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Background Untimely diagnosis of intracranial hypertension may lead to delays in therapy and worsening of outcome. Transcranial Doppler (TCD) detects variations in cerebral blood flow velocity which may correlate with intracranial pressure (ICP). We investigated if intracranial hypertension can be accurately excluded through use of TCD. Method This was a multicenter prospective pilot study in patients with acute brain injury requiring invasive ICP (ICPi) monitoring. ICP estimated with TCD (ICPtcd) was compared with ICPi in three separate time frames: immediately before ICPi placement, immediately after ICPi placement, and 3 hours following ICPi positioning. Sensitivity and specificity, and concordance correlation coefficient between ICPi and ICPtcd were calculated. Receiver operating curve (ROC) and the area under the curve (AUC) analyses were estimated after measurement averaging over time. Results A total of 38 patients were enrolled, and of these 12 (31.6%) had at least one episode of intracranial hypertension. One hundred fourteen paired measurements of ICPi and ICPtcd were gathered for analysis. With dichotomized ICPi (≤20 mmHg vs >20 mmHg), the sensitivity of ICPtcd was 100%; all measurements with high ICPi (>20 mmHg) also had a high ICPtcd values. Bland-Altman plot showed an overestimation of 6.2 mmHg (95% CI 5.08–7.30 mmHg) for ICPtcd compared to ICPi. AUC was 96.0% (95% CI 89.8–100%) and the estimated best threshold was at ICPi of 24.8 mmHg corresponding to a sensitivity 100% and a specificity of 91.2%. Conclusions This study provides preliminary evidence that ICPtcd may accurately exclude intracranial hypertension in patients with acute brain injury. Future studies with adequate power are needed to confirm this result.

Background Stroke risk screening using transcranial Doppler (TCD) is a critical evidence-based tool for children with sickle cell anemia (SCA) that has been poorly implemented in the United States. The Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve rates of stroke risk screening for SCA using interventions informed by an extensive multi-level barriers and facilitators assessment. This report describes the final outcomes of a large, randomized implementation trial comparing two intervention arms: 1) an application designed to track TCD implementation, ProviderMinder™, versus 2) ProviderMinder™ plus a single coordinator intervention. All sites additionally received a rebranding and educational intervention. The primary outcome was the difference in stroke risk screening rates between intervention arms. The intervention group was compared to four sites that did not implement either intervention and to their baseline rates as secondary outcomes. Methods The initial part of DISPLACE included 28 sites from which 16 sites with poor stroke risk screening implementation were included in the trial and randomized to intervention arms. All sites entered patient data into a secure, customized electronic database and were required to use ProviderMinder™ for stroke risk screening data entry. Three sites were unable to adopt ProviderMinder™ and a fourth site from the original DISPLACE cohort was added to this group, resulting in thirteen intervention sites and four non-implementing sites (NIS). NIS collected data retrospectively for the same period as the implementation trial. A generalized quasi-likelihood Poisson mixed effects regression model compared screening rates between groups and timepoints while controlling for baseline screening rates and site size. Unadjusted stroke risk screening rates were also compared via two-proportion Z-tests for all outcomes. Results The intervention-by-timepoint interaction indicated statistically significant improvement for the ProviderMinder™ arm relative to the combined intervention arm (difference of 10.0%) and for the intervention group (both arms) compared to NIS (difference of 15.9%). Screening rates increased by 28.0% from baseline to intervention, with an overall rate of 76.8%. Conclusions Our intervention approach in DISPLACE significantly improved stroke risk screening for children with SCA, with procedure-patient tracking emerging as an important component for improving care. Trial registration Clinical trial number: ClinicalTrials.gov; NCT04173026; 6/4/2020; https://clinicaltrials.gov/study/NCT04173026?cond=NCT04173026&rank=1

