Francisco Romero

Timing of Spontaneous Recanalization and Risk of Hemorrhagic Transformation in Acute Cardioembolic Stroke

Background and Purpose The relationship between reperfusion and hemorrhagic transformation (HT) remains uncertain. Therefore, we aimed to clarify the relationship between the time course of recanalization and the risk of HT in patients with cardioembolic stroke studied within 6 hours of symptom onset. Methods Fifty-three patients with atrial fibrillation and nonlacunar stroke in the middle cerebral artery (MCA) territory admitted within the first 6 hours after symptom onset were prospectively studied. Serial TCD examinations were performed on admission and at 6, 12, 24, and 48 hours. CT was performed within 6 hours after stroke onset and again at 36 to 48 hours. Results Proximal and distal MCA occlusions were detected in 32 patients (60.4%) and 18 patients (34%), respectively. Early spontaneous recanalization occurring within 6 hours was identified in 10 patients (18.8%). Delayed recanalization (>6 hours) occurred in 28 patients (52.8%). HT on CT scan was detected in 17 patients (32%) within the first 48 hours. Only large parenchymal hemorrhage (PH2) was significantly associated with an increase (P =0.038, Kruskal-Wallis test) in the National Institutes of Health Stroke Scale (NIHSS) score compared with the other subtypes of HT. Univariate analysis revealed that an NIHSS score of >14 on baseline (P =0.001), proximal MCA occlusion (P =0.004), hypodensity >33% of the MCA territory (P =0.012), and delayed recanalization occurring >6 hours of stroke onset (P =0.003) were significantly associated with HT. With a multiple logistic regression model, delayed recanalization (OR 8.9; 95% CI 2.1 to 33.3) emerged as independent predictor of HT. Conclusions Delayed recanalization occurring >6 hours after acute cardioembolic stroke is an independent predictor of HT.

Thrombolysis-Related Hemorrhagic Infarction A Marker of Early Reperfusion, Reduced Infarct Size, and Improved Outcome in Patients With Proximal Middle Cerebral Artery Occlusion

Background and Purpose— The role of early and delayed recanalization after thrombolysis in the development of hemorrhagic transformation (HT) subtypes remains uncertain. We sought to explore the association between the timing of recanalization and HT risk in patients with proximal middle cerebral artery (MCA) occlusion treated with intravenous recombinant tissue plasminogen activator (rtPA) <3 hours of stroke onset and to investigate the relationship between HT subtypes, infarct volume, and outcome. Methods— Thirty-two patients with acute stroke caused by proximal MCA occlusion treated with rtPA <3 hours of symptom onset were prospectively studied. Serial transcranial Doppler examinations were performed on admission and at 6, 12, 24, and 48 hours. Presence and type of HT were assessed on CT at 36 to 48 hours. Modified Rankin scale was used to assess outcome at 3 months. Results— Early and delayed recanalization was identified in 17 patients (53.1%) and 8 patients (25%), respectively. HT was detected in 14 patients (43.7%): 4 (12.5%) with hemorrhagic infarction (HI1), 5 (15.6%) with HI2, 3 (9.3%) with parenchymal hematoma (PH1), and 2 (6.8%) with PH2. Distribution of HT subtypes differed significantly (P =0.025), depending on the time to artery reopening. Eight of 9 (89%), 1 of 5 (20%), and 8 of 18 (44.4%) with HI1-HI2, with PH1-PH2, and without HT, respectively, recanalized in <6 hours. Delayed recanalization was observed in 1 patient with HI1-HI2 (11%), 4 with PH1-PH2 (80%), and 3 without HT (16.6%). Neurological improvement was significantly (P <0.001) more frequent in patients with HI1-HI2 (88%) than in those without HT (39%). Infarct volume was significantly (P <0.031) lower in patients with HI1-HI2 (51.4±42 cm3) than in patients with PH1-PH2 (83.8±48 cm3) and those without HT (98.4±84 cm3, P =0.021). The modified Rankin scale score was significantly lower in HI1-HI2 compared with PH1-PH2 patients (1.9±1.1 versus 4.6±1.2, P <0.001) and with those without HT (1.9±1.1 versus 3.5±2.0, P =0.009.). Conclusions— Thrombolysis-related HI (HI1-HI2) represents a marker of early successful recanalization, which leads to a reduced infarct size and improved clinical outcome.

