehension, attention, and testing conditions. It is possible that the developmental process is more obvious and prolonged in other aspects of binaural hearing, which require more dynamic or more central processing.

Impact of early hearing screening and treatment on language development and education level: Evaluation of 6 years of universal newborn hearing screening (ALGO®) in Flanders, Belgium

OBJECTIVES Early intervention in hearing-impaired children may improve language outcomes and subsequent school and occupational performance. The objective of this study was to retrospectively analyze over 6 years the educational outcome and language development of a first cohort of children, detected by the Flemish universal newborn hearing screening (UNHS) program based on automated auditory brainstem response (AABR), with the oldest children being in primary school. METHODS We studied 229 hearing-impaired children from 1998 till 2003. The following variables were considered: the age during the school year 2005-2006, the degree of hearing loss, additional impairments including presence of intellectual disability, school placement and early intervention. RESULTS Analysis showed that 85.4% of the children with moderate, severe or profound hearing loss and no additional disability, older than 5.5 years, reach mainstream education. Further detailed description was provided for the outcomes of children with uni- and bilateral cochlear implants. Overall results stress that 46% of all children with a cochlear implant obtain mainstream education. Of all cochlear implant (CI) children above 5.5 years, without additional handicaps, 78.9% of children attend primary mainstream school. Data on language development show that up to 45% of the children with unilateral cochlear implant and no additional disabilities had normal to slight delay on language development. These data are fulfilling the goals stated by the JCIH and the American Academy of Pediatrics (AAP) in 2000. The role and impact of additional handicaps is discussed. The importance of early hearing loss identification and hearing therapy for appropriate language development is highlighted. Finally our preliminary results on children with bilateral cochlear implants without additional handicaps present an improved language development in comparison to unilateral CI-children. CONCLUSION A vast majority of the children detected by the UNHS program, with moderate, severe or profound hearing loss and no additional disability, older than 5.5 years, reach mainstream education. Additional disabilities have a major influence.

Bilateral cochlear implants in children: binaural unmasking.

Bilateral cochlear implants (CIs) may offer deaf children a range of advantages compared to unilateral CIs. However, speech perception in noise is mainly facilitated by better-ear effects and much less by interaural comparisons or true ‘binaural’ hearing. Little is known about the development of the binaural auditory system with CIs provided at a young age. It is possible that, as with adults, binaural sensitivity exists but is not accessed due to technical limitations in electrical stimulation methods. In this paper, we present results on binaural hearing in children with bilateral CIs. Binaural masking level differences (BMLDs) were measured for a 180-degree phase shift in a 125-Hz sinusoid, presented in a 50-Hz-wide noise band and modulating a 1000-pps carrier pulse train. Stimuli were presented to a single electrode in the middle of the electrode array at both ears. Eight children between 6 and 15 years of age participated in this study. Six children had a significantly better detection threshold when the signal was out of phase (dichotic) between two ears than when it was in phase (diotic), with a mean difference (BMLD) of 6.4 dB. The present results show that children with bilateral CIs are sensitive to binaural cues in electrical stimuli, similar to adults, even when implants are provided at a later age and with a longer delay between implantations.

Functional outcome of sequential bilateral cochlear implantation in young children: 36 months postoperative results §

OBJECTIVE To examine the effects of sequential bilateral cochlear implantation (CI) on the life of young children after 36 months of bilateral implant use. METHOD Thirty-five children were assessed prior to and 3 until 36 months after activation of the second CI. Main outcome measures were: the Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR), communication mode, classroom placement, parent reports and the Würzburg questionnaire. Results were analysed separately for children younger and older than 6 years at the time of the second implantation. RESULTS At the 3-year test interval, 80% of the younger children attended mainstream schools and were comprehensible for all listeners. They all used oral communication and almost 70% of them could have a conversation over the telephone. After 3 years of bilateral implant use less than 50% of the older children obtained the highest score on the SIR and CAP. Approximately 70% of them was integrated in mainstream schools and used oral communication. All parents reported a more natural communication and an improved quality of life. CONCLUSIONS Sequential bilateral implantation seems to offer a wide range of participation benefits to all children and facilitates the social intercourse with their hearing environment.

