Clinical guidelines for the management of craniofacial fibrous dysplasia.

Fibrous dysplasia (FD) is a non-malignant condition caused by post-zygotic, activating mutations of the GNAS gene that results in inhibition of the differentiation and proliferation of bone-forming stromal cells and leads to the replacement of normal bone and marrow by fibrous tissue and woven bone. The phenotype is variable and may be isolated to a single skeletal site or multiple sites and sometimes is associated with extraskeletal manifestations in the skin and/or endocrine organs (McCune-Albright syndrome). The clinical behavior and progression of FD may also vary, thereby making the management of this condition difficult with few established clinical guidelines. This paper provides a clinically-focused comprehensive description of craniofacial FD, its natural progression, the components of the diagnostic evaluation and the multi-disciplinary management, and considerations for future research.

Chondrosarcomas of the skull base and temporal bone.

OBJECTIVE: To evaluate the clinical presentation and outcomes of treatment for patients with chondrosarcomas involving the skull base and temporal bone. STUDY DESIGN: Retrospective review. SETTING: Tertiary medical centre. PATIENTS: Cases of histologically confirmed chondrosarcoma involving the skull base and temporal bones. INTERVENTION: Surgery. MAIN OUTCOME MEASURES: Demographic features of presenting patients; presenting symptoms and signs; surgical approach employed; use of post-operative radiation therapy; histological grade of tumour; and interval of post-operative follow up. RESULTS: Twelve patients were identified with chondrosarcomas involving the skull base, with post-operative follow up ranging from three to 33 years. The average age at presentation was 42 years. The most common presenting symptoms were diplopia, decreased visual acuity and headaches. Five of the 12 patients required multiple surgical procedures. CONCLUSIONS: Patients with chondrosarcoma involving the skull base and temporal bone may present in a variety of ways. Surgical resection, even subtotal, in combination with radiation therapy, can often provide good tumour control over many years for these rare tumours.

Cochlear implantation in patients with osteogenesis imperfecta.

OBJECTIVE: Hearing loss has been shown to occur in 42% to 58% of patients with osteogenesis imperfecta (OI), with deafness arising in 25% to 60% of the patients. Implantation in patients with OI is relatively rare, with only 4 prior single case reports published in the English-language literature. The goal of this study was to evaluate the feasibility and functional outcome of cochlear implantation in 2 patients with OI tarda type I with profound sensorineural hearing loss. STUDY DESIGN: Case series. SETTING: The implantations were performed in a tertiary academic referral center (Johns Hopkins University). RESULTS: Though promontory vascularity was encountered, full insertion of a normal cochlear implant array could be achieved in both cases. One-year postimplant scores demonstrated 20 to 40 dB hearing thresholds, Consonant-Nucleus-Consonant Test word scores of 54% and 70%, Consonant-Nucleus-Consonant Test phoneme scores of 75% and 83%, Hearing in Noise Test scores of 76% and 99%, and Central Institute of the Deaf Sentence Score sentence scores of 99% and 100%, for patients 1 and 2, respectively. CONCLUSIONS: Cochlear implantation in patients with OI is not only technically possible but the results are similar to implant outcomes for patients with sensorineural hearing loss from a variety of other causes. EBM RATING: C.

Benign positional vertigo after cochlear implantation.

