Nima Kashani

BACKGROUND: Restoring blood flow to ischemic tissue is the cornerstone of acute stroke therapy and is usually beneficial. However, when reperfusion is achieved for severely injured tissue, it is often futile and may occasionally cause harm. We aim to determine the prevalence and variables associated with clinical no improvement or acute worsening at 24 hours despite reperfusion in patients with large-vessel occlusion stroke treated with endovascular thrombectomy. METHODS: Data are from ESCAPE-NA1 (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a randomized trial of nerinetide in patients with acute large-vessel occlusion stroke undergoing endovascular thrombectomy. Patients with unsuccessful recanalization (expanded Thrombolysis in Cerebral Infarction <2b), infarcts in new vascular territories, vessel perforation, or remote parenchymal hemorrhage were excluded. Clinical outcomes after reperfusion were classified by 24-hour National Institutes of Health Stroke Scale changes compared with baseline: improvement (≥4-point improvement), no improvement (±3-point from baseline), and worsening (≥4-point worsening). Baseline variables associated with worsening were identified using logistic regression. In the computed tomography perfusion subgroup, prevalence of parenchymal hemorrhage (any parenchymal hematoma) and infarct progression (final infarct volume exceeding the initial hypoperfused region) were evaluated. RESULTS: A total of 833 patients were included (median age, 70.9 years [interquartile range, 60.7–79.4]; 51.4% men). After reperfusion, 669 (80.3%) patients improved, 135 (16.2%) showed no improvement, and 29 (3.5%) worsened. Independent predictors of worsening were longer onset-to-reperfusion time (adjusted odds ratio, 1.02 [95% CI, 1.00–1.04] per 10-minute increase) and greater degree of sedation (adjusted odds ratio, 1.78 [95% CI, 1.29–2.46] per category of none, conscious sedation, and general anesthesia). In the computed tomography perfusion subgroup (n=414), among patients with worsening after reperfusion, parenchymal hemorrhage was seen in 5 patients (31.3%) and infarct progression in 4 patients (25%). CONCLUSIONS: Clinical worsening in the acute period (ie, early neurological deterioration) despite reperfusion and the absence of procedure-related complications was rare in this selected large-vessel occlusion stroke cohort (3.5%). Factors associated with worsening after reperfusion were a longer time from symptom onset-to-reperfusion and a higher degree of sedation.

Background: The Alberta Stroke Program Early CT Score (ASPECTS) and CT angiography (CTA) Collateral Score (CS) are routinely used to estimate ischemic core burden and collateral status in acute ischemic stroke due to large vessel occlusion, but suffer from limited reliability. Whether automated CT perfusion (CTP) maps improve scoring consistency remains unclear. Objectives: To assess the reliability of these scores on non-contrast computed tomography (NCCT) and CTA among numerous raters, with and without access to automated perfusion maps, and their correlations with endovascular thrombectomy (EVT) decisions. Methods: Twenty-nine clinicians independently rated 60 imaging cases from 30 late-window stroke patients with large vessel occlusion, each presented twice: once using NCCT and CTA alone (‘non-CTP cases’), and once with the addition of perfusion maps (‘CTP cases’). Twenty-eight raters (97%) completed the survey twice. Inter- and intra-reliability was assessed using Gwet’s AC1/2 coefficients (κ _G ). Correlations with EVT decisions were evaluated using Cramer V. Results: Inter-rater reliability for ASPECTS was substantial and similar between non-CTP (κ _G = 0.65, 95% CI: 0.53 to 0.78) and CTP cases (κ _G = 0.64, 95% CI: 0.51 to 0.77). CS showed an almost perfect reliability in both scenarios (κ _G = 0.82 and 0.83). Intra-rater agreement was at least substantial. Dichotomizing ASPECTS as 0-2/3-10 improved reliability to almost perfect. ASPECTS strongly correlated with EVT decisions (V=0.80), whereas CS showed moderate correlation (V=0.56), both remaining similar with the addition of CTP (V=0.75 and 0.54, respectively). Conclusion: Automated perfusion imaging did not improve the reliability of ASPECTS or CS. Strong reliability was achieved with NCCT and CTA alone.

Background: Socioeconomic status (SES) has long been recognized as an important determinant of ischemic stroke outcomes, with increased stroke severity and mortality found in patients with lower SES. However, the impact of SES on outcomes post-endovascular thrombectomy in Canada remains largely unknown. Methods: This study is a retrospective cohort analysis of patients from 2015–2024 who received endovascular thrombectomy for large vessel occlusion in Manitoba, Canada (study catchment area 650,000 km ² , population 1.4 million). Patient residence postal codes were matched with neighborhood-level socioeconomic factors using the Canadian Material and Social Deprivation Index and the Canadian Index of Multiple Deprivation (CIMD). Regression analyses adjusting for baseline demographics, geographic variables, presenting National Institutes of Health Stroke Scale (NIHSS), and time to angiography were conducted to analyze the association between socioeconomic factors and a binarized 90-day modified Rankin Scale (mRS). Results: Overall, 793 patients (51% females, median age 74 years) were included. Unadjusted analyses showed a positive association between poor clinical outcomes and increased economic dependency scores in the CIMD index (OR = 1.18 [95%CI 1.03, 1.37]), as well as decreased CIMD ethno-cultural composition scores (OR = 0.84 [0.73–0.98]). Adjusted analysis did not show consistent associations between procedural outcomes or functionally independent outcomes at 90 days. Interpretation: This Canadian provincial stroke registry study showed SES-related discrepancies in stroke outcomes on an unadjusted basis, but no definite discrepancies after adjustment for age, presenting severity, and time to angiography. These findings suggest that SES-related differences in these variables mediate the observed relationship between SES and poor clinical outcomes.

