Transcranial Doppler Measurements Research Articles

Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults

AbstractThis study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4–7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P > 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).

Prediction of neurocritical care intensity through automated infrared pupillometry and transcranial doppler in blunt traumatic brain injury: the NOPE study.

This pilot study aimed to determine the capacity of automated infrared pupillometry (AIP) alone and in combination with transcranial doppler (TCD) on admission to rule out need for intense neuroAQ2 critical care (INCC) in severe traumatic brain injury (TBI). In this observational pilot study clinicians performed AIP and TCD measurements on admission in blunt TBI patients with a Glasgow Coma Score (GCS) < 9 and/or motor score < 6. A Neurological Pupil index (NPi) < 3, Pulsatility Index (PI) > 1,4 or diastolic blood flow velocity (dV) of < 20 cm/s were used to rule out the need for INCC (exceeding the tier 0 Seattle Consensus Conference). The primary outcome was the negative likelihood ratio (nLR) of NPi < 3 alone or in combination with TCD to detect need for INCC. A total of 69 TBI patients were included from May 2019 to September 2020. Of those, 52/69 (75%) median age was 45 [28-67], median prehospital GCS of 7 [5-8], median Injury Severity Scale of 13.0 [6.5-25.5], median Marshall Score of 4 [3-5], the median Glasgow Outcome Scale at discharge was 3 [1-5]. NPi < 3 was an independent predictor of INCC. NPi demonstrated a nLR of 0,6 (95%CI 0.4-0.9; AUROC, 0.65, 95% CI 0.51-0.79), a combination of NPi and TCD showed a nLR of 0.6 (95% CI 0.4-1.0; AUROC 0.67 95% CI 0.52-0.83) to predict INCC. This pilot study suggests a possible useful contribution of NPi to determine the need for INCC in severe blunt TBI patients on admission.

Barriers and facilitators to a task-shifted stroke prevention program for children with sickle cell anemia in a community hospital: a qualitative study

BackgroundChildren with sickle cell anemia (SCA) are at high risk for stroke. Protocols for stroke prevention including blood transfusions, screening for abnormal non-imaging transcranial Doppler (TCD) measurements, and hydroxyurea therapy are difficult to implement in low-resource environments like Nigeria. This study aimed to examine the contextual factors around TCD screening in a community hospital in Nigeria using qualitative interviews and focus groups.MethodsWe conducted a descriptive qualitative study in a community hospital in Kaduna, Nigeria, using focus groups and interviews. Interview guides and analysis were informed by the Consolidated Framework for Implementation Research (CFIR) framework and the Theory of Planned Behavior. Transcripts were coded and analyzed using an iterative deductive (CFIR)/Inductive (transcribed quotes) qualitative methodology.ResultsWe conducted two focus groups and five interviews with health care workers (nurses and doctors) and hospital administrators, respectively. Themes identified key elements of the inner setting (clinic characteristics, resource availability, implementation climate, and tension for change), characteristics of individuals (normative, control, and behavioral beliefs), and the implementation process (engage, implement, and adopt), as well as factors that were influenced by external context, caregiver needs, team function, and intervention characteristics. Task shifting, which is already being used, was viewed by providers and administrators as a necessary strategy to implement TCD screening in a clinic environment that is overstressed and under-resourced, a community stressed by poverty, and a nation with an underperforming health system.ConclusionTask shifting provides a viable option to improve health care by making more efficient use of already available human resources while rapidly expanding the human resource pool and building capacity for TCD screening of children with SCD that is more sustainable.Trial registrationNCT05434000.

Age of Onset of High Transcranial Doppler Measurements Predicts Discrepant Cognitive Profiles in Children with Sickle Cell Disease

