Diagnostic Transcranial Doppler Research Articles

Impact of Transcranial Doppler Ultrasound on Logistics and Outcomes in Stroke Thrombolysis: Results From the SITS-ISTR.

Diagnostic transcranial Doppler ultrasound (TCD) is commonly used in patients with acute stroke before or during treatment with intravenous thrombolysis (IVT). We aimed to assess how much TCD delays IVT initiation and whether TCD influences outcomes. We analyzed data from the SITS-ISTR (Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register) collected from December 2002 to December 2011. Outcomes were door-to-needle time, symptomatic intracerebral hemorrhage, functional outcome per the modified Rankin Scale, and mortality at 3 months. In hospitals performing any TCD pre-IVT, 1701 of 11 265 patients (15%) had TCD before IVT initiation. Door-to-needle time was higher in patients with pre-IVT TCD (74 versus 60 minutes; P<0.001). At hospitals performing any TCD during IVT infusion, of 9044 patients with IVT, 747 were examined with TCD during IVT. No treatment delay was seen with TCD during IVT. After multivariate adjustment, TCD during IVT was independently associated with modestly increased excellent functional outcome (modified Rankin Scale, 0-1; adjusted odds ratio, 1.28; 95% confidence interval, 1.06-1.55; P=0.012) and lower mortality (adjusted odds ratio, 0.73; 95% confidence interval, 0.55-0.95; P=0.022). We recommend that TCD, if performed, should be done during IVT infusion, to avoid treatment delay. The association of hyperacute TCD with beneficial outcomes suggests potential impact on patient management, which warrants further study.

The Combination of Clinical Features, Transcranial Doppler, and Alberta Stroke Program Early Computed Tomography Score (Computed Tomography Angiography) in Predicting Outcome in Intravenous Recombinant Tissue Plasminogen Activator-Treated Patients

Little data exist on using combined baseline clinical neuroimaging and transcranial Doppler (TCD) information in predicting clinical outcome in stroke patients treated with intravenous (IV) thrombolysis. Stroke patients received IV recombinant tissue plasminogen activator (rt-PA) and had diagnostic TCD within 3 hours of symptom onset. The TCD result was interpreted using the thrombolysis in brain ischemia (TIBI) flow grading system. Following multiple regression analysis, a grading system was created with 1 point for each of the following: National Institutes of Health Stroke Scale (NIHSS) score of 16 or higher, TIBI score of 1 or lower, and Alberta Stroke Program Early CT Score (ASPECTS) of 6 or lower. The patients' scores were compared to modified Rankin Scale (mRS) scores at 90 days. A total of 349 patients were included. In unvaried analysis, age of 80 years or older (P = .002), an ASPECTS of 6 or lower (P < .001), an NIHSS score of 16 or higher (P < .001), a TIBI score of 1 or lower (P < .001), and a glucose level ≥ 200 mg/dl (P = .04) were associated with poor outcome (mRS score > 2). In the multiple regression analysis, age of 80 years or older, an ASPECTS of 6 or lower, an NIHSS score of 16 or higher, and hyperglycemia were predictors of poor outcome (P < .05). Based on our scoring system, the patients' odds ratios for poor outcome were 7 (95% confidence interval [CI]: 2-23, P = .003), 8 (95% CI: 3-25, P < .001), and 24 (95% CI: 4-151, P = .001) for scores of 1, 2, and 3, respectively, after adjustment for common stroke risk factors. The mean time to recanalization increased as the score increased (score of 0: 160 ± 45 minutes versus score of 3: 186 ± 38 (P = .70). A multimodal grading system is useful in predicting outcome in patients treated with IV rt-PA. Those withhigher scores might be candidates for interventional therapy.

Diagnostic TCD for intracranial stenosis in acute stroke patients: experience from a tertiary care stroke center in Karachi, Pakistan.

BackgroundStroke is a common cause of morbidity and mortality around the world. Intracranial large artery atherosclerosis (ICAD) is a frequent etiology of stroke in the South Asian population. There is a need for widely available screening tools to identify patients that are at high risk of stroke due to ICAD for aggressive risk management. This study describes the experience of using the transcranial Doppler (TCD) as a screening tool for this purpose at a tertiary care hospital in a developing country.Methods86 Patients admitted with stroke due to ICAD underwent TCD for six arteries (Right and left middle cerebral arteries, right and left anterior cerebral arteries, right and left posterior cerebral arteries) in addition to the magnetic resonance angiography (MRA) that is done routinely at the stroke center. Arteries were labeled with either <50 or >50% stenosis by TCD using two separate criteria. These findings were compared with those from the MRA which was used as the gold standard. The proportion of patients that had complete exams (all six arteries insonated by TCD) was reported. The success rate of each TCD criteria in detecting arteries with >50% stenosis was also calculated.ResultsThere was an attempt to visualize 516 arteries (86 patients with 6 arteries each) of which 375 (72.7%) were successfully insonated. 38 of the 86 (55.8%) patients had complete examinations. MRA reported 43 (8.3%) arteries as stenosed >50%. The TCD did not categorize any artery as stenosed using either criterion and hence failed to classify any stenosed artery correctly. The positive predictive and sensitivity was 0 for this study and the negative predictive value was 93.3%.ConclusionsThis study indicates the poor sensitivity of TCD to be a reliable screening tool for the presence of ICAD in the South Asian population in a real life clinical setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1289-3) contains supplementary material, which is available to authorized users.

