We categorized our cohort of patients into two groups according to the detection of TAMM asymmetry: “normal and symmetric” (NS), “normal and asymmetric” (NA). A significant TAMM asymmetry (NA Group) was observed

in 13/31 patients (41.9%). Silent ischemic lesions were detected in 6/13 (46.2%) NA and 7/18 (38.9%) NS patients. No significant difference was found in silent stroke rate (Chi square test with continuity correction, χ2 = 0.598), lesion number (t-student test, p = 0.09) and lesion burden (t-student test, p = 0.22) between the two groups ( Table 1). According to this study, TAMM asymmetry does not seem to be a significant predictor of silent cerebral ischemia as evaluated by brain MRI; in particular, it Ruxolitinib mw does not have a prognostic value in terms of silent stroke rate, lesion number and lesion burden. Furthermore, this study confirms the high prevalence of brain ischemic lesions (>40%) in so-called 17-AAG manufacturer “normals” and underlines the importance of stroke prevention even when TCD findings are within a normal range. The lack of association between TAMM asymmetry detected by TCD and MRI findings

might be related to the pathogenesis of ischemic stroke in sickle cell disease. Even though an increase in TAMM velocities has been proven to be a predictor of ischemic stroke, the site of brain ischemia does not correlate with the vessel in which blood flow velocity was found to be increased. This finding suggests that factors other than major cerebral artery stenosis concur to determine RAS p21 protein activator 1 brain ischemia [6]. In fact, rheological or hemodynamic impairment might undermine parenchymal lesions. A recent study pointed out that SCD patients have an impaired cerebral blood flow autoregulation compared with age-matched healthy subjects, independently from their hemolysis

rate [7]. Furthermore, small vessels disease might play a role in the stroke pathogenesis of these children. Side-to-side asymmetry of blood flow velocity is a common finding during TCD examination of the major arteries, both in adult than in children, but it is considered pathological whenever velocity values lie outside a standard range [8]. Nevertheless, a recent study indicated that SCD patients have a slightly wider physiological range of blood flow velocity values than normal children [9]. Furthermore, since SCD patients harbor a widespread tortuosity of intracranial vessels [3] and [4], a significant TAMM asymmetry might just represent this anatomical variation and not necessarily a pathological finding. Finally, we have also to consider some of the limits related to the TCD equipment: different location of the sample volume and/or angle of insonation when recording from each side; in fact, in children the temporal acoustic window is larger than in adults, allowing the operator to insonate the artery from different angles with potential measurement errors [9].