Prenatal diagnostic errors in hemoglobin Bart's hydrops fetalis caused by rare genetic interactions of α-thalassemia.

OBJECTIVES: To describe rare genetic interactions of α-thalassemia alleles causing Hb H disease and Hb Bart's hydrops fetalis which could lead to diagnostic errors in a routine practice. METHODS: Hematological and molecular characterization were carried out in a Thai family with a risk of having fetus with Hb Bart's hydrops fetalis. RESULTS: Both parents were found to be the thalassemia intermedia patients associated with unusual forms of Hb H disease. DNA analysis of common α-thalassemia mutations in Thailand identified α+-thalassemia (-α3.7 kb del) and unknown α0-thalassemia in the father and α0-thalassemia (--SEA) with unknown α+-thalassemia in the mother. Fetal DNA analysis unlikely identified a homozygosity for α0-thalassemia (--SEA/--SEA). Further analysis identified that the father carried a rare South African α0-thalassemia in combination with α+-thalassemia (--SA/-α), whereas the mother was a patient with Hb H-Queens Park disease (--SEA/ααQP). The fetus was, in fact, a compound heterozygote for (--SA/--SEA). CONCLUSIONS: As shown in this study, routine screening for α-thalassemia at prenatal diagnosis in the region should include both common and rare α0-thalassemia alleles found in the population to effectively prevent a fatal condition of Hb Bart's hydrops fetalis syndrome.

A Pediatric Case of Cogan's Syndrome With Internal Otitis.

Cogan's syndrome is characterized by ocular symptoms and auditory vestibular dysfunction. Auditory vestibular dysfunction in Cogan's syndrome is believed to be similar to Ménière's disease, but the cause is not known in detail. We present the case of a 10-year-old boy with Cogan's syndrome. The patient had panuveitis, bilateral hearing loss, and bilateral vestibular dysfunction. MRI revealed no evidence of endolymphatic hydrops, which is a cause of Ménière's disease, and enhanced contrast effects on the bilateral cochlear and vestibular apparatus. The caloric test, the video-head impulse test, and the vestibular evoked muscle potential test also showed severe vestibular dysfunction. Based on the above, the auditory vestibular dysfunction in this patient was considered to be caused by internal otitis. The patient's vision recovered after treatment with steroids and immunosuppressive drugs, but his hearing did not recover. He underwent bilateral cochlear implantation and had a good postoperative course but we encountered difficulty in deciding when to perform cochlear implantation. This case demonstrates the importance of determining the timing of surgery in consideration of the ossification and fibrosis of the inner ear and the drug administration status.

New ZNHIT3 Variants Disrupting snoRNP Assembly Cause Prenatal PEHO Syndrome with Isolated Hydrops.

ZNHIT3 (zinc finger HIT type containing protein 3) is an evolutionarily conserved protein required for ribosome biogenesis by mediating the assembly of small nucleolar RNAs (snoRNAs) of class C/D into ribonucleoprotein complexes (snoRNPs). Missense mutations in the gene encoding ZNHIT3 protein have been previously reported to cause PEHO syndrome, a severe neurodevelopmental disorder typically presenting after birth. We discuss here the case of two fetuses from a single family who presented with isolated hydrops during the early second trimester of pregnancy, resulting in intrauterine demise. Autopsy revealed no associated malformation. Through whole-genome quartet analysis, we identified two novel variants within the ZNHIT3 gene, both inherited from healthy parents and occurring as compound heterozygotes in both fetuses. The c.40T>C p.Cys14Arg variant originated from the father, while the c.251_254delAAGA variant was of maternal origin. Analysis of the variants in human cell culture models reveals that both variants reduce cell growth, albeit to different extents, and impact the protein's stability and function in distinct ways. The c.251_254delAAGA results in production of a stable form of ZNHIT3 that lacks a domain required for mediating snoRNP biogenesis, whereas the c.40T>C p.Cys14Arg variation behaves similarly to the previously described PEHO-associated ZNHIT3 variants that destabilize the protein. Interestingly, both variations lead to a marked decrease in specific box C/D snoRNA levels, reduced rRNA levels and cellular translation. Analysis of rRNA methylation pattern in fetus samples reveals distinct sites of hypo 2'-O-methylation. RNA-seq analysis of undifferentiated and differentiated SHSY5Y cells transfected with the ZNHIT3 variants reveals differential expression of a set of genes, many of which are associated with developmental processes and RNA binding compared to cells expressing wild-type ZNHIT3. In summary, this work extends the phenotype of PEHO syndrome to include antenatal manifestations and describe the molecular defects induced by two novel ZNHIT3 variants.