Background: Children with Sickle Cell Disease (SCD) have documented compromises in neurocognitive functioning, with notable weaknesses in executive functioning. There is limited published research to define the impact of SCD on the development of visual spatial processing, which is the brain's ability to use and interpret visual stimuli and then apply it to novel situations. We hypothesized that the risk for deficits in visual spatial processing is correlated to high velocity transcranial dopplers (TCD) measurements and the age at which a high TCD velocity first occurred. Our team hypothesized that younger age at time of initial high TCD is associated with a larger impact on visual spatial skills in school aged children. Methods: This review includes data from standard of care practices within our pediatric multidisciplinary sickle cell program. Our clinic began offering neurocognitive screenings in January 2023 to patients who are school entry age (between 5 to 6 years old) or older. Children are identified to participate in screening based on age, parental interest, and provider recommendation. Patients ranging in age from 5 to 15 years of age were screened using either the Weschler Preschool and Primary Scale of Intelligence, fourth edition (WPPSI-IV) or the Wechsler Intelligence Scale for Children, fifth edition (WISC-V). Retrospective chart reviews were performed to identify relevant data including TCD and MRI results. The Visual Spatial Index (VSI) is a primary index obtained from the Wechsler standard batteries. VSI assesses a child's ability to construct designs utilizing visual spatial reasoning, attention to visual detail, and visual-motor integration. The average child can demonstrate these skills at age 5 by mentally rotating an object such as a block and matching it with a picture or into a shaped hole. This requires the appropriate development of the basal ganglia, thalamus, parietal lobe, and temporal lobe. The Mean Index Score (MIS) is a broad representation of all cognitive domains measured on the assessment. The difference between the obtained VSI score and a child's MIS is used to determine whether a statistically significant difference exists within the Wechsler assessment system. The difference between the VSI and MIS is compared to a critical value, and if the difference of the VSI and MIS is greater than the critical value then we can say with confidence (p&amp;lt;0.05) that the difference in scores is not due to chance. Chi-square was then used to explore the relationship between the presence of a high TCD before age 5 (the age at which primary visual spatial skills are onboard) and the presence of a statistically significant visual spatial skill weakness. Results: 11 children (mean age 9.73 years; 82% Hemoglobin SS and 18% Hemoglobin SC) were assessed during the first 6 months of this new protocol. 27% (3) of the children had both a high TCD prior to age 5 and a statistically significant (p&amp;lt;0.05) visual spatial weakness, 9% (1) had only high TCD before age 5 but not VSI weakness, and 64% (7) had neither. Due to the small sample size, we used Fisher's exact to test the hypothesis that these two categorical variables (high TCD velocity before age 5 and VSI weakness) were related (P&amp;lt;0.05, P=0.024). We rejected the null hypothesis and found evidence to support a relationship between the presence of high velocities in early childhood and visual spatial skills deficit. Therefore, there is clinical indication that high TCD velocities in early childhood impact the development of visual spatial skills. Conclusion: The impact of sickle cell disease on brain development has been explored, but most published data focus on broad executive functioning skills. Our data yields evidence that the presence of high velocities in the brain before age five may be predictive of future visual spatial abilities as measured using standardized measures (i.e., Wechsler Assessments). It is anticipated that further data exploration will inform the optimization of standard of care practices within our clinic. This may include medical practices such as neuroimaging, changing how we communicate with children and their families, and enhanced practices for supporting students at school through IEPs.

Sphenopalatine ganglion block with or without greater occipital nerve block for treatment of obstetric post-dural puncture headache after spinal anesthesia: randomized controlled trial

BackgroundConservative treatments of post-dural puncture headache (PDPH) may be unsuccessful, and the relief that is provided is frequently insufficient. This study aimed to meticulously explore the analgesic efficacy of the sphenopalatine ganglion (SPG) block when administered alone or in conjunction with the greater occipital nerve block (GONB) for the purpose of treating PDPH and with the aid of transcranial Doppler (TCD) to evaluate the cerebral hemodynamics before and after the block.This study was conducted on 63 women with post-partum PDPH randomized into the following: control group (Group C = 21 participants), received conservative management; SPG block group (Group S = 21 participants), received conservative management with SPG block; and combined nerve and ganglion block group (Group NAG = 21 participants), received conservative management with SPG block and ultrasound guided GONB. Visual analog score (VAS), modified Lybecker score, and transcranial Doppler (TCD) measures were used to determine PDPH severity at 0 (baseline), 1, 6, and 24 h. Additionally, the three groups’ needs for EBP were noted.ResultsVAS and modified Lybecker scores at 1, 6, and 24 h were statistically significantly lower in S and NAG groups compared to the control group with no statistically significant difference between S and NAG groups. With TCD, the mean velocity (MV) was significantly lower at 1, 6, and 24 h compared to baseline reading in both S and NAG groups. Also, the pulsatility index (PI) was statistically higher at 1, 6, and 24 h compared to baseline readings in S and NAG groups. There was no statistically significant difference regarding the need for EBP.ConclusionsIn terms of headache relief or the need for EBP, there is no difference between individual SPG block or combined SPG block and GONB in the treatment of PDPH.

