The natural history of the cerebral blood flow regulation after acute ischaemic stroke

Acute stroke is known to lead to impairment of cerebral blood flow (CBF) regulation, but its natural history and techniques for its comprehensive assessment have not been previously reported. Noninvasive measurements of blood pressure (BP), end-tidal CO2 and CBF velocity (CBFv, using transcranial Doppler ultrasound) during active, passive and motor imagery paradigms were performed in healthy older controls (n=27) and in stroke patients (n=27). Two innovative analytical techniques were firstly used in stroke studies: subcomponent analysis and multivariate dynamic modeling. In controls, significant increase in CBFv during the paradigms with no significant difference in the response amplitude was found. A reproducibility study, not previously reported, was also performed. Following acute stroke, subcomponents analysis revealed a decrease of CBFv response to the passive paradigm and impairment of the myogenic pathways of CBF regulation. Multivariate dynamic modeling removed the influences of BP and PaCO[subscript 2] showing that the reduced CBFv response to neural activation was directly related and better expressed by the contribution of the stimulation component, instead of the CBFv raw change. The contribution of motor imagery in the CBFv increase was lower compared to the other two paradigms. Impairment of cerebrovascular reactivity to CO[subscript 2] was also detected by the model, without the need of performing specific tests for this purpose. The natural history of CBF regulation revealed a deterioration of control mechanisms in both the acute (< 72h) and subacute (2 weeks) phases, reaching the controls’ levels in the chronic phases (1 and 3 months). It has been demonstrated in this thesis that CBF regulation changes significantly over time after stroke (particularly in the first weeks after onset), having potential impact not only immediately post ictus but also during the subsequent rehabilitation phase.