Successful stenting seven days after atherothrombotic occlusion of the intracranial internal carotid artery.

PURPOSE: To report a case of successful stenting after a subacute stroke. CASE REPORT: A 75-year-old man presented with sudden onset of right-sided weakness and difficulty speaking. Imaging revealed an occlusion of the left petrous to lacerum internal carotid artery (ICA) segment and slightly decreased cerebral blood flow in the left hemisphere; there were stenoses of the ostial and cavernous ICA segments on the right. On the seventh day after the stroke, he underwent protected carotid angioplasty of the left intracranial ICA occlusion to reduce the high risk of ischemic stroke owing to bilateral disease. An external arteriovenous shunt was established with an occluding balloon in the proximal ICA and a filter in the femoral vein. After protected balloon dilation of the ICA occlusion, a 3.5 x 18-mm balloon-expandable coronary stent was deployed across the residual stenotic segment. An intraluminal filling defect of the petrous ICA segment suggested an arterial dissection or intraluminal thrombus, so another 2 coronary stents were deployed. Macroscopically visible materials were captured in the filter. The patient had a good clinical course and was discharged without neurological deficits on the twelfth day after the stroke. Angiography at 3 months confirmed no restenosis of the stented vessel. CONCLUSION: This experience suggests that short atherothrombotic intracranial ICA occlusions can be opened in the subacute stroke stage without distal migration of thrombi under proximal protection and flow reversal.

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.

Sonothrombolysis: experimental evidence.

Reopening of the occluded artery is the primary therapeutic goal in hyperacute ischemic stroke. Systemic treatment with tissue recombinant plasminogen activator (tPA) has been shown to be beneficial at least in a 3-hour door to needle window. Intra-arterial thrombolysis is favorable and opens the window of treatment up to at least 6 h but consequences invasive intra-arterial angiography in a high number of patients, of whom a significant number do not finally receive thrombolysis. The combination of ultrasound with thrombolytic agents may enhance the potential benefit by means of enzyme-mediated thrombolysis. When ultrasound is applied externally through skin or chest, attenuation will be very low. Attenuation, however, is significantly higher if penetration through the skull is required. Attenuation is frequency dependent, with ultrasound intensity being <10% of the output intensity for diagnostic frequencies (>1 MHz). This ratio nearly reverses in the kiloHertz range (>500 kHz). Ultrasound insonation is efficient for accelerating enzymatic thrombolysis within a wide range of intensities, from 0.5W/cm2 (MI approximately 0.3) to several watts per square centimeter, particularly in the nonfocused ultrasound field. Insonation with ultrasound increased tPA-mediated thrombolysis up to 20% in a static model, while it enhanced the recanalization rate from 30 to 90% in a flow model. Results from embolic rat models suggest that low-frequency ultrasound with 0.6W/cm2 significantly reduces infarct volume compared to pure tPA treatment. Safety of ultrasound exposure of the brain for therapeutic purposes has to address hemorrhage, heating, and direct tissue damage. Since animal studies suggested no increase of bleeding rate or harm to the blood-brain barrier, a clinical phase II study applying low-frequency ultrasound at approximately 300 kHz found a high number of secondary hemorrhages. Heating depends critically on the characteristics of the ultrasound. The most significant heating of the brain tissue itself is >1 degrees C per hour using a 2W/cm2 probe; however, no significant heating could be found when using an emission protocol pulsing the ultrasound. The current experimental data helps to identify the optimal ultrasound characteristics for sonothrombolysis and supports the hypothesis combined treatment being a perspective in optimizing thrombolytic therapy in acute stroke.

Acute stroke: therapeutic transcranial Doppler sonography.

Ultrasound (US) has emerged as a new tool to treat ischemic stroke. The potential advantage of US is decreased risk of systemic bleeding complications due to its site-specific effect. Moreover, external application is noninvasive and is readily available. Experimental studies showed that low intensity (

Acute stroke: therapeutic transcranial color duplex sonography.

