Diagnostic accuracy of transcranial doppler for brain death confirmation: Systematic review and meta-analysis

Background and Purpose: Transcranial Doppler is a useful ancillary test for brain death confirmation because it is safe, noninvasive, and done at the bedside. Transcranial Doppler confirms brain death by evaluating cerebral circulatory arrest. Case series studies have generally reported good correlations between transcranial Doppler confirmation of cerebral circulatory arrest and clinical confirmation of brain death. The purpose of this study is to evaluate the utility of transcranial Doppler as an ancillary test in brain death confirmation. Materials and Methods: We conducted a systematic review of the literature and a diagnostic test accuracy meta-analysis to compare the sensitivity and specificity of transcranial Doppler confirmation of cerebral circulatory arrest, by using clinical confirmation of brain death as the criterion standard. Results: We identified 22 eligible studies (1671 patients total), dating from 1987 to 2014. Pooled sensitivity and specificity estimates from 12 study protocols that reported data for the calculation of both values were 0.90 (95% CI, 0.87-0.92) and 0.98 (95% CI, 0.96-0.99), respectively. Between-study differences in the diagnostic performance of transcranial Doppler were found for both sensitivity (I2=76%; P<.001) and specificity (I2=74.3%; P<.001). The threshold effect was not significant (Spearman r= 0.173; P=.612). The area under the curve with the corresponding standard error (SE) was 0.964 ± 0.018, while index Q test ± SE was estimated at 0.910 ± 0.028. Conclusions: The results of this meta-analysis suggest that transcranial Doppler is a highly accurate ancillary test for brain death confirmation. However, transcranial Doppler evaluates cerebral circulatory arrest rather than brain stem function, and this limitation needs to be taken into account when interpreting the results of this meta-analysis

Quantification of microspheres appearance in brain vessels: Implications for residual flow velocity measurements, dose calculations, and potential drug delivery

BACKGROUND AND PURPOSE-: Characteristics of ultrasound-activated gaseous microspheres (μS) reflective of their size and quantities are needed for future dose-escalation and drug delivery trials. METHODS-: A double-blind, interobserver-validated analysis of multi-gate power-motion Doppler μS traces included large (>8μ) μS from agitated saline injections in the right-to-left shunt (RLS) positive stroke patients and small (<5μ) μS from acute patients without shunts receiving thrombolysis and perflutren-lipid μS. RESULTS-: In 101 μS traces from 50 RLS-positive and 10 thrombolysis+μS treated patients, a large μS passage had median maximum duration 30.8 ms (interquartile range [IQR] 22.0ms), multi-gate travel time (MGTT) 58.6±19.3 ms versus small μS: duration 8.3ms (IQR 4.3ms), MGTT 43.2±13.9ms, P<0.001. Small μS had higher embolus-to-blood ratio (EBR): 17.5 (IQR 9.3) versus 7.5 (IQR 4), P<0.001. Receiver-operating curve areas were: duration 0.989 (95% CI 0.968 to 1.000), MGTT 0.766 (0.672 to 0.859), and EBR (Embolus-to-Blood Ratio) 0.927 (0.871 to 0.982), P<0.001. A 15.1-ms duration discriminated size ranges with 98% to 99% accuracy. On average, 130 sequential large (range 51 to 260) and 500 (265-588) small μS can produce continuous flow enhancement for 4 seconds. Small μS velocities on m-mode in obstructed vessels (39.8±11.3 cm/s) were similar to large μS in patent vessels (40.8±11.5 cm/s; P=0.719) and higher than surrounding red blood cell velocities (28.8±13.8 cm/s, P<0.001). CONCLUSIONS-: With normal or reduced flow, activated μS passage duration through a small power motion Doppler gate can quantify the dose of delivered μS. Ultrasound can determine a minimum number of μS needed to achieve constant flow enhancement and targeted drug delivery. Propagation speed of μS smaller than red blood cells may reflect plasma flow velocities around acute occlusions. © 2008 American Heart Association, Inc

Sulfonylurea Pretreatment and In-Hospital Use Does Not Impact Acute Ischemic Strokes (AIS) Outcomes Following Intravenous Thrombolysis