Cognitive paradigms induce changes in cerebral blood flow (CBF) associated with increased metabolic demand, namely neurovascular coupling (NVC). We tested the hypothesis that the effect of complexity and duration of cognitive paradigms will either enhance or inhibit the NVC response. Bilateral CBF velocity (CBFV) in the middle cerebral arteries (MCAs) via transcranial Doppler ultrasound (TCD), blood pressure (BP), electrocardiogram (ECG) and end-tidal CO 2 (EtCO 2 ) of 16 healthy participants (aged 21–71 years) were simultaneously recorded at rest and during randomized paradigms of different complexities (naming words beginning with P-,R-,V- words and serial subtractions of 100–2,100–7,1000–17), and durations (5s, 30s and 60s). CBFV responses were population mean normalized from a 30-s baseline period prior to task initiation. A significant increase in bilateral CBFV response was observed at the start of all paradigms and provided a similar pattern in most responses, irrespective of complexity or duration. Although significant inter-hemispherical differences were found during performance of R-word and all serial subtraction paradigms, no lateralisation was observed in more complex naming word tasks. Also, the effect of duration was manifested at late stages of 100–7, but not for other paradigms. CBFV responses could not distinguish different levels of complexity or duration with a single presentation of the cognitive paradigm. Further studies of the ordinal scalability of the NVC response are needed with more advanced modelling techniques, or different types of neural stimulation.

Background Although surviving sepsis campaign (SSC) guidelines are the standard for sepsis and septic shock management, outcomes are still unfavourable. Given that perfusion pressure in sepsis is heterogeneous among patients and within the same patient; we evaluated the impact of individualized hemodynamic management via the transcranial Doppler (TCD) pulsatility index (PI) on mortality and outcomes among sepsis-induced encephalopathy (SIE) patients. Methods In this prospective, single-center randomized controlled study, 112 patients with SIE were randomly assigned. Mean arterial pressure (MAP) and norepinephrine (NE) titration were guided via the TCD pulsatility index to achieve a pulsatility index < 1.3 in Grou p I, whereas the SSC guidelines were used in Grou p II to achieve a MA P  ≥ 65 mmHg. The primary outcome was intensive care unit (ICU) mortality and the secondary outcomes were; MA P that was measured invasively and values were recorded; daily in the morning, at the end of NE infusion and the end of ICU stay, duration of ICU stay, cerebral perfusion pressure (CPP), sequential organ failure assessment (SOFA) score, norepinephrine titration and Glasgow coma scale (GCS) score at discharge. Results ICU mortality percentage wasn`t significantly different between the two groups ( p value 0.174). There was a significant increase in the MA P at the end of norepinephrine infusion (mean value of 69.54 ± 10.42 and p value 0.002) and in the GCS score at ICU discharge (Median value of 15 and p value 0.014) in the TCD group, and episodes of cerebral hypoperfusion with CP P  < 60 mmHg, were significantly lower in the TCD grou p (median value of 2 and p value 0.018). Heart rate values, number of episodes of tachycardia or bradycardia, Total norepinephrine dosing, duration of norepinephrine infusion, SOFA score, serum lactate levels, and ICU stay duration weren`t significantly different between the two groups. Conclusions Individualizing hemodynamic management via the TCD pulsatility index in SIE patients was not associated with significant mortality reduction. However, it reduces episodes of cerebral hypoperfusion and improves GCS outcome but doesn’t significantly affect heart rate values, SOFA score, serum lactate level, length of ICU stay, total NE dosing, and duration of NE infusion. Trial registration The clinical trial was registered on clinucaltrials.gov under the identifier NCT05842616 https://clinicaltrials.gov/study/NCT05842616?cond=NCT05842616&rank=1 on 6-May-2023 before the enrolment of the first patient.

