Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. METHODS: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. RESULTS: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. CONCLUSION: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Pulse pressure variability is associated with unfavorable outcomes in acute ischaemic stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. METHODS: Pulse pressure variability was calculated from 24-h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST-ER) trial. The outcomes of interest were the pre-specified efficacy and safety end-points of CLOTBUST-ER. All associations were adjusted for potential confounders in multivariable regression models. RESULTS: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24-h neurological improvement and 90-day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90-day mortality (P < 0.001). Every 5-mmHg increase in the 24-h PP variability was independently associated with a 36% decrease in the likelihood of 90-day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52-0.80) and a 60% increase in the odds of 90-day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23-2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. CONCLUSIONS: Increased PP variability appears to be independently associated with adverse short-term and long-term functional outcomes of AIS patients treated with IVT.

Practice recommendations for neurovascular ultrasound investigations of acute stroke patients in the setting of the COVID-19 pandemic: an expert consensus from the European Society of Neurosonology and Cerebral Hemodynamics.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke are at high-risk for contracting COVID-19 infection. Additionally, healthcare professionals including neurovascular ultrasound providers are also at risk of being infected by SARS-CoV-2 virus. Yet, preparedness to continue to guarantee hyperacute treatment is vital for patients outcome. In light of this situation, the European Society of Neurosonology and Cerebral Hemodynamic (ESNCH) appointed a task force to provide consensus recommendations for the performance of neurovascular ultrasound investigations in acute ischemic stroke during the COVID-19 pandemic with the aim of protecting both patients and ultrasound providers. METHODS: The "ultrasound in acute stroke working group" of the ESNCH examined literature articles and reviews using the following key words: "corona virus" or "COVID-19" or "SARS-CoV-2 virus", and "acute stroke" or "cerebrovascular disease", and "ultrasound". Thereafter, a thorough discussion was conducted with the "education and guidelines working group" of the ESNCH. RESULTS: We propose rapid up-to-date recommendations for healthcare personnel involved in the pre-hospital and intra-hospital assessment of stroke patients, with a particular attention to neurovascular ultrasound performance. CONCLUSION: The ESNCH provides a guidance summary for the performance of neurovascular ultrasound investigations in acute ischemic stroke in the time of COVID-19.

Fatal intracranial haemorrhage occurring after oral anticoagulant treatment initiation for secondary stroke prevention in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: In this pooled analysis of seven multicentre cohorts potential differences were investigated in the incidence, characteristics and outcomes between intracranial haemorrhages (ICHs) associated with the use of non-vitamin K antagonist oral anticoagulants (NOAC-ICH) or with vitamin K antagonists (VKA-ICH) in ischaemic stroke patients after oral anticoagulant treatment initiation for atrial fibrillation (AF). METHODS: Data from 4912 eligible AF patients who were admitted in a stroke unit with ischaemic stroke or transient ischaemic attack and who were treated with either VKAs or NOACs within 3 months post-stroke were included. Fatal ICH was defined as death occurring during the first 30 days after ICH onset. A meta-analysis of available observational studies reporting 30-day mortality rates from NOAC-ICH or VKA-ICH onset was additionally performed. RESULTS: During 5970 patient-years of follow-up 71 participants had an ICH, of whom 20 were NOAC-ICH and 51 VKA-ICH. Patients in the two groups had comparable baseline characteristics, except for the higher prevalence of kidney disease in VKA-ICH patients. There was a non-significant higher number of fatal ICH in patients with VKAs (11 events per 3385 patient-years) than in those with NOACs (three events per 2623 patient-years; hazard ratio 0.32, 95% confidence interval 0.09-1.14). Three-month functional outcomes were similar (P > 0.2) in the two groups. The meta-analysis showed a lower 30-day mortality risk for patients with NOAC-ICH compared to VKA-ICH (relative risk 0.70, 95% confidence interval 0.51-0.95). CONCLUSIONS: Non-vitamin K oral anticoagulants for intracranial haemorrhages and VKA-ICH occurring during secondary stroke prevention of AF patients have comparable baseline characteristics and outcomes except for the risk of fatal ICH within 30 days, which might be greater in VKA-ICH.

