Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Implementing Telestroke in the Inpatient Setting: Identifying Factors for Success.

BACKGROUND: Inpatient telestroke programs have emerged as a solution to provide timely stroke care in underserved areas, but their successful implementation and factors influencing their effectiveness remain underexplored. This study aimed to qualitatively evaluate the perspectives of inpatient clinicians located at spoke hospitals participating in a newly established inpatient telestroke program to identify implementation barriers and facilitators. METHODS: This was a formative evaluation relying on semistructured qualitative interviews with 16 inpatient providers (physicians and nurse practitioners) at 5 spoke sites of a hub-and-spoke inpatient telestroke program. The Integrated-Promoting Action on Research Implementation in Health Services framework guided data analysis, focusing on the innovation, recipients, context, and facilitation aspects of implementation. Interviews were transcribed and coded using thematic analysis. RESULTS: Fifteen themes were identified in the data and mapped to the Integrated-Promoting Action on Research Implementation in Health Services framework. Themes related to the innovation (the telestroke program) included easy access to stroke specialists, the benefits of limiting patient transfers, concerns about duplicating tests, and challenges of timing inpatient telestroke visits and notes to align with discharge workflow. Themes pertaining to recipients (care team members and patients) were communication gaps between teams, concern about the supervision of inpatient telestroke advanced practice providers and challenges with nurse empowerment. With regard to the context (hospital and system factors), providers highlighted familiarity with telehealth technologies as a facilitator to implementing inpatient telestroke, yet highlighted resource limitations in smaller facilities. Facilitation (program implementation) was recognized as crucial for education, standardization, and buy-in. CONCLUSIONS: Understanding barriers and facilitators to implementation is crucial to determining where programmatic changes may need to be made to ensure the success and sustainment of inpatient telestroke services.

Reduced Intracerebral Hemorrhage and Perihematomal Edema Volumes in Diabetics on Sulfonylureas.

Background and Purpose- Sulfonylurea medications have been linked to reduced brain edema and improved outcome following ischemic stroke, but their effects on primary intracerebral hemorrhage (pICH) have not been thoroughly explored. Increasing ICH volume and perihematomal edema (PHE) volume are predictors of poor outcome in pICH. We investigated whether preexisting sulfonylurea use influenced ICH volume, PHE volume, and discharge disposition in patients with type 2 diabetes mellitus presenting with pICH. Methods- We performed a retrospective chart review of all diabetic patients presenting with pICH to 2 tertiary academic centers from 2006 to 2016. All patients with diabetes mellitus, pICH, admission computed tomography scan, and sulfonylurea use on admission were included in our study. For each case, 2-matched controls (admission date, age, hematoma location [deep versus lobar], use of antiplatelet, or anticoagulant) with diabetes mellitus and pICH were consecutively selected. ICH and PHE volumes were measured via region of interest analysis on admission computed tomography. To mitigate the influence of ICH volume on PHE, the PHE/ICH surface area ratio was calculated. Hospital discharge disposition was determined via chart abstraction. We used the Wilcoxon rank-sum test and Fisher exact test to compare cases and controls. Results- Of 317 patients screened, 21 sulfonylurea cases and 42-matched controls met criteria for study inclusion. Sulfonylurea cases had significantly lower admission ICH volumes (median, 4 mL; interquartile range [IQR], 2-30 versus median, 25 mL; IQR, 6-60; P=0.011), PHE volumes (median, 4 mL; IQR, 0.9-24 versus median, 17; IQR, 6-37; P=0.0095), and PHE/ICH surface area ratios (median, 0.28; IQR, 0.1-0.4 versus median, 0.43; IQR, 0.3-0.6; P=0.013) as compared with controls. Sulfonylureas were associated with improved discharge disposition ( P=0.0062). Conclusions- In patients with diabetes mellitus and pICH, sulfonylurea use predicted lower ICH and PHE volumes, lower relative PHE, and improved discharge disposition. Given the paucity of treatment options for pICH, further study of sulfonylureas is warranted.

Blood Pressure after Endovascular Therapy for Ischemic Stroke (BEST): A Multicenter Prospective Cohort Study.

Background and Purpose- To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan. Methods- Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0-2 versus 3-6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression. Results- Among 485 enrolled patients (median age, 69 [interquartile range, 57-79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52-3.29], P<0.01; adjusted odds ratio, 1.29 [0.81-2.06], P=0.28, after adjustment for prespecified variables). Conclusions- A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.

