Golden Hour Intravenous Thrombolysis for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVES: The benefits of intravenous thrombolysis are time-dependent, with maximum efficacy when administered within the first "golden" hour after onset. Nevertheless, the impact of golden hour thrombolysis has not been well quantified. METHODS: Medline, Embase, and Web of Science databases were systematically searched from inception to August 27, 2023. We included studies that reported safety and efficacy outcomes of ischemic stroke patients treated with intravenous thrombolysis in the golden hour versus later treatment window. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at 90 days. The secondary efficacy outcome was a good functional outcome (defined as modified Rankin Scale score of 0-2). The main safety outcome was symptomatic intracerebral hemorrhage. RESULTS: Seven studies involving 78,826 patients met the selection criteria. Golden hour thrombolysis was associated with higher odds of 90-day excellent functional outcomes (OR 1.40, 95% CI 1.16-1.67) and 90-day good functional outcomes (OR 1.38, 95% CI 1.13-1.69) compared with thrombolysis outside the golden hour. The number needed to treat to benefit for golden hour thrombolysis to reduce disability by at least 1 level on the modified Rankin Scale per patient was 2.6. Rates of symptomatic intracerebral hemorrhage and mortality were similar between groups. INTERPRETATION: Golden hour thrombolysis significantly improved acute ischemic stroke outcomes. The findings provide rationale for intensive efforts aimed at expediting thrombolytic therapy within the golden hour window following the onset of acute ischemic stroke. ANN NEUROL 2024.

Time Course of Early Hematoma Expansion in Acute Spot-Sign Positive Intracerebral Hemorrhage: Prespecified Analysis of the SPOTLIGHT Randomized Clinical Trial.

BACKGROUND: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 µg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. METHODS: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. RESULTS: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2-2.6). Median time from baseline CT to study drug was 62.5 (55-80) minutes, and from study drug to early post-dose CT was 19 (14.5-30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (-0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8-8.3) in the placebo arm (P=0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (-2.6 to 8.3) in the rFVIIa arm and 0.7 mL (-1.6 to 2.1) in the placebo arm (P=0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71-1.43]; P=0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994-1.003]; P=0.50; Table 3). CONCLUSIONS: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01359202.

Comparison of Three Scores of Collateral Status for Their Association With Clinical Outcome: The HERMES Collaboration.

BACKGROUND: Leptomeningeal collateral status on baseline computed tomographic angiography (CTA) is associated with clinical outcome after acute ischemic stroke treatment. However, assessment of collateral status is not uniform. To compare 3 different CTA collateral scores (CS) and imaging techniques about their association with clinical outcome. METHODS: Pooled analysis of patient-level data from the Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration. Patients with large vessel occlusion from 7 randomized controlled trials that compared endovascular thrombectomy with standard medical care were included. Three different CS (Tan CS, regional CS [rCS], and regional Alberta Stroke Program Early CT Score CS) and 2 imaging techniques (single-phase [sCTA] and multiphase/dynamic CTA) were evaluated. Functional independence (modified Rankin Scale score 0-2) at 3 months poststroke was the primary outcome. Furthermore, we assessed the effect of sCTA image acquisition time on collateral status assessment using an adjusted ordinal logistic regression model to obtain predicted values for the trichotomized rCS. RESULTS: Among 1147 pooled patients, 948 (82.7%) had sCTA and 199 (17.3%) multiphase/dynamic CTA as baseline angiography. With all 3 collateral scales, better CSs were associated with better 3-month functional outcome. With sCTA images, the rCS (area under the curve [AUC] 0.63) and regional Alberta Stroke Program Early CT Score CS (AUC 0.62) better predicted functional outcome than the Tan CS (AUC 0.60, respectively; P<0.001 and P=0.02). With multiphase/dynamic CTA images, all collateral scales performed similarly in predicting functional outcome (rCS [AUC 0.61]; regional Alberta Stroke Program Early CT Score CS [AUC 0.61] versus Tan CS [AUC 0.61], respectively; P=0.93 and P=0.91). Overall, no endovascular thrombectomy treatment effect modification by collateral status (rCS) was demonstrated (P=0.41). sCTA timing independently influenced CS assessment. On earlier timed sCTA, the predicted proportions of scans with poor collaterals was higher and vice versa. CONCLUSIONS: In this data set of highly selected patients with stroke, using a regional CS on sCTA likely allows for the most accurate prediction of functional outcome while on time-resolved CTA, the type of CS did not matter. Patients across all collateral grades benefit from endovascular thrombectomy. sCTA timing independently influenced CS assessment.