Association of contrast-enhanced MRI of inner ear and caloric response in patients with clinically diagnosed ipsilateral delayed endolymphatic hydrops.

BACKGROUND: Patients with delayed endolymphatic hydrops (DEH) often show caloric hypofunction and endolymphatic hydrops (ELH) on gadolinium (Gd) enhanced magnetic resonance imaging (MRI) of the inner ear. OBJECTIVES: We aimed to investigate the relationship between the ELH in vivo and caloric results in ipsilateral DEH. MATERIAL AND METHODS: Twelve patients with ipsilateral DEH were included, who underwent delayed MRI following intratympanic Gd application, pure-tone audiometry, caloric test, and video head impulse test (vHIT). RESULTS: For the affected ears, the overall prevalence of inner ear hydrops was 91.7%, including 75% in the cochlear and 50% in vestibular compartment. For the non-affected ears, the overall prevalence of inner ear hydrops was 25%, including 25% in cochlear and 16.7% in vestibular region. Caloric hypofunction was demonstrated in 75% of the affected ears. No pathologic vHIT were found. Caloric results were in agreement with the radiological evidence of inner ear hydrops on affected and non-affected ears in 9 cases. There was fair concordance between inner ear hydrops and canal paresis abnormality on the affected side. CONCLUSIONS AND SIGNIFICANCE: MRI provides auxiliary evidence of ELH in vivo in the ipsilateral DEH-affected ears. The association between morphological alterations and caloric hypofunction warrants further investigation.

The clinical manifestation and treatment of Meniere's Disease from the viewpoint of the water homeostasis of the inner ear.

Endolymphatic hydrops, a pathological feature of Ménière's disease, has been experimentally and clinically confirmed to be influenced by the blood circulation of vasopressin (VP). VP is a well-known hormonal regulator of water homeostasis. In addition, VP is influenced by various environmental changes, dehydration, fluctuation of atmospheric pressure, pregnancy, and other factors. Furthermore, VP is a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is a major neuroendocrine system that controls reactions to emotional and physical stresses, as well as the sleep/wake cycle (circadian rhythm). Therefore, VP is susceptible to change via the HPA axis. This review considers possible mechanisms of the formation of endolymphatic hydrops from the perspective of the vasopressin-aquaporin 2 system.

Severe generalized edema in a premature neonate: A case report and literature review.

Key Clinical Message: With no family history, and an atypical phenotype, the clinical diagnosing of Noonan syndrome (NS) can be very difficult. The present case emphasized that generalized edema in neonates may be the potential first symptom of NS. Abstract: Severe generalized edema is a rare pathological condition with high mortality in newborns, in particular the premature infants. It is characterized by the extensive subcutaneous tissue edema and the accumulation of fluid in neonatal body fluid compartments. The etiology and pathogenesis of hydrops in neonates are quite complex. Generally speaking, hydrops can be divided into immune hydrops and non-immune hydrops according to the etiology. It is still challenging in treating severe neonatal edema. In this study, we presented a preterm newborn with severe generalized edema after birth, which was finally diagnosed with Noonan syndrome (NS). The infant clinically manifested as severe generalized edema alone, without the involvement of multiple organ malformation. Generalized edema in neonates was probably the first symptom of NS. Therefore, differential diagnosis of NS is necessary for infants developing generalized edema.

The ANTI-LAMBDA: A Non-statical Tonal Indicator Low-Frequency Air-Bone Gap of Ménière's Bouts and Disease Activity.