A decade of aging in healthy older adults: longitudinal findings on cerebrovascular and cognitive health

Research suggests an association between cerebrovascular health and cognitive decline, but previous work is limited by its cross-sectional nature or short (< 1–2 years) follow-up. Our aim was to examine, across 10 years of follow-up in healthy older adults, changes in cerebrovascular health and their relationship with subjective memory complaints as an early marker of cognitive decline. Between 2008 and 2010, twenty-eight healthy older adults (69 ± 4 years) underwent baseline blood pressure and transcranial Doppler measurements to assess middle cerebral artery blood velocity (MCAv), cerebrovascular resistance index (CVRi), and measures of cerebral autoregulation (CA). After 9–12 years of follow-up, these measurements were repeated, and presence of memory complaints was evaluated. Linear mixed-model analyses explored effects of aging on cerebrovascular parameters and whether memory complaints were associated with cerebrovascular changes. Across a median follow-up of 10.9 years, no changes in MCAv, CVRi, or CA were found. At baseline, these parameters were not different between subjects with (n = 15) versus without (n = 13) memory complaints. During follow-up, subjects with memory complaints showed larger decreases in MCAv (− 10% versus + 9%, P = 0.041) and increases in CVRi (+ 26% versus − 9%, P = 0.029) compared to other peers without memory complaints, but no distinct changes in CA parameters (P > 0.05). Although a decade of aging does not lead to deterioration in cerebral blood flow or autoregulation, our findings suggest that reductions in cerebral blood flow and increases in cerebrovascular resistance are associated with early subjective cognitive decline.

Evaluation of transcranial Doppler use in patients with acute liver failure listed for emergency liver transplantation.

Acute liver failure (ALF) is characterized by hepatic encephalopathy (HE) often due to intracranial hypertension (ICH). The risk/benefit-balance of intraparenchymal pressure catheter monitoring is controversial during ALF. Perform an evaluation of transcranial Doppler (TCD) use in patients with ALF listed for emergency liver transplantation. Single center retrospective cohort study including all patients registered on high emergency LT list between 2012 and 2018. All TCD measurements performed during ICU stay after listing and after LT (when performed) were recorded. TCD was considered abnormal when pulsatility index (PI) was >1.2. Among 106 patients with ALF, forty-seven (44%) had a TCD while on list. They had more severe liver and extrahepatic organ failure. When performed, TCD was abnormal in 51% of patients. These patients more frequently developed ICH events (45% vs. 13%, p=.02) and more frequently required increase in sedative drugs and vasopressors. While 22% of patients with normal TCD spontaneously survived, all of those with abnormal TCD died or were transplanted (p=.02). All transplanted patients who had abnormal exams normalized their TCD within 2 (1-2)days after LT. TCD may be a useful non-invasive tool for ICH detection and management, then guide sedation withdrawal.

The effects of aneurysmal subarachnoid hemorrhage on cerebral vessel diameter and flow velocity

BackgroundTranscranial Doppler flow velocity is used to monitor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Generally, blood flow velocities appear inversely related to the square of vessel diameter representing local fluid dynamics. However, studies of flow velocity-diameter relationships are few, and may identify vessels for which diameter changes are better correlated with Doppler velocity. We therefore studied a large retrospective cohort with concurrent transcranial Doppler velocities and angiographic vessel diameters. MethodsThis is a single-site, retrospective, cohort study of adult patients with aneurysmal subarachnoid hemorrhage, approved by the UT Southwestern Medical Center Institutional Review Board. Study inclusion required transcranial Doppler measurements within </= 24 hours of vessel imaging. Vessels assessed were: bilateral anterior, middle, posterior cerebral arteries; internal carotid siphons; vertebral arteries; and basilar artery. Flow velocity-diameter relationships were constructed and fitted with a simple inverse power function. A greater influence of local fluid dynamics is suggested as power factors approach two. Results98 patients were included. Velocity-diameter relationships are curvilinear, and well fit by a simple inverse power function. Middle cerebral arteries showed the highest power factors (>1.1, R2>0.9). Furthermore, velocity and diameter changed (P<0.033) consistent with the signature time course of cerebral vasospasm. ConclusionsThese results suggest that middle cerebral artery velocity-diameter relationships are most influenced by local fluid dynamics, which supports these vessels as preferred endpoints in Doppler detection of cerebral vasospasm. Other vessels showed less influence of local fluid dynamics, pointing to greater role of factors outside the local vessel segment in determining flow velocity.

