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.

Establishment of primary vestibular schwannoma cultures from neurofibromatosis type-2 patients.

Primary cultures were established from vestibular schwannomas of NF2 patients. The cultured tumor cells were selectively amplified by growth factor supplemented medium and characterized by immunocytochemistry. NF2 cDNA was amplified by RT-PCR and mutations were detected by both the non-isotopic RNase cleavage assay and direct DNA sequencing, no detectable wild-type NF2 transcript was found in cDNA from the cultured cells. Distinguishable morphology and growth rate differences have been observed in different passages of the primary cells. The data suggest that a pure schwannoma primary culture can be established and could be very useful in vitro model for further understanding the NF2 gene function in Schwann cells.

Recent advances in neuro-otology.

Four advances in the field of neuro-otology are described: (1) auditory brain-stem response audiometry, (2) electroneuronography, (3) the cochlear implant, and (4) the infratemporal fossa approach to the skull base. Auditory brain-stem response audiometry is an accurate method for the early detection of hearing impairment and early diagnosis of acoustic neurinomas. Electroneuronography accurately assesses the degree of injury to the facial nerve, thereby improving management of facial nerve lesions. The cochlear implant restores the sensation of sound to totally deaf patients. The infratemporal fossa approach is used to treat extensive lesions of the skull base.

Jacobson's nerve schwannoma presenting as middle ear mass.

Schwannoma is one of the common benign middle ear space tumors. Middle ear space schwannomas may originate from the nerves of the tympanic cavity or by extensions from outside the middle ear space. In the English-language literature, the facial nerve and chorda tympani nerve, but not yet the tympanic branch of glossopharyngeal nerve (Jacobson's nerve), have been reported as the origins of intrinsic middle ear space schwannomas. We present the clinical and radiologic features of a middle-space schwannoma originating from Jacobson's nerve, and suggest that such a tumor be included in the differential diagnosis of middle ear tumors.

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.

Report of 190 consecutive cases of large acoustic tumors (vestibular schwannoma) removed via the translabyrinthine approach.

OBJECT: The choice of approach for surgical removal of large acoustic neuromas is still controversial. The authors reviewed the results in a series of patients who underwent removal of large tumors via the translabyrinthine approach. METHODS: The authors conducted a database analysis of 190 patients (89 men and 101 women) with acoustic neuromas 3 cm or greater in size. The mean age of these patients was 46.1+/-15.6 years. One hundred seventy-eight patients underwent primary translabyrinthine surgical removal and 12 underwent surgery for residual tumor. Total tumor removal was accomplished in 183 cases (96.3%). The tumor was adherent to the facial nerve to some degree in 64% of the cases, but the facial nerve was preserved anatomically in 178 (93.7%) of the patients. Divided nerves were repaired by primary attachment or cable graft. Facial nerve function was assessed immediately after surgery, at the time of discharge, and at 3 to 4 weeks and 1 year after discharge. Excellent function (House-Brackmann facial nerve Grade I or II) was present in 55%, 33.9%, 38.8%, and 52.6% of the patients for each time interval, respectively, with acceptable function (Grades I-IV) in 81% at 1 year. Cerebrospinal fluid leakage that required surgical repair occurred in only 1.1% of the patients and meningitis in 3.7%. There were no deaths. CONCLUSIONS: Use of the translabyrinthine approach for removal of large tumors resulted in good anatomical and functional preservation of the facial nerve, with minimum incidence of morbidity and no incidence of mortality. The authors continue to recommend use of this approach for acoustic tumors larger than 3 cm and for smaller tumors when hearing preservation is not an issue.

The cochlear implant; basic principles.