OBJECTIVE: To identify patients who underwent cochlear implantation (CI) and who subsequently developed benign positional vertigo (BPV) after the procedure and to identify any contributing factors. STUDY DESIGN AND SETTING: Academic tertiary referral center. Cochlear implant recipients' medical records were retrospectively reviewed to identify patients with both vertigo and, more specifically, BPV. Preoperative, intraoperative, and postoperative factors were studied vis-a-vis the development of BPV. RESULTS: BPV was newly diagnosed in 12 patients after CI. The etiology of hearing loss included presbycusis (16.6%), autoimmune inner ear disease (16.6%), congenital hearing loss (41.6%), Meniere's disease (8.3%), prematurity (8.3%), and idiopathic factors (8.3%). The onset of BPV varied after the procedure (mean +/- SD, 292 +/- 309 days). BPV symptoms did not affect implant performance. All patients were treated for BPV by Epley's maneuver and vestibular exercises. Symptoms disappeared in 11 patients and persisted in 1. CONCLUSIONS: BPV is an uncommon development after CI, although it occurs more frequently than in the general population. Two theories are proposed: the introduction of bone dust into the labyrinth and the dislodging of otoconia during surgery. The diagnosis, treatment, and prognosis of BPV after CI do not differ from those for non-CI-associated BPV. SIGNIFICANCE: Dizziness after CI usually develops as a result of vestibular hypofunction. BPV, which is a hyperfunctioning form of vestibular dysfunction, should be recognized as a possible sequelae of CI.

Fibrous dysplasia involving the skull base and temporal bone.

OBJECTIVE: To gain a broader appreciation of the clinical presentation, operative treatment, and outcome of patients with fibrous dysplasia involving the skull base. DESIGN: Retrospective review of a clinical case series. SETTING: A single tertiary academic medical center. PATIENTS: Twenty-one patients with histopathologically confirmed fibrous dysplasia involving the skull base cared for over a 15-year-period (1983-1998). MAIN OUTCOME MEASURES: Clinical and radiographic location of the fibrous dysplasia lesions within the skull base, clinical presentation, surgical intervention, and clinical outcome were tabulated for each patient. RESULTS: The ethmoids were most commonly involved (71%), followed by the sphenoid (43%), frontal (33%), maxilla (29%), temporal (24%), parietal (14%), and occipital (5%) bones. The most common presenting features included atypical facial pain and headache, complaints referable to the sinuses, proptosis and diplopia, hearing loss, and facial numbness. Surgical treatment, guided by clinical presentation, ranged from simple biopsy with conservative follow-up to craniofacial resection. CONCLUSIONS: Fibrous dysplasia can present in myriad ways within the skull base. Modern imaging modalities and histopathologic analysis have made diagnosis relatively straightforward. Surgery, particularly in such a challenging region as the skull base, should be reserved for patients with functional impairment or a cosmetic deformity. Because of the benign nature of the condition, the surgery itself should be relatively conservative, with the primary goal being preservation of existing function.

Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice.

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.

Hemangioblastoma of the internal acoustic canal in a patient with von Hippel-Lindau disease: a case report and review of the literature.

We report a case of von Hippel-Lindau disease in a 55-year-old woman who presented with an intracanalicular hemangioblastoma and discuss the otologic manifestations of this disease. A review of the literature revealed no previous reports of this entity originating in the internal acoustic canal.

Doxycycline sclerosis of benign lymphoepithelial cysts in patients infected with HIV.

Benign lymphoepithelial cysts (BLCs) are a widely recognized cause of parotid gland swelling in HIV-infected patients. Although they are neither invasive nor associated with malignant degeneration, BLCs can become large and disfiguring. Multiple modalities have been used to control these cysts, but no ideal treatment has been identified. The current study examines the efficacy of doxycycline as a BLC sclerosant in eight patients, and nine BLCs (bilateral BLC in one patient). Follow-up ranged from 12 to 17 months in all cases. Doxycycline sclerosis controlled further cyst growth in 100% of cases with no serious complications. The BLCs became negligible or unnoticeable in two patients, and in six patients (seven BLCs) the cyst became fibrosed and showed no evidence of further growth over the follow-up period. Although further studies are needed to determine the long-term efficacy of this treatment modality, doxycycline sclerosis appears to offer a simple, safe, cost-effective, office-based therapeutic option for the treatment of BLCs in patients infected with HIV.

Contemporary presentation and management of a spectrum of mastoid abscesses.

