Transcranial Doppler Ultrasound Monitoring Research Articles

Application of quantitative electroencephalography in predicting early cerebral ischemia in patients undergoing carotid endarterectomy.

Quantitative electroencephalography (QEEG) has emerged as a promising monitoring method in cerebral ischemia, but the feasibility of QEEG in intraoperative cerebral perfusion-related ischemia monitoring is still uncertain. The purpose of this study was to investigate the value of QEEG monitoring in Carotid Endarterectomy (CEA) and the thresholds for intraoperative cerebral perfusion-related ischemia monitoring. Sixty-three patients who underwent carotid endarterectomy with continuous Transcranial Doppler ultrasound (TCD) monitoring and QEEG monitoring at Xuanwu Hospital Capital Medical University from January 2021 to August 2021 were enrolled in this study. Each patient received total intravenous anesthesia. Middle cerebral artery blood flow velocity (V-MCA) was obtained by TCD. Relative alpha percentage (RA) and alpha-delta ratio (ADR) were obtained by QEEG monitoring. Patients were divided into ischemic and non-ischemic groups using a decline of more than 50% in the V-MCA monitored by TCD as the gold standard. Of the 63 patients, twenty patients were divided into the ischemic group, and forty-three patients into the non-ischemic group. Ipsilateral post-clamp RA and ADR values of QEEG were decreased for all patients in the ischemic group. The optimal threshold for RA and ADR to predict cerebral ischemia was a 14% decrease from baseline (sensitivity 90.0%, specificity 90.7%, Kappa value 0.786), a 21% decrease from baseline (sensitivity 85.0%, specificity 81.4%, Kappa value 0.622), respectively, indicated by TCD monitoring. Our study demonstrated that QEEG is a promising monitoring method undergoing CEA under general anesthesia and has good consistency with TCD.

A One-Day Prospective National Observational Study on Sedation-Analgesia of Patients with Brain Injury in French Intensive Care Units: The SEDA-BIP-ICU (Sedation-Analgesia in Brain Injury Patient in ICU) Study.

Sedation/analgesia is a daily challenge faced by intensivists managing patients with brain injury (BI) in intensive care units (ICUs). The optimization of sedation in patients with BI presents particular challenges. A choice must be made between the potential benefit of a rapid clinical evaluation and the potential exacerbation of intracranial hypertension in patients with impaired cerebral compliance. In the ICU, a pragmatic approach to the use of sedation/analgesia, including the optimal titration, management of multiple drugs, and use of any type of brain monitor, is needed. Our research question was as follows: the aim of the study is to identify what is the current daily practice regarding sedation/analgesia in the management of patients with BI in the ICU in France? This study was composed of two parts. The first part was a descriptive survey of sedation practices and characteristics in 30 French ICUs and 27 academic hospitals specializing in care for patients with BI. This first step validates ICU participation in data collection regarding sedation-analgesia practices. The second part was a 1-day prospective cross-sectional snapshot of all characteristics and prescriptions of patients with BI. On the study day, among the 246 patients with BI, 106 (43%) had a brain monitoring device and 74 patients (30%) were sedated. Thirty-nine of the sedated patients (53%) suffered from intracranial hypertension, 14 patients (19%) suffered from agitation and delirium, and 7 patients (9%) were sedated because of respiratory failure. Fourteen patients (19%) no longer had a formal indication for sedation. In 60% of the sedated patients, the sedatives were titrated by nurses based on sedation scales. The Richmond Agitation Sedation Scale was used in 80% of the patients, and the Behavioral Pain Scale was used in 92%. The common sedatives and opioids used were midazolam (58.1%), propofol (40.5%), and sufentanil (67.5%). The cerebral monitoring devices available in the participating ICUs were transcranial Doppler ultrasound (100%), intracranial and intraventricular pressure monitoring (93.3%), and brain tissue oxygenation (60%). Cerebral monitoring by one or more monitoring devices was performed in 62% of the sedated patients. This proportion increased to 74% in the subgroup of patients with intracranial hypertension, with multimodal cerebral monitoring in 43.6%. The doses of midazolam and sufentanil were lower in sedated patients managed based on a sedation/analgesia scale. Midazolam and sufentanil are frequently used, often in combination, in French ICUs instead of alternative drugs. In our study, cerebral monitoring was performed in more than 60% of the sedated patients, although that proportion is still insufficient. Future efforts should stress the use of multiple monitoring modes and adherence to the indications for sedation to improve care of patients with BI. Our study suggests that the use of sedation and analgesia scales by nurses involved in the management of patients with BI could decrease the dosages of midazolam and sufentanil administered. Updated guidelines are needed for the management of sedation/analgesia in patients with BI.

