Elefterios Stamboulis

Safety and outcomes of intravenous thrombolysis in stroke mimics: a 6-year, single-care center study and a pooled analysis of reported series.

Background and Purpose— Efforts to increase the availability and shorten the time delivery of intravenous thrombolysis in patients with acute ischemic stroke carry the potential for tissue plasminogen activator administration in patients with diseases other than stroke, that is, stroke mimics (SMs). We aimed to determine safety and to describe outcomes of intravenous thrombolysis in SM. Methods— We retrospectively analyzed stroke registry data of consecutive acute ischemic stroke admissions treated with intravenous thrombolysis over a 6-year-period. The admission National Institutes of Health Stroke Scale score, vascular risk factors, ischemic lesions on brain MRI (routinely performed as part of diagnostic work-up), and discharge modified Rankin Scale scores were documented. Initial stroke diagnosis in the emergency department was compared with final discharge diagnosis. SM diagnosis was based on the absence of ischemic lesions on diffusion-weighted imaging sequences in addition to an alternate discharge diagnosis. Symptomatic intracranial hemorrhage was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by National Institutes of Health Stroke Scale score increase of ≥4 points. Results— Intravenous thrombolysis was administered in 539 patients with acute ischemic stroke (55% men; mean age, 66±15 years). Misdiagnosis of acute ischemic stroke was documented in 56 cases (10.4%; 95% CI, 7.9% to 13.3%). Conversion disorder (26.8%), complicated migraine (19.6%), and seizures (19.6%) were the 3 most common final diagnoses in SM. SMs were younger (mean age, 56±13 years) and had milder baseline stroke severity (median National Institutes of Health Stroke Scale, 6; interquartile range, 4) compared with patients with confirmed acute ischemic stroke (mean age, 67±14 years; median National Institutes of Health Stroke Scale, 8; interquartile range, 10; P<0.001). There was no case of symptomatic intracranial hemorrhage in SMs (0%; 95% CI, 0% to 5.5%); 96% of SMs were functionally independent at hospital discharge (modified Rankin Scale, 0 to 1). Conclusions— Our single-center data indicate favorable safety and outcomes of intravenous thrombolysis administered to SM.

Impact of Prehypertension on Common Carotid Artery Intima-Media Thickness and Left Ventricular Mass

Background and Purpose— Prehypertension has been recently introduced by JNC 7 as a new blood pressure (BP) category, associated with increased target-organ damage. Subclinical atherosclerosis by means of common artery intima-media thickness (CCA-IMT) has been incompletely investigated in prehypertensive patients. The aim of our study was to assess the extent of CCA-IMT and left ventricular mass (LVM) in prehypertensive adults in comparison to normotensive and untreated hypertensive subjects. Methods— From a total of 5221 consecutive patients screened to our Hypertension Unit we selected 896 consecutive individuals according to prespecified inclusion criteria, who underwent 24-hour ambulatory BP monitoring, carotid artery ultrasonographic, and echocardiographic measurements. Patients who received antihypertensive treatment during the BP monitoring were excluded. According to the office BP levels, patients were divided into 3 subgroups: normotensives (office BP <120/80 mm Hg), prehypertensives (120/80 mm Hg≤office BP<140/90 mm Hg), and hypertensives (office BP ≥140/90 mm Hg). Statistical analyses were performed by means of 1-way ANOVA, &khgr;2 test, and ANCOVA. Results— According to the office BP levels, the distribution of the study population was: normotensives (14.4%), prehypertensives (23.7%), and hypertensives (61.9%). Prehypertensive patients had higher CCA-IMT (P=0.038) and LVM (P=0.030) values than normotensive subjects, even after adjustment for baseline characteristics. Greater CCA-IMT values were observed in hypertensive patients in comparison to prehypertensives (P=0.002). Conclusions— Prehypertensive patients had higher CCA-IMT and LVM than their normotensive counterparts. Prehypertension status is cross-sectionally associated with subclinical atherosclerosis and target-organ damage.

