Silent brain infarcts (SBIs) are detected by neuroimaging in approximately 20% of elderly patient... more Silent brain infarcts (SBIs) are detected by neuroimaging in approximately 20% of elderly patients in population-based studies. Limited evidence is available for hypertensives at low cardiovascular risk countries. Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study (ISSYS) is aimed to assess the prevalence and risk factors of SBIs in a hypertensive Mediterranean population. This is a cohort study in randomly selected hypertensives, aged 50 to 70 years old, and free of clinical stroke and dementia. On baseline, all participants underwent a brain magnetic resonance imaging to assess prevalence and location of silent infarcts, and data on vascular risk factors, comorbidities, and the presence of subclinical cardiorenal damage (left ventricular hypertrophy and microalbuminuria) were collected. Multivariate analyses were performed to determine SBIs associated factors. A total of 976 patients (49.4% men, mean age 64 years) were enrolled, and 163 SBIs were det...
Administration of microbubbles (MB) may augment the effect of ultrasound-enhanced systemic thromb... more Administration of microbubbles (MB) may augment the effect of ultrasound-enhanced systemic thrombolysis in acute stroke. Bubble structural characteristics may influence the effect of MB on sonothrombolysis. We aimed to compare the effects of galactose-based air-filled MB (Levovist) and sulphur hexafluoridefilled MB (Sonovue) on recanalization and clinical outcome. One hundred thirty-eight i.v. recombinant tissue plasminogen activator-(tPA-) treated patients with middle cerebral artery (MCA) occlusion were studied. Presence and location of arterial occlusion and recanalization (RE) were assessed using the thrombolysis in brain ischemia (TIBI) flow grading system. Patients underwent 2 h of continuous transcranial Doppler (TCD) monitoring and received three bolus of MB after 2, 20 and 40 min of tPA bolus. Ninety-one patients received Levovist (LV) and 47 received Sonovue (SV). NIHSS scores were obtained at baseline and after 24 h. Modified Rankin Scale (mRS) score was used to assess outcome at 3 mo. Median admission NIHSS was 17. On TCD, 96 (69.6%) patients had a proximal and 42 (30.4%) a distal MCA occlusion. Age, baseline NIHSS, clot location, stroke subtypes and time to treatment were similar between LV and SV groups. Recanalization rates after 1 h (32.2%/35.6%), 2 h (50.0%/46.7%) and 6 h (63.8%/54.5%) were similar in LV/SV groups (p > 0.3). Clinical improvement (NIHSS decrease > 4 points) at 24 h was similar in both groups (54.9%/51.1%, p ؍ 0.400), as well as symptomatic intracranial haemorrhage rate (3.3%/2.1%, p ؍ 0.580) and in-hospital mortality (8.1%/9.3%, p ؍ 0.531).
Background and Purpose-We sought to evaluate the impact of the speed of recanalization on the evo... more Background and Purpose-We sought to evaluate the impact of the speed of recanalization on the evolution of diffusionweighted imaging (DWI) lesions and outcome in stroke patients treated with tissue-type plasminogen activator (tPA). Methods-We evaluated 113 consecutive stroke patients with a middle cerebral artery occlusion who were treated with intravenous tPA. All patients underwent multiparametric magnetic resonance imaging studies, including DWI and perfusion-weighted imaging before and 36 to 48 hours after administration of a tPA bolus. Patients were continuously monitored with transcranial Doppler during the first 2 hours after tPA administration. The pattern of recanalization on transcranial Doppler was defined as sudden (Ͻ1 minute), stepwise (1 to 29 minutes), or slow (Ͼ30 minutes).
Safety and efficacy of the &a... more 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. 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. 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). Bridging IV-IA treatment may improve recanalization and clinical outcome in nonresponder IV tPA-treated patients.
Background and Purpose-Good collateral pial circulation (CPC) predicts a favorable outcome in pat... more 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 Ͻ3, defined total time of ischemia (TTI) as onset-to-recanalization time, and clinical improvement Ͼ4-point decline in admission-discharge National Institutes of Health Stroke Scale.
Lower serum low-density lipoprotein cholesterol (LDL-C) levels have been associated with increase... more 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. 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. 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). Lower serum LDL-C level independently predicts HG, early neurological deterioration, and 3-month mortality after acute ICH.
