Andrei V Alexandrov

Publications (131)560.74 Total impact

• Source

  Available from: Pitchaiah Mandava

  Article: Explicit Consideration of Baseline Factors to Assess Recombinant Tissue-Type Plasminogen Activator Response With Respect to Race and Sex.

  Pitchaiah Mandava, Santosh B Murthy, Melody Munoz, Dawn McGuire, Roger P Simon, Andrei V Alexandrov, Karen C Albright, Amelia K Boehme, Sheryl Martin-Schild, Sharyl Martini, Thomas A Kent
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  ABSTRACT: BACKGROUND AND PURPOSE: Sex and race reportedly influence outcome after recombinant tissue-type plasminogen activator (rtPA). It is, however, unclear whether baseline imbalances (eg, stroke severity) or lack of response to thrombolysis is responsible. We applied balancing methods to test the hypothesis that race and sex influence outcome after rtPA independent of baseline conditions. METHODS: We mapped group outcomes from the National Institute of Neurological Disorders and Stroke (NINDS) dataset based on race and sex onto a surrogate-control function to assess differences from expected outcomes at their respective National Institutes of Health Stroke Scale and age. Outcomes were also compared for subjects matched individually on key baseline factors using NINDS and 2 recent datasets from southeastern United States. RESULTS: At similar National Institutes of Health Stroke Scale and age, 90-day good outcomes (modified Rankin Score, 0-2) in NINDS were similarly improved after rtPA for white men and women. There was a strong trend for improvement in black men. Conversely, black women treated with rtPA showed response rates no different from the controls. After baseline matching, there were nonsignificant trends in outcomes except for significantly fewer good outcomes in black versus matched white women (37% versus 63%; P=0.027). Pooling the 3 datasets showed a similar trend for poorer short-term outcome for black women (P=0.054; modified Rankin Score, 0-1). CONCLUSIONS: Matching for key baseline factors indicated that race and sex influence outcome most strikingly in black women who demonstrated poorest outcomes after rtPA. This finding supports the hypothesis that poor response to rtPA, rather than differences in baseline conditions, contributes to the worse outcome. This finding requires prospective confirmation.
  Stroke 05/2013; · 5.73 Impact Factor
• Article: Adherence to a Mediterranean diet and risk of incident cognitive impairment.

  Georgios Tsivgoulis, Suzanne Judd, Abraham J Letter, Andrei V Alexandrov, George Howard, Fadi Nahab, Frederick W Unverzagt, Claudia Moy, Virginia J Howard, Brett Kissela, Virginia G Wadley
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  ABSTRACT: OBJECTIVE: We sought to determine the relationship of greater adherence to Mediterranean diet (MeD) and likelihood of incident cognitive impairment (ICI) and evaluate the interaction of race and vascular risk factors. METHODS: A prospective, population-based, cohort of individuals enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study 2003-2007, excluding participants with history of stroke, impaired cognitive status at baseline, and missing data on Food Frequency Questionnaires (FFQ), was evaluated. Adherence to a MeD (scored as 0-9) was computed from FFQ. Cognitive status was evaluated at baseline and annually during a mean follow-up period of 4.0 ± 1.5 years using Six-item-Screener. RESULTS: ICI was identified in 1,248 (7%) out of 17,478 individuals fulfilling the inclusion criteria. Higher adherence to MeD was associated with lower likelihood of ICI before (odds ratio [lsqb]OR[rsqb] 0.89; 95% confidence interval [lsqb]CI[rsqb] 0.79-1.00) and after adjustment for potential confounders (OR 0.87; 95% CI 0.76-1.00) including demographic characteristics, environmental factors, vascular risk factors, depressive symptoms, and self-reported health status. There was no interaction between race (p = 0.2928) and association of adherence to MeD with cognitive status. However, we identified a strong interaction of diabetes mellitus (p = 0.0134) on the relationship of adherence to MeD with ICI; high adherence to MeD was associated with a lower likelihood of ICI in nondiabetic participants (OR 0.81; 95% CI 0.70-0.94; p = 0.0066) but not in diabetic individuals (OR 1.27; 95% CI 0.95-1.71; p = 0.1063). CONCLUSIONS: Higher adherence to MeD was associated with a lower likelihood of ICI independent of potential confounders. This association was moderated by presence of diabetes mellitus.
  Neurology 04/2013; 80(18):1684-1692. · 8.31 Impact Factor
• Article: The Role of Sonolysis and Sonothrombolysis in Acute Ischemic Stroke: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Case-Control Studies.

