Identification of hemodynamic compromise by cerebrovascular reserve and oxygen extraction fraction in occlusive vascular disease.

Cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) are used to identify hemodynamic compromise in symptomatic patients with carotid occlusive vascular disease, but evidence suggests that they are not equivalent. The authors studied the relationship between CVR and OEF to evaluate their equivalence and stages of hemodynamic compromise. Symptomatic patients (N = 12) with carotid occlusion were studied by stable xenon-computed tomography CBF after intravenous acetazolamide administration for CVR, followed within 24 hours by positron emission tomography (PET) for OEF. Middle cerebral artery territories were analyzed by hemisphere and level. Hemispheric subcortical white matter infarctions were graded with magnetic resonance imaging. Both hemispheric and level analysis of CVR and OEF showed a significant (P = 0.001), negative linear relationship [CVR (%) = -1.5 (OEF) + 83.4, (r = -0.57, P = 0.001, n = 24]. However, 37.5% of the hemispheres showed compromised CVR but normal OEF and were associated (P = 0.019) with subcortical white matter infarction. CMRO2 was elevated in stage II hemodynamic compromise (CVR < 10%, OEF > 50%). CVR and OEF showed a significant negative linear relationship in stage II hemodynamic compromise but revealed hemispheres in hemodynamic compromise by CVR but normal OEF that were associated with subcortical white matter infarction.     

PET OEF Reactivity for Hemodynamic Compromise in Occlusive Vascular Disease

Background and Purpose. Hemodynamic compromise in symptomatic patients with occlusive vascular disease (OVD) identified by cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) is an independent predictor of high stroke risk. However, up to 60% of patients compromised by CVR have normal OEF indicating a high rate of discordance. CVR is measured with an acetazolamide challenge, and OEF reactivity (OEFR) to acetazolamide, ie, a hemodynamic challenge, may reveal hemodynamic compromise and less discordance with measurements of CVR. Methods. Nine symptomatic patients with OVD were studied by positron emission tomography before and 15 minutes after 15 mg/kg intravenous acetazolamide in the middle cerebral artery territories of each hemisphere. Results. A close correlation between hemispheric CVR and OEFR was observed. Two hemispheres from two different patients showed an increase in OEF to acetazolamide challenge despite a normal baseline OEF. The two hemispheres showing an increase in OEF in response to acetazolamide were also associated with the lowest CVR and severest white matter hyperintensities. Conclusions. These observations suggest that positive OEFR may distinguish hemispheres in hemodynamic compromise despite normal OEF and show less discordance with CVR. However, these preliminary observations require confirmation in a larger study.     

Selective neuronal damage and chronic hemodynamic cerebral ischemia

OBJECTIVE: In atherothrombotic internal carotid artery or middle cerebral artery (MCA) occlusive disease, chronic hemodynamic compromise may increase the risk for cerebral ischemic damage. To determine whether selective neuronal damage demonstrated as a decrease in central benzodiazepine receptor (BZR) in the normal-appearing cerebral cortex is associated with increased oxygen extraction fraction (OEF) (misery perfusion). METHODS: We measured BZR and OEF using positron emission tomography in 105 nondisabled patients with atherothrombotic internal carotid artery or MCA occlusive disease and no cortical infarction. By using three-dimensional stereotactic surface projections and the stereotactic extraction estimation method, without correction for partial volume effects, the abnormally decreased BZR index [(the extent of the pixels with Z-score more than 2 compared with controls) x (average Z-score in those pixels)] in the cerebral cortex of the MCA distribution with arterial disease was calculated, and it was found to be correlated with the mean hemispheric value of OEF and several clinical variables. RESULTS: All patients had pixels with abnormally decreased BZR, with the extent varying from 0.04 to 60.91%. Multivariate analysis showed that the abnormally decreased BZR index was positively correlated with the value of OEF and the history of stroke, whereas it was negatively correlated with the presence of hypercholesterolemia with statin treatment. Follow-up examinations of 17 patients without ischemic episode showed that a decrease of BZR was associated with an increase of OEF. INTERPRETATION: In atherothrombotic internal carotid artery or MCA occlusive disease, misery perfusion may cause selective neuronal damage, and statins might have beneficial effects against neuronal damage.     

