Hearing loss is a common symptom in Fabry disease, but neither its natural course nor its aetiology has been defined precisely. The aim of this study was to provide a detailed epidemiological description of hearing impairment in patients in the Fabry Outcome Survey (FOS), which is the largest available database of Fabry patients. Questionnaires were completed by 566 Fabry patients, of whom 316 reported ear-related symptoms. Pure-tone audiograms from 86 patients, performed before starting enzyme replacement therapy, were analysed and compared with age-and sex-specific normal values (International Organization for Standardization, ISO 7029). When compared to an age-matched population (ISO 7029), 74% of patients had a threshold elevated above the 95th centile in at least one tested frequency. All frequencies were affected to a similar degree. However, only 14 patients (16%) were clinically affected by hearing impairment according to the age-independent World Health Organization (WHO) classification (mean threshold at 0.5, 1 and 2 kHz worse than 25 dB). Hearing loss was sensorineural in 63 patients (73%) of whom 7 patients (8%) had also a conductive component. One patient had a purely conductive hearing loss. Episodes of sudden hearing loss seemed to occur more frequently than in the general population. Men were affected earlier and more severely than women. Hearing in Fabry disease is significantly worse than in an age-matched general population but leads to clinically relevant hearing impairment in only 16% of cases. It resembles accelerated presbycusis with an additional Fabry-specific strial-type hearing loss. AbstractBackground Hearing loss is a common symptom in Fabry disease, but neither its natural course nor its aetiology has been defined precisely. The aim of this study was to provide a detailed epidemiological description of hearing impairment in patients in the Fabry Outcome Survey (FOS), which is the largest available database of Fabry patients. Materials and methodsQuestionnaires were completed by 566 Fabry patients, of whom 316 reported ear-related symptoms. Pure-tone audiograms from 86 patients, performed before starting enzyme replacement therapy, were analysed and compared with age-and sex-specific normal values (International Organization for Standardization, ISO 7029).Results When compared to an age-matched population (ISO 7029), 74% of patients had a threshold elevated above the 95th centile in at least one tested frequency. All frequencies were affected to a similar degree. However, only 14 patients (16%) were clinically affected by hearing impairment according to the age-independent World Health Organization (WHO) classification (mean threshold at 0·5, 1 and 2 kHz worse than 25 dB). Hearing loss was sensorineural in 63 patients (73%) of whom 7 patients (8%) had also a conductive component. One patient had a purely conductive hearing loss. Episodes of sudden hearing loss seemed to occur more frequently than in the general population. Men were affected earlier and more severely than wom...

Aim: This study aimed to evaluate audiological and vestibular involvement in Fabry disease and the early effects of enzyme replacement therapy with human α‐galactosidase A. Methods: Fourteen patients (10 males, 4 females) aged 14–57 years were studied. Each patient underwent a clinical (history of otological and vestibular aspects, otoscopy) and instrumental (pure tone and speech audiometry, impedance, auditory brainstem response and otoacoustic emission recordings, vestibular caloric tests, electronystagmography during acceleratory stimulation, dynamic posturography) evaluation before starting enzyme replacement therapy. Results: Fifty per cent of patients complained of hearing symptoms (hearing loss, tinnitus, ear fullness). Subjective hearing loss was present in six cases and in three cases it was the first reported symptom of Fabry disease. In six of the seven cases the onset and/or progression of hearing symptoms were sudden. Vertigo or dizziness was reported by four patients and in two cases was associated with hearing symptoms. Audiological evaluation showed sensorineural hearing loss in eight patients (5 males, 3 females). Hearing loss was unilateral in six cases and bilateral in the remaining two cases. The hearing loss (HL) ranged from 30 to 80 dB HL (mean, 43 dB HL) and the lesion was always cochlear. Vestibular examination showed abnormalities in four patients (bilateral weak/abolished response in three cases, side prevalence in one case), which were not related to either the audiological results or the history of vertigo/dizziness. Conclusion: Involvement of the inner ear is common in men and women with Fabry disease. We found a high incidence of cochlear hearing loss, which was typically unilateral and showed onset and/or progression by sudden episodes. Vascular or hydropic mechanisms could be hypothesized to explain audiological findings. Vestibular involvement had a lower incidence and showed a different pattern, thus suggesting that several pathophysiological mechanisms could play a role in determining inner ear damage in Fabry disease. Our preliminary results show that enzyme replacement therapy may stabilize hearing function; however, further follow‐up is required.