In recent years the cochlear implant has been a subject of much discussion and controversy. The clinician has often been confused by the conflicting reports of success and failure. In this paper the development of the cochlear implant is reviewed and its present status summarized. It is hoped that the clinician may thereby gain an understanding of this device so that he can better evaluate its present and future status. Selection of Patients for Cochlear Implantation. The cochlear implant will benefit only those patients with hair cell loss who have remaining viable auditory neurons. In order to determine whether viable neurons remain, an electric current is passed through a small needle which is place into the promontory through the tympanic membrane. If patients experience an auditory sensation as a result of this electrical stimulation, it is felt that they are suitable candidates for a cochlear implant. Feasibility of Long-Term VIIIth Nerve Stimulation. Many questions have been raised regarding the feasibility of long-term stimulation of the auditory nerve. The first question raised was whether the auditory nerve would survive severe hair cell degeneration. Studies have shown that in most cases at least a few auditory neurons remain. The next question was whether the cochlear implant itself would destroy the remaining auditory neurons. Preliminary studies have shown that the nerve will survive the placement of electrodes both into the modiolus and the scala tympani. Several electrode materials and insulation have been found to be well tolerated, and there has been minimal damage from thermal or electrolytic processes; therefore, it appears feasible to stimulate the auditory nerve over a long period. Information Transfer by Electrical Stimulation. Single-channel stimulation produces only periodicity pitch, and information transfer is insufficient for speech discrimination. Experience to date indicates that it will be possible to produce both place and volley pitch by electrical stimulation with multiple electrodes in the scala tympani. These findings give promise for the feasibility of producing a device which will transfer sufficient information to produce speech discrimination. Present Status of the Cochlear Implant. To the present time 15 patients have been implanted with a unipolar electrode under the direction of the Ear Research Institute. These patients have all benefited from their devices. They are able to perceive background sounds and receive a cadence or rhythm to speech which makes the device helpful in lipreading. None of the patients have developed significant speech discrimination.

Effects of preoperative embolization on glomus jugulare tumors.

The charts of 35 patients were reviewed retrospectively to determine the effects of embolization on glomus jugulare tumors. Eighteen patients underwent embolization; 17 did not. All tumors were removed with a type A infratemporal fossa approach. The charts were evaluated for operative blood loss, operative time, length of hospitalization, new postoperative cranial nerve deficits and recurrence of tumor. Embolized patients had significantly less operative blood loss and operative time. Embolization did not affect length of hospitalization or reduce the incidence of new postoperative cranial nerve deficits. The surgeon's experience also plays a central role in reducing operative blood loss and operative time. The potential risks of embolization must be considered in the treatment regimen of glomus jugulare tumors.

Facial paralysis in longitudinal temporal bone fractures: a review of 26 cases.

The management of facial nerve injury resulting from temporal bone fracture continues to be a topic of discussion. The indications for surgery as well as the proper timing and extent of surgical exploration are the principal questions debated. This study reviews a large series of patients (26), treated for facial paralysis following a longitudinal temporal bone fracture. The most frequent site of injury was the area of the geniculate ganglion. The injury to the facial nerve was often severe. We recommend early exploration in these cases when electrical studies indicate a severe injury. In most cases a combined mastoid and middle fossa approach is required.

Tympanoplasty: TORPS and PORPS.

We reviewed 106 cases in which PlastiPoreTM prostheses were used for ossicular reconstruction. In all cases a piece of cartilage was interposed between the prosthesis and the tympanic membrane graft to prevent the potential problem of prosthesis extrusion. With total ossicular replacement prostheses (TORPs) 55% closed to within 10 db and 85% closed to within 20 db of the bone conduction level. Closure to within 10 db of the bone conduction level was accomplished in 64% of partial ossicular replacement prostheses (PORPs) cases. These results are better than obtained previously with either ossicles or cartilage alone.

Cholesteatoma surgery: management of the labyrinthine fistula--a report of 97 cases.

