Risk of Aneurysm Rupture After Thrombolysis in Patients With Acute Ischemic Stroke and Unruptured Intracranial Aneurysms

Background and ObjectivesUnruptured intracranial aneurysms (UIAs) are considered to be a relative contraindication for IV thrombolysis (IVT) in acute ischemic stroke (AIS). Currently, however, data are limited on the risk of UIA rupture after IVT. Our objective was to assess whether IVT for AIS can lead to a UIA rupture and intracranial hemorrhages (ICHs) in patients with unruptured UIAs.MethodsThis was a prospective cohort study of consecutive patients treated in a comprehensive stroke center between 2005 and 2019. We assessed radiology reports and records at the Finnish Care Register for Health Care to identify patients with UIAs among all patients with AIS treated with IVT at the center. We analyzed patient angiograms for aneurysm characteristics and other brain imaging studies for ICHs after IVT. The main outcome was in-hospital ICHs attributable to a UIA rupture after IVT. Secondary outcomes were in-hospital symptomatic ICHs (European-Australian Cooperative Acute Stroke Study [ECASS-2] criteria, i.e., NIH Stroke Scale score increase ≥4 points) and any in-hospital ICHs.ResultsA total of 3,953 patients were treated with IVT during the 15-year study period. One hundred thirty-two (3.3%) of the 3,953 patients with AIS had a total of 155 UIAs (141 saccular and 14 fusiform). The mean diameter of UIAs was 4.7 ± 3.8 mm, with 18.7% being ≥7 mm and 9.7% ≥10 mm in diameter. None of the 141 saccular UIAs ruptured after IVT. Three patients (2.3%, 95% confidence interval [CI] 0.6%–5.8%) with large fusiform basilar artery UIAs had a fatal rupture at 27 hours, 43 hours, and 19 days after IVT. All 3 were administered anticoagulation treatments after IVT, and anticoagulation took effect during the UIA rupture. Any ICHs and symptomatic ICHs were detected in 18.9% (95% CI 12.9%–26.2%) and 8.3% (95% CI 4.4%–13.8%) of all patients with AIS, respectively.DiscussionIVT appears to be safe in patients with AIS with saccular UIAs, including larges UIAs (≥10 mm). Anticoagulation after AIS in patients with large fusiform posterior circulation UIAs may increase the risk of aneurysm rupture.

Post-stroke fatigue is associated with resting state posterior hypoactivity and prefrontal hyperactivity

Background Fatigue is associated with poor functional outcomes and increased mortality following stroke. Survivors identify fatigue as one of their key unmet needs. Despite the growing body of research into post-stroke fatigue, the specific neural mechanisms remain largely unknown. Aim This observational study aimed to identify resting state brain activity markers of post-stroke fatigue. Method Sixty-three stroke survivors (22 women; age 30–89 years; mean 67.5 ± 13.4 years) from the Cognition And Neocortical Volume After Stroke study, a cohort study examining cognition, mood, and brain volume in stroke survivors following ischemic stroke, underwent brain imaging three months post-stroke, including a 7-minute resting state functional magnetic resonance imaging. We calculated the fractional amplitude of low-frequency fluctuations, which is measured at the whole-brain level and can detect altered spontaneous neural activity of specific regions. Results Forty-five participants reported experiencing post-stroke fatigue as measured by an item on the Patient Health Questionnaire-9. Fatigued compared to non-fatigued participants demonstrated significantly lower resting-state activity in the calcarine cortex ( p < 0.001, cluster-corrected pFDR = 0.009, k = 63) and lingual gyrus ( p < 0.001, cluster-corrected pFDR = 0.025, k = 42) and significantly higher activity in the medial prefrontal cortex ( p < 0.001, cluster-corrected pFDR = 0.03, k = 45). Conclusions Post-stroke fatigue is associated with posterior hypoactivity and prefrontal hyperactivity reflecting dysfunction within large-scale brain systems such as fronto-striatal-thalamic and frontal-occipital networks. These systems in turn might reflect a relationship between post-stroke fatigue and abnormalities in executive and visual functioning. This whole-brain resting-state study provides new targets for further investigation of post-stroke fatigue beyond the lesion approach.

