Jukka T. Saarinen

The mid-M1 segment of the middle cerebral artery is a cutoff clot location for good outcome in intravenous thrombolysis.

Background and purpose:  We studied the impact of the location of the thrombus (internal carotid artery, proximal M1 segment, distal M1 segment, M2 segment, and M3 segment of the middle cerebral artery) in predicting the clinical outcome of patients treated with intravenous thrombolytic therapy (<3 h) in a retrospective cohort.

CT Perfusion ASPECTS in the Evaluation of Acute Ischemic Stroke: Thrombolytic Therapy Perspective

Background and Purpose: Advances in the management of acute ischemic stroke and medical imaging are creating pressure to replace the rigid one-third middle cerebral artery (MCA) and non-contrast-enhanced CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) thresholds used for the selection of patients eligible for intravenous thrombolytic therapy. The identification of potentially salvageable ischemic brain tissue lies at the core of this issue. In this study, the role of CT perfusion ASPECTS in the detection of reversible ischemia was analyzed. Materials and Methods: We retrospectively reviewed the clinical and imaging data of 92 consecutive patients who received intravenous thrombolytic therapy for acute (duration <3 h) ischemic stroke. Most of the patients underwent admission multimodal CT, and all patients had follow-up NCCT at 24 h. ASPECTS was assigned to all modalities and correlated with clinical and imaging parameters. Receiver-operating characteristic curve analysis was performed to determine optimal thresholds for different parameters to predict clinical outcome. Results: A perfusion defect could be detected in 50% of the patients. ASPECTS correlated inversely with the clinical outcome in the following order: follow-up NCCT > cerebral blood volume (CBV) > mean transit time (MTT) > admission NCCT. The follow-up NCCT and the CBV displayed a statistically significant difference from the admission NCCT, while the MTT did not reach statistical significance. The threshold that best differentiated between good and bad clinical outcome on admission was CBV ASPECTS ≧7. In patients with CT perfusion ASPECTS mismatch, MTT and CBV ASPECTS essentially provided the lower and upper limits for the follow-up NCCT ASPECTS, thus defining the spectrum of possible outcomes. Furthermore, CT perfusion ASPECTS mismatch strongly correlated (r = 0.83) with the mismatch between the tissue at risk and the final infarct, i.e. the amount of salvaged tissue. This finding suggests that the CT perfusion ASPECTS mismatch adequately identifies the amount of potentially salvageable ischemic brain tissue. Conclusions: Parameters derived from the use of CT perfusion ASPECTS can detect reversible ischemia and are correlated with clinical outcome.

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

Background Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. Methodology/Principal Findings We characterized the genes generally involved in human advanced atherosclerotic (AHA type V–VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). Conclusions This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds.

Location of the Clot and Outcome of Perfusion Defects in Acute Anterior Circulation Stroke Treated with Intravenous Thrombolysis

These investigators studied the impact of clot location in patients with acute stroke receiving IV thrombolysis. Four locations (ICA, proximal M1, distal M1, and M2 segment and more distal) of clots were correlated with CT perfusion maps, mismatches, salvaged brain volumes, and outcomes in 105 patients. Clots that were more proximal in location produced larger perfusion defects and lesion volumes. The amount of tissue salvaged was greater in patients with more distally located clots. In conclusion, admission CBV defects were larger in proximal vessel occlusions. More of the penumbra was salvaged if the occlusion was located more distally. This effect reached a plateau in the distal M1 segment of the MCA. BACKGROUND AND PURPOSE: The location of the clot is a major determinant of ischemic stroke outcome. We studied the impact of the location (ICA, proximal M1 segment of the MCA, distal M1 segment, and M2 segment and more distally) of the clot on the CT perfusion parametric maps, the mismatch ratio, the amount of salvaged brain tissue, and the imaging and clinical outcomes in a retrospective acute (<3 hours) stroke cohort treated with intravenous thrombolysis. MATERIALS AND METHODS: We reviewed 105 patients who underwent admission multimodal CT that revealed an occluded vessel on CTA. CT perfusion was successfully performed in 58 patients (55%). Differences among the parameters in different vessel positions were studied with the ANCOVA by using onset-to-imaging time as a covariate followed by pair-wise testing. RESULTS: There were no significant differences in potential confounding variables among the groups. A clot proximal to the M2 segment produced a significantly larger defect on the MTT map. A clot in the ICA resulted in a significantly larger CBV lesion compared with the distal M1 segment, the M2 segment, and the M3 segment. In general, a more proximal thrombus created a larger CBV defect. The fraction of penumbra that was salvaged at 24 hours was higher in the more distal vessel positions. CONCLUSIONS: Admission CBV defects are larger in proximal vessel occlusions. More of the penumbra can be salvaged if the occlusion is located distally. This effect seems to reach a plateau in the distal M1 segment of the MCA.

