Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience.

The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years' (2001-2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder.

Current Trends, Controversies, and Future Directions in the Evaluation and Management of Superior Canal Dehiscence Syndrome.

Patients with superior canal dehiscence syndrome (SCDS) can present with a range of auditory and/or vestibular signs and symptoms that are associated with a bony defect of the superior semicircular canal (SSC). Over the past two decades, advances in diagnostic techniques have raised the awareness of SCDS and treatment approaches have been refined to improve patient outcomes. However, a number of challenges remain. First, there is currently no standardized clinical testing algorithm for quantifying the effects of superior canal dehiscence (SCD). SCDS mimics a number of common otologic disorders and established metrics such as supranormal bone conduction thresholds and vestibular evoked myogenic potential (VEMP) measurements; although useful in certain cases, have diagnostic limitations. Second, while high-resolution computed tomography (CT) is the gold standard for the detection of SCD, a bony defect does not always result in signs and symptoms. Third, even when SCD repair is indicated, there is a lack of consensus about nomenclature to describe the SCD, ideal surgical approach, specific repair techniques, and type of materials used. Finally, there is no established algorithm in evaluation of SCDS patients who fail primary repair and may be candidates for revision surgery. Herein, we will discuss both contemporary and emerging diagnostic approaches for patients with SCDS and highlight challenges and controversies in the management of this unique patient cohort.

COVID-19 infection rate among tertiary referral center otorhinolaryngology healthcare workers.

IMPORTANCE: Otorhinolaryngology is considered one of the medical specialties with a high risk for exposure to corona disease 2019 (COVID-19). Uncontrolled transmission in a hospital department poses a risk to both healthcare workers (HCWs) and patients. OBJECTIVE: To monitor SARS-CoV-2 incidence, transmission, and antibody development among HCWs to identify high risk procedures, pathways, and work areas within the department. METHODS: Prospective cohort study of HCWs using repetitive oro- and nasopharygeal swab samples, antibody tests, and self-reported symptoms questionnaires at a tertiary referral center in Copenhagen, Denmark. RESULTS: 347/361 (96%) HCWs participated. Seven (1.9%) were positive on swab tests and none had symptoms. Fifteen (4.2%) developed antibodies. Only one case of potential transmission between HCWs was identified. Infection rates were low and no procedures or areas within the department were identified as exposing HCWs to a higher risk. CONCLUSIONS AND RELEVANCE: Adherence to the surveillance program was high. The low incidence among HCW during the first wave of the COVID-19 pandemic may reflect local transmission and infection control precautions, as well as a low infectious burden in the Danish society.

The impact and prevalence of SARS-CoV-2 in patients with head and neck cancer and acute upper airway infection in a tertiary otorhinolaryngology referral center in Denmark.

PURPOSE: To determine the prevalence of SARS-CoV-2 at a Danish tertiary referral otorhinolaryngology clinic during the first wave of the COVID-19 pandemic among patients with suspected acute upper airway infection (UAI) and patients operated for head and neck cancer (HNC), respectively. To monitor changes in the number of patient encounters for acute UAI and the number of referrals for the workup of HNC. TRIAL REGISTRATION: NCT-04356560 (Clinicaltrials.gov). METHODS: Prospective enrolled case series of all patients with suspected acute UAI (n = 88) and of patients undergoing surgery for HNC (n = 96), respectively, from March 23rd to May 5th, 2020, at a public tertiary referral otorhinolaryngology clinic in Denmark. SARS-CoV-2 was diagnosed with nasopharyngeal and oropharyngeal swabbing. Patients with suspected acute UAI had symptoms and definitive diagnoses registered in a database. Trends in the number of referrals and patient encounters were retrieved from an electronic patient journal system and analyzed retrospectively. RESULTS: Eighty-eight patients with acute UAI were enrolled including 55 men and 34 women, median age of 31 years (range: 10 months to 82 years). One patient (1.1%) tested positive. Among 96 patients operated for HNC, zero tested positive. The number of referrals for HNC workup, and patient encounters for peritonsillar abscesses, decreased markedly in the first 3 weeks. CONCLUSION: The prevalence of SARS-CoV-2 during the first 6 weeks of the first wave was minimal among patients with acute UAI and zero among patients operated for HNC. The decrease in referrals for the workup of HNC may increase time to treatment initiation and patient morbidity.

