Intracranial Pulsatility in Relation to Severity and Progression of Cerebral White Matter Hyperintensities.

BACKGROUND AND PURPOSE: Previous studies suggested an association between increased intracranial arterial pulsatility and the severity of microangiopathic white matter hyperintensities (WMH). However, possible confounders such as age and hypertension were seldomly considered and longitudinal data are lacking. We here aimed to explore whether increased middle cerebral artery pulsatility is associated with baseline severity and progression of cerebral small vessel disease-related WMH in elderly individuals. METHODS: The study population consisted of elderly participants from the community-based ASPS (Austrian Stroke Prevention Study). Baseline and follow-up assessment comprised transcranial Doppler sonography, brain magnetic resonance imaging, and clinical/laboratory examination of vascular risk factors. Pulsatility index on transcranial Doppler sonography was averaged from baseline indices of both middle cerebral arteries and was correlated with baseline WMH severity and WMH progression over a median follow-up period of 5 years in uni- and multivariable analyses. WMH severity was graded according to the Fazekas scale, and WMH load was quantified by semiautomated volumetric assessment. RESULTS: The study cohort comprised 491 participants (mean age: 60.7±6.9 years; female: 48.5%). Pulsatility index was increased in participants with more severe WMH at baseline (P<0.001) but was not associated with WMH progression during follow-up (rs: 0.097, P=0.099). In multivariable analyses, only arterial hypertension remained significantly associated with baseline severity (P=0.04) and progression (P=0.008) of WMH, although transcranial Doppler sonography pulsatility index was not predictive (P>0.1, respectively). CONCLUSIONS: This community-based cohort study of elderly individuals does not support the pulsatility index of the middle cerebral artery on transcranial Doppler sonography as an independent marker of microangiopathic WMH severity and progression over time.

Mean Platelet Volume Does Not Predict Restenosis After Carotid Artery Stenting in Whites.

Background and Purpose- Mean platelet volume (MPV) indicates platelet activity possibly affecting patient's risk for progressive atherosclerotic disease. A recent study identified elevated MPV as a predictor of in-stent restenosis (ISR) after carotid artery stenting (CAS) in a Chinese population. However, the role of MPV on the development of ISR following CAS in whites is yet unknown. Methods- We retrospectively identified all consecutive patients who underwent CAS for atherosclerotic disease at our center from 2005 to 2017. All patients were followed clinically and by duplex sonography at 1, 3, and 6 months and annually after CAS. ISR was defined as ≥50% stenosis (NASCET [North American Symptomatic Carotid Endarterectomy Trial] criteria) in the treated vessel. MPV was assessed before CAS, at last follow-up and at the time of ISR detection. Results- Of 392 patients with CAS (mean age 68.5±9.5 years, 26.8% women, 42.3% symptomatic stenosis), 54 had ISR after a mean follow-up time of 32 months. Baseline MPV was not different in ISR compared with non-ISR patients (10.7 versus 10.6 fL, P=0.316). MPV levels did also not change from baseline to ISR detection (P=0.310) and were not associated with recurrent stroke or vascular events (P>0.5). Multivariable analysis identified active smoking as the sole risk factor for carotid ISR (odds ratio, 2.53 [95% CI, 1.21-5.29]). Conclusions- We did not identify MPV as a risk factor for ISR after CAS in whites. Smoking cessation is an important target to avoid this complication.

Abnormal Blood Flow on Transcranial Duplex Sonography Predicts Poor Outcome After Stroke Thrombectomy.

Background and Purpose- Hemodynamic changes following mechanical thrombectomy for large vessel occlusion stroke could be associated with complications and might affect prognosis. We investigated postinterventional middle cerebral artery blood flow on transcranial duplex sonography (TCD) and its prognostic value for anterior large vessel occlusion stroke patients. Methods- We identified all ischemic stroke patients who had undergone mechanical thrombectomy for anterior circulation large vessel occlusion from 2010 onwards. Postinterventional middle cerebral artery flow was graded according to the sonographic Thrombolysis in Brain Ischemia score and related to patient outcome stratified by the angiographic Thrombolysis in Cerebral Infarction reperfusion status. Results- Of 215 large vessel occlusion stroke patients, 193 patients (90%) showed successful angiographic recanalization (Thrombolysis in Cerebral Infarction grade 2b-3). Of those, 69 (36%) patients had abnormal sonographic middle cerebral artery blood flow (Thrombolysis in Brain Ischemia grade 0-4) within 72 hours after mechanical thrombectomy, which was an independent predictor for poor 90-day outcome. Conclusions- TCD indicates abnormal middle cerebral artery hemodynamics in a substantial proportion of patients with angiographically defined successful mechanical thrombectomy of the anterior cerebral circulation. Such changes are associated with poor short-term outcome.