Dynamic cerebral autoregulation measured by diffuse correlation spectroscopy

Dynamic cerebral autoregulation (dCA) can be derived from spontaneous oscillations in arterial blood pressure (ABP) and cerebral blood flow (CBF). Transcranial Doppler (TCD) measures CBF-velocity and is commonly used to assess dCA. Diffuse correlation spectroscopy (DCS) is a promising optical technique for non-invasive CBF monitoring, so here we aimed to validate DCS as a tool for quantifying dCA. In 33 healthy adults and 17 acute ischemic stroke patients, resting-state hemodynamic were monitored simultaneously with high-speed (20 Hz) DCS and TCD. dCA parameters were calcaulated by a transfer function analysis using a Fourier decomposition of ABP and CBF (or CBF-velocity). Strong correlation was found between DCS and TCD measured gain (magnitude of regulation) in healthy volunteers (r = 0.73, p < 0.001) and stroke patients (r = 0.76, p = 0.003). DCS-gain retained strong test-retest reliability in both groups (ICC 0.87 and 0.82, respectively). DCS and TCD-derived phase (latency of regulation) did not significantly correlate in healthy volunteers (r = 0.12, p = 0.50) but moderately correlated in stroke patients (r = 0.65, p = 0.006). DCS-derived phase was reproducible in both groups (ICC 0.88 and 0.90, respectively). High-frequency DCS is a promising non-invasive bedside technique that can be leveraged to quantify dCA from resting-state data, but the discrepancy between TCD and DCS-derived phase requires further investigation.

Transcranial Doppler as an early predictor of neurological outcome in mild and moderate traumatic brain injury: An observational study

Background: Traumatic brain injury (TBI) is a major cause of disability and mortality globaly. The transcranial Doppler (TCD) method may show low diastolic blood flow velocity (FVd) and high pulsatility index (PI) measurements brought on by high vascular bed resistance. This study aimed to assess the usefulness of the TCD-PI for the early detection of secondary neurological deterioration (SND) in mild and moderate TBI. Materials and Methods: This prospective study was carried out on 105 mild and moderate TBI patients, who had TCD measurements within 12 h of the initial trauma, and initial computerized tomography (CT) showed mild lesion or no detected abnormality. Results: Primary end point was assessed (SND) within 1st week post trauma. Of the 105 patients with mild and moderate TBI, 29 (27.6%) showed SND. We evaluated the value of our intervention (TCD) to predict SND after mild and moderate TBI in 1st week. PI could predict SND at cutoff 1.21 with good sensitivity of 96.5% and specificity of 94.7%, area under curve (AUC) value of 0.98, negative predictive value (NPV) of 98.6%, and positive predictive value (PPV) of 87.5%. To amplify our finding, we measured FVd, and at 25 cm/s it showed good sensitivity 86.2% and specificity 89.5% when AUC 0.93, NPV 94.4%, and PPV 75.8%. Conclusion: TCD on admission may provide a valuable tool of early prediction of neurological outcome for mild and moderate TBI patients. Closing the gap in poor prediction of commonly used evaluation by CT especially with mild lesion.

Relationships Between Resting Energy Expenditure and Transcranial Doppler Measurements in Patients With and Without Brain Death.

Introduction Brain metabolism deteriorates during brain death, suggesting that cerebral metabolic measurements could serve as a prognostic factor. The application of transcranial Doppler can be useful in evaluating patients evolving to brain death. Resting energy expenditure is lower than expected in patients with brain death, and this is caused by the decrease in cerebral blood flow and consequently lower oxygen supply. The primary aim of this retrospective study is to investigate the early metabolic changes in patients with clinical criteria of brain death and examine if these changes are related to a gradual decrease in blood flow velocities in the middle cerebral artery. Methods All consecutive patients from 1st June 2018 to 30th April 2022, admitted to the ICU with brain injury and a GCS ≤8, were included retrospectively in the study. Patients were allocated into two groups: Group A, patients without clinical signs of brain death (n = 32), and Group B, patients with brain death (n = 34). In each group, three sets of metabolic measurements were performed concomitantly with cerebral blood flow velocities using transcranial Doppler (a) upon admission to the ICU, (b) once hemodynamic stabilization was obtained, and (c) 48 hours after their hemodynamic stabilization or when brain death was confirmed by clinical criteria. Resting energy expenditure (REE) measurements were performed using a metabolic computer. Cerebral blood flow velocities were measured after a period of 30 min using a 2-MHZ 2D ultrasound probe. Results Brain-dead patients had a significant decrease in their metabolic parameters as the cerebral blood flow velocities recorded with the transcranial Doppler deteriorated, (REE Group A = 1667.65 ± 597 vs Group B = 1376.12 ± 615, p = 0.05 and REE predictedGroup A = 113.19 ± 44.9 vs Group B = 93.29 ± 41.5, p = 0.066 for measurement 1;REE Group A = 1844 ± 530.9 vs Group B = 1219.97 ± 489, p < 0.001 and REE predictedGroup A = 124.38 ± 39 vs Group B = 81.35 ± 30.4, p < 0.001 for measurement 2; REE Group A = 1750.97 ± 414, p < 0.001 and REE predicted Group A = 116.38 ± 19.2 vs Group B = 56.09 ± 19.6, p < 0.001 for measurement 3).Multiple stepwise regression analysis revealed a strong relationship between age, the worsening of the blood flow velocities pattern, and the decrease in REE (multiple R = 0.264, F = 5.55, p = 0.009).Furthermore, a statistically significant correlation was found between temperature and REE (correlation coefficient = 0.500, 0.674, 0.784 for measurements 1, 2, and 3, respectively, and p < 0.001 for all measures). Conclusions In brain-dead patients, the gradual decrease in cerebral blood flow leads to a decrease in REE as well as thermogenetic control. These changes can be detected early after the patient's admission to the ICU.