Increased Pulsatility of the Intracranial Blood Flow Spectral Waveform on Transcranial Doppler Does Not Point to Peripheral Arterial Disease in Stroke Patients

Peripheral arterial disease (PAD) is common in patients with acute cerebral ischemia. Indexes of resistance derived from the systolic and diastolic velocities are routinely used in diagnostic transcranial Doppler (TCD) to detect intracranial arterial disease. We sought to explore whether these indexes can predict the presence of PAD in acute cerebral ischemia. We prospectively evaluated consecutive patients with acute cerebral ischemia. On TCD, peak-systolic and end-diastolic velocities in both middle cerebral and basilar arteries were manually measured to calculate pulsatility index (PI) and resistance index (RI). Increased resistance was defined as PI equal to 1.2 or more and RI equal to .75 or more. Ankle-brachial index (ABI) measurements were performed and an ABI equal to .9 or more was considered predictive of definite PAD. We included 95 patients (45 male, 50 female) aged 66 ± 9 years with a median National Institutes Health Stroke Scale score of 3 (interquartile range, 8) points. The ABI was abnormal and consistent with definite PAD in 24 of 95 (25.3%; 95% confidence interval [CI], 16.4-34.2) patients. Increased PI did not differ among patients with and without PAD (20.8% vs. 28.2%, P = .60). Only 1 patient with PAD had increased RI as opposed to 4 patients without PAD (4.2% vs. 5.6%, P = 1.0). Increased PI was not found to be an independent predictor of PAD (odds ratio [OR], .68; 95% CI, .22-2.12; P = .51). Increases in both PI and RI independently predicted arterial hypertension (OR, 1.62; 95% CI, 1.19-2.21; P = .002 and OR, 3.20; 95% CI, 1.51-6.77; P = .002, respectively). Our findings indicate that PAD cannot be inferred from intracranial flow parameters predictive of arterial disease and risk factors such as hypertension among patients with acute cerebral ischemia.

Sonothrombolysis: Is the story (t)old or just the beginning

Intravenous administration of recombinant tissue plasminogen activator, fastest and widely feasible treatment in acute ischemic stroke induces arterial recanalization, a prerequisite for neurological recovery. THE THERAPEUTIC ROLE OF ULTRASOUND AND POTENTIAL MECHANISM OF SONOTHROMBOLYSIS: Augmentation of recanalization can be achieved safely in combination with diagnostic transcranial Doppler by delivering mechanical pressure waves to the thrombus and exposing more thrombus surface to circulating drug. The addition of microspheres can further improve thrombolytic effect. International multicenter CLOTBUST trial showed that acute ischemic stroke patients treated with sonothrombolysis had higher rate of arterial recanalization and dramatic clinical recovery without increasing risk of symptomatic intracranial hemorrhage. A microsphere dose-escalation study called TUCSON showed that rates of recanalization and clinical recovery tended to be higher in target groups compared with controls. META-ANALYSIS OF CLINICAL TRIALS OF SONOTHROMBOLYSIS: Cochrane Stroke Group found that sonothrombolysis was likely to reduce death or dependency. A meta-analysis of sonothrombolysis showed that patients who received any form of sonothrombolysis had more than twofold higher likelihood of achieving complete arterial recanalization. PERSPECTIVES FOR SONOTHROMBOLYSIS - OPERATOR-INDEPENDENT DEVICE FOR SONOTHROMBOLYSIS: The collaborative group of the CLOTBUST trial designed multi-transducer assembly to cover conventional windows used for transcranial Doppler examinations. Operator-independent device can be quickly mounted by medical personnel with no prior experience in ultrasound. Sonothrombolysis for acute ischemic stroke is now tested in a pivotal efficacy multi-national trial called CLOTBUSTER. Ultrasound is a promising tool to enhance systemic thrombolysis.