BACKGROUND: The incidence of complications resulting from suppurative otitis media has significantly decreased since the introduction of antibiotics. At the start of the 20th century 50% of all cases of otitis media developed a coalescent mastoiditis. By 1959, the incidence had fallen to 0.4%. Recent studies suggest a current incidence of only 0.24%. Additionally, during the time of Friedrich Bezold (1824-1908), 20% of patients with mastoiditis developed subperiosteal abscess. Interestingly, this has incidence increased; today nearly 50% of patients diagnosed with coalescent mastoiditis have subperiosteal abscess. OBJECTIVE: To review the contemporary presentation, diagnosis, and management of a spectrum of mastoid abscesses. DESIGN: Retrospective case series. SETTING: Hospitals associated with the Department of Otolaryngology/Head and Neck Surgery at the University of California, San Francisco. PATIENTS: Three patients with mastoid abscesses are reported. One patient displayed "classic" Bezold's abscess, with pus escaping the mastoid near the incisura digastrica and tracking along the digastric and sternocleidomastoid muscles into the neck. The second and third patients exhibited temporoparietal swelling secondary to mastoid abscess eroding the root of the zygomatic process, a complication noted by Bezold in 1908 as occurring "in only very rare cases." RESULTS AND CONCLUSIONS: Since only one third of patients show pathologic tympanic membrane changes, and since complaints of otalgia, fever, and tenderness are inconstant, subperiosteal mastoid abscess is frequently a delayed diagnosis. The clinical presentation, pathogenesis, and routes of abscess spread are presented with photographic and radiographic illustration. Medical and surgical management is reviewed, and methods for accurate diagnosis are emphasized.

Acoustic neuromas presenting with normal or symmetrical hearing: factors associated with diagnosis and outcome.

OBJECTIVE: To evaluate the clinical features leading to diagnosis in patients with acoustic neuroma (AN) who present with normal or symmetrical hearing. Underlying tumor characteristics are also studied to identify a possible explanation for this unique presentation in the AN population. STUDY DESIGN: Retrospective case review comprising patients who were identified as having AN that presented with normal audiometry. SETTING: A tertiary referral center. PATIENTS: Patients with AN who met the criteria for normal were included in the report. For this study, abnormal audiometry is defined as an interaural difference of > or =15 dB at a single frequency or > or =10 dB at two or more frequencies, and an interaural speech reception threshold difference of > or =20 dB, or a speech discrimination score of > or =20%. MAIN OUTCOME MEASURES: Presenting symptoms and signs, clinical features that led to the diagnosis of AN, auditory brain stem response results, tumor location, size and relationship to temporal bone landmarks, surgical intervention, surgical outcome, and results of hearing preservation attempts were tabulated for each patient. RESULTS: A total of 29 patients (5%) were identified who had normal or symmetrical pure-tone audiograms between 500 and 4,000 Hz. The average difference in speech reception threshold between tumor and nontumor ear was 3.2 dB, and the average difference in speech detection score was 2.6%. The most common presenting symptoms that led to the diagnosis of the AN were dysequilibrium/vertigo (12 cases), cranial nerve V and VII abnormalities (11 cases), routine screening for families with neurofibromatosis type 2 (5 cases), asymmetrical tinnitus (4 cases), headaches (4 cases), unilateral subjective hearing difficulty (4 cases), and incidental finding during evaluation for another problem (4 cases). The average tumor size was 19 mm, with five cases presenting with tumors of size > or =30 mm. Nineteen patients underwent a hearing preservation procedure (middle fossa or retrosigmoid), 11 of whom had useful hearing postoperatively. CONCLUSIONS: Despite normal audiometry, patients presenting with imbalance or vertigo, Vth or VIIth cranial nerve deficits, or unilateral hearing complaints may warrant further evaluation to rule out the possibility of AN or other retrocochlear lesion. To seek an explanation for this phenomenon, the incidence of various tumor characteristics (e.g., depth of penetration into the internal auditory canal and degree of porous erosion) is discussed and compared with the entire AN population.

The vulnerability of the vein of labbé during combined craniotomies of the middle and posterior fossae.

