Renzo Manara1, Sara Ponticorvo2, Silverio Perrotta3, Maria Rosaria Barillari4, Giuseppe Costa4, Davide Brotto5, Rosanna Di Concilio6, Angela Ciancio7, Elisa De Michele8, Pasquale Alessandro Carafa9, Antonietta Canna2, Andrea Gerardo Russo2, Donato Troisi2, Martina Caiazza10, Federica Ammendola10, Domenico Roberti10, Claudia Santoro10,11, Stefania Picariello10, Maria Sole Valentino10, Emanuela Inserra10, Roberta Carfora10, Mario Cirillo12, Simona Raimo13, Gabriella Santangelo13, Francesco di Salle2, Fabrizio Esposito2,12, Immacolata Tartaglione10. 1. Neuroradiology, Department of Neuroscience, University of Padova, Padua, Italy. 2. Dipartimento di Medicina e Chirurgia, Scuola Medica Salernitana, Università di Salerno, Fisciano, Italy. 3. Dipartimento della Donna, del Bambino e della Chirurgia Generale e Specialistica, Università degli Studi della Campania "Luigi Vanvitelli", Via L. De Crecchio 4, 80138, Naples, Italy. silverio.perrotta@unicampania.it. 4. Università degli Studi della Campania, Naples, Italy. 5. Università di Padova, Padua, Italy. 6. Dipartimento di Pediatria, Ospedale "Umberto I", Nocera Inferiore, Italy. 7. Unità Operativa Ematologia - Day Hospital di Talassemia, Ospedale "Madonna Delle Grazie", Matera, Italy. 8. Medicina Trasfusionale AUO "San Giovanni di Dio e Ruggi D'Aragona", Salerno, Italy. 9. Università di Salerno, Fisciano, Italy. 10. Dipartimento della Donna, del Bambino e della Chirurgia Generale e Specialistica, Università degli Studi della Campania "Luigi Vanvitelli", Via L. De Crecchio 4, 80138, Naples, Italy. 11. Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. 12. Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. 13. Department of Psychology, University of Campania 'Luigi Vanvitelli', Caserta, Italy.
Abstract
BACKGROUND: Sensorineural hearing loss in beta-thalassemia is common and it is generally associated with iron chelation therapy. However, data are scarce, especially on adult populations, and a possible involvement of the central auditory areas has not been investigated yet. We performed a multicenter cross-sectional audiological and single-center 3Tesla brain perfusion MRI study enrolling 77 transfusion-dependent/non transfusion-dependent adult patients and 56 healthy controls. Pure tone audiometry, demographics, clinical/laboratory and cognitive functioning data were recorded. RESULTS: Half of patients (52%) presented with high-frequency hearing deficit, with overt hypoacusia (Pure Tone Average (PTA) > 25 dB) in 35%, irrespective of iron chelation or clinical phenotype. Bilateral voxel clusters of significant relative hypoperfusion were found in the auditory cortex of beta-thalassemia patients, regardless of clinical phenotype. In controls and transfusion-dependent (but not in non-transfusion-dependent) patients, the relative auditory cortex perfusion values increased linearly with age (p < 0.04). Relative auditory cortex perfusion values showed a significant U-shaped correlation with PTA values among hearing loss patients, and a linear correlation with the full scale intelligence quotient (right side p = 0.01, left side p = 0.02) with its domain related to communication skills (right side p = 0.04, left side p = 0.07) in controls but not in beta-thalassemia patients. Audiometric test results did not correlate to cognitive test scores in any subgroup. CONCLUSIONS: In conclusion, primary auditory cortex perfusion changes are a metabolic hallmark of adult beta-thalassemia, thus suggesting complex remodeling of the hearing function, that occurs regardless of chelation therapy and before clinically manifest hearing loss. The cognitive impact of perfusion changes is intriguing but requires further investigations.
BACKGROUND:Sensorineural hearing loss in beta-thalassemia is common and it is generally associated with iron chelation therapy. However, data are scarce, especially on adult populations, and a possible involvement of the central auditory areas has not been investigated yet. We performed a multicenter cross-sectional audiological and single-center 3Tesla brain perfusion MRI study enrolling 77 transfusion-dependent/non transfusion-dependent adult patients and 56 healthy controls. Pure tone audiometry, demographics, clinical/laboratory and cognitive functioning data were recorded. RESULTS: Half of patients (52%) presented with high-frequency hearing deficit, with overt hypoacusia (Pure Tone Average (PTA) > 25 dB) in 35%, irrespective of iron chelation or clinical phenotype. Bilateral voxel clusters of significant relative hypoperfusion were found in the auditory cortex of beta-thalassemiapatients, regardless of clinical phenotype. In controls and transfusion-dependent (but not in non-transfusion-dependent) patients, the relative auditory cortex perfusion values increased linearly with age (p < 0.04). Relative auditory cortex perfusion values showed a significant U-shaped correlation with PTA values among hearing losspatients, and a linear correlation with the full scale intelligence quotient (right side p = 0.01, left side p = 0.02) with its domain related to communication skills (right side p = 0.04, left side p = 0.07) in controls but not in beta-thalassemiapatients. Audiometric test results did not correlate to cognitive test scores in any subgroup. CONCLUSIONS: In conclusion, primary auditory cortex perfusion changes are a metabolic hallmark of adult beta-thalassemia, thus suggesting complex remodeling of the hearing function, that occurs regardless of chelation therapy and before clinically manifest hearing loss. The cognitive impact of perfusion changes is intriguing but requires further investigations.