Abstract TP254: Clot Dissolution Is Better With Ultrasound Assisted Thrombolysis For Fresh Clots With Higher Cholesterol Content

Background: Intravenous tissue plasminogen activator (IV-tPA) remains the only drug for arterial recanalization in acute ischemic stroke (AIS). Clot composition differs according to the stroke etiology- clot from heart being fresh and rich in fibrin while the clot from an ulcerated plaque is rich in cholesterol. These characteristics might influence the therapeutic response to tPA as well as ultrasound-enhanced thrombolysis. We evaluated the impact of cholesterol content and age of the clot on its dissolution with tPA and ultrasound in an in-vitro model. Methods: Clot was prepared by mixing horse blood with Calcium-chloride solution. Cholesterin was added to increase cholesterol level up to 100 mg/dL. Periodic serum replacement was used to ‘age’ the clot. The clots were exposed to continuous 2-MHZ diagnostic transcranial Doppler (TCD) ultrasound (acoustic intensity 340mW/cm2) during thromolysis with tPA (355 IU/ml). Efficiency of thrombolysis was calculated as the percentage of clot weight-loss after 60 minutes. Clot characteristics after lysis were evaluated with surface emission microscope (SEM). Results: Significant increase in the weight of clot occurred with its increasing age (from 2 to 10 hours, the clot-weight increased from 37.28±2.87mg to 51.56±5.34mg; p&lt;0.005). Exposure to ultrasound and tPA resulted in significant reduction in the clot-weight at 1 hour (from 35.50±3.23% to 24.71±2.11%; p&lt;0.005). Although, no significant differences were noted between clot-cholesterol levels and lysis with TCD or tPA alone, combination of these modalities induced significant lysis in clots with higher cholesterol levels (clot-weight reduced by 41.68±2.3%) as compared to clots with normal cholesterol (30.60±4.10%; p&lt;0.005). SEM demonstrated thicker and denser fibrin network in aged clots while higher number of activated platelets were noted on the surface of cholesterol-rich clots. Conclusion: Ultrasound-assisted thrombolysis with tPA work better for fresh thrombi with higher cholesterol levels. Our findings provide insights into the differential recanalization rates in acute ischemic stroke of various etiologies

Transcranial Doppler in acute stroke management – A “real-time” bed-side guide to reperfusion and collateral flow

Summary Introduction Assessment of cerebral hemodynamics with transcranial Doppler (TCD) can provide real-time, bed-side assessment of important prognostic variables in acute stroke such as the status of collateral flow and vessel recanalization status. In acute middle cerebral artery (MCA) occlusion, anterior cerebral artery (ACA) flow diversion (FD) is correlated with leptomeningeal collateral flow and may be a clinically useful prognostic indicator. Continuous TCD monitoring of MCA recanalization may also provide useful prognostic information including changes in flow pattern and the occurrence of microembolic signals (MES). We present studies examining associations between ACA FD, MCA recanalization and MES patterns on the characteristics of ischemia and infarction in acute MCA stroke. Methods Patients studied were consecutive sub-6 h from onset internal carotid artery (ICA) territory ischemic stroke cases. A subset of these cases with MCA occlusion were studied with 2 h of continuous MCA monitoring. All patients underwent baseline multimodal computed tomographic (CT) scanning, baseline diagnostic TCD, and 24 h post stroke magnetic resonance (MR) imaging. All MCA occlusion patients studied with continuous monitoring were treated with intravenous thrombolysis. ACA flow diversion was defined as ipsilateral mean velocity of 30% or greater than the contralateral artery. Recanalization status was assessed using the Thrombolysis In Brain ischemic (TIBI) grading system and MES counted “off-line” by experienced observers. Leptomeningeal collateralisation (LMC) was graded on CT angiography. Infarct core and penumbral volumes were defined using CT perfusion thresholds. Infarct volume, reperfusion, and vessel status were measured at 24 h using MR techniques. In patients undergoing recanalization monitoring, comparison was made between those with and without major reperfusion. Multivariable regression analysis was performed to assess for any associations between ACA flow diversion, TIBI grades and MES on infarction controlling for other important clinical variables. Results Flow diversion : 53 patients qualified for FD analysis. ACA FD was associated with good collateral flow on CT angiography ( p p p p Recanalization monitoring : 27 patients with MCA occlusion treated with intravenous thrombolysis were included in the analysis of recanalization patterns (16 cases with major reperfusion, 11 cases of non-reperfusion). Major TIBI grade improvement ( Δ ≥ 3 grades overall) was associated with major reperfusion ( p = 0.04) excellent 90 day clinical outcome ( p = 0.03), improvement in clinical outcome at 24 h ( p = 0.049) and attenuated infarct growth ( p = 0.06). MES did not associate with reperfusion status or outcome variables. Conclusions ACA FD is independently associated with the smaller infarction volumes and more favourable 90 day clinical outcome. Flow diversion may provide enhanced perfusion of ischemic tissue, offering some protection against infarct expansion and “buying-time” for effective reperfusion and tissue salvage. Major TIBI grade improvement associates with major reperfusion, favourable 24 h and 90 day clinical outcomes along with a trend to smaller infarct volumes in patients treated with intravenous thrombolysis. Acute bedside transcranial Doppler assessment of ACA FD and recanalization aids prognostication and therapeutic decision making in acute stroke.

