Wisdom tooth extraction causing lingual nerve and styloglossus muscle damage: a mimic of multiple cranial nerve palsies.

The combination of tongue hemianaesthesia, dysgeusia, dysarthria and dysphagia suggests the involvement of multiple cranial nerves. We present a case with sudden onset of these symptoms immediately following wisdom tooth extraction and highlight the clinical features that allowed localisation of the lesion to a focal, iatrogenic injury of the lingual nerve and adjacent styloglossus muscle.

Asymmetry of balance responses to monaural galvanic vestibular stimulation in subjects with vestibular schwannoma.

OBJECTIVE: We investigated the potential of galvanic vestibular stimulation (GVS) to quantify lateralised asymmetry of the vestibulospinal pathways by measuring balance responses to monaural GVS in 10 subjects with vestibular schwannoma and 22 healthy control subjects. METHODS: Subjects standing without vision were stimulated with 3 s, 1 mA direct current stimuli delivered monaurally. The mean magnitude and direction of the evoked balance responses in the horizontal plane were measured from ground-reaction forces and from displacement and velocity of the trunk. Vestibular-evoked myogenic potentials (VEMPs) to 500 Hz air and bone-conducted tones were also recorded. RESULTS: In healthy subjects, the magnitudes of the force, velocity and displacement responses were not significantly different for left compared to right ear stimulation. Their individual asymmetry ratios were always < 30%. Subjects with vestibular schwannoma had significantly smaller force, velocity and displacement responses to stimulation of the affected compared with non-affected ear. Their mean asymmetry ratios were significantly elevated for all three measures (41.2 ± 10.3%, 40.3 ± 15.1% and 21.9 ± 14.6%). CONCLUSIONS: Asymmetry ratios of balance responses to monaural GVS provide a quantitative and clinically applicable lateralising test of the vestibulospinal pathways. SIGNIFICANCE: This method offers a more clinically relevant measure of standing balance than existing vestibular function tests which assess only vestibuloocular and vestibulocollic pathways.

The NFTI-QOL: A Disease-Specific Quality of Life Questionnaire for Neurofibromatosis 2.

The objective of this study was to develop a reliable, validated disease-specific score measuring quality of life (QOL) in clinical practice and treatment trials in Neurofibromatosis 2 (NF2) individuals. In NF2 patients, qualitative interviews (n = 15) and a focus group session (n = 30) generated items for a pilot questionnaire. This was tested and refined (n = 20). The final version (NFTI-QOL) was validated (n = 50) with two generic QOL questionnaires (SF-36 and EuroQOL). The NFTI-QOL was also administered to patients with solitary vestibular schwannoma (SVS) (n = 30) and normal controls (n = 30). The participants were NF2 patients, SVS patients, and normal controls. NFTI-QOL score, SF-36 score, and EuroQOL score were the main outcome measures. Mean NFTI-QOL score was 9.4 (range: 0 to 20, maximum possible score = 24). The NFTI-QOL score correlated strongly with EuroQOL (r = 0.71, p < 0.001) and SF-36 (r = 0.81, p < 0.001). NF2 individuals were significantly worse than the SVS patients, who in turn were worse than the controls on the NIFTI-QOL. The NFTI-QOL showed good internal reliability (Cronbach's α = 0.87). We developed an eight-item disease-specific QOL score for NF2 patients, validated against SF-36 and EuroQOL. It correlated strongly with clinician-rated disease severity in NF2, with better correlation than the SF-36 in this regard.

Copy number and loss of heterozygosity detected by SNP array of formalin-fixed tissues using whole-genome amplification.

The requirement for large amounts of good quality DNA for whole-genome applications prohibits their use for small, laser capture micro-dissected (LCM), and/or rare clinical samples, which are also often formalin-fixed and paraffin-embedded (FFPE). Whole-genome amplification of DNA from these samples could, potentially, overcome these limitations. However, little is known about the artefacts introduced by amplification of FFPE-derived DNA with regard to genotyping, and subsequent copy number and loss of heterozygosity (LOH) analyses. Using a ligation adaptor amplification method, we present data from a total of 22 Affymetrix SNP 6.0 experiments, using matched paired amplified and non-amplified DNA from 10 LCM FFPE normal and dysplastic oral epithelial tissues, and an internal method control. An average of 76.5% of SNPs were called in both matched amplified and non-amplified DNA samples, and concordance was a promising 82.4%. Paired analysis for copy number, LOH, and both combined, showed that copy number changes were reduced in amplified DNA, but were 99.5% concordant when detected, amplifications were the changes most likely to be 'missed', only 30% of non-amplified LOH changes were identified in amplified pairs, and when copy number and LOH are combined ∼50% of gene changes detected in the unamplified DNA were also detected in the amplified DNA and within these changes, 86.5% were concordant for both copy number and LOH status. However, there are also changes introduced as ∼20% of changes in the amplified DNA are not detected in the non-amplified DNA. An integrative network biology approach revealed that changes in amplified DNA of dysplastic oral epithelium localize to topologically critical regions of the human protein-protein interaction network, suggesting their functional implication in the pathobiology of this disease. Taken together, our results support the use of amplification of FFPE-derived DNA, provided sufficient samples are used to increase power and compensate for increased error rates.