The enhancement of thrombolysis by ultrasound energy (sonothrombolysis) is an emerging field of interest in the treatment of acute ischemic stroke. Recent in vitro and clinical studies have investigated the effects of using transcranially applied 'diagnostic' ultrasound for this purpose. Using transcranial color duplex sonography (TCDS) allows an examiner to identify the site of occlusion and focus the ultrasound beam on it. Clinical studies using TCDS to enhance thrombolysis in acute middle cerebral artery occlusions have revealed an accelerating effect on recanalization, as well as a tendency for a better outcome. Data from small sample studies suggest that this effect on recanalization is present not only in combination with recombinant tissue plasminogen activator (rt-PA), but also with any thrombolytic drug. However, when TCDS was used in combination with rt-PA, an increase in the rate of asymptomatic and symptomatic intracerebral hemorrhages tended to occur compared to patients treated with thrombolysis alone. Larger sample-sized clinical studies should be conducted in the future to evaluate the safety and efficacy of using TCDS for sonothrombolysis. This method should also be further developed to determine its effect when used in combination with other types of ultrasound and thrombolytic drugs.

Detection of microembolic signals with transcranial Doppler ultrasound.

Detection of microembolic signals (MES) with transcranial Doppler was introduced in the late 1980s; several animal and in vitro models reported a high sensitivity and specificity with this technique. Monitoring for MES in various patient groups has provided valuable insights on stroke pathophysiology, although its clinical value remains a matter of debate. Diagnosis of imminent occlusion of the internal carotid artery following carotid endarterectomy, selection of high-risk patients with asymptomatic carotid disease, and evaluation of drug efficacy constitute potential applications of this technique.

Contrast-enhanced transcranial Doppler ultrasound for diagnosis of patent foramen ovale.

The suspected cause of clinical manifestations of patent foramen ovale (PFO) is a transient or a permanent right-to-left shunt (RLS). Contrast-enhanced transcranial Doppler ultrasound (c-TCD) is a reliable alternative to transesophageal echocardiography (TEE) for diagnosis of PFO, and enables also the detection of extracardiac RLS. The air-containing echo contrast agents are injected intravenously and do not pass the pulmonary circulation. In the presence of RLS, the contrast agents bypass the pulmonary circulation and cause microembolic signals (MES) in the basal cerebral arteries, which are detected by TCD. The two main echo contrast agents in use are agitated saline and D-galactose microparticle solutions. At least one middle cerebral artery (MCA) is insonated, and the ultrasound probe is fixed with a headframe. The monitored Doppler spectra are stored for offline analysis (e.g., videotape) of the time of occurrence and number of MES, which are used to assess the size and functional relevance of the RLS. The examination is more sensitive, if both MCAs are investigated. In the case of negative testing, the examination is repeated using the Valsalva maneuver. Compared to TEE, c-TCD is more comfortable for the patient, enables an easier assessment of the size and functional relevance of the RLS, and allows also the detection of extracardiac RLS. However, c-TCD cannot localize the site of the RLS. Therefore, TEE and TCD are complementary methods and should be applied jointly in order to increase the diagnostic accuracy for detecting PFO and other types of RLS.

Cerebral circulation monitoring in carotid endarterectomy and carotid artery stenting.

In the near future it is likely that surgeons, anesthesiologists, and interventional radiologists and cardiologists will care for increasing numbers of patients undergoing carotid endarterectomy (CEA) and carotid angioplasty and stenting (CAS). Perhaps the most important factor in assuring technically acceptable interventions is the availability of an experienced team with demonstrable low periprocedural morbidity and mortality and a proper understanding of both vascular principles and cerebral physiology. Although different monitoring techniques have proven successful during both surgical and endovascular carotid interventions, the advantages of periprocedural transcranial Doppler (TCD) monitoring, such as its sensitivity for recording blood flow velocities and microembolism in real-time, are convincing. Because of its high temporal resolution, it provides additional information about the cerebral circulation, especially during cross-clamping, clamp release, and balloon inflation and deflation, respectively. If made audible during the procedure, it also provides unique information concerning cerebral micro-embolization. In CEA, TCD monitoring gives a better understanding of the pathophysiology of complications and makes the operation safer. In CAS, it gives insight into the clinical relevance of cerebral embolism and the possible effects of protection devices.

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.

Detection of cardiac right-to-left shunts by contrast-enhanced harmonic carotid duplex sonography.

