Transient Hyperemic Response Research Articles

Impaired cerebrovascular reactivity correlates with reduced retinal vessel density in patients with carotid artery stenosis: Cross-sectional, single center study.

The cerebral and retinal circulation systems are developmentally, anatomically, and physiologically interconnected. Thus, we hypothesized that hypoperfusion due to atherosclerotic stenosis of the internal carotid artery (ICA) can result in disturbances of both cerebral and retinal microcirculations. We aimed to characterize parameters indicating cerebrovascular reactivity (CVR) and retinal microvascular density in patients with ICA stenosis, and assess if there is correlation between them. In this cross-sectional study the middle cerebral artery (MCA) blood flow velocity was measured by transcranial Doppler (TCD) and, simultaneously, continuous non-invasive arterial blood pressure measurement was performed on the radial artery by applanation tonometry. CVR was assessed based on the response to the common carotid artery compression (CCC) test. The transient hyperemic response ratio (THRR) and cerebral arterial resistance transient hyperemic response ratio (CAR-THRR) were calculated. Optical coherence tomography angiography (OCTA) was used to determine vessel density (VD) on the papilla whole image for all (VDP-WIall) and for small vessels (VDP-WIsmall). The same was done in the peripapillary region: all (VDPPall), and small (VDPPsmall) vessels. The VD of superficial (VDMspf) and deep (VDMdeep) macula was also determined. Significance was accepted when p<0.05. Twenty-four ICA stenotic patients were evaluated. Both CVR and retinal VD were characterized. There was a significant, negative correlation between CAR-THRR (median = -0.40) and VDPPsmall vessels (median = 52%), as well as between VDPPall vessels (median = 58%), and similar correlation between CAR-THRR and VDP-WIsmall (median = 49.5%) and between VDP-WIall (median = 55%). The significant correlation between impaired cerebrovascular reactivity and retinal vessel density in patients with ICA stenosis suggests a common mechanism of action. We propose that the combined use of these diagnostic tools (TCD and OCTA) helps to better identify patients with increased ischemic or other cerebrovascular risks.

Assessment of cerebral autoregulatory function and inter-hemispheric blood flow in older adults with internal carotid artery stenosis using transcranial Doppler sonography-based measurement of transient hyperemic response after carotid artery compression

Unhealthy vascular aging promotes atherogenesis, which may lead to significant internal carotid artery stenosis (CAS) in 5 to 7.5% of older adults. The pathogenic factors that promote accelerated vascular aging and CAS also affect the downstream portion of the cerebral microcirculation in these patients. Primary treatments of significant CAS are eversion endarterectomy or endarterectomy with patch plasty. Factors that determine adequate hemodynamic compensation and thereby the clinical consequences of CAS as well as medical and surgical complications of carotid reconstruction surgery likely involve the anatomy of the circle of Willis (CoW), the magnitude of compensatory inter-hemispheric blood flow, and the effectiveness of cerebral microcirculatory blood flow autoregulation. This study aimed to test two hypotheses based on this theory. First, we hypothesized that patients with symptomatic and asymptomatic CAS would exhibit differences in autoregulatory function and inter-hemispheric blood flow. Second, we predicted that anatomically compromised CoW would associate with impaired inter-hemispheric blood flow compensation. We enrolled older adults with symptomatic or asymptomatic internal CAS (>70% NASCET criteria; n = 46) and assessed CoW integrity by CT angiography. We evaluated transient hyperemic responses in the middle cerebral arteries (MCA) after common carotid artery compression (CCC; 10 s) by transcranial Doppler sonography (TCD). We compared parameters reflecting autoregulatory function (e.g., transient hyperemic response ratio [THRR], return to baseline time [RTB], changes of vascular resistance) and inter-hemispheric blood flow (residual blood flow velocity). Our findings revealed that CAS was associated with impaired cerebral vascular reactivity. However, we did not observe significant differences in autoregulatory function or inter-hemispheric blood flow between patients with symptomatic and asymptomatic CAS. Moreover, anatomically compromised CoW did not significantly affect these parameters. Notably, we observed an inverse correlation between RTB and THRR, and 49% of CAS patients exhibited a delayed THRR, which associated with decreased inter-hemispheric blood flow. Future studies should investigate how TCD-based evaluation of autoregulatory function and inter-hemispheric blood flow can be used to optimize surgical techniques and patient selection for internal carotid artery revascularization.