INTRODUCTION:  There have been reports of patients with Ménière´s disease (MD) showing unexplained audiometric air-bone gaps at low frequencies. Little is known about the clinical significance of this finding. The objective of this study was to describe this phenomenon while relating it with clinical features, namely the incidence of attacks. METHODS: Unilateral MD patients were selected and cerebral magnetic resonance imaging (cMRI) was assessed to exclude structural pathology. A retrospective longitudinal analysis regarding disease activity and audiometric details was performed. A coincidence index and regression predictive models were considered to assess the relationship between the air-bone gap and MD activity. RESULTS:  A total of 70 MD patients were enrolled and 252 audiograms were assessed. Low-frequency air-bone gaps (LFABGs) were significantly associated with unstable MD (p < 0.001), demonstrating a sensitivity and specificity of 93.8% and 82.7%, respectively. The incidence of unstable disease with the presence of LFABG was 89.1 %. A higher LFABG magnitude correlated with increased disease activity (p < 0.001) and was particularly pronounced at 250 Hz and 500 Hz. CONCLUSION: The typical LFABG encountered was here called ANTI-LAMBDA (A Non-statical Tonal Indicator Low-Frequency Air-Bone Gap of Ménière's Bouts and Disease Activity). It relates to MD activity and is a potential new tool to assess MD stability/need for additional therapeutics.

Perinatal lethal form Gaucher disease with compound heterozygosity of single nucleotide variants and copy number variations presenting as nonimmune hydrops fetalis and cerebellar hypoplasia: A case report.

OBJECTIVE: To present the ultrasound imaging and genetic diagnosis of a fetus with prenatal lethal form of Gaucher disease. CASE REPORT: A 37-year-old primiparous woman was pregnant at her 23 weeks of gestation and the prenatal fetal ultrasound revealed hydrops fetalis, cerebellum hypoplasia, and fetal immobility. The pregnancy was terminated due to major fetal anomaly, and whole exome sequencing (WES) analysis of fetal tissue and parental blood unveiled a pathogenic variant in exon 10 of the GBA gene (NM_001005741.3: c.1265T > G: p.L422R) originating from the mother. Additionally, a novel CNV (chr1: 155204785-155205635 deletion, 0.85 kb) spanning exon 10-12 in the GBA gene was identified from the father. This compound heterozygosity confirmed the diagnosis of prenatal lethal form of Gaucher disease and was informative for genetic counseling. CONCLUSION: WES is a powerful tool to detect pathogenic variants among fetuses with nonimmune hydrops fetalis and complex abnormality from prenatal ultrasound. Compound heterozygosity consisted of single nucleotide variants (SNV) and copy number variations (CNVs) may lead rare inherited metabolic disorders including prenatal lethal form of Gaucher disease.

The characteristics of three-dimensional real inversion recovery MRI sequence in delayed Meniere's disease.

BACKGROUND: Delayed Meniere's disease (DMD) is characterized by episodic vertigo occurring after a significant delay following longstanding sensorineural hearing loss. However, its pathogenesis and characteristics remain unclear. OBJECTIVES: To explore the characteristics of endolymphatic hydrops (EH) in DMD and investigate its pathology using MRI. MATERIALS AND METHODS: 17 patients diagnosed with DMD were included in this study. A 3D-real-IR MRI sequence was utilized to visualize and grade EH. The signal intensity of the basal cochlear turn was compared to that of the cerebellar white matter to calculate the CC ratio. A paired t-test was employed to assess the differences in the CC ratio between the affected and unaffected sides in patients with unilateral DMD. RESULTS: EH was present in 100% of cases on the affected side. Unilateral EH was seen in 82.4%, and bilateral EH in 23.5%. Vestibular EH without cochlear involvement occurred in 29.4%, and cochlear EH without vestibular involvement in 5.9%. The CC ratio was significantly higher on the affected side (p < 0.01). CONCLUSIONS AND SIGNIFICANCE: A significant grade of vestibular EH was observed in DMD, with bilateral EH being relatively common. The increased contrast on the affected side may reflect the underlying pathology in DMD patients.

The relationship between endolymphatic hydrops features and hearing loss in Bilateral Meniere's disease.

BACKGROUND: This study aimed to investigate the relationship between the features of endolymphatic hydrops and hearing loss in patients with Bilateral Meniere's Disease. METHODS: A retrospective analysis was conducted on 77 patients diagnosed with Bilateral Meniere's Disease. The features of endolymphatic hydrops in the affected ear were evaluated through gadolinium-enhanced inner ear Magnetic resonance imaging. The Spearman correlation coefficient, paired t-tests, and Wilcoxon signed-rank tests were employed for data analysis. RESULTS: The analysis revealed a significant correlation between the degree of endolymphatic hydrops and hearing loss across all frequencies(0.125-8 kHz), including the cochlear, vestibular, and overall degree of endolymphatic hydrops. The strongest correlation between the overall degree of endolymphatic hydrops and hearing loss was observed at low frequencies (r = 0.571, p < 0.05), followed by mid-frequencies (r = 0.508, p < 0.05), and high-frequencies (r = 0.351, p < 0.05), with a correlation of r = 0.463, p < 0.05 for the staging of Meniere's disease. Affected Ears with endolymphatic hydrops both in the cochlea and vestibule exhibited more severe hearing loss and Meniere's disease staging compared to those with isolated endolymphatic hydrops within the same patient. CONCLUSIONS: The features of endolymphatic hydrops in patients with Bilateral Meniere's Disease were found to correlate with the severity of hearing loss and the staging of Meniere's disease.