Velocity Criteria for Intracranial Stenosis Revisited An International Multicenter Study of Transcranial Doppler and Digital Subtraction Angiography

Background and Purpose— Intracranial atherosclerotic disease is associated with a high risk of stroke recurrence. We aimed to determine accuracy of transcranial Doppler screening at laboratories that share the same standardized scanning protocol. Methods— Patients with symptoms of cerebral ischemia were prospectively studied. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) criteria were used for identification of ≥50% stenosis. We determined velocity cutoffs for ≥70% stenosis on digital subtraction angiography by Warfarin–Aspirin Symptomatic Intracranial Disease criteria and evaluated novel stenotic/prestenotic ratio and low-velocity criteria. Results— A total of 102 patients with intracranial atherosclerotic disease (age 57±13 years; 72% men; median National Institutes of Health Stroke Scale 3, interquartile range 6) provided 690 transcranial Doppler/digital subtraction angiography vessel pairs. On digital subtraction angiography, ≥50% stenosis was found in 97 and ≥70% stenosis in 62 arteries. Predictive values for transcranial Doppler SONIA criteria were similar (P>0.9) between middle cerebral artery (sensitivity 78%, specificity 93%, positive predictive value 73%, negative predictive value 94%, and overall accuracy 90%) and vertebral artery/basilar artery (69%, 98%, 88%, 93%, and 92%). As a single velocity criterion, most sensitive mean flow velocity thresholds for ≥70% stenosis were: middle cerebral artery >120 cm/s (71%) and vertebral artery/basilar artery >110 cm/s (55%). Optimal combined criteria for ≥70% stenosis were: middle cerebral artery >120 cm/s, or stenotic/prestenotic ratio ≥3, or low velocity (sensitivity 91%, specificity 80%, receiver operating characteristic 0.858), and vertebral artery/basilar artery >110 cm/s or stenotic/prestenotic ratio ≥3 (60%, 95%, 0.769, respectively). Conclusions— At laboratories with a standardized scanning protocol, SONIA mean flow velocity criteria remain reliably predictive of ≥50% stenosis. Novel velocity/ratio criteria for ≥70% stenosis increased sensitivity and showed good agreement with invasive angiography.

Pre–Tissue Plasminogen Activator Blood Pressure Levels and Risk of Symptomatic Intracerebral Hemorrhage

Background and Purpose— From small pilot studies, uncontrolled pretreatment systolic blood pressure >185 mm Hg and diastolic blood pressure >110 mm Hg in patients with acute ischemic stroke were introduced in the National Institute of Neurological Diseases and Stroke rtPA Stroke Study as a contraindication for thrombolysis. We sought to determine if pretreatment blood pressure protocol violations in patients with acute ischemic stroke receiving intravenous tissue plasminogen activator are related to the subsequent risk of symptomatic intracranial hemorrhage (sICH). Methods— We reviewed medical records of consecutive ischemic stroke admissions treated with intravenous thrombolysis over a 10-year period at our tertiary care hospital. The National Institutes of Health Stroke Scale score on admission was used to determine baseline stroke severity. The closest documented blood pressure values to the time of tissue plasminogen activator bolus (range, 0 to 10 minutes) were considered as pretreatment blood pressure. Pretreatment blood pressure protocol violations were identified as systolic blood pressure >185 or diastolic blood pressure >110 mm Hg prebolus. sICH was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by the National Institutes of Health Stroke Scale score increase of ≥4 points. Results— Among 510 patients with ischemic stroke treated with intravenous tissue plasminogen activator (282 men; mean age, 65±15 years), sICH occurred in 31 patients (6.1%). Blood pressure protocol violations were present in 63 patients (12.4%) and they were more frequent in patients with sICH (26% versus 12%; P=0.019). After adjusting for demographic characteristics, onset-to-treatment time, baseline National Institutes of Health Stroke Scale, stroke risk factors and medications, pretreatment blood pressure protocol violations were independently associated with a higher likelihood of sICH (OR, 2.59; 95% CI, 1.07 to 6.25; P=0.034). Conclusions— These data support current guidelines advising not to use intravenous tissue plasminogen activator when pretreatment blood pressure exceeds the prespecified thresholds by showing that blood pressure protocol violations are independently associated with a higher likelihood of sICH.

