Visualization and clinical relevance of the endolymphatic duct and sac in Ménière's disease.

Background: Ménière's disease (MD) is a chronic inner ear disorder with a multifactorial etiology. Decreased visualization of the endolymphatic duct (ED) and sac (ES) is thought to be associated with MD, although controversy exists about whether this finding is specific to MD. Recent literature has revealed that two distinct ES pathologies, developmental hypoplasia and epithelial degeneration, can be distinguished in MD using the angular trajectory of the vestibular aqueduct (ATVA) or ED-ES system as a radiographic surrogate marker. It has been suggested that these two subtypes are associated with distinct phenotypical features. However, the clinical differences between the ATVA subtypes require further validation. Research objective: The objective of this study is to investigate whether (1) non-visualization of the ED-ES system is a discriminative radiological feature for MD in a cohort of vertigo-associated pathologies (VAPs) and whether (2) different angular trajectories of the ED-ES system in MD are associated with distinguishable clinical features. Setting: The study was conducted in the Vertigo Referral Center (Haga Teaching Hospital, The Hague, the Netherlands). Methods: We retrospectively assessed 301 patients (187 definite MD and 114 other VAPs) that underwent 4h-delayed 3D FLAIR MRI. We evaluated (1) the visibility of the ED-ES system between MD and other VAP patients and (2) measured the angular trajectory of the ED-ES system. MD patients were stratified based on the angular measurements into αexit ≤ 120° (MD-120), αexit 120°-140° (MD-intermediate), or αexit ≥ 140° (MD-140). Correlations between ATVA subgroups and clinical parameters were evaluated. Results: Non-visualization of the ED-ES system was more common in definite MD patients compared with other VAPs (P < 0.001). Among definite MD patients, the MD-140 subtype demonstrated a longer history of vertigo (P = 0.006), a higher prevalence of bilateral clinical disease (P = 0.005), and a trend toward a male preponderance (p = 0.053). No significant differences were found between ATVA subgroups regarding the presence or severity of auditory symptoms, or the frequency of vertigo attacks. Conclusion: Non-visualization of the ED-ES system is significantly associated with MD. Among MD patients with a visible ED-ES system, we demonstrated that the MD-140 subtype is associated with a longer disease duration, a higher prevalence of bilateral MD, and a trend toward a male preponderance.

Hydropic Ear Disease: Correlation Between Audiovestibular Symptoms, Endolymphatic Hydrops and Blood-Labyrinth Barrier Impairment.

Research Objective: To investigate the correlation between clinical features and MRI-confirmed endolymphatic hydrops (EH) and blood-labyrinth barrier (BLB) impairment. Study Design: Retrospective cross-sectional study. Setting: Vertigo referral center (Haga Teaching Hospital, The Hague, the Netherlands). Methods: We retrospectively analyzed all patients that underwent 4 h-delayed Gd-enhanced 3D FLAIR MRI at our institution from February 2017 to March 2019. Perilymphatic enhancement and the degree of cochlear and vestibular hydrops were assessed. The signal intensity ratio (SIR) was calculated by region of interest analysis. Correlations between MRI findings and clinical features were evaluated. Results: Two hundred and fifteen patients with MRI-proven endolymphatic hydrops (EH) were included (179 unilateral, 36 bilateral) with a mean age of 55.9 yrs and median disease duration of 4.3 yrs. Hydrops grade is significantly correlated with disease duration (P < 0.001), the severity of low- and high-frequency hearing loss (both P < 0.001), and the incidence of drop attacks (P = 0.001). Visually increased perilymphatic enhancement was present in 157 (87.7%) subjects with unilateral EH. SIR increases in correlation with hydrops grade (P < 0.001), but is not significantly correlated with the low or high Fletcher index (P = 0.344 and P = 0.178 respectively). No significant differences were found between the degree of EH or BLB impairment and vertigo, tinnitus or aural fullness. Conclusion: The degree of EH positively correlates with disease duration, hearing loss and the incidence of drop attacks. The BLB is impaired in association with EH grade, but without clear contribution to the severity of audiovestibular symptoms.

Mathematical Models for Tumor Growth and the Reduction of Overtreatment.