Cerebral Air Embolism after Esophagogastroduodenoscopy: Insight on Pathophysiology, Epidemiology, Prevention and Treatment.

BACKGROUND: Air embolism is an extremely rare complication that can follow gastrointestinal endoscopy. The most accepted treatment of cerebral air embolism (CAE) is hyperbaric oxygen (HBO). Limited evidence suggests that lidocaine may have a neuroprotective effect. The exact mechanism does not appear to be well elucidated. METHODS: We conducted a literature search using multiple combinations of keywords from PubMed and Ovid Medline databases according to the PRISMA guidelines. We included articles with cases of air embolism caused by an esophagogastroduodenoscopy (EGD). We excluded cases related to other procedures e.g. colonoscopy, endoscopic retrograde cholangiopancreatography, cholangioscopy, Kasai procedure, bronchoscopy, laparoscopy or thoracoscopy. We were able to identify 30 cases of CAE associated with EGD. We included our experience in treating one patient with CAE after elective EGD. RESULTS: Given the results of our literature search and this patient's characteristics, we chose to treat our patient with HBO and lidocaine infusion. Our case series consists of 31 patients of post EGD CAE, the mean age was 63.7 ± 11.14 years, 38.7% of the patients were women (n = 12). 38.7% of the cases underwent esophageal dilatation (n = 12), while 19.35% had EGD biopsy (n = 6), 9.6% had variceal ligation (n = 3), and 3.22% had variceal banding (n = 1). In 20 out of 31 cases, echocardiography has been documented, 20% of those patients (n = 4) had patent foramen ovale. HBO was used in treatment of 48% of cases (n = 15), among the included patients, 61% survived (n = 19). Our patient showed significant neurological improvement. CONCLUSIONS: Despite the rare incidence of CAE during or after EGD, physicians should be aware of this potential complication. In patients who develop sudden acute neurological symptoms, early diagnosis and intervention may prevent devastating neurological injury and death. The most accepted emergent treatment for CAE includes HBO, consideration of lidocaine, and work-up of source of the air embolism.

A Systematic Literature Review of Patients With Carotid Web and Acute Ischemic Stroke.

Background and Purpose- Carotid web (CW) is a rare form of focal fibromuscular dysplasia defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. It is theorized that CW leads to ischemic stroke secondary to blood flow stasis and subsequent embolization. The natural history and optimal management of CW are unclear. To address this knowledge gap, we performed a systematic literature review (SLR) of CW. Methods- Our librarians performed a SLR for CW and related terminology. Patient-level demographics, stroke risk factors, neuroimaging findings, stroke recurrence or stroke free-duration, and treatment modality were extracted. We used descriptive statistics to characterize our results. When specific patient-level metrics were not reported, the denominators for reporting percentage calculations were adjusted accordingly. Results- Our literature search produced 1150 articles. Thirty-seven articles including 158 patients (median age 46 years [range 16-85], 68% women, 76% symptomatic) met entry criteria and were included in our SLR. Of the symptomatic CW patients: 57% did not have stroke risk factors, 56% who received medical therapy had recurrent stroke (median 12 months, range 0-97), and 72% were ultimately treated with carotid revascularization (50% carotid stenting, 50% carotid endarterectomy). There were no periprocedural complications or recurrent strokes in carotid revascularization patients. Conclusions- CW leads to ischemic stroke in younger patients without conventional stroke risk factors. We found a high stroke recurrence rate in medically managed symptomatic CW patients, whereas carotid revascularization effectively prevented recurrent stroke. Our findings should be interpreted with caution because of risk of publication and reporting bias.

Basal ganglia hemorrhage in a case report following spinal surgery.

BACKGROUND: Intracranial hemorrhage is a rare but potentially severe complication of spinal surgery. Most reported post-operative ICH cases consist of cerebellar hemorrhage. There are fewer reported cases of supratentorial ICH following spinal surgery. CASE PRESENTATION: A 56-year-old woman underwent spinal surgery complicated by bilateral supratentorial intraparenchymal basal ganglia hemorrhage with both intraventricular extension and subarachnoid hemorrhage in both cerebral hemispheres. CONCLUSION: The occurrence of neurological deterioration post-operatively following spinal surgery should alert physicians to the possibility of intracranial hemorrhage in order to facilitate rapid and optimal management. To our knowledge, this is the first case reporting basal ganglia hemorrhage following spinal surgery. Moreover, consideration should be given to the possibility of this complication prior to recommendation of elective spinal surgery.

