Internal Carotid Artery Territory Research Articles

Cerebral hemodynamics in patients with Moyamoya disease and in patients with atherosclerotic occlusion of the major cerebral arterial trunks

To determine the difference in cerebral hemodynamics between Moyamoya disease and atherosclerotic occlusion of the major cerebral arterial trunks, we measured local cerebral blood flow (CBF) and local CO2 reactivity (CO2R) by xenon-enhanced computed tomography (CT). A total of 11 adult patients with Moyamoya disease (mean age, 39.6±7.8 years) and eight patients with atherosclerotic occlusion of the major arterial trunks (mean age, 62.4±15.4 years) were studied. Regions of interest were frontal, temporal and occipital cortex, caudate, putamen and thalamus in each hemisphere. In patients with Moyamoya disease, local CBF values in the internal carotid artery territory (frontal and temporal cortex, caudate, putamen) were significantly higher than those in the occluded side of patients with atherosclerotic occlusion. Local CO2R values in the caudate and putamen were significantly higher than those in the occluded side of patients with atherosclerotic occlusion. These results suggest that the cerebral hemodynamics of Moyamoya disease differ from those of atherosclerotic occlusion of the major cerebral arterial trunks, and may be a result of the abundant collateral circulation through basal `Moyamoya' vessels.

内頚動脈系脳梗塞の急性期症状進行例の検討

内頚動脈系脳梗塞の急性期症状進行例の検討

Open Trial of Intravenous Tissue Plasminogen Activator in Acute Carotid Territory Stroke

Pilot studies using early thrombolytic therapy in stroke have suggested that recombinant tissue plasminogen activator (rTPA) might be effective. While large, double-blind, randomized studies are needed, open trials could generate hypotheses concerning (1) the clinical correlations of outcome, (2) the significance of CT scan data during the first week, and (3) the use of adjunctive therapies. We performed an open trial of intravenous rTPA on patients referred to our emergency service with all types of ischemic stroke in the carotid territory. All patients between 20 and 81 years hospitalized during 1994 with completed stroke in the internal carotid artery territory and a baseline Scandinavian Stroke Scale score lower than 48, even with severe disturbances of consciousness, were included. The inclusion time was within 7 hours after stroke onset. A 0.8-mg/kg dose of rTPA was infused for 90 minutes. Intravenous heparin was given either immediately at efficient dosage or after 24 hours. Mannitol was used in patients with severe presentation. The Scandinavian Stroke Scale evaluation was done at baseline, 3 hours, and 1, 7, 30, and 90 days. The CT scan was performed before the treatment and at days 1 (24 +/- 6 hours) and 7. Forty-three consecutive patients met the criteria of the protocol. The mean age at inclusion was 65 +/- 10.4 years, and the mean interval to treatment was 232 +/- 79 minutes. At day 90, 25 patients (58.1%) exhibited a complete regression of symptoms, and 3 had moderate neurological sequelae. Thirteen patients had severe neurological sequelae, 11 with infarcts and 2 with secondary parenchymal hematomas. Two patients died (4.6%), 1 with hematoma. The overall hematoma rate was 6.9%. Excellent outcome at day 90 was significantly correlated with major neurological improvement at day 1. Intravenous immediate heparin versus delayed heparin after 24 hours improved the ischemic outcome but not the overall outcome. Reinfarction syndromes after major neurological improvement, likely to be rethrombosis syndromes, were observed in 3 patients (6.9%). For the day 1 CT scan, poor outcome was associated with the presence of structured and homogeneous hypodensities likely to represent classic infarcts, as confirmed by day 7 CT scan. Conversely, total recovery was significantly associated with the absence of any image or with unstructured hypodensities, a particular type of image characterized by its heterogeneous darkness and often polylobar shape. This type of image disappeared at day 7 in 17.6% of the cases and is likely to represent reperfusion images and/or incomplete ischemic damage. The results obtained in this open, small study suggest safety and effectiveness of rTPA thrombolysis at the dose of 0.8 mg/kg within 7 hours in acute strokes of the carotid territory, including highly serious baseline neurological presentations, until age 81 years and under special therapeutic conditions. Complete recovery is significantly associated with major neurological improvement during the first 24 hours and the presence of a particular type of image at day 1 CT scan characterized by an unstructured hypodensity, often polylobar and heterogeneous, which is likely to correspond to reperfusion images.