Abstract 3290: Timing Of Recanalization After Intravenous Thrombolysis Determines The Functional Outcomes In Acute Ischemic Stroke

Background and Purpose: Intravenously administered tissue plasminogen activator (IV-TPA) is the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Wide variations in rates and timing of neurological recovery are observed in thrombolyzed patients. Although, recanalization of acutely occluded intracranial artery remains the major aim IV-TPA, timing and impact of this phenomenon on functional outcomes has not been evaluated properly. We evaluated the relationship between the arterial patency and timing of recanalization with functional outcomes at 3-months in AIS. Methods: Data for consecutive AIS patients treated with IV-TPA within 4.5 hours of symptom-onset during 2007-2010 were prospectively entered in the thrombolysis registry maintained at our tertiary care center. Data were collected for demographic characteristics, vascular risk factors, stroke subtypes and blood pressure before IV-TPA bolus. National Institute of Health Stroke Scale (NIHSS) scores were obtained before IV-TPA, at 2-hours and at 24-hours. Patients were continuously monitored with 2-MHz pulsed wave diagnostic transcranial Doppler (TCD) for 2-hours after IV-TPA bolus for early recanalization (ER). ER was assessed using the Thrombolysis in Brain Ischemia grading TCD system. Arterial patency was assessed on day 2 in patients who underwent CT angiography or magnetic resonance angiography, labeled as delayed recanalization (DR). Absence of recanalization on early TCD or imaging on day 2 was called persistent arterial occlusion (PAO). Favorable functional outcomes at 3 months were determined by modified Rankin scale (mRS) of 0-1. Results: Of the 2238 AIS patients admitted during the study period, 240 (11%) received IV-TPA within 4.5-hours of symptom-onset. Median age was 65yrs (range 19-92), 63% males, median NIHSS 17points (range 3-35) and median onset-to-treatment time 149 minutes. Overall, 122 (50.8%) patients achieved favorable functional outcome at 3-months. Information about ER, DR and PAO was available for 160 patients- ER in 55(34.4%), DR in 44(27.5%) and PAO in 61(38.1%) patients. Timing of recanalization was associated with favorable outcome (ER 72.7%, DR 63.6% and PAO 31.1%; p&lt;0.005). Factors associated with favorable outcome at 3-months on univariable analysis were younger age, female gender, atrial fibrillation, baseline NIHSS, onset-to-treatment time and timing of recanalization. However, on multivariable analysis, NIHSS at onset (OR per 1-point increase 0.907, 95%CI 0.848-0.969), ER (OR 3.32, 95%CI 1.295-9.474) and DR (OR 3.021 95%CI 1.197-7.634) were found as independent predictors of favorable outcome at 3-months. Conclusions: Timing of arterial recanalization induced by IV-TPA in acute ischemic stroke is a strong predictor of favorable outcome at 3-months.

The Diagnosis of Vertebrobasilar Insufficiency Using Transcranial Doppler Ultrasound

Background. Vertebrobasilar insufficiency (VBI) is a hemodynamic posterior circulation transient ischemic attack (TIA) caused by intermittent vertebral artery occlusion that is induced by a head rotation or extension. VBI may result from large vessel atherosclerotic disease, dissection, cervical compressive lesions, and subclavian steal phenomenon. Diagnostic transcranial Doppler (TCD) of VBI disease and hemodynamic posterior circulation TCD monitoring in symptomatic positions might prove a useful tool in establishing the diagnosis. Patient and Material/Method. A 50-year-old Caucasian man presented with a one-year history of episodic positional vertigo and ataxic gait that were induced by a neck extension and resolved by an upright position or a neck flexion. Computed tomography angiogram (CTA) and TCD confirmed the presence of VBI where no blood flow was detected through posterior cerebral arteries in the symptomatic position (head extension position). Conclusion. TCD is a promising noninvasive technique that might have a role as a diagnostic test in VBI.

