Ricardo de Carvalho Nogueira

Sonothrombolysis for acute ischemic stroke: a systematic review of randomized controlled trials

OBJECT Sonothrombolysis has recently been considered an emerging modality for the treatment of stroke. The purpose of the present paper was to review randomized clinical studies concerning the effects of sonothrombolysis associated with tissue plasminogen activator (tPA) on acute ischemic stroke. METHODS Systematic searches for literature published between January 1996 and July 2011 were performed for studies regarding sonothrombolysis combined with tPA for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on ultrasound variables, patient characteristics, and outcome variables (rate of intracranial hemorrhages and arterial recanalization). RESULTS Four trials were included in this study; 2 trials evaluated the effect of transcranial Doppler (TCD) ultrasonography on sonothrombolysis, and 2 addressed transcranial color-coded duplex (TCCD) ultrasonography. The frequency of ultrasound waves varied from 1.8 to 2 MHz. The duration of thrombus exposure to ultrasound energy ranged from 60 to 120 minutes. Sample sizes were small, recanalization was evaluated at different time points (60 and 120 minutes), and inclusion criteria were heterogeneous. Sonothrombolysis combined with tPA did not lead to an increase in symptomatic intracranial hemorrhagic complications. Two studies demonstrated that patients treated with ultrasound combined with tPA had statistically significant higher rates of recanalization than patients treated with tPA alone. CONCLUSIONS Despite the heterogeneity and the limitations of the reviewed studies, there is evidence that sonothrombolysis associated with tPA is a safe procedure and results in an increased rate of recanalization in the setting of acute ischemic stroke when wave frequencies and energy intensities of diagnostic ultrasound systems are used.

Dynamic Cerebral Autoregulation Changes during Sub-Maximal Handgrip Maneuver

Purpose We investigated the effect of handgrip (HG) maneuver on time-varying estimates of dynamic cerebral autoregulation (CA) using the autoregressive moving average technique. Methods Twelve healthy subjects were recruited to perform HG maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood flow velocity, end-tidal CO2 pressure (PETCO2), and noninvasive arterial blood pressure (ABP) were continuously recorded during baseline, HG and recovery. Critical closing pressure (CrCP), resistance area-product (RAP), and time-varying autoregulation index (ARI) were obtained. Results PETCO2 did not show significant changes during HG maneuver. Whilst ABP increased continuously during the maneuver, to 27% above its baseline value, CBFV raised to a plateau approximately 15% above baseline. This was sustained by a parallel increase in RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could be associated with metabolic vasodilation. The time-varying ARI index dropped at the beginning and end of the maneuver (p<0.005), which could be related to corresponding alert reactions or to different time constants of the myogenic, metabolic and/or neurogenic mechanisms. Conclusion Changes in dynamic CA during HG suggest a complex interplay of regulatory mechanisms during static exercise that should be considered when assessing the determinants of cerebral blood flow and metabolism.

Cerebral blood flow autoregulation in ischemic heart failure

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20-45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.

Meta-analysis of Vascular Imaging Features to Predict Outcome Following Intravenous rtPA for Acute Ischemic Stroke.

Background The present review investigated which findings in vascular imaging techniques can be used to predict clinical outcome and the risk of symptomatic intracerebral hemorrhage (sICH) in patients who underwent intravenous thrombolytic treatment. Methods Publications were searched, and the inclusion criteria were as follows: (1) published manuscripts, (2) patients with acute ischemic stroke managed with intravenous recombinant tissue plasminogen activator (rtPA), and (3) availability of imaging assessment to determine vessel patency or the regulation of cerebral blood flow prior to, during, and/or after thrombolytic treatment. Clinical outcomes were divided into neurological outcome [National Institutes of Health Stroke Scale (NIHSS) within 7 days] and functional outcome (modified Rankin score in 2–3 months). sICH was defined as rtPA-related intracerebral bleeding associated with any worsening of NIHSS. Results Thirty-nine articles were selected. Recanalization was associated with improved neurological and functional outcomes (OR = 7.83; 95% CI, 3.71–16.53; p < 0.001 and OR = 11.12; 95% CI, 5.85–21.14; p < 0.001, respectively). Both tandem internal carotid artery/middle cerebral artery (ICA/MCA) occlusions and isolated ICA occlusion had worse functional outcome than isolated MCA occlusion (OR = 0.26, 95% CI, 0.12–0.52; p < 0.001 and OR = 0.24, 95% CI, 0.07–0.77; p = 0.016, respectively). Reocclusion was associated with neurological deterioration (OR = 6.48, 95% CI, 3.64–11.56; p < 0.001), and early recanalization was associated with lower odds of sICH (OR = 0.36, 95% CI, 0.18–0.70; p = 0.003). Conclusion Brain circulation data before, during, and after thrombolysis may be useful for predicting the clinical outcome. Cerebral arterial recanalization, presence and site of occlusion, and reocclusion are all important in predicting the clinical outcome.

Encephalic hemodynamic phases in subarachnoid hemorrhage： how to improve the protective effect in patient prognoses

Subarachnoid hemorrhage is frequently associated with poor prognoses. Three different hemodynamic phases were identified during subarachnoid hemorrhage: oligemia, hyperemia, and vasospasm. Each phase is associated with brain metabolic changes. In this review, we correlated the hemodynamic phases with brain metabolism and potential treatment options in the hopes of improving patient prognoses.