Real-time Validation of Transcranial Doppler Criteria in Assessing Recanalization During Intra-arterial Procedures for Acute Ischemic Stroke An International, Multicenter Study

Background and Purpose— 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 &kgr;: 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.

Prevalence of Symptomatic Intracranial Atherosclerosis in Caucasians: A Prospective, Multicenter, Transcranial Doppler Study

There are limited data available regarding symptomatic intracranial atherosclerosis (SIA) prevalence in Caucasians. We sought to investigate SIA prevalence among Caucasian patients hospitalized with acute cerebral ischemia (ACI) in a prospective, multicenter Transcranial Doppler sonography (TCD) study.

Safety of transcranial Doppler ‘bubble study’ for identification of right to left shunts: an international multicentre study

Background and purpose A recent retrospective study using an online list service established by the American Academy of Neurology has suggested that ischaemic cerebrovascular events may occur in patients who undergo ‘bubble studies’ (BS) with either transcranial Doppler (TCD) or transoesophageal echocardiography (TOE). The safety of TCD-BS for right to left shunt (RLS) identification was evaluated prospectively in an international multicentre study. Methods Consecutive patients with cerebral ischaemia (ischaemic stroke or transient ischaemic attack (TIA)) were screened for potential ischaemic cerebrovascular events following injection of microbubbles during TCD-BS for identification of RLS at three tertiary care stroke centres. TCD-BS was performed according to the standardised International Consensus Protocol. TOE-BS was performed in selected cases for confirmation of TCD-BS. Results 508 patients hospitalised with acute cerebral ischaemia (mean age 46±12 years, 59% men; 63% ischaemic stroke, 37% TIA) were investigated with TCD-BS within 1 week of ictus. RLS was identified in 151 cases (30%). TOE-BS was performed in 101 out of 151 patients with RLS identified on TCD-BS (67%). It was positive in 99 patients (98%). The rate of ischaemic cerebrovascular complications during or after TCD-BS was 0% (95% CI by the adjusted Wald method: 0–0.6%). Structural cardiac abnormalities were identified in 38 patients, including atrial septal aneurysm (n=23), tetralogy of Fallot (n=1), intracardiac thrombus (n=2), ventricular septal defect (n=3) and atrial myxoma (n=1). Conclusion TCD-BS is a safe screening test for identification of RLS, independent of the presence of cardiac structural abnormalities.

End-Diastolic Velocity Increase Predicts Recanalization and Neurological Improvement in Patients With Ischemic Stroke With Proximal Arterial Occlusions Receiving Reperfusion Therapies