During combined middle and posterior cranial fossae ("petrosal") approaches to the skull base, the anastamotic vein of Labbe, which bridges between the inferior surface of the temporal lobe and the transverse sinus is placed at risk. Occlusion of this vein, which may drain a large section of the temporal and parietal lobes, may lead to speech, memory, and/or other cognitive disorders. Labbe may be injured along its course on the inferior aspect of the temporal lobe where it may be laceraed during dural incision or thrombosed due to prolonged or overly vigorous retraction. The anastamotic segment of the vein, which bridges between the temporal lobe and transverse sinus, may be avulsed during elevation of the temporal lobe or injured during tentorial division. Labbé may course in close proximity to the upper surface of the tentorium or even travel within it for a short segment of its course en route to the transverse sinus. This article reviews the anatomy of the vein of Labbé, discusses its clinical significance, and highlights the technical points relevant to the preservation of this important structure.

Radiation-induced tumors of the temporal bone.

OBJECTIVE: To discuss a rare but devastating complication following radiotherapy to the head and neck: radiation-induced malignancies of the temporal bone. STUDY DESIGN: A retrospective case review comprising five patients with radiation-induced tumors involving the temporal bone. SETTING: A tertiary referral center. PATIENTS: Patients with tumors involving the temporal bone who have satisfied the criteria for being considered radiation-associated. MAIN OUTCOME MEASURES: Initial tumor histology, radiation-induced tumor histology, latency between radiotherapy and diagnosis of the radiation-associated malignancy, amount of radiation received, therapeutic interventions, and survival statistics for each patient. RESULTS: Five cases of radiation-induced tumors of the temporal bone are presented (two osteosarcomas, two fibrosarcomas, and one squamous cell carcinoma). All five temporal bone tumors occurred in individuals that had previously received > 5,000 cGy of radiation. The initial histologic diagnoses included two astrocytomas, a glomus jugulare, a malignant meningioma, and a vestibular schwannoma. There was an average latency period of 15 years (range, 7-23 years) between completion of radiation and diagnosis of the malignancy. Four patients were treated with resection plus chemotherapy, and one decided against therapy. The prognosis was poor, with survival time of 7-14 months after the diagnosis of the radiation-induced tumor. Only one patient survived > 14 months and is currently free of disease, 3 years after diagnosis of the radiation-induced tumor. CONCLUSIONS: Although radiation-induced tumors of the temporal bone occur with a very low incidence, their prognosis is extremely poor. The remote possibility of a radiation-associated tumor should be factored in when deciding upon the most appropriate therapeutic modality for individuals with neoplasms of the CNS and head and neck. Such considerations are particularly germane when contemplating radiation therapy for a benign lesion (e.g., glomus jugulare, acoustic neuroma, or meningioma) in an individual with a long predicted lifespan.

The early history of the neurofibromatosis. Evolution of the concept of neurofibromatosis type 2.

Although neurofibromatosis (NF) became widely recognized as a pathologic entity in the late 19th century, only relatively recently has a clear distinction been made between its generalized form and the central variety. The latter form is typified by bilateral acoustic neuromas (ANs), which may be accompanied by other intracranial tumors, in particular, meningiomas. Up until almost the current era, confusion regarding the protean manifestations of the 2 types of NF existed in the minds of clinicians and in the literature. In 1987, a consensus panel of the National Institutes of Health differentiated the clinical manifestations associated with classic von Recklinghausen syndrome from those of the predominantly intracranial subtype and they were subsequently deemed NF type 1 (NF-1) and NF type 2 (NF-2), respectively. During the last few years, the genetic flaws that underlie these 2 syndromes have been elucidated, revealing that their origins lie in defects on separate chromosomes. The early literature on the subject included repeated descriptions of patients with manifestations typical of NF-2. The investigators, however, considered the intracranial lesions to be merely 1 facet of the generalized form of the disease. A few prescient individuals, however, demonstrated an appreciation for the distinguishing characteristics between these superficially similar, yet quite different, syndromes. The goals of this article are to trace the evolution of the concept of NF-2 as a distinct clinical entity from NF-1 and to assess the early awareness of and attitudes toward bilateral ANs, familial ANs, and ANs associated with other intracranial tumors.