Assessment of impaired cerebral autoregulation and its correlation with neurological outcome in aneurysmal subarachnoid hemorrhage: A prospective and observational study.

Cerebral autoregulation (CA) is crucial for the maintenance of cerebral homeostasis. It can be assessed by measuring transient hyperemic response ratio (THRR) using transcranial Doppler (TCD). We aimed at assessing the incidence of impaired CA (ICA) and its correlation with the neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). One hundred consecutive patients with aSAH scheduled for aneurysmal clipping were enrolled in this prospective and observational study. Preoperative and consecutive 5-day postoperative THRR measurements were taken. Primary objective of the study was to detect the incidence of ICA and its correlation with vasospasm (VS) postclipping, and neurological outcome at discharge and 1, 3, and 12 months was secondary objectives. ICA (THRR < 1.09) was observed in 69 patients preoperatively, 74 patients on the 1st and 2nd postoperative day, 76 patients on 3rd postoperative day, and 78 patients on 4th and 5th postoperative day. Significant VS was seen in 13.4% and 61.5% of patients with intact THRR and deranged THRR, respectively (P < 0.000). Out of 78 patients who had ICA, 42 patients (53.8%) at discharge, 60 patients (76.9%) at 1 month, 54 patients (69.2%) at 3 month, and 55 patients (70.5%) at 12 months had unfavorable neurological outcome significantly more than those with preserved CA. Incidence of ICA assessed in aSAH patients varies from 69% to 78% in the perioperative period. The deranged CA was associated with significantly poor neurological outcome. Therefore, CA assessment using TCD-based THRR provides a simple, noninvasive bedside approach for predicting neurological outcome in aSAH.

Autoregulation Disturbance Events Correlate with History of Loss of Consciousness in Mild Traumatic Brain Injury Patients

Abstract Introduction: Cerebral autoregulation disturbance may compromise cerebral blood flow, thereby increasing the risk of hypoperfusion, which increases the risk of loss of consciousness (LOC). Transient hyperemic response test (THRT) using transcranial Doppler (TCD) can be used to assess cerebral autoregulation disturbance. The goal of this study was to assess the relationship between impaired cerebral autoregulation assessed using TCD and a history of LOC in patients with a mild head injury. Patients and Methods: This study was a comparative analytic study with unpaired data and cross-sectional design that involved 73 people divided into two groups. Group A (36 subjects) consists of mild brain injury patients with a history of LOC, and Group B (37 subjects) consists of mild brain injury patients without a history of LOC. THRT was assessed using TCD by identifying the absence (negative result) in flow velocity increase upon applying pressure on ipsilateral carotid artery. We employed the chi-square and logistic regression tests to assess any correlation between variables. A value of P &lt; 0.05 was considered significant. Results: Approximately 93% of subjects who experienced LOC also showed negative THRT results. We found a statistically significant relationship (P &lt; 0.001) between the history of LOC and THRT. In the logistic regression test, we found that age, gender, and hematocrit were not statistically related to negative THRT results. Conclusion: There is a statistically significant relationship between cerebral autoregulation disturbance and decreased consciousness event in mild head injury patients.

Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive

BackgroundCerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes.MethodsThis was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score.ResultsOne hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1–2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1–2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05).ConclusionsCommon pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.

Relationship Between Cerebral Hemodynamics, Tissue Oxygen Saturation, and Delirium in Patients With Septic Shock: A Pilot Observational Cohort Study.