Safety of cerebral angiography and neuroendovascular therapy in patients with chronic kidney disease.

PURPOSE: Contrast-induced nephropathy is a common clinical concern in patients undergoing neuroendovascular procedures, especially in those with pre-existent kidney disease. We aimed to define the incidence of contrast-induced nephropathy in these high-risk patients in our practice. METHODS: We analyzed data retrospectively from patients undergoing neuroendovascular procedures at two academic medical centers over a 4-year period. Contrast-induced nephropathy was determined by an absolute increase in serum creatinine of 0.5 mg/dL or a rise from its baseline value by ≥ 25%, at 48-72 h after exposure to contrast agent after excluding other causes of renal impairment. High-risk patients were identified as those with pre-procedural estimated glomerular filtration rate < 60 mL/min irrespective of creatinine level, corresponding to stages 3-5 of chronic kidney disease. RESULTS: One hundred eighty-five high-risk patients undergoing conventional cerebral angiography and neuroendovascular interventions were identified. Only 1 out of 184 (0.54%) high-risk patients developed contrast-induced nephropathy. That one patient had stage 5 chronic kidney disease and multiple other risk factors. CONCLUSION: We have observed a very low rate of renal injury in patients with chronic kidney disease, traditionally considered high risk for neuroendovascular procedures. Multiple factors may be responsible in the risk reduction of contrast-induced nephropathy in this patient population.

Home-based transcranial direct current stimulation plus tracking training therapy in people with stroke: an open-label feasibility study.

BACKGROUND: Transcranial direct current stimulation (tDCS) is an effective neuromodulation adjunct to repetitive motor training in promoting motor recovery post-stroke. Finger tracking training is motor training whereby people with stroke use the impaired index finger to trace waveform-shaped lines on a monitor. Our aims were to assess the feasibility and safety of a telerehabilitation program consisting of tDCS and finger tracking training through questionnaires on ease of use, adverse symptoms, and quantitative assessments of motor function and cognition. We believe this telerehabilitation program will be safe and feasible, and may reduce patient and clinic costs. METHODS: Six participants with hemiplegia post-stroke [mean (SD) age was 61 (10) years; 3 women; mean (SD) time post-stroke was 5.5 (6.5) years] received five 20-min tDCS sessions and finger tracking training provided through telecommunication. Safety measurements included the Digit Span Forward Test for memory, a survey of symptoms, and the Box and Block test for motor function. We assessed feasibility by adherence to treatment and by a questionnaire on ease of equipment use. We reported descriptive statistics on all outcome measures. RESULTS: Participants completed all treatment sessions with no adverse events. Also, 83.33% of participants found the set-up easy, and all were comfortable with the devices. There was 100% adherence to the sessions and all recommended telerehabilitation. CONCLUSIONS: tDCS with finger tracking training delivered through telerehabilitation was safe, feasible, and has the potential to be a cost-effective home-based therapy for post-stroke motor rehabilitation. TRIAL REGISTRATION: NCT02460809 (ClinicalTrials.gov).

Relationship Between Lesion Topology and Clinical Outcome in Anterior Circulation Large Vessel Occlusions.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) Alberta Stroke Program Early CT Score (ASPECTS), a surrogate of infarct volume, predicts outcome in anterior large vessel occlusion strokes. We aim to determine whether topological information captured by DWI ASPECTS contributes additional prognostic value. METHODS: Adults with intracranial internal carotid artery, M1 or M2 middle carotid artery occlusions who underwent endovascular therapy were included. The primary outcome measure was poor clinical outcome (3-month modified Rankin Scale score, 3-6). Prognostic value of the 10 DWI ASPECTS regions in predicting poor outcome was determined by multivariable logistic regression, controlling for final infarct volume, age, and laterality. RESULTS: Two hundred and thirteen patients (mean age, 66.1±14.5 years; median National Institutes of Health Stroke Scale, 15) were included. Inter-rater reliability was good for DWI ASPECTS (deep regions, κ=0.72; cortical regions, κ=0.63). All DWI ASPECTS regions with the exception of the putamen were significant predictors (P<0.05) of poor outcome in univariate analyses. Statistical collinearity among ASPECTS regions was not observed. Using penalized multivariable logistic regression, only M4 (odds ratio, 2.82; 95% confidence interval, 1.39-5.76) and M6 (odds ratio, 2.45; 95% confidence interval, 1.15-5.3) involvement were associated with poor outcome. M6 involvement independently predicted poor outcome in right hemispheric strokes (odds ratio, 5.8; 95% confidence interval, 1.9-20.3), whereas M4 (odds ratio, 4.3; 95% confidence interval, 1.3-15.0) involvement predicted poor outcome in left hemispheric strokes adjusting for infarct volume. Topologic information modestly improved the predictive ability of a prognostic score that incorporates age, infarct volume, and hemorrhagic transformation. CONCLUSIONS: Involvement of the right parieto-occipital (M6) and left superior frontal (M4) regions affect clinical outcome in anterior large vessel occlusions over and above the effect of infarct volume and should be considered during prognostication.