Sex-related differences of acute stroke unit care: results from the Austrian stroke unit registry.

BACKGROUND AND PURPOSE: Sex-related differences in quality of acute stroke care are an important concern with limited data available, specifically regarding stroke unit (SU) setting. We used the prospective nationwide Austrian SU registry to address this issue. METHODS: Our analysis covered an 8-year time period (January 2005 to December 2012) during which all patients with transient ischemic attack or ischemic stroke admitted to 1 of 35 Austrian SU had been captured in the registry. These data were analyzed for age-adjusted preclinical and clinical characteristics and quality of acute stroke care in men and women. In addition, we assessed the outcome at 3 months in multivariate analysis. RESULTS: A total of 47 209 individuals (47% women) had received SU care. Women were significantly older (median age: 77.9 versus 70.3 years), had higher pre-existing disability and more severe strokes. Correcting for age, no significant sex-related differences in quality of care were identified with comparable onset-to-door times, times to and rates of neuroimaging, as well as door-to-needle times and rates of intravenous thrombolysis (14.5% for both sexes). Despite equal acute stroke care and a comparable rate of neurorehabilitation, women had a worse functional outcome at 3-month follow-up (modified Rankin scale 3-5: odds ratio, 1.26; 95% confidence interval [1.17-1.36]), but a lower mortality (odds ratio, 0.70; 95% confidence interval [0.78-0.88]) after correcting for confounders. CONCLUSIONS: We identified no disproportions in quality of care in the acute SU setting between men and women, but the outcome was significantly different. Further studies on the poststroke period including socioeconomic aspects are needed to clarify this finding.

Post-reperfusion hyperperfusion after endovascular stroke treatment: a prospective comparative study of TCD versus MRI.

BACKGROUND: Increased middle cerebral artery (MCA) blood flow velocities on transcranial duplex sonography (TCD) were recently reported in individual patients after successful mechanical thrombectomy (MT) and were related to intracranial hemorrhage and poor outcome. However, the retrospective study design of prior studies precluded elucidation of the underlying pathomechanisms, and the relationship between TCD and brain parenchymal perfusion still remains to be determined. METHODS: We prospectively investigated consecutive patients with stroke successfully recanalized by MT with TCD and MRI including contrast-enhanced perfusion sequences within 48 hours post-intervention. Increased MCA flow on TCD was defined as >30% mean blood flow velocity in the treated MCA compared with the contralateral MCA. MRI blood flow maps served to assess hyperperfusion rated by neuroradiologists blinded to TCD. RESULTS: A total of 226 patients recanalized by MT underwent post-interventional TCD and 92 patients additionally had perfusion MRI. 85 patients (38%) had increased post-interventional MCA flow on TCD. Of these, 10 patients (12%) had an underlying focal stenosis. Increased TCD blood flow in the recanalized MCA was associated with larger infarct size, vasogenic edema, intracranial hemorrhage and poor 90-day outcome (all p≤0.005). In the subgroup for which both TCD and perfusion MRI were available, 29 patients (31%) had increased ipsilateral MCA flow velocities on TCD. Of these, 25 patients also showed parenchymal hyperperfusion on MRI (sensitivity 85%; specificity 62%). Hyperperfusion severity on MRI correlated with MCA flow velocities on TCD (rs=0.379, p<0.001). CONCLUSIONS: TCD is a reliable bedside tool to identify post-reperfusion hyperperfusion, correlates well with perfusion MRI, and indicates risk of reperfusion injury after MT.

Long-term risk of recurrent cerebrovascular events after patent foramen ovale closure: Results from a real-world stroke cohort.