Computed-tomography-guided transforaminal intrathecal nusinersen injection in adults with spinal muscular atrophy type 2 and severe spinal deformity. Feasibility, safety and radiation exposure considerations.

BACKGROUND AND PURPOSE: The purpose was to investigate our centre's experience on computed-tomography-guided (CT-guided), transforaminal, intrathecal administration of nusinersen in adult subjects with spinal muscular atrophy (SMA) type 2 and severe spinal deformity. METHOD: This is a retrospective, single-centre study investigating the feasibility and safety of CT-guided, transforaminal, lumbar puncture for the intrathecal administration of nusinersen (Spinranza®; Biogen; Cambridge, MA, USA) in a cohort of adult subjects with SMA type 2, severe neuromuscular scoliosis and previous spinal surgery. Between January 2019 and October 2019, five male, adult, SMA type 2 subjects were eligible to be treated in our centre with nusinersen. The mean age of the patients was 31 ± 9 years (range 19-43 years). The study's outcome measures were technical success, adverse events and radiation exposure. RESULTS: In total, four patients completed the four loading doses, whilst the fifth patient received only one loading dose; two patients also received their first maintenance doses. Overall, 20 consecutive transforaminal, intrathecal treatments were analysed. Technical success was 100% (20/20 intrathecal infusions). No adverse events were documented following the procedures. Mean dose-length product (DLP) value per injection was 665.4 ± 715.5 mGy*cm. Estimated mean effective dose per injection was 12.7 ± 12.9 mSv. Subgroup analysis between the chronologically first 10 versus subsequent 10 procedures demonstrated a clear trend towards less radiation exposure in the latter, although this difference did not reach statistical significance (DLP: 984.7 ± 903.3 vs. 436.7 ± 321.5 mGy*cm, P = 0.165; respectively). CONCLUSIONS: In this retrospective series, CT-guided transforaminal access for intrathecal injection of nusinersen was proven feasible and safe. A decrease in radiation dose over time was noted. Protocols to minimize radiation exposure are essential.

Statin treatment and accrual of covert cerebral ischaemia on neuroimaging: a systematic review and meta-analysis of randomized trials.

BACKGROUND AND PURPOSE: Prevention of ischaemic stroke and cardiovascular events is an established benefit of statin therapy, but the effects of statin treatment on the accrual of magnetic resonance imaging (MRI) markers of ischaemic cerebral injury remain unknown. A systematic review was performed to identify all studies that randomized patients with cardiovascular risk factors to statin treatment and assessed the effect of statin treatment on covert infarcts (asymptomatic, evident only on neuroimaging) and white matter hyperintensity (WMH) accrual on MRI. METHODS: A systematic review in MEDLINE and Scopus from inception to 23 October 2019 was performed. A random-effects model was used to calculate the pooled estimates of the crude risk ratios and standardized mean differences. RESULTS: Data from three randomized controlled trials (1430 participants) were included evaluating the effect of rosuvastatin (10 mg/day) in 668 hypertensive patients older than 60 years of age over 5 years, pravastatin (40 mg/day) in 554 elderly people more than 70 years of age over 3 years and simvastatin (20 mg/day) in 208 patients with asymptomatic middle cerebral artery stenosis over 2 years. Patients randomized to statin treatment had decreased accrual of new covert infarcts (risk ratio 0.63, 95% confidence interval 0.46-0.88) during a mean follow-up of 2-6 years. Only one study reported WMH decreased volume change in patients randomized to statin treatment compared to patients randomized to non-statin treatment (standardized mean difference -1.17; 95% confidence interval -1.33, -1.00). CONCLUSION: Our findings suggest that, in addition to stroke prevention, statin treatment can reduce the accrual of covert MRI markers of ischaemic cerebral injury.