Background: Septic shock patients have tendencies toward impairment in cerebral autoregulation and imbalanced cerebral oxygen metabolism. Tissue Oxygen Saturation (StO2) and Transcranial Doppler (TCD) monitoring were undertaken to observe the variations of cerebral hemodynamic indices and cerebral/peripheral StO2 to find risk factors that increase the sepsis-associated delirium (SAD).Materials and Methods: The research cohort was chosen from septic shock patients received in the Department of Critical Care Medicine, Xiangya Hospital, Central South University between May 2018 and March 2019. These patients were separated into two groups, SAD and non-SAD as assessed by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Comparisons were made between the two groups in terms of peripheral StO2, fluctuations in regional cerebral oxygen saturation (rSO2), cerebral vascular automatic regulation function [Transient Hyperemic Response Ratio (THRR) index], cerebral hemodynamic index, organ function indicators, blood gas analysis indices, and patient characteristics.Results: About 39% of the patients (20/51) suffered from SAD. Nearly 43% of the patients died within 28 days of admission (22/51). Individuals in the SAD cohort needed a longer period of mechanical ventilation [5 (95% CI 2, 6) vs. 1 days (95% CI 1, 4), p = 0.015] and more time in ICU [9 (95% CI 5, 20) vs. 5 days (95% CI 3, 9), p = 0.042]; they also experienced more deaths over the 28-day period (65 vs. 29%, p = 0.011). The multivariate regression analysis indicated that independent variables associated with SAD were THRR index [odds ratio (OR) = 5.770, 95% CI: 1.222–27.255; p = 0.027] and the mean value for rSO2 was < 55% (OR = 3.864, 95% CI: 1.026–14.550; p = 0.046).Conclusion: Independent risk factors for SAD were mean cerebral oxygen saturation below 55% and cerebrovascular dysregulation (THRR < 1.09).

Cerebral autoregulation after aneurysmal subarachnoid haemorrhage. A preliminary study comparing dexmedetomidine to propofol and/or midazolam.

Cerebral autoregulation is often impaired after aneurysmal subarachnoid haemorrhage (aSAH). Dexmedetomidine is being increasingly used, but its effects on cerebral autoregulation in patients with aSAH have not been studied before. Dexmedetomidine could be a useful sedative in patients with aSAH as it enables neurological assessment during the infusion. The aim of this preliminary study was to compare the effects of dexmedetomidine on dynamic and static cerebral autoregulation with propofol and/or midazolam in patients with aSAH. Ten patients were recruited. Dynamic and static cerebral autoregulation were assessed using transcranial Doppler ultrasound during propofol and/or midazolam infusion and then during three increasing doses of dexmedetomidine infusion (0.7, 1.0 and 1.4μg/kg/h). Transient hyperaemic response ratio (THRR) and strength of autoregulation (SA) were calculated to assess dynamic cerebral autoregulation. Static rate of autoregulation (sRoR)% was calculated by using noradrenaline infusion to increase the mean arterial pressure 20mmHg above the baseline. Data from nine patients were analysed. Compared to baseline, we found no statistically significant changes in THRR or sROR%. THRR was (mean±SD) 1.20±0.14, 1.17±0.13 (P=.93), 1.14±0.09 (P=.72) and 1.19±0.18 (P=1.0) and sROR% was 150.89±84.37, 75.22±27.75 (P=.08), 128.25±58.35 (P=.84) and 104.82±36.92 (P=.42) at baseline and during 0.7, 1.0 and 1.4μg/kg/h dexmedetomidine infusion, respectively. Dynamic SA was significantly reduced after 1.0μg/kg/h dexmedetomidine (P=.02). Compared to propofol and/or midazolam, dexmedetomidine did not alter static cerebral autoregulation in aSAH patients, whereas a significant change was observed in dynamic SA. Further and larger studies with dexmedetomidine in aSAH patients are warranted.

Effect of dexmedetomidine on dynamic cerebral autoregulation and carbon dioxide reactivity during sevoflurane anesthesia in healthy patients.