Thrombus Migration and Fragmentation After Intravenous Alteplase Treatment: The INTERRSeCT Study.

BACKGROUND AND PURPOSE: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke. METHODS: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0-3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated. RESULTS: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2-3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0-1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0-2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72-20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21-5.51]). CONCLUSIONS: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

Comparison of different methods of thrombus permeability measurement and impact on recanalization in the INTERRSeCT multinational multicenter prospective cohort study.

PURPOSE: To compare the association of different measures of intracranial thrombus permeability on non-contrast computerized tomography (NCCT) and computed tomography angiography (CTA) with recanalization with or without intravenous alteplase. METHODS: Patients with anterior circulation occlusion from the INTERRSeCT study were included. Thrombus permeability was measured on non-contrast CT and CTA using the following methods: [1] automated method, mean attenuation increase on co-registered thin (< 2.5 mm) CTA/NCCT; [2] semi-automated method, maximum attenuation increase on non-registered CTA/NCCT (ΔHUmax); [3] manual method, maximum attenuation on CTA (HUmax); and [4] visual method, residual flow grade. Primary outcome was recanalization with intravenous alteplase on the revised AOL scale (2b/3). Regression models were compared using C-statistic, Akaike (AIC), and Bayesian information criterion (BIC). RESULTS: Four hundred eighty patients were included in this analysis. Statistical models using methods 2, 3, and 4 were similar in their ability to discriminate recanalizers from non-recanalizers (C-statistic 0.667, 0.683, and 0.634, respectively); method 3 had the least information loss (AIC = 483.8; BIC = 492.2). A HUmax ≥ 89 measured with method 3 provided optimal sensitivity and specificity in discriminating recanalizers from non-recanalizers [recanalization 55.4% (95%CI 46.2-64.6) when HUmax > 89 vs. 16.8% (95%CI 13.0-20.6) when HUmax ≤ 89]. In sensitivity analyses restricted to patients with co-registered CTA/NCCT (n = 88), methods 1-4 predicted recanalization similarly (C-statistic 0.641, 0.688, 0.640, 0.648, respectively) with Method 2 having the least information loss (AIC 104.8, BIC 109.8). CONCLUSION: Simple methods that measure thrombus permeability are as reliable as complex image processing methods in discriminating recanalizers from non-recanalizers.

Interrater and Intrarater Measurement Reliability of Noncontrast Computed Tomography Predictors of Intracerebral Hemorrhage Expansion.

Background and Purpose- Early hematoma expansion after intracerebral hemorrhage is a potentially modifiable predictor of outcome and a promising therapeutic target. Radiological markers seen on noncontrast computed tomography can help predict hematoma expansion and risk stratify patients presenting with intracerebral hemorrhage. Our objective was to assess the interrater and intrarater reliability of 5 commonly reported noncontrast computed tomographic markers of hematoma expansion. Methods- Four readers independently reviewed images from 40 patients from 2 intracerebral hemorrhage imaging databases (PREDICT Collaboration [Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT] and Massachusetts General Hospital). Readers were blind to all demographic and outcome data and used accepted definitions to establish the presence or absence of intrahematoma hypodensities, blend sign, fluid level, irregular hematoma morphology, and heterogeneous hematoma density. We calculated interrater and intrarater agreement and stratified kappas for the 5 imaging markers. Results- Interrater agreement was excellent for all 5 markers, ranging from 94% to 98%. Interrater kappas ranged from 0.67 to 0.91 (the lowest for fluid level). Interrater agreement had a similar pattern, ranging from 89% to 93%, with Kappas ranging from 0.60 to 0.89. Conclusions- We show that 5 commonly used noncontrast computed tomographic imaging findings all have good-to-excellent interrater and intrarater reliabilities, with the best kappa for blend sign, hypodensities, and heterogeneity.

