Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas.

BACKGROUND: Paragangliomas are rare and highly heritable tumours of neuroectodermal origin that often develop in the head and neck region. Germline mutations in the mitochondrial complex II genes, SDHB, SDHC, and SDHD, cause hereditary paraganglioma (PGL). METHODS: We assessed the frequency of SDHB, SDHC, and SDHD gene mutations by PCR amplification and sequencing in a set of head and neck paraganglioma patients who were previously managed in two otolaryngology clinics in the USA. RESULTS: Fifty-five subjects were grouped into 10 families and 37 non-familial cases. Five of the non-familial cases had multiple tumours. Germline SDHD mutations were identified in five of 10 (50%) familial and two of 37 ( approximately 5%) non-familial cases. R38X, P81L, H102L, Q109X, and L128fsX134 mutations were identified in the familial cases and P81L was identified in the non-familial cases. Both non-familial cases had multiple tumours. P81L and R38X mutations have previously been reported in other PGL families and P81L was suggested as a founder mutation. Allelic analyses of different chromosomes carrying these mutations did not show common disease haplotypes, strongly suggesting that R38X and P81L are potentially recurrent mutations. Germline SDHB mutations were identified in two of 10 (20%) familial and one of 33 ( approximately 3%) non-familial cases. P131R and M71fsX80 were identified in the familial cases and Q59X was identified in the one non-familial case. The non-familial case had a solitary tumour. No mutations could be identified in the SDHC gene in the remaining four families and 20 sporadic cases. CONCLUSIONS: Mutations in SDHD are the leading cause of head and neck paragangliomas in this clinic patient series. SDHD and SDHB mutations account for 70% of familial cases and approximately 8% of non-familial cases. These results also suggest that the commonness of the SDHD P81L mutation in North America is the result of both a founder effect and recurrent mutations.

Intraoperative auditory assessments as predictors of hearing preservation after vestibular schwannoma surgery.

The purpose of this study was to determine the association of intraoperative auditory brainstem responses (ABRs) and near-field cochlear nerve action potentials (CNAPs) with postoperative hearing preservation in acoustic tumor surgery. Thirty-three consecutive patients undergoing middle fossa surgery had intraoperative surface ABR and direct CNAP assessments. Postoperatively, hearing was assessed. Hearing preservation was defined as any measurable hearing at any frequency and also by the American Academy of Otolaryngology--Head and Neck Surgery (AAO-HNS) hearing preservation classification system. The presence of an ABR or CNAP was associated with hearing preservation and the absence of an ABR, and CNAP was associated with no hearing preservation in 75.6 percent of the cases. The presence of either the ABR or CNAP was not related to AAO-HNS class outcome. ABR and CNAP had a useful rate of prediction of hearing preservation surgery outcome. However, in nearly one-quarter of the cases, no association between ABR or CNAP responses and hearing preservation was found. This finding must be taken into account when determining the clinical usefulness of these techniques.

Perioperative morbidity of acoustic neuroma surgery.

OBJECTIVE: To review complications that occur during the course of acoustic neuroma surgery. STUDY DESIGN: Database and retrospective case review. SETTING: Tertiary referral center, private neurotologic practice. PATIENTS: A series of 1,687 patients undergoing acoustic neuroma surgery between 1987 and 1997. The 822 male and 865 female patients ranged in age from 10 to 87 years (mean age at time of surgery, 50 yr; standard deviation, 14 yr). The most common surgical approach was translabyrinthine (72.5%), followed by middle fossa (25.7%). The tumors ranged in size from 3 to 7 cm in diameter (mean, 2.0 cm; SD, 1.1 cm). MAIN OUTCOME MEASURE: Frequency of occurrence of all surgical and medical complications. RESULTS: The most common complications were cerebrospinal fluid leaks (9.4%; 2.1% requiring reoperation) and meningitis (1.5%). Other surgical complications included cerebral edema, hydrocephalus, pneumocephalus, lower cranial nerve dysfunction, and wound infection. Medical complications in order of frequency included cystitis, sacral root syndrome, anemia, and pneumonia/bronchitis. Complications were related to tumor size and diagnosis of neurofibromatosis type 2. CONCLUSIONS: Perioperative complications will occur with acoustic neuroma surgery, but the overall rate in this large series was low. The authors believe that this supports an aggressive treatment approach for management of acoustic tumors. The findings of this study provide a basis for comparison with other treatment approaches and also are useful for preoperative patient counseling.