Colchicine for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Although clinical trials suggest that colchicine may reduce the risk of vascular events in patients with a history of coronary artery disease, its effect on the prevention of cerebrovascular events still remains unclear. METHODS: A systematic review and meta-analysis was performed of all available randomized controlled trials (RCTs) reporting on incident strokes during the follow-up of patients with a history of cardiovascular disease randomized to colchicine treatment or control (placebo or usual care). RESULTS: Four RCTs were identified, including a total of 5553 patients (mean age 61 years, 81% males), with a follow-up ranging from 1 to 36 months. Colchicine treatment was associated with a significantly lower risk of incident stroke during follow-up compared to control (risk ratio 0.31, 95% confidence interval 0.13-0.71), without heterogeneity across included studies (I2  = 0%). Based on the pooled incident stroke rate of control groups (0.9%) in the included RCTs, it was estimated that administration of low-dose colchicine to 161 patients with coronary artery disease would prevent one stroke during a follow-up of 23 months. CONCLUSION: Colchicine treatment decreases stroke risk in patients with a history of coronary artery disease. The effect of colchicine in secondary stroke prevention is currently being evaluated in an ongoing RCT.

Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity.

BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Atrophy of optic nerve detected by transorbital sonography in patients with demyelinating diseases of the central nervous system.

BACKGROUND AND PURPOSE: Transorbital sonography (TOS) has emerged as promising imaging method for the diagnosis and follow-up of acute optic neuritis (ON). Available studies report an increase in the optic nerve diameter (OND) and the optic nerve sheath diameter (ONSD) in the case of a first episode of ON in the affected eye compared to either the contralateral unaffected eye or controls. However, the utility of TOS in the case of recurrent episodes of ON has never been assessed. METHODS: In our prospective cohort study, the diagnostic utility of TOS in patients with demyelinating diseases of the central nervous system was assessed, and the association between TOS, optical coherence tomography (OCT) and visual evoked potentials was examined further. RESULTS: Seventy-eight patients with a history of demyelinating disorders of the central nervous system (mean age 38.2 ± 14.2 years; 24% with acute ON) were included. No differences in the OND (3.2 ± 0.5 mm vs. 3.2 ± 0.4 mm) and ONSD (5.1 ± 0.8 mm vs. 5.1 ± 0.7 mm) measurements were found between patients with and without acute ON. Papillary swelling was more frequent in patients with acute ON (14.2% vs. 1.5%, P = 0.002). Patients with a history of previous ON were found to have lower OND (P < 0.001) and ONSD (P = 0.007) compared to patients without a history of previous ON. TOS measurements were inversely associated with disease duration and positively correlated with OCT findings. No association with visual evoked potential measurements was found. CONCLUSION: No evidence was found for TOS-sensitive differences in the OND and ONSD of patients with demyelinating diseases, according to the presence of acute ON. The association between TOS and OCT measurements deserves further investigation.

Association of malnutrition with surgical site infection following spinal surgery: systematic review and meta-analysis.

BACKGROUND: Surgical site infection (SSI) following spinal surgery is a frequent clinical problem with significant clinical and socio-economic consequences. Malnutrition has been linked with SSI in various other surgical procedures. AIM: To investigate whether malnutrition is a risk factor for SSI following spinal surgery. METHODS: Two electronic databases (PUBMED and SCOPUS) and the Cochrane Library were searched systematically from inception to May 2019. Cohort and case-control studies assessing malnutrition as a risk factor for SSI in patients undergoing spinal procedures were considered eligible. Μalnutrition was defined according to laboratory measurements or by relevant International Classification of Diseases-9 codes. SSI was the outcome of interest. Two reviewers independently abstracted study data and assessed the risk of bias for each study. Pooled effect estimates were calculated using random effects models. FINDINGS: In total, 22 studies (20 retrospective cohort and two case-control) with over 175,000 participants (of whom 2.14% developed postoperative SSI) were analysed. SSIs were more likely to develop in malnourished patients [odds ratio (OR) 2.31, 95% confidence interval (CI) 1.75-3.05]. While pre-operative malnutrition was significantly associated with SSI in patients undergoing thoracolumbar spinal and sacral surgery, no significant difference was seen in patients undergoing cervical spinal surgery. In subgroup analyses, similar results were observed for both hospital-based (OR 3.16, 95% CI 1.84-5.43) and population-based (OR 2.00, 95% CI 1.63-2.46) studies. CONCLUSIONS: Malnutrition is associated with increased risk of developing SSI after spinal surgery. Further high-quality research is warranted to investigate whether improvement of pre-operative nutritional status can decrease SSI rates.

