Magnetic resonance perfusion and cerebrovascular studies in sickle cell disease
Sickle cell disease (SCD) is a group of inherited haemoglobinopathies caused by a mutation resulting in an abnormal haemoglobin (HbS). Sickle cell anaemia is the homozygous state (HbSS). Under deoxygenated conditions, the red cell acquires an elongated 'sickle' shape in association with vaso-occlusive events and haemolysis. Cerebrovascular disease (CVD) is a serious complication of SCD, which is one of the commonest causes of childhood stroke. Stroke occurs in up 8% of young patients with SCD with an additional 25% having silent infarction on magnetic resonance imaging (MRI). Recurrent stroke occurs in up 67% of patients without regular blood transfusion, the currently recommended treatment. There are few data on the natural history of CVD in SCD or abnormality in cerebral perfusion of these patients in relation to the clinical presentation. In addition, there has been a lack of scientific evaluation of the physiological effects of blood transfusion for patients with SCD and neurological complications and its effects on cerebral perfusion and CVD. The research described in this thesis investigates, in both cross-sectional and longitudinal studies, the association of neurological events (coma, stroke, transient ischaemic attacks, seizures, headaches) with perfusion abnormality and progression of CVD in patients with SCD, and the effect of short- and long-term blood transfusion. This research has used MRI, MRA, and perfusion MRI (dynamic susceptibility contrast MRI), transcranial Doppler (TCD) ultrasound, and clinical, haematological, and oxygen saturation data. The focus has been on studying cerebral perfusion abnormality in different neurological symptoms in patients with SCD and comparing perfusion MRI with other neuroimaging techniques on investigating factors involved in the progression of CVD and perfusion abnormality over time and on identifying predictors of recurrent neurological symptoms in this population. In addition, the effect of blood transfusion on cerebral perfusion and CVD is described and discussed.