The correlation between neonatal parameters and late-onset inner ear disorders in congenital cytomegalovirus infection: a 10-year population-based cohort study.

OBJECTIVE: To evaluate the correlation of neonatal parameters with late-onset sensorineural hearing loss (SNHL) and vestibular dysfunction in individuals with congenital cytomegalovirus (cCMV) infection using the National Health Insurance Research Database (NHIRD) in Taiwan. DESIGN: Retrospective cohort study. SETTING: The whole Taiwanese population. PARTICIPANTS: Patients with related diagnostic codes and examinations in their records were regarded as having cCMV infection. Each subject in that group was matched to 10 control individuals with noncongenital CMV infection on the basis of several neonatal parameters, including low gestational age, low birth weight, low Apgar score, maternal history of CMV infection and prolonged cCMV infection. A total of 5893 and 58 930 participants were enrolled in the study and control groups, respectively. MAIN OUTCOME MEASURES: The main outcomes were the development of SNHL and the development of vestibular dysfunction within one year after birth as reflected by diagnostic codes and specific examinations. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (HR) and 95% confidence interval (CI) of each primary outcome between the two groups. RESULTS: Overall, 109 and 397 episodes of SNHL developed in the study group and the control group, respectively, and the study group demonstrated a significantly higher incidence of SNHL (adjusted HR: 2.56; 95% CI: 2.07-3.18). In addition, similar incidence rates of vestibular dysfunction were found in the study group and the control group, with 7 and 90 events, respectively (adjusted HR: 0.77; 95% CI: 0.36-1.67). In subgroup analyses, a higher incidence of SNHL was correlated with lower gestational age (GA) (adjusted HR: 2.09; 95% CI: 1.29-3.39), lower birth weight (BW) (adjusted HR: 2.05; 95% CI: 1.28-3.30) and prolonged cCMV infection (adjusted HR: 3.92; 95% CI: 1.95-7.88). CONCLUSIONS: Low GA, low BW and a long disease course are significantly correlated with late-onset SNHL in cCMV infection.

Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis.

Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by the blood-labyrinthine barrier, remains poorly understood. We recently showed that, as audiosensory receptor cells, cochlear hair cells (HCs) are protected by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker's organ) cells (GERCs) against viral infections. Here, we found that virus-infected SCs and GERCs induce HC death via production of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, the HCs expressed the TRAIL death receptors (DR) DR4 and DR5, and virus-induced HC death was suppressed by TRAIL-neutralizing antibodies. TRAIL-induced HC death was not caused by apoptosis, and was inhibited by necroptosis inhibitors. Moreover, corticosteroids, the only effective drug for SHL, inhibited the virus-induced transformation of SCs and GERCs into macrophage-like cells and HC death, while macrophage depletion also inhibited virus-induced HC death. These results reveal a novel mechanism underlying virus-induced HC death in the cochlear sensory epithelium and suggest a possible target for preventing virus-induced SHL.

Bilateral Sudden Sensorineural Hearing Loss and Intralabyrinthine Hemorrhage in a Patient With COVID-19.

OBJECTIVE: To describe a case of bilateral sudden sensorineural hearing loss (SSNHL) and intralabyrinthine hemorrhage in a patient with COVID-19. STUDY DESIGN: Clinical capsule report. SETTING: Tertiary academic referral center. PATIENT: An adult woman with bilateral SSNHL, aural fullness, and vertigo with documented SARS-CoV-2 infection (IgG serology testing). INTERVENTIONS: High-dose oral prednisone with taper, intratympanic dexamethasone. MAIN OUTCOME MEASURES: Audiometric testing, MRI of the internal auditory canal with and without contrast. RESULTS: A patient presented with bilateral SSNHL, bilateral aural fullness, and vertigo. Serology testing performed several weeks after onset of symptoms was positive for IgG COVID-19 antibodies. MRI showed bilateral intralabyrinthine hemorrhage (left worse than right) and no tumor. The patient was treated with two courses of high-dose oral prednisone with taper and a left intratympanic dexamethasone injection, resulting in near-resolution of vestibular symptoms, a fluctuating sensorineural hearing loss in the right ear, and a severe to profound mixed hearing loss in the left ear. CONCLUSIONS: COVID-19 may have otologic manifestations including sudden SSNHL, aural fullness, vertigo, and intralabyrinthine hemorrhage.