Predicting Intracerebral Hemorrhage Expansion With Noncontrast Computed Tomography: The BAT Score.

BACKGROUND AND PURPOSE: Although the computed tomographic angiography spot sign performs well as a biomarker for hematoma expansion (HE), computed tomographic angiography is not routinely performed in the emergency setting. We developed and validated a score to predict HE-based on noncontrast computed tomography (NCCT) findings in spontaneous acute intracerebral hemorrhage. METHODS: After developing the score in a single-center cohort of patients with intracerebral hemorrhage (n=344), we validated it in a large clinical trial population (n=954) and in a multicenter intracerebral hemorrhage cohort (n=241). The following NCCT markers of HE were analyzed: hypodensities, blend sign, hematoma shape and density, and fluid level. HE was defined as hematoma growth >6 mL or >33%. The score was created using the estimates from multivariable logistic regression after final predictors were selected from bootstrap samples. RESULTS: Presence of blend sign (odds ratio, 3.09; 95% confidence interval [CI],1.49-6.40; P=0.002), any intrahematoma hypodensity (odds ratio, 4.54; 95% CI, 2.44-8.43; P<0.0001), and time from onset to NCCT <2.5 hours (odds ratio, 3.73; 95% CI, 1.86-7.51; P=0.0002) were predictors of HE. A 5-point score was created (BAT score: 1 point for blend sign, 2 points for any hypodensity, and 2 points for timing of NCCT <2.5 hours). The c statistic was 0.77 (95% CI, 0.70-0.83) in the development population, 0.65 (95% CI 0.61-0.68) and 0.70 (95% CI, 0.64-0.77) in the 2 validation cohorts. A dichotomized score (BAT score ≥3) predicted HE with 0.50 sensitivity and 0.89 specificity. CONCLUSIONS: An easy to use 5-point prediction score can identify subjects at high risk of HE with good specificity and accuracy. This tool requires just a baseline NCCT scan and may help select patients with intracerebral hemorrhage for antiexpansion clinical trials.

Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra-Early Reperfusion.

In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting 20 to 23 seconds and cerebral blood flow <5 to 7 ml/min-1/(100 g)-1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.

Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke.

Importance: Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design. Objective: To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase. Design, Setting, and Participants: Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA). Exposures: Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA. Main Outcomes and Measures: Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]). Results: Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]). Conclusions and Relevance: In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.

Vessel Patency at 24 Hours and Its Relationship With Clinical Outcomes and Infarct Volume in REVASCAT Trial (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset).

BACKGROUND AND PURPOSE: Higher rates of target vessel patency at 24 hours were noted in the thrombectomy group compared with control group in recent randomized trials. As a prespecified secondary end point, we aimed to assess 24-hour revascularization rates by treatment groups and occlusion site as they related to clinical outcome and 24-hour infarct volume in REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset). METHODS: Independent core laboratory adjudicated vessel status according to modified arterial occlusive lesion classification at 24 hours on computed tomographic/magnetic resonance (94.2%/5.8%) angiography and 24-hour infarct volume on computed tomography were studied (95/103 patients in the thrombectomy group versus 94/103 in the control group, respectively). Complete revascularization was defined as modified arterial occlusive lesion grade 3. Its effect on clinical outcome was analyzed by ordinal logistic regression. RESULTS: Complete revascularization was achieved in 70.5% of the solitaire group and in 22.3% of the control group (P<0.001). Significant differences in complete revascularization rates were found for terminus internal carotid artery, M1, and tandem occlusions (all P<0.001) but not for M2 occlusions. In the thrombectomy group, 2 out of 63 patients (3.1%) with modified Thrombolysis in Cerebral Infarction 2b/3 after thrombectomy showed arterial reocclusion (modified arterial occlusive lesion grade 0/1) at 24 hours. Complete revascularization was associated with improved outcome in both thrombectomy (adjusted odds ratio, 4.5; 95% confidence interval, 1.9-10.9) and control groups (adjusted odds ratio, 2.7; 95% confidence interval, 1.0-6.7). Revascularization (modified arterial occlusive lesion grade 2/3) was associated with smaller infarct volumes in either treatment arm. CONCLUSIONS: Complete revascularization at 24 hours is a powerful predictor of favorable clinical outcome, whereas revascularization of any type results in reduced infarct volume in both thrombectomy and control groups. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.