Benign prognosis of never-symptomatic carotid occlusion

OBJECTIVE: To determine the prognosis of asymptomatic carotid artery occlusion. BACKGROUND: As opposed to symptomatic carotid occlusion, little information is available on the prognosis of asymptomatic carotid occlusion. METHOD: Thirty never-symptomatic and 81 symptomatic patients with carotid occlusion underwent baseline assessment of 15 risk factors together with PET measurements of oxygen extraction fraction (OEF). Every 6-month telephone contact recorded interval medical treatment and subsequent stroke occurrence during an average follow-up of 32 months. Patients, treating physicians, and an end point adjudicator were blinded to PET results. RESULTS: Ischemic stroke occurred in 1 of 30 of never-symptomatic patients (3.3%) and 15 of 81 of symptomatic patients (18.5%; p = 0.03). No strokes in the carotid territory distal to the occluded vessel occurred in the never-symptomatic patients. Multivariate analysis of baseline risk factors for all 111 patients revealed that age, plasma fibrinogen level, and PET findings of high OEF distal to the occluded carotid artery were the only independent predictors of subsequent stroke (p < 0.05). Previous ipsilateral hemispheric or retinal symptoms was not a significant predictive variable. The lower risk of stroke in never-symptomatic patients was associated with a lower incidence of high OEF (4 of 30) as opposed to symptomatic patients (39 of 81; p = 0.002), but there was no significant difference in age or fibrinogen level. CONCLUSIONS: Never-symptomatic carotid occlusion carries a very low risk of subsequent ischemic stroke. This benign prognosis is associated with a low incidence of cerebral hemodynamic compromise in these patients. These data support further the importance of hemodynamic factors in the pathogenesis of ischemic stroke in patients with carotid occlusion.     

Cerebellum as the normal reference for the detection of increased cerebral oxygen extraction

Hemispheric ratios of oxygen extraction fraction (OEF), a proven methodology for the detection of severe hemodynamic impairment and stroke risk, are not sensitive for detecting bilateral hemispheric increases in OEF. The aim of this study was to investigate the use of cerebellum as the reference normal. We analyzed positron emission tomographic (PET) measurements of count-based OEF and clinical data from 57 patients with unilateral atherosclerotic carotid occlusion and 13 controls enrolled in a prospective study of stroke risk. The ipsilateral, contralateral, and total cerebellum were each evaluated as possible reference regions, and the ratios of the middle cerebral artery (MCA) hemispheric OEF counts against those in each reference region were determined. A statistically significant correlation (P<0.0001) was observed with all three MCA-to-cerebellar ratios when compared with the gold standard of ipsilateral-to-contralateral MCA hemispheric ratio. Kaplan–Meier analyses showed all MCA-to-cerebellar ratios to be predictive of stroke. By using the total cerebellum method, 7 strokes were found to have occurred in 20 patients with increased OEF (P=0.0007), compared with 7 strokes out of 16 patients with elevated OEF using the ipsilateral or contralateral cerebellum methods (P<0.0001). These methods may be useful for categorizing the hemodynamic status of patients with bilateral cerebral occlusive diseases, including atherosclerosis and moyamoya, to determine the association with the risk of subsequent stroke.     

Hemodynamic and metabolic effects of extracranial carotid disease

Cerebral blood flow (CBF), cerebral blood volume (CBV), the CBF/CBV ratio - an index of the hemodynamic reserve capacity - the rate of oxygen metabolism (CMRO2), and the fractional extraction of oxygen by the brain (OEF) were studied by positron emission tomography (PET) in the cortical territory of both internal carotid arteries in 15 cases of transiently symptomatic or progressive extracranial atherosclerotic carotid disease. None of the patients had a major stroke or had a significant neurological deficit except 1 whose damaged hemisphere is excluded from study. All were asymptomatic at the time of PET scanning. Values were obtained in the middle cerebral artery (MCA) distribution, and in the anterior and posterior borderzone regions. Eight cases had unilateral carotid stenosis of 80% or greater and 7 had unilateral or bilateral occlusion of the origin of the internal carotid artery. Results obtained in patients were compared using Student's t-test, to those obtained in neurologically normal, elderly volunteers. Patients with carotid stenosis had a significantly decreased CBF (p less than .025) and CBF/CBV ratio (p less than .025) selectively in the anterior borderzone regions. This was accompanied by a trend toward elevated OEF and declining CMRO2 values. Patients with carotid occlusion had significantly decreased CBF (p less than .005), decreased CBF/CBV ratio (p less than .005) and decreased CMRO2 (p less than .025) in the ipsilateral anterior borderzone and MCA territories. Similar changes were present in the opposite hemisphere of patients with bilateral carotid disease. These results indicate that carotid stenosis is associated with hypoperfusion and diminished hemodynamic reserve capacity in the anterior borderzone, and that carotid occlusion produces more widespread hypoperfusion and metabolic depression.     

