Endothelin-1 gene polymorphism in sudden sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: Endothelin-1 is a potent vasoconstrictor peptide that is widely distributed throughout the mammalian body including the spiral modiolar artery, vestibule, and cochlea. This study aimed to investigate the association between the Lys198Asn (G/T) polymorphism (rs5370) of the endothelin-1 gene and sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Case-control study. METHODS: Seventy-two SSNHL patients (mean age, 58.3 ± 14.0 years) were compared with 2,159 controls included in a community-based study of aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL. In subgroup analysis, patients with SSNHL who visited to the hospital within the first month of onset were selected to assess audiometric features according to genotype. Pure-tone averages at 250, 500, 1,000, 2,000, and 4,000 Hz were calculated in the affected ear. RESULTS: Under the recessive genetic model, after adjustment for age, sex, histories of hypertension, dyslipidemia and diabetes, the crude and adjusted ORs for SSNHL risk were 2.209 (95% confidence interval [CI]: 1.140-4.281) and 2.173 (95% CI: 1.086-4.348), respectively. No significant ORs were observed under the additive and dominant models. The severity of SSNHL differed significantly between genotypes. The mean pure-tone averages at the initial visit were 78.6, 66.4, and 57.8 dB for the GG, GT, and TT genotypes, respectively (P = .034). CONCLUSIONS: Our study indicates that the recessive genotype was significantly associated with increased SSNHL risk; however, the severity was lower in these individuals than it was in those with the wild-type genotype. Endothelin-1 may be implicated in SSNHL.

Polymorphisms in genes encoding aquaporins 4 and 5 and estrogen receptor α in patients with Ménière's disease and sudden sensorineural hearing loss.

AIMS: The etiologies of Ménière's disease and idiopathic sudden sensorineural hearing loss (SSNHL) remain unclear. The homeostasis of the water and blood circulation in the inner ear is essential for maintaining its hearing and equilibrium functions, and aquaporins and estrogen are involved in the fluid or ion balance in the inner ear. We investigated the associations between genetic polymorphisms in aquaporin 4 (AQP4, rs2075575), aquaporin 5 (AQP5, rs3736309), and estrogen receptor α (ERα1, rs2234693; ERα2, rs9340799) and susceptibility to Ménière's disease or SSNHL. MAIN METHODS: We compared 86 patients affected by Ménière's disease, 85 patients affected by SSNHL, and 2136 adults who were participants in a comprehensive longitudinal study of aging. KEY FINDINGS: With the AQP5 polymorphism, the odds ratio for Ménière's disease was 0.676 (95% confidence interval: 0.477-0.957) after adjustment for age and sex, when an additive genetic model was used. The AQP5 polymorphism entailed no significant risk of SSNHL and the polymorphisms of AQP4, ERα1, and ERα2 entailed no significant risk of Ménière's disease or SSNHL in the additive genetic model, regardless of adjustments for age and sex. SIGNIFICANCE: Our study suggests that the variant G allele of AQP5 polymorphism rs3736309 reduces the risk of Ménière's disease.

Progressive hearing loss following acquired cytomegalovirus infection in an immunocompromised child.

We report a rare case of progressive hearing loss after acquired CMV infection in a child with Langerhans cell histiocytosis (LCH). A 5-month-old female was diagnosed as having LCH. When she was 14 months old, she received an unrelated donor umbilical cord blood transfusion for the treatment of intractable LCH. CMV infection was confirmed after the blood transfusion. Because her own umbilical cord had no CMV, the CMV infection was not congenital. When she was 7 years old, mixed hearing loss was noted with bilateral otitis media with effusion. After that time, the sensorineural hearing loss progressed to bilateral profound hearing loss over 3 years. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging with gadolinium contrast enhancement revealed a high intensity area in the inner ear that suggested bilateral labyrinthitis. This case demonstrates the possibility that, under the immunodeficiency, the acquired CMV infection causes progressive sensorineural hearing loss.