Safety of urgent endarterectomy in acute non-disabling stroke patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: International recommendations advocate that carotid endarterectomy (CEA) should be performed within 2 weeks from the index event in symptomatic carotid artery stenosis (sCAS) patients. However, there are controversial data regarding the safety of CEA performed during the first 2 days of ictus. The aim of this international, multicenter study was to prospectively evaluate the safety of urgent (0-2 days) in comparison to early (3-14 days) CEA in patients with sCAS. METHODS: Consecutive patients with non-disabling (modified Rankin Scale scores ≤2) acute ischaemic stroke or transient ischaemic attack due to sCAS (≥70%) underwent urgent or early CEA at five tertiary-care stroke centers during a 6-year period. The primary outcome events included stroke, myocardial infarction or death during the 30-day follow-up period. RESULTS: A total of 311 patients with sCAS underwent urgent (n = 63) or early (n = 248) CEA. The two groups did not differ in baseline characteristics with the exception of crescendo transient ischaemic attacks (21% in urgent vs. 7% in early CEA; P = 0.001). The 30-day rates of stroke did not differ (P = 0.333) between patients with urgent (7.9%; 95% confidence interval 3.1%-17.7%) and early (4.4%; 95% confidence interval 2.4%-7.9%) CEA. The mortality and myocardial infarction rates were similar between the two groups. The median length of hospitalization was shorter in urgent CEA [6 days (interquartile range 4-6) vs. 10 days (interquartile range 7-14); P < 0.001]. CONCLUSIONS: Our findings highlight that urgent CEA performed within 2 days from the index event is related to a non-significant increase in the risk of peri-procedural stroke. The safety of urgent CEA requires further evaluation in larger datasets.

Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with VKA-related ICH. METHODS: We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC-related ICH in patients treated with and without NOAC-specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30-90 days following symptom onset. RESULTS: Our literature search identified six eligible studies (four randomized controlled trials and two open-label trials of NOAC-specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36-0.58] with no heterogeneity (I2 = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC-related and VKA-related (RR, 1.00; 95% CI, 0.84-1.19) ICH with no evidence of heterogeneity (I2 = 0%). In the indirect analysis, the case fatality rate of NOAC-related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11-24%) vs. 41% (95% CI, 34-49%); P < 0.001]. CONCLUSIONS: Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH.

Differential leukocyte counts on admission predict outcomes in patients with acute ischaemic stroke treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: To determine the association of differential leukocyte counts on admission with efficacy and safety outcomes in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). METHODS: Consecutive patients with AIS receiving IVT were evaluated at two stroke centers. Differential leukocyte counts and neutrophil:lymphocyte ratio (NLR) were determined during the initial 12 h of admission. Efficacy outcomes were favorable functional outcome (FFO) (modified Rankin Scale scores of 0-1) and functional independence (FI) (modified Rankin Scale scores of 0-2) at 3 months, whereas safety outcomes were symptomatic intracranial hemorrhage and 3-month mortality. RESULTS: Among 657 IVT-treated patients with AIS, the mean age was 64 ± 14 years, 50% were female and median National Institutes of Health Stroke Scale score was 7 points (interquartile range, 4-13). Lower neutrophil and leukocyte counts and NLR counts were observed in patients with 3-month FFO and FI, whereas higher counts were observed in patients who died at 3 months. The best discriminative factors for 3-month FFO and FI were NLR < 2.2 (sensitivity 51.4%, specificity 63.1%) and leukocyte count <8100/µL (sensitivity 57.5%, specificity 55.1%), respectively. After adjustment for potential confounders, NLR < 2.2 was associated with higher odds of FFO [odds ratio (OR), 1.56; 95% confidence interval (CI), 1.08-2.24; P = 0.018], whereas leukocyte count <8100/µL demonstrated higher odds of 3-month FI (OR, 1.69; 95% CI, 1.11-2.57; P = 0.014) and lower odds of 3-month mortality (OR, 0.31; 95% CI, 0.16-0.60; P = 0.001). Combined neutrophil (<6800/µL) and leukocyte (<8100/µL) counts demonstrated a strong interaction for 3-month FI (OR, 1.73; 95% CI, 1.13-2.67; P interaction = 0.012). CONCLUSIONS: Differential leukocyte counts on admission were independently associated with clinical outcomes in patients with AIS treated with IVT. These inflammatory biomarkers are potential targets for adjunctive neuroprotection in this stroke subgroup.