Cerebral hemodynamics and risk for recurrent stroke in symptomatic internal carotid artery occlusion]

PURPOSE: In internal carotid artery occlusion, patients with inadequate blood supply relative to metabolic demand (misery perfusion) may be at increased risk for cerebral ischemia. This study investigated whether patients demonstrating misery perfusion on positron emission tomography (PET) have a high risk of subsequent stroke in symptomatic internal carotid artery occlusion. METHODS: We prospectively evaluated the relationship between the regional hemodynamic status of cerebral circulation and the subsequent risk of stroke in 40 patients with symptomatic internal carotid artery occlusion who underwent PET. Patients were divided into two hemodynamic categories according to the mean hemispheric value of oxygen extraction fraction (OEF) in the hemisphere supplied by the artery with symptomatic disease: patients with increased OEF and those with normal OEF. All patients were followed with medical treatment until the recurrence of stroke or death for 3 years. RESULTS: The three-year incidence of ipsilateral ischemic strokes for patients with normal OEF and those with increased OEF were 1 of 34 and 3 of 6 patients, respectively. A significantly higher incidence of ipsilateral strokes was found in patients with increased OEF (Kaplan-Meier analysis and log-rank test; p < 0.001). Multivariate analysis with the Cox proportional hazards model demonstrated that increased OEF significantly increased stroke recurrence: the relative risk was 19.5 (95% CI, 2.0-188.6) for ipsilateral stroke. An increase in the absolute OEF value was a better predictor of recurrent ischemic stroke than an OEF asymmetry. CONCLUSION: These findings suggest that patients with symptomatic internal carotid artery occlusion and misery perfusion have a high risk for subsequent stroke. Thus, identification and optimal treatment of patients with misery perfusion may be essential in preventing stroke.     

A transcranial Doppler study of basilar hemodynamics in progressive carotid artery disease

Abstract

In carotid artery disease (CAD) the basilar artery (BA) may act as an important intracranial collateral to supply hypoperfused middle cerebral artery (MCA) territories. Transcranial Doppler studies were performed to study the dependency between BA hemodynamics in relation to the MCA perfusion status. BA and MCA blood flow velocities (BFV), pulsatility indices (API) and cerebrovascular reactivity (CVR) were assessed in 40 patients with a progressive MCA hypoperfusion due to progressive CAD. All patients had patent cervical segments of their vertebral arteries with an antegrade vertebral flow profile. Duplex studies were performed to diagnose the severi~ of CAD. Hypoperfusion of the MCA was diagnosed by the degree of vasoparalysi assessed by a Diamox procedure. Analysis showed that the basilar BFV significantly increased in cases of progressive CAD; the basilar PI decreased but the basilar CVR remained unchanged. However, in cases of bilateral hemodynamic significant CAD and bilateral exhausted CVR in the MCA territory, the basilar artery did not exhibit an increase of BFVs or a decrease of the basilar PI, but the basilar CVR showed a significant decrease. Basilar artery CVR is not impaired if this artery has a function as intracranial collateral in CAD. However in cases of bilateral hypoperfused MeA territories the basilar artery does not function as a collateral pathway. The basilar CVR declines under these circumstances which merely reflects the exhausted hemodynamics in the anterior/posterior borderzones. This situation might lead to an increased stroke risk in the distal basilar supply zones. [Neural Res 1998; 20: 493-498]     

Evaluation of cerebrovascular reserve using xenon-enhanced CT scanning in patients with symptomatic middle cerebral artery stenosis