Pittsburgh outcomes after stroke thrombectomy score predicts outcomes after endovascular therapy for anterior circulation large vessel occlusions.

BACKGROUND AND PURPOSE: Prognostication tools that predict good outcome in patients with anterior circulation large vessel occlusions after endovascular therapy are lacking. We aim to develop a tool that incorporates clinical and imaging data to predict outcomes after endovascular therapy. METHODS: In a derivation cohort of anterior circulation large vessel occlusion stroke patients treated with endovascular therapy within 8 hours from time last seen well (n=247), we performed logistic regression to identify independent predictors of good outcome (90-day modified Rankin Scale, 0-2). Factors were weighted based on ß-coefficients to derive the Pittsburgh Outcomes After Stroke Thrombectomy (POST) score. POST was validated in an institutional endovascular database (University of Pittsburgh Medical Center, n=393) and the Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) data set (n=105), as well as in patients treated beyond 8 hours (n=194) and in octogenarians (n=111). RESULTS: In the derivation cohort, independent predictors (P<0.1) of good outcome included 24- to 72-hour final infarct volume (in cm(3), P<0.001), age (years, P<0.001), and parenchymal hematoma types 1 and 2 (H, P=0.01). POST was calculated as age+0.5×final infarct volume+15×H. Patients with POST score <60 had a 91% chance of good outcome compared with 4% with POST score ≥120. POST accurately predicted good outcomes in the derivation (area under the curve [AUC]=0.85) and validation cohorts (University of Pittsburgh Medical Center, AUC=0.81; DEFUSE-2, AUC=0.86), as well as in patients treated beyond 8 hours (AUC, 0.85) and octogenarians (AUC=0.76). POST had better predictive accuracy for good and poor outcome than the ischemic stroke predictive risk score (iSCORE). CONCLUSIONS: POST score is a validated predictor of outcome in patients with anterior circulation large vessel occlusions after endovascular therapy.

Tenecteplase for Acute Ischemic Stroke Thrombolysis: Practical Considerations and Real-World Implementation.

The only FDA-approved medical treatment for acute ischemic stroke (AIS) is alteplase (commonly referred to as "tPA"). The utilization of a newer fibrinolytic agent, tenecteplase, in routine stroke care is increasing because of recent clinical trial findings, streamlined clinical workflows, and cost-effectiveness. The stroke community is monitoring this development with considerable interest and special attention to the following questions: (1) Does the current evidence support superiority or noninferiority of tenecteplase compared with standard-of-care alteplase? (2) What are the ramifications of off-label treatment with tenecteplase? (3) And what are the real-world considerations when transitioning from alteplase to tenecteplase for AIS thrombolysis? This commentary provides a practical synthesis of the current evidence and discusses our institutional experience with tenecteplase including treatment considerations, off-label use, patient consent, stroke center accreditation, and cost savings. Necessary "Code Stroke" workflow changes to ensure a safe transition from alteplase to tenecteplase are detailed.

Artery of Percheron Infarction: Clinical Presentation and Outcomes.