Multimodal brain monitoring in fulminant hepatic failure

Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting.

Embolic Signals during Routine Transcranial Doppler Ultrasonography in Aneurysmal Subarachnoid Hemorrhage

Introduction. Cerebral emboli may occur in subarachnoid hemorrhage (SAH) and intracranial aneurysm surgery. Although embolic signs (ES) have been reported in SAH, their origin remains unclear. The aim of this study was to report the detection of ES during routine TCD monitoring in patients with aneurysmal SAH. Methods. A total of 105 patients with aneurysmal SAH were submitted to TCD evaluation. Patients were monitored almost daily (5 times per week). In each monitoring session, one experienced operator performed TCD to detect or assess vasospasm and ES in arteries of the Willis polygon. Results. Four patients out of a total of 105 patients with aneurysmal SAH were found to present spontaneous cerebral embolization during routine TCD monitoring. The average age of the 4 patients (mean ± standard deviation) was 59.5 ± 8.34 years (range 49–68 ys); female patients predominated representing 75% (3/4) of subjects. Conclusion. Although detection of ES was relatively rare in this study, rates of emboli occurrence may be higher under systematic monitoring. The detection of ES after SAH surgery reinforces the need to study the role of embolus in this condition and may be an indicator for prophylactic antithrombotic treatment.

Higher arterial stiffness is associated with lower cognitive performance in patients with hypertension

Cognitive impairment and elevated arterial stiffness have been described in patients with arterial hypertension, but their association has not been well studied. We evaluated the correlation of arterial stiffness and different cognitive domains in patients with hypertension compared with those with normotension. We evaluated 211 patients (69 with normotension and 142 with hypertension). Patients were age matched and distributed according to their blood pressure: normotension, hypertension stage 1, and hypertension stage 2. Cognitive function was assessed using the Mini‐Mental State Examination, Montreal Cognitive Assessment, and a battery of neuropsychological evaluations that assessed six main cognitive domains. Pulse wave velocity was measured using a Complior device, and carotid properties were assessed by radiofrequency ultrasound. Central arterial pressure and augmentation index were obtained using applanation tonometry. The hypertension stage 2 group had higher arterial stiffness and worse performance either by Mini‐Mental State Examination (26.8±2.1 vs 27.3±2.1 vs 28.0±2.0, P=.003) or the Montreal Cognitive Assessment test (23.4±3.5 vs 24.9±2.9 vs 25.6±3.0, P<.001). On multivariable regression analysis, augmentation index, intima‐media thickness, and pulse wave velocity were the variables mainly associated with lower cognitive performance at different cognitive domains. Cognitive impairment in different domains was associated with higher arterial stiffness.

Dynamic cerebral autoregulation is impaired during sub-maximal isometric handgrip in patients with heart failure

The incidence of neurological complications, including stroke and cognitive dysfunction, is elevated in patients with heart failure (HF) with reduced ejection fraction. We hypothesized that the cerebrovascular response to isometric handgrip (iHG) is altered in patients with HF. Adults with HF and healthy volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery) and arterial blood pressure (BP; Finometer) were continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3 min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of recovery. The resistance-area product was calculated from the instantaneous BP-CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the time-varying autoregulation index estimated from the CBV step response derived by an autoregressive moving-average time-domain model. Forty patients with HF and 23 BP-matched healthy volunteers were studied. Median left ventricular ejection fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with control subjects, patients with HF exhibited lower time-varying autoregulation index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were steep rises in CBV, BP, and heart rate in control subjects but with different temporal patterns in HF, which, together with the temporal evolution of resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF were more likely to have impaired dCA during iHG compared with age-matched control subjects. Our results also suggest an impairment of myogenic, neurogenic, and metabolic control mechanisms in HF. The relationship between impaired dCA and neurological complications in patients with HF during exercise deserves further investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence that cerebral blood flow regulatory mechanisms can be affected in patients with heart failure during isometric handgrip exercise. As a consequence, eventual blood pressure modulations are buffered less efficiently and metabolic demands may not be met during common daily activities. These deficits in cerebral autoregulation are compounded by limitations of the systemic response to isometric exercise, suggesting that patients with heart failure may be at greater risk for cerebral events during exercise.

The carotid artery as an alternative site for dynamic autoregulation measurement: an inter-observer reproducibility study

The internal carotid artery (ICA) has been proposed as an alternative site to the middle cerebral artery (MCA) to measure dynamic cerebral autoregulation (dCA) using transcranial Doppler ultrasound (TCD). Our aim was to test the inter-operator reproducibility of dCA assessment in the ICA and the effect of interaction amongst different variables (artery source × operator × intra-subject variability). Two operators measured blood flow velocity using TCD at the ICA and MCA simultaneously on each side in 12 healthy volunteers. The autoregulation index (ARI) was estimated by transfer function analysis. A two-way repeated measurements ANOVA with post-hoc Tukey tested the difference between ARI by different operators and interaction effects were analysed based on the generalized linear model. In this healthy population, no significant differences between operator and no interaction effects were identified amongst the different variables. This study reinforced the validity of using the ICA as an alternative site for the assessment of dCA. Further work is needed to confirm and extend our findings, particularly to disease populations.