Progressive multifocal leukoencephalopathy presenting with acute sensorineural hearing loss in an intestinal transplant recipient.

A 20-year-old male presented 3.5 years after intestinal transplantation with rapidly progressive sensorineural hearing loss. Initial brain imaging was consistent with inflammation and/or demyelination. Lumbar puncture was initially non-diagnostic and a broad infectious workup was unrevealing. Three months after presentation, a repeat LP detected JC virus for which tests had not earlier been conducted. He continued to deteriorate despite withdrawal of prior immunosuppression and addition of mirtazapine, maraviroc, and steroids. He died of progressive neurologic decompensation 5 months after his initial presentation. This case highlights progressive multifocal leukoencephalopathy (PML) as a rare complication after solid organ transplantation and acute sensorineural hearing loss as an unusual first presenting symptom of PML. JC virus should be considered in the differential diagnosis of acute sensorineural hearing loss in any immunocompromised patient.

[Therapy Options for Infants with Congenital Cytomegalovirus Infection - Implications for Setting Up Neonatal Screening Programs]. / Therapeutische Optionen bei konnataler Zytomegalievirus (CMV)-Infektion ­ Implikationen für die Einführung eines Screeningprogramms.

INTRODUCTION: The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and congenital hip dysplasia) in 2018. Treatment, however, of disorders diagnosed by screening may harm children, as failed neuroblastoma screening has shown. There are several pilot studies to detect congenital cytomegalovirus (CMV) infection but no consensus as to the treatment of the infants identified. METHODOLOGY: Systematic search for studies investigating therapy of congenital CMV infection, using PubMed and the WHO International Clinical Trials Registry Platform (ICTRP). RESULTS: We found only one controlled trial that randomized infants with symptomatic congenital CMV infection (involving the central nervous system) to treatment (intravenous ganciclovir for 6 weeks) or no treatment. Treatment was associated with significantly less hearing deterioration. A second trial comparing 6 weeks vs. 6 months of treatment with valganciclovir, an oral prodrug of ganciclovir, found no benefit for hearing but modestly improved developmental outcomes associated with 6 months of treatment. In contrast, an open-label registry reported benefits for infants with congenital CMV infection and isolated hearing who received valganciclovir for 12 months, with hearing improvement in 2/3 of cases after a median follow-up of 4½ years. CONCLUSIONS: Antiviral treatment of neonates with congenital CMV infection and few symptoms including isolated hearing loss remains controversial. A generally accepted therapy, however, is pivotal before introducing universal or targeted screening for congenital CMV infection.

Zika Virus Infection during Pregnancy and Sensorineural Hearing Loss among Children at 3 and 24 Months Post-Partum.

OBJECTIVE: The objectives of this study were to describe the findings of the auditory screening in children of mothers with ZIKV during pregnancy or suspicious of congenital ZIKV, and to determine whether hearing loss was in the first 2 years in life, regardless of whether microcephaly was also present. METHODS: This is a cases report. The information was collected and recorded in a database between January 2016 and April 2018. We perform two auditory tests to 3 and 24 months of life. The study was developed in Aguachica (Cesar, Colombia). It is considered a high-risk area for ZIKV infection. Participants included children of mothers with confirmed ZIKV during pregnancy or suspicious of congenital ZIKV exposure of ZIKV infection during an epidemic period in a tropical area. We defined a positive case according to the epidemiological definition and clinical criteria based on maternal symptoms. However, other children of mothers without clinical signs of Zika were evaluated at the same time. The main outcome was the presence of sensorineural hearing loss. RESULTS: The median age in the study group (n = 43) was 3.5 months (rank: 0-6) and the comparison group (n: 23, children of mothers without clinical signs of ZIKV) was 3 months (rank: 0-12). Screening hearing test was done using distortion product otoacustic emissions. At 3 months follow-up, children were evaluated using distortion product otoacustic emissions and automatized auditory brainstem response. None of the patients evaluated in this study were found to have sensorineural hearing loss. CONCLUSIONS: We did not find hearing loss during the first 2 years in the children whose mother showed Zika during pregnancy. We recommend these children must be assessed to closed because there is a high risk the hearing loss as it usually may occur with CMV.