  Maher Saqqur, Georgios Tsivgoulis, Francois Nicoli, David Skoloudik, Vijay K Sharma, Vincent Larrue, Jürgen Eggers, Fabienne Perren, Paris Charalampidis, Dale Storie, Ashfaq Shuaib, Andrei V Alexandrov
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  ABSTRACT: OBJECTIVES: To assess the evidence on the safety and efficacy of sonothrombolysis in acute stroke. SEARCH METHODS: Electronic databases and grey literature were searched under different MeSH terms from 1970 to present. SELECTION CRITERIA: Randomized control trials (RCTs) and case control studies (CCSs) on sonolysis and sonothrombolysis alone or with microsphere in acute stroke patients (>18 old). Outcome measures included complete recanalization (CR) at 1-2 and 24 hours, 3 months modified Rankin Scale (mRS), and symptomatic intracerebral hemorrhage (sICH). Data was extracted to Review Manager software. RESULTS: Fifty-seven studies were retrieved and analyzed. Ten studies (7 RCTs and 3 CCSs) were included in our meta-analysis, which revealed that sonolysis and sonothrombolysis are safe (OR of sICH: 1.14; 95% confidence interval (CI): 0.56- 2.34;P=0.71) and effective (OR of CR at 1-2 hours: 2.95;95% CI: 1.81-4.81;P<0.00001) and have more than two-fold higher likelihood of favourable long-term outcome (3-month mRS 0-2; OR: 2.20; CI:1.52-3.19;P<0.0001). Further subgroup analysis based on the presence of microsphere revealed that it is safe (OR of sICH: 1.18; CI:0.433.24;P=0.75) and effective (OR of CR: 2.61; CI: 1.36-4.99;P=0.004). Subgroup analysis based on sonolysis revealed to be safe and effective. CONCLUSIONS: This novel treatment appears safe and effective. The evidence of microsphere as an enhancement of sonothrombolysis is evolving.
  Journal of neuroimaging: official journal of the American Society of Neuroimaging 04/2013; · 1.72 Impact Factor
• Article: CLOTBUST-Hands Free: Initial Safety Testing of a Novel Operator-Independent Ultrasound Device in Stroke-Free Volunteers.

  Kristian Barlinn, Andrew D Barreto, April Sisson, David S Liebeskind, Mark E Schafer, John Alleman, Limin Zhao, Loren Shen, Luis F Cava, Mohammad H Rahbar, James C Grotta, Andrei V Alexandrov
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  ABSTRACT: BACKGROUND AND PURPOSE: We aimed to evaluate safety and tolerability of a novel operator-independent ultrasound device among stroke-free volunteers. METHODS: A headframe containing 18 ultrasound transducers (each operating at 2 MHz, pulsed-wave) was used to expose both temporal windows and the suboccipital window. The transmission characteristics were set to emulate the acoustic characteristics of the exposure levels in the Combined Lysis of Thrombus in Brain Ischemia using Transcranial Ultrasound and Systemic tPA trial and to never exceed Food and Drug Administration-mandated diagnostic ultrasound exposure limits. Volunteers underwent 2 hours of insonation with transducer activation one at a time. Safety was captured using serial neurological examinations and pre- and postinsonation MRI for detection of the blood brain barrier permeability. RESULTS: A total of 15 volunteers (40% men; 49±16 years; 27% black; all pre-exposure National Institutes of Health Stroke Scale scores 0) were enrolled. Five volunteers received pulsed-wave ultrasound via the best pair temporal transducers, 5 via sequential activation of the suboccipital transducers, and 5 via sequential activation of all bilateral temporal and suboccipital transducers. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure, and at 24 hours, and no abnormality of the blood brain barrier was found on any of the MRIs. CONCLUSIONS: Our novel device was well tolerated by stroke-free volunteers and did not cause any neurological dysfunction nor did it affect blood brain barrier integrity. The safety and efficacy of the device are now being tested in stroke patients receiving intravenous tissue-type plasminogen activator in phase II-III clinical trials.
  Stroke 04/2013; · 5.73 Impact Factor
• Article: How to Prepare and Deliver a Scientific Presentation. Teaching Course Presentation at the 21st European Stroke Conference, Lisboa, May 2012.