Purpose Studies examining neurovascular coupling (NVC) require participants to refrain from exercise for 12–24 hours. However, there is a paucity of empirical evidence for this restriction. The objectives for this study were to delineate the time‐course recovery of NVC metrics following exercise and establish the NVC within‐ and between‐day reliability. Methods Nine participants completed a complex visual search paradigm to assess NVC via transcranial Doppler ultrasound of the posterior cerebral artery blood velocity (PCA). Measurements were performed prior to and throughout the 8‐hour recovery period following three randomized conditions: 45 minutes of moderate‐intensity exercise (at 50% heart‐rate reserve), 30 minutes high‐intensity intervals (10, 1‐minute intervals at 85% heart‐rate reserve), and control (30 minutes quiet rest). In each condition, baseline measures were collected at 8:00am with serial follow‐ups at hours zero, one, two, four, six, and eight. Results Area‐under‐the‐curve and time‐to‐peak PCA velocity during the visual search were attenuated at hour zero following high‐intensity intervals (all p < 0.05); however, these NVC metrics recovered at hour one (all p > 0.13). Conversely, baseline PCA velocity, peak PCA velocity, and the relative percent increase were not different following high‐intensity intervals compared to baseline (all p > 0.26). No NVC metrics differed from baseline following both moderate exercise and control conditions (all p > 0.24). The majority of the NVC parameters demonstrated high levels of reliability (intraclass correlation coefficient: >0.90). Conclusion Future NVC assessments can take place a minimum of one hour following exercise. Moreover, all metrics did not change across the control condition, therefore future studies using this methodology can reliably quantify NVC between 8:00am and 7:00 pm. Previous studies examining neurovascular coupling (NVC) metrics, required participants to refrain from exercise for 4‐24 hours prior to data collection, despite a lack of objective evidence for this time restriction. The results in the current investigation demonstrated that the NVC response was attenuated immediately following high‐intensity exercise within the posterior cerebral artery (PCA); however, the NVC response was comparable to baseline values one‐hour following exercise. Additionally, NVC metrics displayed high levels of within‐ and between‐day reliability across the control condition (8:00am – 7:00pm) when using a complex visual scene search paradigm (“Where’s Waldo”).

Objective In recent years, increasing attention has been paid to cryptogenic stroke (CS) caused by the patent foramen ovale (PFO). This study aims to compare contrast transthoracic echocardiography (cTTE) and contrast transcranial Doppler (cTCD) to determine whether cTTE is more suitable and reliable than cTCD for clinical use. Methods From March 2017 to May 2018, patients who suffered from migraines, stroke, hypomnesis, or asymptomatic stroke found casually were included in our study. Patients with CS were semirandomly divided into two groups (cTTE and cTCD) according to the date of the outpatient visit. Patients with either of the examination above found positive were selected to finish transesophageal echocardiography (TEE). Results In our study, the sensitivities of group cTTE positive (group cTTE+) and group cTCD positive (group cTCD+) did not have any statistical difference (89% vs. 80%, p = 0.236). Focusing on group cTCD+, we discovered that the semiquantitative shunt grading was not correlated with whether a PFO was present or not (p = 0.194). However, once the PFO has been diagnosed, the shunt grading was shown to be related to the width of the gaps (p = 0.032, pdeviation = 0.03). Conclusion Both cTTE and the cTCD can be used for preliminary PFO findings. The semiquantitative shunt grading of cTCD and cTTE can suggest the size of the PFO and the next course of treatment. The cTTE may be more significant to a safe PFO (a PFO does not have right‐to‐left shunts, RLSs). Combining cTTE and TEE could help diagnose PFO and assess CS risk. The semiquantitative shunt grading of the contrast transcranial Doppler (cTCD) and contrast transthoracic echocardiography (cTTE) could suggest the size of patent foramen ovale (PFO), and makes sense for the next treatment. The cTTE may be more significant to a safe PFO (a PFO do not have right‐to‐left shunts, RLSs). Combining cTTE and transesophageal echocardiography could make up for each other to diagnose PFO and assess CS risk.