INTRODUCTION: Patent foramen ovale (PFO)-closure is recommended for stroke prevention in selected patients with suspected PFO-associated stroke. However, studies on cerebrovascular event recurrence after PFO-closure are limited by relatively short follow-up periods and information on the underlying aetiology of recurrent events is scarce. PATIENTS AND METHODS: All consecutive patients with a cerebral ischaemic event and PFO-closure at the University Hospital Graz were prospectively identified from 2004 to 2021. Indication for PFO-closure was based on a neurological-cardiological PFO board decision. Patients underwent standardized clinical and echocardiographic follow-up 6 months after PFO-closure. Recurrent cerebrovascular events were assessed via electronical health records. RESULTS: PFO-closure was performed in 515 patients (median age: 49 years; Amplatzer PFO occluder: 42%). Over a median follow-up of 11 years (range: 2-18 years, 5141 total patient-years), recurrent ischaemic cerebrovascular events were observed in 34 patients (ischaemic stroke: n = 22, TIA: n = 12) and associated with age, hyperlipidaemia and smoking in multivariable analysis (p < 0.05 each). Large artery atherosclerosis and small vessel disease were the most frequent aetiologies of recurrent stroke/TIA (27% and 24% respectively), and only two events were related to atrial fibrillation (AF). Recurrent ischaemic cerebrovascular event rates and incident AF were comparable in patients treated with different PFO occluders (p > 0.1). DISCUSSION AND CONCLUSION: In this long-term follow-up-study of patients with a cerebral ischaemic event who had received PFO-closure with different devices, rates of recurrent stroke/TIA were low and largely related to large artery atherosclerosis and small vessel disease. Thorough vascular risk factor control seems crucial for secondary stroke prevention in patients treated for PFO-related stroke.

Complication rates using balloon-expandable and self-expanding stents for the treatment of intracranial atherosclerotic stenoses : analysis of the INTRASTENT multicentric registry.

INTRODUCTION: Using balloon-expandable stents (BES) for treatment of intracranial stenoses, high inflation pressures and rigidity of the device are regarded as major drawbacks limiting feasibility and safety of the procedure. Self-expanding stents (SES) were developed to facilitate lesion access and to allow for less aggressive dilatation. We analyzed data of the INTRASTENT multicentric registry to assess whether self-expanding stents significantly reduced peri-interventional complication rates. METHODS: Records of intracranial stent procedures were entered consecutively into the registry. Datasets were divided into two groups according to the type of stent used. For outcome measurement, we chose three categories: TIA/minor stroke [modified Rankin score (mRS) <2], disabling stroke, and patient death. Clinical outcome was compared between BES and SES. We analyzed types of adverse events occurring in each group in addition. RESULTS: Of 409 atherosclerotic lesions, 254 were treated with BES and 155 with SES. Technical success rates were 97.6% and 98.7%, respectively. Adverse event rates were 4.9%, 3.7%, and 0.8% for TIA/nondisabling stroke, disabling stroke, and death in the BES group compared with 5.3%, 6.0%, and 4.0% in the SES group. The differences were not statistically significant. We observed more perforator strokes after use of BES, but thromboembolic events occurred more often in the SES treatment group. CONCLUSION: Data of the INTRASTENT registry do not support the hypothesis that introduction of SES lowered the overall complication rate of intracranial stent procedures. There might be an advantage using self-expanding stents in vessel segments with important perforating arteries.

Relevance of Cognition and Emotion for Patient-Reported Quality of Life After Stroke in Working Age: An Observational Cohort Study.

Background: Patient-reported quality of life (QoL) may help to capture sequela of stroke more comprehensively. We aimed to investigate QoL in working age persons with ischemic stroke regarding impaired domains and identify factors associated with better QoL. Methods: We invited persons with stroke aged 18-55 years to participate in this prospective observational study. We assessed QoL and self-rated health using the EuroQol 5 Dimension questionnaire (EQ-5D) during hospital stay (baseline) and at 3-months follow-up (FU). Additionally, the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), cognition (Montreal Cognitive assessment, MOCA), emotion (Hospital Anxiety and Depression Scale), and return to work were evaluated. We used hierarchical regression to identify predictors of QoL (self-rated health and QoL Index score) at FU. Results: We included 138 persons with stroke (mean age = 43.6 ± 10 years; 41% female; median admission NIHSS = 2), of whom 99 participated at FU. QoL Index and self-rated health were correlated with NIHSS, mRS, anxiety, and depression at both timepoints. Although 80% had favorable functional outcome at FU (mRS < 2), high proportions of these persons reported problems in the "Pain and/or Discomfort" (25.3%) and "Anxiety/Depression" (22.8%) dimensions. Only discharge NIHSS and baseline MOCA independently predicted self-rated health at FU. Female sex, higher discharge NIHSS, and higher baseline depression scores predicted worse QoL Index scores at FU. Conclusions: Three months post-stroke, working age persons with stroke frequently reported problems in dimensions not assessed by the routinely used mRS. Despite correlations between clinical scales and QoL, patient-reported outcomes and screening for cognition and emotion ensure a more comprehensive assessment of post-stroke consequences relevant for QoL.