Parvovirus B19 Infection in Pregnancy-Course of the Disease, Fetal Complications and Management Tools: A Case Series and Literature Review.

Parvovirus B19 is a virus that causes a common and usually harmless infection in both children and adults. If the virus is transmitted transplacentally during pregnancy, it can have serious consequences for both the pregnant woman and the fetus. Potential complications include severe fetal anemia, which can lead to intrauterine fetal death. A common ultrasound finding in fetuses affected by parvovirus B19 is fetal edema, which is associated with a poor prognosis. Additionally, a rare but serious complication in pregnant women with parvovirus B19 infection is mirror syndrome. The diagnosis of parvovirus B19 infection during pregnancy necessitates close monitoring of the fetal condition. If fetal anemia is suspected, intrauterine transfusion is indicated to increase fetal survival. This study presents eight cases of parvovirus B19 infection in pregnant women, highlighting the various maternal-fetal complications encountered, along with diagnostic and treatment strategies.

Clinical Management of Hydrops Fetalis in a Premature Neonate in India: A Case Report.

Hydrops fetalis has classically been defined as the presence of extracellular fluid in at least two fetal body compartments. This fluid collection includes skin edema (> 5 mm thickness), pericardial effusion, pleural effusion, and ascites. Here we present a case of a 29-year-old female with antenatally diagnosed severe hydrops fetalis which was postnatally successfully managed. Despite recent advances, immune hydrops are still a challenge for healthcare workers in third-world nations.

Predictive nomograms and an algorithm for managing patients with probable Meniere's disease.

PURPOSE: To explore the efficacy of diagnostic tests in accurately reclassifying patients initially diagnosed with probable Meniere's disease (MD) into either definite or non-MD categories. MATERIALS AND METHODS: A retrospective cohort study was conducted at a neurotology clinic between 1/2016 and 5/2022. Patients underwent a battery of tests, from which sensitivity, specificity, positive and negative predictive values, as well as positive and negative likelihood ratios, were calculated. Additionally, prediction nomograms were developed. RESULTS: Of the 69 patients, 25 (36.2 %) were initially classified as definite MD, 21 (30.4 %), probable MD, and 23 (33.4 %) non-MD. The mean follow-up was 3.5 years. The sensitivity of electrocochleography (ECochG) was the highest (92 %), with a negative likelihood ratio of 15 %. Magnetic resonance imaging (MRI) with MD-protocol had the highest specificity (100 %), with a positive likelihood ratio of 100 %. Videonystagmography, video head impulse test, and cervical vestibular-evoked myogenic potentials, had lower sensitivity and specificity. We were able to reclassify 18 (86 %) patients with probable MD: 12 (57 %) were diagnosed with definite MD, and 6 (29 %) were diagnosed with non-MD, consistent with their clinical course. CONCLUSIONS: The combination of ECochG and MRI with MD-protocol provides the most reliable approach to reclassify patients with Probable MD, ensuring a precise and accurate diagnosis. Vestibular tests express the functional status of the labyrinth and may not be reliable. Our findings provide valuable insights into clinical decision-making for patients with Probable MD and raise the consideration of additional diagnostic tests as supplementary to the existing clinical-only diagnosis criteria.

New non-contrast MRI of endolymphatic hydrops in Ménière's disease considering inversion time.