Video head impulse test saccades and loss of cervical vestibular evoked myogenic potentials are late vestibular footprints of cochlear implantation.

BACKGROUND: Cochlear implantation may be complicated by concurrent injury to the vestibular apparatus, potentially resulting in disabling vertigo and balance problems. Information on vestibular function before implantation as measured by the video head impulse test (VHIT) and cervical vestibular evoked myogenic potentials (cVEMPs) is scarce and literature on long-term effects is non-existing. OBJECTIVE: We aimed to evaluate how vestibular function was affected by cochlear implantation (CI), as measured by VHIT and cVEMPs in the late phase after implantation. METHODS: Retrospective repeated measurement study. PATIENTS: Among the 436 patients elected for CI surgery during 2013 to 2018, 45 patients met the inclusion criteria (CI recipients with a vestibular assessment prior to the first CI and a repeated vestibular assessment after the CI operation). INTERVENTION: VHIT and cVEMPs before and after cochlear implantation. Main outcome measures were vestibular function as evaluated by VHIT gain, saccades and cVEMPs. RESULTS: The mean time between first and second vestibular screening was 19 months. The mean VHIT gain on implanted ears was 0.79 before the operation and showed no change at follow-up (p = 0.65). Likewise, the number of abnormal VHIT gain values was equal before and after the operation (p = 0.31). Preoperatively, saccades were present on 12 ears (14%) compared with 25 ears (29%) postoperatively (p = 0.013) and were associated with significantly lower VHIT gain values. Preoperatively, positive cVEMPs were found in 20 CI ears (49%) and 24 contralateral ears (62%). 10 CI ears lost cVEMP postoperatively compared with 2 ears on the contralateral side (p = 0.0047). CONCLUSIONS: Even though VHIT gain has been reported to be affected in the immediate post-implantation period, the findings in this study show that VHIT gain is normalized in the long-term. However, cochlear implantation is associated with the occurrence of VHIT saccades in the long-term and these are associated with lower VHIT gain values. In addition, cVEMP responses are significantly reduced long-term on implanted ears, which agrees with other studies with shorter follow-up.

Vestibular Screening Before Cochlear Implantation: Clinical Implications and Challenges in 409 Cochlear Implant Recipients.

OBJECTIVE: Cochlear implantation (CI) carries a risk of loss of vestibular function following surgery. Thus, vestibular assessment presurgery is used to identify vestibulopathy that may contraindicate implantation and guide in selecting the candidate ear. The aim of this study was to evaluate the clinical implications of preoperative vestibular assessment, and to identify challenges in performing vestibular testing in patients with profound hearing loss, i.e., CI candidates. STUDY DESIGN: Retrospective study of all CI recipients implanted since the introduction of a vestibular screening program. SETTING: Tertiary referral center in 2013. PATIENTS AND INTERVENTION: CI candidates routinely underwent testing with the video head impulse test (VHIT) and the cervical vestibular evoked myogenic potential (cVEMP) test as a part of the CI work up. RESULTS: Three hundred thirty-five individuals were screened before the first CI and 74 individuals before the second CI. In 301 cases (73.6%), the vestibular function was considered normal and consequently carried no contraindications for surgery or implications for choice of ear to be implanted. Bilateral vestibular loss was found in 43 cases (10.5%) and unilateral vestibular loss was found in 62 cases (15.2%). In the latter cases, evaluation of multiple variables was indicated to select candidate ear. In nine implanted patients (2.2%), a relative contraindication to operate based on an "only balancing" ear was overruled by other factors. Vestibular testing was challenged by various factors (e.g., neck immobility, eye tracking issues, communication, and other patient issues), limiting the vestibular data output. This resulted in omittance, testing failure, or interpretation uncertainty 24 times (5.9%) for VHIT and 65 times (15.9%) for cVEMP. CONCLUSION: Vestibular screening is an important part of the clinical workup with respect to selection of candidate ear for cochlear implantation, as 15.2% of CI candidates present with unilateral vestibulopathy. Challenges in performing the vestibular tests are not uncommon, as test failure occurred in 15.9% of cases for the cVEMP and 5.9% for the VHIT. The most common reasons for test failure were neck immobility, communication issues, and problems of pupil tracking.