Cerebrovascular reserve (CVR) is an important prognostic factor in patients with major cerebral arterial steno-occlusive disease. However, few studies have examined CVR in symptomatic intracranial stenosis without ipsilateral extracranial internal carotid artery stenosis. This study sought to evaluate CVR in patients with symptomatic middle cerebral artery (MCA) stenosis using xenon-enhanced computed tomography (Xe/CT) with acetazolamide (ACZ) challenge. Twelve patients with symptomatic MCA stenosis were recruited. All patients were examined by Xe/CT to quantitatively measure resting cerebral blood flow (CBF) and received ACZ challenge to evaluate CVR. For resting CBF, no significant differences were found between the sides in four regions of interest. After the ACZ challenge test, the CVR was significantly different between hemispheres (ipsilateral versus contralateral CVR: 12.9 ± 24.3% versus 28.0 ± 16.8%, respectively; p = 0.005) and in the MCA territory (ipsilateral versus contralateral CVR: 8.7 ± 24.7% versus 29.3 ± 24%, respectively; p = 0.003). However, no significant differences in CVR were detected between cortical comparisons and white matter comparisons from the two sides. Thus, ACZ-challenge Xe/CT is useful for the measurement of CBF and CVR in these patients. Impaired CVR is an important characteristic of patients with symptomatic MCA stenosis.     

Blood flow reactivity to hypercapnia in strictly unilateral carotid disease: preliminary results.

To show relationship between degree of carotid arterial stenosis and cerebral blood flow reactivity (RES%) to induced hypercapnia, fluorine-18-fluoromethane and positron emission tomography (PET) was used to study 18 patients with carotid distribution transient ischaemic attacks (TIA), all free of stroke, who had angiographic-proven unilateral arterial disease. Non-involved carotid arteries were either normal or had non-stenotic plaque. Either normal arteries or nonstenotic ulcerations in the symptomatic carotid arteries were present in five of 18 (28%), ipsilateral carotid stenosis from 50-99% was present in eight of 18 (44%), and ipsilateral internal carotid occlusion was present in five of 18 (28%) patients. In comparison with 14 normal controls, all patients with symptomatic middle cerebral artery (MCA) flow territories had significantly lower mean (SEM) RES% [5.0' (0.2) vs 4.0 (0.9), p less than 0.04]. Symptomatic anterior borderzone (ABZ) RES% was also significantly lower [4.6 (0.4) vs 3.3 (0.9), p less than 0.04], than controls. In patient subgroup comparisons, the 50-99% stenosis subgroup clearly had the lowest MCA RES% [3.4 (0.2)] as well as the lowest ABZ RES% [2.8 (0.4)] on their symptomatic sides. Age, expired pCO2, mean arterial blood pressure, serum glucose, serum haematocrit and number, type and estimated duration of TIAs were not significantly different between subgroups. Linear regression showed a significant relationship between RES% and both measured percentage-stenosis (p = 0.04) and residual luminal diameter (p = 0.05) in symptomatic MCA territories. This approached significance in symptomatic ABZ regions. This preliminary data set suggests that unilateral carotid stenosis can and does result in impaired CO2 reactivity following hypercapnia. The relative normality of CO2 reactivity in those with carotid occlusion is discussed.     

Brain arteriolosclerosis and hemodynamic disturbance may induce leukoaraiosis

OBJECTIVE: To investigate whether internal carotid artery (ICA) occlusive disease-induced hemodynamic disturbance is associated with extensive white matter high-intensity lesions (WMLs) on T2-weighted MR images in the hemisphere with lacunar infarct in the basal ganglia. BACKGROUND: Hemodynamic disturbance in the brain with arteriolosclerosis may be one of the mechanisms by which ischemic injury induces extensive WMLs. METHODS: The authors used MRI and PET to study 21 patients with unilateral ICA occlusion or stenosis and lacunar infarct in the bilateral basal ganglia. In hemispheres with ICA disease, the association of WMLs with the mean hemispheric values of oxygen extraction fraction (OEF)-an index of hemodynamic compromise-measured with the 15O-labeled gas steady-state technique was analyzed. Twenty-five patients with ICA occlusive disease without lacunar infarct were studied as control subjects. RESULTS: In the hemispheres with ICA disease, patients with lacunar infarct had a significantly greater severity of WMLs than control subjects, although the mean hemispheric values of the OEF showed no significant difference. The severity of WMLs correlated significantly with the mean hemispheric values of the OEF in patients with lacunar infarct, but not in control subjects. Multivariate analysis revealed that lacunar infarcts and increased OEF were independent predictors of extensive WMLs, with lacunar infarcts the most heavily weighted factor. CONCLUSION: Internal carotid artery occlusive disease-induced hemodynamic disturbance is associated with extensive WMLs in hemispheres with lacunar infarct. Hemodynamic disturbance may contribute to the development of extensive WMLs, although brain arteriolosclerosis may be a major contributing factor.     

