Computer-assisted intraaneurysmal thrombus visualization.

OBJECTIVE: Improved visualization of intraaneurysmal thrombi can contribute to understanding their impact on clinical courses and treatments. Digital subtraction angiography (DSA) demonstrates the hemodynamic portion of aneurysm domes and vasculature structures and has been considered by many to be the principal technique used for aneurysm diagnosis. An intraaneurysmal thrombus may be visualized as a filling defect on DSA, but DSA does not reliably indicate the presence of an intraaneurysmal thrombus or its details. Computerized tomography (CT) and magnetic resonance (MR) imaging may have advantages over DSA, particularly because of their capacity to visualize soft tissue. Hence, we investigated the reconstruction of MR and CT images and compared it to DSA for assessment of intraaneurysmal thrombi. METHODS: Thirty-one patients with 34 aneurysms were enrolled. The entire group was examined with DSA. Sixteen cases were also examined with MR imaging; the remaining 15 were examined with CT imaging. Images of intraaneurysmal thrombi were rendered from corresponding MRI and soft tissue scans using CT. Intracranial vessels and aneurysms were defined from MR and CT angiography. Whole images were linked via imaging software for the reconstruction of vasculature structures. Images were superimposed to produce visualizations of thrombi situated in aneurysmal bodies. RESULTS: Reconstruction of the MR and CT images clearly demonstrated the presence and details of intraaneurysmal thrombi in 9 (26.4 %) of 34 aneurysms. DSA detected only 4 (11.7 %) of the cases as a filling defect. Significant differences in thrombus visualization were observed between DSA used alone or in conjunction with either MRA (P = .02) or CTA (P = .04) images. Mean volume of thrombosed aneurysms was 3.2 +/- 0.84 mL (mean +/- SEM) and thrombosis volume was 0.9 +/- 0.31 mL. Aneurysm and nested thrombus volumes were highly correlated (r = 0.987; P < .001). CONCLUSION: Intraaneurysmal thrombi were clearly visualized by computerized MR and CT image reconstruction. MR and CT were superior to DSA alone in demonstrating the presence of intra-aneurysmal thrombi. Computer-assisted 3-D visualization can be invaluable in understanding the shape and volume of intraaneurysmal thrombi, which may contribute to more accurate assessment and effective treatment of aneurysms cases.

Analysis of combined treatment of embolic stroke in rat with r-tPA and a GPIIb/IIIa inhibitor.

Suppression of platelet activation improves the efficacy of thrombolytic therapy for stroke. Thus, combination treatment with recombinant tissue plasminogen activator (r-tPA) and 7E3 F(ab')2, a GPIIb/IIIa inhibitor that binds the platelet to fibrin, may improve the efficacy of thrombolytic therapy in embolic stroke. Magnetic resonance imaging (MRI) was used to monitor treatment response in rats subjected to embolic middle cerebral artery (MCA) occlusion (MCAo). Animals were randomized into treated (n=12) and control (n=10) groups and received intravenous combination therapy or saline, respectively, 4 hours after MCAo. Magnetic resonance imaging (MRI) measurements performed 1 hour after MCAo showed no difference between groups. However, an increased incidence (50%) of MCA recanalization was found in the treated group at 24 hours compared with 20% in the control group. The area of low cerebral blood flow at 24 and 48 hours was significantly smaller in the combination treatment group, and the lesion size, as indicated from the T2 and T1 maps, differed significantly between groups. Fluorescence microscopy measurements of cerebral microvessels perfused with fluorescein isothiocyanate-dextran and measurements of infarct volume revealed that the combination treatment significantly increased microvascular patency and reduced infarct volume, respectively, compared with the control rats. The efficacy of combination treatment 4 hours after ischemia is reflected by MRI indices of tissue perfusion, MCA recanalization, and reduction of lesion volume. The treatment also reduced secondary microvascular perfusion deficits.

Detection of Doppler embolic signals: psychoacoustic considerations.