Background and Purpose Preliminary studies have indicated that sulfonylurea drugs (SUD) may confer protection against cerebral swelling and hemorrhagic transformation in severe acute ischemic stroke (AIS). We sought to determine whether pretreatment and in-hospital use of SUD may be associated with better outcomes in diabetic AIS patients treated with intravenous thrombolysis (IVT). Subjects and Methods We analyzed consecutive diabetic AIS patients treated with IVT during a 3-year period. Pretreatment with SUD, admission NIHSS (National Institutes of Health Stroke Scale) score, NIHSS at 48 hours, and modified Rankin Scale (mRS) at discharge were documented. Patients who discontinued SUD during hospitalization were excluded. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH with NIHSS score increase of greater than or equal to 4 points within 72 hours. Early neurological improvement was defined as an NIHSS score decrease of greater than or equal to 4 points or NIHSS score of 0 at 48 hours. Cerebral edema was documented by neuroradiology reports. Favorable functional outcome (FFO) was defined as discharge mRS of 0-1. Results A total of 148 diabetic AIS patients were evaluated (mean age 64 ± 11 years, 49% men, median admission NIHSS score: 8 points). We identified 42 (28%) cases pretreated with SUD. The prevalence of complications and favorable outcomes did not differ (P > .1) between patients pretreated and nonpretreated with SUD: sICH (2% versus 5%), cerebral edema (5% versus 4%), early neurological improvement (42% versus 43%), in-hospital mortality (12% versus 5%), and FFO (22% versus 32%). Conclusions Pretreatment and in-hospital use of SUD appears not to be associated with early favorable outcomes and lower likelihood of potential complications in diabetic AIS patients treated with IVT. © 2017 National Stroke Associatio

International beliefs and head positioning practices in patients with spontaneous hyperacute intracerebral hemorrhage

Background: Prior to the conduct of the Head Position in Stroke Trial (HeadPoST), an international survey (n = 128) revealed equipoise for selection of head position in acute ischemic stroke. Objectives: We aimed to determine whether equipoise exists for head position in spontaneous hyperacute intracerebral hemorrhage (ICH) patients following HeadPoST. Design: This is an international, web-distributed survey focused on head positioning in hyperacute ICH patients. Methods: A survey was constructed to examine clinicians’ beliefs and practices associated with head positioning of hyperacute ICH patients. Survey items were developed with content experts, piloted, and then refined before distributing through stroke listservs, social media, and purposive snowball sampling. Data were analyzed using descriptive statistics and χ2 test. Results: We received 181 responses representing 13 countries on four continents: 38% advanced practice providers, 32% bedside nurses, and 30% physicians; overall, participants had median 7 [interquartile range (IQR) = 3–12] years stroke experience with a median of 100 (IQR = 37.5–200) ICH admissions managed annually. Participants disagreed that HeadPoST provided ‘definitive evidence’ for head position in ICH and agreed that their ‘written admission orders include 30-degree head positioning’, with 54% citing hospital policies for this head position in hyperacute ICH. Participants were unsure whether head positioning alone could influence ICH longitudinal outcomes. Use of serial proximal clinical and technology measures during the head positioning intervention were identified by 82% as the most appropriate endpoints for future ICH head positioning trials. Conclusion: Interdisciplinary providers remain unconvinced by HeadPoST results that head position does not matter in hyperacute ICH. Future trials examining the proximal effects of head positioning on clinical stability in hyperacute ICH are warranted. © The Author(s), 2023

Safety of Intravenous Thrombolysis in Stroke Mimics

Background and Purpose - Shortening door-to-needle time may lead to inadvertent intravenous thrombolysis (IVT) administration in stroke mimics (SMs). We sought to determine the safety of IVT in SMs using prospective, single-center data and by conducting a comprehensive meta-analysis of reported case-series. Methods - We prospectively analyzed consecutive IVT-treated patients during a 5-year period at a tertiary care stroke center. A systematic review and meta-analysis of case-series reporting safety of IVT in SMs and confirmed acute ischemic stroke were conducted. Symptomatic intracerebral hemorrhage was defined as imaging evidence of ICH with an National Institutes of Health Stroke scale increase of ≥4 points. Favorable functional outcome at hospital discharge was defined as a modified Rankin Scale score of 0 to 1. Results - Of 516 consecutive IVT patients at our tertiary care center (50% men; mean age, 60±14 years; median National Institutes of Health Stroke scale, 11; range, 3-22), SMs comprised 75 cases. Symptomatic intracerebral hemorrhage occurred in 1 patient, whereas we documented no cases of orolingual edema or major extracranial hemorrhagic complications. In meta-analysis of 9 studies (8942 IVT-treated patients), the pooled rates of symptomatic intracerebral hemorrhage and orolingual edema among 392 patients with SM treated with IVT were 0.5% (95% confidence interval, 0%-2%) and 0.3% (95% confidence interval, 0%-2%), respectively. Patients with SM were found to have a significantly lower risk for symptomatic intracerebral hemorrhage compared with patients with acute ischemic stroke (risk ratio=0.33; 95% confidence interval, 0.14-0.77; P=0.010), with no evidence of heterogeneity or publication bias. Favorable functional outcome was almost 3-fold higher in patients with SM in comparison with patients with acute ischemic stroke (risk ratio=2.78; 95% confidence interval, 2.07-3.73; P<0.00001). Conclusions - Our prospective, single-center experience coupled with the findings of the comprehensive meta-analysis underscores the safety of IVT in SM. © 2015 American Heart Association, Inc