BACKGROUND: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide’s effect on infarct volume. METHODS: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo. Patients not receiving intravenous alteplase were included in this post hoc secondary analysis of the trial data. Final infarct volume was manually segmented on 24-hour noncontrast computed tomography or diffusion-weighted magnetic resonance imaging. Predictors of final infarct volume were identified using multivariable linear regression with cubic-root-transformed infarct volume as the dependent variable. Evidence of treatment-by-predictor interaction was tested by including interaction terms in the model. RESULTS: Four hundred forty-six patients (219 who received nerinetide and 227 who received a placebo) out of a total of 1105 enrolled patients were included in this secondary post hoc analysis of the randomized ESCAPE-NA1 trial. Nerinetide was a strong predictor of smaller infarct volume (adjusted β coefficient, −0.35 [95% CI, −0.67 to −0.02]). Other predictors of smaller infarct volume were history of hypertension, good pial collateral filling on multiphase computed tomography angiography, a middle cerebral artery occlusion compared with an internal carotid artery occlusion, lower baseline National Institutes of Health Stroke Scale score, lower baseline systolic blood pressure, lower baseline serum glucose, shorter onset-to-randomization time, and higher Alberta Stroke Program Early CT Score. There was evidence of a treatment-by-systolic blood pressure and treatment-by-anesthesia interaction: nerinetide attenuated the negative effects of elevated baseline ( P _interaction =0.02) and postdose ( P _interaction =0.04) systolic blood pressure and use of general anesthesia ( P _interaction =0.06) on final infarct volume. We observed a marginally significant interaction with reperfusion status, such that nerinetide may attenuate the harmful effect of poor reperfusion status on infarct volume ( P _interaction =0.08). CONCLUSIONS: Nerinetide treatment was strongly associated with smaller final infarct volumes among patients not cotreated with alteplase. The reduction in infarct volume was greater among patients with poor prognostic factors. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02930018.

With recent trials suggesting that endovascular thrombectomy (EVT) alone may be noninferior to combined intravenous thrombolysis (IVT) with alteplase and EVT and that tenecteplase is non-inferior to alteplase in treating acute ischemic stroke, we sought to understand current practices around the world for treating acute ischemic stroke with large vessel occlusion (LVO) depending on the center of practice (IVT-capable vs IVT and EVT-capable stroke center). The electronic survey launched by the Practice Current section of Neurology: Clinical Practice included 6 clinical and 8 demographic questions. A single-case scenario was presented of a 65-year-old man presenting with right hemiplegia with aphasia with a duration of 1 hour. Imaging showed left M1-MCA occlusion with no early ischemic changes. The respondents were asked about their treatment approach in 2 settings: the patient presented to (1) the IVT-only capable center and (2) the IVT and EVT-capable center. They were also asked about the thrombolytic agent of choice in current and ideal circumstances for these settings. A total of 203 physicians (42.9% vascular neurologists) from 44 countries completed the survey. Most participants (55.2%) spent ≥50% of their time delivering stroke care. The survey results showed that in current practice, more than 90% of respondents would offer IVT + EVT to patients with LVO stroke presenting to either an EVT-capable (91.1%) or IVT-only-capable center (93.6%). Although nearly 80% currently use alteplase for thrombolysis, around 60% would ideally like to switch to tenecteplase independent of the practice setting. These results were similar between stroke and non-stroke neurologists. Most physicians prefer IVT before EVT in patients with acute ischemic stroke attributable to large vessel occlusion independent of the practice setting.

BACKGROUND AND PURPOSE: Hemorrhagic transformation can occur as a complication of endovascular treatment for acute ischemic stroke. This study aimed to determine whether ischemia depth as measured by admission CTP metrics can predict the development of hemorrhagic transformation at 24 hours. MATERIALS AND METHODS: Patients with baseline CTP and 24-hour follow-up imaging from the ESCAPE-NA1 trial were included. RAPID software was used to generate CTP volume maps for relative CBF, CBV, and time-to-maximum at different thresholds. Hemorrhage on 24-hour imaging was classified according to the Heidelberg system, and volumes were calculated. Univariable and multivariable regression analyses assessed the association between CTP lesion volumes and hemorrhage/hemorrhage subtypes. RESULTS: Among 408 patients with baseline CTP, 142 (35%) had hemorrhagic transformation at 24-hour follow-up, with 89 (63%) classified as hemorrhagic infarction (HI1/HI2), and 53 (37%), as parenchymal hematoma (PH1/PH2). Patients with HI or PH had larger volumes of low relative CBF and CBV at each threshold compared with those without hemorrhage. After we adjustied for baseline and treatment variables, only increased relative CBF <30% lesion volume was associated with any hemorrhage (adjusted OR, 1.14; 95% CI, 1.02–1.27 per 10 mL), as well as parenchymal hematoma (adjusted OR, 1.23; 95% CI, 1.06–1.43 per 10 mL). No significant associations were observed for hemorrhagic infarction. CONCLUSIONS: Larger “core” volumes of relative CBF <30% were associated with an increased risk of PH following endovascular treatment. This particular metric, in conjunction with other clinical and imaging variables, may, therefore, help estimate the risk of post-endovascular treatment hemorrhagic complications.