The purpose of this study was to improve reliability in the identification of Doppler embolic signals by determining the decibel threshold for reproducible detection of simulated "emboli" as a function of signal duration, frequency and cardiac-cycle position. The auditory sensitivity of 16 participants to 574 simulated "emboli" was examined using psychoacoustic techniques to assess how the probability of detection varies with embolic signal parameters. Detailed measurements of the threshold for detection of simulated embolic signals are presented. These provide evidence that the measured embolus-to-blood threshold ranges between 2 dB and 14 dB as a continuous function of signal duration and frequency. The level of the threshold is closely linked to both embolic signal parameters and the properties of the blood flow signal. We conclude that the current fixed choice of threshold does not provide a good approximation to the true threshold of detection across the full range of embolic signal parameters.

Bilateral paramedian thalamic contrast enhancement on CT after Intra-arterial thrombolysis.

A 58-year-old woman presented with an acute embolic occlusion of the distal basilar artery. She underwent angioplasty and intra-arterial thrombolysis. Angiography performed after recanalization revealed a single perforating thalamic artery. A nonenhanced CT scan carried out immediately after the procedure revealed hyperdense lesions in the bilateral paramedian portions of the thalami, which disappeared on the 24-hour follow-up CT scan. Three months later, the patient improved to functional independence, but had some memory dysfunction and vertical gaze palsy. This case suggests that contrast enhancement or extravasation can occur in the thalamus after intra-arterial thrombolysis performed to recanalize a basilar artery occlusion.

Cardioembolic stroke, early anticoagulation, and brain hemorrhage. Cerebral Embolism Study Group.

Brain hemorrhage is a feared complication of early anticoagulation therapy in patients with cardioembolic brain infarction. We describe nine patients with cardioembolic stroke who experienced clinical deterioration associated with computed tomography-documented hemorrhagic transformation. The clinical features of these nine patients combined with 15 previously reported cases were analyzed to determine factors associated with hemorrhagic worsening. Patient age, embolic source, and intensity of anticoagulation were not associated with hemorrhagic worsening. Large infarct size and initiation of anticoagulation after early (less than 12 hours) computed tomography were associated with hemorrhagic transformation and clinical worsening in patients who received anticoagulation therapy.

Nonseptic cerebral emboli of cardiac origin.

There is considerable debate regarding immediate anticoagulation with heparin sodium for patients suspected of having acute cerebral embolism from a cardiac source. We studied 60 consecutive hospitalized patients suspected of having a nonseptic cardiogenic cerebral embolism who, with one exception, were treated with immediate full-dose anticoagulation. None of the patients had progression of their neurologic deficits secondary to intracranial hemorrhage or recurrent embolism, and there were no deaths secondary to anticoagulant therapy. One patient had punctate hemorrhages in the area of infarction, but remained clinically stable. In light of our experience and a review of the literature, we conclude that immediate anticoagulation is judiciously safe in selected patients after nonseptic embolic stroke of cardiac origin, provided early cranial computed tomography fails to demonstrate hemorrhagic infarction.

Correlative assay of computerized cranial tomography CCT, water content and specific gravity in normal and pathological postmortem brain.

An assay of water content and specific gravity in normal and pathological autopsy brain has been correlated with CCT attenuation values obtained just prior to brain cutting. Formalin fixation does not alter normal values so that fixed brain appears to be suitable for this type of study. Low attenuation values in CCT correlate better with changes in specific gravity, rather than water in infarcts, but they have a close relationship to water content in edema. The high water content in infarcts of the white matter reveals a striking disparity in fluid control between cortex and white matter, which has not been emphasized in experimental studies. Water movement within and around blood clots has been discussed.

Effect of delayed thrombolysis with rt-PA in a rat embolic stroke model.