Pre-tissue plasminogen activator blood pressure levels and risk of symptomatic intracerebral hemorrhage

BACKGROUND AND PURPOSE-: From small pilot studies, uncontrolled pretreatment systolic blood pressure >185 mm Hg and diastolic blood pressure >110 mm Hg in patients with acute ischemic stroke were introduced in the National Institute of Neurological Diseases and Stroke rtPA Stroke Study as a contraindication for thrombolysis. We sought to determine if pretreatment blood pressure protocol violations in patients with acute ischemic stroke receiving intravenous tissue plasminogen activator are related to the subsequent risk of symptomatic intracranial hemorrhage (sICH). METHODS-: We reviewed medical records of consecutive ischemic stroke admissions treated with intravenous thrombolysis over a 10-year period at our tertiary care hospital. The National Institutes of Health Stroke Scale score on admission was used to determine baseline stroke severity. The closest documented blood pressure values to the time of tissue plasminogen activator bolus (range, 0 to 10 minutes) were considered as pretreatment blood pressure. Pretreatment blood pressure protocol violations were identified as systolic blood pressure >185 or diastolic blood pressure >110 mm Hg prebolus. sICH was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by the National Institutes of Health Stroke Scale score increase of ≤4 points. RESULTS-: Among 510 patients with ischemic stroke treated with intravenous tissue plasminogen activator (282 men; mean age, 65±15 years), sICH occurred in 31 patients (6.1%). Blood pressure protocol violations were present in 63 patients (12.4%) and they were more frequent in patients with sICH (26% versus 12%; P=0.019). After adjusting for demographic characteristics, onset-to-treatment time, baseline National Institutes of Health Stroke Scale, stroke risk factors and medications, pretreatment blood pressure protocol violations were independently associated with a higher likelihood of sICH (OR, 2.59; 95% CI, 1.07 to 6.25; P=0.034). CONCLUSIONS-: These data support current guidelines advising not to use intravenous tissue plasminogen activator when pretreatment blood pressure exceeds the prespecified thresholds by showing that blood pressure protocol violations are independently associated with a higher likelihood of sICH. © 2009 American Heart Association, Inc

Safety and outcomes of intravenous thrombolysis in stroke mimics: A 6-year, single-care center study and a pooled analysis of reported series

Background And Purpose- Efforts to increase the availability and shorten the time delivery of intravenous thrombolysis in patients with acute ischemic stroke carry the potential for tissue plasminogen activator administration in patients with diseases other than stroke, that is, stroke mimics (SMs). We aimed to determine safety and to describe outcomes of intravenous thrombolysis in SM. Methods- We retrospectively analyzed stroke registry data of consecutive acute ischemic stroke admissions treated with intravenous thrombolysis over a 6-year-period. The admission National Institutes of Health Stroke Scale score, vascular risk factors, ischemic lesions on brain MRI (routinely performed as part of diagnostic work-up), and discharge modified Rankin Scale scores were documented. Initial stroke diagnosis in the emergency department was compared with final discharge diagnosis. SM diagnosis was based on the absence of ischemic lesions on diffusion-weighted imaging sequences in addition to an alternate discharge diagnosis. Symptomatic intracranial hemorrhage was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by National Institutes of Health Stroke Scale score increase of 4 points. Results- Intravenous thrombolysis was administered in 539 patients with acute ischemic stroke (55% men; mean age, 66±15 years). Misdiagnosis of acute ischemic stroke was documented in 56 cases (10.4%; 95% CI, 7.9% to 13.3%). Conversion disorder (26.8%), complicated migraine (19.6%), and seizures (19.6%) were the 3 most common final diagnoses in SM. SMs were younger (mean age, 56±13 years) and had milder baseline stroke severity (median National Institutes of Health Stroke Scale, 6; interquartile range, 4) compared with patients with confirmed acute ischemic stroke (mean age, 67±14 years; median National Institutes of Health Stroke Scale, 8; interquartile range, 10; P<0.001). There was no case of symptomatic intracranial hemorrhage in SMs (0%; 95% CI, 0% to 5.5%); 96% of SMs were functionally independent at hospital discharge (modified Rankin Scale, 0 to 1). Conclusions- Our single-center data indicate favorable safety and outcomes of intravenous thrombolysis administered to SM. © 2011 American Heart Association, Inc

Safety and outcomes of intravenous thrombolysis in dissection-related ischemic stroke: an international multicenter study and comprehensive meta-analysis of reported case series