Background and Objectives: Occlusion of the artery of Percheron (AOP) produces bilateral thalamic infarction classically leading to deficits of arousal. This nonspecific presentation complicates the diagnosis of acute ischemic stroke. We sought to describe the spectrum of clinical presentation, diagnostic neuroimaging findings, and outcomes in AOP infarction (AOPi). Methods: We conducted a keyword search of our health system's neuroimaging database from 2014 to 2022 to identify patients with AOPi. We abstracted patient demographics, clinical presentation, neuroimaging findings, acute treatment, and modified Rankin Scale (mRS) scores (at baseline, 3 months, and 12 months). We used descriptive statistics to report our findings. Results: Our initial keyword search identified 192 potential AOPi cases. Fifteen cases of AOPi were confirmed and included in our study (8 female [53%], median age 65 years [interquartile range (IQR): 59.5-79.5], median presenting NIHSS 6 [IQR: 2-22]). Common clinical findings on presentation were systolic blood pressure (SBP) > 140: 12 patients (80%); decreased level of consciousness (LOC): 11 patients (73%); diplopia: 8 patients (57%); disorientation: 6 patients (42%); dysarthria: 4 patients (28%); and acute memory/cognitive disturbance: 3 patients (21%). Twelve cases (80%) presented to the emergency department (ED). Median time from symptom onset to ED arrival was 774.5 minutes (IQR: 202.25-3789.0), 4 cases (27%) arrived within 4.5 hours, and one patient (7%) received intravenous thrombolysis. The median time from ED arrival to stroke diagnosis was 519.0 minutes (IQR: 227.5-1307). Head CT was only diagnostic when obtained >570 minutes from time last known well; MRI was diagnostic at all time points. Rates of functional independence (mRS ≤2) at baseline, 3 months, and 12 months were 64%, 21%, and 18%, respectively. Discussion: The diagnosis of stroke was considerably delayed in patients with AOPi, and only one patient received IV thrombolysis. SBP >140, impaired consciousness, and diplopia were the most common findings at presentation. CT was often nondiagnostic, but MRI demonstrated bilateral thalamic infarct in all cases. AOPi caused considerable long-term morbidity. Clinicians should maintain a high degree of suspicion for AOP stroke and consider thrombolysis in appropriately selected patients.

Occult Amyloid-ß-Related Angiitis: Neuroimaging Findings at 1.5T, 3T, and 7T MRI.

Cerebral amyloid angiopathy (CAA) is a progressive neurodegenerative small vessel disease that is associated with intracranial hemorrhage and cognitive impairment in the elderly. The clinical and radiographic presentations have many overlapping features with vascular cognitive impairment, hemorrhagic stroke, and Alzheimer disease (AD). Amyloid-ß-related angiitis (ABRA) is a form of primary CNS vasculitis linked to CAA, with the development of spontaneous autoimmune inflammation against amyloid in the vessel wall with resultant vasculitis. The diagnosis of ABRA and CAA is important. ABRA is often fatal if untreated and requires prompt immunosuppression. Important medical therapies such as anticoagulation and antiamyloid agents for AD are contraindicated in CAA. Here, we present a biopsy-proved case of ABRA with underlying occult CAA. Initial 1.5T and 3T MR imaging did not suggest CAA per the Boston Criteria 2.0. ABRA was not included in the differential diagnosis due to the lack of any CAA-related findings on conventional MR imaging. However, a follow-up 7T MR imaging revealed extensive cortical/subcortical cerebral microbleeds, cortical superficial siderosis, and intragyral hemorrhage in extensive detail throughout the supratentorial brain regions, which radiologically supported the diagnosis of ABRA in the setting of CAA. This case suggests an increased utility of high-field MR imaging to detect occult hemorrhagic neuroimaging findings with the potential to both diagnose more patients with CAA and diagnose them earlier.

Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke: A Post Hoc Analysis of the ARCADIA Randomized Clinical Trial.

Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke. Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke. Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024. Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined. Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage. Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]). Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Ischemic Stroke and Pulmonary Arteriovenous Malformations: A Review.