BackgroundThere are conflicting opinions on the effect of dexmedetomidine on cerebral autoregulation. This study assessed its effect on dynamic cerebral autoregulation (dCA) using a transcranial Doppler (TCD).MethodsThirty American Society of Anesthesiologists physical status I and II patients between 18 and 60 years, who underwent lumbar spine surgery, received infusions of dexmedetomidine (Group D) or normal saline (Group C), followed by anesthesia with propofol and fentanyl, and maintenance with oxygen, nitrous oxide and sevoflurane. After five minutes of normocapnic ventilation and stable bispectral index value (BIS) of 40–50, the right middle cerebral artery flow velocity (MCAFV) was recorded with TCD. The transient hyperemic response (THR) test was performed by compressing the right common carotid artery for 5–7 seconds. The lungs were hyperventilated to test carbon dioxide (CO2) reactivity. Hemodynamic parameters, arterial CO2 tension, pulse oximetry (SpO2), MCAFV and BIS were measured before and after hyperventilation. Dexmedetomidine infusion was discontinued ten minutes before skin-closure. Time to recovery and extubation, modified Aldrete score, and emergence agitation were recorded.ResultsDemographic parameters, durations of surgery and anesthesia, THR ratio (Group D: 1.26 ± 0.11 vs. Group C: 1.23 ± 0.04; P = 0.357), relative CO2 reactivity (Group D: 1.19 ± 0.34 %/mmHg vs. Group C: 1.23 ± 0.25 %/mmHg; P = 0.547), blood pressure, SpO2, BIS, MCAFV, time to recovery, time to extubation and modified Aldrete scores were comparable.ConclusionsDexmedetomidine administration does not impair dCA and CO2 reactivity in patients undergoing spine surgery under sevoflurane anesthesia.

Role of flow velocity and transient hyperemic response evaluated by transcranial doppler for assesing brain autoregulation in mild traumatic brain injury: a case report

Role of flow velocity and transient hyperemic response evaluated by transcranial doppler for assesing brain autoregulation in mild traumatic brain injury: a case report

Early Transcranial Doppler Evaluation of Cerebral Autoregulation Independently Predicts Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

Cerebral autoregulation (CA) impairment after aneurysmal subarachnoid hemorrhage (SAH) has been associated with delayed cerebral ischemia and an unfavorable outcome. We investigated whether the early transient hyperemic response test (THRT), a transcranial Doppler (TCD)-based CA evaluation method, can predict functional outcome 6months after aneurysmal SAH. This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between January 2016 and February 2017. CA was evaluated within 72h of hemorrhage by THRT, which describes the changes in cerebral blood flow velocity after a brief compression of the ipsilateral common carotid artery. CA was considered to be preserved when an increase ≥ 9% of baseline systolic velocity was present. According to the modified Rankin Scale (mRS: 4-6), the primary outcome was unfavorable 6months after hemorrhage. Secondary outcomes included cerebral infarction, vasospasm on TCD, and an unfavorable outcome at hospital discharge. Forty patients were included (mean age = 54 ± 12years, 70% females). CA was impaired in 19 patients (47.5%) and preserved in 21 (52.5%). Impaired CA patients were older (59 ± 13 vs. 50 ± 9, p = 0.012), showed worse neurological conditions (Hunt&Hess 4 or 5-47.4% vs. 9.5%, p = 0.012), and clinical initial condition (APACHE II physiological score-12 [5.57-13] vs. 3.5 [3-5], p = 0.001). Fourteen patients in the impaired CA group and one patient in the preserved CA group progressed to an unfavorable outcome (73.7% vs. 4.7%, p = 0.0001). The impaired CA group more frequently developed cerebral infarction than the preserved CA group (36.8% vs. 0%, p = 0.003, respectively). After multivariate analysis, impaired CA (OR 5.15 95% CI 1.43-51.99, p = 0.033) and the APACHE II physiological score (OR 1.67, 95% CI 1.01-2.76, p = 0.046) were independently associated with an unfavorable outcome. Early CA impairment detected by TCD and admission APACHE II physiological score independently predicted an unfavorable outcome after SAH.

Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes in Children with Cerebral Malaria

To evaluate neurovascular changes in pediatric patients with cerebral malaria. African children with cerebral malaria were enrolled and underwent daily transcranial Doppler ultrasound (TCD) examinations through hospital day 8, discharge, or death. Neurologic outcomes were assessed 2 weeks after enrollment. In total, 160 children with cerebral malaria and 155 comparison patients were included. In patients with cerebral malaria, TCD flow changes characterized as hyperemia were seen in 42 (26%), low flow in 46 (28%), microvascular obstruction in 35 (22%), cerebral vasospasm in 21 (13%), and isolated posterior hyperemia in 7 (4%). Most had a single neurovascular phenotype observed throughout participation. Among comparison patients, 76% had normal TCD findings (P < .001). Impaired autoregulation was present in 80% of cases (transient hyperemic response ratio 1.01 ± 0.03) but improved through day 4 (1.1 ± 0.02, P = .014). Overall mortality was 24% (n = 39). Neurologic deficits were evident in 21% of survivors. Children meeting criteria for vasospasm were most likely to survive with sequelae, and children meeting criteria for low flow were most likely to die. Autoregulation was better in children with a normal neurologic outcome (1.09, 95% CI 1.06-1.12) than in others (0.98, 95% CI 0.95-1) (P ≤ .001). Several distinct changes in TCD measurements were identified in children with cerebral malaria that permitted phenotypic grouping. Groups had distinct associations with neurologic outcomes. Validation of pathogenic mechanisms associated with each phenotype may aid in developing TCD as a portable, easy-to-use tool to help guide targeted adjunctive therapy in cerebral malaria aimed at causative mechanisms of injury on an individual level.

Early abnormal transient hyperemic response test can predict delayed ischemic neurologic deficit in subarachnoid hemorrhage

BackgroundEarly detection of vasospasm is crucial to prevent significant delayed ischemic neurological deficit post subarachnoid hemorrhage. The standard methods of detection, including cerebral angiogram and computed tomography are invasive and not safe to be repeated, as is very often indicated clinically. Transient hyperemic response test has been previously used to predict autoregulation failure in traumatic brain injury and subarachnoid hemorrhage.AimsWe investigate the usability of transient hyperemic response test as a predictor of clinical vasospasm in a cohort of patients with aneurismal subarachnoid hemorrhage.MethodsA retrospective review of all THRT examinations done between January 2011 and July 2012 conducted at Montreal Neurological Institute and Hospital and the Montreal General Hospital. Patients diagnosed with aSAH in which the THRT was performed within the first 24–48 h of admission were included in the study. Two-dimensional transcranial Doppler images were obtained and velocities were recorded. A positive response was one in which the velocity was increased by more than 9% of the baseline systolic velocity, indicating an intact cerebral autoregulation. Lindegaard ratio > 3 is considered abnormal and in the context of elevated systolic velocity of the MCA, is highly suggestive of DIND.ResultsFifteen patients met the inclusion criteria. A total of 6 patients developed clinical and radiological vasospasm. Out of these 6 patients, 5 (83%) had an abnormal THRT in the initial TCD assessment (p = 0.0406). We found that abnormal transient hyperemic response test readings are predictive of subsequent vasospasm development.ConclusionsThe results of this small retrospective study support the notion that transient hyperemic response test has predictive value in vasospasm development and may prove useful in patient monitoring and successful clinical management.

Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part I: A Scoping Review of Intermittent/Semi-Intermittent Methods.