Hearing preservation in patients with vestibular schwannomas with sudden sensorineural hearing loss.

OBJECTIVE: We evaluated hearing outcomes in patients with sudden hearing loss and vestibular schwannoma who underwent a hearing preservation operation for tumor resection in an effort to determine whether a history of sudden sensorineural hearing loss has an impact on subsequent hearing preservation surgery. METHODS: Retrospective chart review of 45 patients operated between 1990 and 1998. Patients were divided into "Recovery" (n = 22) and "No Recovery" (n = 23) groups based on preoperative hearing recovery. Hearing preservation was assessed using the AAO-HNS hearing classification system. RESULTS: Measurable hearing was preserved in 73% of patients, with 47% having good postoperative hearing (AAO-HNS Classes A-B). There was no significant difference in hearing outcome from patients presenting with progressive hearing loss (45% Classes A-B). There was also no difference in postoperative hearing between the "Recovery" and "No Recovery" groups. CONCLUSIONS: Patients with sudden hearing loss and vestibular schwannoma have the same chance of hearing preservation after tumor removal as those with progressive loss. Preoperative recovery of hearing is not predictive of hearing preservation. Available data support the nerve compression theory as the mechanism of sudden hearing loss in patients with vestibular schwannoma.

Early proactive management of vestibular schwannomas in neurofibromatosis type 2.

OBJECTIVE: The treatment of patients with neurofibromatosis Type 2 has always been challenging for neurosurgeons and neurotologists. Guidelines for appropriate management of this devastating disease are controversial. METHODS: A retrospective study of 28 patients with neurofibromatosis Type 2 who underwent 40 middle fossa craniotomies for excision of their acoustic tumors is reported. Eleven patients underwent bilateral procedures. The study focused on hearing preservation and facial nerve results for this group of patients. The 16 male patients and 12 female patients ranged in age (at the time of surgery) from 10 to 70 years, with a mean age of 22.6 years. The mean tumor size was 1.1 cm (range, 0.5-3.2 cm), and the majority of tumors were less than 1.5 cm. RESULTS: Measurable hearing was preserved in 28 ears (70%), with 42.5% being within 15 dB pure-tone average and 15% speech discrimination score of preoperative levels. In 55% of cases there was no change in the hearing class, as defined by the American Academy of Otolaryngology-Head and Neck Surgery. Of the 11 patients who underwent bilateral operations, 9 (82%) retained some hearing bilaterally. After 1-year follow-up periods (mean, 12.8 mo), 87.5% of patients exhibited normal facial nerve function (House-Brackmann Grade I). CONCLUSION: Early surgical intervention to treat acoustic tumors among patients with neurofibromatosis Type 2 is a feasible treatment strategy, with high rates of hearing and facial nerve function preservation.

Proportion of heritable paraganglioma cases and associated clinical characteristics.