Collateral Score Complements Clot Location in Predicting the Outcome of Intravenous Thrombolysis

BACKGROUND AND PURPOSE: Collateral circulation is an important determinant of stroke outcome. We studied the impact of leptomeningeal collateral circulation with respect to the location of the thrombus in predicting the clinical outcome of patients treated with intravenous thrombolytic therapy (<3 hours) in a retrospective cohort. MATERIALS AND METHODS: Anterior circulation thrombus was detected with CT angiography in 105 patients. Baseline clinical and imaging information was collected, and the site of the occlusion was recorded. Collaterals were assessed by using a 5-grade collateral score and were entered into logistic regression analysis to predict favorable clinical outcome (3-month modified Rankin Scale score of 0–2). RESULTS: Two-thirds of patients with a proximal occlusion displayed poor collateral filling (collateral score 0–1), whereas in more distal clot locations, approximately one-third had poor collaterals. Only 36% of patients with a proximal occlusion and good collaterals experienced favorable clinical outcome. In multivariate analysis, both clot location and collateral score were highly significant (P = .003 and P = .001) and independent predictors of favorable clinical outcome. Good collateral status increased the odds of favorable clinical outcome about 9-fold (OR = 9.3; 95% CI, 2.4–35.8). After dichotomization, a distal clot location had a larger odds ratio (OR = 13.3; 95% CI, 3.0–60.0) compared with the odds ratio of good collaterals (OR = 5.9; 95% CI, 1.8–19.0). CONCLUSIONS: A proximal occlusion in the anterior circulation is associated with poorer collateral status compared with a more distal occlusion. Both the clot location and collateral score are important and independent predictors of favorable clinical outcome of hyperacute stroke treated with intravenous thrombolysis. The location of the clot is a stronger determinant of the outcome than the collateral score.

Collateral Circulation Predicts the Size of the Infarct Core and the Proportion of Salvageable Penumbra in Hyperacute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

Background: We studied the impact of collateral circulation on CT perfusion (CTP) parametric maps and the amount of salvaged brain tissue, the imaging and clinical outcome at 24 h and at 3 months in a retrospective acute (<3 h) stroke cohort (105 patients) with anterior circulation thrombus treated with intravenous thrombolysis. Methods: Baseline clinical and imaging information were collected and groups with different collateral scores (CS) were compared. Binary logistic regression analyses using good CS (CS ≥2) as the dependent variable were calculated. Results: CTP Alberta Stroke Program Early CT Score (ASPECTS) was successfully assessed in 58 cases. Thirty patients displayed good CS. Poor CS were associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (15 vs. 7, p = 0.005) and at 24 h (10 vs. 3, p = 0.003) after intravenous thrombolysis. Good CS were associated with a longer mean onset-to-treatment time (141 vs. 121 min, p = 0.009) and time to CTP (102 vs. 87 min, p = 0.047), better cerebral blood volume (CBV) ASPECTS (9 vs. 6, p < 0.001), better mean transit time (MTT) ASPECTS (6 vs. 3, p < 0.001), better noncontrast CT (NCCT) ASPECTS (10 vs. 8, p < 0.001) at arrival and with favorable clinical outcome at 3 months (modified Rankin Scale ≤2, p = 0.002). The fraction of penumbra that was salvageable at arrival and salvaged at 24 h was higher with better CS (p < 0.001 and p = 0.035, respectively). In multivariate analysis, time from the onset of symptoms to imaging (p = 0.037, OR 1.04 per minute, 95% CI 1.00-1.08) and CBV ASPECTS (p = 0.001, OR 2.11 per ASPECTS point, 95% CI 1.33-3.34) predicted good CS. In similar multivariable models, MTT ASPECTS (p = 0.04, OR 1.46 per ASPECTS point, 95% CI 1.02-2.10) and NCCT ASPECTS predicted good CS (p = 0.003, OR 4.38 per CT ASPECTS point, 95% CI 1.66-11.55) along with longer time from the onset of symptoms to imaging (p = 0.045, OR 1.03 per minute, 95% CI 1.00-1.06 and p = 0.02, OR 1.05 per minute, 95% CI 1.00-1.09, respectively). CBV ASPECTS had a larger area under the receiver operating characteristic curve for good CS (0.837) than NCCT ASPECTS (0.802) or MTT ASPECTS (0.752) at arrival. Conclusions: Favorable CBV ASPECTS, NCCT ASPECTS and MTT ASPECTS are associated with good CS along with more salvageable tissue and longer time from the onset of symptoms to imaging in ischemic stroke patients treated with intravenous thrombolysis.

The association of blood pressure and collateral circulation in hyperacute ischemic stroke patients treated with intravenous thrombolysis.