Video Head Impulse Test Results in Patients With a Vestibular Schwannoma-Sensitivity and Correlation With Other Vestibular System Function Tests, Hearing Acuity, and Tumor Size.

OBJECTIVE: No previous studies have investigated a vestibular function test battery combining the Video Head Impulse Test (VHIT), the caloric test, and the cervical vestibular evoked myogenic potential (cVEMP) test. The objective was to investigate the sensitivity of the three vestibular tests to the presence of a vestibular schwannomas (VS), and possible correlations between test results, hearing acuity, and tumor size. STUDY DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: Fifty-nine patients with a unilateral VS. INTERVENTION: Audio-vestibular tests; the VHIT, cVEMP, caloric irrigation, pure-tone audiometry, and speech discrimination. MAIN OUTCOME MEASURE: Findings, sensitivity, and correlations between VHIT saccades and gain; cVEMP potentials, unilateral caloric weakness; hearing acuity. RESULTS: The sensitivity for VS was 80% for the VHIT, 93% for the caloric test, and 73% for the cVEMP test. VHIT gain and saccades were associated, and both had a positive correlation to caloric function. Medium-sized tumors demonstrated the highest gain asymmetry while larger tumors were associated with saccades. There was a weak correlation between vestibular findings and hearing acuity. CONCLUSION: The VHIT is sensitive to the occurrence of a VS, but less so than the caloric test, and vestibular function deteriorates to some extent with increasing tumor size. VHIT outcomes are positively correlated to caloric function, but only vaguely to cVEMP and hearing acuity. The combined vestibular function test battery reached a sensitivity of 97% to the occurrence of a VS and could thus potentially substitute MRI for tumor screening upon the diagnosis of an asymmetrical hearing loss.

Superior Canal Dehiscence Surgery Outcomes Following Failed Round Window Surgery.

OBJECTIVE: Round window (RW) occlusion or reinforcement is a less-invasive option compared with direct repair approaches to improve symptoms of superior canal dehiscence (SCD) syndrome. However, RW surgery is associated with variable outcomes. Middle fossa craniotomy or transmastoid repair is an option for SCD patients who fail RW surgery, but it is unknown whether sequential repair following RW plugging improves SCD symptoms or increases complications. The objective of this study is to evaluate outcomes of SCD repair via middle fossa craniotomy following failed RW surgery. STUDY DESIGN: Retrospective review. SETTING: Academic tertiary care center. PATIENTS: Adult patients with SCD syndrome who underwent failed RW surgery followed by sequential middle fossa craniotomy and plugging of the arcuate eminence defect. Patients with SCD associated with the superior petrosal sinus were excluded. INTERVENTION: None. MAIN OUTCOME MEASURE: Prospectively collected pre- and postoperative symptom questionnaires, threshold audiograms, and cervical vestibular evoked myogenic potentials (cVEMP). RESULTS: Seven SCD patients (out of a total of 194 surgical cases at our institution) underwent sequential middle-fossa SCD repair following failed RW surgery. Resolution of symptoms and reversal of diagnostic indicators were observed in the majority of subjects following sequential repair. Two of seven patients underwent a third procedure with plugging of the superior semicircular canal by a transmastoid approach due to the presence of residual symptoms. CONCLUSION: Middle fossa craniotomy and SCD occlusion is a safe and reasonable option for patients who fail RW surgery. Our cohort did not show increased risks of auditory or vestibular dysfunction.

Repositioning chairs in benign paroxysmal positional vertigo: implications and clinical outcome.