Sudden bilateral sensorineural hearing loss in a patient immunocompromised by the human immunodeficiency virus.

It is known that in less than a third of patients presenting sudden hearing loss, the disorder can be attributed to viral infection, trauma, neoplasms, and vascular and autoimmune diseases. However, the role of the HIV in the onset of this disease has not yet been well described. A 46-year-old female, in an immunosuppression state induced by HIV infection, presented with sudden bilateral hearing loss, with no improvement despite treatment. Several mechanisms were reported by which the virus could induce damage to the auditory pathway. However, little is known regarding the prevention and treatment of this morbidity.

Sudden bilateral sensorineural hearing loss in a patient immunocompromised by the human immunodeficiency virus

Abstract It is known that in less than a third of patients presenting sudden hearing loss, the disorder can be attributed to viral infection, trauma, neoplasms, and vascular and autoimmune diseases. However, the role of the HIV in the onset of this disease has not yet been well described. A 46-year-old female, in an immunosuppression state induced by HIV infection, presented with sudden bilateral hearing loss, with no improvement despite treatment. Several mechanisms were reported by which the virus could induce damage to the auditory pathway. However, little is known regarding the prevention and treatment of this morbidity.

Anti-mumps IgM antibody positive rate with sudden sensorineural hearing loss using second-generation enzyme immunoassay: A retrospective, multi-institutional investigation in Hokkaido, Japan.

OBJECTIVE: Although elevated anti-mumps IgM antibody levels were reported in 5.7%-7.2% of Japanese patients with sudden sensorineural hearing loss (SSNHL), there were several reports of false-positive cases, such as the continually IgM positive case and the IgM positive case in normal adults. To improve specificity, the new enzyme immuno assay (EIA) anti-mumps IgM antibody measurement kit was introduced in December 2009. This study re-examined the frequency of anti-mumps IgM antibody test positivity with SSNHL using the new measurement kit and compared the results with those from a previous report that used old kit. METHODS: This is a retrospective multi-institutional study involving patients diagnosed with SSNHL who exhibited the anti-mumps IgM antibody. We compared the positive rate of anti-mumps IgM antibody and the annual average number of mumps cases per sentinel in Hokkaido between the patients in the present study and patients previously evaluated. RESULTS: Overall, 100 patients with SSNHL were enrolled. One case (1.0%) was positive for anti-mumps IgM antibody. Of the 69 patients evaluated in the previous study, 5 cases (7.2%) were positive for anti-mumps IgM antibody. The positive rate of the anti-mumps IgM antibody in the present cases was significantly lower than that previously reported (p=0.042). The annual average number of mumps cases per sentinel in Hokkaido of the present and previous surveillance period was 34.47 and 42.77, respectively; no significant difference was seen in these data (p=0.4519). CONCLUSION: The present study revealed that 1.0% of SSNHL was positive for the anti-mumps IgM antibody using the new EIA-IgM measurement kit. After the introduction of the new EIA-IgM measurement kit, anti-mumps IgM antibody positive rate with SSNHL significantly decreased, indicating that the proportion of asymptomatic mumps among etiology of SSNHL may be lower than those previously reported.

Evaluation and management of cytomegalovirus-associated congenital hearing loss.

PURPOSE OF REVIEW: The current article reviews the current literature related to congenital cytomegalovirus (CMV)-related hearing loss. The discussion will focus on the epidemiology, pathogenesis, and clinical presentation of human CMV infection as it pertains to hearing loss. Current methods of CMV diagnosis with a focus on the evolving trend toward broader neonatal screening protocols will also be explored. Discussion of medical, surgical, and audiologic management of the condition will also be addressed. RECENT FINDINGS: Much of the current research on this topic is focused on improving detection of CMV through screening programs. Some advances in understanding cochlear pathogenesis have also been made. SUMMARY: Congenital CMV infection remains an important cause of hearing loss in infants and children. Early detection of CMV infection can broaden treatment options and allow for improved hearing and language outcome for patients with CMV-associated sensorineural hearing loss.

Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis presenting with acute sensorineural hearing loss: a case report and review of the literature.

Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening catastrophic and rarely seen complication of EBV infection especially in adults. While typical presentation of EBV infection is easily diagnosed as mononucleosis syndrome in teenagers and adults, some atypical clinical presentations may be challenged. We did not encounter any patient presenting with sudden sensorineural hearing loss associated with EBV infection in our English medical literature research (1966-2016). In this study, we report an adult patient who was complicated with EBV-HLH under high dose steroid therapy after diagnosis as sensorineural hearing loss. Our aim is to emphasise the atypical presentation of EBV infection and to discuss steroid therapy complication in sensorineural hearing loss that had been simply defined as idiopathic.

Does severity of cerebral MRI lesions in congenital CMV infection correlates with the outcome of cochlear implantation?

The objective is to investigate whether there is a correlation between the severity of typical brain lesions in congenital cytomegalovirus (cCMV) infection and cochlear implant (CI) outcome. The design of the study is a retrospective single-institutional chart review (2005-2015), performed in a tertiary academic referral center. 23 children with typical signs of cCMV infection on cerebral magnetic resonance imaging (MRI) and bilateral severe-to-profound sensorineural hearing loss were retrospectively evaluated. They were graded in three groups according to the severity of brain involvement. The average implantation age of the first CI is 1.8 years (range 0.6-5.8). Five patients were implanted unilaterally, 18 bilaterally. The average follow-up time after implantation was 3.3 years (range 0.6-6.9). Hearing performance was assessed using the Categories of Auditory Performance (CAP), and speech development was assessed using Speech Intelligibility Rating (SIR). The outcome in each group showed great variation. The majority of children achieved moderate-to-good auditory and speech rehabilitation. The children with severe MRI changes had comparatively better auditory than speech scores. There were children with good auditory performance (CAP ≥6) both in grades II and III, while poor performers (CAP ≤3) were encountered in each group. The severity of brain lesions on its own does not directly correlate with the outcome of cochlear implantation. Despite good retrospective diagnostic evidence of cCMV infection through MRI patterns, this has no predictive role for future hearing and speech rehabilitation.

Human cytomegalovirus downregulates SLITRK6 expression through IE2.

Congenital human cytomegalovirus (HCMV) infection causes sensorineural hearing loss (SNHL) and other neurological disorders, although the neuropathogenesis of HCMV infection is not well understood. Here, we show that the expression of SLITRK6, one of causative genes for hereditary SNHL, was robustly downregulated by HCMV infection in cultured neural cells. We also show that HCMV-encoded immediate-early 2 (IE2) proteins mediate this downregulation and their carboxy-terminal region, especially amino acid residue Gln548, has a critical role. These findings suggest that the downregulation of SLITRK6 expression by IE2 may have a role in HCMV-induced SNHL and other neurological disorders.

Sensorineural hearing loss after otitis media with effusion and subacute mastoiditis after viral infections of the upper respiratory tract: A comparative study of conservative and surgical treatment.

