Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in... Show morePatients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom-first, do no harm-should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs. Show less
Background: T4-classified squamous cell carcinoma (SCC) of external auditory canal (EAC) can potentially involve different anatomical structures, which could translate into different treatment... Show moreBackground: T4-classified squamous cell carcinoma (SCC) of external auditory canal (EAC) can potentially involve different anatomical structures, which could translate into different treatment strategies and survival outcomes within one classification. Our aim is to evaluate the clinical added value of T4-subclasses proposed by Lavieille and by Zanoletti. Methods: Retrospective data, including patients with primary operated cT4-classified EAC SCC, was obtained from 12 international hospitals. We subclassified according to the T4-subclasses. The treatment strategies, disease-free survival (DFS) and overall survival per subclass were calculated. Results: A total of 130 T4-classified EAC SCC were included. We found commonly used treatment strategies per subclass according to Lavieille and the DFS seems also to differ per subclass. Subclass according to Zanoletti showed comparable treatment strategies and survival outcomes per subclass. Conclusion: Our study suggests that the subclass according Lavieille might have added value in clinical practice to improve care of T4-classified EAC SCC. Show less
This study investigates whether there exist differences in facial emotion detection accuracy in patients suffering from Vestibular Schwannoma (VS) due to their facial paresis. Forty-four VS... Show moreThis study investigates whether there exist differences in facial emotion detection accuracy in patients suffering from Vestibular Schwannoma (VS) due to their facial paresis. Forty-four VS patients, half of them with, and half of them without a facial paresis, had to classify pictures of facial expressions as being emotional or non-emotional. The visual information of images was systematically manipulated by adding different levels of visual noise. The study had a mixed design with emotional expression (happy vs. angry) and visual noise level (10% to 80%) as repeated measures and facial paresis (present vs. absent) and degree of facial dysfunction as between subjects' factors. Emotion detection accuracy declined when visual information declined, an effect that was stronger for anger than for happy expressions. Overall, emotion detection accuracy for happy and angry faces did not differ between VS patients with or without a facial paresis, although exploratory analyses suggest that the ability to recognize emotions in angry facial expressions was slightly more impaired in patients with facial paresis. The findings are discussed in the context of the effects of facial paresis on emotion detection, and the role of facial mimicry, in particular, as an important mechanism for facial emotion processing and understanding. Show less
BackgroundHearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the... Show moreBackgroundHearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the genetic causes are largely unknown, which is in contrast to childhood-onset hearing loss.MethodsFamily and cohort studies included exome sequencing and characterisation of the hearing phenotype. Ex vivo protein expression addressed the functional effect of a DNA variant.ResultsAn in-frame deletion of 12 nucleotides in RIPOR2 was identified as a highly penetrant cause of adult-onset progressive hearing loss that segregated as an autosomal dominant trait in 12 families from the Netherlands. Hearing loss associated with the deletion in 63 subjects displayed variable audiometric characteristics and an average (SD) age of onset of 30.6 (14.9) years (range 0-70 years). A functional effect of the RIPOR2 variant was demonstrated by aberrant localisation of the mutant RIPOR2 in the stereocilia of cochlear hair cells and failure to rescue morphological defects in RIPOR2-deficient hair cells, in contrast to the wild-type protein. Strikingly, the RIPOR2 variant is present in 18 of 22 952 individuals not selected for hearing loss in the Southeast Netherlands.ConclusionCollectively, the presented data demonstrate that an inherited form of adult-onset hearing loss is relatively common, with potentially thousands of individuals at risk in the Netherlands and beyond, which makes it an attractive target for developing a (genetic) therapy. Show less
Background Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate... Show moreBackground Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate the predictive performance of this classification in relation to disease-free survival (DFS). Methods We examined retrospective data from a nationwide Dutch cohort study including patients with primary EAC SCC. These data were combined with individual patient data from the literature. Using the combined data, the predictive performances were calculated using the c-index. Results A total of 381 patients were included, 294 for clinical and 281 for the pathological classification analyses. The c-indices of the clinical and the pathological modified Pittsburgh classification predicting DFS were 0.725 (0.668-0.782) and 0.729 (0.672-0.786), respectively. Conclusion The predictive performance of the modified Pittsburgh classification system as such appears to be acceptable to predict the DFS of EAC SCC. Other factors need to be added to a future model to improve the predicted performance. Show less
Objective(s) The present study aimed to replicate the finding that vestibular schwannoma (VS) patients with facial paresis experience lower health related quality of life (QoL) than those without... Show moreObjective(s) The present study aimed to replicate the finding that vestibular schwannoma (VS) patients with facial paresis experience lower health related quality of life (QoL) than those without facial paresis in a Dutch sample, and to extend these findings by measuring VS patients' overall satisfaction with life, social function, and emotion. Methods Forty-seven VS patients, differing in degree of facial functioning, half of them with and half of them without a facial paresis, answered questionnaires about health related QoL (SF-36 and PANQOL), overall satisfaction with life, fear of being evaluated negatively by others, social avoidance and distress, and characteristics and symptoms of depression. Results We observed that VS patients with facial paresis experience lower health-related QoL as well negatively impacted social function and emotion compared to VS patients without facial paresis. VS patients with facial paresis experienced lower overall satisfaction with life, more characteristic symptoms of depression, and more fear of being evaluated negatively by others than VS patients without facial paresis. Conclusion These findings corroborate previous research showing an association between impaired facial functioning and lower QoL, but also extend them by showing differences on the quality of social function and emotion. Being aware of this difference between VS patients with and without facial paresis informs health practitioners regarding the specific support these patients might need. Moreover, it is also relevant to consider the influence of a facial paresis on patients' life when deciding between treatment options and in case of surgery the type of resection. Level of evidence 3 Show less
Objective This study investigates whether there exist differences in lateralization of facial emotion processing in patients suffering from Vestibular Schwannoma (VS) based on the presence of a... Show moreObjective This study investigates whether there exist differences in lateralization of facial emotion processing in patients suffering from Vestibular Schwannoma (VS) based on the presence of a facial paresis and their degree of facial functioning as measured by the House Brackmann Grading scale (HBG).Methods Forty-four VS patients, half of them with a facial paresis and half of them without a facial paresis, rated how emotive they considered images of faces showing emotion in the left versus right visual field. Stimuli consisted of faces with a neutral half and an emotional (happy or angry) half. The study had a mixed design with emotional expression (happy vs. angry) and emotional half (left vs. right visual field) of the faces as repeated measures, and facial paresis (present vs. absent) and HBG as between subjects' factors. The visual field bias was the main dependent variable.Results In line with typical findings in the normal population, a left visual field bias showed in the current sample: patients judged emotional expressions shown in the left visual field as more emotive than those shown in the right visual field. No differences in visual field bias showed based on the presence of a facial paresis nor based on patients' HBG.Conclusion VS patients show a left visual field bias when processing facial emotion. No differences in lateralization showed based on the presence of a facial paresis or on patients' HBG. Based on this study, facial paresis thus does not affect the lateralization of facial emotion processing in patients with VS. Show less