Children with severe or moderate obstructive sleep apnoea syndrome show a high incidence of persistence after adenotonsillectomy.

CONCLUSION: Persistent obstructive sleep apnoea syndrome (OSAS) occurs in approximately 20% of normal-weight children after adenotonsillectomy (T&A) and, in nearly 70% of them, it is caused by adenoid regrowth. Patients with severe or moderate OSAS showed a high incidence of persistent disease even after T&A. Allergic disease, severity and large adenoid size are associated with adenoid regrowth and persistent disease. OBJECTIVES: To investigate factors contributing to persistent OSAS and adenoid regrowth after T&A in normal-weight children. METHODS: This was a prospective, observational study at a single institute and involved 49 normal-weight children with severe or moderate OSAS (apnoea-hypopnoea index, AHI, ≥ 5) who underwent T&A. Background information, nasal endoscopic data and pre- and postoperative polysomnographic data were collected. A third polysomnography (PSG) was performed 1.5 year postoperatively in children who subsequently developed symptoms of sleep disturbance. RESULTS: Thirteen children (27%, 13/49) were symptomatic 1.5 years after T&A. Allergic rhinitis (38.5% vs 11.1%, p = 0.03) and allergic disease (69.2% vs 30.6%, p = 0.02) were seen more frequently in these children. A third PSG confirmed persistent disease (AHI ≥ 5) in nine children (18.4%, 9/49). Six children (12.2%, 6/49) were diagnosed as having adenoid regrowth and three (6.1%, 3/49) underwent revision adenoidectomy.

Relationship between adenoid size and severity of obstructive sleep apnea in preschool children.

OBJECTIVE: To investigate the contributions of adenoid and tonsil sizes to obstructive sleep apnea syndrome (OSAS) in normal-weight children in two age categories: preschool and schoolchildren. METHODS: Fifty-eight normal-weight (body mass index z-score<2) symptomatic children with OSAS (apnea-hypopnea index ≥ 2) were evaluated. The patients were divided into two age categories: preschool (age<6; n=33) and schoolchildren (age ≥ 6; n=25). Polysomnographic findings and adenoid and tonsil sizes were compared. The relative contributions of body mass index and adenoid and tonsil sizes were also investigated with a regression analysis. RESULTS: Adenoid grade and apnea index correlated significantly in preschool children (r=0.45, p<0.01). On regression analysis, adenoid grade was a significant predictor of the apnea index in preschool children. The influence of adenoid hypertrophy decreased from preschool to schoolchildren. Tonsil size had little influence on the apnea index in either group. CONCLUSION: Adenoid hypertrophy was a major contributor to OSAS in normal-weight preschool children. The upper airway morphology of younger children with OSAS differed from that of older children with OSAS.

Contribution of complement factor H Y402H polymorphism to sudden sensorineural hearing loss risk and possible interaction with diabetes.

Sudden sensorineural hearing loss (SSNHL) is one of the most common diseases encountered by otolaryngologists; however, the etiology is unclear. The aim of this study was to assess the association between SSNHL and polymorphism of complement factor H (CFH) Y402H, which is implicated in age-related macular degeneration. We conducted a case-control study, in which the cases were 72 SSNHL patients and the controls were 2161 residents selected randomly from the resident register. The odds ratio (OR) for SSNHL risk was determined using the additive-genetic model of CFH Y402H polymorphism. The OR for SSNHL risk was 1.788 (95% confidence interval [CI]: 1.008-3.172) with no adjustments and 1.820 (CI: 1.025-3.232) after adjusting for age and sex. Of the three lifestyle-related diseases hypertension, dyslipidemia, and diabetes, only diabetes was significantly associated with SSNHL risk. We classified both the controls and SSNHL patients into those with or without diabetes, and the OR for SSNHL risk was 6.326 (CI: 1.885-21.225) in diabetic subjects and 1.214 (CI: 0.581-2.538) in nondiabetic subjects. We conclude that CFH Y402H polymorphism and SSNHL risk are significantly related, and that diabetic CFH Y402H minor allele carriers may be susceptible to SSNHL.

