von Hippel-Lindau disease: Updated guideline for diagnosis and surveillance.

von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families. This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations. RECOMMENDATIONS: vHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.

Correlation between subjective and objective measures in bilateral vestibulopathy.

BACKGROUND: Bilateral vestibulopathy (BVP) is a chronic and potentially very disabling condition. The impact of the vestibular loss on quality of life (QoL) is variable and still up for discussion. However, previous studies have reported that BVP has a negative impact of QoL. AIMS/OBJECTIVES: The aim of the study was to evaluate the association between vestibulo-ocular reflex (VOR) gain and saccade pattern and patient reported QoL. MATERIALS AND METHODS: Ten patients fulfilling the Bárány criteria of BVP were included in the study. All patients underwent vestibular evaluation using Head Impulse Paradigm (HIMP) and Suppression Head Impulse Paradigm (SHIMP) and responded to Dizziness Handicap Inventory (DHI). DHI was used as a measurement for QoL. RESULTS: Linear regression revealed a tendency to a correlation between lateral VOR-gain measured by HIMP or SHIMP and total DHI score. Covert saccades were related to low total DHI scores. No association was found between type of SHIMP saccade and QoL. No significant correlations were found. CONCLUSION AND SIGNIFICANCE: A tendency was found towards a relationship between lateral VOR-gain by HIMP or SHIMP and total DHI score. The study also indicates that covert saccades are related to low impact on QoL.

Correction to: The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management.

The following information was inadvertently omitted in the original publication.

The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management.

Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients.

Clinically isolated laryngeal sarcoidosis.

Laryngeal sarcoidosis is rare (0.5% of patients with sarcoidosis), the pathogenesis is unknown and the optimal treatment remains a matter of debate. We undertook this study to elucidate possible pathogenic factors in clinically isolated laryngeal sarcoidosis and to describe results of supraglottoplastic surgery. From 1995 to 2009, we identified six patients with histologically proven sarcoidosis of the larynx treated at Rigshospitalet. All patients were subjected to a panel of blood tests and MR scan of the head and neck. All patients had dyspnoea at admission, and five were subjected to a combination of CO(2)-laser excision of supraglottic tissue and closure of the incision with sutures. All serological tests were negative or normal, including angiotensin 1 converting enzyme. The clinical expression was uniform with pale, smooth swellings of the supraglottic structures. Surgery proved successful to maintain normal breathing. None of the many parameters examined--some previously having been found to be abnormal in sarcoidosis--were abnormal in the present cohort. We are therefore unable to elucidate the pathogenesis. The combined surgical approach re-established normal airway function for all five patients and complete remission without further swellings was seen in two patients.

Cholesteatoma of the external ear canal: etiological factors, symptoms and clinical findings in a series of 48 cases.

BACKGROUND: To evaluate symptoms, clinical findings, and etiological factors in external ear canal cholesteatoma (EECC). METHOD: Retrospective evaluation of clinical records of all consecutive patients with EECC in the period 1979 to 2005 in a tertiary referral centre. Main outcome measures were incidence rates, classification according to causes, symptoms, extensions in the ear canal including adjacent structures, and possible etiological factors. RESULTS: Forty-five patients were identified with 48 EECC. Overall incidence rate was 0.30 cases per year per 100,000 inhabitants. Twenty-five cases were primary, while 23 cases were secondary: postoperative (n = 9), postinflammatory (n = 5), postirradiatory (n = 7), and posttraumatic (n = 2). Primary EECC showed a right/left ratio of 12/13 and presented with otalgia (n = 15), itching (n = 5), occlusion (n = 4), hearing loss (n = 3), fullness (n = 2), and otorrhea (n = 1). Similar symptoms were found in secondary EECC, but less pronounced. In total the temporomandibular joint was exposed in 11 cases, while the mastoid and middle ear was invaded in six and three cases, respectively. In one primary case the facial nerve was exposed and in a posttraumatic case the atticus and antrum were invaded. In primary EECC 48% of cases reported mechanical trauma. CONCLUSION: EECC is a rare condition with inconsistent and silent symptoms, whereas the extent of destruction may be pronounced. Otalgia was the predominant symptom and often related to extension into nearby structures. Whereas the aetiology of secondary EECC can be explained, the origin of primary EECC remains uncertain; smoking and minor trauma of the ear canal may predispose.