Auditory evoked responses were recorded in 16 normally hearing subjects in order to investigate the mechanisms underlying the generation of the 40 Hz steady-state response (SSR). In the first part of our study, auditory potentials were evoked by 0.1 ms clicks presented at 105 dB p.e. SPL with repetition rates of 7.9 (to obtain middle latency response, MLR), 20, 30, 40, 50, 60 Hz. In each subject predictions of the responses recorded at stimulus repetition rates of 30, 40, 50, 60 Hz were synthesized by superimposing MLRs at suitable time intervals. The calculated mean amplitude/rate and phase/rate functions behaved similarly for the recorded and predicted curves, showing the highest amplitude at 40 Hz and a linear increase of phase values when increasing the stimulus rate. Nevertheless the synthetic curves closely predicted amplitude and phase values of the recorded responses only at 40 Hz. At frequencies below 40 Hz, the mean amplitude of the predicted curve was lower than that of the recorded one while at frequencies above 40 Hz the mean amplitude was higher. Predicted phase values were found lagging at 30 Hz, and leading at 50 Hz and 60 Hz in comparison to phase values calculated on the recorded responses. Our findings suggest that a model based on the linear addition of transient MLRs is not able to adequately predict steady-state responses at stimulus rates other than at 40 Hz. Other mechanisms related to the recovery cycle of the activated system come into play in the steady-state response generation causing a decrease in amplitude and an increase in phase lag when increasing the stimulus repetition rate.

The long-term outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are still unknown. We performed a single-center, prospective, observational study of newborns born from mothers with microbiologically confirmed SARS-CoV-2 infection in pregnancy or at time of delivery. Infants were offered a multidisciplinary follow-up consisting of nasopharyngeal Polymerase Chain Reaction test at birth and at 48–72 h of life, auxological growth and neurological development, serologic testing, and audiological and ophthalmological assessments. One-hundred ninety-eight mothers and 199 newborns were enrolled. Of the 199 newborns, 171 underwent nasopharyngeal swab, four (2.3%) and two (1.15%) children tested positive at birth and 48–72 h of life, respectively. None had SARS-CoV-2 related symptoms. Auxologic and neurologic development were normal in all children during follow-up. Nine out of 59 infants had SARS-CoV-2 IgG at 3 months of life, which was associated with a positive nasopharyngeal swab at birth ( P = 0.04). Twenty seven out of 143 (18.8%) newborns had pathologic transitory evoked otoacoustic emissions at birth, although 14/27 repeated after 1 month were normal. Audiological evaluation was completed with Auditory Brainstem Response between the third and sixth month of life in 34 children, showing in all normal hearing threshold. The ophthalmological evaluation found retinal vascular anomalies in 3/20 (15%) children, immature visual acuity in 5/20 (25%) children, and reduced distance attention in 6/20 cases (30%). Conclusions : Our study showed that the neonatal and mid-term multidisciplinary outcomes of newborns exposed to SARS-CoV-2 infection in utero or during the first hours of life are mostly positive, with the exception of ophthalmologic findings which, in a preliminary cohort, were abnormal in about 15% of cases. Further prospective, longitudinal studies are needed to better understand the clinical outcomes of children exposed to SARS-CoV-2 in utero and in the early postnatal life. What is Known: • In utero mother-to-child transmission of SARS-CoV-2 has been documented by several independent studies. • Neonatal COVID-19 is a systemic disease that can be severe, although rarely. What is New: • Newborns exposed in utero to SARS-CoV-2 have mostly a normal auxological, audiological, and neurological development during the first months of life. • Fundus fluorescein angiography revealed that up to 5% of newborns exposed in utero to SARS-CoV2 can show retinal and choroidal abnormalities, including peripheral hypofluorescence of the choroid and increased vascular tortuosity. Supplementary Info...