Polymorphisms in genes involved in inflammatory pathways in patients with sudden sensorineural hearing loss.

Although the etiology of idiopathic sudden sensorineural hearing loss (SSNHL) remains unclear, the pathologically increased permeability of blood vessels, elucidated by gadolinium-enhanced magnetic resonance imaging (MRI), suggests the involvement of inflammation. Because SSNHL is considered a multifactorial disease, possibly caused by interactions between genetic factors and environmental factors, the authors investigated the associations of polymorphisms of inflammatory mediator genes with susceptibility to SSNHL. The authors compared 72 patients affected by SSNHL and 2010 adults (1010 men and 1000 women; mean age 59.2 years; range 40-79) who participated in the National Institute for Longevity Sciences Longitudinal Study of Aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with polymorphisms in the genes IL-6 C - 572G, IL-4R G1902A, IL-10 A - 592C, TNFα C - 863A, TNFRSF1B G593A, VEGF C936T, VEGF C - 2578A, and VEGF G - 1154A, with adjustment for age, gender, and any history of hypertension, diabetes, or dyslipidemia. The per-allele OR for the risk of SSNHL in subjects bearing IL-6 C - 572G was 1.480 (95% confidence interval [CI], 1.037-2.111) in model 1 (no adjustment), 1.463 (CI, 1.022-2.094) in model 2 (adjusted for age and gender), and 1.460 (CI, 1.016-2.097) in model 3 (adjusted for age, gender, and a history of hypertension, diabetes, or dyslipidemia). Under the dominant model of inheritance, the ORs were 1.734 (CI, 1.080-2.783) in model 1, 1.690 (CI, 1.050-2.721) in model 2, and 1.669 (CI, 1.035-2.692) in model 3. The remaining seven polymorphisms failed to show any associations with the risk of SSNHL. These data need to be confirmed on larger series of patients. In conclusion, the IL-6 C - 572G polymorphism is associated with a risk of SSNHL. Because permeability of blood vessels in the inner ear is frequently increased in patients with SSNHL, inflammation of the inner ear might be involved.

Endolymphatic hydrops and blood-labyrinth barrier in Ménière's disease.

CONCLUSIONS: The blood-labyrinth barrier is impaired in association with the hydrops grade in Ménière's disease. OBJECTIVES: To investigate the relationship between endolymphatic hydrops and the clinical characteristics of patients with Ménière's disease revealed by 3 T magnetic resonance imaging (MRI). METHODS: A double dose of gadoteridol (Gd; 0.2 mmol/kg) was injected intravenously in 12 patients with Ménière's disease. We performed three-dimensional fluid attenuated inversion recovery MRI and three-dimensional real inversion recovery MRI 4 h later using a 3 T MRI unit. Ten patients had unilateral and two had bilateral Ménière's disease. RESULTS: Fourteen ears with Ménière's disease showed intense Gd contrast on MRI compared with that in the 10 asymptomatic contralateral ears of patients with unilateral Ménière's disease (1.12 ± 0.36 vs 0.82 ± 0.15). The hydrops grade was correlated significantly with the contrast effect. The 14 ears with Ménière's disease had endolymphatic hydrops. Of the 10 contralateral ears of patients with unilateral Ménière's disease, 2 had endolymphatic hydrops in the cochlea and 6 had endolymphatic hydrops in the vestibule.

Pathogenetic role of increased nasal resistance in obese patients with obstructive sleep apnea syndrome.