Optimizing the Frequency of Transcranial Doppler (TCD) Exams in Children with Sickle Cell Anemia

Background Transcranial Doppler (TCD) screening of the large intracranial arteries can detect elevated blood velocity and is a strong predictor of stroke risk in children with sickle cell anemia (SCA, HbSS and HbSβ0-thalassemia). Initiation of chronic blood transfusion for patients with confirmed abnormal TCD velocities (time-averaged mean velocity, TAMV≥200 cm/sec) is shown to effectively reduce primary stroke. Current guidelines recommend annual TCD screening for children with SCA ages 2-16 years. Screening intervals were developed following evidence from the STOP studies1 (Figure 1). The estimated prevalence of normal TCD velocities is 83%2 and these children will have received 15 TCD exams from ages 2 to 16 if all results remain within normal range. The cumulative incidence of conversion from normal to conditional TCD velocities is dependent on age, whereby the risk is four times lower in children >10 years, compared to those <10 years of age3. Although TCD screening is non-invasive and safe, it consumes time and requires specialized equipment and trained examiners. Identifying sub-populations for whom TCD screening frequency could be safely reduced could lessen time burden on patients and caregivers and could be cost saving. Main objective To estimate the risk of TAMV conversion from normal to conditional or abnormal categories among children with SCA relative to age. Design/Method We included all participants with SCA from the Sickle Cell Clinical Research and Intervention Program, a longitudinal lifetime cohort of patients with SCD with at least one TCD measurement available both before and after age 10 years. We classified participants into two groups based on TCD screening results before 10 years of age; one group with all normal TCDs, and the other group with at least one non-normal TCD. We then compared the time to first non-normal study after ten years of age between the two groups using the log rank test. Time to first conversion was defined as time from age 10, to time of conversion if conversion occurred, or time to last follow up if no conversion occurred. We correlated the number of TCD exams before age 10 with time to first conversion using the Cox proportional regression model. Exposure to chronic transfusion or hydroxyurea before age 10 and age at first TCD measurement were covariates and were correlated with the time to first conversion. Results Of the 614 patients with TCD screening, 297 had SCA and at least 1 screening before and after age 10 (Table 1). Of these, 174 patients had only normal TCD screening before age 10 and the remaining 123 patients had at least 1 non-normal TCD screening before age 10. During the time they were followed,no patients with only normal TCD screenings before age 10, regardless of exposure to hydroxyurea or transfusions, had a conditional or abnormal TCD exam. Conversely, 41.5% of patients with at least one non-normal TCD before age 10 had a conditional or abnormal TCD screening after age 10. Conclusion In a large retrospective cohort study analysis of children with SCA, patients with TCD exams consistently within the normal range under age 10 years were not at risk of conversion to conditional or abnormal TAMV. These results suggest that children with SCA with all normal TCD velocities before age 10 years may not require additional TCD screening exams after age 10. These results translate to 6 fewer TCD exams per each child with SCA over age 10 with all prior normal TCD exams, potentially conserving resources and reducing burden on patients, families, and the health system. De-implementation studies to reduce the use of TCD screening exams in low-risk cases are needed

A single dose of exenatide had no effect on blood flow velocity in the middle cerebral artery in elderly healthy volunteers: Randomized, placebo-controlled, double-blind clinical trial.

Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) are widely used for the treatment of type 2 diabetes, and recent studies indicate that they may be cardio- and neuroprotective. The safety and effect of a single dose of exenatide, a short-acting GLP-1RA, on cerebral and peripheral arterial function remain unknown. In this randomized, double-blind pilot trial, we assigned elderly healthy volunteers without diabetes and no previous history of stroke to receive a single dose of subcutaneous exenatide (5 μg) or placebo. Primary outcome was immediate changes over time in blood flow velocity of the middle cerebral arteries (VMCA) assessed by repeated transcranial Doppler measurements. Secondary outcomes were changes in peripheral arterial function with finger plethysmography, ankle-brachial index (ABI), and inflammatory- and endothelial-specific biomarkers. Healthy volunteers (13 women and 17 men) were included: (mean ± standard deviation) age: 62 ± 8 years; body weight: 79.6 ± 12.7 kg; VMCA: 65.3 ± 10.7 cm/s; fasting plasma glucose: 5.5 ± 0.5 mmol/L; HbA1c: 33.9 ± 4.1 mmol/mol (5.3 ± 0.38%). No differences between exenatide and placebo group were seen regarding VMCA (p = 0.058), systolic ABI (p = 0.71), plethysmography (p = 0.45), tumor necrosis factor (p = 0.33), interleukin-6 (p = 0.11), interleukin-1β (p = 0.34), vascular cell adhesion molecule 1 (p = 0.73), intercellular adhesion molecule 1 (p = 0.74), or E-selectin (p = 0.31). No severe adverse events were observed. A single dose of exenatide did not change cerebral blood flow velocity or peripheral vessel function in elderly healthy volunteers. The medication was safe to use in persons without diabetes allowing us to investigate this drug further in search of the neuroprotective mechanisms. https://clinicaltrials.gov, Identifier NCT02838589.

Primary Prevention of Stroke in Children With Sickle Cell Anemia in Nigeria: Protocol for a Mixed Methods Implementation Study in a Community Hospital.

BackgroundIn Nigeria, approximately 150,000 children with sickle cell anemia (SCA) are born annually, accounting for more than half of all SCA births worldwide. Without intervention, about 11% of children with SCA will develop a stroke before their 20th birthday. Evidence-based practices for primary stroke prevention include screening for abnormal transcranial Doppler (TCD) measurements coupled with regular blood transfusion therapy for at least one year, followed by hydroxyurea (HU) therapy indefinitely. In high-resource countries, this strategy contributes to a 92% decrease in stroke incidence rates. In 2016, as part of a capacity building objective of the Stroke Prevention Trial in Nigeria (1R01NS094041: SPRING), TCD screening was adopted as standard care at Barau Dikko Teaching Hospital in Kaduna. However, with just 70 radiologists and only 3 certified in TCD screening in the state, just 5.49% (1101/20,040) of eligible children with SCA were screened. Thus, there is a need to explore alternate implementation strategies to ensure children with SCA receive standard care TCD screening to decrease stroke incidence.ObjectiveThis protocol describes a study to create a stroke prevention program in a community hospital in Kaduna through task shifting TCD screening to nurses and training medical officers to initiate and monitor HU utilization for stroke prevention.MethodsThis study will be conducted at 2 sites (teaching hospital and community hospital) over a period of 3 years (November 2020 to November 2023), in 3 phases using both quasi-experimental and effectiveness-implementation study designs. In the needs assessment phase, focus groups and structured interviews will be conducted with health care providers and hospital administrators to identify barriers and facilitators to evidence-based stroke prevention practices. Results from the needs assessment will inform intervention strategies and a process plan to fit the needs of the community hospital. In the capacity building phase, nurses and medical officers at the community hospital will be trained on TCD screening and HU initiation and monitoring. In the implementation phase, children with SCA aged 2-16 years will be recruited into a nonrandomized single-arm prospective trial to determine the feasibility of initiating a task-shifted stroke prevention program by recording recruitment, retention, and adherence rates. The Reach and Effectiveness components of the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework will be used to evaluate implementation outcomes between the community and teaching hospitals.ResultsThe needs assessment phase of the study was completed in February 2021. Manuscript on findings is currently in preparation. Capacity building is ongoing with TCD training and sickle cell disease and stroke education sessions for nurses and doctors in the community hospital. Recruitment for the implementation trial is expected to commence in July 2022.ConclusionsThis study proposes a structured, theory-driven approach to create a stroke prevention program in a community hospital in Kaduna, Nigeria, to decrease stroke incidence among children with SCA. Results will provide preliminary data for a definitive randomized clinical trial in implementation science.International Registered Report Identifier (IRRID)PRR1-10.2196/37927

Patient-Specific Cerebral Blood Flow Simulation Based on Commonly Available Clinical Datasets.