  Andrei V Alexandrov, Michael G Hennerici
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  ABSTRACT: Background: A scientific presentation is a professional way to share your observation, introduce a hypothesis, demonstrate and interpret the results of a study, or summarize what is learned or to be studied on the subject. Presentation Methods: Commonly, presentations at major conferences include podium (oral, platform), poster or lecture, and if selected one should be prepared to PRESENT: Plan from the start (place integral parts of the presentation in logical sequence); Reduce the amount of text and visual aids to the bare minimum; Elucidate (clarify) methods; Summarize results and key messages; Effectively deliver; Note all shortcomings, and Transform your own and the current thinking of others. We provide tips on how to achieve this. Presentation Results: After disclosing conflicts, if applicable, start with a brief summary of what is known and why it is required to investigate the subject. State the research question or the purpose of the lecture. For original presentations follow a structure: Introduction, Methods, Results, Conclusions. Invest a sufficient amount of time or poster space in describing the study methods. Clearly organize and deliver the results or synopsis of relevant studies. Include absolute numbers and simple statistics before showing advanced analyses. Remember to present one point at a time. Stay focused. Discuss study limitations. In a lecture or a podium talk or when standing by your poster, always think clearly, have a logical plan, gain audience attention, make them interested in your subject, excite their own thinking about the problem, listen to questions and carefully weigh the evidence that would justify the punch-line. Conclusions: Rank scientific evidence in your presentation appropriately. What may seem obvious may turn erroneous or more complex. Rehearse your presentation before you deliver it at a conference. Challenge yourself to dry runs with your most critically thinking colleagues. When the time comes, ace it with a clear mind, precise execution and fund of knowledge.
  Cerebrovascular Diseases 03/2013; 35(3):202-208. · 2.72 Impact Factor
• Article: Sonothrombolysis in Ischemic Stroke.

  Kristian Barlinn, Andrei V Alexandrov
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  ABSTRACT: OPINION STATEMENT: Acute ischemic stroke remains one of the most devastating diseases when it comes to morbidity and mortality, not to mention the personal and economic burden that occurs in long-term. Intravenous thrombolysis with tissue plasminogen activator (tPA) is the only effective acute stroke therapy that improves outcome if given up to 4.5 hours from symptom onset. However, recanalization rates are meager and the majority of treated patients still have residual disability after stroke, emphasizing the need for further treatment options that may facilitate or even rival the only approved therapy. Sonothrombolysis, the adjuvant continuous ultrasound sonication of an intra-arterial occlusive thrombus during thrombolysis, enhances the clot-dissolving capabilities of intravenous tPA presumably by delivering acoustic pressure to the target brain vessel. Higher recanalization rates produce a trend towards better functional outcomes that could be safely achieved with the combination of high-frequency ultrasound and intravenous tPA. However, data on ultrasound targeting of intracranial proximal occlusive lesions other than those in the middle cerebral arteries are sparse. Moreover, recent sonothrombolysis trials were exclusively conducted with operator-dependent hand-held technology hindering its further testing in clinical sonothrombolysis trials. An operator-independent 2-MHz transcranial Doppler device has been developed allowing health care professionals not formally trained in ultrasound apparatus to provide therapeutic ultrasound as needed. Currently, this operator-independent device covering 12 proximal intracranial segments that most commonly contain thrombo-embolic occlusions enters testing in a pivotal multicenter sonothrombolysis efficacy trial. If this trial demonstrates safety and efficacy, adjuvants, such as gaseous microbubbles that further potentiate the thrombolytic effect of intravenous tPA, could be tested along with this device.
  Current Treatment Options in Neurology 02/2013; · 1.29 Impact Factor
• Article: Real-time Validation of Transcranial Doppler Criteria in Assessing Recanalization During Intra-arterial Procedures for Acute Ischemic Stroke: An International, Multicenter Study.