OBJECTIVE: Paradoxical embolization by cardiac right-to-left shunts (RLS) is increasingly recognized as an important factor for embolic stroke. Contrast-enhanced transcranial Doppler sonography (ce-TCDS) is an established diagnostic tool for RLS detection but is frequently limited because of an inadequate temporal acoustic bone window. The purpose of this study was to determine whether extracranial sonography (ECS) using harmonic frequencies improves detection of RLS. METHODS: Extracranial color duplex sonography using harmonic frequencies enables visualization of even single ultrasound contrast agent microbubbles because of oscillation. Patients with stroke and positive RLS findings on transesophageal echocardiography underwent a simultaneous extracranial and transcranial sonographic examination of the proximal common carotid artery (CCA) and middle cerebral artery (MCA) on the same side. A Valsalva strain was performed for 10 seconds after intravenous bolus injection of a galactose-based nontranspulmonary contrast agent. The B-mode frame sequences of the transverse plane of the CCA obtained by harmonic ECS and the ce-TCDS recordings of high-intensity transient signals from the MCA were analyzed offline. RESULTS: In all patients with RLS, the shunts could be identified by harmonic ECS. A close correlation could be seen between the count of visualized microbubbles in the CCA and the number of high-intensity transient signals detected on ce-TCDS in the ipsilateral MCA. CONCLUSIONS: The results of this study indicate that contrast-enhanced ultrasound harmonic imaging of the CCA using a Valsalva strain might be an optional screening tool for detection of cardiac RLS in patients with insufficient acoustic bone windows.

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.

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.

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.

Fate of left atrial thrombi in patients with atrial fibrillation determined by transesophageal echocardiography and cerebral magnetic resonance imaging.

Patients with atrial fibrillation (AF) and atrial thrombi have an increased risk for cerebral embolism. However, there is little knowledge about the long-term fate of atrial thrombi and the incidence of cerebral embolism in patients receiving continued oral anticoagulation. Forty-three consecutive patients with AF and atrial thrombi were enrolled in the study. Serial and prospective transesophageal echocardiographic studies, cranial magnetic resonance imaging (MRI), and clinical examinations were performed during a period of 12 months. Oral anticoagulation was continued or initiated in all patients. An international normalized ratio of 2.0 to 3.0 was regarded as effective. During follow-up, 56% of the thrombi disappeared (7 [16%] at 1 month, 18 [42%] at 3 months, 21 [49%] at 6 months, and 24 [56%] at 12 months). Patients with the disappearance of thrombi had significantly smaller thrombi compared with patients with persistent thrombi (1.5 +/- 0.8 cm in length and 0.8 +/- 0.5 cm in width vs 1.9 +/- 0.6 cm in length and 1.3 +/- 0.4 cm in width, p = 0.04), reduced echogenicity of thrombi (46% vs 89%, p <0.01), and smaller left atrial (LA) volume (83 +/- 27 vs 116 +/- 55 cm(3)). Seven patients (16%) had embolic lesions during follow-up MRI. Six of these patients (86%) had clinically apparent embolisms, and 1 died from stroke. The only independent predictors of cerebral embolism were an elevated peak emptying velocity of the LA appendage (p <0.01) and previous thromboembolic events (p = 0.02). Patients with AF and atrial thrombi have a large likelihood of cerebral embolism (16%) and/or death despite oral anticoagulation therapy. Thrombus size may predict thrombus resolution under continued anticoagulation.

Solid and gaseous cerebral microembolization during off-pump, on-pump, and open cardiac surgery procedures.