The Monitoring and Application of Transcranial Doppler Ultrasound in Patients with Severe Neurovascular Diseases

To investigate the monitoring effect and application of transcranial Doppler ultrasound (TCD) in patients with severe neurovascular cerebrovascular diseases. From December 2016 to October 2018, 96 patients with cerebrovascular disease in Department of Neurology and ICU, West China Hospital, Sichuan University were monitored by bedside TCD, including the detection of bilateral middle cerebral arteries (MCAs) through temporal window, and the detection of the basilar artery (BA) through occipital window, characterized by the peak systolic blood flow velocity, peak diastolic blood flow velocity, average peak blood flow velocity, vascular pulsatility index, vascular pulsatility index, vascular resistance index and blood flow spectrum morphology in local hemodynamic changes. According to the monitoring results, it was divided into vasospasm group, increased blood flow group and insufficient blood supply group. Relevant data of monitoring results were analysed. Bedside TCD monitoring was successfully used to all cerebrovascular diseases patients. Among 96 patients, 37 patients (38.54%) had increased cerebral blood flow, 15 patients (15.62%) had cerebral vasospasm, and 93 patients had insufficient cerebral blood supply (90.62%, including insufficient blood supply to the MCA and BA). Patients mainly with cerebral aneurysm and hypertensive intracerebral hemorrhage types contributed the highest proportion of insufficient blood supply, followed by the increase of blood flow, and the incidence of vasospasm was relatively low. In cerebral aneurysm group and hypertensive intracerebral hemorrhage group, and differences in the incidence of insufficient blood supply, increased blood flow, and vasospasm were statistically significant ( P<0.05). The bedside TCD monitoring can assess the patient's craniocerebral hemodynamic information and provide a clinical guidance.

Cerebral Microembolization in Left Ventricular Assist Device Associated Ischemic Events

IntroductionThe significance of microembolic signals (MES) detected by transcranial Doppler ultrasound emboli monitoring (TCD-e) in patients supported with left ventricular assist devices (LVAD) remains unclear. We aimed to investigate the relationship between cerebral microembolization detected by TCD-e and acute ischemic events in LVAD patients. MethodsWe reviewed consecutive patients with acute ischemic stroke or transient ischemic attack (TIA) in a prospectively collected database of LVAD patients. TCD-e exams consisted of monitoring the middle cerebral arteries for microembolic signals (MES) over 30 minutes. ResultsOf 515 persons with LVAD, 41 TCD-e studies were performed in 35 patients with acute ischemic stroke or transient ischemic attack (TIA) in a median of 1 day (Interquartile range [IQR]: 0-2) after the event. MES were present in 15 (44%) TCD-e studies with a median MES count of 4 (IQR: 2-15.5). Bloodstream infections were more common in patients with MES (38% versus 8%, P = .039). There were trends for lower international normalized ratio (1.39 versus 1.69, P = .214), lower activated partial thromboplastin (33.2 versus 36.6, P = .577), higher lactate dehydrogenase (531 versus 409, P = .323) and a higher frequency of pump thrombosis (13% versus 8%, P = .637) in patients with MES compared with those without MES. ConclusionsLVAD patients with acute ischemic stroke or TIA have a high prevalence of MES on TCD-e, which may serve as a marker for a prothrombotic state. Further study of MES in LVAD patients is warranted.