The safety and efficacy of intravenous thrombolysis (IVT) in dissection-related ischemic stroke (DRIS) has not been established. We sought to determine safety and recovery rates of IVT in DRIS using prospective, international, multicenter data and by conducting a comprehensive meta-analysis of reported case series. We analyzed consecutive DRIS patients treated with IVT according to national guidelines during a 5-year period at six tertiary-care stroke centers, and also conducted a comprehensive review and meta-analysis of all available case series reporting safety outcomes in DRIS treated with IVT according to PRISMA guidelines. A total of 39 DRIS patients (mean age 60 ± 18 years; 59 % men; median NIHSS 13 points, IQR 9–17) received IVT in our multicenter study. Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, complete recanalization, favorable functional outcome (FFO; mRS-score of 0–1) and functional independence (FI; mRS-score of 0–2) were 0 % (adjusted Wald 95 % CI 0–8 %), 10 % (3–24 %), 55 % (40–70 %), 61 % (45–74 %) and 68 % (52–81 %). The pooled sICH and mortality rates in meta-analysis including 10 case series (234 IVT-DRIS patients) were 2 % (0–5 %) and 4 % (0–8 %). The pooled recanalization, FFO and FI rates were 45 % (26–67 %), 41 % (29–54 %) and 61 % (48–72 %), respectively. Substantial heterogeneity was only found for FFO (I2 = 61 %; p = 0.006). Subsequent meta-regression analysis identified baseline NIHSS and dissection in the posterior circulation as independent predictors of FFO (p < 0.05), accounting for FFO variance across different studies. Our prospective, international data coupled with comprehensive meta-analysis results underscore IVT safety in DRIS, while further independent validation is required in larger observational registries or RCTs. © 2015, Springer-Verlag Berlin Heidelberg

Prognostication via early computed tomography head in patients treated with targeted temperature management after cardiac arrest

Background: We evaluated computed tomography head (CTH) imaging obtained prior to targeted temperature management (TTM) in patients after cardiac arrest, and its role in prognostication. Methods: In this retrospective cohort study in a tertiary-care hospital, 341 adults presenting with out-of-hospital cardiac arrest received a CTH prior to TTM. Associations between outcomes and neuroimaging variables were evaluated with Chi-square analysis for significant associations that yielded a composite neuroimaging score—Tennessee Early Neuroimaging Score (TENS). Univariable and multivariable logistic regression analysis including TENS as an independent variable and the four outcome dependent variables were analyzed. Results: Four of the neuroimaging variables—sulcal effacement, partial gray-white matter effacement, total gray-white matter effacement, deep nuclei effacement—had significant associations with each of the four outcome variables and yielded TENS. In multivariable logistic regression models adjusted for potential confounders, TENS was associated with poor discharge CPC (OR 2.15, 95%CI 1.16–3.98, p = .015), poor disposition (OR 2.62, 95%CI 1.37–5.02, p = .004), in-hospital mortality (OR 1.99, 95%CI 1.09–3.62, p = .024), and ICU mortality (OR 1.89, 95%CI 1.12–3.20, p = .018). Conclusion: Imaging prior to TTM may help identify post-cardiac arrest patients with severe anoxic brain injury and poor outcomes. © 2019 Elsevier B.V

Safety and outcomes of intravenous thrombolysis in dissection-related ischemic stroke: an international multicenter study and comprehensive meta-analysis of reported case series

The safety and efficacy of intravenous thrombolysis (IVT) in dissection-related ischemic stroke (DRIS) has not been established. We sought to determine safety and recovery rates of IVT in DRIS using prospective, international, multicenter data and by conducting a comprehensive meta-analysis of reported case series. We analyzed consecutive DRIS patients treated with IVT according to national guidelines during a 5-year period at six tertiary-care stroke centers, and also conducted a comprehensive review and meta-analysis of all available case series reporting safety outcomes in DRIS treated with IVT according to PRISMA guidelines. A total of 39 DRIS patients (mean age 60 ± 18 years; 59 % men; median NIHSS 13 points, IQR 9–17) received IVT in our multicenter study. Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, complete recanalization, favorable functional outcome (FFO; mRS-score of 0–1) and functional independence (FI; mRS-score of 0–2) were 0 % (adjusted Wald 95 % CI 0–8 %), 10 % (3–24 %), 55 % (40–70 %), 61 % (45–74 %) and 68 % (52–81 %). The pooled sICH and mortality rates in meta-analysis including 10 case series (234 IVT-DRIS patients) were 2 % (0–5 %) and 4 % (0–8 %). The pooled recanalization, FFO and FI rates were 45 % (26–67 %), 41 % (29–54 %) and 61 % (48–72 %), respectively. Substantial heterogeneity was only found for FFO (I2 = 61 %; p = 0.006). Subsequent meta-regression analysis identified baseline NIHSS and dissection in the posterior circulation as independent predictors of FFO (p < 0.05), accounting for FFO variance across different studies. Our prospective, international data coupled with comprehensive meta-analysis results underscore IVT safety in DRIS, while further independent validation is required in larger observational registries or RCTs.SCOPUS: ar.jinfo:eu-repo/semantics/publishe