  Georgios Tsivgoulis, Marc Ribo, Marta Rubiera, Spyros N Vasdekis, Kristian Barlinn, Dimitrios Athanasiadis, Reza Bavarsad Shahripour, Sotirios Giannopoulos, Elefterios Stamboulis, Mark R Harrigan, Carlos A Molina, Andrei V Alexandrov
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  ABSTRACT: Background-We sought to evaluate the diagnostic accuracy of ultrasound criteria for recanalization during real-time transcranial Doppler monitoring of intra-arterial reperfusion procedures in acute ischemic stroke patients in an international, multicenter study. METHODS: Consecutive acute ischemic stroke patients with proximal intracranial occlusions underwent intra-arterial reperfusion procedures with simultaneous real-time transcranial Doppler monitoring at 3 tertiary-care stroke centers. Residual flow signals at the site of angiographically confirmed occlusions were monitored at a constant transtemporal insonation angle using a standard head-frame. Recanalization was assessed simultaneously by digital subtraction angiography and ultrasound using thrombolysis in myocardial infarction and thrombolysis in brain ischemia (TIBI) criteria, respectively. Independent readers blinded to digital subtraction angiography performed validation of TIBI flow grades. The interrater reliability for assessment of TIBI grades was investigated. RESULTS: We evaluated time-linked real-time digital subtraction angiography transcranial Doppler images from 96 diagnostic digital subtraction angiography runs during intra-arterial reperfusion procedures in 62 acute ischemic stroke patients (mean age, 59±17 years; 58% men; median baseline National Institutes of Health Stroke Scale score, 18 [interquartile range 12-21]; median time from symptom onset to intra-arterial procedure initiation, 240 minutes [interquartile range 163-308]). The interrater reliability for evaluation of TIBI grades and assessment of recanalization was good (Cohen κ: 0.838 and 0.874, respectively; P<0.001). Compared with angiography, transcranial Doppler had the following accuracy parameters for detection of complete recanalization (TIBI 4 and 5 versus thrombolysis in myocardial infarction 3, flow grades): sensitivity, 88% (95% confidence interval, 72%-96%); specificity, 89% (79%-95%); positive predictive value, 81% (65%-91%); negative predictive value, 93% (84%-98%); and overall accuracy 89% (80%-94%). CONCLUSIONS: At laboratories with high-interrater reliability, TIBI criteria can accurately predict brain recanalization in real time as compared with thrombolysis in myocardial infarction angiographic scores.
  Stroke 01/2013; · 5.73 Impact Factor
• Article: Early sleep apnea screening on a stroke unit is feasible in patients with acute cerebral ischemia.

  Jessica Kepplinger, Kristian Barlinn, Karen C Albright, Wiebke Schrempf, Amelia K Boehme, Lars-Peder Pallesen, Uta Schwanebeck, Xina Graehlert, Alexander Storch, Heinz Reichmann, Andrei V Alexandrov, Ulf Bodechtel
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  ABSTRACT: Early screening for sleep apnea (SA) is rarely considered in patients with acute cerebral ischemia. We aimed to evaluate the feasibility of early SA screening on a stroke unit, its impact on post-discharge SA care and the relation of SA to clinical features. Patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) prospectively underwent overnight cardiorespiratory polygraphy within 3 ± 2 days of symptom-onset. Feasibility was defined as analyzable polygraphy in 90 % of studied patients. We enrolled 61 patients (84 % AIS, 16 % TIA): mean age 66 ± 8 years, 44 % men, median NIHSS 1 (0-15), median ESS 5 (0-13). Analyzability was given in 56/61 (91.8 %; one-sided 95 % CI, lower-bound 86.0 %) patients indicating excellent feasibility of early SA screening with no significant differences in stroke severity (100 % in TIA, 91 % minor stroke, 83 % major stroke, p = 0.474). Ninety-one percent (51/56) had an apnea-hypopnea index ≥5/h (median: 20/h [0-79]); 32 % (18/56) mild, 30 % (17/56) moderate, and 29 % (16/56) severe SA. When comparing sleep-related ischemic stroke (SIS) and non-SIS patients, no differences were found regarding the presence (95 vs. 89 %, p = 0.49) or severity (e.g., severe SA: 32 vs. 27 %, p = 0.69) of SA. After 12 months, 27/38 (71 %) patients given specific recommendations completed in-laboratory sleep work-up and 7/27 (25 %) were prescribed for non-invasive ventilatory correction. In conclusion, early SA screening is feasible in patients with acute cerebral ischemia and may have a positive impact on post-discharge SA care. Given the high frequency and atypical presentation of SA, early screening for SA should be considered in all acute cerebral ischemia patients.
  Journal of Neurology 12/2012; · 3.47 Impact Factor
• Article: Timing and mechanism of ischemic stroke due to extracranial blunt traumatic cerebrovascular injury.

  Christoph J Griessenauer, J Brett Fleming, Boyd F Richards, Luis P Cava, Joel K Curé, Duraid S Younan, Limin Zhao, Andrei V Alexandrov, Kristian Barlinn, Tracy Taylor, Mark R Harrigan
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  ABSTRACT: Object 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). Methods 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. Results 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. Conclusions Most ischemic strokes due to TCVI are embolic in nature and occur prior to screening CTA and initiation of treatment with aspirin.
  Journal of Neurosurgery 12/2012; · 2.96 Impact Factor
• Article: Slim stroke scales for assessing patients with acute stroke: ease of use or loss of valuable assessment data?