Background: Limited research exists regarding the impact of neuroimaging on endovascular thrombectomy (EVT) decisions for late-window cases of large vessel occlusion (LVO) stroke.Objective: T0 assess whether perfusion CT imaging: (1) alters the proportion of recommendations for EVT, and (2) enhances the reliability of EVT decision-making compared with non-contrast CT and CT angiography.Methods: We conducted a survey using 30 patients drawn from an institutional database of 3144 acute stroke cases. These were presented to 29 Canadian physicians with and without perfusion imaging. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κ_G).Results: The percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. Individual decisions changed in 21.4% of cases (11.3% against EVT and 10.1% in favor). Inter-rater agreement (κ_G) among the 29 raters was similar between non-perfusion and perfusion CT neuroimaging (κ_G=0.487; 95% CI 0.327 to 0.647 and κ_G=0.552; 95% CI 0.430 to 0.675). The 95% CIs overlapped with moderate agreement in both. Intra-rater agreement exhibited overlapping 95% CIs for all 28 raters. κ_Gwas either substantial or excellent (0.81–1) for 71.4% (20/28) of raters in both groups.Conclusions: Despite the minimal difference in overall EVT recommendations with either neuroimaging protocol one in five decisions changed with perfusion imaging. Regarding agreement we found that the use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for patients with late-window LVO.

BACKGROUND AND PURPOSE: Baseline CTP sometimes overestimates the size of the infarct core (“ghost core” phenomenon). We investigated how often CTP overestimates infarct core compared with 24-hour imaging, and aimed to characterize the patient subgroup in whom a ghost core is most likely to occur. MATERIALS AND METHODS: Data are from the randomized controlled ESCAPE-NA1 trial, in which patients with acute ischemic stroke undergoing endovascular treatment were randomized to intravenous nerinetide or placebo. Patients with available baseline CTP and 24-hour follow-up imaging were included in the analysis. Ghost infarct core was defined as CTP core volume minus 24-hour infarct volume > 10 mL). Clinical characteristics of patients with versus without ghost core were compared. Associations of ghost core and clinical characteristics were assessed by using multivariable logistic regression. RESULTS: A total of 421 of 1105 patients (38.1%) were included in the analysis. Forty-seven (11.2%) had a ghost core > 10 mL, with a median ghost infarct volume of 13.4 mL (interquartile range 7.6–26.8). Young patient age, complete recanalization, short last known well to CT times, and possibly male sex were associated with ghost infarct core. CONCLUSIONS: CTP ghost core occurred in ∼1 of 10 patients, indicating that CTP frequently overestimates the infarct core size at baseline, particularly in young patients with complete recanalization and short ischemia duration.

Background: Limited research exists regarding the impact of neuroimaging modality on endovascular thrombectomy (EVT) decisions for late window large vessel occlusion (LVO) stroke cases. Purpose: This study assesses whether perfusion CT imaging: 1) alters the proportion of recommendations for EVT, and 2) enhances the reliability of EVT decision-making compared to non-contrast CT and CT angiography. Materials and Methods: We conducted an online survey using 30 patients drawn from an institutional database of 3144 acute stroke cranial CT scans. These cases were presented to 29 stroke or neurointerventional physicians from Canada across two sessions. Physicians evaluated each patient both with and without perfusion imaging and gave EVT recommendations. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κ _G ). Our outcomes were: 1) the proportion of EVT recommendations, and 2) interrater and intrarater agreement, with or without perfusion imaging. Results: In the first round, 29 raters completed the assessment, with 28 finishing the second round. The percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. However, individual decisions changed in 21.4% of cases, with 11.3% against EVT and 10.1% in favor. Interrater agreement (κG) among the 29 raters was similar between non-perfusion CT neuroimaging and perfusion CT neuroimaging (κG = 0.487; 95% CI 0.327, 0.647 and κG = 0.552; 95% CI 0.430, 0.675). The 95% CIs overlapped with moderate agreement in both. Intrarater agreement exhibited overlapping 95% CIs for all 28 raters. κG was either substantial or excellent (0.81-1) for 71.4% (20/28) of raters in both groups. Conclusion: The difference in EVT recommendations is minimal with either neuroimaing protocol. Regarding agreement we found that use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for late window LVO patients.