Induction of cerebral thrombosis with phenytoin in rats.

This study was conducted to explore whether intra-arterial infusion of phenytoin causes cerebral ischemia and to examine the mechanism of cerebral ischemia induced by phenytoin. Ten rats were infused with phenytoin (150 microL, 3.75 mg) retrogradely from the left external carotid artery, followed by perfusion of carbon black transcardially. The removed brain was photographed from above, and the nonperfused area was compared with control rats (n = 10) with the use of an image analyzer. Eight animals with or without phenytoin treatment were perfusion-fixed for transmission electron microscopic analyses of cerebral vasculature. To determine the effect of tissue plasminogen activator (TPA) on phenytoin-infused rat cerebrum, 20 rats were treated with or without TPA (120,000 IU) 5 minutes after the phenytoin infusion (n = 10 each). All rats suffered from respiratory distress 25 to 40 minutes after the injection and received carbon black transcardially. The nonperfused area was seen in the territory of the left internal carotid artery. Thrombi were observed from arterioles to capillaries. Under electron microscopy, endothelial cells were partially exfoliated, and the vascular lumen was obstructed by thrombi predominantly consisting of platelets. Eight rats with TPA survived more than 60 minutes, whereas only 2 rats survived without the treatment (P < .005). Nonperfused areas were 7 +/- 5% and 50 +/- 11% of cerebral surface area in rats with and without TPA treatment, respectively (P < .001). Intra-arterial infusion of phenytoin results in a nonperfused area in rat cerebrum primarily due to thrombosis of arterioles and capillaries.

Changes in cerebral blood flow induced by balloon test occlusion of the internal carotid artery under hypotension

Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with cerebral blood flow (CBF) study has proved to be a sensitive test for prediction of the outcome of permanent vessel occlusion. In this study, we evaluated the acute changes in regional CBF during BTO under hypotension in order to examine the possible risk of cerebral ischaemia after surgical treatment. Eleven patients in whom surgical carotid sacrifice was planned underwent BTO combined with CBF studies using technetium-99m hexamethyl-propylene amine oxime single-photon emission tomography under hypotension by decreasing the systemic blood pressure by about 50 mm Hg using a ganglion blocking agent. All patients showed a mild to severe decrease in CBF in the ipsilateral ICA territory relative to the contralateral side. A decrease in CBF of greater than 20% was observed in nine patients (82%), and two of them showed a decrease exceeding 40%. However, no ischaemic symptoms were demonstrated during scanning with hypotensive BTO. Our results suggest that in many patients with negative normotensive BTO, a considerable reduction in CBF would occur during hypotension. This procedure may predict a possible risk of hypotensive accident during and/or after surgery.

Large hemispheric infarction, deterioration, and intracranial pressure.

Neurologic deterioration from large hemispheric infarction with edema (LHIE) often leads to the use of therapies directed at decreasing intracranial pressure (ICP). Many of these ICP therapies can potentially accentuate tissue shifts from unilateral mass lesions and lead to rebound ICP elevations. We sought to determine whether ICP elevation is a common cause of deterioration from LHIE by measuring the initial ICP and cerebral perfusion pressure (CPP) in 19 patients deteriorating to stupor from LHIE within 3 hours of deterioration, after ruling out metabolic aberrations, medication side effects, infection, and seizures and prior to commencement of any ICP-lowering therapies. We evaluated 19 patients aged 23 to 77 years--14 with complete middle cerebral artery and five with complete internal carotid artery territory infarctions. Stupor began 59 +/- 37 hours after the stroke onset. ICP monitoring (12 ipsilateral Camino, five contralateral ventriculostomy, and two ipsilateral epidural) demonstrated elevation of ICP (> 15 mm Hg) in only five patients (26.3%), with group mean initial ICP = 13.4 +/- 10 mm Hg. Similarly, the initial CPP was diminished (< 55 mm Hg) in only two patients (10.5%), with group mean initial CPP = 74.9 +/- 14 mm Hg. Globally elevated ICP is not a common cause of initial neurologic deterioration from LHIE mass effect.

Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients

Aspirin is proposed to be effective in stroke-prophylaxis because it completely inhibits the platelet prostanoid-pathway. In about 90% of stroke victims, increased platelet reactivity (PR) can be reduced to the normal range by aspirin. Twelve hours later, about one third of them show an enhanced PR again. These patients are called secondary aspirin non responders (SANR). In this study the potential pathogenetic and prognostic impact of this biological feature on stroke recurrence was evaluated. Before discharge from the hospital, PR was determined 12 hours after an oral administration of 500 mg aspirin in 180 patients aged 58 ± 15 years; 74 were female and 106 male. All had suffered a stroke in the internal carotid artery territory. Patients were treated with 3 × 500 mg aspirin/d and were followed up over a 24-month period. Major endpoints of this study were stroke, myocardial infarction or vascular death. On discharge from the hospital, 120 of the 180 patients showed a normal PR under aspirin treatment. High test values were found in 60 patients (SANR). Six patients were lost for follow-up. Because of side effects 36 (20%) of the 180 patients enrolled discontinued medication. Major endpoints occurred in 4 of these 36 patients (11%) and in 25 of the 138 remaining patients (18.1%); 19 patients died in consequence of a vascular event during the observation period. Major endpoints were seen in only 5 of 114 (4.4%) of the aspirin responders, but in 24 out of 60 SANR (40%, p<0.0001). It may be assumed that early identification of SANR's is a clinically useful tool to classify patients at high risk for recurrence of vascular events. This may be an important step to a more effective prevention in post-stroke patients.

Magnetic resonance imaging with gadolinium contrast agent in small deep (lacunar) cerebral infarcts.

To assess gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) contrast-enhanced magnetic resonance (MR) imaging as an index of recent symptomatic small deep cerebral infarcts (SDCIs). Prospective case series. Primary-care center. Thirty-one consecutive patients presenting with the clinical diagnosis of SDCI in the territory of the perforators of the internal carotid artery or the vertebrobasilar system and confirmed by MR imaging. Rapid intravenous infusion of Gd-DTPA 5 to 10 minutes prior to acquisition of T1-weighted images. Precise clinicotopographic correlation on MR scans. Non-contrast-enhanced MR imaging allowed precise clinicotopographic correlation in five (38%) of 13 patients with SDCI symptoms in the internal carotid artery territory. After Gd-DTPA administration, precise clinicotopographic correlation improved in 11 (85%) of 13 patients. In five patients, precise correlation was possible only after Gd-DTPA enhancement. Nonenhanced MR imaging allowed precise clinicotopographic correlation in 15 (83%) of 18 patients with SDCI symptoms in the vertebrobasilar territory. After Gd-DTPA administration, we could establish precise clinicotopographic correlation in all patients with SDCIs in the vertebrobasilar territory. In three patients, precise correlation was possible only after Gd-DTPA contrast enhancement. In seven (23%) of 31 patients, Gd-DTPA failed to enhance symptomatic lesion: in five patients MR scans were performed early (less than 7 days) and in two patients later in the course (greater than 7 days). Although Gd-DTPA administration is unlikely to improve the sensitivity of MR images in visualizing SDCIs, it significantly improves the rate of precise clinicoanatomic correlation. All enhancing lesions showed precise clinicotopographic correlation. Enhancement may be absent in the acute phase (less than 7 days).

Human focal cerebral ischemia: evaluation of brain pH and energy metabolism with P-31 NMR spectroscopy.