Involvement of the middle ear after viral infections of the upper airways may lead to serous otitis media with effusion in the absence of bacterial infection. This can be accompanied by a concomitant shading of the mastoid air cells, which could manifest as a reduced opacity on computed tomography (CT) in the absence of a history of chronic mastoiditis or acute inflammatory signs. This can lead to a subsequent impairment of inner ear function. CT scans reveal an extended pneumatization of the temporal bones in affected patients. Inner ear hearing impairment can probably be attributed to a concomitant labyrinthine reaction-the so-called toxic inner ear lesion. If no remission occurs within 5 days after initial conservative treatment (paracentesis or hemorrheologic infusions), surgical treatment with a mastoidectomy can accelerate hearing restoration. We conducted a retrospective, nonrandomized study of short- and long-term hearing outcomes in patients with a toxic inner ear lesion who had been treated with conservative measures alone (CONS group) or with surgery (SURG group) in a tertiary care referral center. Our study group was made up of 52 consecutively presenting patients (57 ears) who had been seen over a 10-year period; there were 20 patients (21 ears) in the CONS group and 32 patients (36 ears) in the SURG group. Initially, 15 CONS patients (75%) and 18 SURG patients (56%) complained of dizziness or a balance disorder. The initial averaged sensorineural hearing loss (over 0.5, 1.0, 2.0, and 3.0 kHz) was 32.4 ± 15.6 dB in the CONS group and 35.4 ± 12.0 dB in the SURG group. At follow-up (mean: 31.7 mo), the SURG group experienced a significantly greater improvement in hearing (p = 0.025). We conclude that patients with viral otitis media and concomitant noninflammatory mastoiditis with impairment of inner ear function (sensorineural hearing loss) experience a better hearing outcome when a mastoidectomy is performed during primary treatment.

Cochlear Spiral Ganglion Neuron Apoptosis in Neonatal Mice with Murine Cytomegalovirus-Induced Sensorineural Hearing Loss.

BACKGROUND: Sensorineural hearing loss (SNHL) is the most common consequence of congenital cytomegalovirus (CMV) infection, and could result in neurological abnormalities and intellectual and developmental disabilities. PURPOSE: To explore the mechanism of murine CMV (MCMV)-induced SNHL in neonatal mice model. RESEARCH DESIGN: A repeated measures design was used. STUDY SAMPLE: Total 72 neonatal BALB/C mice (36 males and 36 females) were randomly divided into two groups. DATA COLLECTION AND ANALYSIS: MCMV suspension (50% tissue culture infective dose = 10(4.15) IU/0.1 ml, 15 µl) or physiological saline was intracranially injected into neonatal mice in the experimental or control group, respectively. Auditory brainstem response (ABR) was measured at three weeks postinjection. At 1, 3, 5, 7, 14, and 21 days postinjection, MCMV-DNA polymerase chain reaction analysis was performed to detect MCMV infection in cochlea, followed by terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling analysis and immunohistochemistry staining. RESULTS: Extended latency, decreased amplitude, and increased threshold of ABR wave I were observed in the experimental group. Polymerase chain reaction test was positive from 3 to 21 days postinjection in the experimental group and negative at each time point in the control group. The average apoptosis index was higher in the experimental group than that in the control group from 3 to 21 days postinjection (p < 0.01). In addition, compared with the control group, B-cell lymphoma 2 and B-cell lymphoma 2-associated protein ratio was decreased in the experimental group (p < 0.01). CONCLUSION: Spiral ganglion neuron apoptosis was an important component of the mechanism of SNHL in MCMV-infected mice.

Congenital cytomegalovirus infection: contribution and best timing of prenatal MR imaging.

OBJECTIVE: To predict sensorineural hearing loss (SNHL) and neurological impairment in congenital cytomegalovirus (cCMV) infection using MR imaging and define the best timing in pregnancy for prenatal assessment. METHODS: In 121 patients with confirmed cCMV infection, brain features at MR imaging were respectively graded from 1 to 5: normal; isolated frontal/parieto-occipital hyperintensity; temporal periventricular hyperintensity; temporal/occipital cysts and/or intraventricular septa; migration disorders. Grading was correlated with postnatal SNHL and neurological impairment using regression analysis. In 51 fetuses with MR examinations at 26.9 and 33.0 weeks, the predictive value of SNHL and neurological impairment was compared using ROC curves. RESULTS: Postnatal follow-up showed SNHL in 18 infants and neurological impairment in 10. MR grading was predictive of SNHL and of neurological impairment (P < 0.001). In grade 1 or 2, none had SNHL and 1/74 had neurological impairment. The areas under ROC curves for prediction of postnatal SNHL and of neurological impairment from first and second MR examination were comparable. CONCLUSION: Our data suggest that in cCMV infection, prediction of SNHL and neurological impairment is feasible by fetal MR imaging with a high negative predictive value and can equally be done at 27 or 33 weeks of gestation. KEY POINTS: • In cCMV, isolated periventricular T2-weighted signal hyperintensity has a good postnatal prognosis. • In cCMV, SNHL and neurological impairment can be predicted at 27 or 33 weeks. • In cCMV, fetal MR has a high NPV in predicting SNHL. • In cCMV, fetal MR has a high NPV in predicting neurological impairment.