OBJECTIVE/HYPOTHESIS: To determine the heritable proportion of paraganglioma (PGL) and identify clinical features associated with heritable PGL. STUDY DESIGN: Patients diagnosed with head and neck PGLs, identified retrospectively through clinical otolaryngology practices and/or participation in previous PGL research studies, were given a medical and family history questionnaire. METHODS: Questionnaire information was used to classify participants as having "heritable" or "non-heritable" cases of PGL. Classification of the participants identified through otolaryngology clinics was used to estimate the heritable proportion of PGL. Statistical analysis was performed to identify significant differences in the clinical characteristics of the heritable versus non-heritable groups. RESULTS: Among the otolaryngology clinic population, 35% were classified as having heritable PGL. Individuals with heritable PGL were younger on average than those with non-heritable PGL. The majority of non-heritable participants were female, but there was an equal gender ratio among the heritable participants. Individuals diagnosed with a carotid body tumor (CBT) were 5.8 times more likely to be classified as heritable than those diagnosed with PGL at other anatomic locations. CONCLUSIONS: Approximately 35% of individuals who present to an otolaryngologist with a head and neck PGL have inherited a predisposition for this growth. Among individuals diagnosed with head and neck PGL, those diagnosed with CBT are 5.8 times more likely to have an inherited predisposition than those diagnosed with PGL at other anatomic locations.

Effects of electrode location on speech recognition with the Nucleus-22 cochlear implant.

Speech recognition performance was measured as a function of electrode in two experiments with the Nucleus-22 cochlear implant using 4-electrode SPEAK speech processors. In experiment 1, the four stimulated electrode pairs were shifted in 0.75-mm steps over 3 mm in the apical-basal direction. In experiment 2, the four electrodes were closely spaced and positioned apically, medially, or basally. An additional condition spaced the four electrodes as widely as possible. In experiment 1, City University of New York sentence scores showed a significant decrease in performance as the electrodes were shifted basally; no other speech measures showed a significant change with electrode location. For experiment 2, all scores were the best with the processor that had the electrodes spaced as widely as possible. In both experiments, all 4-electrode SPEAK processors produced significantly poorer speech recognition than the subject's own 20-electrode processor. These results indicate that the location of electrodes is an important factor in implant performance.

Prognostic factors for hearing preservation in vestibular schwannoma surgery.

OBJECTIVE: To determine whether prognostic indicators for hearing preservation could be identified in patients with vestibular schwannoma undergoing middle fossa craniotomy resection. STUDY DESIGN: Prospective case review. SETTING: Private practice tertiary referral center. PATIENTS: 333 patients with serviceable hearing and vestibular schwannoma resected by middle fossa craniotomy from 1992 to 1998. MAIN OUTCOME MEASURES: Potential prognostic indicators, including tumor size and nerve of origin, preoperative pure-tone average, speech discrimination, distortion product otoacoustic emission testing, age, auditory brainstem response (ABR), and electronystagmography. RESULTS: Postoperative hearing near preoperative levels was attained in 167 patients (50%), with an American Academy of Otolaryngology-Head and Neck Surgery Class A hearing result in 33% and a Class B result in 26%. Comparison of potential prognostic indicators between groups with hearing preserved and the group with no measurable hearing revealed significant differences in preoperative hearing, ABR, and tumor origin data. Better preoperative hearing, shorter intraaural wave V latency, shorter absolute wave V latency, and superior vestibular nerve origin were associated with higher rates of hearing preservation. CONCLUSIONS: Preoperative hearing status, ABR, and intraoperative tumor origin data were shown to be of value as prognostic indicators.

The effect of frequency allocation on phoneme recognition with the nucleus 22 cochlear implant.

HYPOTHESIS: Phoneme recognition performance in patients implanted with the Nucleus 22 cochlear implant is affected by the frequency-to-electrode assignment. BACKGROUND: Multiple electrodes in modern cochlear implants are intended to deliver frequency-specific information to different tonotopic locations along the cochlea. However, the relation between the electrode locations, distribution of frequency information, and performance has not been explored thoroughly. METHODS: Ten listeners were tested on vowel and consonant identification tasks immediately after receiving each of the 15 speech processors. Experimental processors were created with 4, 7, and 20 activated electrodes. Five different frequency allocations were tested with all electrode conditions. RESULTS: For 7- and 20-electrode maps, best vowel recognition performance was obtained with frequency tables 7 and 9, with subjects showing best performance with the table with which they were most familiar. With 4-electrode maps, no change in vowel recognition performance was observed as a function of the frequency allocation. Consonant scores showed only a small effect of frequency allocation across all processors. Results were similar across listeners with different electrode insertion depths. CONCLUSION: The allocation of frequency ranges to electrodes in the Nucleus-22 cochlear implant can affect vowel recognition, when more than four electrodes are used, but is less important for consonant recognition. The allocation of frequency ranges to electrodes is an important factor in multichannel implants with more than four electrodes. The similarity of results across implant listeners with different electrode insertion depths implies that the optimal frequency allocation is one that best matches the allocation to which they've become accustomed, rather than one that matches the original tonotopic location of the electrodes.