Preoperative, operative and postoperative findings in 97 cases of labyrinthine fistula are presented. Most of these patients had had symptoms of chronic otitis media for 20 years or more and manifested some degree of sensorineural hearing impairment. Two-thirds had experienced dizziness. The fistula was limited to the lateral semicircular canal in 83 cases and involved the labyrinth more extensively in 14 instances. The intact canal wall technique was used in less than 60% and an open cavity technique in 25% of the cases. Severe or total sensorineural hearing impairment developed postoperatively in 8% of the lateral canal cases and in over half of the extensive fistula cases. Five percent had incapacitating dizziness for up to six months postoperatively. When a labyrinthine fistula is encountered in an only hearing ear we usually recommend a classical modified radical mastoidectomy. In other instances the procedure performed will vary with the status of the opposite ear, the extent of the fistula, the sensorineural function of the involved ear and the size of the mastoid.

Retrolabyrinthine approach: technique and newer indications.

Excellent exposure of the cerebellopontine angle is obtained by an approach through the mastoid posterior to the labyrinth. Since the major portion of the dissection is extradural, this approach is associated with a very low morbidity. The retrolabyrinthine approach has been used for several years for selective partial section of the posterior root of the trigeminal nerve in cases of trigeminal neuralgia. Complete relief of pain has been accomplished in 25 of 28 cases, and the other 3 patients had partial relief of pain. The only complications in these patients were partial hearing impairment in 2, and 1 partial abducens nerve paralysis which subsequently recovered completely. Two patients required secondary closure of cerebrospinal fluid leaks. This approach has also been used for exploration and biopsy of cerebellopontine angle tumors and for treatment of other cranial nerve problems. We conclude that the retrolabyrinthine approach is the preferred route to the cerebellopontine angle in a variety of clinical conditions.

Iatrogenic facial nerve injury during otologic surgery.

Perhaps the most devastating complication in otologic surgery is that of inadvertent injury to the facial nerve. A review of 22 patients who had sustained an iatrogenic facial nerve injury was conducted. Although the most common procedure being performed during the injury was mastoidectomy (55%), a surprising number of patients had injury during tympanoplasty (14%) or during removal of exostoses (14%). The most common area of injury to the facial nerve in this series was in the tympanic segment. In 79% of the patients, the facial nerve injury was not detected at the time of surgery. All patients underwent surgical exploration of the facial nerve. Otologic surgeons are cautioned to be familiar with the normal course of the facial nerve and to be aware of the potential for facial nerve injury when performing transcanal surgery.

Retrolabyrinthine vestibular neurectomy: a reevaluation.

Selective vestibular neurectomy is considered an effective means of relieving intractable vertigo while preserving hearing. In order to determine the effectiveness of the retrolabyrinthine approach to selective vestibular neurectomy, we evaluated 161 patients who underwent vestibular neurectomy between April 1981 and September 1985. Questionnaire responses indicated that 97% of the Meniere's disease patients and 68% of the non-Meniere's disease patients experienced a substantial improvement or resolution of their vertiginous symptoms. Hearing was maintained within 10 dB of the preoperative level in the majority of the patients. Neurological complications were limited to 2 cases of meningitis which resolved with medical therapy, 7 cases of cerebral spinal fluid leaks, and 3 cases of complete sensorineural hearing loss. Based on this review, we concluded that retrolabyrinthine vestibular neurectomy continues to be a safe and effective approach to relieve ear-related vertigo.

Middle fossa acoustic tumor surgery: results in 106 cases.

Although the middle cranial fossa approach has been used less frequently in recent years than in the past, it continues to be a useful technique for the removal of small acoustic tumors with possible hearing preservation. The approach provides complete exposure of the contents of the internal auditory canal, thus allowing positive facial nerve identification and facilitating total tumor removal. This paper reports the results of 106 middle fossa acoustic tumor removals over a 25-year period. Measurable postoperative hearing remained in 59% of cases. In 89% of cases, normal or near-normal postoperative facial nerve function was obtained. Total tumor removal was achieved in 98% of cases. Preoperative selection criteria are discussed, and postoperative complications are reported.

Management of intratemporal vascular tumors.

