Role of Multimodal Evaluation of Cerebral Hemodynamics in Selecting Patients with Symptomatic Carotid or Middle Cerebral Artery Steno-occlusive Disease for Revascularization

Severe steno-occlusive lesions of the carotid and cerebral arteries increase the risk of cerebral ischemic events.1, 2 The two main mechanisms of ischemic stroke in these patients are thromboembolism and cerebral hemodynamic insufficiency.3–6 Transcranial Doppler (TCD) monitoring can demonstrate thrombo-embolic phenomena by identifying the spontaneous microembolic signals in the appropriate branches distal to the steno-occlusive lesion7–9 and thus help in planning the appropriate treatment.10 However, assessment of dynamic cerebral hemodynamic insufficiency remains a complex issue. Cerebral autoregulation is the ability of the vasculature of the brain to maintain adequate blood supply to meet metabolic demands by compensating for acute and chronic changes in cerebral perfusion pressure. It enables constant regional cerebral blood flow over a wide range of systemic blood pressure by adjusting the diameter of the intracranial arterioles.11 The Circle of Willis provides collateral pathways to perfuse the affected vascular territories in patients with severe steno-occlusive disease of major arteries. Although, steno-occlusive lesions, and (in some cases) collateral pathways can be readily detected by digital subtraction cerebral angiography12, computerized tomographic angiography (CTA)13, 14, magnetic resonance angiography (MRA)15 or TCD16, none of these diagnostic modalities provides any information about cerebral perfusion or the cerebral blood flow vasodilatory reserve. The hemodynamic effect of a severe stenoocclusive lesion can be categorized into three stages: stage 0, normal cerebral hemodynamics; stage 1, autoregulatory vasodilatation; and stage 2, increased oxygen extraction.17 The last stage is often called “misery perfusion”.18 Various imaging techniques currently used to measure perfusion include positron emission tomography (PET)19, dynamic first-pass perfusion CT20, xenon-enhanced CT21, perfusion weighted MR imaging22, and single-photon emission CT (SPECT).23 Cerebral perfusion in regions distal to the steno-occlusive lesion may be normal at rest. However, it may become insufficient in certain physiological circumstances due to a failed vasodilatory reserve and intracranial steal phenomenon. We have previously described the intracranial steal phenomenon as ‘Reversed-Robinhood syndrome’ in acute ischemic stroke patients with persisting intracranial steno-occlusive lesions.24 Intracranial steno-occlusive disease is fairly common in Asian patients, especially of Chinese ethnicity.25 In this pilot non-randomized study, we studied the cerebral hemodynamic status and vasodilatory reserve in patients with chronic and symptomatic severe steno-occlusive disease of the internal carotid artery (ICA) or middle cerebral artery (MCA) with continuous TCD-monitoring during voluntary breath-holding and HMPAO-SPECT with acetazolamide challenge. We aimed to establish the relationship between breath holding index by TCD and cerebral vasodilatory reserve by SPECT with acetazolamide challenge. Additionally, we evaluated the ability of combined TCD and SPECT with acetazolamide challenge to identify patients at risk of ischemic events. Some patients with impaired vasodilatory reserve underwent various cerebral revascularization procedures. Changes in their cerebral hemodynamic patterns and vasodilatory reserves after these revascularization procedures are also described.