Intraoperative corticosteroids in acoustic tumor surgery.

BACKGROUND: Corticosteroids are frequently used for the prevention and treatment of neural edema. Although perioperative steroid therapy has been used in patients undergoing acoustic neuroma removal, the efficacy of such therapy has not been previously documented. METHODS: A retrospective review of 169 patients who underwent acoustic neuroma surgery with (n = 75) or without (n = 94) a single dose of intraoperative corticosteroids was performed. Tumor size ranged from 0.4 cm to 6 cm (mean, 2.1; SD, 1.0) The translabyrinthine approach was used in 85% of the patients, and the middle cranial fossa approach was used in 13%. Data were analyzed for differences in postoperative facial function and complication rates. RESULTS: After controlling for differences in tumor size, no significant effects of steroid therapy were found for any of the outcome variables. CONCLUSIONS: This retrospective study showed no apparent benefit from intraoperative steroid use in acoustic neuroma surgery. A prospective, randomized, placebo-controlled trial should be performed to confirm these findings.

Stapedectomy in children.

Stapes surgery for correction of conductive hearing loss in adults with otosclerosis is a well-established procedure. Its effectiveness in children, however, has received less scrutiny in the literature. Previous studies from our and other institutions demonstrated similar results in children and adults. Between 1980 and 1994 stapedectomies were done on 95 ears of 81 patients younger than 18 years (83 primary and 12 revisions). Data regarding age of onset, family history, associated anomalies, surgical findings, technique, hearing results, and complications were reviewed. Two groups were identified: congenital stapedial fixation and juvenile otosclerosis. Patients with congenital stapedial fixation had an earlier onset of hearing loss (3 vs 10 years, P < 0.001), a greater incidence of abnormalities of the malleus and incus (25% vs 3%, P < 0.001), and a slightly greater preoperative air-bone gap (35.2 +/- 12.9 vs 27.8 +/- 8.9, P = 0.002). Patients with otosclerosis had a greater frequency of a positive family history of deafness (53% vs 10%, P < 0.001). Overall, 79% of primary cases and 89% of revision cases had an improvement in hearing, with mean postoperative air-bone gaps of 15 dB and 22 dB, respectively. The gap did not widen significantly during the entire length of follow-up (mean 72 months). In primary cases, 59.1% obtained a postoperative air-bone gap of 10 dB or less. Eighty-two percent of children operated on for otosclerosis obtained excellent results (postoperative air-bone gap < or = 10 dB), compared with only 44% of children with congenital stapedial ankylosis (P = 0.02). In revision surgery, 29% of children obtained excellent results. Poorer results in both cases of congenital stapedial fixation and revision stapedectomy appear to be related to the greater incidence of associated anomalies of the malleus and incus. Indications, technique, complications, and considerations pertinent to childhood stapedectomy are discussed.

Cochlear implant performance after reimplantation: a multicenter study.