Vascular tumors (vascular malformations and hemangiomas) of the temporal bone are uncommon, and guidelines for their management have not been published. In an effort to develop an approach to their management, the present study examined the pathological, clinical, and surgical experience with ten of these lesions treated at the Otologic Medical Group, Inc., and St. Vincent Medical Center in Los Angeles from 1960 to 1980. Intratemporal vascular tumors occurred most frequently at two sites, the internal auditory canal and the geniculate ganglion. Histological features and clinical behavior did not correlate. Both vascular malformations and hemangiomata invaded the facial nerve. Surgical excision in these cases required severence and repair of the involved facial nerve. Complete surgical excision is the treatment of choice of vascular lesions of the temporal bone.

Hearing preservation after acoustic tumor removal: long-term results.

This report examines the durability of preserved postoperative hearing in 25 middle fossa acoustic tumor patients with a minimum follow-up of 3 years. The mean follow-up time for this group was more than 8 years, with a maximum of almost 20 years. The initial postoperative audiogram was compared to the most recent audiogram for each patient, with change in the nonoperated ear serving as the control. Fourteen of the patients (56%) had a significant loss of the preserved hearing in the operated ear over time. The mean loss of speech discrimination was 25%, and the mean loss of speech reception threshold was 12 dB. Only one of the 14 patients had a similar loss in the contralateral ear. No recurrent tumors were identified. Good preoperative hearing is an obvious criterion for selection of candidates for hearing preservation surgery. Results of this study emphasize that a good initial postoperative hearing level is necessary to offset the potential deterioration of hearing that may occur over time.

Magnetic resonance imaging and computerized tomography in malignant external otitis.

In malignant external otitis (MEO), determining the anatomic extent of disease and evaluating the physiologic response to therapy remain a problem. Magnetic resonance imaging (MRI) has recently become available in limited clinical settings. Four patients with MEO were evaluated using MRI, computerized tomography (CT), technetium-99 (Tc-99) bone scanning, and gallium-67 citrate (Ga-67 citrate) scanning. MRI is superior to CT, Tc-99 bone scanning, and Ga-67 citrate scanning in evaluating the anatomic extent of soft tissue changes in MEO. MRI alone cannot be relied upon to determine the physiologic response to therapy. MRI can, however, serve as a valuable guide to the interpretation of Tc-99 bone and Ga-67 citrate scans, and in this respect, MRI is extremely useful in the treatment of MEO.

Endolymphatic sac surgery in congenital malformations of the inner ear.

A retrospective analysis of 40 patients (49 ears) with congenital progressive sensorineural hearing loss who underwent endolymphatic sac surgery was performed. The inner ears were radiographically abnormal in 57% of operated ears. In the remaining cases, subtle malformations beyond the resolving power of radiographic studies were suspected. Early postsurgical hearing loss (defined as a loss greater than 10 dB in three-tone average or greater than 15% in speech discrimination score) was found in 29% of operated ears (14/49). However, only two of these patients lost all of their residual hearing postoperatively (2/49 or 4%). An enlarged endolymphatic sac was noted at surgery in 50% of those with significant postoperative hearing losses. Longer-term stability of hearing was assessed in 22 patients with bilateral inner-ear pathology who underwent surgery on one side only. A comparison of the hearing fate of the operated and nonoperated ears suggested no benefit from the surgical intervention when compared to the natural history of the disease. Based upon this experience, endolymphatic sac surgery for the purpose of hearing stabilization in patients with congenital malformations of the inner ear is no longer recommended.

Reclassification of aggressive adenomatous mastoid neoplasms as endolymphatic sac tumors.

The emerging concept that aggressive adenomatous tumors of the temporal bone arise from the endolymphatic sac and constitute a distinct clinicopathologic entity merits wider recognition. These tumors share a common clinical pattern and exhibit consistent imaging and histopathologic features. Endolymphatic sac tumors (ELSTs) have been mistaken for other neoplasms such as paragangliomas, adenomatous tumors of mixed histology, ceruminomas, and choroid plexus papillomas. A review of the literature shows similarities among case studies of these aggressive adenomatous lesions. An analysis of the data supports the endolymphatic sac as an origin for these tumors. This report also presents an additional case of a less differentiated variant of this rare but important clinicopathologic entity.