Cerebral hemodynamics play an important role in the development of cerebrovascular diseases. In this work, we propose a numerical framework for modeling patient-specific cerebral blood flow, using commonly available clinical datasets. Our hemodynamic model was developed using Simscape Fluids library in Simulink, based on a block diagram language. Medical imaging data obtained from computerized tomography angiography (CTA) in 59 patients with aneurysmal subarachnoid hemorrhage was used to extract arterial geometry parameters. Flow information obtained from transcranial Doppler (TCD) measurement was employed to calibrate input parameters of the hemodynamic model. The results show that the proposed numerical model can reproduce blood flow in the circle of Willis (CoW) per patient per measurement set. The resistance at the distal end of each terminal branch was the predominant parameter for the flow distribution in the CoW. The proposed model may be a promising tool for assessing cerebral hemodynamics in patients with cerebrovascular disease.

Cerebral hemodynamic effects of early blood pressure lowering after TIA and stroke in patients with carotid stenosis.

Effects of early blood pressure (BP) lowering on cerebral perfusion in patients with moderate/severe occlusive carotid disease after transient ischemic attack (TIA) and non-disabling stroke are uncertain. We aimed to evaluate the changes in transcranial Doppler (TCD) indices in patients undergoing blood pressure lowering soon after TIA/non-disabling stroke. Consecutive eligible patients (1 November 2011 to 30 October 2018) attending a rapid-access clinic with TIA/non-disabling stroke underwent telemetric home blood pressure monitoring (HBPM) for 1 month and middle cerebral artery velocities measurements ipsilateral to carotid stenosis on TCD ultrasound in the acute setting and at 1 month. Hypertensive patients (HBPM ⩾ 135/85) underwent intensive BP-lowering guided by HBPM unless they had bilateral severe occlusive disease (⩾ 70%). Changes in BP and TCD parameters were compared in patients with extracranial moderate/severe carotid stenosis (between 50% and occlusion) versus those with no or mild (< 50%) stenosis. Of 764 patients with repeated TCD measures, 42 had moderate/severe extracranial carotid stenosis without bilateral severe occlusive disease. HBPM was reduced from baseline to 1 month in hypertensive patients both with versus without moderate/severe carotid stenosis (-12.44/15.99 vs -13.2/12.2 mmHg, respectively, p-difference = 0.82), and changes in TCD velocities (4.69/14.94 vs 2.69/13.86 cm/s, respectively, p-difference = 0.52 for peak systolic velocity and 0.33/7.06 vs 1.75/6.84 cm/s, p-difference = 0.34 for end-diastolic velocity) were also similar, with no evidence of greater hemodynamic compromise in patients with stenosis/occlusion. There was no evidence of worsening of TCD hemodynamic indices in patients with moderate/severe occlusive carotid disease treated with BP-lowering soon after TIA/non-disabling stroke, suggesting that antihypertensive treatment in this group of patients is safe in the acute setting of TIA clinics.

Role of noninvasive imaging techniques as outcome predictors in traumatic brain injury

ObjectivesWe aimed to assess the predictive value of early transcranial Doppler (TCD) in patients with traumatic brain injury (TBI) in terms of secondary neurological insult and to establish the comparison between TCD and other diagnostic methods as predictors of outcome in those patients.BackgroundPatients with mild to moderate TBI are at risk of grave neurologic outcomes. Early use of TCD for these patients could be a good predictor.Patients and methodsThis prospective cohort study enrolled adult patients with mild and moderate TBI. Early TCD was done, and the peak systolic velocities, end-diastolic velocity, and time-averaged mean velocity in the middle cerebral artery were recorded. The pulsatility index and the resistance index were calculated. Secondary neurological deterioration (SND) was assessed on the seventh day from injury. Prognosis was also assessed by the Glasgow outcome scale (GOS) on the 28th day of admission.ResultsIn all, 120 patients were enrolled. Of these, 78 patients had SND, and 44 patients developed bad 28-day GOS. Age and severity of trauma (mild and moderate TBI) were significantly associated with both SND and bad GOS. TCD measurements were good predictors to detect patients at risk of SND and the 28-day GOS. Using receiver-operating characteristic analysis, the best threshold limit was found to be 25 cm/s for diastolic cerebral blood flow velocity and 1.2 for pulsatility index. Combination cutoffs of TCD parameters could be good predictors of SND.ConclusionEarly TCD measurements after mild to moderate TBI could predict patients at risk of SND and bad neurological outcome.