Use of Noncontrast Computed Tomography and Computed Tomographic Perfusion in Predicting Intracerebral Hemorrhage After Intravenous Alteplase Therapy.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is a feared complication of intravenous alteplase therapy in patients with acute ischemic stroke. We explore the use of multimodal computed tomography in predicting this complication. METHODS: All patients were administered intravenous alteplase with/without intra-arterial therapy. An age- and sex-matched case-control design with classic and conditional logistic regression techniques was chosen for analyses. Outcome was parenchymal hemorrhage on 24- to 48-hour imaging. Exposure variables were imaging (noncontrast computed tomography hypoattenuation degree, relative volume of very low cerebral blood volume, relative volume of cerebral blood flow ≤7 mL/min·per 100 g, relative volume of Tmax ≥16 s with all volumes standardized to z axis coverage, mean permeability surface area product values within Tmax ≥8 s volume, and mean permeability surface area product values within ipsilesional hemisphere) and clinical variables (NIHSS [National Institutes of Health Stroke Scale], onset to imaging time, baseline systolic blood pressure, blood glucose, serum creatinine, treatment type, and reperfusion status). RESULTS: One-hundred eighteen subjects (22 patients with parenchymal hemorrhage versus 96 without, median baseline NIHSS score of 15) were included in the final analysis. In multivariable regression, noncontrast computed tomography hypoattenuation grade (P<0.006) and computerized tomography perfusion white matter relative volume of very low cerebral blood volume (P=0.04) were the only significant variables associated with parenchymal hemorrhage on follow-up imaging (area under the curve, 0.73; 95% confidence interval, 0.63-0.83). Interrater reliability for noncontrast computed tomography hypoattenuation grade was moderate (κ=0.6). CONCLUSIONS: Baseline hypoattenuation on noncontrast computed tomography and very low cerebral blood volume on computerized tomography perfusion are associated with development of parenchymal hemorrhage in patients with acute ischemic stroke receiving intravenous alteplase.

Central Nervous System Brucellosis Granuloma and White Matter Disease in Immunocompromised Patient.

Brucellosis is a multisystem zoonotic disease. We report an unusual case of neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia who underwent renal transplantation. Magnetic resonance imaging of the brain showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive for Brucella sp. Granuloma was detected in a brain biopsy specimen.

Intra-Arterial Therapy and Post-Treatment Infarct Volumes: Insights From the ESCAPE Randomized Controlled Trial.

BACKGROUND AND PURPOSE: The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. METHODS: The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 315 enrolled subjects (endovascular treatment n=165; control n=150), 314 subject's infarct volumes at 24 to 48 hours on magnetic resonance imaging (n=254) or computed tomography (n=60) were measured. Post-treatment infarct volumes were compared by treatment assignment and recanalization/reperfusion status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post-treatment infarct volume, and functional status at 90 days (modified Rankin Scale). RESULTS: Median post-treatment infarct volume in all subjects was 21 mL (interquartile range =65 mL), in the intervention arm, 15.5 mL (interquartile range =41.5 mL), and in the control arm, 33.5 mL (interquartile range =84 mL; P<0.01). Baseline National Institute of Health Stroke Scale (P<0.01), site of occlusion (P<0.01), baseline noncontrast computed tomographic scan Alberta Stroke Program Early CT score (ASPECTS) (P<0.01), and recanalization (P<0.01) were independently associated with post-treatment infarct volume, whereas age, sex, treatment type, intravenous alteplase, and time from onset to randomization were not (P>0.05). Post-treatment infarct volume (P<0.01) and delta National Institute of Health Stroke Scale (P<0.01) were independently associated with 90-day modified Rankin Scale, whereas laterality (left versus right) was not. CONCLUSIONS: These results support the primary results of the ESCAPE trial and show that the biological underpinning of the success of endovascular therapy is a reduction in infarct volume. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Infarct in a New Territory After Treatment Administration in the ESCAPE Randomized Controlled Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