[The very severe sensorineural deafness patients caused by rubella virus infection: two cases report].

To explore the audiological features in children who were sever sensorineural hearing loss infected with rubella virus. There were two cases of rubella virus infection in children who were deaf, they conducted the distortion product otoacoustic emission, ABR and auditory steady-state evoked response (ASSR) examination, then analyzed the results comprehensively. Two patients' mothers were prompted to have infected rubella virus during the early three months pregnant period by history and laboratory tests. The two patients were not detected deafness gene mutation. Audiology results implied the two patients were very severe binaural sensorineural deafness, so they were recommended to equipped with hearing aids and cochlear implant surgery. Early pregnancy women infected with rubella virus can cause very severe offspring sensorineural deafness. The crowd whose mother were suspected to infect with rubella virus in early pregnancy, that should be tracked and detected hearing in order to achieve early detection, early intervention and early treatment.

Congenital cytomegalovirus: what the otolaryngologist should know.

PURPOSE OF REVIEW: Cytomegalovirus (CMV) is an important cause of congenital sensorineural hearing loss (SNHL) that may represent up to 20% of nonsyndromic cases. Congenital CMV is an unrecognized cause of SNHL that all otolaryngologists should be aware of as it represents the only treatable cause of congenital SNHL. RECENT FINDINGS: The current review highlights the recent advances on congenital CMV, including methods of diagnosis and prevention of progression of hearing loss with valganciclovir treatment. A recent study has shown that 6 months of oral valganciclovir treatment of infants with congenital CMV disease improves audiologic and neurodevelopmental outcomes to at least 2 years of age. Early treatment could, thus, have an important impact on these children. SUMMARY: Increased awareness of congenital CMV SNHL by an otolaryngologist should lead to increased testing, and thus diagnosis, of this condition in newborns diagnosed with congenital SNHL. Prompt treatment with valganciclovir in these patients may consequently lead to prevention of progressive SNHL. Further research toward a CMV vaccine is hoped to eventually lead to prevention of congenital CMV.

Idiopathic sudden sensorineural hearing loss: vascular or viral?

OBJECTIVE: To demonstrate that sudden sensorineural hearing loss is possibly of viral origin rather than vascular. STUDY DESIGN: The histopathologic morphology in 7 temporal bones with known vascular impairment due to surgical interventions was compared with that of 11 bones with a history of idiopathic sudden sensorineural hearing loss (ISSNHL). Attention was paid to the spiral ligament, stria vascularis, organ of Corti hair cells, tectorial membrane, ganglion cell population, and degree of perilymph fibrosis and the auditory nerve. SETTING: A temporal bone laboratory that has been in operation for more than 50 years and includes a database consisting of clinical and histopathological information that facilitates quantitative and qualitative analysis. SUBJECTS: Eight hundred forty-nine individuals who pledged their temporal bones for scientific study, of which 18 were selected for this study by means of the database criteria of sudden sensorineural hearing loss and postmiddle fossa and retro sigmoid sinus tumor removal or vestibular nerve section. RESULTS: Sudden sensorineural hearing loss bones exhibited no perilymph fibrosis compared with 6 of 7 vascular cases with fibrosis (P ≤ .001), exhibited less loss of ganglion cells (P ≤ .026), exhibited greater survival of spiral ligament (P ≤ .029), and averaged twice the survival of hair cells and more widespread tectorial membrane abnormalities. CONCLUSION: Analysis of human temporal bones from patients with a sudden sensorineural hearing loss does not support a vascular insufficiency but is more suggestive of a viral etiology.