Blood biomarkers of progressive atherosclerosis and restenosis after stenting of symptomatic intracranial artery stenosis.

In-stent restenosis (ISR) represents a major complication after stenting of intracranial artery stenosis (ICAS). Biomarkers derived from routine blood sampling including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) have been associated with progressive atherosclerosis. We investigated the role of CRP, NLR, PLR and MPV on the development of intracranial ISR and recurrent stroke risk. We retrospectively included all patients who had undergone stenting of symptomatic ICAS at our university hospital between 2005 and 2016. ISR (≥ 50% stenosis) was diagnosed by regular Duplex sonography follow-up studies and confirmed by digital subtraction angiography or computed tomography angiography (mean follow-up duration: 5 years). Laboratory parameters were documented before stenting, at the time of restenosis and at last clinical follow-up. Of 115 patients (mean age: 73 ± 13 years; female: 34%), 38 (33%) developed ISR. The assessed laboratory parameters did not differ between patients with ISR and those without (p > 0.1). While ISR was associated with the occurrence of recurrent ischemic stroke (p = 0.003), CRP, NLR, PLR and MPV were not predictive of such events (p > 0.1). Investigated blood biomarkers of progressive atherosclerosis were not predictive for the occurrence of ISR or recurrent ischemic stroke after ICAS stenting during a 5-year follow-up.

Severe hypercholesterolemia in a 2-year-old.

Routine and selective cholesterol screening of children is an effective tool to help identify those with familial hypercholesterolemia. In children found to have elevated levels of cholesterol, secondary causes should be excluded, including hypothyroidism. Thyroid hormone has multiple effects on the regulation of lipid synthesis, absorption, and metabolism. In this case report, we described a 2-year-old with a history of congenital hypothyroidism who was found to have severe hypercholesterolemia. A detailed medical history and appropriate screening tests are important in determining the underlying cause of elevated low-density lipoprotein cholesterol to help inform clinical decision-making.

Improved cerebral vasoreactivity following percutaneous transluminal angioplasty with stenting of high-grade internal carotid artery stenosis.

BACKGROUND: The aim of this study was to assess the effects of percutaneous transluminal angioplasty with stenting on cerebral vasoreactivity in carotid stenosis (CS). METHODS: We studied the changes in the middle cerebral artery using transcranial Doppler and the breath-holding index (BHI) after hypercapnia in 33 patients with CS (15 symptomatic, 18 asymptomatic) before and 1 day and 1 month after stenting. RESULTS: One day after stenting, the BHI significantly increased (p < 0.01) on the previously stenotic side in all patients. One month after stenting, the BHI was significantly higher on the contralateral side of asymptomatic (p < 0.05) and symptomatic patients (p < 0.01). CONCLUSION: Percutaneous transluminal angioplasty with stenting results in increasing improvement close to normalization of impaired cerebral vasoreactivity in patients with symptomatic and asymptomatic high-grade CS.

C-reactive protein, carotid atherosclerosis, and cerebral small-vessel disease: results of the Austrian Stroke Prevention Study.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) is an inflammatory marker known to be a risk factor for stroke. We examined the associations between CRP, carotid atherosclerosis, white matter lesions, and lacunes as manifestations of cerebral large- and small-vessel disease. METHODS: In the community-based Austrian Stroke Prevention Study, CRP concentrations were measured by a highly sensitive assay in 700 participants at baseline. All underwent carotid duplex scanning, and a subset of 505 subjects underwent brain magnetic resonance imaging. Imaging was repeated after 3 and 6 years. We graded carotid atherosclerosis in both common and internal carotid arteries on a 5-point scale and calculated the sum of scores as an index of the severity of carotid atherosclerosis. The volume of white matter lesions and the number of lacunes were considered small vessel disease-related brain abnormalities. RESULTS: After adjustment for vascular risk factors, the severity and progression of extracranial carotid atherosclerosis increased with increasing quintiles of CRP. Only study participants in the fourth and fifth quintile (>2.50 mg/L) had significantly more baseline atherosclerosis and greater progression when we used the first quintile (<0.80 mg/L) as a reference. No interactions were seen between CRP quintiles and vascular risk factors for carotid atherosclerosis. The associations between severity and progression of small vessel disease-related brain abnormalities and CRP were nonsignificant. CONCLUSIONS: We found evidence for differential effects of CRP in different beds of the arterial brain supply. CRP was a marker for active carotid atherosclerosis but not for small vessel disease-related brain lesions.