SIGNIFICANTLY LOWER RIGHT MIDDLE CEREBRAL ARTERY BLOOD FLOW VELOCITY IN THE FIRST EPISODE OF PSYCHOSIS DURING NEUROCOGNITIVE TESTING

Changes in cerebral hemodynamics have been reported in schizophrenia and proposed as underlying the cognitive deficits seen in patients. The objective of our study was to compare changes of the cerebral blood flow velocity (BFV) during neurocognitive tasks between the patients with the first episode of psychosis and healthy controls. We recruited 46 patients with the first episode of psychosis (FEP), admitted to the University Hospital Centre Zagreb during 2016-2017 and 41 control subjects. Transcranial Doppler ultrasonography monitoring of BFV in both middle cerebral arteries was recorded during 25-minute long neurocognitive assessment with Phonemic Verbal Fluency test, Trial Making Test B and Stroop test. Between every consecutive test resting periods were recorded. After the adjustment for age, sex and education by quantile regression, patients with FEP had significantly lower BFV in middle cerebral arteries during the 3rd (Δ-15, Δ%-28% p=0.023) and 4th task (Δ-15, Δ%-28% p=0.031) of the Stroop test and the 1st task of Foot tapping test (Δ -16, Δ% -30% p=0.034). We observed significantly lower changes of right middle cerebral artery BFV in FEP between two consecutive tests in all four tasks of the Phonemic verbal fluency test, 1st and 2nd task of the Stroop test and Trail making test, and the1st task of Foot tapping test; and of the left artery between first three tasks of the Phonemic verbal fluency test, the last one of the Phonemic verbal fluency test and all first three tasks of the Stroop test. Decreased middle BFV during the execution of particular neurocognitive tasks in patients with FEP, compared to control subjects might indicate impaired hemodynamic function in the prefrontal/parietal brain areas, and possibly provide an explanation of some of the observed neurocognitive deficits in patients with the first episode of psychosis.

Abstract WP113: Evidence of Ongoing Platelet Activation in Micro-emboli Negative Recently Symptomatic versus Asymptomatic Carotid Stenosis

Introduction: Cerebral microembolic signals (MES) predict increased stroke risk in carotid stenosis however micro-emboli negative symptomatic patients also demonstrate increased risk compared to asymptomatic patients. Enhanced platelet activation may contribute to this risk disparity. Methods: We performed a prospective, observational analytical study assessing platelet counts, platelet activation status, and the relationship between platelet activation and MES in asymptomatic versus symptomatic moderate (≥50-69%) or severe (≥70-99%) carotid stenosis. Full blood count measurements were performed, and whole-blood flow cytometry used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous Transcranial Doppler (TCD) ultrasound monitoring of the middle cerebral arteries was performed to classify patients’ MES status. Results: Complete TCD data from 28 asymptomatic patients were compared with 35 symptomatic patients in the ‘early phase’ (≤4 weeks) and 30 of these patients in the ‘late phase’ (≥3 months) after TIA/ischaemic stroke. The %MES positive patients were higher in early symptomatic (31.4%; P = 0.027), but not in late symptomatic (6.7%; P = 0.996) vs. asymptomatic patients (7.1%). There were no significant differences in platelet counts, mean platelet volume, %CD62P or %CD63 expression between early/late symptomatic and asymptomatic MES negative patients (P&gt;0.05). There were however, a significantly higher %circulating lymphocyte-platelet complexes in early symptomatic vs. asymptomatic patients (2.7% vs. 2.17%;P=0.02) Discussion: Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in carotid stenosis.

Frequency and clinical course of cerebral embolism in patients undergoing transcatheter left atrial appendage closure.