Temporal Profile of Recanalization After Intravenous Tissue Plasminogen Activator Selecting Patients for Rescue Reperfusion Techniques

Background and Purpose— Intravenous thrombolysis in stroke achieves arterial recanalization in ≈50% of cases. Determining temporal profile of recanalization may address patient selection and potential benefits of further rescue reperfusion techniques. Methods— We studied 179 consecutive intravenous tissue plasminogen activator (t-PA)–treated patients with intracranial artery occlusion. Continuous transcranial Doppler assessed recanalization (none-partial-complete) at 60 minutes (early), 120 minutes (delayed) after t-PA bolus, and 6 hours (late) from symptom onset. Outcomes were determined: National Institutes of Health Stroke Scale (NIHSS; 48-hour NIHSS) and 3-month modified Rankin Scale (mRS). Results— On admission, 68% of patients presented proximal middle cerebral artery occlusion, median NIHSS 17. Early recanalization was complete for 30 patients (17%), partial for 50 (28%), and none for 99 (55%). Delayed recanalization was complete for 56 patients (31%), partial for 39 (22%), and none for 84 (47%). Although early flow improvement was observed in up to 45% of patients, only 19% of patients with persistent occlusion (11% of total) presented delayed recanalization (odds ratio [OR] delayed/early recanalization, 0.16; 95% CI, 0.085 to 0.304; P<0.001). Among patients with persistent occlusion at 2 hours, only 13 (7% of total) presented late flow improvement (OR late/early recanalization, 0.09; 95% CI, 0.043 to 0.196; P<0.001). The few patients with late recanalization presented comparable median 48-hour NIHSS to those with early/delayed recanalization (3 versus 4.5; P=0.9) and much lower than those with persistent occlusion after 6 hours (3 versus 15; P=0.005). At 3 months, the rate of mRS ≤2 was not statistically different between patients with early/delayed versus late recanalization (55% versus 86%; P=0.12) but was lower if occlusion persisted 6 hours after onset (22%; P<0.001). Conclusion— The majority of t-PA-induced recanalizations occur during the first hour after treatment. Recanalizations during the following hours are rare but still related to clinical improvement if achieved within 6 hours from onset. Rescue reperfusion techniques should be considered if flow improvement is not observed 60 minutes after t-PA bolus.

Bridging Intravenous–Intra-Arterial Rescue Strategy Increases Recanalization and the Likelihood of a Good Outcome in Nonresponder Intravenous Tissue Plasminogen Activator-Treated Patients A Case–Control Study

Background and Purpose— Safety and efficacy of the “bridging therapy” (intra-arterial [IA] reperfusion rescue for nonresponder intravenous [IV] tissue plasminogen activator [tPA]-treated patients) is a matter of debate. Our aim was to compare IV and IV–IA thrombolysis using a case–control approach. Methods— Consecutive patients with proximal intracranial occlusion who received IA reperfusion procedures after unsuccessful IV tPA (lack of clinical improvement and arterial recanalization 1 hour after tPA bolus) were studied (IV–IA group). They were compared with occluded vessel, clot location, stroke severity, and time to treatment-matched 1 to 2 historical patients from our prospective IV tPA database with persistent occlusion 1 hour after IV tPA (IV-NR group). Arterial occlusion and recanalization were assessed with transcranial Doppler. Clinical evaluation was assessed by National Institutes of Health Stroke Scale at baseline, 24 hours, and at discharge. Symptomatic intracranial hemorrhage was defined according to the National Institute of Neurological Disorders and Stroke trial. Functional evaluation was determined by modified Rankin Scale, being functional independency defined by modified Rankin Scale score ≤2. Results— Forty-two IV–IA patients were compared with 84 matched IV-NR. Mean age was 71.5±2.9 years, 58 (46%) were women, and baseline median National Institutes of Health Stroke Scale score was 20 (interquartile range, 5). Mean time from symptoms to IV tPA was 176.9±113 minutes. On transcranial Doppler, complete recanalization was significantly higher in IV–IA than control subjects (12 hours: 45.2% versus 18.1%, P=0.002; 24 hours: 46.3% versus 25.3%, P=0.016) with nonsignificant better clinical evolution at 24 hours (40.5% versus 30.1%, P=0.169) and discharge (52.5% versus 39.5%, P=0.123). Symptomatic intracranial hemorrhage was similar (IV–IA 11.9% versus IV-NR 6%, P=0.205). Mortality at 3 months was 50% in the IV–IA group and 35.8% in the IV-NR (P=0.154). Forty percent of IV–IA patients were functionally independent at 3 months and only 14.9% IV-NR (P=0.012). Conclusions— Bridging IV–IA treatment may improve recanalization and clinical outcome in nonresponder IV tPA-treated patients.

Extending the time window for endovascular procedures according to collateral pial circulation.

