Auto-Regulation And Cerebral Blood Flow In Tia Patients Attending A Stroke/Tia Clinic: Implications For Stroke Prevention In Qatar

Background and objectives: Cerebral auto-regulation is an intrinsic protective mechanism guaranteeing hemodynamic integrity of cerebral circulation. It modulates cerebral blood flow (CBF) in order to meet regional perfusion demands despite variations in arterial blood pressure. Impaired cerebral auto-regulation is associated with poor functional and prognostic outcomes in patients with ischemic stroke. The aims of this study are to: (i) correlate CBF and cerebral auto-regulation with microalbuminuria in TIA patients; and (ii) assess the prognostic outcomes of such impairment. Methods: Blood flow in the middle cerebral artery was measured on both sides of the brain, using a trans-cranial Doppler. Cerebral auto-regulation was estimated non-invasively by calculating the correlation coefficient between slow changes of arterial blood pressure, evaluated by finger plethysmograph, and slow changes of cerebral blood flow velocity measured with trans-cranial Doppler. Microalbuminuria was measured first by calculating the Albumin/Creatinine Ratio (ACR). Then 24hr urinary protein was collected to calculate total urine albumin excreted in 24hr. Urine samples with microalbuminuria (30-300mg/24hr) and with normal levels of albumin (<30mg/24hr) were also examined (using SDS-PAGE electrophoresis). Protein bands were identified by their rate of migration in comparison with standard molecular weight markers. The presence of albumin was confirmed further by immuno-blotting (Figure-1). Results: The SDS-gel, revealed the presence of three unknown protein bands (Figure-2). Band (A) is heavily stained, representing albumin. Specimens collected from patients 2, 5, 8 and 9 reveal a particularly dense band, and this is supported by the biochemical assay results, which estimated protein content at 35mg/L for sample 9, 40mg/L for sample 5, and 80mg/L for samples 2 and 8. Band (B) was shown in three of the urine samples, namely from patients 2, 5, and 8. Its position on the gel is roughly equidistant between bands A and C. Band (C), denoting a slower migration band, representing Tamm-Horsfall protein. Tamm-Horsfall protein is suspected since not only is it the most abundant protein in urine after albumin, but also its position is in concordance with the relative molecular weight of Tamm-Horsfall protein (between 85 and 110kDa). The intensity of this band is generally not as great as band A. Conclusions: This study has just started in Qatar and the UK. The outcomes will enable us to answer the following questions: Whether testing for cerebral auto-regulation in Stroke/TIA clinics will help in identifying a subgroup of TIA patients who are at grave risk of developing microvascular and macrovascular diseases, including stroke. Do TIA patients with impaired cerebral auto-regulation and microalbuminuria have more vascular events than TIA patients with normal cerebral auto-regulation without microalbuminuria? Is there any statistically significant difference in the short-term (3-6 months) and long-term (3 years) prognosis (between the two groups of TIA patients? Whether there is any correlation between CBF/auto-regulation and microalbuminuria in TIA patients with microalbuminuria. Whether post TIA stroke is independently affected by impaired cerebral auto-regulation, taking into account other confounding factors that might affect the outcome of this study (such as diabetes, hypertension, age, other cardiovascular co-morbidity).