The authors investigated early human focal ischemia with phosphorus-31 nuclear magnetic resonance spectroscopy at 1.89 T to characterize the temporal evolution and relationship of brain pH and phosphate energy metabolism. Data from 65 symptomatic patients were prospectively studied; none of the patients had had ischemic stroke in the internal carotid artery territory before. Twenty-eight neurologically normal individuals served as control subjects. Serial ischemic brain pH levels indicated a progression from early acidosis to subacute alkalosis. When acidosis was present there was a significant elevation in the relative signal intensity of inorganic phosphate (Pi) and significant reductions in signal intensities of alpha-adenosine triphosphate (ATP) and gamma-ATP compared with those of control subjects. Ischemic brain pH values directly correlated with the relative signal intensity of phosphocreatine (PCr) and the PCr index and inversely correlated with the signal intensity of Pi. There was a general lack of correlation between either ischemic brain pH or phosphate energy metabolism and the initial clinical stroke severity. The data suggest a link between high-energy phosphate metabolism and brain pH, especially during the period of ischemic brain acidosis, and the authors propose that effective acute stroke therapy should be instituted during this period.

Detection of intracranial emboli in patients with symptomatic extracranial carotid artery disease.

Cerebral embolism from extracranial sources is an important cause of ischemic stroke. The purpose of this limited study using long-term transcranial Doppler ultrasonographic monitoring was to estimate the frequency of clinically silent intracranial embolisms in patients with symptomatic extracranial carotid artery disease. By means of a 2-MHz pulsed-wave transcranial Doppler instrumentation, three consecutive patients with extracranial internal carotid artery stenosis (n = 2) or occlusion (n = 1) and recurrent ipsilateral ischemic events were monitored (19 hours total recording time). In addition, 10 control subjects without cerebrovascular disease were studied (25 hours total recording time). Formed-element emboli were defined as distinct signals within the fast Fourier-transform Doppler spectrum that were < 70 msec in duration and > 9dB greater in intensity than the background signal. Clinically silent formed-element embolism of ophthalmic or cerebral arteries was demonstrated in all three patients. Embolic events occurred only in the territory of the symptomatic internal carotid artery. The average rate of cerebral embolization at transcranial Doppler ultrasonography was 4.1/hr, with a mean signal duration of 47 msec. No emboli were found in control subjects. The observed high frequency of silent embolism of the intracranial arteries detected by transcranial Doppler monitoring in patients with recurrently symptomatic extracranial carotid artery disease should encourage studies of the prognostic and therapeutic implications of this method.

閉塞性脳血管障害患者の脳循環代謝異常

Cerebral hemodynamics associated with ischemic stroke and hemodynamic changes due to reconstructive cerebral vascular surgery were evaluated using positron emission tomography (PET) on 20 ischemia patients who showed symptoms of internal carotid artery territory and five who had reconstructive surgery. Two cases had STA-MCA anastomosis and three had carotid endarterectomy. In patients with chronic ischemia, hemodynamic disturbance appeared in the border-zone areas. On the three carotid endarterectomy cases, the hemodynamic factors showed improvement postoperatively, though no remarkable improvement was found on two cases of STA-MCA anastomosis.

Intraoperative Monitoring of the Somatosensory Evoked Potentials and Cerebral Blood Flow During Aneurysm Surgery

Somatosensory evoked potentials (SEPs) and cerebral blood flow (CBF) were monitored during temporary vascular occlusion in 67 aneurysm operations to evaluate the usefulness of SEP as an indicator for cerebral ischemia. The SEP N20 component completely disappeared during temporary vascular occlusion in 24 cases, 23 of which demonstrated complete recovery following recirculation and had no postoperative neurological sequelae. The only one with postoperative sequelae demonstrated rapid, within 1 minute, loss of N20 followed by no recovery. Another eight cases showed prolongation of central conduction time during vascular occlusion and had no postoperative sequelae. The SEP N20 attenuation reflected the CBF reduction in the middle cerebral artery (MCA) territory during MCA occlusion. However, CBF changes in the internal carotid artery (ICA) territory during ICA occlusion greatly varied. No detectable changes in SEP were found during anterior cerebral artery occlusion for anterior communicating artery aneurysms. This study indicates that intraoperative SEP monitoring is useful to detect ischemia in the MCA territory and that rapid disappearance of the N20 component is a danger signal.