Early hematoma growth is one of the main determinants of mortality in patients with intracranial ... more Early hematoma growth is one of the main determinants of mortality in patients with intracranial hemorrhage (ICH). Transcranial duplex sonography (TDS) might represent a useful tool for the bedside monitoring of early ICH enlargement. We aimed to correlate ICH volumes measured by TDS and CT scan in patients with ICH evaluated <3 hours of symptom onset. We prospectively studied 34 patients with supratentorial ICH evaluated <3 hours of onset. All patients underwent emergent CT scan and TDS examination on admission and at 6 hours. Major longitudinal, sagittal, and coronal hematoma diameters were measured on CT scan by a neuroradiologist and on TDS by a blinded operator with a time delay <30 minutes between both techniques. Total hematoma volume was determined using the formula for irregular volumes (longitudinalxsagittalxcoronal)/2. Early hematoma growth was defined as an increase >20% in the hematoma volume at 6 hours. ICH was identified on TDS as an hyperechogenic mass located in the basal ganglia in 28 patients and in the lobar position in 6. Mean hematoma volume at baseline was 86+/-4 5 mL. At 6 hours, early hematoma growth was seen in 9 (26%) patients. An excellent correlation was found between TDS and CT measurements for all diameters: longitudinal (r=0.91, P<0.001), sagittal (r=0.85, P=0.002), coronal (r=0.79, P=0.022) and for total hematoma volume (r=0.82, P=0.001). When all obtained measures were matched, the intraclass correlation coefficient was 0.888 (95% CI, 0.8 to 0.937). TDS showed an excellent correlation with CT in measuring the extent of bleeding in patients with hyperacute ICH. TDS may represent a reliable useful tool for monitoring ICH noninvasively at the patient's bedside.
Although ultrasound-activated microbubbles (MB) accelerate clot lysis, MB activation has shown to... more Although ultrasound-activated microbubbles (MB) accelerate clot lysis, MB activation has shown to promote blood barrier disruption and bleeding in animal models. We conducted a case-control study aimed to investigate the risk of hemorrhagic transformation (HT) after MB-enhanced sonothrombolysis in acute stroke. We evaluated a total of 296 patients with acute stroke treated with IV tissue plasminogen activator (tPA) <3 hours after stroke onset. One hundred eighty-eight patients received continuous 2-hour TCD monitoring plus 3 doses of 2.5 g of MB after tPA bolus (MB group). These patients were compared with 98 historic stroke patients (control group). The presence and extent of HT on 24-hour CT were blindly assessed. Recanalization rates were higher in the MB compared with the control group at 1, 2, 6, and 12 hours (p < 0.05). MB administration was associated with an increased risk of hemorrhagic infarction (HI)1-HI2 (21% vs 12%, p = 0.026) and a higher degree of clinical improvement at 24 hours (54.9% vs 31.1%, p = 0.004). Parenchymal hematoma (PH)1-PH2 and symptomatic intracranial hemorrhage rates were similar in both groups. Moreover, the extent of bleeding after MB-enhanced sonothrombolysis was correlated with the time to reperfusion. Early (<6 hours) recanalization independently predicted HI in the MB group (odds ratio 6.3, 95% confidence interval 2.3-56) but not in the control group. Delayed (>6 hours) or no recanalization was associated with PH1-PH2 in both the MB group (p = 0.024) and the control group (p = 0.045). This hypothesis-generating study shows that microbubble administration was associated with early recanalization and a high rate of hemorrhagic transformation but does not seem to increase the risk of symptomatic intracranial hemorrhage. However, definitive conclusions cannot be made based on these data.
Cerebral amyloid angiopathy (CAA) is a well-established cause of lobar intracerebral hemorrhage (... more Cerebral amyloid angiopathy (CAA) is a well-established cause of lobar intracerebral hemorrhage (ICH). The aim of the authors was to investigate the influence of clinical characteristics and genetic variants in the ACE, LRP, MMP9, Tafi, VEGFA, CYP11B2, A2M and APOE on ICH recurrence in a cohort of CAA-related ICH patients. Sixty patients were enrolled and new symptomatic ICHs in the 36 mo following the index event were recorded. Leukoaraiosis degree, microbleeds count and variants in the APOE and ACE were associated with ICH recurrence. The rs4311 variant of the ACE was an independent risk factor (p ϭ 0.001), resisting Bonferroni correction. Moreover, carriers of 2 of the APOE and TT of the rs4311 of the ACE reached 100% recurrence before 18 mo (p Ͻ 0.001). Finally, ACE protein level was measured in serum of controls and depended on the rs4311 genotypes, TT carriers presenting higher level than CC carriers (p ϭ 0.012). These results suggest that variants in the ACE are associated with CAA-related ICH recurrence, possibly by modulating ACE protein level.