The aim of this study was to assess silent and clinically apparent cerebral embolic events in patients undergoing transcatheter left atrial appendage closure. In this prospective single-centre study, 28 patients underwent percutaneous closure of the left atrial appendage. In all patients, a diffusion-weighted magnetic resonance imaging (DW-MRI) study was performed before, the day after the procedure, and during routine follow-up after 45 days. All patients underwent neurological assessment at the time of DW-MRI. Additionally, transcranial Doppler ultrasound monitoring (TCD) for the detection of microembolic material during the procedure was performed. The procedure was successfully completed in all patients. New embolic lesions were detected in nine patients (32%) after the procedure, of which three (33%) were detectable as gliotic lesions at follow-up. One (3.6%) new lesion was observed at 45-day follow-up. Neurological assessment showed no neurological deficits. We observed no relationship between the numbers of microembolic signals on TCD monitoring and the occurrence of cerebral infarctions on DW-MRI. New cerebral embolic events occur after transcatheter closure of the left atrial appendage. However, most of the lesions demonstrate no gliotic transformation at follow-up. In all patients, the cerebral lesions were clinically unapparent.

Assessment of ‘on-treatment platelet reactivity’ and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis

IntroductionThe relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients. MethodsConsecutive eligible patients with ≥50% asymptomatic or recently symptomatic carotid stenosis (≤4weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the ‘late’ phase (≥3months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100® to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES +ve or MES −ve. Results31 patients with ≥50% asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of ‘high on-treatment platelet reactivity’ (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in ‘symptomatic post-intervention’ than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p=0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63% vs. 34%; p=0.017), including those on aspirin monotherapy (p=0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES +ve or MES −ve patients. DiscussionCarotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients.

Clinical Development and Implementation of an Institutional Guideline for Prospective EEG Monitoring and Reporting of Delayed Cerebral Ischemia.

Delayed cerebral ischemia (DCI) is the most common and disabling complication among patients admitted to the hospital for subarachnoid hemorrhage (SAH). Clinical and radiographic methods often fail to detect DCI early enough to avert irreversible injury. We assessed the clinical feasibility of implementing a continuous EEG (cEEG) ischemia monitoring service for early DCI detection as part of an institutional guideline. An institutional neuromonitoring guideline was designed by an interdisciplinary team of neurocritical care, clinical neurophysiology, and neurosurgery physicians and nursing staff and cEEG technologists. The interdisciplinary team focused on (1) selection criteria of high-risk patients, (2) minimization of safety concerns related to prolonged monitoring, (3) technical selection of quantitative and qualitative neurophysiologic parameters based on expert consensus and review of the literature, (4) a structured interpretation and reporting methodology, prompting direct patient evaluation and iterative neurocritical care, and (5) a two-layered quality assurance process including structured clinician interviews assessing events of neurologic worsening and an adjudicated consensus review of neuroimaging and medical records. The resulting guideline's clinical feasibility was then prospectively evaluated. The institutional SAH monitoring guideline used transcranial Doppler ultrasound and cEEG monitoring for vasospasm and ischemia monitoring in patients with either Fisher group 3 or Hunt-Hess grade IV or V SAH. Safety criteria focused on prevention of skin breakdown and agitation. Technical components included monitoring of transcranial Doppler ultrasound velocities and cEEG features, including quantitative alpha:delta ratio and percent alpha variability, qualitative evidence of new focal slowing, late-onset epileptiform activity, or overall worsening of background. Structured cEEG reports were introduced including verbal communication for findings concerning neurologic decline. The guideline was successfully implemented over 27 months, during which neurocritical care physicians referred 71 SAH patients for combined transcranial Doppler ultrasound and cEEG monitoring. The quality assurance process determined a DCI rate of 48% among the monitored population, more than 90% of which occurred during the duration of cEEG monitoring (mean 6.9 days) beginning 2.7 days after symptom onset. An institutional guideline implementing cEEG for SAH ischemia monitoring and reporting is feasible to implement and efficiently identify patients at high baseline risk of DCI during the period of monitoring.