Sickle cell trait and stroke in the young adult

Two young patients with sickle cell trait (AS haemaglobinopathy) and ischaemic stroke are reported. The stroke involved the internal carotid artery territory in one and the brainstem in the other. A review of the literature is presented to suggest that the association of sickle cell trait and cerebral infarction is more than coincidental. Haemoglobin electrophoresis should be undertaken routinely in young subjects with ischaemic stroke.

No evidence for transhemispheric diaschisis after human cerebral infarction.

Forty-four studies of regional cerebral blood flow (rCBF), fractional oxygen extraction (rOER) and oxygen consumption (rCMRO2) were made on twenty-five patients with recent internal carotid artery territory infarcts. The purpose was to study flow-metabolism relationships in the contralateral hemispheres, and to investigate whether contralateral rCMRO2 was depressed as a result of the recent infarcts. Two groups of controls were included for comparison--seventeen normal volunteers, and ten patients with proven extracranial cerebrovascular disease but without evidence of cerebral infarction. The results demonstrated that: contralateral hemispheric rCMRO2 was less variable than regional oxygen availability (the product of rCBF and arterial oxygen content). This was due, in part, to the effect of individual variations in PaCO2 on rCBF, but other uncontrolled factors, such as intracranial pressure, may have had influences. As a result, rCMRO2 did not correlate with rCBF; mean rCMRO2 in the contralateral hemispheres was 12% lower than normal (a significant difference), but was not different from the value found in patients with extracranial vascular disease in whom there was no evidence of infarction or ischemia; contralateral rCMRO2 did not correlate with the size of the infarct in the opposite hemisphere. It is concluded that rCMRO2 cannot be inferred from rCBF measurements in uncontrolled human studies (as frequently done in the past), and that depression of contralateral rCMRO2 may have preceded infarction in the opposite hemisphere, a consequence of the previous influences of diseases that predispose to stroke.

A case of anorexia nervosa with necropsy findings and a discussion of secondary hypopituitarism.

<h3>Background</h3> Arterial spin labelling (ASL) is an MRI technique for measuring perfusion at the brain tissue level. The aim of the study was to investigate cerebrovascular reactivity (CVR) at brain-tissue level in patients with an internal carotid artery (ICA) occlusion by combining ASL-MRI with a vascular challenge, and determine whether the CVR varies within the perfusion territory of the brain-feeding arteries. <h3>Methods</h3> Sixteen patients with a symptomatic ICA occlusion and 16 age-matched healthy control subjects underwent perfusion and perfusion-territory selective ASL-MRI before and after acetazolamide administration. CVR was assessed throughout the brain in the grey matter supplied by the unaffected asymptomatic ICA and the basilar artery. <h3>Results</h3> Cerebral blood flow increased (p&lt;0.01) in all perfusion territories after acetazolamide in the patients and controls. In the tissue supplied by the unaffected contralateral ICA, CVR was lower in the tissue supplied by the unaffected contralateral ICA in the patients when compared with the controls (22.8±16.1 vs 54.2±13.1%; mean difference, −31.5%, 95% CI −42.1 to −20.8). Within the perfusion territory of the unaffected ICA, the CVR was lower in the brain tissue on the side of the occluded ICA than on the side of the unaffected ICA (13.5±20.4 vs 26.2±16.0%; paired mean difference −12.5%, 95% CI −20.3 to −4.7). <h3>Conclusion</h3> ASL-MRI can assess impaired cerebrovascular reactivity at the brain-tissue level in patients with a symptomatic ICA occlusion. Assessment of CVR with ASL-MRI may help to identify the tissue most at risk for future stroke and as such may guide medical treatment.