Auditory cortex hypoperfusion: a metabolic hallmark in Beta Thalassemia

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

Brain iron content in systemic iron overload: a beta-thalassemia quantitative MRI study

Multisystem iron poisoning is a major concern for long-term beta-thalassemia management. Quantitative MRI-based techniques routinely show iron overload in heart, liver, endocrine glands and kidneys. However, data on the brain are conflicting and monitoring of brain iron content is still matter of debate

Cognitive, Brain and Intracranial Artery Involvement in Beta Thalassemia

Background: Brain involvement in beta thalassemia is scarcely known so far, and available data show different degrees of abnormalities in terms of neuroradiologic findings and cognitive impairment, mainly showing asymptomatic white matter lesions in transfusion dependent thalassemia (TDT; Karimi et al, Ann Hematol 2016) or in non transfusion dependent thalassemia (NTDT; Karimi et al, Ann Hematol 2012; Pazgal et al, Thrombosis Research 2016), arterial stenosis in NTDT (Musallam et al, EJH 2011) and a general impairment in cognitive function in TDT (Elalfy et al, Hematology 2017). To our knowledge there are no studies investigating neuroimaging and cognitive function in both groups of patients, comparing results to healthy subjects. Methods: In our observational study thalassemic patients from 4 major Centers in the South of Italy, aged more than 16 year

Brain functional impairment in beta-thalassaemia: the cognitive profile in Italian neurologically asymptomatic adult patients in comparison to the reported literature

Cognitive involvement in beta-thalassaemia is strikingly controversial and poorly studied in adulthood. This multicentre prospective study investigated 74 adult neurologically-asymptomatic beta-thalassaemia patients (mean-age 34·5&nbsp;±&nbsp;10·3&nbsp;years; 53 transfusion-dependent [TDT], 21 non-transfusion dependent [NTDT]) and 45 healthy volunteers (mean-age 33·9&nbsp;±&nbsp;10·7&nbsp;years). Participants underwent testing with Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), Brief Psychiatric Rating Scale (BPRS) and multiparametric brain 3T-magnetic resonance imaging (MRI) for parenchymal, vascular and iron content evaluation. Patients had lower Full-Scale Intelligence Quotient (FSIQ) than controls (75·5&nbsp;±&nbsp;17·9 vs. 97·4&nbsp;±&nbsp;18·1, P&nbsp;&lt;&nbsp;0·0001) even after correction for education level. Compared to TDT, NTDT showed a trend of higher FSIQ (P&nbsp;=&nbsp;0·08) but a similar cognitive profile at WAIS-subtests. FSIQ correlated with total and indirect bilirubin (P&nbsp;&lt;&nbsp;0·0001 and P&nbsp;=&nbsp;0·002, respectively); no correlation was found with splenectomy, intracranial MRI/magnetic resonance-angiography findings, brain tissue iron content or other disease-related clinical/laboratory/treatment data. FSIQ did not correlate with BPRS scores, although the latter were higher among patients (28·74&nbsp;±&nbsp;3·1 vs. 27·29&nbsp;±&nbsp;4·8, P&nbsp;=&nbsp;0·01) mainly because of increased depression and anxiety levels. Occupation rate was higher among controls (84·4% vs. 64·9%, P&nbsp;=&nbsp;0·004) and correlated with higher FSIQ (P&nbsp;=&nbsp;0·001) and education level (P&nbsp;=&nbsp;0·001). In conclusion, Italian adult beta-thalassaemia patients seem to present a characteristic cognitive profile impairment and an increased rate of psychological disorders with possible profound long-term socio-economic consequences