The purpose of this study was to perform a systematic, scoping review of commonly described intermittent/semi-intermittent autoregulation measurement techniques in adult traumatic brain injury (TBI). Nine separate systematic reviews were conducted for each intermittent technique: computed tomographic perfusion (CTP)/Xenon-CT (Xe-CT), positron emission tomography (PET), magnetic resonance imaging (MRI), arteriovenous difference in oxygen (AVDO2) technique, thigh cuff deflation technique (TCDT), transient hyperemic response test (THRT), orthostatic hypotension test (OHT), mean flow index (Mx), and transfer function autoregulation index (TF-ARI). MEDLINE®, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two tier filter of references was conducted. The total number of articles utilizing each of the nine searched techniques for intermittent/semi-intermittent autoregulation techniques in adult TBI were: CTP/Xe-CT (10), PET (6), MRI (0), AVDO2 (10), ARI-based TCDT (9), THRT (6), OHT (3), Mx (17), and TF-ARI (6). The premise behind all of the intermittent techniques is manipulation of systemic blood pressure/blood volume via either chemical (such as vasopressors) or mechanical (such as thigh cuffs or carotid compression) means. Exceptionally, Mx and TF-ARI are based on spontaneous fluctuations of cerebral perfusion pressure (CPP) or mean arterial pressure (MAP). The method for assessing the cerebral circulation during these manipulations varies, with both imaging-based techniques and TCD utilized. Despite the limited literature for intermittent/semi-intermittent techniques in adult TBI (minus Mx), it is important to acknowledge the availability of such tests. They have provided fundamental insight into human autoregulatory capacity, leading to the development of continuous and more commonly applied techniques in the intensive care unit (ICU). Numerous methods of intermittent/semi-intermittent pressure autoregulation assessment in adult TBI exist, including: CTP/Xe-CT, PET, AVDO2 technique, TCDT-based ARI, THRT, OHT, Mx, and TF-ARI. MRI-based techniques in adult TBI are yet to be described, with the main focus of MRI techniques on metabolic-based cerebrovascular reactivity (CVR) and not pressure-based autoregulation.

Effect of Loading Dose of Dexmedetomidine on Dynamic Cerebral Blood Flow Autoregulation in Patients With Intracranial Glial Neoplasms.

Dexmedetomidine has been widely used in neuroanesthesia and critical care settings. The effects of dexmedetomidine on cerebral vascular autoregulation and hemodynamics in patients with intracranial pathology are not well defined. This study is aimed to address this issue. Fifteen patients with unilateral supratentorial glial tumor (group S) and 15 patients without any intracranial pathology (group C) were included in this study. Transient hyperemic response testing was conducted bilaterally in both groups with transcranial color Doppler. Dynamic autoregulation was assessed with transient hyperemic response ratio (THRR) and strength of autoregulation (SA) at baseline and after infusion of inj. dexmedetomidine (1 mcg/kg) over 10 minutes. THRR and SA values in the hemisphere that had tumor (group S) showed no difference from baseline after a loading dose of dexmedetomidine (P=0.914, 0.217). In the nontumor hemisphere of group S and in both the hemispheres of group C, significant reduction in THRR and SA values were observed (P<0.001) after administration of a loading dose of dexmedetomidine. THRR values were higher in the tumor hemisphere when compared with the nonpathologic hemispheres (P<0.001), suggesting the possibility of baseline hyperemia. In the hemisphere that had glial tumor, autoregulatory indices showed no significant change after dexmedetomidine. It can be because of abnormal vascular architecture and its altered reactivity to dexmedetomidine, or because of baseline hyperemia itself, but the exact mechanism needs to be elucidated. In the nonpathologic hemispheres, THRR and SA values were decreased, suggesting impaired autoregulation with the use of loading dose of dexmedetomidine.

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Introduction: Intracerebral complications are the most common cause of morbidity and mortality in children with diabetic ketoacidosis (DKA). Emerging evidence suggests that ischemic injury may be a factor in the development of cerebral edema in this setting. Impairment of cerebral autoregulation may contribute to neurologic injury in DKA and this can be quantified non-invasively using transcranial Doppler ultrasound (TCD). Methods: In this prospective, observational study, we enrolled patients ≤18 years admitted to a tertiary care center pediatric intensive care unit with moderate to severe DKA (serum glucose > 200 mg/dl, pH < 7.15, bicarbonate < 15 mmol/L, and urine ketones). Within 4 hours of admission, we measured the mean flow velocities in the middle cerebral arteries and basilar artery (BA) using TCD. Cerebral autoregulation was evaluated using the transient hyperemic response ratio (THRR), with values ≥ 1.1 defined as normal. TCD was repeated after resolution of DKA. Results: 21 patients have been studied to date [median age 11 yrs (0.75-17), 52% female, median initial glucose 553 (289-553) g/dL, median initial pH 6.99 (6.8-7.13), admission GCS 14 (9-15)]. 66.67% of patients were newly diagnosed with diabetes. Cerebral autoregulation during DKA was impaired in 95% of patients [median THRR on right 0.98 (0.65-1.14), on left 0.98 (0.39-1.26)] and remained abnormal in 50% after resolution of DKA. 7 patients had acute head imaging on presentation (4 with cerebral edema, 1 also with a left basal ganglia infarct, 3 normal). Patients with clinical and imaging evidence of cerebral edema had significantly lower BA mean flow velocities than patients without cerebral edema (p = 0.03). Conclusions: Our data is the first to show prolonged impairment of cerebral autoregulation in children with DKA. They suggest that decreased cerebral blood flow and loss of autoregulation is common during DKA. Understanding these disruptions in cerebral blood flow may lead to future therapeutic targets and should be the subject of further study in hopes of improving neurologic outcomes in diabetic children.