The potential of covert pulmonary arteriovenous malformations (PAVMs) to cause early onset, preventable ischemic strokes is not well known to neurologists. This is evident by their lack of mention in serial American Heart Association/American Stroke Association (AHA/ASA) Guidelines and the single case report biased literature of recent years. We performed PubMed and Cochrane database searches for major studies on ischemic stroke and PAVMs published from January 1, 1974, through April 3, 2021. This identified 24 major observational studies, 3 societal guidelines, 1 nationwide analysis, 3 systematic reviews, 21 other review/opinion articles, and 18 recent (2017-2021) case reports/series that were synthesized. Key points are that patients with PAVMs have ischemic stroke a decade earlier than routine stroke, losing 9 extra healthy life-years per patient in the recent US nationwide analysis (2005-2014). Large-scale thoracic CT screens of the general population in Japan estimate PAVM prevalence to be 38/100,000 (95% confidence interval 18-76), with ischemic stroke rates exceeding 10% across PAVM series dating back to the 1950s, with most PAVMs remaining undiagnosed until the time of clinical stroke. Notably, the rate of PAVM diagnoses doubled in US ischemic stroke hospitalizations between 2005 and 2014. The burden of silent cerebral infarction approximates to twice that of clinical stroke. More than 80% of patients have underlying hereditary hemorrhagic telangiectasia. The predominant stroke mechanism is paradoxical embolization of platelet-rich emboli, with iron deficiency emerging as a modifiable risk factor. PAVM-related ischemic strokes may be cortical or subcortical, but very rarely cause proximal large vessel occlusions. Single antiplatelet therapy may be effective for secondary stroke prophylaxis, with dual antiplatelet or anticoagulation therapy requiring nuanced risk-benefit analysis given their risk of aggravating iron deficiency. This review summarizes the ischemic stroke burden from PAVMs, the implicative pathophysiology, and relevant diagnostic and treatment overviews to facilitate future incorporation into AHA/ASA guidelines.

Acute Amnestic Syndrome and Ischemic Stroke: A Case Series.

PURPOSE OF REVIEW: Stroke is an uncommon cause of amnesia. We describe in detail 3 cases of anterograde amnesia and confabulation secondary to acute ischemic stroke and review the available literature. RECENT FINDINGS: In our case series, all 3 patients presented with anterograde amnesia and 2 of 3 copresented with prominent confabulation. These symptoms were recognized in delayed fashion, and no patients received IV tissue plasminogen activator (tPA). Although stroke infarct topology was variable, all 3 patients had infarction of the fornix. Long-term follow-up was obtained in 2 of 3 patients: both had persistent memory impairment and were no longer functionally independent. SUMMARY: Acute onset anterograde amnesia and confabulation may uncommonly represent acute ischemic stroke. Delays in this diagnosis typically exclude patients from emergent stroke treatment or timely diagnostic stroke evaluation. Clinicians should maintain a high degree of suspicion for ischemic stroke in this setting, especially in patients with comorbid vascular risk factors. Memory impairment secondary to ischemic stroke can produce considerable long-term disability.

Thrombectomy in DAWN- and DEFUSE-3-Ineligible Patients: A Subgroup Analysis From the BEST Prospective Cohort Study.

BACKGROUND: Because of the overwhelming benefit of thrombectomy for highly selected trial patients with large vessel occlusion (LVO), some trial-ineligible patients are being treated in practice. OBJECTIVE: To determine the safety and efficacy of thrombectomy in DAWN/DEFUSE-3-ineligible patients. METHODS: Using a multicenter prospective observational study of consecutive patients with anterior circulation LVO who underwent late thrombectomy, we compared symptomatic intracerebral hemorrhage (sICH) and good outcome (90-d mRS 0-2) among DAWN/DEFUSE-3-ineligible patients to trial-eligible patients and to untreated DAWN/DEFUSE-3 controls. RESULTS: Ninety-eight patients had perfusion imaging and underwent thrombectomy >6 h; 46 (47%) were trial ineligible (41% M2 occlusions, 39% mild deficits, 28% ASPECTS <6). In multivariable regression, the odds of a good outcome (aOR 0.76, 95% CI 0.49-1.19) and sICH (aOR 3.33, 95% CI 0.42-26.12) were not different among trial-ineligible vs eligible patients. Patients with mild deficits were more likely to achieve a good outcome (aOR 3.62, 95% CI 1.48-8.86) and less sICH (0% vs 10%, P = .16), whereas patients with ASPECTS <6 had poorer outcomes (aOR 0.14, 95% CI 0.05-0.44) and more sICH (aOR 24, 95% CI 5.7-103). Compared to untreated DAWN/DEFUSE-3 controls, trial-ineligible patients had more sICH (13%BEST vs 3%DAWN [P = .02] vs 4%DEFUSE [P = .05]), but were more likely to achieve a good outcome at 90 d (36%BEST vs 13%DAWN [P < .01] vs 17%DEFUSE [P = .01]). CONCLUSION: Thrombectomy is used in practice for some patients ineligible for the DAWN/DEFUSE-3 trials with potentially favorable outcomes. Additional trials are needed to confirm the safety and efficacy of thrombectomy in broader populations, such as large core infarction and M2 occlusions.