  Brandon R Nye, Christina E Hyde, Georgios Tsivgoulis, Karen C Albright, Andrei V Alexandrov, Anne W Alexandrov
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  ABSTRACT: Background Scientific guidelines recommend the National Institutes of Health Stroke Scale for ischemic stroke assessment. However, many nurses find "slim" National Institutes of Health Stroke Scale versions or the Glasgow Coma Scale easier to use. Objective To compare 3 "slim" versions of the National Institutes of Health Stroke Scale and the Glasgow Coma Scale with the full National Institutes of Health Stroke Scale. Methods Components of the full National Institutes of Health Stroke Scale and Glasgow Coma Scale were abstracted from records of consecutive stroke patients. Items were subtracted from the full National Institutes of Health Stroke Scale, with items contained in "slim" versions retained. False-negative rates for neurological disability were calculated for the "slim" versions and the Glasgow Coma Scale. Results Data were collected from 172 acute stroke patients (median [interquartile range] 6 [3-12] for National Institutes of Health Stroke Scale, 15 [12-15] for Glasgow Coma Scale): 143 (83%) were ischemic stroke patients (27% posterior circulation strokes) and 29 (17%) were intracerebral hemorrhage patients. The value of "slim" scales and the Glasgow Coma Scale declined in a stepwise manner as the full National Institutes of Health Stroke Scale decreased because of false-negative results despite the presence of a measurable disabling deficit. False-negative rates were 5% to 19% on "slim" versions and 56% with the Glasgow Coma Scale. Conclusions Use of "slim" scales, and in particular the Glasgow Coma Scale, substantially decreases the value of a structured neurological assessment, particularly in patients with low National Institutes of Health Stroke Scale scores.
  American Journal of Critical Care 11/2012; 21(6):442-8. · 1.66 Impact Factor
• Article: Ancillary approaches to plasminogen activators.

  Reza Bavarsad Shahripour, Andrei V Alexandrov
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  ABSTRACT: Acute ischemic stroke develops from an interruption in focal cerebral blood flow. In many cases, it is caused by an acute thromboembolism. Although systemic fibrinolytic therapy for acute ischemic stroke has been a significant breakthrough in the management of this disease, additional agents and methods that could improve or restore cerebral flow are necessary. Similarly to findings in acute myocardial infarction, combination pharmacotherapy has the potential to improve current thrombolytic treatment in acute ischemic stroke. In recent years, research efforts were directed toward various combination therapy with pharmacological and nonpharmacological methods. Several trials tested tissue plasminogen activator (t-PA) in combination with antiplateletes and anticoagulants. Combination of t-PA with nonpharmacological agents included sonothrombolysis (amplifying the thrombolytic effect), laser (neuro-recovery), hypothermia (cytoprotection and decreasing brain swelling), and blood flow augmentation (increasing residual flow and recruitment of collateral vessels). This paper will review ongoing clinical trials and safety of these promising combinatory treatments.
  Annals of the New York Academy of Sciences 09/2012; 1268(1):113-9. · 3.15 Impact Factor
• Article: Exploratory analysis of estimated acoustic peak rarefaction pressure, recanalization, and outcome in the transcranial ultrasound in clinical sonothrombolysis trial.

  Kristian Barlinn, Georgios Tsivgoulis, Carlos A Molina, Dmitri A Alexandrov, Mark E Schafer, John Alleman, Andrei V Alexandrov
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  ABSTRACT: PURPOSE.: Acoustic peak rarefaction pressure (APRP) is the main factor that influences ultrasound-enhanced thrombolysis. We sought to determine whether recanalization rate and functional outcomes in the Transcranial Ultrasound in Clinical SONothrombolysis (TUCSON) trial could be predicted by estimated in vivo APRP. METHODS.: We developed an acoustic attenuation model to estimate the in vivo APRP at the arterial occlusion site in each subject of the TUCSON trial with CT scans eligible for measurements. Variables included temporal bone thickness, depth of arterial occlusion site, and average attenuation of skin and brain tissues. Recanalization was defined as partial or complete using the Thrombolysis in Brain Infarction flow grades. Functional independence was assessed at 3 months using the modified Rankin Scale score (mRS, 0-1). RESULTS.: APRP was calculated in 20 acute ischemic stroke patients treated with sonothrombolysis (mean age, 64 ± 15 years, 65% men; median NIHSS score, 13; IQR, 6-17). The mean APRP was 30.2 ± 15.5 kPa (range, 8-68 kPa). Patients with persisting occlusion had nonsignificantly lower APRP than patients with partial or complete recanalization (25.2 ± 8.0 versus 32.3 ± 17.7 kPa; p = 0.228). Patients who were functionally independent at 3 months had nonsignificantly higher APRP than patients with worse outcome (35.1 ± 19.5 versus 25.9 ± 11.2 kPa; p = 0.217). CONCLUSIONS.: Our exploratory analysis suggests a potentially important role of successful energy delivery to augment thrombolysis with 2-MHz ultrasound in acute ischemic stroke patients. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2012.
  Journal of Clinical Ultrasound 08/2012; · 0.81 Impact Factor
• Article: Clopidogrel load for emboli reduction in patients with symptomatic carotid stenosis undergoing urgent carotid endarterectomy.