BACKGROUND AND PURPOSE: Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized controlled trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). METHODS: The core laboratory identified INTs on 24-hour follow-up imaging, blinded to treatment allocation, after assessing all baseline imaging. INTs were classified into 3 types (I-III) and 2 subtypes (A/B) based on size and if catheter manipulation was likely performed across the vessel territory ostium. Logistic regression was used to understand the effect of multiple a priori identified variables on INT occurrence. Ordinal logistic regression was used to analyze the effect of INTs on modified Rankin Scale shift at 90 days. RESULTS: From 308 patients included, 14 INTs (4.5% overall; 2.8% on follow-up noncontrast computed tomography, 11.7% on follow-up magnetic resonance imaging) were identified (5.0% in endovascular treatment arm versus 4.0% in control arm [P=0.7]). The use of intravenous alteplase was associated with a 68% reduction in the odds of INT occurrence (3.0% with versus 9.1% without; odds ratio, 0.32; 95% confidence interval, 0.11-0.96; adjusted for age, sex, and treatment type). No other variables were associated with INTs. INT occurrence was associated with reduced probability of good clinical outcome (common odds ratio, 0.25; 95% confidence interval, 0.09-0.74; adjusted for age, type of treatment, and follow-up scan). CONCLUSIONS: INTs are uncommon, detected more frequently on follow-up magnetic resonance imaging, and affect clinical outcome. In experienced centers, endovascular treatment is likely not causal, whereas intravenous alteplase may be therapeutic. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

The Role of Vascular Imaging in the Initial Assessment of Patients with Acute Ischemic Stroke.

Over the last few years, improvement in radiological imaging and treatment has changed the management of acute ischemic stroke. We have made significant advances in not only the imaging modalities themselves but also in identifying imaging parameters that can help us predict patient outcomes with both intravascular thrombolysis and endovascular thrombectomy. In this review, we describe the added utility of baseline vascular imaging including computed tomography angiography and magnetic resonance angiography in the diagnosis and management of patients with acute ischemic stroke. We focus on information these imaging modalities provide on clot characteristics, tissue state, collateral status, and endovascular planning. We also highlight the benefits of newer imaging modalities like dynamic computed tomography angiography (CTA) and multi-phase CTA. Lastly, we also describe some of the disadvantages of vascular imaging in ischemic stroke.

Levodopa-Carbidopa Intestinal Gel Infusion Therapy in Advanced Parkinson's Disease: Single Middle Eastern Center Experience.

BACKGROUND: Levodopa therapy in Parkinson's disease (PD) is often associated with disabling motor and non-motor complications in patients with advanced disease due to the variable absorption of levodopa because of an irregular or erratic emptying of the gastric content. METHODS: Prospective single movement disorder center study using pre-set selection criteria, unified PD scale (UPDRS III), non-motor symptoms scale (NMSS), and PD questionnaire-8 (PDQ-8) to evaluate the efficacy, safety, and long-term treatment outcomes using levodopa-carbidopa intestinal gel (LCIG) infusion in patients with advanced PD, who were followed up every 6 months. RESULTS: Twenty patients were recruited over a period of 6 years. Disease duration prior to LCIG infusion ranged from 5 to 18 years (mean 11.4 ± 4.2). The mean follow-up time on LCIG therapy was 48.5 ± 23.2 months (range 11-83 months). Mean 'off' time, UPDRS III, NMSS, and PDQ-8 improvement were statistically significant. Two patients dropped out and 66.7% of patients required tube replacement. CONCLUSION: LCIG infusion monotherapy demonstrated significant improvement in reducing the 'off' time, reducing levodopa-induced dyskinesia, and improving non-motor symptoms and quality of life. This therapy is recommended for patients in whom motor fluctuations are inadequately treated with traditional oral PD therapy.