Platinum compounds constitute the standard treatment for solid tumors in pediatric oncology. The purpose of this study is to assess the impact of platinum compounds in the development of ototoxicity in children following chemotherapy. This study included 160 patients treated with cisplatin and carboplatin for malignant solid diseases from 2007 to 2014. Their audiograms were classified according to the Boston SIOP ototoxicity scale. Twenty-five percent of the children treated with platinum compounds developed ototoxicity. The incidence of ototoxicity was correlated with the type of platinum derivative (i.e. cisplatin vs. carboplatin), coadministration of both drugs and concomitant cranial radiotherapy, but not with sex and age. Cumulative dose was correlated only with the cisplatin administration. Nine patients (8.6%) showed further progression of hearing impairment after the end of chemotherapy. The low rate of ototoxicity suggests the pivotal role of auditory monitoring in children treated with platinum compounds in order to be able to identify hearing loss at an early stage and to provide, jointly with pediatric oncologists, strategies to reduce further progression of cochlear toxicity.

Objective: To analyze and compare the preoperative factors that potentially influence the outcome of stapedotomy in our study group. Materials and Methods: 161 cases were enrolled. Clinical variables considered to influence functional results – air conduction (AC) and bone conduction (BC) pure-tone average (PTA), air-bone gaps (ABG), sensorineural hearing loss (SNHL), ABG gain and ΔSNHL – were gender, age, case type (unilateral vs. bilateral), ear side (right vs. left), pregnancy, vascular disease and family history of otosclerosis. The audiometric variables were preoperative AC- and BC-PTA, SNHL and ABG. Results: Univariate logistic regression analysis showed that the probability of obtaining a ≥10 dB gain is significantly affected by the following factors: age <50 years, AC-PTA ≥50 dB and preoperative ABG ≥30 dB. All the other factors included into the registration (gender, familiarity, side, bilateral vs. unilateral, pregnancy, vascular diseases and preoperative BC-PTA) were not found to significantly affect postoperative gain (p > 0.05). Nevertheless, multivariate logistic regression analysis maintained a statistically significant correlation only between gain ≥10 dB and both preoperative ABG ≥30 dB and age <50 years. Conclusions: The accurate knowledge of predictive factors is a valuable tool that permits the surgeon to plan surgery with a better case selection as well as assisting in counseling the patient with regard to the likelihood of success of the procedure.

In order to investigate the generation of the 40 Hz steady-state response (SSR), auditory potentials evoked by clicks were recorded in 16 healthy subjects in two stimulating conditions. Firstly, repetition rates of 7.9 and 40 Hz were used to obtain individual middle latency responses (MLRs) and 40 Hz-SSRs, respectively. In the second condition, eight click trains were presented at a 40 Hz repetition rate and an inter-train interval of 126 ms. We extracted from the whole train response: (1) the response-segment taking place after the last click of the train (last click response, LCR), (2) a modified LCR (mLCR) obtained by clearing the LCR from the amplitude enhancement due to the overlapping of the responses to the clicks preceding the last within the stimulus train.In comparison to MLRs, the most relevant feature of the evoked activity following the last click of the train (LCRs, mLCRs) was the appearance in the 50-110 ms latency range of one (in 11 subjects) or two (in 2 subjects) additional positive-negative deflections having the same periodicity as that of MLR waves.The grand average (GA) of the 40 Hz-SSRs was compared with three predictions synthesized by superimposing: (1) the GA of MLRs, (2) the GA of LCRs, (3) the GA of mLCRs. Both the MLR and mLCR predictions reproduced the recorded signal in amplitude while the LCR prediction amplitude resulted almost twice that of the 40 Hz-SSR. With regard to the phase, the MLR, LCR and mLCR closely predicted the recorded signal.Our findings confirm the effectiveness of the linear addition mechanism in the generation of the 40 Hz-SSR. However the responses to individual stimuli within the 40 Hz-SSR differ from MLRs because of additional periodic activity. These results suggest that phenomena related to the resonant frequency of the activated system may play a role in the mechanisms which interact to generate the 40 Hz-SSR.

The present findings indicate that both ABR and MLR latencies are increased by isoflurane in a concentration-dependent manner, whilst the anesthetic-induced attenuation in amplitude does not appear to be related to the isoflurane concentration.