Transient Neurological Symptoms During Contrast Transcranial Doppler Right‐to‐Left Shunt Testing in Patients with Cryptogenic Neurological Disease

Paradoxical embolization from right-to-left shunt (RLS) resulting in neurological events is well described and patients with cryptogenic neurological disease are commonly evaluated for this condition. In the course of testing for RLS by bubble contrast transcranial Doppler (TCD), we observed that some patients developed transient neurological symptoms. This report describes our findings. We performed diagnostic TCD on 445 consecutive patients with cryptogenic neurological disease (cerebral vascular accident, 21%; transient ischemic attack, 30%; migraine, 48%; and abnormal magnetic resonance brain imaging, 68%). Immediately following the procedure, patients were questioned about neurological symptoms. One hundred and sixty-three (37%) of the 445 patients had absent or minimal shunting (Spencer grades 0-1) and 233 of 445 (52%) had severe RLS (Spencer grades 4-5+). One or more TCD-associated neurological symptoms (TCD-SX) developed in 95 of 445 (21%) of the patients. Compared to patients with absent or minimal shunting, patients with shunt grades 2-5+ were two and one half times more likely to develop TCD-SX (18/164 [11%] vs. 77/283 [27%], P < 0.001). TCD-SX were fourfold more common among patients with a history of migraine compared to history-negative subjects (35 vs. 8.7%, P < 0.0001). Diagnostic bubble-contrast TCD provoked transient neurological symptoms. The symptoms correlated with the severity of RLS and were more common in migraine patients, suggesting that migraine patients are sensitized to chemical and/or microembolic shunt factors. There was no significant residual morbidity, and bubble-contrast echocardiograph continues to be a safe and valuable diagnostic procedure.

Ultrasound- and Microspheres-Enhanced Thrombolysis for Stroke Treatment: State of the Art

Intravenous administration of recombinant tissue-plasminogen activator (rt-PA) remains the fastest and widely feasible strategy to initiate treatment in acute ischemic stroke. Because it works by inducing recanalization of an occluded vessel, augmentation of this process is desirable and diagnostic transcranial Doppler (TCD) ultrasound can accomplish this safely. A 2-MHz pulsed-wave monitoring can at least double the chance of early complete arterial recanalization at no increase in the risk of symptomatic intracerebral hemorrhage. Gaseous microspheres, initially developed as ultrasound contrast agents, can further increase the effectiveness of rt-PA. A recent microsphere dose-escalation study called TUCSON showed sustained complete recanalization rates of 67% in patients receiving TCD monitoring with a 1.4-mL perflutren-lipid microsphere dose compared with controls receiving rt-PA alone with no increase in hemorrhage rate. In this article, we review the current and emerging applications of ultrasound and microspheres in stroke management including augmentation of systemic thrombolysis and implications for future reperfusion strategies.

Real‐Time Hemodynamic Assessment of Intracranial Stenosis in a Patient with Orthostatic Aphasia: Potential Applications of Transcranial Doppler

Intracranial atherosclerotic stenosis is thought to be responsible for 8% of all ischemic stroke subtypes. Transcranial Doppler (TCD) ultrasonography allows for noninvasive and dynamic evaluation of the cerebral circulation within the circle of Willis. We present a case of recurrent, orthostatic transient ischemic attacks in which, using TCD, we were able to correlate dynamically between the orthostatic symptomatology and a significant drop in the mean flow velocity (MFV) across the stenotic middle cerebral artery (MCA) segment. A 56-year-old male presented with recurrent episodes of orthostatic right-sided weakness and expressive aphasia. Diagnostic TCD revealed a stenotic signal in the left internal carotid artery (ICA) siphon. Subsequent TCD monitoring of both MCAs demonstrated a significant orthostatic drop in MFV of the left MCA, which closely correlated with his symptoms. The cerebral angiogram confirmed a high-grade stenosis at the supraclinoid segment of the left ICA. TCD is a useful, noninvasive, and dynamic tool for assessment of the intracranial circulation, and should be considered in the workup of patients with hypoperfusion cerebrovascular events.

Vasospasm after SAH due to aneurysm rupture of the anterior circle of Willis: value of TCD monitoring