Towards automation of transcranial Doppler ultrasound data in pediatric cerebral malaria

ObjectiveTo work towards automating Transcranial Doppler (TCD) imaging data in cerebral malaria (CM) patients. MethodsFunctional principal component analysis (FPCA) was used to identify important features of TCD data and quantify its variation explained by each feature. Cox regression was used to test the association between TCD measurements and mortality hazards rate. A functional clustering algorithm was also employed to cluster TCD waveform data into distinct phenotypic groups. Fisher's exact test and one-way analysis of variance (ANOVA) were used to test the association between the TCD-defined phenotypic groups and 14 variables including demographic data, laboratory measurements, and clinical features. ResultsThe systolic, diastolic, and mean velocities as well as the Windkessel notch together explained more than 98% of total TCD data variation in the middle cerebral arteries (MCAs) and the basilar artery (BA). TCD measurements were associated with the survival hazards rates after adjusting for age and gender (chi-squared test statistic = 31.56, p-value = 0.025). A functional data clustering algorithm identified 7 clusters for the MCA TCD data. No associations between phenotypic groups and demographics, clinical features, or laboratory measurements were detected. ConclusionTCD may be useful as a diagnostic and monitoring tool in CM. Developing an algorithm-driven approach to interpreting the waveforms will enhance the scalability of this tool.

Transcranial-Doppler-Measured Vasospasm Severity is Associated with Delayed Cerebral Infarction After Subarachnoid Hemorrhage.

Angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed cerebral ischemia (DCI)-related cerebral infarction (radiological DCI) and worsened neurological outcome. Transcranial Doppler (TCD) measurements of cerebral blood flow velocity are commonly used after aSAH to screen for vasospasm; however, their association with cerebral infarction is not well characterized. We sought to determine whether time-varying TCD-measured vasospasm severity is associated with cerebral infarction and investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction. We conducted a retrospective single-center cohort study of consecutive adult patients with aSAH with at least one TCD study between 2011 and 2020. The primary outcome was radiological DCI, defined as a cerebral infarction developing at least 2days after any surgical or endovascular intervention without an alternative cause. Cox proportional hazards models were used to examine associations between time-varying vasospasm severity and radiological DCI. Optimal TCD-based time/severity thresholds for predicting radiological DCI were then determined. Of 262 patients with aSAH who underwent TCD studies, 27 (10%) developed radiological DCI. Patients with radiological DCI had higher modified Fisher scale scores and trended toward earlier onset of vasospasm. Adjusted for age, Hunt and Hess scores, and modified Fisher scale scores, the worst-vessel vasospasm severity was associated with radiological DCI (adjusted hazard ratio 1.7 [95% confidence interval 1.1-2.4]). Vasospasm severity within a specific vessel was associated with risk of delayed infarction in the territory supplied by that vessel. Optimal discrimination of patients with radiological DCI was achieved with thresholds of mild vasospasm on days 4-5 or moderate vasospasm on days 6-9, with negative predictive values greater than 90% and positive predictive values near 20%. TCD-measured vasospasm severity is associated with radiological DCI after aSAH. An early, mild TCD-based vasospasm severity threshold had a high negative predictive value, supporting its role as a screening tool to identify at-risk patients.

P.199 Variability descriptors of cerebral blood flow velocity as predictors of vasospasm in Subarachnoid Hemorrhage: A feasibility study

Background: Transcranial Doppler (TCD) measurements poorly predict vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean cerebral blood flow velocity (mean-CBFV) may improve this prediction. We assessed the feasibility of generating reliable mean-CBFV variability metrics using extended TCD recordings in aSAH patients and healthy controls. We also explored whether these parameters are capable to discriminate aSAH patients from healthy controls, and between patients with and without vasospasm. Methods: Bilateral mean-CBFV, systemic blood pressure and heart rate were recorded for 40 minutes in 3 groups: aSAH patients (n=8) within the first 5 days post-ictus, age-matched healthy controls (n=8) and young healthy controls (n=8). We obtained linear [standard deviations, coefficient of variations, very-low, low and high-frequency power-spectra] and non-linear [Fractality, deterministic Chaos analyses] variability metrics. Results: All TCD recordings provided consistent variability metrics. aSAH patients showed higher correlation dimensions, increased high-frequency spectral power, and decreased very-low frequency power than healthy controls. aSAH patients who developed vasospasm (n=3) showed higher mean-CBFV and lower coefficient of variations than those without vasospasm (n=5). Conclusions: Descriptors of mean-CBFV variability may distinguish between aSAH patients with and without vasospasm. Future studies are required to evaluate the role of these variability parameters for risk stratification in aSAH.