Endovascular therapy versus best medical management for isolated posterior cerebral artery occlusion: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Isolated posterior cerebral artery occlusions (iPCAO) were underrepresented in pivotal randomized clinical trial (RCTs) of endovascular thrombectomy (EVT) in ischemic stroke, and the benefit of EVT in this population is still indeterminate. We performed a systematic review and a meta-analysis to compare the safety and efficacy of EVT compared to best medical management (BMM) in patients with iPCAO. METHODS: We searched Medline/PubMed, Embase, Web of Science, and the Cochrane databases up to May 2023 for eligible studies reporting outcomes of patients with iPCAO treated with EVT or BMM. We pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI) using a random-effects model. RESULTS: Seven studies involving 2560 patients were included. EVT was associated with significantly higher likelihood of early neurological improvement (OR, 2.31 [95% CI, 1.38-2.91]; p < 0.00001) and visual field normalization (OR, 3.08 [95% CI, 1.76-5.38]; p < 0.0001) compared to BMM. Rates of good functional outcomes (mRS 0-2) were comparable between the two arms (OR, 0.88 [95% CI, 0.70-1.10]; p = 0.26). Symptomatic intracranial hemorrhage (sICH) was comparable between the two groups (OR, 1.94 [95% CI, 0.96-3.93]; p = 0.07). Mortality was also similar between the two groups (OR, 1.36; [95% CI, 0.77-2.42]; p = 0.29). CONCLUSIONS: In patients with iPCAO, EVT was associated with visual and early neurological improvement but with a strong trend toward increased sICH. Survival and functional outcomes may be slightly poorer. The role of EVT in iPCAO remains uncertain.

Posterior reversible encephalopathy syndrome post stem cell transplantation in sickle cell disease: case series and literature review.

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation (SCT). We report 8 patients with sickle cell disease (SCD) who developed PRES, which is likely to be related to immunosuppression. Methods: This is retrospective cohort analysis of the SCD registry at the King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia. Inclusion criteria included all adults SCD patients who underwent SCT from 2011 until 2022. We explored all cases of PRES in patients with SCT. PRES was diagnosed with MRI imaging showing reversible vasogenic cerebral edema associated with neurological symptoms including severe headache, seizures, encephalopathy, delirium, and visual disturbances. Results: During ten years follow-up (2011-2022) we found 8 patients with PRES (age range between 14 to 37 years at diagnosis) PRES occurred 8 to 124 days following SCT in 7 cases and one patient developed PRES 8 months prior to SCT. All patients were on immunosuppressive medications, including tacrolimus, cyclosporine, sirolimus and or mycophenolate mofetil. Headache, seizures, visual hallucinations, confusion, and drowsiness were the most common presenting symptoms. MRI showed abnormalities in the occipital, parietal and frontal lobes in most cases. Recovery was complete in all patients and no recurrences were noted. Two patients had graft versus host disease (GVHD). We compared risk factors for PRES among the 8 cases and 136 SCT in SCD patients who did not develop PRES. There was a significant association between PRES and imaging abnormalities, including previous bi-hemispheric infarctions (p = 0.001), and cerebral microbleeds (CBMs). PRES was strongly associated with presence (p = 0.006), size (p = 0.016) and number (p = 0.005) of CMBs. Conclusion: PRES can develop days to weeks following SCT in patients with SCD, and is associated with immunosuppressive therapy, previous bi-hemispheric infarctions and CMB. Prompt recognition and intervention leads to good recovery.