Assessment of ophthalmic artery collateral pathway in the hemispheric cerebral hemodynamics in patients with severe unilateral carotid stenosis

The role of ophthalmic artery collateral pathway in hemispheric hemodynamics in patients with severe carotid stenosis is controversial. The aim of the present study was to address this question comparing the asymmetry of the velocity in middle and anterior cerebral arteries (MCAs and ACAs) and cerebrovascular reactivity (CVR) in MCA on stenotic side in the patients with unilateral severe stenosis of internal carotid artery (ICA) in patients with and without ophthalmic artery collateral pathway. The cohort of 118 patients with carotid stenosis was prospectively assembled. Fifty patients who had severe unilateral ICA stenosis (71%-99%) by Duplex Ultrasound (DUS) were observed by transcranial Doppler (TCD). Cerebral blood flow velocity in MCA and ACA in both sides, direction of blood flow in ophthalmic artery (OA) and CVR on the side of stenosis were determined. There were 14 patients with retrograde blood flow in OA (Group I). The remaining 36 patients with anterograde flow in OA composed Group II. The degree of interarterial asymmetry of peak and mean velocity (Vpeak and Vmean) in MCA and ACA and CVR in MCA were compared in both groups. The degree of ACA asymmetry by Vpeak was 44.0% +/- 6.9% in Group I and 38.3% +/- 3.9% in Group II (p = 0.49), by Vmean 40.3% +/- 6.7% and 36.6% +/- 3.8% (p = 0.63) respectively. The degree of MCA asymmetry by Vpeak was 24.2% +/- 2.8% in Group I and 19.5% +/- 5.0% in Group II (p = 0.42), by Vmean 23.5% +/- 2.9% and 20.6% +/- 5.1% (p = 0.63) respectively. CVR in Group I was 26.1% +/- 6.1%, in Group II 29.0% +/- 6.7% (p = 0.65). The ophthalmic collateral pathway has no influence on hemispheric cerebral hemodynamics in patients with severe unilateral carotid stenosis.     

Cerebrovascular reserve capacity

Cerebrovascular reserve capacity (CVR) describes how far cerebral perfusion can increase from a baseline value after stimulation. Measurement of cerebral blood flow (CBF) can be done by PET or SPECT. Noninvasive and easily performed transcranial Doppler sonography (TCD) is mostly used as indirect perfusion measurement. Stimulation of cerebral perfusion is often done by CO2 inhalation or acetazolamide injection. Alternative stimuli are breath holding or cerebral activation by hand-gripping. Normal values for these tests are presented. The hemodynamic effect of stenoses of the internal carotid artery (ICA) can be estimated using CVR. The relevance of CVR is discussed controversially, since cerebral infarction due to stenosis of arteries supplying the brain is probably mostly of embolic, not hemodynamic origin. The indication for carotid artery surgery according the NASCET and ECST investigations takes into account only the degree of the stenoses and not the CVR. According to recent studies, the risk of cerebral infarction in these patients is considerably higher with reduced CVR. Therefore, CVR can be used as an additional parameter if the indication for surgery is not defined, especially in asymptomatic carotid artery stenosis. It seems also possible to identify patients who might profit from an extra-intracranial bypass operation and high-risk patients for cerebral ischemia with cerebral microangiopathy. Furthermore, the risk of cerebral infarction during carotid artery surgery and also during heart surgery can be estimated using CVR. More studies with a higher number of patients are needed to confirm the potential predictive diagnostic value of CVR in order to establish CVR measurement as part of a routine diagnostic neuroangiologic program.     