The objective was to evaluate the clinical value of repositioning chairs in management of refractory benign paroxysmal positional vertigo (BPPV) and to study how different BPPV subtypes respond to treatment. We performed a retrospective chart review of 150 consecutive cases with refractory vertigo referred to our clinic within a 10-month period. The BPPV patients were managed with classical manual manoeuvres, the Epley Omniax(®) rotator (EO) or the TRV chair (TRV). In addition, a comprehensive review of the literature was performed. BPPV was identified in 95 cases. The number of needed treatments for posterior canalolithiasis versus posterior cupulolithiasis, horizontal cupulolithiasis and multi-canal affection was significant (p < 0.01). Thirty-seven (38 %) patients required only one repositioning manoeuvre and the overall symptom relief was 91.7-100 % after 3 treatments. Eleven patients (12 %) experienced relapse within the ½-year follow-up period. Horizontal cupulolithiasis and multi-canal affection constituted the most resilient cases. The literature search identified 9 repositioning chair studies. The EO and the TRV are highly valuable assets in diagnosis and management of BPPV of particularly complex and refractory cases. However, further validation is anticipated through controlled clinical trials.

Antisecretory therapy with no improvement in functional level in Ménière's disease.

Conclusion Antisecretory factor-inducing (AF) specially processed cereals (SPC) were not shown to significantly improve the functional level in patients with MD. Objectives The aim of this study was to evaluate the effect of AF-inducing SPC in patients suffering from Ménière's disease (MD). Methods A randomized double-blinded, placebo-controlled cross-over study was conducted. All patients had a 2 months intake of SPC and control cereal with a 2 months washout period in between. The severity of MD was classified according to the American Academy of Otolaryngology-Head and Neck Surgery (AOO-HNS) functional scale, and the frequency of attacks was registered. Results Thirty-two patients completed the study. No carryover effect was found. In both functional level and frequency of attacks no significant effect of SPC was found. Seventeen patients showed improvement in functional level when treated with SPC (mean improvement = 0.9 points) and 14 when treated with placebo (mean improvements = 0.7 points). No patients showed worsening in functional level during treatment with SPC, but three showed worsening when treated with placebo. Seventeen patients reported fewer attacks when treated with SPC, and 22 when treated with placebo. Three patients reported more frequent attacks when treated with SPC, and three when treated with placebo. A non-parametric comparison and a parametric analysis supported the findings.

[Ménière's-like symptoms following meningioma]. / Menière-lignende symptomer efter meningeom.

A 36-year-old woman who presented with a right sided hearing loss, tinnitus and attacks of dizziness was initially diagnosed with Ménière's disease. A meningioma was found along the posterior surface of the petrosal bone, centred partly on the external aperture of the vestibular aqueduct with no relation to the meatal canal. Removal of the meningial tumour improved the hearing but Ménière's-like symptoms recurred after 18 months despite surgery. Ménière's-like symptoms could hypothetically be caused by changes of the endolymphatic duct or the vein of the vestibular aqueduct.

Increasing annual incidence of vestibular schwannoma and age at diagnosis.

During the last 26 years the annual number of diagnosed vestibular schwannomas (VS) has been increasing. The aim of this study is to describe and analyse this increase. Since 1976, 1446 new cases of VS have been diagnosed at the authors' centre. Special focus was on the age at diagnosis, the localization and the size of the tumour. The size of the tumour was registered as either intrameatal or with the largest extrameatal diameter. The annual number of diagnosed VS has increased from 26 in 1976 to 101 in 2001. The size of the diagnosed tumours has decreased from a median of 35 mm in 1979 to 10 mm in 2001. In the first years large and giant tumours dominated, in contrast to recent years in which intrameatal and small tumours dominated. The median age at the time of diagnosis has been almost unchanged through the period (median 55 years). If the decreasing size of the tumour and the increasing incidence of VS can be explained only by earlier diagnosis and easier access to magnetic resonance (MR) scanning it should be expected that the median age at the time of diagnosis would decrease simultaneously. In this study, the median age at the time of diagnosis has been almost unchanged throughout the 26-year period. This paradox can be explained by the fact that, with easier access to MR scanning, the examination has been offered also to elderly patients, in whom the small and intrameatal tumours dominate.