Silent brain infarcts (SBIs) are detected by neuroimaging in approximately 20% of elderly patient... more Silent brain infarcts (SBIs) are detected by neuroimaging in approximately 20% of elderly patients in population-based studies. Limited evidence is available for hypertensives at low cardiovascular risk countries. Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study (ISSYS) is aimed to assess the prevalence and risk factors of SBIs in a hypertensive Mediterranean population. This is a cohort study in randomly selected hypertensives, aged 50 to 70 years old, and free of clinical stroke and dementia. On baseline, all participants underwent a brain magnetic resonance imaging to assess prevalence and location of silent infarcts, and data on vascular risk factors, comorbidities, and the presence of subclinical cardiorenal damage (left ventricular hypertrophy and microalbuminuria) were collected. Multivariate analyses were performed to determine SBIs associated factors. A total of 976 patients (49.4% men, mean age 64 years) were enrolled, and 163 SBIs were det...
Administration of microbubbles (MB) may augment the effect of ultrasound-enhanced systemic thromb... more Administration of microbubbles (MB) may augment the effect of ultrasound-enhanced systemic thrombolysis in acute stroke. Bubble structural characteristics may influence the effect of MB on sonothrombolysis. We aimed to compare the effects of galactose-based air-filled MB (Levovist) and sulphur hexafluoridefilled MB (Sonovue) on recanalization and clinical outcome. One hundred thirty-eight i.v. recombinant tissue plasminogen activator-(tPA-) treated patients with middle cerebral artery (MCA) occlusion were studied. Presence and location of arterial occlusion and recanalization (RE) were assessed using the thrombolysis in brain ischemia (TIBI) flow grading system. Patients underwent 2 h of continuous transcranial Doppler (TCD) monitoring and received three bolus of MB after 2, 20 and 40 min of tPA bolus. Ninety-one patients received Levovist (LV) and 47 received Sonovue (SV). NIHSS scores were obtained at baseline and after 24 h. Modified Rankin Scale (mRS) score was used to assess outcome at 3 mo. Median admission NIHSS was 17. On TCD, 96 (69.6%) patients had a proximal and 42 (30.4%) a distal MCA occlusion. Age, baseline NIHSS, clot location, stroke subtypes and time to treatment were similar between LV and SV groups. Recanalization rates after 1 h (32.2%/35.6%), 2 h (50.0%/46.7%) and 6 h (63.8%/54.5%) were similar in LV/SV groups (p > 0.3). Clinical improvement (NIHSS decrease > 4 points) at 24 h was similar in both groups (54.9%/51.1%, p ؍ 0.400), as well as symptomatic intracranial haemorrhage rate (3.3%/2.1%, p ؍ 0.580) and in-hospital mortality (8.1%/9.3%, p ؍ 0.531).
Background and Purpose-We sought to evaluate the impact of the speed of recanalization on the evo... more Background and Purpose-We sought to evaluate the impact of the speed of recanalization on the evolution of diffusionweighted imaging (DWI) lesions and outcome in stroke patients treated with tissue-type plasminogen activator (tPA). Methods-We evaluated 113 consecutive stroke patients with a middle cerebral artery occlusion who were treated with intravenous tPA. All patients underwent multiparametric magnetic resonance imaging studies, including DWI and perfusion-weighted imaging before and 36 to 48 hours after administration of a tPA bolus. Patients were continuously monitored with transcranial Doppler during the first 2 hours after tPA administration. The pattern of recanalization on transcranial Doppler was defined as sudden (Ͻ1 minute), stepwise (1 to 29 minutes), or slow (Ͼ30 minutes).
Safety and efficacy of the &a... more 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. 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. 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). Bridging IV-IA treatment may improve recanalization and clinical outcome in nonresponder IV tPA-treated patients.
Background and Purpose-Good collateral pial circulation (CPC) predicts a favorable outcome in pat... more 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 Ͻ3, defined total time of ischemia (TTI) as onset-to-recanalization time, and clinical improvement Ͼ4-point decline in admission-discharge National Institutes of Health Stroke Scale.
Lower serum low-density lipoprotein cholesterol (LDL-C) levels have been associated with increase... more 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. 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. 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). Lower serum LDL-C level independently predicts HG, early neurological deterioration, and 3-month mortality after acute ICH.