The physiological and clinical significance of nonlinear TCD waveform analysis in occlusive cerebrovascular disease

Abstract

In order to compare the results of nonlinear analysis of hemodynamically compromised and noncompromised cerebral circulations we measured consecutive transcranial Doppler (TCD) waveforms of fourteen patients with a unilateral or bilateral occlusion of the internal carotid artery. The cerebral vasomotor reactivity (VMR) to acetazolamide in both middle cerebral artery (MCA) territories was established by using TCD. Conventional TCD data and nonlinear TCD analysis of data were compared. Nonlinear analysis of the TCD time series suggested dynamical chaos based on the fractal dimension of the TCD curve and the positive Lyapunov exponents in the compromised and noncompromised MCA territories. In the areas with the compromised circulation the positive Lyapunov exponents were significantly lower compared to the noncompromised side and in some cases with a negative VMR, the Lyapunov exponent was almost zero. The latter is suggestive for periodic behavior of the impaired cerebral circulation instead of the dynamical chaos which is found under normal conditions. The TCD time series of a hemodynamic compromised cerebral territory not only shows phenomena related to a decreased perfusion pressure (such as a 'damped waveform') but also phenomena which are related to a more prominent periodicity. We speculate that conventional and nonlinear TCD analysis could be used to determine the VMR. [Neurol Res 1995; 17: 384-388]     

Silent cortical neuronal damage in atherosclerotic disease of the major cerebral arteries

In atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA) disease, hemodynamic compromise may cause selective neuronal damage manifested as loss of central benzodiazepine receptors (BZRs) in the normal-appearing cerebral cortex, without overt episode of stroke. To investigate the association of decreases in cortical BZRs with hemodynamic compromise and the effect of angiotensin receptor blockers (ARBs) on these receptors in patients whose atherosclerotic ICA or MCA disease is asymptomatic, we measured BZRs using positron emission tomography and ¹¹C-flumazenil in 79 patients with asymptomatic atherosclerotic ICA or MCA disease and no cortical infarction. Three-dimensional stereotactic surface projections were used to calculate the BZR index, a measure of abnormally decreased BZRs in the cerebral cortex within the MCA distribution. Multiple regression analysis showed this index to be positively correlated with the value of oxygen extraction fraction, with the presence of silent subcortical infarcts, and with the presence of ischemic heart disease, whereas it was negatively correlated with the treatment of hypertension with ARBs. In asymptomatic atherosclerotic ICA or MCA disease, hemodynamic compromise is associated with selective neuronal damage manifested as decreases in cortical BZRs in the noninfarcted cerebral cortex, whereas ARBs are associated with preservation of cortical BZRs.     

The Usefulness of the Ivy Sign on Fluid-Attenuated Intensity Recovery Images in Improved Brain Hemodynamic Changes after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis in Adult Patients with Moyamoya Disease

Objective

MR perfusion and single photon emission computerized tomography (SPECT) are well known imaging studies to evaluate hemodynamic change between prior to and following superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis in moyamoya disease. But their side effects and invasiveness make discomfort to patients. We evaluated the ivy sign on MR fluid attenuated inversion recovery (FLAIR) images in adult patients with moyamoya disease and compared it with result of SPECT and MR perfusion images.

Methods

We enrolled twelve patients (thirteen cases) who were diagnosed with moyamoya disease and underwent STA-MCA anastomosis at our medical institution during a period ranging from September of 2010 to December of 2012. The presence of the ivy sign on MR FLAIR images was classified as Negative (0), Minimal (1), and Positive (2). Regions were classified into four territories: the anterior cerebral artery (ACA), the anterior MCA, the posterior MCA and the posterior cerebral artery.

Results

Ivy signs on preoperative and postoperative MR FLAIR were improved (8 and 4 in the ACA regions, 13 and 4 in the anterior MCA regions and 19 and 9 in the posterior MCA regions). Like this result, the cerebrovascular reserve (CVR) on SPECT was significantly increased in the sum of CVR in same regions after STA-MCA anastomosis.

Conclusion

After STA-MCA anastomosis, ivy signs were decreased in the cerebral hemisphere. As compared with conventional diagnostic modalities such as SPECT and MR perfusion images, the ivy sign on MR FLAIR is considered as a useful indicator in detecting brain hemodynamic changes between preoperatively and postoperatively in adult moyamoya patients.     