Detection of Intracerebral Hemorrhage and Transient Blood-Supply Shortage in Focused-Ultrasound-Induced Blood–Brain Barrier Disruption by Ultrasound Imaging

Focused ultrasound (FUS) in the presence of microbubbles can selectively open the blood–brain barrier (BBB). However, since overexcitation by FUS probably induces intracerebral hemorrhage, it is essential to develop an imaging approach for real-time detection of hemorrhage and blood-flow changes during FUS-induced BBB disruption. Here we investigated the feasibility of using ultrasound imaging to monitor the transient responses of FUS-induced BBB disruption. The BBB was disrupted with in-house-manufactured microbubbles in rats by 1-MHz FUS with a pressure of 1.1 MPa (pulse repetition frequency: 1 Hz, pulse duration: 10 ms, exposure time: 60 s) and imaged for the next 2 h. Ultrasound B-mode imaging was used to detect hyperechoic changes induced by hemorrhage and contrast-enhanced ultrasound (US) imaging was performed to analyze changes in blood flow. Hyperechoic spots appeared in B-mode images at 5 s after FUS sonication and contrast-enhanced US images simultaneously showed a region of transient blood-supply shortage in the sonicated area. Thus, the location of hyperechoic spots correlated with hemorrhagic patterns and the blood-supply-shortage region was consistent with the BBB-disrupted areas. Furthermore, we detected a transient hyperemic response in the unsonicated contralateral hemisphere brain. Our approach has potential as an immediate-feedback control tool for preventing the induction of intracerebral hemorrhage during FUS treatment.

The “Time” to Timely Predict Ischemic Deficit After Subarachnoid Hemorrhage

Cerebral vasospasm still represents the leading cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Nevertheless, ischemic deficits due to cerebral vasospasm are—at least in part—preventable. We know that vasospasm affects primarily patients with a major rupture resulting in an initial poor clinical condition, but it remains difficult to accurately and timely predict who, among patients with SAH, will develop symptomatic vasospasm and eventually a cerebral infact or infarcts. The only way to avoid possible disastrous delays in recognizing a decrease of cerebral perfusion is the continuous analysis of state of cerebral hemodynamics. We have some instruments to do this, some with detailed probing into brain physiology, but one simple tool—the transcranial Doppler Ultrasound (TCD)—developed about 3 decades ago [1], still remains the only system to monitor cerebral vasospasm: The expert operator knows that precious information on the status of cerebral hemodynamics is hidden in the indistinct noise produced by the TCD during vasospasm. Sometime, this is when the sound of TCD looses its unpleasant noisy character and becomes ‘‘musical’’, as a consequence of regular vibration of a spastic segment of an artery [1]. Spectral analysis of ultrasound echoes provides different quantitative measures, the most obvious of which is the velocity of blood flow. The quantification of the flow velocity (FV) can detect vasospasm, but this is insufficient for predicting its course and clinical relevance. In fact, an increase of the flow velocities over 120 cm/s can be recorded in more than 70% of patients with aneurysmal SAH, while the incidence of ‘‘clinical’’ vasospasm averages 30% half of whom will develop a stroke [2]. Therefore many TCD findings have been used in an attempt to predict outcome after SAH [3]. For example, an average rise in FV of more than 20 cm/s/day between day 3-7 after SAH, a rapid early rise of FV (more than 25%/ day), a mean maximal absolute rise in FV in the middle or anterior cerebral arteries of 65 ± 5 cm/s over a 24-h period, and a higher Lindegaard ratio (6 ± 0.3) have been noted in patients who develop a delayed ischemic deficit. Increased pulsatility index and poor cerebrovascular reactivity to acetazolamide have also been associated with incipient cerebral ischemia and poor prognosis. The loss of cerebrovascular reserve leads also to an impairment of cerebral autoregulation. Its determination—using the transient hyperemic response test—can distinguish patients who are at risk of developing neurological symptoms [4]. This latter observation was done by the group of the University of Cambridge, UK. In this issue of Neurocritical Care, this leading group in the study of cerebral hemodynamics presents a novel hemodynamic index, the ‘‘time constant’’ of cerebral arterial bed. The time constant describes how fast the cerebral arterial bed, distal to the point of TCD insonation, is filled with blood after cardiac contraction. The authors continuously and simultaneously recorded FV and arterial blood pressure and used a relatively simple mathematical model to decode information hidden in the spectral display of the TCD. Indeed, the spectrum of the TCD reflects the flow velocities of each single blood cell moving into the brain arteries. The spectral distribution of different velocities is therefore expression of the arterial blood pressure during the different phases of the cardiac cycle, the section of the arteries of the cranial base, the resistance of the whole system to the downstreaming and blood outflow. A. Conti (&) F. Tomasello Department of Neurosurgery, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy e-mail: alfredo.conti@unime.it