BACKGROUND: The role of increased nasal resistance in obstructive sleep apnea syndrome (OSAS) remains controversial. The aim of this study was to examine the pathogenetic role of nasal obstruction in obese patients with OSAS. METHODS: Patients with OSAS (n = 125) at a university hospital were divided into three groups according to body mass index (BMI): nonobese (BMI < 25 kg/m(2)), mildly obese (25 kg/m(2) < or = BMI < 30 kg/m(2)), and obese (BMI > or = 30 kg/m(2)). The subjects underwent nasopharyngoscopy, measurement of nasal resistance, and polysomnography. RESULTS: We studied 42 nonobese, 47 mildly obese, and 36 obese patients with OSAS. Among the obese, but not the nonobese and mildly obese patients, we found significant correlations between the oxygen desaturation index (ODI) and bilateral nasal resistance (BNR; r = 0.412; p = 0.013), between the ODI and unilateral higher nasal resistance (UHNR; r = 0.413; p = 0.012), and between the apnea index and UHNR (r = 0.334; p = 0.046). Multiple regression analysis incorporating all patients showed that BMI (p < 0.001) and BNR (p = 0.033) were independently related to the ODI. CONCLUSION: In obese patients with OSAS, increased nasal resistance could play an important pathogenetic role in hypoxemic apnea.

3 Tesla magnetic resonance imaging obtained 4 hours after intravenous gadolinium injection in patients with sudden deafness.

CONCLUSION: 3 Tesla (3T) magnetic resonance imaging (MRI) performed 4 h after intravenous gadolinium (Gd) injection provides sufficient anatomic resolution of the inner ear fluid spaces in sudden deafness. The signal intensity ratio (SIR) between the cochlea and cerebellum may be a good indicator of disruption of the blood-labyrinthine barrier. OBJECTIVES: We evaluated the inner ear 4 h after intravenous Gd injection to determine whether 3T MRI enables the acquisition of images of the affected inner ear in sudden deafness. METHODS: Ten patients underwent 3T MRI scanning 4 h after intravenous Gd injection. Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI was performed. RESULTS: The SIR varied from 0.45 to 2.17 in 11 affected ears and from 0.43 to 1.48 in 9 unaffected ears. The difference of contrast (affected ear vs unaffected ear) could be detected in five of the nine patients with unilateral sudden deafness. The Gd distribution was recognized in the vestibule of 10 affected ears and in the cochlea of 5 affected ears, in which no significant hydrops was observed. In the remaining vestibules and cochleas of affected ears, the Gd enhancement was too faint to evaluate the endolymphatic hydrops.

Endolymphatic hydrops revealed by intravenous gadolinium injection in patients with Ménière's disease.

CONCLUSION: Visualization of endolymphatic hydrops became possible after intravenous gadolinium (Gd) injection in patients with Ménière's disease. OBJECTIVE: To visualize endolymphatic hydrops after intravenous Gd injection. METHODS: Gd (gadoteridol; 0.2 mmol/kg) was injected intravenously in three patients with unilateral Ménière's disease. We performed three-dimensional fluid attenuated inversion recovery (3D-FLAIR) and three-dimensional real inversion recovery (3D-real IR) magnetic resonance imaging (MRI) 4 h after the injection using a 3-Tesla MRI unit. We used a 32-channel array coil to obtain a high signal-to-noise ratio. RESULTS: Endolymphatic hydrops was observed in the ears of patients with Ménière's disease. However, Gd concentration in the perilymph was lower compared with that obtained after intratympanic Gd injection.

Pharyngeal morphology: a determinant of successful nasal surgery for sleep apnea.