  Georgios Tsivgoulis, Antonios Kerasnoudis, Christos Krogias, Konstantinos Vadikolias, Saskia H Meves, Ioannis Heliopoulos, Efstratios Georgakarakos, Charitomeni Piperidou, Andrei V Alexandrov
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  ABSTRACT: Microembolic signals (MES) on transcranial Doppler are an independent risk factor for recurrent stroke in patients with extracranial symptomatic/asymptomatic carotid artery stenosis (CARAS). Clopidogrel load (300 mg) combined with dual antiplatelet therapy has been shown to reduce MES in patients with symptomatic CARAS. We sought to determine feasibility of clopidogrel load in decreasing asymptomatic embolization in patients with symptomatic CARAS undergoing urgent carotid endarterectomy within the first 2 weeks from the index event. Subjects and Consecutive patients with symptomatic CARAS (70%-99%) and presence of MES on 1-hour baseline (<24 hours from the index event) transcranial Doppler monitoring of ipsilateral middle cerebral artery were treated with clopidogrel load followed by clopidogrel (75 mg)±aspirin (100 mg) during the elapsed time period between hospital admission and urgent carotid endarterectomy at 3 tertiary-care stroke centers. Repeat 1-hour transcranial Doppler monitoring was performed the day before surgery. Bleeding complications during surgery and recurrent strokes or transient ischemic attacks during the first month of ictus were prospectively recorded. A total of 11 symptomatic CARAS patients (mean age, 66±7 years; 73% men; 64% acute ischemic strokes) were treated with clopidogrel load followed by dual (67%) or single (33%) antiplatelet therapy. MES count was significantly reduced between baseline (median count, 8 MES/h; interquartile range, 6-19) and repeat transcranial Doppler monitoring (0 MES/h; interquartile range, 0-3; P=0.003). No bleeding complications, recurrent strokes, or transient ischemic attacks were documented. Our pilot observational study provides preliminary nonrandomized data regarding the potential efficacy of clopidogrel load to reduce asymptomatic embolization in patients with symptomatic CARAS before urgent carotid endarterectomy.
  Stroke 05/2012; 43(7):1957-60. · 5.73 Impact Factor
• Article: Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats

  Andrei V. Alexandrov, Kristian Barlinn, Roger Strong, Anne W. Alexandrov, Jaroslaw Aronowski
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  ABSTRACT: It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long–Evans rats with permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power (128 or 10mW) or no ultrasound (controls). We measured cerebral hemorrhage, indirect and direct infarct volume as well as edema volume at 24h. No cerebral hemorrhages were detected in all animals. Exposure to low-power (10mW) ultrasound resulted in a significantly decreased indirect infarct volume (p = 0.0039), direct infarct volume (p = 0.0031), and brain edema volume (p = 0.01) compared with controls. High-power (128mW) ultrasound had no significant effects. An additional experiment with India ink showed a greater intravascular penetration of dye into ischemic tissues exposed to low-power ultrasound. Insonation with high-frequency, low-power ultrasound reduces ischemic brain damage in rat. Its effect on edema reduction and possible promotion of microcirculation could be used to facilitate drug and nutrient delivery to ischemic areas. KeywordsCerebral ischemia–Transcranial ultrasound–Brain edema reduction–Microcirculation
  04/2012; 2(3):376-381.
• Article: Advances in transcranial doppler ultrasonography

  Georgios Tsivgoulis, Andrei V. Alexandrov, Michael A. Sloan
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  ABSTRACT: Transcranial Doppler ultrasonography (TCD) is the only noninvasive real-time neuroimaging modality for the evaluation of characteristics of blood flow in basal intracerebral vessels that adds physiologic information to structural imaging. TCD has been rapidly evolving from a simple noninvasive diagnostic tool to an imaging modality with a broad spectrum of clinical applications. In acute stroke, TCD can provide rapid information about vascular stenosis and occlusion, the hemodynamic status of the cerebral circulation, and real-time monitoring of recanalization. Extended applications such as vasomotor reactivity testing, emboli monitoring, and right-to-left shunt detection help clinicians ascertain stroke mechanisms at the bedside, plan and monitor treatment, and determine prognosis. In the neurointensive care unit, TCD is useful for detecting increased intracranial pressure and confirming cerebral circulatory arrest. TCD is of established value for screening children with sickle cell disease and detecting and monitoring vasospasm after spontaneous subarachnoid hemorrhage.
  Current Neurology and Neuroscience Reports 04/2012; 9(1):46-54. · 3.45 Impact Factor
• Article: The argatroban and tissue-type plasminogen activator stroke study: final results of a pilot safety study.