The variable relationship between the lower cranial nerves and jugular foramen tumors: implications for neural preservation.

Tumors involving the jugular foramen (JF) have a variable relationship to the neurovascular structures (jugular vein, cranial nerves IX-XI) that traverse this conduit through the skull base. The surgeon familiar with the site of origin, growth pattern, and geometry of each of the common lesions affecting this region with respect to surrounding nerves and vessels is at a considerable advantage when undertaking a function-sparing procedure. Anatomically, the JF has two vascular compartments that may be affected by tumor: the jugular bulb laterally and a passage for the inferior petrosal sinus medially. Tumors may also penetrate the JF along the fibro-osseous diaphragm, which divides these two vascular channels. The lower cranial nerves lie on either side of this partition, which is connected to the posterior cranial fossa via a curved, funnel-shaped cone of dura. Tumors that arise within or penetrate the JF lateral to this neural plane displace the nerves medially, a position favorable for their preservation during tumor extirpation. By contrast, medially positioned tumors displace the cranial nerves onto the lateral tumor surface, where they interpose between surgeon and tumor-an unfavorable location. Glomus tumors consistently arise in the lateral aspect of the JF, displacing the lower cranial nerves medially. This positioning accounts for the high rate of neural preservation in small and medium-size glomus tumors that have not invaded the foramen's central partition. Meningiomas that arise lateral to the JF (e.g., the posterior petrous surface, sigmoid sinus) favorably displace the lower cranial nerves medially. By contrast, tumors that originate medial to the JF (e.g., clivus, foramen magnum) are unfavorable, laterally displacing the multiple small rootlets that coalesce into cranial nerves IX-XI into a vulnerable location. Schwannomas arise within the neural plane and have a variable geometry that depends, in part, upon the nerve of origin. Theoretically, tumors that arise from the ninth nerve, which is located on the lateral surface of the neural plane, should be more favorable than those originating from the tenth or eleventh nerves, which lie on its deep surface. The propensity of these three tumor types toward thrombosis of the jugulosigmoid complex also carries important surgical implications. Because glomus tumors arise from the jugular bulb, the jugulosigmoid complex is nearly always occluded. In both meningiomas and schwannomas, however, the jugular system may occasionally remain patent. This is important to recognize through angiography and/or magnetic resonance venography, since sacrifice of a patent, dominant system risks intracerebral venous infarction.

Lemierre's syndrome: two cases of postanginal sepsis.

Lemierre's disease consists of suppurative thrombophlebitis of the IJV in the presence of oropharyngeal infection and can be complicated by septic pulmonary emboli. If a patient has an oropharyngeal or deep neck infection and neck pain suspicious for IJV thrombosis, a CT or MRI is warranted to establish the diagnosis. Blood cultures should be obtained to establish the responsible organism. In most cases F. necrophorum, an anaerobic bacterium, is responsible for the sepsis. Once the diagnosis of Lemierre's disease is made, long-term, high-dose intravenous antibiotics with beta-lactamase anaerobic activity should be initiated. In cases with persistent sepsis and emboli despite appropriate medical management, ligation or excision of the IJV should be performed. Finally, if there is clinical or radiologic evidence of retrograde cavernous sinus thrombosis, the use of anticoagulants should be considered.

Repair of chronic tympanic membrane perforations using epidermal growth factor.

Perforation of the tympanic membrane (TM) is a frequent cause of conductive hearing loss. Persistent TM perforations often require surgical repair with an autologous tissue graft to restore hearing and prevent recurrent infection. While highly efficacious, this method of closure requires a relatively complex and expensive microsurgical procedure. We have recently developed a chronic TM perforation model in the chinchilla for use in the exploration of novel methods of TM repair.