OBJECTIVES/HYPOTHESIS: To estimate the effectiveness of nasal surgery on the occurrence of sleep apnea, and to analyze the pharyngeal morphology of apnea patients whose sleep-disordered breathing was ameliorated postoperatively. STUDY DESIGN: Prospective study. METHODS: Thirty-five consecutive patients with apnea and nasal obstruction underwent polysomnography and a morphological examination of the upper airway before and after nasal surgery, which included septoplasty, inferior turbinectomy, and/or functional endoscopic sinus surgery. RESULTS: Sleep apnea was significantly ameliorated in only eight patients. The postoperative reduction in the apnea-hypopnea index tended to be lower in those with a low-positioned soft palate, reflected in an elevated modified Mallampati score, and a narrow retroglossal space. Neither swollen tonsils nor narrow fauces affected the surgical outcome. Regression analysis showed that the modified Mallampati score (P < .05) and the retroglossal space (P < .05) were significant predictors of postoperative improvement in the apnea-hypopnea index. CONCLUSIONS: Among sleep apnea patients suffering from nasal obstruction, nasal surgery is effective in those with a high-positioned soft palate and/or a wide retroglossal space.

Morphological examination of upper airway in obstructive sleep apnea.

OBJECTIVES: An aim of this study was to assess the predictive power of an otorhinolaryngological examination of the upper airway to identify risk factors of obstructive sleep apnea syndrome (OSAS) in the patients. METHODS: We examined 141 consecutive patients with OSAS. The morphological features were assessed by the designated otorhinolaryngologist while the subjects were sitting relaxedly with tidal breathing. The bilateral nasal resistance was measured using the active anterior rhinomanometry during daytime wakefulness. RESULTS: The body mass index (BMI), fauces's narrowness, neck circumference, lowest oxygen saturation, tonsil size and modified Mallampati grade (MMP) showed the statistically significant correlations with the apnea-hypopnea index (AHI) of an index of apnoeseverity, however, the age, Epworth sleepiness scale (ESS), nasal resistance and retroglossal space were not significantly associated with the AHI. CONCLUSIONS: The upper airway morphology significantly associated with AHI are fauces's narrowness, tonsil size, and MMP, but not nasal resistance and retroglossal space.

Significance of a screening device (Apnomonitor 5) for sleep apnea syndrome.

OBJECTIVES: The objective was to evaluate the significance of a portable sleep-monitoring device (Apnomonitor 5, Chest Co., Tokyo, Japan) to diagnose sleep apnea syndrome (SAS). METHODS: The Apnomonitor 5 comprised an oronasal thermistor, a pulse oximeter, chest and abdominal belts to monitor the circumferences of the chest and abdomen, a microphone to monitor tracheal sound, a position detector, and an integrative unit. This screening device was commercially available and it had been used to diagnose SAS in our country. Twenty-two consecutive adults who attended Inazawa City Hospital who were suspected for SAS were prospectively enrolled and they undertook the standard polysomnography (PSG) and Apnomonitor 5 simultaneously. The designated polysomnographers analyzed the records of the PSG and Apnomonitor 5. These sleep and respiratory parameters of the devices were compared, the results of which were double-checked by the designated sleep specialist. RESULTS: The apnea-hypopnea index (AHI), apnea index, total number of apnea, and oxygen desaturation index obtained by the PSG and Apnomonitor 5 correlated significantly, whereas the averaged sleep time, total number of hypopnea, hypopnea index, and nadir oxygen saturation differed between the devices. The sensitivity of the Apnomonitor 5 versus PSG was 95% in the SAS patients with the AHI> or =15. CONCLUSIONS: The Apnomonitor 5 can be a sensitive and useful screening device for SAS especially in patients with the AHI> or =15.

Recombination of a maternal pericentric inversion results in 22q13 deletion syndrome.

We describe a 10-month-old boy with 22q13 deletion syndrome. Chromosomal analysis showed a partial duplication of 22p11.2-pter and a terminal deletion of 22q13.31-qter. Maternal chromosomal analysis showed a pericentric inversion of chromosome 22, with breakpoints at p11.2 and q13.31 [inv(22)(p11.2q13.31)]. The deleted chromosome resulted from a recombinant chromosome inherited from his mother. This is a rare case of 22q13 deletion syndrome associated with parental pericentric inversion of chromosome 22.