The effect of delayed thrombolysis with recombinant tissue plasminogen activator was tested in an embolic stroke model. The carotid territory was embolized in 103 rats with fibrin-rich clots formed and washed in polyethylene tubes. Hemispheric cerebral blood flow before and after embolization was measured by the intra arterial 133Xe injection method. At five delay times, 15-240 min after embolization, 69 animals were treated with tissue plasminogen activator, 20 mg/kg, and 34 animals with saline. Carotid angiography displayed the grade of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volume measured. Cerebral blood flow was reduced by 56-71% after embolization. Reperfusion induced by thrombolytic therapy was demonstrated by comparing the posttreatment angiography of the pooled five treatment groups to control animals. Thrombolytic therapy significantly reduced the infarct volume and improved the prekill clinical score by up to 2 h of treatment delay, and treatment might have been beneficial even after 4 h delay. Prolonging the delay of treatment increased the infarct volume (p < 0.001, Jonck-heere-Terpstra test). Only a few hemorrhagic complications were observed. Thus, thrombolytic therapy in embolic stroke induced recanalization. The effect on clinical outcome and infarct volume was dependent on delay time.

Serial changes in cerebral blood flow and flow-metabolism uncoupling in primates with acute thromboembolic stroke.

The authors recently developed a primate thromboembolic stroke model. To characterize the primate model, the authors determined serial changes in cerebral blood flow (CBF) and the relation between CBF and cerebral metabolic rate of glucose (CMRglc) using high-resolution positron emission tomography. Thromboembolic stroke was produced in male cynomolgus monkeys (n = 4). Acute obstruction of the left middle cerebral artery was achieved by injecting an autologous blood clot into the left internal carotid artery. Cerebral blood flow was measured with [15O]H2O before and 1, 2, 4, 6, and 24 hours after embolization. CMRglc was measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) 24 hours after embolization. Lesion size and location 24 hours after embolization was determined by the 2,3,5-triphenyltetrazolium chloride (TTC) staining method. The results are summarized as follows: (1) 1 hour after embolization, CBF in the temporal cortex and the basal ganglia decreased to < 40% of the contralateral values. In these regions, regarded as an ischemic core, CBF decreased further with time and CMRglc at 24 hours also decreased. Infarcted lesions as indicated by being unstained with TTC were consistently observed in these regions. (2) In the parietal cortex and several regions surrounding the ischemic core, CBF was > 40% of the contralateral values 1 hour after embolization and recovered gradually with time (ischemic penumbra). In these regions, CMRglc at 24 hours increased compared with that in the contralateral regions, indicating an uncoupling of CBF and CMRglc. No obvious TTC-unstained lesions were detected in these regions. The authors demonstrated a gradual recovery of reduced CBF, an elevated CMRglc and a CBF-CMRglc uncoupling in the penumbra regions of the primate model. Positron emission tomography investigations using this model will provide better understanding of the pathophysiology of thromboembolic stroke in humans.

Cerebral infarction: shortcomings of angiography in the evaluation of intracranial cerebrovascular disease in 25 cases.

We studied the utility and limitations of conventional cerebral angiography in 25 patients with cerebral infarction unassociated with extracranial cerebrovascular disease during a 7-year period. In only one-third of cases was the angiogram diagnostic, and in a single case it altered the pre-angiogram diagnosis by revealing a previously unsuspected embolus. Among the cases clinically diagnosed as cerebral emboli, the 2 confirmatory angiograms were performed early (within 48 hours), and demonstrated medium-large or large vessel filling defects. Two-thirds of the negative angiograms in the embolic clinical category were delayed, but there was no statistically relevant predilection for specific vessel size involvement. The category, primary cerebral vasculopathy, comprised the largest group, 10 in all, and one-half had angiographic confirmation despite time delays. Angiographic recognition was dependent on a characteristic picture of vascular involvement, and not on timing or vessel size predilection. Mitral valve prolapse figured prominently in the clinical cases of vasculopathy of uncertain etiology, which contained a total of 4 cases. The 3 cases with nondiagnostic angiograms were all delayed and demonstrated nonspecific radiographic changes. Clinically, these cases demonstrated signs or symptoms of autoimmune dysfunction, raising the specter of primary cerebral vasculopathy as a cause of cerebral infarction, in contrast to recurrent cerebral emboli.

Giant lambl excrescences. An unusual source of cerebral embolism.