  Andrew D Barreto, Andrei V Alexandrov, Pat Lyden, Jessica Lee, Sheryl Martin-Schild, Loren Shen, Tzu-Ching Wu, April Sisson, Renganayaki Pandurengan, Zhongxue Chen, [......], Clotilde Balucani, Kristian Barlinn, Rebecca M Sugg, Zsolt Garami, Georgios Tsivgoulis, Nicole R Gonzales, Sean I Savitz, Robert Mikulik, Andrew M Demchuk, James C Grotta
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  ABSTRACT: Argatroban is a direct thrombin inhibitor that safely augments recanalization achieved by tissue-type plasminogen activator (tPA) in animal stroke models. The Argatroban tPA Stroke Study was an open-label, pilot safety study of tPA plus Argatroban in patients with ischemic stroke due to proximal intracranial occlusion. During standard-dose intravenous tPA, a 100-μg/kg bolus of Argatroban and infusion for 48 hours was adjusted to a target partial thromboplastin time of 1.75× baseline. The primary outcome was incidence of significant intracerebral hemorrhage defined as either symptomatic intracerebral hemorrhage or Parenchymal Hematoma Type 2. Recanalization was measured at 2 and 24 hours by transcranial Doppler or CT angiography. Sixty-five patients were enrolled (45% men, mean age 63±14 years, median National Institutes of Health Stroke Scale=13). The median (interquartile range) time tPA to Argatroban bolus was 51 (38-60) minutes. Target anticoagulation was reached at a median (interquartile range) of 3 (2-7) hours. Significant intracerebral hemorrhage occurred in 4 patients (6.2%; 95% CI, 1.7-15.0). Of these, 3 were symptomatic (4.6%; 95% CI, 0.9-12.9). Seven patients (10%) died in the first 7 days. Within the 2-hour monitoring period, transcranial Doppler recanalization (n=47) occurred in 29 (61%) patients: complete in 19 (40%) and partial in another 10 (21%). The combination of Argatroban and intravenous tPA is potentially safe in patients with moderate neurological deficits due to proximal intracranial arterial occlusions and may produce more complete recanalization than tPA alone. Continued evaluation of this treatment combination is warranted. URL: www.clinicaltrials.gov. Unique identifier: NCT00268762.
  Stroke 03/2012; 43(3):770-5. · 5.73 Impact Factor
• Source

  Available from: Zeljko Zivanovic

  Article: Intracranial vessel localization with power motion Doppler (PMD-TCD) compared with CT angiography in patients with acute ischaemic stroke.

  Kristian Barlinn, Zeljko Zivanovic, Limin Zhao, Maruthi Kesani, Clotilde Balucani, Georgios Tsivgoulis, Andrei V Alexandrov
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  ABSTRACT: INTRODUCTION: With a view to develop an operator-independent monitoring system for sonothrombolysis, we aimed to evaluate the per cent agreement of power motion transcranial Doppler vessel tracks compared with computed tomography angiography in identification of the anterior and posterior circulation vessels in patients with acute ischaemic stroke. METHODS: Consecutive acute ischaemic stroke patients who underwent emergent brain computed tomography angiography and bedside power motion transcranial Doppler were studied. Depth ranges for detecting anterior and posterior circulation vessels were derived from power motion transcranial Doppler flow tracks and computed tomography angiography images of the circle of Willis. We calculated percent agreement of power motion transcranial Doppler with computed tomography angiography for the anterior and posterior circulation vessel localization using computed tomography angiography as reference. RESULTS: Samples were obtained from 34 acute ischaemic stroke patients (mean age 61 ± 16 years, 62% men, median National Institutes of Health Stroke Scale (NIHSS) score 5, interquartile range 2-8). A total of 229 Power motion Doppler computed tomography angiography vessel pairs were analysed. Power motion transcranial Doppler tracks for M1 and proximal M2 middle cerebral artery (MCA) were located at 24-68 mm (M1 MCA: 36-68 mm; M2 MCA: 24-53 mm); anterior cerebral artery (ACA): 50-78 mm; P1 posterior cerebral artery (PCA): 50-74 mm; left vertebral artery: 30-74 mm; right vertebral artery: 30-78 mm; basilar artery: 76-106 mm. The per cent agreement of power motion Doppler-transcranial Doppler for identifying proximal intracranial arteries compared to computed tomography angiography was: M1 and M2 MCA: 100% (95% confidence interval: 96-100%); M1 MCA: 98% (95% confidence interval: 86-100%); M2 MCA: 94% (95% confidence interval: 79-99%); A1 ACA: 82% (95% confidence interval: 68-91%); P1 PCA: 70% (95% confidence interval: 53-83%); left vertebral artery: 96% (95% confidence interval: 80-100%); right vertebral artery: 96% (95% confidence interval: 79-100%); basilar artery: 100% (95% confidence interval: 89-100%). CONCLUSIONS: Power motion transcranial Doppler intercepts proximal vessels with good-to-excellent agreement with computed tomography angiography. Depth ranges (as opposed to average depths) can be used to target intracranial arterial segments for sonothrombolysis.
  International Journal of Stroke 02/2012; · 2.38 Impact Factor
• Article: Adjunctive and alternative approaches to current reperfusion therapy.