Background To evaluate the diagnostic value of transcranial Doppler (TCD) and electroencephalography (EEG) in patients with vertebrobasilar insufficiency (VBI) during clinical diagnosis and treatment Methods Eighty patients diagnosed with VBI in our hospital from June 2018 to December 2019 were randomly selected as the observation group, and 80 healthy people who received physical examination in the same period were selected as the control group. The abnormal rate, main performance and results, and the peak velocity of blood flow and vertebrobasilar artery blood flow of the two groups were compared. Results The abnormal rate of EEG and TCD in VBI patients was 38.75% (31/80) and the 93.75% (75/80), respectively. In TCD examination, ACA, PCA, MCA, and VA of both sides of the observation group were higher than those of the control group, while BA was lower than that of the control group ( P < 0.05). The Vs, Vd, and Vm on both sides of BA and VA in the observation group were lower than those in the control group, while PI and RI were higher than those in the control group ( P < 0.05). Conclusions TCD examination is highly sensitive to the degree and pattern of cerebral ischemia in VBI patients. EEG examination will define the changes of brain cell function after cerebral ischemia. Therefore, EEG and TCD have their own advantages. The application of TCD and EEG can be considered in the early diagnosis, curative effect, and prognosis evaluation of VBI patients, so as to improve the accuracy of diagnosis and prognosis.

Background Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICP tcd ) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICP tcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICP i ), in excluding the presence of intracranial hypertension. Methods This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICP tcd ) with a reference standard (ICP i ), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICP i monitoring, were enrolled in 16 international intensive care units. ICP i measurements (reference test) were compared to simultaneous ICP tcd measurements ( index test) at three different timepoints: before, immediately after and 2 to 3 h following ICP i catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICP i thresholds (> 20, > 22 and > 25 mmHg) to assess ICP tcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICP tcd. Results Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICP tcd and ICP i was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICP tcd in excluding intracranial hypertension. Concordance correlation between ICP tcd and ICP i was 33.3% (95% CI 25.6–40.5%), and Bland–Altman showed a mean bias of -3.3 mmHg. The optimal ICP tcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7–92.6%) and a specificity of 72% (95% CI 51.9–94.0%) with an AUC of 76% (95% CI 65.6–85.5%). Conclusions and relevance ICP tcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. Trial registration :  NCT02322970 .

Brain ultrasonography can be used to evaluate cerebral anatomy and pathology, as well as cerebral circulation through analysis of blood flow velocities. Transcranial colour-coded duplex sonography is a generally safe, repeatable, non-invasive, bedside technique that has a strong potential in neurocritical care patients in many clinical scenarios, including traumatic brain injury, aneurysmal subarachnoid haemorrhage, hydrocephalus, and the diagnosis of cerebral circulatory arrest. Furthermore, the clinical applications of this technique may extend to different settings, including the general intensive care unit and the emergency department. Its increasing use reflects a growing interest in non-invasive cerebral and systemic assessment. The aim of this manuscript is to provide an overview of the basic and advanced principles underlying brain ultrasonography, and to review the different techniques and different clinical applications of this approach in the monitoring and treatment of critically ill patients.

The objective of the following study is to determine the effect of continuous insonation using 2-MHz transcranial Doppler-ultrasound (TCD-US) on the recanalization rate and the short-term outcome in subjects with acute ischemic stroke due to middle cerebral artery (MCA) occlusion. A total of 42 patients with acute ischemic stroke due to MCA occlusion within 24 h were recruited and randomly allotted to two groups (21 patients in each group). Group 1 included patients who received 1 h continuous TCD-US for MCA and Group 2 included patients who did not receive 1 h continuous TCD-US. Patients in both groups were received MCA insonation and TCD study to measure mean flow velocity (MFV) in MCA one after the initial study at 20 and 60 min. All patients received aspirin (150-325 mg). The clinical course during hospital stay was assessed before and after 1 h of US insonation, at 24 h after symptom onset using the National Institutes of Health Stroke Scale. Change in MFV after insonation for Group 1 in comparison to Group 2 at 3 time points was significantly high (P < 0.001). Sonothrombolysis is a therapeutic option to improve the outcomes in patients with acute ischemic stroke due to MCA occlusion.