Acute effects of intraventricular nicardipine on cerebral hemodynamics: A preliminary finding

ObjectiveIntraventricular nicardipine (IVTN) is a treatment option for severe vasospasm in patients with subarachnoid hemorrhage (SAH). However, its acute effects on cerebral hemodynamics have not been studied in detail. MethodsBetween June 2008 and December 2010, IVTN was administered (mainly 4mg every 8h) to 11 SAH patients (54 doses) with multimodality monitoring for refractory vasospasm. Retrospective analyses on physiological parameters were made from baseline and up to 6h after IVTN injection. Statistical analysis was performed with a mixed-effects model. ResultsMean intracranial pressure (ICP) increased slightly, reaching its peak at 20min after IVTN injection (2.5±0.9mmHg (mean±standard error), P<0.01), and decreased gradually thereafter over the next hour. Mean cerebral perfusion pressure transiently decreased 20–30min after injection (3.7±1.8mmHg, P<0.05). Mean arterial pressure, partial pressure of brain oxygen tension (PbtO2), cerebral blood flow (CBF), autoregulation indices did not change significantly. Lactate/pyruvate ratio and glucose remained stable. One patient underwent transcranial Doppler ultrasonography monitoring while on IVTN, which showed a transient increase in mean flow velocity with concomitant decrease in Pulsatility index, suggesting vasodilation in the distal resistance vessels. ConclusionsThe vasodilatory effect of IVTN transiently increased ICP, but did not significantly affect PbtO2, CBF or oxidative glucose metabolism in the immediate phase after injection.

Evaluation of cerebrovascular reserve in patients undergoing carotid artery stenting and its usefulness in predicting significant hemodynamic changes during temporary carotid occlusion.

We investigated the usefulness of cerebrovascular reserve (CVR) testing to predict severe hemodynamic changes during proximally protected carotid artery stenting. Of 90 patients referred, 63 eligible underwent complete evaluation of the extent of carotid artery disease and transcranial Doppler ultrasound (TCD) assessment of CVR by means of a breath-holding test and ophthalmic artery flow pattern evaluation. Periprocedural TCD monitoring of the ipsilateral middle cerebral artery flow was performed in 24 patients undergoing proximally protected procedure (requiring induction of flow arrest within internal carotid artery). Abnormal CVR was significantly less common in patients with unilateral compared to bilateral carotid artery disease (26.3 % vs. 76.9 %, p=0.02), while ophthalmic artery flow reversal was rare in patients with unilateral carotid artery disease (2.5 % vs. 42.9 %, p<0.01). During the induction of carotid flow arrest, the average mean flow velocity drop following external carotid artery occlusion was low (3.5 %, p=0.67) compared to the induction of complete flow arrest (32.8 %, p<0.01). Six patients had a total mean flow velocity drop >50 %, including 2 patients with normal pre-procedural CVR. Our results suggest that TCD evaluation of CVR is not a reliable predictor of hemodynamic changes induced during proximally protected carotid artery stenting in patients with unilateral carotid artery disease.

Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli

IntroductionThe importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively...

Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic‐signal‐negative patient subgroups

von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown. In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4weeks) and 'late' (≥3months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative. Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8μg/ml; P<0.001), late (10.6μg/ml; P=0.01) and late post-intervention (10.6μg/ml; P=0.038) symptomatic patients than asymptomatic patients (8.9μg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P=0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0μg/ml; P<0.001) than asymptomatic MES-negative patients. Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study.

Clinical study of cerebral hyperperfusion following carotid endarterectomy according to transcranial Doppler ultrasonography monitoring