OBJECTIVE: This study compares auditory performance between original and replacement cochlear implants. STUDY DESIGN AND SETTING: Data from 18 U.S. cochlear implant programs were obtained by retrospective chart review. Patients received and returned subjective questionnaires. PATIENTS: Twenty-eight adults with once-functioning Nucleus 22 cochlear implants that failed received replacement Nucleus 22 cochlear implants in the same ears. MAIN OUTCOME MEASURES: Objective measures included sentence (CID Everyday Sentences or Iowa Sentences) and monosyllabic word (NU-6 Words or CNC Words) speech discrimination scores. Patients also rated and compared performance using subjective scales. RESULTS: Thirty-seven percent of patients had significantly higher sentence or word scores with their replacement cochlear implants than with their original implants, 26% had no significant change, and 37% had significantly poorer scores. Subjectively, 57% of patients reported that the performance of their replacement device was better or the same and 43% reported that it was poorer. There was no correlation between performance with the replacement cochlear implant and cause of the original device failure, duration of original device use before failure, surgical complications with either implantation, changes in electrode insertion depths, or preoperative variables, such as age, etiology, or duration of deafness. CONCLUSIONS: Speech recognition ability with a replacement cochlear implant may significantly increase or decrease from that with the original implant. Experienced cochlear implant patients facing reimplantation must be counseled regarding the possibility of differences in sound quality and speech recognition performance with their replacement device.

Hearing preservation in neurofibromatosis type 2.

OBJECTIVE: The aim of the study was to provide a clinical review of the middle fossa approach for hearing preservation in patients with neurofibromatosis type 2 (NF2). STUDY DESIGN: The study design was a prospective case review. SETTING: The study was conducted at a private practice tertiary neurotologic referral center. PATIENTS: Eighteen patients diagnosed with NF2 underwent 23 middle fossa procedures between 1992 and 1996 for removal of an acoustic neuroma. The nine males and nine females ranged in age from 11-73 years with a mean age of 28 years. Tumor size ranged from 0.5-2.5 cm with a mean of 1.1 cm. MAIN OUTCOME MEASURES: House-Brackmann facial nerve grade was measured. In addition, hearing level was classified both by the American Academy of Otolaryngology-Head and Neck Surgery criteria for reporting results of hearing preservation surgery and by comparison with preoperative level (15 dB/15%). RESULTS: Measurable hearing was preserved in 65%, 48% within 15 dB of preoperative pure-tone average (PTA) and within 15% of preoperative speech discrimination. Bilateral hearing preservation occurred in five patients. Excellent facial nerve function (House-Brackmann grades I-II) was obtained in all patients with normal preoperative facial nerve function. CONCLUSIONS: In this series of patients with NF2, outcomes in hearing and preservation of preoperative facial nerve function are similar to results seen in patients suffering a sporadic unilateral acoustic neuroma. However, early intervention is crucial in obtaining such favorable outcomes.

Germline screening of the NF-2 gene in families with unilateral vestibular schwannoma.

Vestibular schwannoma may present clinically in two forms: sporadic unilateral or hereditary bilateral. Familial transmission of vestibular schwannoma is known to occur only in neurofibromatosis type II (NF-2). We have previously described the clinical characteristics of unilateral vestibular schwannoma presenting in families, in the absence of ther criteria necessary for the diagnosis of NF-2. Polymerase chain reaction-single strand chain polymorphism was used to screen for germline NF-2 gene mutations in six families with unilateral vestibular schwannoma. Direct sequencing of DNA from blood was done in affected subjects from three families. No germline mutations were identified. Because NF-2 gene mutations are detected in only 33% of patients with NF-2, hereditary transmission of mutations cannot be entirely excluded. However, in the absence of germline mutations in the NF-2 gene, familial occurrence of unilateral vestibular schwannoma more likely represents either a chance somatic NF-2 gene mutation or originates from a separate genetic loci.

Bone cement reconstruction of the ossicular chain: a preliminary report.