BACKGROUND: Neurocognitive dysfunction remains a limitation of cardiac surgery with cardiopulmonary bypass. Intraoperative cerebral microembolization is believed to be one of the most important etiologic factors. Using a new generation of transcranial Doppler ultrasonography, we compared the number and nature of intraoperative microemboli in patients undergoing on-pump and off-pump cardiac surgery procedures. METHODS: Bilateral continuous transcranial Doppler monitoring of the middle cerebral arteries was performed in 45 patients (15 off-pump coronary artery bypass grafting, 15 on-pump coronary artery bypass grafting, and 15 open cardiac procedures). All recordings were performed using a multi-range, multifrequency system to allow both measurement of the number and discrimination of the nature of microemboli in the 3 different groups. RESULTS: The median number (interquartile range) of microemboli in the off-pump coronary artery bypass grafting, on-pump coronary artery bypass grafting, and open procedure groups were 40 (28-80), 275 (199-472), and 860 (393-1321), respectively (P <.01). Twelve percent of microemboli in the off-pump coronary artery bypass grafting group were solid compared with 28% and 22% in the on-pump coronary artery bypass grafting and open procedure groups, respectively (P <.05). In the on-pump groups, 24% of microemboli occurred during cardiopulmonary bypass, and 56% occurred during aortic manipulation (cannulation, decannulation, application, and removal of crossclamp or sideclamp). CONCLUSIONS: Cerebral microembolization is significantly reduced with avoidance of cardiopulmonary bypass. The majority of microemboli occurring during cardiac surgery are gaseous, with a higher proportion of solid microemboli in the on-pump group, and may have a different significance for cerebral injury than solid microemboli. The ability to reliably discriminate gas and solid microemboli may have an important role in the implementation of neuroprotective strategies.

[Embolic stroke with mobile thrombus in carotid artery induced by antiphospholipid antibody syndrome].

We report a 56-year-old woman suffering from an embolic brain infarction in her right frontal lobe. Carotid ultrasonogram showed a mass-shaped thrombus with little atherosclerotic change of underlying intima-media in the right common carotid artery. The thrombus was reduced with treatment and changed to mobile slender thrombus on admission. No other embolic sources were detected even using transesophageal echocardiography. Her blood test indicated existence of antiphospholipid antibody syndrome (APS) complicated with mixed connective tissue disease as an etiology of this uncommon carotid thrombus. The thrombus disappeared completely after two-week intensive antithrombotic therapy. This is a valuable report that arterial thrombi accompanied by APS could be detected by carotid ultrasound and observed until thrombus was disappeared. When we manage APS patients, it is important to rule out thrombus formation in the carotid artery using ultrasonography from the point of stroke prevention.

Cerebral microemboli and cognitive impairment.

Transcranial Doppler Ultrasound (TCD) may be used to detect cerebral microemboli in patient groups with an increased stroke risk and during invasive cardiovascular examinations and operations. Although these microemboli do not cause immediate symptoms, there is growing evidence which suggests that they may cause cognitive impairment if they enter the cerebral circulation in significant numbers. This has been studied in detail in patients who have had coronary artery bypass surgery. In these patients, an association has been found between the number of intraoperative cerebral microemboli detected by transcranial Doppler and postoperative neuropsychological outcome. It is also possible that cerebral microemboli may be the cause of cognitive impairment in patients with cerebrovascular disease. Cerebral microemboli are often found in patients with atherosclerosis, especially of the carotid arteries and aortic arch, and in patients with heart disease. There is also an increased risk for silent strokes and cognitive impairment in these patients. Prospective clinical studies are therefore required to determine if continuous cerebral microembolization to the brain will lead to progressive cognitive impairment.

Velocity of microemboli and transit time from the heart to the brain in patients with patent foramen ovale and artificial heart valves.

There is no information about the physical behavior of microemboli en route from their source to the cerebral vessels. Microemboli could abide to a certain laminae, and have a consistent velocity, or wander between different laminae, and keep changing their velocity. Two hundred and seventy four microemboli were recorded by transcranial Doppler (TCD) in six patients with artificial valves, and 119 microemboli were recorded in response to i.v. injection of saline agitated with air in eight patent foramen ovale (PFO) patients. Transit time of microemboli, calculated based on their arrival time at the cerebral vessel (site of monitoring) was explored as a possible function of their measured velocity at the detection point. In the PFO group, the relation between embolus velocity and transit time was: embolus velocityPFO = -41.8 * transit time + 100.6, whereas for the artificial heart valve group it was: embolus velocityValve = -22.6 * transit time + 67.1. Transit time, in both clinical groups, was inversely related to velocity (p < 0.001), thus, early appearing emboli had higher velocity and vice versa. The inverse relation between transit time and measured terminal velocity implies a consistent velocity per microemboli en route, in both groups. Thus, a flow abided to a certain laminae seems to characterize microemboli.