Effect of blood pressure during the acute period of ischemic stroke on stroke outcome: a tertiary analysis of the GAIN International Trial.

BACKGROUND AND PURPOSE: The effects of blood pressure (BP) and its fluctuations during the acute phase on the clinical course of ischemic stroke are incompletely understood. We tested the hypotheses that baseline mean arterial BP [MAP=(2xdiastolic BP+systolic BP)/3], weighted average MAP, and an increase or decrease of >30% from baseline MAP are independently associated with stroke outcome. METHODS: We studied the 1455 patients with ischemic stroke in the Glycine Antagonist (Gavestinel) in Neuroprotection (GAIN) International Trial. BP management was at the discretion of investigators and was measured at 0, 0.5, 4, 12, 12.25, 60, and 60.25 hours. Outcome was assessed by mortality, Barthel Index (dead or 0 to 55 versus 60 to 90 versus > or =95), National Institutes of Health Stroke Scale (NIHSS) score (dead or > or =2), and Rankin Scale (dead or > or =2). Cox proportional-hazards and stepwise logistic regression modeling corrected for demography, medical history, stroke severity, and clinical subtype. RESULTS: Elevated weighted average MAP was associated with poor outcome assessed by mortality at 3 months (hazard ratio, 1.16; 1.06 to 1.27 per 10 mm Hg), NIHSS score (odds ratio [OR] 1.14; 95% confidence interval [CI], 1.01 to 1.28), and Barthel Index at 1 month (OR, 1.12; 95% CI, 1.03 to 1.23). A 30% increase from baseline MAP was associated with poor outcome assessed by NIHSS score and Barthel Index at 1 and 3 months and by Rankin score at 1 month (OR, 2.01; 95% CI, 1.16 to 3.49 to OR, 3.03; 95% CI, 1.30 to 7.02). CONCLUSIONS: Baseline MAP was not associated with poor ischemic stroke outcome. However, variables describing the course of BP over the first 2.5 days have a marked and independent relationship with 1- and 3-month outcome.

Management of right-to-left shunt in cryptogenic cerebrovascular disease: results from the observational Austrian paradoxical cerebral embolism trial (TACET) registry.

Paradoxical embolism due to a patent foramen ovale (PFO) is a possible cause of ischemic stroke, particularly in young cryptogenic stroke patients. In most cases, however, it is difficult to establish a firm etiological association and the debate about management is ongoing. The Austrian Paradoxical Cerebral Embolism Trial was designed as a prospective, national, multi-center, non-randomized registry to add further data on this topic before the completion of randomized controlled trials. Over 27 months 188 cryptogenic stroke/TIA patients ≤55 years were entered by 15 Austrian stroke units. Contrast transesophageal echocardiography demonstrated a cardiac right-to-left shunt (RLS) in 176 patients; a pulmonary RLS was assumed in 10, and 2 showed both. Ninety-seven (55 %) patients with cardiac RLS underwent interventional treatment, and this was more likely for patients with stroke as index event, a symptomatic infarction on MRI and a large size of PFO. Over 2 years, recurrences occurred at a rate of approximately 1.3 % for stroke and 4.3 % for TIA, and were especially frequent in patients with pulmonary RLS. When comparing outcomes in patients with cardiac RLS there was a trend for fewer recurrences with interventional management (closure: four TIA in four patients vs. medical: three strokes and seven TIA in nine patients; p = 0.066 for events, p = 0.085 for patients). The complication rate was 13.4, and 5.7 % had residual shunting. The possible causes for paradoxical embolism in young patients with cryptogenic stroke appear more variable than usually considered, and other causes than PFO should not be neglected. Interventional treatment of a cardiac RLS may offer a small benefit, but has to be weighed against possible complications and the problem of establishing causality.

[Gender aspects of Ischemic stroke. An analysis of the Austrian Stroke-Unit Registry]. / Genderaspekte des ischämischen Schlaganfalls Analyse des österreichischen Stroke-Unit Registers.