  Andrew D Barreto, Andrei V Alexandrov
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  ABSTRACT: BACKGROUND AND PURPOSE: Current ischemic stroke reperfusion therapy consists of intravenous thrombolysis given in eligible patients after review of a noncontrast CT scan and a time-based window of opportunity. Rapid clot lysis has a strong association with clinical improvement but remains incomplete in many patients. This review appraises novel adjunctive or alternative approaches to current reperfusion strategies being tested in all trial phases. Summary of Review- Alternative approaches to current reperfusion therapy can be separated into 4 main categories: (1) combinatory approaches with other drugs or devices; (2) novel systemic thrombolytic agents; (3) endovascular medical or mechanical reperfusion treatments; and (4) noninvasive or minimally invasive methods to augment cerebral blood flow and alleviate intracranial blood flow steal. CONCLUSIONS: Reperfusion treatments must be provided as fast as possible in patients most likely to benefit. Patients who fail to rapidly reperfuse may benefit from other strategies that maintain collateral flow or protect tissue at risk.
  Stroke 02/2012; 43(2):591-8. · 5.73 Impact Factor
• Article: Arterial reocclusion and persistent distal occlusion after thrombus aspiration.

  Limin Zhao, Marta Rubiera, Mark R Harrigan, Andrei V Alexandrov
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  ABSTRACT: Early reocclusion of intracranial arteries can lead to poor clinical outcome. We report reocclusion detection after endovascular clot aspiration, followed by administration of GPIIb-IIIa antagonist under continuous ultrasound monitoring. A 73-year-old man developed the right middle cerebral artery (MCA) occlusion with NIHSS 17 points, 6 days after aortic valve replacement. Recanalization was achieved with Penumbra™ system and reocclusion was detected with transcranial Doppler (TCD) 30 minutes postcompletion of intra-arterial procedure. Proximal recanalization was achieved with the second thrombus aspiration while M2 MCA occlusion persisted beyond the reach of the device. Intravenous abciximab was administered under continuous TCD monitoring. Recanalization with Thrombolysis in Brain Ischemia (TIBI) flow grade 4 was observed at 60 minutes postintervention accompanied with clinical recovery to NIHSS 3 points. Abciximab was given for 12 hours with no hemorrhagic transformation on repeat CT scan. Patient was discharged home with mild left pronator drift and facial droop, and his modified ranking score was 1 at 6-week follow-up visit. Early arterial reocclusion can occur after successful thrombus aspiration while GPIIb-IIIa antagonist administration may lead to subsequent recanalization of persisting distal occlusions not amenable to mechanical removal.
  Journal of neuroimaging: official journal of the American Society of Neuroimaging 01/2012; 22(1):92-4. · 1.72 Impact Factor
• Article: Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study.

  Maurizio Paciaroni, Clotilde Balucani, Giancarlo Agnelli, Valeria Caso, Giorgio Silvestrelli, James C Grotta, Andrew M Demchuk, Sung-Il Sohn, Giovanni Orlandi, Didier Leys, [......], Claudia Trentini, Giuseppe Martini, Charitomeni Piperidou, Ioannis Heliopoulos, Sebastiano D'Anna, Manuel Cappellari, Edoardo Donati, Giorgio Bono, Elisabetta Traverso, Danilo Toni
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  ABSTRACT: The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0-2) or unfavorable (score of 3-6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03-3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36-3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87-58.71; P=0.068) in the cases than in the controls. In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.
  Stroke 01/2012; 43(1):125-30. · 5.73 Impact Factor