Objective: The aim of this study was to verify the presence of angiographic vasospasm in patients with transcranial Doppler (TCD) of high velocities after subarachnoid hemorrhage (SAH).Methods: Seven hundred and eighty-six cases admitted within 48 hours after SAH due to the rupture of anterior circulation aneurysm, were prospectively studied with TCD. In cases of TCD velocities higher than 120 cm/s (TCD vasospasm), the patient underwent a control angiography. Hunt–Hess and Fisher's grade on admission CT and location of the aneurysm were related to occurrence of TCD vasospasm. The increase in TCD velocities within 24 hours was calculated and related to the presence of cerebral ischemia on discharge CT, considering three groups of patients: Group A with an increase in velocities higher than 60%, Group B with an increase in velocities between 30 and 60%, and Group C with an increase in velocities lower than 30%.Results: TCD vasospasm was observed in 216 patients (27%). In 97% of patients with TCD vasospasm on middle cerebral artery (MCA) and in 71% with TCD vasospasm on anterior cerebral artery (ACA), control angiography confirmed the vasospasm, with a significant lower diagnostic TCD predictivity of ACA spasm (χ2=28.204, p=0.000). The overall positive predictive value of TCD was 89%. There was no significant correlation of TCD vasospasm with clinical status on admission and location of the aneurysm, but a significant correlation between occurrence of TCD vasospasm and Fisher's grade (χ2=15.470, p=0.002) and between the increase rate in TCD velocities and cerebral ischemia (χ2=56.564, p=0.000).Conclusion: Our study shows a good correlation between TCD and angiography to detect vasospasm on MCA, but the correlation is low for ACA. TCD alone cannot discriminate different hemodynamic pathways after SAH.

Inadequate Acoustical Temporal Bone Window in Patients with a Transient Ischemic Attack or Minor Stroke: Role of Skull Thickness and Bone Density

Transcranial Doppler (TCD) ultrasonography may provide important diagnostic and prognostic information in patients with ischemic stroke or transient ischemic attack. TCD also enhances the effect of thrombolytic treatment in patients with acute stroke. In some patients, especially elderly women, TCD cannot be performed because of temporal bone window failure (WF). We investigated whether skull thickness or bone density on computed tomography scans predicts WF. In 182 patients with a transient ischemic attack or minor ischemic stroke, skull thickness and bone density measurements were made at the level of the temporal bone window. Multiple logistic regression analysis was used to relate independent variables to WF and to adjust the estimates for possible confounding factors. TCD signals were absent on the symptomatic side in 22 female and 11 male patients (18%). Both skull thickness and radiodensity at the level of the temporal bone window were strongly related to WF as well as age and female gender. After adjustment according to age and gender, skull thickness at the temporal bone window was an independent prognostic factor of WF (odds ratio [OR]: 2.3 per mm increase in skull thickness, 95% confidence interval [CI]: 1.4 to 3.8). Radiodensity of the temporal bone decreased with age in women (−52 HU per 10 y over 50 y of age, 95% CI: −73 to −30) but in men (−10 HU per 10 y over 50 y of age, 95% CI: −33 to 13), no statistically significant association was observed. We computed probabilities of WF for each patient individually. With a probability cut point of 50%, 33% of the patients with WF and 97% of the patient without WF were correctly identified. The area under the receiver operating characteristic (ROC) curve of this simple prediction model including age, gender and skull thickness was 0.88; the area under the ROC curve of a gender-stratified model including age, skull thickness and radiodensity was 0.90. This difference was not statistically or clinically significant p = 0.13). WF is more common in women because density of the temporal bone in elderly women is low. Absence of WF can be predicted by a combination of three simple parameters: skull thickness, age and gender. This may help to select patients with ischemic stroke for diagnostic TCD screening and to facilitate targeted delivery of ultrasound-enhanced thrombolysis. (E-mail: a.wijnhoud@erasmusmc.nl)

Practice Standards for Transcranial Doppler Ultrasound: Part I—Test Performance

Indications for the clinical use of transcranial Doppler (TCD) continue to expand while scanning protocols and quality of reporting vary between institutions. Based on literature analysis and extensive personal experience, an international expert panel started the development of guidelines for TCD performance, interpretation, and competence. The first part describes complete diagnostic spectral TCD examination for patients with cerebrovascular diseases. Cranial temporal bone windows are used for the detection of the middle cerebral arteries (MCA), anterior cerebral arteries (ACA), posterior cerebral arteries (PCA), C1 segment of the internal carotid arteries (ICA), and collateralization of flow via the anterior (AComA) and posterior (PComA) communicating arteries; orbital windows-for the ophthalmic artery (OA) and ICA siphon; the foraminal window-for the terminal vertebral (VA) and basilar (BA) arteries. Although there is a significant individual variability of the circle of Willis with and without disease, the complete diagnostic TCD examination should include bilateral assessment of the M2 (arbitrarily located at 30-40 mm depth), M1 (40-65 mm) MCA [with M1 MCA mid-point at 50 mm (range 45-55 mm), average length 16 mm (range 5-24 mm), A1 ACA (60-75 mm), C1 ICA (60-70 mm), P1-P2 PCA (average depth 63 mm (range 55-75 mm), AComA (70-80 mm), PComA (58-65 mm), OA (40-50 mm), ICA siphons (55-65 mm), terminal VA (40-75 mm), proximal (75-80), mid (80-90 mm), and distal (90-110 mm) BA]. The distal ICA on the neck (40-60 mm) can be located via submandibular windows to calculate the VMCA/VICA index, or the Lindegaard ratio for vasospasm grading after subarachnoid hemorrhage. Performance goals of diagnostic TCD are to detect and optimize arterial segment-specific spectral waveforms, determine flow direction, measure cerebral blood flow velocities and flow pulsatility in the above-mentioned arteries. These practice standards will assist laboratory accreditation processes by providing a standard scanning protocol with transducer positioning and orientation, depth selection and vessel identification for ultrasound devices equipped with spectral Doppler and power motion Doppler.