Cerebral Autoregulation and CO2 Reactivity Before and After Elective Supratentorial Tumor Resection

The effect of surgical decompression of tumor on autoregulation and CO2 reactivity is not known. We examined the effect of elective tumor resection on cerebral autoregulation and CO2 reactivity. Patients with supratentorial tumors undergoing elective craniotomy for tumor resection under standard anesthesia underwent cerebral autoregulation and CO2 reactivity testing immediately before and between 6 and 24 hours after surgery. Transient hyperemic response of the middle cerebral artery after the release of 10 second compression of the ipsilateral common carotid artery was used to calculate the transient hyperemic response ratio (THRR). THRR>1.1 defined the normal autoregulation. Voluntary hyperventilation was titrated to reduce the ETCO2 by 10 mm Hg below baseline and CO2 reactivity was calculated. Thirty-five patients (26 male and 9 female) were studied. Overall, cerebral autoregulation was intact before and after tumor resection for the cohort (THRR 1.27+/-0.10 and 1.30+/-0.12, P=0.11). However, cerebral autoregulation was impaired preoperatively in 7 (20%) patients and remained impaired in all 7 patients after tumor resection. Larger tumor size (P=0.002), and midline shift more than 5 mm (P<0.001) were associated with impaired cerebral autoregulation. Twenty-eight (80%) patients who had intact preoperative cerebral autoregulation maintained autoregulation postoperatively. CO2 reactivity was within normal limits before and after surgery in all patients and did not change between the 2 periods (3.41+/-0.46/mm Hg and 3.60+/-0.63%/mm Hg, P=0.07). Preoperative cerebral autoregulation was impaired in a significant number of patients with large supratentorial tumor size and midline shift more than 5 mm and was associated with postoperative impaired cerebral autoregulation during the first 24 hours after the surgery.

A Model of Cerebrovascular Reactivity Including the Circle of Willis and Cortical Anastomoses

Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral hemodynamics. In this work, a mathematical model of cerebral hemodynamics and intracranial pressure (ICP) dynamics, developed in previous years, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the ICP-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular hemodynamics and cannot only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions.

Factors affecting the transient hyperaemic response test of the cerebral autoregulation

The transient compression of the internal carotid artery (ICA) results in dilatation of cerebral arterioles by effect of autoregulation. In the THR test, the increase in middle cerebral artery (MCA) blood flow immediately after release of transient compression of the ICA is measured, which is proportional to cerebral autoregulation. The aim of the study was to determine the significance of several factors of the test - blood flow inertia (acceleration), dimensions (length and radius) of ICA, patency of the Circle of Willis (WC), and asynchrony between release of ICA compression and arterial pressure pulsations (phase shift).