Synchronous cardiocerebral infarction in the era of endovascular therapy: which to treat first?

A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0-2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.

Good Intracranial Collaterals Trump Poor ASPECTS (Alberta Stroke Program Early CT Score) for Intravenous Thrombolysis in Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In acute ischemic stroke, large early infarct size estimated by the Alberta Stroke Program Early CT Score (ASPECTS) is associated with poorer outcomes and is a relative contraindication for recanalization therapies. The state of the intracranial collateral circulation influences the functional outcome and may be a variable to consider before thrombolysis. We evaluated the prognostic effect of the collateral circulation in patients with thrombolyzed acute ischemic stroke who have large early infarct sizes as indicated by low ASPECTS. MATERIALS AND METHODS: Patients with anterior circulation acute ischemic stroke who received a computed tomographic angiogram and subsequent treatment with intravenous tissue-type plasminogen activator from 2010 to 2013 were studied. Two independent neuroradiologists determined their ASPECTS. We stratified patients using ASPECTS into 2 groups: large volume infarcts (ASPECTS≤7 points) and small volume infarcts (ASPECTS 8-10). In addition, we evaluated a third group with very large volume infarcts (ASPECTS≤5 points). We then analyzed the 3 subgroups using the Maas, Tan, and ASPECTS-collaterals grading systems of the computed tomographic angiogram intracranial collaterals. Good outcomes were defined by modified Rankin Scale score of 0 to 2 at 3 months. RESULTS: A total of 300 patients were included in the final analysis. For patients with very large volume infarcts (ASPECTS≤5 points), univariable analysis showed that younger age, male sex, lower National Institute of Health Stroke Scale (NIHSS), lower systolic blood pressure, and good collaterals by Maas, Tan, or ASPECTS-collaterals grading were predictors of good outcomes. On multivariate analysis, younger age (odds ratio, 0.93; 95% confidence interval, 0.89-0.97; P=0.002) and good collaterals by ASPECTS-collaterals system (odds ratio, 1.34; 95% confidence interval, 1.15-1.57; P<0.001) were associated with good outcomes. CONCLUSIONS: In patients with large and very large volume infarcts, good collaterals as measured by the ASPECTS-collaterals system is associated with improved outcomes and can help select patients for intravenous thrombolysis.

How temporal evolution of intracranial collaterals in acute stroke affects clinical outcomes.

OBJECTIVE: We compared intracranial collaterals on pretreatment and day 2 brain CT angiograms (CTA) to assess their evolution and relationship with functional outcomes in acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA). METHODS: Consecutive AIS patients who underwent pretreatment and day 2 CTA and received IV tPA during 2010-2013 were included. Collaterals were evaluated by 2 independent neuroradiologists using 3 predefined criteria: the Miteff system, the Maas system, and 20-point collateral scale by the Alberta Stroke Program Early CT Score methodology. We stratified our cohort by baseline pre-tPA state of their collaterals and by recanalization status of the primary vessel for analysis. Good outcomes at 3 months were defined by a modified Rankin Scale score of 0-1. RESULTS: This study included 209 patients. Delayed collateral recruitment by any grading system was not associated with good outcomes. All 3 scoring systems showed that collateral recruitment on the follow-up CTA from a baseline poor collateral state was significantly associated with poor outcome and increased bleeding risk. When the primary vessel remained persistently occluded, collateral recruitment was significantly associated with worse outcomes. Interestingly, collateral recruitment was significantly associated with increased mortality in 2 of the 3 grading systems. CONCLUSIONS: Not all collateral recruitment is beneficial; delayed collateral recruitment may be different from early recruitment and can result in worse outcomes and higher mortality. Prethrombolysis collateral status and recanalization are determinants of how intracranial collateral evolution affects functional outcomes.

ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis.

BACKGROUND: Cell surface sialylation is associated with tumor cell invasiveness in many cancers. Glioblastoma is the most malignant primary brain tumor and is highly infiltrative. ST3GAL1 sialyltransferase gene is amplified in a subclass of glioblastomas, and its role in tumor cell self-renewal remains unexplored. METHODS: Self-renewal of patient glioma cells was evaluated using clonogenic, viability, and invasiveness assays. ST3GAL1 was identified from differentially expressed genes in Peanut Agglutinin-stained cells and validated in REMBRANDT (n = 390) and Gravendeel (n = 276) clinical databases. Gene set enrichment analysis revealed upstream processes. TGFß signaling on ST3GAL1 transcription was assessed using chromatin immunoprecipitation. Transcriptome analysis of ST3GAL1 knockdown cells was done to identify downstream pathways. A constitutively active FoxM1 mutant lacking critical anaphase-promoting complex/cyclosome ([APC/C]-Cdh1) binding sites was used to evaluate ST3Gal1-mediated regulation of FoxM1 protein. Finally, the prognostic role of ST3Gal1 was determined using an orthotopic xenograft model (3 mice groups comprising nontargeting and 2 clones of ST3GAL1 knockdown in NNI-11 [8 per group] and NNI-21 [6 per group]), and the correlation with patient clinical information. All statistical tests on patients' data were two-sided; other P values below are one-sided. RESULTS: High ST3GAL1 expression defines an invasive subfraction with self-renewal capacity; its loss of function prolongs survival in a mouse model established from mesenchymal NNI-11 (P < .001; groups of 8 in 3 arms: nontargeting, C1, and C2 clones of ST3GAL1 knockdown). ST3GAL1 transcriptomic program stratifies patient survival (hazard ratio [HR] = 2.47, 95% confidence interval [CI] = 1.72 to 3.55, REMBRANDT P = 1.92 x 10⁻8; HR = 2.89, 95% CI = 1.94 to 4.30, Gravendeel P = 1.05 x 10⁻¹¹), independent of age and histology, and associates with higher tumor grade and T2 volume (P = 1.46 x 10⁻4). TGFß signaling, elevated in mesenchymal patients, correlates with high ST3GAL1 (REMBRANDT gliomacor = 0.31, P = 2.29 x 10⁻¹°; Gravendeel gliomacor = 0.50, P = 3.63 x 10⁻²°). The transcriptomic program upon ST3GAL1 knockdown enriches for mitotic cell cycle processes. FoxM1 was identified as a statistically significantly modulated gene (P = 2.25 x 10⁻5) and mediates ST3Gal1 signaling via the (APC/C)-Cdh1 complex. CONCLUSIONS: The ST3GAL1-associated transcriptomic program portends poor prognosis in glioma patients and enriches for higher tumor grades of the mesenchymal molecular classification. We show that ST3Gal1-regulated self-renewal traits are crucial to the sustenance of glioblastoma multiforme growth.

Treatment of a traumatic carotid-cavernous fistula by the sole use of a flow diverting stent.

Direct caroticocavernous fistula (CCF) has traditionally been treated by detachable balloon placement within the affected cavernous sinus. We describe a case of a direct CCF treated solely with flow-diverting stents. These novel devices may offer a simpler and potentially safer vessel-sparing option in this rare condition.