Intravenous TPA for Very Old Stroke Patients

Background: Although thrombolysis in patients with advanced age is considered more risky, some may benefit from TPA treatment. We studied safety and recanalization/recovery in patients older than 80 years treated with TPA and compared them with younger stroke patients. Methods: We studied patients treated with intravenous TPA and divided them into younger (<80 years) and older (≧80 years) groups for comparison. Diagnostic transcranial Doppler was completed before bolus, and patients were consequently monitored for up to 2 h when feasible. Clinical data included NIH Stroke Scale score, symptomatic intracranial hemorrhage (ICH) and discharge disposition. Results: We studied 127 younger (mean 63 years, range 31–79) and 56 older patients (mean 84 years, range 80–93). Median baseline NIH Stroke Scale score was higher in the older group (18 vs. 14 points, NS). Occlusion locations, onset to needle time (median 130 vs. 120 min) as well as improvement at 24 h (median 5 vs. 4 points) were similar in both groups. Transcranial Doppler monitoring showed similar partial or complete recanalization rates (66 vs. 66%), onset to recanalization time (median 160 vs. 158 min) and reocclusion rates (26 vs. 25%). Symptomatic and fatal ICH was not higher in the older group (7.1 and 3.5% vs. 6.3 and 3.9%, NS). There was higher mortality among older patients (20 vs. 11%, NS). At discharge, 23% of older patients went home, 41% underwent rehabilitation and 16% were transferred to skilled nursing facilities, compared with 31, 43 and 15% respectively, in the younger group. Conclusion: After intravenous TPA treatment, patients over 80 years of age have similar recanalization, short-term improvement and symptomatic ICH rates compared with younger patients. However, older patients tend to have higher in-hospital mortality.

Ultrasound‐Enhanced Thrombolysis for Acute Ischemic Stroke: Phase I. Findings of the CLOTBUST Trial

Tissue plasminogen activator (TPA) activity may be enhanced with ultrasound, potentially 2 MHz transcranial Doppler (TCD). The authors present Phase I data of the CLOTBUST (Combined Lysis of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic TPA). Nonrandomized stroke patients with proximal arterial occlusion on a prebolus TCD receiving intravenous 0.9 mg/kg TPA within 3 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5. 55 patients (mean age 69 +/- 15 years, median baseline NIH Stroke Scale [NIHSS] 18, range 4-29, 90% with 3 9 points) were treated at 125 +/- 36 minutes from symptom onset. TCD monitoring began at 117 +/- 39 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 20 patients (36%). Dramatic recovery (NIHSS score < or = 3) occurred in 20% at 2 hours and in 24% at 24 hours. Overall improvement by > or = 4 NIHSS points was found in 49% at 24 hours. Improvement was associated with recanalization during or shortly after TPA infusion (phi r2 = .5, P = .03); however, in 6/20 patients with complete recanalization (30%), no immediate clinical change was noticed within 2 hours. Overall symptomatic hemorrhage rate was 5.5%. Continuous TCD insonation for up to 2 hours at maximum intensities allowed by current bio-safety guidelines is safe. Dramatic recovery and complete recanalization shortly after TPA bolus are feasible goals for thrombolysis given with TCD monitoring.

CLOTBUST: Design of a Randomized Trial of Ultrasound‐Enhanced Thrombolysis for Acute Ischemic Stroke