Objective To investigate clinical features of cerebral hyperperfusion following carotid endarterectomy (CEA), and to explore the effect of treating cerebral hyperperfusion following CEA according to transcranial Doppler ultrasonography (TCD) monitoring. Methods Sixty-three CEAs were performed under general anesthesia from January to August 2013 and TCD monitoring was performed during the surgery. Carotid shunts were applied on the basis of TCD monitoring. Cerebral hyperperfusion and cerebral hyperperfusion syndrome (CHS) following CEA were determined and treated according to perioperative TCD monitoring. Results Postoperative three-dimensional CTA confirmed that carotid artery stenosis was released in all of those patients. During 30 d after CEA, one patient (1.59%) suffered mild ischemic stroke, one patient (1.59%) myocardial infarction, and one patient (1.59%) hoarseness. There was no cases of cerebral hemorrhage or death. Four patients (6.35%) suffered cerebral hyperperfusion following CEA, lasting for 1-3 d, and among them one patient (1.59%) suffered CHS, the clinical symptoms of which included excitement, hallucination and sleep disorder. In 3 cases (4.76% ), postoperative visual acuity improved significantly, and among them one patient suffered cerebral hyperperfusion. Conclusions TCD monitoring could detect intraoperative and postoperative cerebral hyperperfusion early. On the basis of TCD monitoring, blood pressure control is the key for reducing postoperative intracranial hemorrhage. doi：10.3969/j.issn.1672-6731.2014.01.007 Video: http://www.cjcnn.org/index.php/cjcnn/pages/view/v14n1a7

Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study

Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed. University teaching hospitals. This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic vs. early (≤4weeks after TIA/stroke) and late phase (≥3months) symptomatic moderate or severe (≥50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1h to classify patients as MES positive or MES negative. Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients were followed up to the late phase after symptom onset. The median platelet count (211 vs. 200×10(9) L(-1) ; P=0.03) and the median percentage of lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%; P=0.001). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients with ≥70% carotid stenosis (P=0.0005) and symptomatic patients recruited within 7days of symptom onset (P=0.028). Complete TCD data were available in 25 asymptomatic, 31 early phase symptomatic and 27 late phase symptomatic patients. Twelve per cent of asymptomatic vs. 32% of early phase symptomatic (P=0.02) and 19% of late phase symptomatic patients (P=0.2) were MES positive. Early symptomatic MES-negative patients had a higher percentage of lymphocyte-platelet complexes than asymptomatic MES-negative patients (2.8 vs. 2.3%; P=0.0085). Recently, symptomatic carotid stenosis patients have had higher platelet counts (potentially reflecting increased platelet production, mobilization or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients.

Abstract WP410: Comparison of Transcranial Doppler Ultrasound with Intracardiac Echocardiography in the Detection of Cardiac Right-to-Left shunt in Children and Young Adults

Background and Objectives: Right to left shunts (RLS) found with patent foramen ovale are implicated in the pathophysiology of cryptogenic stroke, migraine headaches as well as decompression illness. Our dysautonomia clinic has described a syndrome of neurocardiogenic syncope, stroke, migraine headaches and positive tilt table testing associated with atrial septal defects (ASD). All patients underwent transcranial Doppler ultrasound (TCD) and intracardiac echocardiogram (ICE) testing. Methods: We performed a restrospective analysis of a prospectively obtained registry of patients that underwent shunt testing ± endovascular ASD closure. All patients had previously undergone a transthoracic echocardiogram bubble study (TTE) to confirm a RLS. Patients underwent general anesthesia and bilateral TCD monitoring of the middle cerebral artery. Valsalva was produced by the anesthesiologist (40mm Hg). Simultaneous assessment of RLS was performed using ICE and TCD monitoring after injection of agitated saline into the femoral vein sheath. If negative, a direct right atrial injection was performed. The size of ASD was measured by ICE independent of TCD results. Results: Between 9/2010 and 7/2012, 112 patients underwent testing. Patient characteristics are displayed in the table. RLS was found in 82.1, 81.1, and 71.4% by TTE, ICE and TCD, respectively. After peripheral injection (n=85), when compared to ICE, TCD had a sensitivity, specificity, PPV, NPV and accuracy of 96, 100, 100, 64 and 95%, respectively. Combined peripheral and intracardiac injections (N=112) when compared to ICE, TCD had a sensitivity, specificity, PPV, NPV and accuracy of 89, 100, 100, 66 and 90%, respectively. Conclusion: Transcranial Doppler ultrasound detection of right to left shunts remains a highly accurate, non-invasive tool. If closure of cardiac shunts is proven to prevent stroke, migraines or treat neurocardiogenic syncope, TCD might be considered the preferred screening method.