Reduced stroke risk in patients with compromised cerebral blood flow reactivity treated with superficial temporal artery to distal middle cerebral artery bypass surgery.

Extracranial-to-intracranial (EC-IC) bypass surgery for the prevention of stroke in patients with symptomatic carotid artery occlusion has nearly ended after a randomized trial showed no benefit of the procedure. Although an EC-IC bypass might benefit patients with compromised cerebrovascular hemodynamics, the randomized trial did not differentiate patients with hemodynamic from embolic etiologies. However, subsequent investigators have identified a subgroup of patients at increased stroke risk from hemodynamic compromise. Methods: We examined the subsequent stroke rate of 42 patients with symptomatic carotid occlusion at high risk for stroke identified as having a baseline cerebral blood flow (CBF)<45 mL/100 g/min and a >5% CBF reduction in one vascular territory after a vasodilatory challenge from 1 g of intravenous acetazolamide on stable xenon-computed tomography (CT) CBF imaging. Results: Thirty patients (group 1) treated medically were a subgroup with carotid occlusion from our long-term natural history study. During a median follow-up of 12 months, 9 patients (30%) had a new stroke within a median of 5 months. Twelve patients (group 2) had recurrent, disabling cerebral ischemic symptoms, with 8 progressing to mild fixed neurological deficits from deep white matter infarction identified on CT. All were treated with superficial temporal artery to distal middle cerebral artery (STA-MCA) bypass with restoration of cerebrovascular reserve postoperatively; none had a stroke during the 18-month minimum follow-up (P=.041). Perioperative morbidity included subendocardial infarction in one and a small, asymptomatic left frontal hemorrhage in another patient. Early postoperative and delayed xenon/CT CBF studies obtained a median of 5 months postoperatively showed maintenance of cerebrovascular reserve. Conclusion: STA-MCA bypass surgery can restore cerebrovascular reserve in high-risk patients with symptomatic internal carotid artery occlusion. This was achieved with minimal perioperative complications, resulting in a subsequent reduction of stroke frequency. We suggest that the efficacy of STA-MCA bypass surgery for symptomatic carotid occlusion be re-examined prospectively using hemodynamic selection criteria.     

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.     

Centrum ovale infarcts: subcortical infarction in the superficial territory of the middle cerebral artery.

The centrum ovale, which contains the core of the hemispheric white matter, receives its blood supply from the superficial (pial) middle cerebral artery (MCA) system through perforating medullary branches (MBs), which course toward the lateral ventricles. Though vascular changes in the centrum ovale have been emphasized in dementia, stroke from acute infarction in the centrum ovale is less well documented. We studied 36 patients with infarct limited to MB territory, without involvement of the lenticulostriate territory. Ten patients had a large infarct, associated with severe disease of the ipsilateral carotid artery and with neurologic-neuropsychological impairment not different from that of large MCA infarcts. In 26 patients, the infarct was small and round or ovoid, and was associated with hypertension or diabetes and with "lacunar syndromes," usually of progressive onset. These findings show that two forms of centrum ovale infarcts can be delineated according to infarct size and shape, clinical picture, risk factors, and associated vascular disease. We propose to classify subcortical infarcts in the carotid system into four main territory groups: (1) deep perforator territory (from the MCA trunk, carotid siphon, anterior choroidal artery, anterior cerebral artery trunk, Heubner's artery, and posterior communicating artery); (2) perforating MB territory (from the superficial MCA branches); (3) junctional (territory between 1 and 2); and (4) combined territories.     

Paradoxical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic study with 15O PET

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBF_b), CBV, OEF, cerebral oxygen metabolic rate (CMRO₂), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by ¹⁵O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBF_b (>47.6 mL/100 mL/min, n = 7) was associated with normal CBF_b/CBV, increased CBV, decreased OEF, and normal CMRO₂. Low CBF_b (<31.8 mL/100 mL/min, n = 9) was associated with decreased CBF_b/CBV, increased CBV, increased OEF, and decreased CMRO₂. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBF_b regions with normal CPP, which has not been described in previous studies.