Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.

Hearing results in a consecutive series of 407 patients with otosclerosis undergoing primary stapes surgery were analysed (437 operated ears). Partial stapedectomy was performed in 70 ears (16%), total stapedectomy in 205 ears (47%), in both groups using the House steel wire prosthesis on fascia in the oval window. The remaining 162 ears (37%) underwent stapedotomy using the Fisch 0.4 mm teflon-platinum piston. No case of cochlear loss (> 15 dB) occurred in the total series. The comparison between the three groups one year postoperatively showed that the air-bone gap was smaller for partial and total stapedectomy for all frequencies except 4 kHz. The air-bone gap was calculated as the difference between the preoperative bone conduction and the postoperative air conduction thresholds. Partial and total stapedectomy also showed larger improvements of bone conduction thresholds compared with stapedotomy for all frequencies but 4 kHz. At the 3-year follow-up, the hearing gain for all frequencies (250-8000 Hz) was larger for partial and total stapedectomy. Yet, when comparing the decline of hearing from 1 to 3 year postoperatively, the hearing gain achieved with partial and total stapedectomy seemed to deteriorate at a higher rate, which was considered to be caused by impaired sensorineural function. Our results show that in the short-term perspective partial or total stapedectomy can still compete for better hearing results even at higher frequencies, but stapedotomy seems to yield more stable hearing results over time and should therefore be considered as the method of choice.

In this study, we examined preoperative verbal cognitive capacity in 11 deafened adults who were cochlear implant candidates and reexamined level of speech understanding after 6-8 months' experience with the implant. Verbal cognitive performance in the implant group was compared in a group of normal hearing subjects and in nonimplanted group of deafened adults. The three groups performed on par with each other with an exception: The individuals in the cochlear implant group and the nonimplanted group of deafened adults performed significatly worse than those of normal hearing in tasks in which use of internal speech is a key feature (i.e., rhyme judgement and lexical decision tasks). Postoperative observations of the implanted individuals' level of speech understanding suggest that it is possible to predict the level of speech understanding by means of a properative cognitive assessment. The characteristics of three verbal cognitive abilities prove to be critical indicators of 6 - 8 months' postoperative outcome: internal speech functioning, speed of verval information processing, and working memory capacity - the first factor proved the most decisive. We discuss the results with respect to direct versus indirect predictors of outcomes from cochlear implant operations and the effect of auditory deprivation on deafened adults' capability to process auditory information.

In the present study cognitive performance in 15 deafened adult cochlear implant candidates was examined and related to level of speech understanding after 12 months of experience with the implant. The implant group performed on par with normal hearing controls in all cognitive tasks used in the study with one exception: Performance was significantly lower in cognitive tasks where use of a phonological representation of sound is a key task-demand. Observations of the implanted individuals' level of speech understanding indicate that only those individuals who, pre-operatively, were in possession of phonological representations comparable to that of normal hearing could follow and understand a speaker that was out of sight. The results are discussed with respect to (a) deterioration in the phonological representation of sounds as a function of absence of external auditory stimulation, and (b) the role of cognitive factors in predicting success in speech understanding with the implant.