Three-Year Postimplantation Auditory Outcomes in Children With Sequential Bilateral Cochlear Implantation

Objectives: We report on the auditory abilities and speech performance in quiet and noise of 35 children with sequential bilateral cochlear implantation after 3 years of bilateral implant use. Methods: Testing was done in bilateral and both unilateral listening conditions. The assessments took place before the second implantation and at several time intervals after fitting. As different auditory tests were used, the children were categorized by their age at the second implantation: Younger or older than 6 years. Results: The pure tone averages for the bilateral condition were significantly better than those for either unilateral condition after 12 months of bilateral implant use and remained so from that test interval onward. The speech recognition outcomes in quiet and noise also improved significantly for almost all children after 36 months, although a linear regression analysis showed a beneficial effect of younger age at first implantation on the speech-in-noise results. Conclusions: Bilateral cochlear implantation offered advantages to all children in comparison with the first implant — Even the children who received the second implant after the age of 6 years. Compared to the younger children, the older children needed a longer adjustment period to gain bilateral benefit. However, they obtained similar results after 2 years of bilateral implant use.

Subjective benefits of sequential bilateral cochlear implantation in young children after 18 months of implant use

Objective: To investigate the subjective benefits of bilateral cochlear implantation in 33 young children after 18 months of second implant use. Method: The Würzburg questionnaire inquiring into a range of hearing functions was filled out by the parents. Additional data concerning the daily life and well-being of the children were gathered with an open-ended questionnaire and the Categories of Auditory Performance. Results were analyzed separately for children younger and older than 6 years at the time of the second implantation. Results: After 18 months of bilateral implant use 30% of the younger and 6% of the older children made the transition to an auditory-oral communication. In this period, 15% of all children switched to mainstream schools. The parents reported an evolution of their children’s auditory abilities, which included a better sound and speech perception. Multiregression analysis revealed that early hearing aid fitting and the age at the second cochlear implantation significantly contributed to the variance of the Würzburg results. Conclusions: The results indicate a wide range of positive subjective changes associated with bilateral cochlear implantation, even in older children. This progress led to a better and easier communication and a better integration in the normal-hearing world.

A comparative study on speech in noise understanding with a direct acoustic cochlear implant in subjects with severe to profound mixed hearing loss.

The aim of this study was to investigate the efficacy of a direct acoustic cochlear implant (DACI) for speech understanding in noise in patients suffering from severe to profound mixed hearing loss (MHL) due to various etiologies compared to the preoperative best-aided condition. The study was performed at five tertiary referral centers in Europe (Belgium, Germany, Poland and Spain). Nineteen adult subjects with severe to profound MHL due to (advanced) otosclerosis, ear canal fibrosis, chronic otitis media, tympanosclerosis or previous cholesteatoma were implanted with a DACI (Codacs™ Investigational Device) combined with a conventional stapes prosthesis. Unaided and aided speech reception scores in quiet and in noise, preoperative and postoperative air and bone conduction thresholds and aided and unaided sound field thresholds were measured prospectively during the study. Subjective benefit analysis was determined through the Abbreviated Profile of Hearing Aid Benefit questionnaire. Quality of life was measured by the Health Utilities Index. All subjects were fitted preoperatively with hearing aids and/or a bone conduction implant on a headband before DACI implantation. This allows direct comparison between different hearing rehabilitation solutions. The mean speech reception threshold in noise improved significantly by 7.9 dB signal-to-noise ratio (SNR) after activation of the DACI compared to the preoperative best-aided condition. For all 19 subjects, a mean postoperative aided speech reception threshold of 2.6 dB SNR (standard deviation: 8.3 dB) was measured. On average, no significant shift in the bone conduction thresholds was noted 4-5 months after implantation. A mean sound field threshold improvement of 46 and 16 dB was measured compared to the preoperative unaided and best-aided condition, respectively. Speech perception tests in quiet showed a mean improvement of the word recognition scores by 65 and 48% at 65 dB SPL compared to the preoperative unaided and best-aided condition, respectively. In summary, DACI provides an effective improvement of the speech perception in noise compared to the best-aided condition in subjects suffering from severe to profound MHL.