Background and Purpose— It is unknown how little flow velocity improvement is necessary to achieve recanalization and clinical recovery. We sought to investigate which flow velocity parameter was associated with complete recanalization/reperfusion and neurological improvement in patients receiving reperfusion therapies. Methods— Patients with proximal intracranial occlusions were treated with systemic or intra-arterial tissue plasminogen activator within 6 hours from symptom onset. Consecutive peak systolic and end-diastolic (EDV) velocities were measured during continuous transcranial Doppler monitoring. Recanalization was graded with Thrombolysis in Brain Ischemia grades. Neurological and functional outcomes were assessed by the National Institutes of Health Stroke Scale and modified Rankin Scale scores. Results— Of 36 patients (mean age 57±19 years, median National Institutes of Health Stroke Scale 15 points, interquartile range 9), 13 (36%) achieved complete recanalization and those had greater EDV increase during transcranial Doppler monitoring (15±11 cm/s versus 6±10 cm/s; P=0.001). Peak systolic velocity increase with complete recanalization was 25±11 cm/s (versus 20±25 cm/s with partial recanalization/persisting occlusion; P=0.123). Neurological improvement at 24 hours positively correlated to EDV increase (Spearman r=0.337, P=0.044) but not to peak systolic velocity (r=0.197, P=0.250). EDV increase at the end of monitoring was higher in patients with favorable functional outcome at 3 months (13±13 cm/s versus 4±8 cm/s; P=0.021). After adjustment for potential confounders, including age, stroke risk factors, and baseline stroke severity, a 10-cm/s increase in EDV was independently associated with a 3-point decline in the National Institutes of Health Stroke Scale score at 24 hours from baseline (95% CI: 0 to 5; P=0.045). Conclusions— A modest increase in the EDV as opposed to peak systolic velocity is associated with complete recanalization/reperfusion, early neurological improvement, and favorable functional outcome. Diastolic flow augmentation may represent a novel target for development of reperfusion therapies.

Cerebrovascular reacivity assessment in patients with carotid artery disease: a combined TCD and NIRS study.

Transcranial Doppler (TCD) and near‐infrared spectroscopy (NIRS) are two noninvasive diagnostic tools that have been shown to evaluate cerebral vasomotor reactivity by measuring changes in mean cerebral blood flow velocities (MCBFV) of proximal intracranial arteries and absolute brain‐tissue oxygen‐saturation (TOS) in microcirculation, respectively, during hemodynamic challenge. We evaluated the potential correlation between TCD and NIRS measurements of vasomotor reactivity (VMR) in patients with carotid artery disease (CARAD).

Validity of HAT Score for Predicting Symptomatic Intracranial Hemorrhage in Acute Stroke Patients with Proximal Occlusions: Data from Randomized Trials of Sonothrombolysis

Background: The Hemorrhage after Thrombolysis (HAT) score has recently been introduced as a practical scale for risk stratification of intracranial hemorrhage (ICH) in patients receiving intravenous tissue plasminogen activator (tPA). We aimed to externally validate and evaluate the predictive ability of the HAT score in patients with proximal arterial occlusions (PAO) enrolled into randomized clinical trials of sonothrombolysis. Methods: The HAT score (range 0, minimum risk, to 5, maximum risk) was retrospectively calculated for each patient using clinical trial data (baseline NIHSS, extent of hypodensity on CT, history of diabetes mellitus and serum glucose). Symptomatic ICH (sICH) was defined as imaging evidence of ICH with clinical worsening (NIHSS ≧4) within 72 h from stroke onset. The predictive ability of the HAT score for sICH and any ICH (both asymptomatic and symptomatic) was calculated using c statistics. Results: A total of 161 tPA-treated patients (mean age 68 ± 13 years, 58% men, median NIHSS 16, interquartile range 9) with PAO were randomized in TUCSON (n = 35) and CLOTBUST (n = 126). sICH occurred in 9 (5.6%) cases, and 6 had asymptomatic ICH. The rates of sICH for the corresponding HAT scores were: HAT 0–1: 3%; 2: 9%; 3: 14%; 4–5: 14%. The risk of sICH (c statistic 0.72, 95% CI: 0.58–0.86; p = 0.027) and any ICH (c statistic 0.70, 95% CI: 0.58–0.82; p = 0.011) increased with higher HAT scores. Higher HAT scores were also associated with higher likelihood of persisting occlusion (c statistic 0.63, 95% CI: 0.54–0.72; p = 0.004). Conclusions: The HAT score has reasonable external validity for predicting the risk of sICH following intravenous thrombolysis in patients with PAO. Moreover, higher HAT scores appear to be associated with higher likelihood of persisting occlusion in tPA-treated patients.