Intravenous alteplase in minor nondisabling ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Minor ischemic stroke, defined as National Institute of Health Stroke Scale score of 0-5 on admission, represents half of all acute ischemic strokes. The role of intravenous alteplase (IVA) among patients with minor stroke is inconclusive; therefore, we evaluated clinical outcomes of these patients treated with or without IVA. MATERIALS AND METHODS: We searched Medline, Embase, Scopus, and the Cochrane library until August 1, 2023. Inclusion was restricted to the English literature of studies that reported on minor nondisabling stroke patients treated with or without IVA. Odds ratios (ORs) with their corresponding 95% CIs were utilized using a random-effects model. Efficacy outcomes included rates of excellent (modified Rankin scale [mRS] of 0-1) and good (mRS of 0-2) functional outcome at 90 days. The main safety outcome was symptomatic intracerebral hemorrhage (sICH). RESULTS: Five eligible studies, two RCTs and three observational studies, comprising 2764 patients (31.8% female) met inclusion criteria. IVA was administered to 1559 (56.4%) patients. Pooled analysis of the two RCTs revealed no difference between the two groups in terms of 90-days excellent functional outcomes (OR 0.76 [95% CI, 0.51-1.13]; I2 = 0%) and sICH rates (OR 3.76 [95% CI, 0.61-23.20]). No significant differences were observed between the groups in terms of good functional outcomes, 90-day mortality, and 90-day stroke recurrence. CONCLUSION: This meta-analysis of minor nondisabling stroke suggests that IVA did not prove more beneficial compared to no-IVA.

Diagnostic accuracy of large and medium vessel occlusions in acute stroke imaging by neurology residents and stroke fellows: A comparison of CT angiography alone and CT angiography with CT perfusion.

INTRODUCTION: Neurology senior residents and stroke fellows are first to clinically assess and interpret imaging studies of patients presenting to the emergency department with acute stroke. The aim of this study was to compare the diagnostic accuracy of brain CT angiography (CTA) with and without CT perfusion (CTP) between neurology senior residents and stroke fellows. METHODS: In this neuroimaging study, nine practitioners (four senior neurology residents (SNRs) and five stroke fellows (SFs)) clinically assessed and interpreted the imaging data of 50 cases (15 normal images, 21 large vessel occlusions (LVOs) and 14 medium vessel occlusions (MeVOs) in two sessions, 1 week apart in comparison to final diagnosis of experienced neuroradiologist and experienced stroke neurologist consensus. Interrater agreement of CTA alone and CTA with CTP was quantified using kappa statistics, sensitivity, specificity and overall accuracy. RESULTS: Overall, arterial occlusions were correctly identified in 221/315 (70.1%) with CTA alone and in 266/315 (84.4%) with CTA and CTP (p < 0.001). The sensitivity of overall arterial occlusions detection with CTA alone was 94.2% (95% CI: 90.8%-96.6%) while with addition of CTP was 98% (95% CI: 95.6%-99.3%), The specificity of CTA alone was 74.7% (95% CI: 67.2%-81.3%) which increased with CTP to 84.4% (95% CI: 77.7%-89.8%). The likelihood of correct identification with CTA alone was 156/189 (82.54%) for LVOs and 65/126 (51.59%) for MeVOs. This increased to 169/189 (89.42%; p = 0.054) for LVOs and 97/126 (76.98%; p < 0.001) for MeVOs when the CTA images with CTP were viewed. There was good overall interrater agreement between readers when using CTA alone (k 0.71, 95% CI, 0.62-0.80) and almost perfect (k 0.85, 95% CI, 0.76-0.94) when CTP was added to the image for interpretation. CTA and CTP had a significantly lower median interquartile range (IQR) interpretation time than CTA alone (114 [IQR, 103-120] s vs 156 [IQR, 133-160] s, p < 0.001). DISCUSSION: In cerebral arterial occlusions, the rate of LVO and MeVOs detections increases when adding CTP to CTA. The accuracy and time for diagnosing arterial occlusion can be significantly improved if CTP is added to CTA. As MeVOs are commonly missed by front-line neurology senior residents or stroke fellows, cases with significant deficits and no apparent arterial occlusions need to be reviewed with neuroradiological expertise.