Background and Purpose— Good collateral pial circulation (CPC) predicts a favorable outcome in patients undergoing intra-arterial procedures. We aimed to determine if CPC status may be used to decide about pursuing recanalization efforts. Methods— Pial collateral score (0–5) was determined on initial angiogram. We considered good CPC when pial collateral score <3, defined total time of ischemia (TTI) as onset-to-recanalization time, and clinical improvement >4-point decline in admission–discharge National Institutes of Health Stroke Scale. Results— We studied CPC in 61 patients (31 middle cerebral artery, 30 internal carotid artery). Good CPC patients (n=21 [34%]) had lower discharge National Institutes of Health Stroke Scale score (7 versus 21; P=0.02) and smaller infarcts (56 mL versus 238 mL; P<0.001). In poor CPC patients, a receiver operating characteristic curve defined a TTI cutoff point <300 minutes (sensitivity 67%, specificity 75%) that better predicted clinical improvement (TTI <300: 66.7% versus TTI >300: 25%; P=0.05). For good CPC patients, no temporal cutoff point could be defined. Although clinical improvement was similar for patients recanalizing within 300 minutes (poor CPC: 60% versus good CPC: 85.7%; P=0.35), the likelihood of clinical improvement was 3-fold higher after 300 minutes only in good CPC patients (23.1% versus 90.1%; P=0.01). Similarly, infarct volume was reduced 7-fold in good as compared with poor CPC patients only when TTI >300 minutes (TTI <300: poor CPC: 145 mL versus good CPC: 93 mL; P=0.56 and TTI >300: poor CPC: 217 mL versus good CPC: 33 mL; P<0.01). After adjusting for age and baseline National Institutes of Health Stroke Scale score, TTI <300 emerged as an independent predictor of clinical improvement in poor CPC patients (OR, 6.6; 95% CI, 1.01–44.3; P=0.05) but not in good CPC patients. In a logistic regression, good CPC independently predicted clinical improvement after adjusting for TTI, admission National Institutes of Health Stroke Scale score, and age (OR, 12.5; 95% CI, 1.6–74.8; P=0.016). Conclusions— Good CPC predicts better clinical response to intra-arterial treatment beyond 5 hours from onset. In patients with stroke receiving endovascular treatment, identification of good CPC may help physicians when considering pursuing recanalization efforts in late time windows.

Differentiating ischemic from hemorrhagic stroke using plasma biomarkers: The S100B/RAGE pathway

Although neuroimaging is useful in differentiating ischemic (IS) from hemorrhagic (ICH) stroke in the Emergency Department, a wide-available rapid biochemical test would add advantages in the pre-hospital triage and management of stroke patients. Our aim was to examine the predictive value of a panel of blood-borne biomarkers to differentiate IS from ICH. Admission blood samples obtained within 24h from stroke symptoms onset were tested by ELISA for CRP, D-dimer, sRAGE, MMP9, S100B, BNP, NT-3, caspase-3, chimerin-II, secretagogin, cerebellin and NPY. The complete protocol was achieved in 915 patients (776 IS, 139 ICH). Among blood samples obtained <6 h from symptoms onset (n=337), S100B levels were increased in ICH (107.58 vs 58.70 pg/mL; p<0.001) whereas sRAGE levels were decreased (0.77 vs 1.02 ng/mL; p=0.009) as compared to IS. In this subset of patients S100B (OR 3.97 95% CI 1.82-8.68; p=0.001) and sRAGE (OR 0.22 95% CI 0.10-0.52; p<0.001) were independently associated with ICH. A regression tree was created by CART method showing good classification ability (AUC=0.762). Similar results were found for samples obtained within 3 h. In conclusion, a combination of biomarkers including those of the S100B/RAGE pathway seems promising to achieve a rapid biochemical diagnosis of IS versus ICH in the first hours from symptoms onset. This article is part of a Special Issue entitled: Translational Proteomics.

Serum Low-Density Lipoprotein Cholesterol Level Predicts Hematoma Growth and Clinical Outcome After Acute Intracerebral Hemorrhage