Giant cell tumour and central giant cell reparative granuloma of the skull: do these represent ends of a spectrum? A case report and literature review.

Giant cell tumour (GCT) of bone is an uncommon primary bone neoplasm typically occurring at the epiphyses of long bones in young adults. They are osteolytic neoplasms with approximate local recurrence rates of 25%, and 2% of patients develop pulmonary metastases. These tumours appear very rarely in the skull, with those few reported cases arising predominantly in the sphenoid and occasionally the temporal bones. They demonstrate benign histological features, but are locally aggressive and surgical excision is the treatment of choice. It is widely believed that giant cell tumours should be distinguished from other giant cell lesions, importantly central giant cell reparative granulomata (CGCG) which are thought to have a lower recurrence rate and for which no cases of malignant transformation or metastases have been reported. Investigators have noted that giant cell lesions in the skull bones may be unique and that GCT and CGCG may be part of a spectrum of a single disease process. We present a case of a giant cell tumour of the temporal bone which illustrates and re-emphasises this concept and review the literature on these lesions.

Expression of HIF-1alpha, HIF-2alpha (EPAS1), and their target genes in paraganglioma and pheochromocytoma with VHL and SDH mutations.

CONTEXT: Activation of the hypoxia-inducible transcription factors HIF-1 and HIF-2 and a HIF-independent defect in developmental apoptosis have been implicated in the pathogenesis of pheochromocytoma (PCC) associated with VHL, SDHB, and SDHD mutations. OBJECTIVE: Our objective was to compare protein (HIF-1alpha, EPAS1, SDHB, JunB, CCND1, CD34, CLU) and gene (VEGF, BNIP3) expression patterns in VHL and SDHB/D associated tumors. RESULTS: Overexpression of HIF-2 was relatively more common in VHL than SDHB/D PCC (12 of 13 vs. 14 of 20, P = 0.02), whereas nuclear HIF-1 staining was relatively more frequent in SDHB/D PCC (19 of 20 vs. 13 of 16, P = 0.04). In addition, CCND1 and VEGF expression (HIF-2 target genes) was significantly higher in VHL than in SDHB/D PCC. These findings suggest that VHL inactivation leads to preferential HIF-2 activation and CCND1 expression as described previously in VHL-defective renal cell carcinoma cell lines but not in other cell types. These similarities between the downstream consequences of VHL inactivation and HIF dysregulation in renal cell carcinoma and PCC may explain how inactivation of the ubiquitously expressed VHL protein results in susceptibility to specific tumor types. Both VHL and SDHB/D PCC demonstrated reduced CLU and SDHB expression. SDHB PCC are associated with a high risk of malignancy, and expression of (proapototic) BNIP3 was significantly lower in SDHB than VHL PCC. CONCLUSION: Although inactivation of VHL and SDHB/D may disrupt similar HIF-dependent and HIF-independent signaling pathways, their effects on target gene expression are not identical, and this may explain the observed clinical differences in PCC and associated tumors seen with germline VHL and SDHB/D mutations.

Bilateral squamous cell carcinoma of the temporal bones.

We report a case of bilateral squamous cell carcinoma of the temporal bones in a 66-year-old woman who underwent a left subtotal petrosectomy and a right lateral temporal bone resection. Hearing rehabilitation was successfully achieved by fitting a bone-anchored hearing aid (BAHA) on the right side. We feel that in cases where the extent of the tumor permits a lateral temporal bone resection in at least one side, fitting of a BAHA can achieve a good outcome without resorting to tympanoplasty techniques that may compromise the medial end of the surgical resection.

Hydroxyurea treatment of meningiomas: a pilot study.

OBJECTIVES: To present a pilot study of hydroxyurea chemotherapy in the management of surgically difficult meningiomas. DESIGN: Prospective case series. SETTING: Tertiary referral center. PARTICIPANTS: Six patients were enrolled: five had symptomatic recurrent or residual WHO Grade I meningiomas and one had an unoperated anterior clinoidal meningioma. MAIN OUTCOME MEASURES: MRI volumetry before and after treatment, hematological state, progression to surgery. RESULTS: Hydroxyurea was administered for 1 year, starting at a dose of 15 mg/kg/day. No tumors reduced in size on treatment and one continued to grow rapidly. Three remained stable. Full volumetry was unavailable on two patients. One patient was withdrawn from the study because of myelosuppression and underwent further surgery. Three experienced significant drug-related side effects. Two patients underwent further surgery. CONCLUSIONS: From this small pilot study we conclude that although hydroxyurea may be associated with disease stabilization in some patients, it did not reduce tumor mass and it caused significant side effects in some of our subjects.

An Osteoma of the Middle Ear Presenting with the Tullio Phenomenon.

The Tullio phenomenon is an extremely rare condition in which loud noise induces a brisk vestibular response. Osteomas of the middle ear cleft are also uncommon. We report a patient with an osteoma of the middle ear cleft that became symptomatic with progressive facial palsy and mixed hearing loss. The onset was heralded by the Tullio phenomenon, which she had experienced for 10 years. The differential diagnosis of the Tullio phenomenon and the management of middle ear osteomas are discussed.