Early hematoma growth is one of the main determinants of mortality in patients with intracranial ... more Early hematoma growth is one of the main determinants of mortality in patients with intracranial hemorrhage (ICH). Transcranial duplex sonography (TDS) might represent a useful tool for the bedside monitoring of early ICH enlargement. We aimed to correlate ICH volumes measured by TDS and CT scan in patients with ICH evaluated <3 hours of symptom onset. We prospectively studied 34 patients with supratentorial ICH evaluated <3 hours of onset. All patients underwent emergent CT scan and TDS examination on admission and at 6 hours. Major longitudinal, sagittal, and coronal hematoma diameters were measured on CT scan by a neuroradiologist and on TDS by a blinded operator with a time delay <30 minutes between both techniques. Total hematoma volume was determined using the formula for irregular volumes (longitudinalxsagittalxcoronal)/2. Early hematoma growth was defined as an increase >20% in the hematoma volume at 6 hours. ICH was identified on TDS as an hyperechogenic mass located in the basal ganglia in 28 patients and in the lobar position in 6. Mean hematoma volume at baseline was 86+/-4 5 mL. At 6 hours, early hematoma growth was seen in 9 (26%) patients. An excellent correlation was found between TDS and CT measurements for all diameters: longitudinal (r=0.91, P<0.001), sagittal (r=0.85, P=0.002), coronal (r=0.79, P=0.022) and for total hematoma volume (r=0.82, P=0.001). When all obtained measures were matched, the intraclass correlation coefficient was 0.888 (95% CI, 0.8 to 0.937). TDS showed an excellent correlation with CT in measuring the extent of bleeding in patients with hyperacute ICH. TDS may represent a reliable useful tool for monitoring ICH noninvasively at the patient's bedside.
Although ultrasound-activated microbubbles (MB) accelerate clot lysis, MB activation has shown to... more Although ultrasound-activated microbubbles (MB) accelerate clot lysis, MB activation has shown to promote blood barrier disruption and bleeding in animal models. We conducted a case-control study aimed to investigate the risk of hemorrhagic transformation (HT) after MB-enhanced sonothrombolysis in acute stroke. We evaluated a total of 296 patients with acute stroke treated with IV tissue plasminogen activator (tPA) <3 hours after stroke onset. One hundred eighty-eight patients received continuous 2-hour TCD monitoring plus 3 doses of 2.5 g of MB after tPA bolus (MB group). These patients were compared with 98 historic stroke patients (control group). The presence and extent of HT on 24-hour CT were blindly assessed. Recanalization rates were higher in the MB compared with the control group at 1, 2, 6, and 12 hours (p < 0.05). MB administration was associated with an increased risk of hemorrhagic infarction (HI)1-HI2 (21% vs 12%, p = 0.026) and a higher degree of clinical improvement at 24 hours (54.9% vs 31.1%, p = 0.004). Parenchymal hematoma (PH)1-PH2 and symptomatic intracranial hemorrhage rates were similar in both groups. Moreover, the extent of bleeding after MB-enhanced sonothrombolysis was correlated with the time to reperfusion. Early (<6 hours) recanalization independently predicted HI in the MB group (odds ratio 6.3, 95% confidence interval 2.3-56) but not in the control group. Delayed (>6 hours) or no recanalization was associated with PH1-PH2 in both the MB group (p = 0.024) and the control group (p = 0.045). This hypothesis-generating study shows that microbubble administration was associated with early recanalization and a high rate of hemorrhagic transformation but does not seem to increase the risk of symptomatic intracranial hemorrhage. However, definitive conclusions cannot be made based on these data.
Cerebral amyloid angiopathy (CAA) is a well-established cause of lobar intracerebral hemorrhage (... more Cerebral amyloid angiopathy (CAA) is a well-established cause of lobar intracerebral hemorrhage (ICH). The aim of the authors was to investigate the influence of clinical characteristics and genetic variants in the ACE, LRP, MMP9, Tafi, VEGFA, CYP11B2, A2M and APOE on ICH recurrence in a cohort of CAA-related ICH patients. Sixty patients were enrolled and new symptomatic ICHs in the 36 mo following the index event were recorded. Leukoaraiosis degree, microbleeds count and variants in the APOE and ACE were associated with ICH recurrence. The rs4311 variant of the ACE was an independent risk factor (p ϭ 0.001), resisting Bonferroni correction. Moreover, carriers of 2 of the APOE and TT of the rs4311 of the ACE reached 100% recurrence before 18 mo (p Ͻ 0.001). Finally, ACE protein level was measured in serum of controls and depended on the rs4311 genotypes, TT carriers presenting higher level than CC carriers (p ϭ 0.012). These results suggest that variants in the ACE are associated with CAA-related ICH recurrence, possibly by modulating ACE protein level.
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Papers by Olga Maisterra