Restless legs syndrome and cerebrovascular/cardiovascular events: Systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis to evaluate the proposed association of restless legs syndrome (RLS) with cerebrovascular/cardiovascular outcomes. METHODS: We calculated the corresponding odds ratios on the prevalence of cerebrovascular/cardiovascular risk factors and standardized mean differences on the reported mean age at baseline between RLS patients and controls. We also calculated the corresponding risk ratios and adjusted for potential confounders hazard ratios (HRsadjusted ) on the reported outcomes of interest between RLS patients and controls. RESULTS: We identified 8 eligible studies (644 506 patients, mean age: 60.2 years, 36.2% males; 3.3% with RLS). RLS patients were found to have significantly higher prevalence of hypertension (P = .002), diabetes (P = .003) and hyperlipidemia (P = .010) compared to controls. In the unadjusted analyses of prospective observational studies, RLS patients were found to have significantly higher risk for cerebrovascular ischaemia (P = .01) and all-cause mortality (P = .04) compared to controls during follow-up, while in the adjusted for potential confounders analyses RLS patients were only found to have a higher risk of all-cause mortality (HR adjusted=1.52, 95% CI: 1.17-1.97, P = .002). CONCLUSIONS: The present report does not provide evidence for an increased risk of cerebrovascular and cardiovascular events in RLS patients, which highlights the vast presence of confounding factors.

Clinical outcome of cardioembolic stroke treated by intravenous thrombolysis.

INTRODUCTION: Cardioembolic stroke (CS) in patients without thrombolytic treatment is associated with a worse clinical outcome and higher mortality compared to other types of stroke. The aim of this study was to determine the clinical outcome of CS in patients treated by intravenous thrombolysis (IVT). MATERIAL AND METHODOLOGY: Data of patients from the SITS-EAST register (Safe Implementation of Treatments in Stroke) were analyzed in patients who received IVT treatment from 2000 to April 2014. The effect of the stroke etiology according to ICD-10 classification on outcome was analyzed using a univariate and multivariate analysis. The outcomes were assessed as follows: excellent clinical outcome (modified Rankin scale (mRS) 0-1) at 3 months, the rate of symptomatic intracranial hemorrhage (sICH), mortality, and improvement at 24 hours after IVT. RESULTS: Data of 13 772 patients were analyzed. CS represented 30% of all strokes. The mean age of patients with CS, atherothrombotic stroke, lacunar stroke, and other stroke was 70.8, 66.7, 66.2, and 63.3 years, respectively (P < .001). Severity of stroke on admission by median NIHSS score was 13 points in patients with CS, 12 points - in atherothrombotic stroke, 7 points - in lacunar stroke, and 10 points-in other stroke types (P < .001). No difference in mortality was detected among atherothrombotic and CS; however, atherothrombotic strokes had higher odds of sICH [OR = 1.63 (95% CI: 1.07-2.47), P = .023], lower odds of early improvement [OR = 0.79 (95% CI: 0.72-0.86), P < .001], and excellent clinical outcome [OR = 0.77 (95% CI: 0.67-0.87), P < .001] compared with CS. CONCLUSIONS: Cardioembolic strokes are not associated with increased mortality. Patients with CS are less likely to have sICH and have better outcome after IVT.

Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. METHODS: Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. RESULTS: A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. CONCLUSIONS: High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required.