Background To improve our understanding of the natural course of head and neck paragangliomas (HNPGL) and ultimately differentiate between cases that benefit from early treatment and those that are best left untreated, we studied the growth dynamics of 77 HNPGL managed with primary observation. Methods Using digitally available magnetic resonance images, tumor volume was estimated at three time points. Subsequently, nonlinear least squares regression was used to fit seven mathematical models to the observed growth data. Goodness of fit was assessed with the coefficient of determination ( R 2 ) and root-mean-squared error. The models were compared with Kruskal-Wallis one-way analysis of variance and subsequent post-hoc tests. In addition, the credibility of predictions (age at onset of neoplastic growth and estimated volume at age 90) was evaluated. Results Equations generating sigmoidal-shaped growth curves (Gompertz, logistic, Spratt and Bertalanffy) provided a good fit (median R 2 : 0.996-1.00) and better described the observed data compared with the linear, exponential, and Mendelsohn equations ( p < 0.001). Although there was no statistically significant difference between the sigmoidal-shaped growth curves regarding the goodness of fit, a realistic age at onset and estimated volume at age 90 were most often predicted by the Bertalanffy model. Conclusions Growth of HNPGL is best described by decelerating tumor growth laws, with a preference for the Bertalanffy model. To the best of our knowledge, this is the first time that this often-neglected model has been successfully fitted to clinically obtained growth data.

Severe Nightly Thoracic Pain Presenting during Pregnancy: A Case Report.

We present the case of a woman who developed severe nightly thoracic pain during pregnancy without neurological deficits upon examination. Spontaneously after childbirth, the pain was markedly reduced. Further investigation showed that her pain was caused by an ependymoma in the cervicothoracic spinal cord. Gross total resection was accomplished, and the patient has been free of pain ever since. With this case, we want to draw attention to a rare, but possibly very disabling, cause of increasing nightly thoracic pain during pregnancy. Spontaneous improvement after childbirth could erroneously cause postponement of further investigation.

Clinical progression and metachronous paragangliomas in a large cohort of SDHD germline variant carriers.

Although it is well established that paternally transmitted germline variants in SDHD are associated with multifocal paragangliomas and lifelong follow-up is generally advised, the risk of metachronous lesions is presently unknown. In a large Dutch cohort of SDHD variant carriers, we studied the development of new paragangliomas, and the evolution of symptoms and cranial nerve impairment. Recurrent event analysis and the Kaplan-Meier product limit estimator were used to study the risk of new lesions. The relation between several predictors and development of new symptoms was assessed using logistic regression. Of the 222 SDHD variant carriers included, 65% presented with symptoms and 11% with cranial nerve dysfunction. Over a median period of 8 years, 42% reported new symptoms, and new cranial nerve impairment was observed in 11% of subjects. The estimated fraction of subjects that developed new HNPGL increased to 73% (95% CI: 52-85%) after 22 years of follow-up. Males were more likely to develop new HNPGL compared to females (HR: 1.63, 95% CI: 1.10-2.40), as were subjects that presented with symptoms, compared to subjects that were asymptomatic at baseline (HR: 1.61, 95% CI: 1.01-2.55). In addition, the risk of new lesions decreased with number of HNPGL present at first diagnosis (HR: 0.68 and 95% CI: 0.56-0.82). Carriers of a paternally inherited SDHD variant face a considerable risk for new HNPGL. In addition, nearly 50% of subjects reported new symptoms. However, new cranial nerve deficits were observed in only 11%, which is less than reported in surgical series. These risks should be taken into account when considering treatment strategies and counseling.

Age and Tumor Volume Predict Growth of Carotid and Vagal Body Paragangliomas.

Objective Treatment for head and neck paragangliomas (HNGPL) can be more harmful than the disease. After diagnosis, an initial period of surveillance is often indicated, and surgery or radiotherapy is reserved for progressive disease. With the aim to optimize this "wait and scan" strategy, we studied growth and possible predictors. Design A retrospective cohort study was conducted. Setting This study was conducted at a tertiary referral center for patients with HNGPL. Methods Tumor volume was estimated for 184 SDHD -related carotid and vagal body paragangliomas using sequential magnetic resonance imaging. Cox regression was used to study predictors of tumor growth. Results The estimated fraction of growing tumors ranged from 0.42 after 1 year of follow-up to 0.85 after 11 years. A median growth rate of 10.4 and 12.0% per year was observed for carotid and vagal body tumors, respectively. Tumor location, initial volume, and age ( p < 0.05) were included in our prediction model. The probability of growth decreased with increasing age and volume, indicating a decelerating growth pattern. Conclusions We created a prediction model (available online), enabling a more individualized "wait and scan" strategy. The favorable natural course of carotid and vagal body paragangliomas was confirmed; although with long follow-up growth will be observed in most cases.