BACKGROUND: A possible association of giant Lambl excrescences (LEs) with stroke has been suggested. However, the treatment of giant LEs is controversial because minimal data are available. OBJECTIVE: To clarify the management of giant LEs through a clinicopathologic study. CASE SERIES: Three young patients (2 women and 1 man) who experienced ischemic stroke were studied. Results of general examinations were normal, as were chest x-ray films, electrocardiograms, ultrasonograms of the neck, and cerebral angiograms. Extensive serological and blood testing failed to show any coagulopathies or systemic disorders that favored a stroke in these patients. Transesophageal echocardiography showed a mitral valve lesion (width, > 1 mm). Two patients (cases 1 and 3) were discharged on a regimen of anticoagulant therapy and sequential transesophageal echocardiographic monitoring was planned, whereas 1 patient (case 2) was promptly scheduled for surgery. A second stroke occurred in patients 1 and 3 at 3 and 6 months, respectively, thus leading to surgery in these 2 patients. Findings from histopathologic studies were consistent with the diagnosis of giant LEs. The patients' outcomes were uneventful after surgery, and none had a recurrence of a stroke. CONCLUSIONS: A relationship between giant LEs and stroke may be suggested. In patients who have transesophageal echocardiographic findings that are consistent with this diagnosis and recurrent stroke despite antithrombotic therapy and without an alternative explanation for the ischemic symptoms, surgery should be considered in view of these findings.

Cerebral microembolism in patients with Sneddon's syndrome.

BACKGROUND: The pathogenesis of Sneddon's syndrome is unclear. This study addresses the question whether cerebral thromboembolism may be involved in the pathogenesis of the neurologic complications of the disorder. The study consisted of 13 patients with Sneddon's syndrome defined by both generalized livedo reticularis and a history of one or more cerebrovascular ischemic events; none had clinical or Doppler ultrasonographic evidence of atherosclerosis. METHODS: Transcranial Doppler microembolic monitoring of the middle cerebral artery; blood screening for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies). RESULTS: Five patients (38%) showed clinically silent microembolism at transcranial Doppler monitoring, with individual microembolic event rates of the middle cerebral artery between 2 per hour and 33 per hour. In this group, the time since the last ischemic symptom was significantly shorter than in the eight patients without microemboli. Antiphospholipid antibodies were detected in three patients (23%), all of whom belonged to the microemboli-positive group. CONCLUSIONS: These data suggest that the detectability of both clinically silent cerebral microembolism and antiphospholipid antibodies may provide paraclinical evidence of active disease in patients with Sneddon's syndrome. The results support the notion that an immune-mediated prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization, and/or triggering in situ thrombosis of cerebral vessels, plays a pathogenetic role in the neurologic manifestations of this disorder.

Evaluation of recent cerebral infarction by computerized tomography.

Twenty patients with cerebral infarction were observed with serial computerized tomographic (CT) scans. Seventy percent of those infarctions showed a mass effect that had disappeared in all patients by the eighth week after the ictus. In 63%, there was enhancement after contrast infusion, with a definite temporal relationship to the day of onset of the neurological deficit. Twenty percent of the patients initially had normal CT scans that became abnormal weeks after the stroke. Radionuclide scans were positive in the patients who showed contrast enhancement, and the area of abnormal uptake correlated well with the area of enhancement. The timing of the performance of the CT scan in relation to the onset of neurological deficit is an important factor to consider when evaluating the stroke syndrome with CT.

Oculomotor nuclear complex infarction. Clinical and radiological correlation.

We describe a patient with an isolated mesencephalic dorsal tegmental infarct affecting the oculomotor nuclear complex and medial longitudinal fasciculus, documented by high-resolution computed tomography, after undergoing percutaneous transluminal coronary artery angioplasty. Clinically, the patient exhibited bilateral ptosis, bilateral internuclear ophthalmoplegia, transient convergence retractory nystagmus, and minimal somnolence. We believe the combined clinical and radiological findings favor the presence of a caudal, dorsal, and paramedian embolic infarct in the territory of the paramedian branches of the mesencephalic artery as the most likely mechanism for these exceptional findings and correlate them with Warwick's scheme of the oculomotor subnuclei.

Positron imaging in ischemic stroke disease using compounds labeled with oxygen 15. Initial results of clinicophysiologic correlations.