Objectives: Three-tesla MRI with gadolinium-based contrast agents is important in diagnosing Ménière's disease. However, contrast agents cannot be used in some patients. By using the compositional difference between the inner ear endolymph and perilymph, we performed basic and clinical research focused on potassium ions and protein to find the optimal parameters for visualizing endolymphatic hydrops on MRI without contrast. We then examined the relationship between severity stage and visualization rate of endolymphatic hydrops. Methods: In phantom experiments simulating the endolymph and perilymph, we explored MRI parameters that could be used to separate endolymph from perilymph by gradually changing the inversion time. We then used these parameters to perform both new non-contrast MRI and contrast MRI on the same day in Ménière's disease patients, and we compared the visualization rates of endolymphatic hydrops under the two modalities. Fifty patients were selected from 478 patients with Ménière's disease of different severity stages; 12 patients had asthma and allergy to contrast agents. Results: The higher the disease stage, the higher the endolymphatic hydrops visualization rate. The new non-contrast MRI gave significantly higher (p < .01) visualization rates of endolymphatic hydrops on the affected side in patients at Stage 3 or above than in Stages 1 and 2 combined. Conclusion: New non-contrast MRI with parameters focusing on the endolymph-perilymph difference in the density of protons surrounding the potassium ions and protein can produce images consistent with endolymphatic hydrops. We believe that this groundbreaking method will be useful for diagnosing Ménière's disease in patients. Evidence Level: Clinical studies are at evidence level 3 in non-randomized controlled trials.

Magnetic resonance imaging evaluation of cochlear and vestibular nerve calibre: a case-control study in Ménière's disease and endolymphatic hydrops.

PURPOSE: To compare the calibre of the cochlear (CN), superior vestibular (SVN) and inferior vestibular (IVN) nerves on magnetic resonance imaging (MRI), both between Ménière's Disease (MD) ears and clinical controls, and between inner ears with and without endolymphatic hydrops (EH) on MRI. METHODS: A retrospective case-control study evaluated patients undergoing MRI for suspected hydropic ear disease from 9/2017 to 8/2022. The CN, SVN, IVN and facial nerve (FN) diameters and cross-sectional areas (CSA) were measured on T2-weighted sequences whilst EH was evaluated on delayed post-gadolinium MRI. Absolute nerve calibre (and that relative to the FN) in unilateral definite MD ears (2015 Barany criteria) was compared to that in both asymptomatic contralateral ears and clinical control ears. Nerve calibre in ears with severe cochlear and vestibular EH was compared to ears without EH. t tests or Wilcoxon signed-rank test/Mann-Whitney U test were applied (p < 0.001). RESULTS: 173 patients (mean age 51.3 ± 15.1, 65 men) with 84 MD (62 unilateral) and 62 clinical control ears were studied. Absolute and relative CN dimensions were decreased in both MD ears (CSA and diameter) and the contralateral asymptomatic ears (CSA) when compared to clinical controls (p < 0.001). Absolute nerve dimensions were reduced in both severe vestibular EH (CN, IVN and SVN) and severe cochlear EH (CN) (p < 0.001), however this was not evident when adjusted according to facial nerve calibre. CONCLUSION: There is decreased absolute CN calibre in both symptomatic and asymptomatic MD ears as well as ears with severe cochlear and vestibular EH on MRI.

PRKAG2-Related Lethal Congenital Glycogen Storage Disease of the Heart as Rare Cause of Fetal Hydrops With Bradycardia and Cardiomyopathy: Clinical Report and Literature Review.

Nonimmune foetal hydrops is a prenatal condition associated with significant perinatal mortality. It has so far been associated with over 200 chromosomal and monogenic conditions, most frequently chromosomal aneuploidies and RASopathies. Thorough clinical phenotyping and genetic evaluation are essential to determine the underlying etiology of this clinical entity and guide obstetrical and postnatal management. In this report, we describe the prenatal presentation and postnatal outcome of a pregnancy with Lethal Congenital Glycogen Storage Disease of the Heart, a rare autosomal dominant non lysosomal cardiac glycogenosis caused by a novel de novo likely pathogenic variant in the Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2 (PRKAG2) gene, [NM_016203.3:c.1150A > G, p.(Arg384Gly)]. To this day, only six other molecularly confirmed prenatal presentations of this condition have been reported. This clinical report adds to the knowledge on the prenatal features, clinical evolution, molecular diagnosis and pathological findings of this disorder and underlines the clinical utility of comprehensive molecular testing in the investigation of nonimmune foetal hydrops and fetal cardiomyopathy.

Non-immune hydrops fetalis is associated with bi-allelic pathogenic variants in the MYB Binding Protein 1a (MYBBP1A) gene.