Intravenous tissue plasminogen activator (TPA) therapy can be monitored with 2 MHz transcranial Doppler (TCD). This article describes the design of CLOTBUST (combined lysis of thrombus in brain ischemia using transcranial ultrasound and systemic TPA), the first prospective international multicenter randomized clinical trial of noninvasive externally applied ultrasound to enhance systemic thrombolysis in human stroke. Patients with acute ischemic stroke eligible for intravenous TPA therapy within 3 hours of symptom onset who have detectable middle cerebral artery occlusion on a prebolus TCD are included in this trial. All patients receive standard 0.9 mg/kg TPA therapy. Patients are randomized (1:1) to either 2 hours of continuous monitoring with TCD or placebo monitoring. FDA-approved portable diagnostic TCD equipment and standard headframes (Marc series, Spencer Technologies, Seattle, WA) are used. Output of TCD units is set at 100% power achievable at depths of insonation that display the worst TIBI flow grade signals. METHODS AND END-POINTS: Acute MCA occlusion on prebolus TCD is defined as thrombolysis in brain ischemia (TIBI) flow grades 0-3. Treating physicians are blinded to randomization assignment, and certified scorers measure stroke severity using the National Institute of Health Stroke Scale (NIHSS). Safety of continuous TCD monitoring is determined by rates of symptomatic (NIHSS score increase by 4+ points) intracerebral hemorrhage within 72 hours after initial symptom onset. Potential enhancement of TPA therapy will be determined using combined primary end-point of early complete recanalization on TCD (TIBI flow grades 4-5), dramatic recovery (NIHSS < or = 3 points), or decline in the NIHSS > or = 10 points repeatedly measured every 30 minutes within 2 hours after TPA bolus. Other end-points include recovery at 24 hours and 3 months, modified Rankin scores (mRS) are obtained at 90 days, and favorable outcome is determined as NIHSS or mRS scores 0-1. The aim of phase II CLOTBUST trial is to determine the rates of early complete recanalization and dramatic/early clinical recovery in TPA + TCD and TPA groups. The sample size is set at 126 patients since a medium effect size (.50) is anticipated for TPA + TCD group vs TPA alone to achieve combined primary end-point.

Transcranial Doppler Enhanced Thrombolysis for Embolic Occlusion of Major Cerebral Arteries

For the treatment of 11 patients with hyperacute embolic occlusion of major cerebral arteries (ten with occlusion of middle cerebral artery and one with occlusion of basilar artery), TCDenhanced thrombolysis (TCDET) was performed in combination with ultrasound irradiation, using diagnostic transcranial Doppler (TCD) (TC2-64B: 2MHz, 100mW/cm(2), pulsed wave) (TCDET group), and the effectiveness of this procedure was compared with that of local intra-arterial fibrinolysis (LIF) in 45 patients with embolic occlusion of the middle cerebral artery (LIF group). Regarding dose of TPA, the LIF group used 1046.7 +/- 607.8 units and the TCDET group 700.0 +/- 431.3 units (p < 0.05). Regarding time technically required to attain recanalization, the LIF group required 68.2 minutes, and the TCDET group 28.6 minutes. A good outcome was noted in 60.8% of the LIF group and 64% of the TCDET group. Haemorrhagic transformation was observed in 7.8% of the LIF group and in 0% of the TCDET group. No complications due to TCD irradiation were observed in the TCDET group. These findings suggest that TCDET can be an effective method of achieving recanalization.

NIH Stroke Scale as a Predictor of Clot Presence, Location, and Persisting Occlusion in Candidates for Thrombolysis

46 Background: In acute stroke, few tools are readily available to determine clot presence and location before thrombolysis, nor whether occlusion persists after intravenous TPA. Because the NIH Stroke Scale (NIHSS) is easily obtained in the Emergency Department, we correlated sequential NIHSS scores and arterial occlusion in prospective candidates for IV TPA. Methods: Potential thrombolysis patients evaluated with transcranial Doppler (TCD) ultrasound and the NIHSS at the time of presentation were studied. TCD was performed using previously validated criteria for clot detection, localization, and subsequent degree of recanalization after thrombolysis. In patients treated at &lt;180 minutes with conventional dose TPA (0.9 mg/kg), repeat NIHSS scores and diagnostic TCD were performed at the end of infusion. Results: 119 ischemic stroke patients met inclusion criteria (age 68±15, NIHSS 15±7, median 14, range 2–36), with 83% having occlusion consistent with symptoms. Occlusion was present in all patients with NIHSS ≥22, none with NIHSS &lt;4, and there was a direct relationship between baseline NIHSS and clot presence (p&lt;0.0001). Each additional NIHSS point increased the odds of occlusion by 1.33(95%CI 1.17–1.51). In patients with anterior circulation symptoms (N=80), increasing NIHSS corresponded with increasing M1 MCA and/or ICA occlusion, and decreasing vascular patency or M2 occlusion (p&lt;0.001). In thrombolysed patients with initial vascular occlusion (N=55), end-of-infusion NIHSS was less predictive of persisting occlusion, with 70% of patients with scores ≥6 having persisting occlusion and 20% of patients with scores ≥16 having complete recanalization. The odds of persisting occlusion per end-of-infusion NIHSS point were 1.14 (95%CI 1.06–1.24,p &lt;0.0008). Conclusions: Baseline NIHSS accurately predicts clot presence with increasing scores corresponding to increasing clot burden. However, NIHSS becomes less predictive of clot persistence at the end of TPA infusion and may less accurately identify patients for further revascularization efforts.