Thrombolysis in Mild Stroke: A Comparative Analysis of the PRISMS and MaRISS Studies

Background and Purpose: Mild ischemic stroke patients enrolled in randomized controlled trials of thrombolysis may have a different symptom severity distribution than those treated in routine clinical practice. Methods: We compared the distribution of the National Institutes of Health Stroke Scale (NIHSS) scores, neurological symptoms/severity among patients enrolled in the PRISMS (Potential of r-tPA for Ischemic Strokes With Mild Symptoms) randomized controlled trial to those with NIHSS score ≤5 enrolled in the prospective MaRISS (Mild and Rapidly Improving Stroke Study) registry using global P values from χ 2 analyses. Results: Among 1736 participants in MaRISS, 972 (56%) were treated with alteplase and 764 (44%) were not. These participants were compared with 313 patients randomized in PRISMS. The median NIHSS scores were 3 (2–4) in MaRISS alteplase-treated, 1 (1–3) in MaRISS non–alteplase-treated, and 2 (1–3) in PRISMS. The percentage with an NIHSS score of 0 to 2 was 36.3%, 73.3%, and 65.2% in the 3 groups, respectively ( P <0.0001). The proportion of patients with a dominant neurological syndrome (≥1 NIHSS item score of ≥2) was higher in MaRISS alteplase-treated (32%) compared with MaRISS nonalteplase-treated (13.8%) and PRISMS (8.6%; P <0.0001). Conclusions: Patients randomized in PRISMS had comparable deficit and syndromic severity to patients not treated with alteplase in the MaRISS registry and lesser severity than patients treated with alteplase in MaRISS. The PRISMS trial cohort is representative of mild patients who do not receive alteplase in current broad clinical practice.

Detection of large vessel occlusion stroke with electroencephalography in the emergency room: first results of the ELECTRA-STROKE study

Background Prehospital detection of large vessel occlusion stroke of the anterior circulation (LVO-a) would enable direct transportation of these patients to an endovascular thrombectomy (EVT) capable hospital. The ongoing ELECTRA-STROKE study investigates the diagnostic accuracy of dry electrode electroencephalography (EEG) for LVO-a stroke in the prehospital setting. To determine which EEG features are most useful for this purpose and assess EEG data quality, EEG recordings are also performed in the emergency room (ER). Here, we report data of the first 100 patients included in the ER. Methods Patients presented to the ER with a suspected stroke or known LVO-a stroke underwent a single EEG prior to EVT. Diagnostic accuracy for LVO-a stroke of frequency band power, brain symmetry and phase synchronization measures were evaluated by calculating receiver operating characteristic curves. Optimal cut-offs were determined as the highest sensitivity at a specificity of ≥ 80%. Results EEG data were of sufficient quality for analysis in 65/100 included patients. Of these, 35/65 (54%) had an acute ischemic stroke, of whom 9/65 (14%) had an LVO-a stroke. Median onset-to-EEG-time was 266 min (IQR 121–655) and median EEG-recording-time was 3 min (IQR 3–5). The EEG feature with the highest diagnostic accuracy for LVO-a stroke was theta–alpha ratio (AUC 0.83; sensitivity 75%; specificity 81%). Combined, weighted phase lag index and relative theta power best identified LVO-a stroke (sensitivity 100%; specificity 84%). Conclusion Dry electrode EEG is a promising tool for LVO-a stroke detection, but data quality needs to be improved and validation in the prehospital setting is necessary. (TRN: NCT03699397, registered October 9 2018).

Effect of Alteplase Use on Outcomes in Patients With Atrial Fibrillation: Analysis of the Initiation of Anticoagulation After Cardioembolic Stroke Study

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90‐day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)‐related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90‐day mortality. There were 1889 patients (90.6%) who had 90‐day follow‐up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57–3.17) but reduced risk of 90‐day mortality (OR, 0.58; 95% CI, 0.39–0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90‐day mortality (OR, 0.68; 95% CI, 0.45–1.04). Conclusions Alteplase reduced 90‐day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.