Non-immune hydrops fetalis (NIHF) is a rare entity characterized by excessive accumulation of fluid within the fetal extravascular compartments and body cavities. Here we present two intrauterine fetal demises with NIHF presenting with oligohydramnios, cystic hygroma, pleural effusion, and generalized hydrops with predominance of subcutaneous edema. The fetuses also presented with ascites, severe and precocious IUGR and skeletal anomalies. Whole exome sequencing was applied in order to screen for a possible genetic cause. The results identified biallelic variants in MYBBP1A in both fetuses. A previous report described another case with a similar phenotype having compound heterozygous variants in the same gene. The protein encoded by MYBBP1A is involved in several cellular processes including the synthesis of ribosomal DNA, the response to nucleolar stress, and tumor suppression. Our functional protein analysis through immunohistochemistry indicates that MYBBP1A is a gene expressed during fetal stages. Altogether, we concluded that MYBBP1A is associated with the development of hydrops fetalis. More cases and further studies are necessary to understand the role of this gene and the mechanism associated with NIHF.

Outcomes of deep anterior lamellar keratoplasty in eyes with healed hydrops - A retrospective interventional analysis.

AIM: The aim of the study was to analyze the techniques and outcomes of deep anterior lamellar keratoplasty (DALK) done in eyes with healed hydrops. METHODS: Thirty-one eyes with paracentral scars following acute hydrops underwent DALK and were included in the study. Manual layer-by-layer dissection with stromal air injection was done in all cases, keeping dissection of the site of preexisting perforation to the end. RESULTS: Out of the 31 eyes, in 28 eyes, DALK could be completed, and in 3 eyes, procedure had to be converted to penetrating keratoplasty. Visual outcomes in all cases were good, with 26 out of 28 eyes (92.8%) achieving a best-corrected visual acuity (BCVA) of 6/12 or better. Preoperative mean BCVA of LogMAR 1.19 ± 0.27 improved to a postoperative mean BCVA of LogMAR 0.23 ± 0.08 (P < 0.00001). Postoperative mean refractive astigmatism at the last follow-up was -2.69 ± 0.82 D with postoperative a spherical equivalent of -2.31 ± 0.7 D. Complications included double anterior chamber in one eye and secondary angle closure in two eyes. Stromal rejection in one eye was managed with steroids and one eye with suture infiltrate needed selective suture removal. CONCLUSION: Layer-by-layer dissection with limited air injection into the stroma has shown good visual outcomes in patients undergoing DALK following healed hydrops, and DALK can very well be the primary treatment option even in such cases with a paracentral posthydrops scar.

Efficacy of endolymphatic duct blockage in treating Ménière's disease. / å† æ·‹å·´ç®¡å¤¹é—­æœ¯æ²»ç–—æ¢ å°¼åŸƒç— çš„æ•ˆæžœ.

OBJECTIVES: Ménière's disease (MD) is an idiopathic inner ear disorder characterized by recurrent episodes of episodic rotational vertigo, fluctuating hearing loss, tinnitus, and a feeling of ear stuffiness. Endolymphatic sac (ES)-related surgery is used primarily in patients with MD who have failed to respond to pharmacologic therapy. Endolymphatic duct blockage (EDB) is a new procedure for the treatment of MD, and related clinical studies are still scarce. This study aims to investigate the dynamic changes in endolymphatic hydrops (EH) and the long-term surgical outcomes in MD patients undergoing EDB, and to evaluate the impact of different types of ES on the surgical efficacy. METHODS: A retrospective analysis was conducted on 33 patients with refractory MD who underwent EDB. Based on the morphology of their endolymphatic sacs, patients were divided into a normal-type group (n=14) and an atrophic-type group (n=19). The frequency of vertigo symptoms, hearing, vestibular function, and the dynamic changes of gadolinium-enhanced MRI of the inner ear were compared were compared before and after surgery between the 2 groups. RESULTS: Compared with the atrophic-type group, the patients in the normal-type group had a higher rate of complete vertigo control, better cochlear and vestibular function, and a lower endolymph to vestibule volume ratio (all P<0.05). In addition, 7 patients in the normal-type group were found to have reversal of EH, while no reversal of EH was detected in the atrophic-type group after surgery. CONCLUSIONS: The response to EDB treatment varies between normal and atrophic MD patients, suggesting that the 2 pathological types of endolymphatic sacs may have different underlying mechanisms of disease.