BACKGROUND: Available studies suggest gender-related differences in the management of stroke patients. We therefore aimed to address this issue in a large cohort of ischemic stroke patients admitted to Stroke-Units in Austria. METHODS: The database contained information on 15746 prospectively documented cases for descriptive statistical analysis. RESULTS: A total of 13831 (6670 women) were classified as ischemic stroke. Concerning risk factors and stroke aetiology female stroke patients were more likely to have a history of atrial fibrillation (31.1% vs. 20.8%, p<0.001) and suffered more often from cardioembolic strokes (19.9% vs. 15.5%) than males. Women were significantly older than men (mean age in years: 73.4+/-13.8 vs. 67.8+/-12.7, p<0.001), had a more severe neurologic deficit at admission (NIH-SS: 7.7 vs. 6.0, Barthel-Index: 52.2 vs. 62.3, p<0.001) and at discharge (NIH-SS: 5.3 vs. 4.2, Barthel-Index: 65.0 vs. 73.9, p<0.001) and were more severely handicapped at 3-month follow-up (Rankin-Score: 2.1 vs. 1.6, p<0.001). However, when comparing age decades statistically significant differences concerning the higher neurological deficit and dependency in women were present only in patient groups over 70 years. Furthermore, women showed a significantly higher in-Stroke-Unit complication rate (20.2% vs. 16.5%, p<0.001) and risk of death (3.5% vs. 2.4%, p<0.001). The 3-month mortality rate was also higher in women (10.9% vs. 7.7%, p<0.001). Concerning stroke management, we did not find a disadvantage of women vs. men regarding the delay between stroke onset and hospital admission (median: 120 vs. 124 min), delay and frequency of first cerebral imaging, frequency of thrombolysis (7.4% vs. 7.8%, n.s.) and of secondary prevention with antiplatelet therapies (76.4% vs. 76.2%, n.s.). Despite their higher prevalence of atrial fibrillation, female patients were not put on oral anticoagulation more often than men (19.4% vs. 20.6%, at 3 months, n.s.). CONCLUSIONS: This analysis of a large patient population did not show gender disparities in the quality of management of stroke patients treated in Austrian Stroke-Units. However, women had a worse outcome after stroke, which appears to be related primarily to greater deficits at onset in combination with higher age and associated factors. We also confirmed the prominent role of cardiac disorders especially for female stroke patients.

Percutaneous transluminal angioplasty with stenting in extended supra-aortic artery dissection.

A 51-year-old man underwent two percutaneous transluminal angioplasties with stenting for a dissection that extended from the right brachiocephalic trunk into the proximal part of the internal carotid artery. The patient presented with transient dysphasia one month after surgical treatment of a type A dissecting aortic aneurysm. Initially, he was managed with conservative treatment, with no effect on the dissected arteries. Two stents were then successfully placed over the site of dissection to prevent further embolization. At follow-up 29 months after stent implantation, the patient was asymptomatic and ultrasound examination demonstrated no recurrence of dissection at the stented segment. This case suggests that stenting could be a successful treatment of cervical artery dissection.

Right-to-left shunt assessed by contrast transcranial Doppler sonography: new insights.

OBJECTIVE: Simple diagnostic techniques such as contrast transcranial Doppler sonography (cTCDS) are popular for assessing a right-to-left shunt (RLS) because of their high sensitivity. In this study, we applied cTCDS to a large patient group with a patent foramen ovale, proved by contrast transesophageal echocardiography (TEE). METHODS: One hundred one patients with stroke, in whom a patent RLS had been shown on contrast TEE, were investigated by TCDS of both middle cerebral arteries. Injection of 10 mL of agitated saline was applied without and subsequently with the Valsalva maneuver (VM) at the beginning of the contrast agent injection, and then 10 mL of a galactose-based contrast agent was applied in the same protocol. RESULTS: In all patients, cTCDS with the galactose contrast agent showed an RLS when performed with VM, but it showed an RLS in only 59 patients without VM. In contrast, saline showed an RLS in 54 patients with VM and in 20 patients without VM. The differences in diagnostic sensitivity were statistically significant (P < .001). Eighteen patients had only 1 microembolic signal (MES) after galactose injection, whereas others had more. The mean (SD) arrival times of the MES were 9 (6) seconds (range, 1-51 seconds) after galactose injection with VM and 9 (3) seconds (range, 2-20 seconds) after agitated saline with VM. The differences were not significant. CONCLUSIONS: Contrast TCDS with VM shows a TEE-proven RLS with 100% sensitivity, but this was not true with galactose application without VM or agitated saline with or without VM. Therefore, use of the galactose contrast agent with VM is strongly recommended for detecting an RLS on TCDS. However, the arrival time and number of MESs detected need to be tested further.