Relative Mean Transit Time Predicts Subsequent Stroke in Symptomatic Carotid Occlusion.

BACKGROUND: Mean transit time (MTT) measurements to assess cerebral hemodynamics are easily obtained by computed tomography and magnetic resonance imaging. We reviewed hemodynamic and clinical outcome data from the St. Louis Carotid Occlusion Study to determine if increased MTT was associated with an increased risk of stroke in patients with symptomatic complete carotid artery occlusion. METHODS: Positron emission tomography (PET) studies of cerebral blood volume-to-cerebral blood flow ratios were used to calculate MTTs. Mean ipsilateral (side of the occluded internal carotid artery)-to-contralateral ratios of MTTs in the middle cerebral artery territories were determined. MTT was tested as a predictor of stroke risk using Cox regression analysis. Receiver operating characteristic curves for stroke risk prediction were generated by varying the mean ispilateral-to-contralateral MTT ratio to identify an optimal cutpoint. RESULTS: Increased MTT ratio was associated with an increased risk of ipsilateral stroke (P < .001). The maximum combination of sensitivity (.778) and specificity (.763) was obtained at a cutpoint ratio of 1.387 or higher. Subjects with a MTT ratio of 1.387 or higher had a 29.3% 2-year risk of ipsilateral stroke compared to 4.6% for those without (P < .001). CONCLUSIONS: PET relative MTT ratio identified patients with symptomatic complete internal artery occlusion who were at high risk for subsequent ipsilateral stroke. Confirmation using measurements of relative MTT from other imaging modalities in a patient cohort receiving contemporary medical management is needed.

Patent foramen ovale and stroke: Should PFOs be closed in otherwise cryptogenic stroke?

Since initial reports of its association with ischemic stroke appeared in 1988, there has been continued controversy regarding the existence and strength of the association between patent foramen ovale (PFO) and ischemic stroke. Many case-control studies have reported an association between incident cryptogenic ischemic stroke and PFO, yet population-based studies have failed to confirm this association. Studies of the risk of recurrent stroke in patients with cryptogenic stroke with or without PFO have not shown an increased risk of recurrent stroke in patients with PFO. Meanwhile, use of devices to close PFOs and atrial septal defects percutaneously has increased dramatically since their introduction. Completion of the randomized clinical trials of PFO closure currently in progress is vital to determine if the benefits of PFO closure in cryptogenic stroke outweigh its risks.

No effect of low-dose statins treatment on cerebral blood flow in humans with atherosclerotic cerebrovascular disease.

Animal studies have suggested that the reduction in stroke risk observed with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) therapy is owing to an increase in basal cerebral blood flow (CBF). The purpose of the study was to determine if statin therapy was associated with increased CBF in humans with cerebrovascular atherosclerotic disease. Quantitative measurements of CBF were obtained on study entry in 97 patients with carotid artery occlusion enrolled in a prospective study of cerebral hemodynamics and stroke risk. This study represents a post hoc analysis of CBF measurements based on whether patients were receiving statin therapy at the time of CBF measurement. Global and regional CBF (including hemispheric, basal ganglia, and arterial borderzones), and baseline clinical, epidemiologic, and laboratory stroke risk factors were compared between the two groups. Nineteen of the 97 patients were on a statin agent on study entry. The statin group was younger, had significantly lower LDL levels and included more women. Statin therapy was not associated with higher baseline values of CBF in global or regional analyses. Mean middle cerebral artery territory CBF (+/-s.d.) ipsilateral to the occluded carotid artery was 37.6+/-12.7 mL/100 g min for the statin group (n=19) compared with 38.6+/-12.7 mL/100 g min for the nonstatin group (n=78). Contralateral values were 42.9+/-13.5 and 44.2+/-13.3 mL/100 g min for the statin and nonstatin groups, respectively. We conclude that the stroke risk reduction observed with statin therapy in humans likely involves mechanisms other than an increased basal CBF.

Patterns of infarction in hemodynamic failure.

BACKGROUND AND PURPOSE: The mechanism of stroke in patients with atherosclerotic occlusive disease and hemodynamic failure may be primarily hemodynamic or a combination of hemodynamic and embolic factors. The purpose of this study was to investigate the clinical and imaging features of stroke in these patients. METHODS: Eleven patients with complete atherosclerotic carotid artery occlusion and increased oxygen extraction fraction measured in the hemisphere distal to the occlusion developed an ischemic stroke during the observation phase of a prospective study of cerebral hemodynamics and stroke risk. The medical and study records related to the endpoint event for these 11 patients were reviewed. Records were reviewed for evidence of associated hypotension and for specific details of the neurological deficit. Infarct location was characterized, based on review of imaging and clinical features, as: (1) middle cerebral artery (MCA) core; (2) possible cortical border zone, or (3) internal border zone. RESULTS: One patient had a retinal infarction; the remaining 10 had MCA territory strokes. Six of the 10 infarctions occurred in the MCA core territory. Two of these 6 were fatal hemispheric events. One of the 10 infarctions occurred in the cortical border zone region. Two of the remaining 3 infarctions were localized to the internal border zone. One was indeterminate. CONCLUSIONS: The clinical features and radiological patterns of stroke in many patients with hemodynamic impairment failure and carotid occlusion are most consistent with large artery thromboembolic stroke. These data suggest a synergistic effect between embolic and hemodynamic mechanisms for large artery thromboembolic stroke.

Variability of cerebral blood volume and oxygen extraction: stages of cerebral haemodynamic impairment revisited.

The presence or degree of haemodynamic impairment due to occlusive cerebrovascular disease is often inferred from measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF) and the cerebral rate for oxygen metabolism (CMRO2). However, the relationship of these variables, in particular CBV, to regional cerebral haemodynamics is not clearly established in humans with subacute or chronic disease. In the present study, we investigated the relationship of CBV to OEF, CBF and CMRO2, and to subsequent stroke risk in patients with unilateral carotid artery occlusion, in order to define better the associated haemodynamic and metabolic changes. We reviewed data from 81 patients with symptomatic carotid occlusion enrolled in a prospective study of haemodynamic factors and stroke risk. Measurements of CBV, CBF, OEF and CMRO2 were made on entry using PET. Patients were divided into groups by hemispheric ratios and absolute ipsilateral values of OEF and CBV, based on comparison with normal controls. Haemodynamic and metabolic values, risk factors and stroke risk were compared between groups. Based on hemispheric ratios, 45 patients had increased ipsilateral OEF; CBV was increased in 19 of these 45 patients. No differences in CBF, CMRO2 or clinical risk factors were found between these 19 patients and the remaining 26 patients with increased OEF and normal or reduced CBV. Thirteen ipsilateral strokes occurred during follow-up, and 10 of the 13 occurred in the 19 patients with increased OEF and CBV (log rank P < 0.0001). Thirty-two of the 68 patients with complete quantitative PET data had increased OEF by absolute ipsilateral values. CBV was increased in 20 of the 32 patients. No differences in CBF, CMRO2 or clinical risk factors were found between these 20 patients and the remaining 12 patients with increased OEF and normal CBV. Seven of the nine ipsilateral strokes that occurred in the 68 patients occurred in those 20 patients with increased OEF and increased CBV (log rank P = 0.003). The higher risk of ischaemic stroke in patients with increased OEF and CBV suggests that their degree of haemodynamic compromise is more severe than those with increased OEF and normal CBV. In patients with chronic carotid occlusion and increased OEF, increased CBV may indicate pronounced vasodilation due to exhausted autoregulatory vasodilation. The physiological explanation for the measurement of normal CBV in patients with increased OEF is less certain and may reflect preserved autoregulatory capacity.