Initial results in over 50 patients with stroke suggest that positron images made during continuous inhalation of carbon dioxide labeled with oxygen 15 and molecular oxygen labeled with oxygen 15 provide data on tissue function that may be relevant to acute stroke management. Five cases illustrate the following findings: 15O-activity patterns observed in areas of ischemic injury or infarction are what one would expect if the 15O distributions represented physiologic functions, such as cerebral blood flow and metabolism. Areas of abnormal 15O activity correlate with the clinical or computed tomographic (CT) localization of the deficit. In studies performed acutely, changes in 15O distributions anticipate alterations in CT scans and may be predictive of outcome. Data related to oxygen metabolism correlate better with tissue viability than do those reflecting cerebral blood flow.

Cerebral venous thrombosis associated with epoetin alfa therapy.

BACKGROUND: Cerebral venous thrombosis is a rare complication of polycythemia. To our knowledge, epoetin alfa-induced polycythemia has not previously been reported in association with cerebral venous thrombosis. CASE DESCRIPTION: A 37-year-old patient who was receiving peritoneal dialysis and epoetin alfa (Epogen) therapy presented with a several-day history of worsening headache, and a neuroimaging scan demonstrated thrombosis of the sagittal and transverse sinus. Epoetin alfa therapy, which had been initiated 3 months earlier according to an institutional protocol, was associated with a problematic increase in hematocrit values. CONCLUSIONS: Headache should raise the suspicion of cerebral venous thrombosis in patients who are being treated with epoetin alfa, particularly in the presence of elevated hematocrit values. Monitoring hematocrit parameters in accordance with "standard guidelines" is recommended.

'Silent' brain metastasis from lung carcinoma determined by computerized tomography.

Computerized tomography (CT) was utilized as a preoperative screening procedure in a series of 50 patients with lung carcinoma who were neurologically asymptomatic and whose radionuclide brain scans and skull roentgenograms were normal. Three patients (6%) were discovered to have metastasis (cerebellum, occipital, corpus callosum). The metastatic lesions were only directly visualized after administration of contrast substance. The CT findings greatly influenced the therapeutic planning in these patients, and surgery was avoided in two. When feasible, patients with lung carcinoma should have CT examinations (with contrast administration) prior to thoracic surgery even if they do not have neurologic symtoms.

Isotope localization of infarcts in aphasia.

Radionucleide localization of infarcts producing aphasia was undertaken in 65 patients with a scan-test and onset-test interval of one months or less. The scans were traced on anatomical templates without knowledge of the aphasias. A phasics were classified by their test scores according to taxonomic criteria, independently from localization. Scans belonging to each clinically distinct group were overlapped "blindly". The results showed distinct areas for Broca's conduction and Wernicke's aphasics along the parasylvian axis of the lateral templates. Lesions of global aphasics covered all these areas, while transcorticals were outside of them. Lesion size and severity of aphasia showed significant correlation. It is concluded that a brief systematic survey of aphasia like ours is useful in predicting the anteroposterior location and often the depth and extent of lesions.

Failure of downward gaze: the site and nature of the lesion.

We report four patients with paralysis of downward gaze but with intact upward gaze, including one with detailed clinico-pathological studies and another with a focal computerized axial tomographic (CT) scan abnormality confirming the presence of bilateral lesions of the dorsomedial red nucleus, including the fasciculus retroflexus. It is suggested that sudden, permanent selective failure of downward gaze accompanied by transient disturbance of consciousness is an embolic syndrome of the posterior thalamosubthalamic or rubral artery.

Carotid artery occlusion. Delayed embolic ischemia from vertebrobasilar atheromatosis.

We described a patient with occlusion of an internal carotid artery in whom delayed transient ischemic attacks distal to the occlusion alternated with vertebrobasilar attacks. Microembolization through the vertebrobasilar system was emphasized because the middle cerebral artery was filled by the basilar artery through the posterior communicating artery, and one vertebral artery showed important atheromatous emboligenic changes. Other mechanisms appeared improbable because of the type of collateral circulation and absence of other associated emboligenic changes and hemodynamic phenomena.