Background and Purpose— Lower serum low-density lipoprotein cholesterol (LDL-C) levels have been associated with increased risk of death after intracerebral hemorrhage (ICH). Nevertheless, their link with hematoma growth (HG) is unknown. Therefore, we aimed to investigate the relationship between LDL-C levels, HG, and clinical outcome in patients with acute ICH. Methods— We prospectively studied 108 consecutive patients with primary supratentorial ICH presenting within 6 hours from symptoms onset. National Institutes of Health Stroke Scale score and ICH volume on computed tomography scan were recorded at baseline and at 24 hours. Lipid profile was obtained during the first 24 hours. Significant HG was defined as hematoma enlargement >33% or >6 mL at 24 hours. Early neurological deterioration as well as mortality and poor long-term outcome (modified Rankin Scale score >2) at 3 months were recorded. Results— Although LDL-C levels were not correlated with ICH volume (r=−0.18; P=0.078) or National Institutes of Health Stroke Scale score (r=−0.17; P=0.091) at baseline, lower LDL-C levels were associated with HG (98.1±33.7 mg/dL versus 117.3±25.8 mg/dL; P=0.003), early neurological deterioration (89.2±31.8 mg/dL versus 112.4±29.8 mg/dL; P=0.012), and 3-month mortality (94.9±37.4 mg/dL versus 112.5±28.5 mg/dL; P=0.029), but not with poor long-term outcome (109.5±31.3 mg/dL versus 108.3±30.5 mg/dL; P=0.875). Moreover, LDL-C levels were inversely related to the amount of hematoma enlargement at 24 hours (r=−0.31; P=0.004). In multivariate logistic regression analysis, LDL-C level <95 mg/dL emerged as an independent predictor of HG (OR, 4.24; 95% CI, 1.26–14.24; P=0.020), early neurological deterioration (OR, 8.27; 95% CI, 1.66–41.16; P=0.010), and 3-month mortality (OR, 6.34; 95% CI, 1.29–31.3; P=0.023). Conclusions— Lower serum LDL-C level independently predicts HG, early neurological deterioration, and 3-month mortality after acute ICH.

Comparison of High and Low Doses of Trimethoprim-Sulfamethoxazole for Primary Prevention of Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

To evaluate the influence of the dose of co-trimoxazole prophylaxis on the risk of toxoplasmosis in human immunodeficiency virus (HIV)-infected patients, we performed a nested case-control study of 32 patients with toxoplasmosis (case patients) and 64 patients without toxoplasmosis (control patients) who were matched by CD4 cell count and Toxoplasma gondii serostatus; these patients were from a cohort of 521 HIV-infected patients who underwent a diagnostic neuroimaging study between March 1993 and January 1997. Twenty-seven (84.4%) of 32 case patients and 33 (51.6%) of 64 control patients received low doses of co-trimoxazole, a finding associated with an adjusted odds ratio (OR) of 9.36 (95% confidence interval [CI], 2.05-42.75) and indicating 89% protective efficacy for high doses. Fifteen (46.9%) of 32 case patients and 16 (25%) of 64 control patients were exposed to rifampin (adjusted OR, 3.38; 95% CI, 1.08-10.61). These results indicate that high doses of co-trimoxazole appear to be more effective than low doses for lowering the risk of toxoplasmosis in HIV-infected patients and that rifampin therapy may reduce the efficacy of co-trimoxazole.

Effect of N‐Acetylcysteine on Antioxidant Status in Glycerol‐Induced Acute Renal Failure in Rats

Myoglobinuric acute renal failure has three pathogenic mechanisms: tubular obstruction, renal vasoconstriction, and oxidative stress. The latter is generated through the iron released from the group hemo of the myoglobin. Iron induces the formation of high‐activity oxygen free radicals that increase oxidative stress and provoke lipid peroxidation and cellular death. This oxidative stress can be measured in several ways, both total or partially with the total antioxidant status or the intermediate enzymes. On the other hand, N‐acetylcysteine is a demonstrated substance with antioxidant properties. The aim of the present work was to assess the effect of N‐acetylcysteine on the oxidative stress in the glycerol‐induced acute renal failure in rats model. We observed that the animals treated with N‐acetylcysteine showed an improvement in the antioxidant activity given by an increase in the total antioxidant status and glutathione reductase levels in serum. This improvement was greater when treatment was administered before the induction of rhabdomyolysis. Nevertheless, the observed increase in antioxidant status was only statistically significant for glutathione reductase but not for total antioxidant status. Our results support an important role for N‐acetylcysteine in the treatment of this form of acute renal failure, although we think that oxidative stress is not the main pathogenic mechanism of the tubular necrosis induced by rhabdomyolysis, tubular obstruction and renal vasoconstriction being still more important.

Embolismo en la arteria cerebral media por perdigón de escopeta de caza

Presentamos un caso de embolizacion traumatica por perdigon de escopeta de caza, desde el ventriculo izquierdo a la arteria cerebral media derecha, con isquemia cerebral y el posterior infarto con secuelas neurologicas. Se discuten los problemas que surgen debidos a la presencia de un embolo metalico en la circulacion cerebral y como debe tratarse esta lesion nada corriente.