Timing and mechanism of ischemic stroke due to extracranial blunt traumatic cerebrovascular injury

Extracranial cerebrovascular injury is believed to be an important cause of neurological injury in patients who have suffered blunt trauma. The authors sought to determine the timing and mechanisms of ischemic stroke in patients who suffered traumatic cerebrovascular injury (TCVI). This is a prospective study of all patients with TCVI who were admitted to a Level I trauma center during a 28-month period. All patients who suffered blunt trauma and had risk factors for TCVI underwent screening CT angiography (CTA) of the head and neck on admission. All patients with either an ischemic stroke or CTA suggesting TCVI underwent confirmatory digital subtraction angiography (DSA). Patients with DSA-confirmed TCVI were treated with 325 mg aspirin daily; all patients were observed during their hospitalization for the occurrence of new ischemic stroke. In addition, a subset of patients with TCVI underwent transcranial Doppler ultrasonography monitoring for microembolic signals. A total of 112 patients had CTA findings suggestive of TCVI; 68 cases were confirmed by DSA. Overall, 7 patients had an ischemic stroke in the territory of the affected artery prior to or during admission. Four of the patients had their event prior to diagnosis with CTA and 2 occurred prior to DSA. In 1 patient the ischemic stroke was found to be due to an extracranial atherosclerotic carotid plaque, and this patient was excluded from further analysis. All patients with ischemic stroke had brain CT findings consistent with an embolic mechanism. Two (8.7%) of 23 monitored patients with TCVI had microembolic signals on transcranial Doppler ultrasonography. Most ischemic strokes due to TCVI are embolic in nature and occur prior to screening CTA and initiation of treatment with aspirin.

The effect of formal training on the clinical utility of transcranial Doppler ultrasound monitoring in patients with aneurysmal subarachnoid haemorrhage

We have previously shown that the clinical utility of transcranial Doppler (TCD) ultrasound monitoring for vasospasm in patients with aneurysmal subarachnoid haemorrhage, as performed by untrained operators in a busy neurosurgical unit, is questionable, despite the recommendations for its use in the literature. We determined if formal training improved the utility of TCD. Twelve untrained operators and one trained operator performed a total of 206 TCD examinations. There was poor agreement of results between trained and untrained operators. For the left middle cerebral artery (MCA), right MCA, left anterior cerebral artery (ACA) and right ACA, the blood flow velocities (BFV) recorded by the trained operator were greater than those recorded by the untrained operators by a mean (95% confidence interval) of 27.7 (25.0–30.4), 24.3 (21.4–27.1), 28.2 (25.6–30.9) and 28.1 (24.9–31.1) cm/s, respectively (p<0.001 for all vessels). Greater sensitivity was observed in TCD measurements from the trained operator (100%) compared to untrained operators (40%). To improve the utility of TCD, operators should be provided with training or a professional sonographer employed.

Microembolus Detection by Transcranial Doppler Ultrasound Monitoring (P07.037)