OBJECTIVE: To determine the feasibility and efficacy of using a bone cement, Oto-Cem, to reconstruct the ossicular chain. STUDY DESIGN: Prospective clinical trial on nine consecutively chosen adult patients with ossicular chain defects. PATIENTS AND SETTING: Nine patients with ossicular chain defects involving the long process of the incus were treated at the Carolina Ear and Hearing Clinic. The ossicular chain was reconstructed using bone cement by itself or in conjunction with a stapes prosthesis. MAIN OUTCOME MEASURES: Preoperative audiograms were compared with audiograms 3, 6, and 12 months after reconstruction. RESULTS: There was a mean pure-tone average (PTA) improvement of 15 dB in patients undergoing incus to stapes suprastructure reconstruction with the bone cement. The incus to mobile footplate reconstruction (using a stapes prosthesis attached to the newly reconstructed incus) resulted in a 34-dB PTA postoperative improvement. Two of the three patients with incus to oval window repairs experienced a 10-dB improvement in PTA. One of the three patients experienced a loss in speech discrimination and a 2-dB loss in PTA. CONCLUSIONS: Despite the limited number of patients, this preliminary study demonstrates the effectiveness of Oto-Cem in reconstructing a foreshortened incus. There was a substantial hearing improvement in all but one patient in the incus to stapes or the incus to footplate categories.

Automobile airbag impulse noise: otologic symptoms in six patients.

Automobile airbag safety systems have successfully reduced the number of occupant injuries from motor vehicle accidents. Unfortunately, airbags are also associated with some inherent risk, including a high-amplitude, short-duration noise from airbag deployment. A review of the available research in the automobile industry indicates that the peak amplitude of this noise may exceed 170 dB sound pressure level. Despite the increasingly wide application of airbags in automobiles, there have been no previous reports of airbag-related otologic injuries. We have encountered six patients with otologic symptoms that appear to be related to airbag impulse noise. Five of these patients have documented hearing loss, one patient reported persistent tinnitus, and two patients have significant dysequilibrium. Although permanent hearing loss from airbag noise appears to be rare, temporary threshold shifts are probably much more common. It is important, therefore, that the clinician be aware of the noise associated with airbag inflation and the possibility of acoustic trauma from these safety devices.

Speech recognition as a function of the number of electrodes used in the SPEAK cochlear implant speech processor.

Speech recognition was measured in listeners with the Nucleus-22 SPEAK speech processing strategy as a function of the number of electrodes. Speech stimuli were analyzed into 20 frequency bands and processed according to the usual SPEAK processing strategy. In the normal clinical processor each electrode is assigned to represent the output of one filter. To create reduced-electrode processors the output of several adjacent filters were directed to a single electrode, resulting in processors with 1, 2, 4, 7, 10, and 20 electrodes. The overall spectral bandwidth was preserved, but the number of active electrodes was progressively reduced. After a 2-day period of adjustment to each processor, speech recognition performance was measured on medial consonants, vowels, monosyllabic words, and sentences. Performance with a single electrode processor was poor in all listeners, and average performance increased dramatically on all test materials as the number of electrodes was increased from 1 to 4. No differences in average performance were observed on any test in the 7-, 10-, and 20-electrode conditions. On sentence and consonant tests there was no difference between average performance with the 4-electrode and 20-electrode processors. This pattern of results suggests that cochlear implant listeners are not able to make full use of the spectral information on all 20 electrodes. Further research is necessary to understand the reasons for this limitation and to understand how to increase the amount of spectral information in speech received by implanted listeners.

Familial occurrence of unilateral vestibular schwannoma.

Vestibular schwannoma (VS) may present clinically in one of two forms: sporadic unilateral or hereditary bilateral. Almost all cases of familial transmission have been associated with the diagnosis of neurofibromatosis type II (NF-2). In this report, we describe nine families (18 individuals) presenting with unilateral VS without evidence of NF-2. In four of the nine families, the affected individuals were of parent-offspring relationship, in three families they were cousin-cousin, and in the remaining two families, they were sibling-sibling and aunt-nephew. No other members of the families were diagnosed with NF-2. There was no evidence for gender predilection or genomic imprinting among affected individuals. This study suggests that familial occurrence of unilateral VS may be genetically inherited as it occurs more commonly than would be estimated by chance alone. Future genetic studies will elucidate whether occurrence of unilateral VS in these families represents a variable expression of NF-2, chance occurrence of unilateral VS in families, or a new genetic disorder.