Background: The integrity of collateral circulation is a major prognostic factor in ischemic stroke. Patients with good collateral status have larger penumbra and respond better to intravenous thrombolytic therapy. High systolic blood pressure is linked with worse clinical outcome in patients with acute ischemic stroke treated with intravenous thrombolytic therapy. We studied the effect of different blood pressure parameters on leptomeningeal collateral circulation in patients treated with intravenous thrombolytic therapy (<3 h) in a retrospective cohort. Methods: Anterior circulation thrombus was detected with computed tomography angiography and blood pressure was measured prior to intravenous thrombolytic therapy in 104 patients. Baseline clinical and imaging information were collected. Group comparisons were performed; Collateral Score (CS) was assessed and entered into logistic regression analysis. Results: Fifty-eight patients out of 104 displayed good collateral filling (CS ≥2). Poor CS was associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (16 vs. 11, p = 0.005) and at 24 h (15 vs. 3, p < 0.001) after the treatment. Good CS was associated with higher systolic blood pressure (p = 0.03), but not with diastolic blood pressure (p = 0.26), pulse pressure (p = 0.20) or mean arterial pressure (p = 0.07). Good CS was associated with better Alberta Stroke Program Early CT Score (ASPECTS) in 24 h follow-up imaging (p < 0.001) and favorable clinical outcome at three months (mRS ≤2, p < 0.001). Median CS was the highest (CS = 3) when systolic blood pressure was between 170 and 190 mm Hg (p = 0.03). There was no significant difference in the number of patients with good (n = 11) and poor (n = 12) CS who received intravenous antihypertensive medication (p = 0.39) before or during the thrombolytic therapy. In multivariate analysis age (p = 0.02, OR 0.957 per year, 95% CI 0.92-0.99), time from the onset of symptoms to treatment (p = 0.005, OR 1.03 per minute, 95% CI 1.01-1.05), distal clot location (p = 0.02, OR 3.52, 95% CI 1.19-10.35) and systolic blood pressure (p = 0.04, OR 1.03 per unit mm Hg, 95% CI 1.00-1.05) predicted good CS. Higher systolic blood pressure (p = 0.049, OR 0.96 per unit mm Hg, 95% CI 0.93-1.00) and pulse pressure (p = 0.005, OR 0.94 per unit mm Hg, 95% CI 0.90-0.98) predicted unfavorable clinical outcome at three months in multivariate analysis. Conclusion: Moderately elevated systolic blood pressure is associated with good collateral circulation in patients treated with intravenous thrombolytic therapy. However, there is an inverse association of systolic blood pressure with the three-month clinical outcome. Diastolic blood pressure, mean arterial pressure and pulse pressure are not statistically and significantly associated with collateral status.

Randomized clinical trial comparing surgery, endovenous laser ablation and ultrasound‐guided foam sclerotherapy for the treatment of great saphenous varicose veins

Endovenous ablation techniques and ultrasound‐guided foam sclerotherapy (UGFS) have largely replaced open surgery for treatment of great saphenous varicose veins. This was a randomized trial to compare the effect of surgery, endovenous laser ablation (EVLA) (with phlebectomies) and UGFS on quality of life and the occlusion rate of the great saphenous vein (GSV) 12 months after surgery.

Long-Term Experience of Endovascular Repair for Thoracic Aortic Aneurysms and Dissections

Purpose: To report the long-term results of thoracic endovascular aortic repair (TEVAR) in both elective and emergency cases of thoracic aortic aneurysm (TAA) and type B dissection. Material and Methods: A prospective single-center study of 78 TEVAR patients treated between February 1998 and February 2013. Stent-graft implantation was performed in 51 (65%) patients for TAA (43 elective and 8 emergency cases) and in 27 (35%) patients for type B dissection (11 elective and 16 emergency cases). Short- and long-term results were evaluated, and a subgroup of patients with left subclavian artery (LSA) coverage was also analyzed. Results: The patients were followed for a mean of 55 months (1-160 months). The technical success rate was 81% and 30-day mortality 6.4% (n = 5). The stroke rate was 7.7% (n = 6) and permanent paraparesis 2.6% (n = 2). In follow-up, there were 28 (36%) primary (15 type I and 13 type II) and 10 secondary endoleaks (8 type I and 2 type II). Multivariate analysis showed no significant predictive factors for developing a type I endoleak. Secondary interventions were required in 24% of the patients. There was 1 late thoracic aortic rupture and 1 late conversion (1.3%). Patients with LSA coverage had a higher incidence of stroke (12.5% vs 4.3%, P = .18) and paraparesis (3.1% vs 2.2%, P = .79) compared to those without LSA coverage, although this difference was not statistically significant. Stroke rates were significantly higher in patients treated in an emergency setting (P = .048). Conclusion: Thoracic endovascular aortic repair is a relatively safe and effective therapy for different aortic pathologies with good long-term success. The risk of stroke and paraparesis is notable whether the LSA is covered, and strokes clearly accumulate in the emergency setting. A type I endoleak is the most common complication, but there are no predictive factors for its development.

Hemophagocytic lymphohistiocytosis in 2 patients with multiple sclerosis treated with alemtuzumab

Alemtuzumab is a highly effective treatment of relapsing-remitting multiple sclerosis (RRMS) with a complex safety profile, including secondary autoimmunity in 40% of patients.1 We report 2 cases of hemophagocytic lymphohistiocytosis (HLH) in patients after alemtuzumab treatment of RRMS. This hyperinflammatory syndrome consists of fever, lymphadenopathy, pancytopenia, liver abnormalities, hyperferritinemia, raised soluble interleukin 2 (IL-2) receptor, and hemophagocytosis; it may be secondary to malignancies, autoimmune diseases, or infections.2 The table summarizes the diagnostic criteria for secondary HLH.