Objective: To evaluate the presence of Microembolic Signals (MES) in stroke and transient ischemic attacks, using Transcranial Doppler ultrasound monitoring. Background TCD is a sensitive technique for real time detection of MES which are characterized by unidirectional, high intensity, short duration, random occurrence, and a whistling sound. MES have been detected in carotid artery stenosis, aortic arch plaques, atrial fibrillation, myocardial infarction, prosthetic heart valves, patent foramen ovale, valvular stenosis, during invasive procedures (angiography, percutaneous transluminal angioplasty) and surgery (carotid and cardiopulmonary bypass). Design/Methods: Prospective, observational cross sectional study from Chennai, India of 3200 consecutive stroke or Transient Ischemic Attacks and acute stroke patients seen from 2000 till 2010 at Chennai. Bilateral TCD monitoring were done by insonation of Temporal windows, using the Mark II head frame and Power M Mode TCD machine (PMD100, Spencer Technologies, USA) to detect MES. TCD findings were correlated with magnetic resonance imaging and Angiography (MRI/MRA), computed tomography angiography (CTA), and digital subtraction angiography (DSA). Results: MES was detected in 35 % of patients with symptomatic and in 12.8 % with asymptomatic carotid stenosis. The absolute annual risk of ipsilateral stroke or transient ischaemic attack from baseline and 3 years was 12 % and 6.24 % in patients with and without symptomatic carotid stenosis. 38.4% had MES during carotid endarterectomy and 44 % during carotid angioplasty and stenting. During Sonothrombolysis, MES at the site of arterial obstruction were seen in 22 % and was associated with good outcome (modified Rankin Scale of less than 2). Intracranial stenosis with MES were detected in 22.6 %. Conclusions: Detection of MES by transcranial Doppler, indicates patients with increased risk of stroke. The prence of MES during sonothrombolysis is an indicator of good outcome. A high frequency of MES is observed during Carotid revascularization procedures and intracranil arterial stenosis. Disclosure: Dr. Sivakumar has nothing to disclose. Dr. Sivakumar has nothing to disclose.

Increased Lymphocyte-Platelet Complex Formation as a Measure of Enhanced Platelet Activation in Recently Symptomatic Versus Asymptomatic 'Microembolic Signal Negative' Carotid Stenosis Patients - Results from the Platelets and Carotid Stenosis (PACS) Study (IN3-2.004)

Objective: We hypothesised that patients with more marked platelet activation would have a greater number of MES in the ipsilateral middle cerebral artery than those with less marked platelet activation. Background Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis patients. However, the relationship between MES and platelet activation status in symptomatic vs asymptomatic carotid stenosis has not been comprehensively assessed. Design/Methods: This pilot, observational analytical study compared MES and platelet activation status in early (≤4 weeks after TIA/stroke) and late phase (≥3 months) symptomatic versus asymptomatic moderate or severe (≥50%) carotid stenosis patients. Whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P & CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1 hour to classify patients as MES+ve or MES-ve. Results: Complete data were available in 31 early phase symptomatic, 27 late phase symptomatic (19 post-carotid intervention), and 25 asymptomatic carotid stenosis patients. 32% of early phase and 19% of late phase symptomatic patients vs 12% of asymptomatic patients were MES+ve (p ≥ 0.07). Early symptomatic MES-ve patients had higher % lymphocyte-platelet complexes than asymptomatic MES-ve patients (2.8 vs 2.3%; p=0.0085). Within the symptomatic subgroup, CD63 expression was lower in early phase MES+ve than MES-ve patients (5.88 vs 14.5%; p=0.0028), but higher in late phase MES+ve than MES-ve patients (12.8 vs 10.0%; p=0.023). Conclusions: Increased lymphocyte-platelet complex formation in recently symptomatic compared with asymptomatic MES-ve patients indicates enhanced platelet activation status in this early symptomatic subgroup. The lack of statistically significant differences in 9MES positivity9 between early symptomatic and asymptomatic patients may reflect a type II error. Larger longitudinal studies are needed to determine whether platelet biomarkers aid risk-stratification in patients with symptomatic and asymptomatic carotid stenosis. Disclosure: Dr. Kinsella has nothing to disclose. Dr. Tobin has nothing to disclose. Dr. Tierney has nothing to disclose. Dr. Feeley has nothing to disclose. Dr. Egan has nothing to disclose. Dr. Collins has nothing to disclose. Dr. Coughlan has nothing to disclose. Dr. O9Neill has nothing to disclose. Dr. Harbison has nothing to disclose. Dr. Doherty has received personal compensation for activities with UCB Pharamaceuticals, Eiasi, and Jansen-Cilag. Dr. Madhavan has nothing to disclose. Dr. Moore has nothing to disclose. Dr. O9Neill has nothing to disclose. Dr. Murphy has nothing to disclose. Dr. Saqqur has nothing to disclose. Dr. Hamilton has nothing to disclose. Dr. Mccabe has nothing to disclose.