Cerebral venous sinus thrombosis associated with cancer: analysis of the ACTION-CVT study.

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer.

Systemic thrombolysis in patients with acute stroke and active cancer: a systematic review and meta-analysis.

Cancer patients frequently have concomitant cerebrovascular diseases, which significantly worsen their prognosis. Prospective studies validating intravenous thrombolysis (IVT) safety profile in patients with acute ischemic stroke and active cancer are still lacking. Therefore, we aimed to evaluate IVT's efficacy and safety profile in acute ischemic stroke patients with comorbid active cancer. We included in a meta-analysis all relevant published studies, including patients with acute ischemic stroke with or without active cancer and receiving IVT, according to recommendations for IVT treatment for acute ischemic stroke. The primary outcomes were: any intracerebral hemorrhage, all-cause mortality, and good functional outcome reported as modified Rankin Scale (mRS) ≤ 2 at the end of the scheduled follow-up period. We included 11 studies in the meta-analysis. IVT was not associated with a significant increase in the incidence of intracerebral hemorrhage (OR 1.35; 95% CI 0.85-2.14; I2 76%), nor with a significant increase in death for any cause (OR 1.26; 95% CI 0.91-1.75; I2 71%); furthermore, IVT did not influence mRS between cancer and non-active cancer stroke patients (OR 0.72; 95% CI 0.35-1.49; I2 59%). IVT seems safe and effective in patients with ischemic stroke and concomitant cancer. Due to the low overall quality of the evidence, high-quality randomized controlled trials with adequate sample sizes are needed.

Outcome Prediction in Cerebral Venous Thrombosis: The IN-REvASC Score.

BACKGROUND: We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT). METHODS: We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated. RESULTS: A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P<0.001), age (OR, 1.02 per year; 95% CI, 1.00 to 1.04; P=0.039), Black race (OR, 2.17; 95% CI, 1.10 to 4.27; P=0.025), encephalopathy or coma on presentation (OR, 2.71; 95% CI, 1.39 to 5.30; P=0.004), decreased hemoglobin (OR, 1.16 per g/dL; 95% CI, 1.03 to 1.31; P=0.014), higher NIHSS on presentation (OR, 1.07 per point; 95% CI, 1.02 to 1.11; P=0.002), and substance use (OR, 2.34; 95% CI, 1.16 to 4.71; P=0.017). The derived IN-REvASC score outperformed ISCVT-RS for the prediction of poor outcome at 90-day follow-up (area under the curve [AUC], 0.84 [95% CI, 0.79 to 0.87] vs. AUC, 0.71 [95% CI, 0.66 to 0.76], χ2 P<0.001) and mortality (AUC, 0.84 [95% CI, 0.78 to 0.90] vs. AUC, 0.72 [95% CI, 0.66 to 0.79], χ2 P=0.03). CONCLUSIONS: Seven factors were associated with poor neurological outcome following CVT. The INREvASC score increased prognostic accuracy compared to ISCVT-RS. Determining patients at highest risk of poor outcome in CVT could help in clinical decision making and identify patients for targeted therapy in future clinical trials.

Clinical Features of Patients With Cervical Artery Dissection and Fibromuscular Dysplasia.

BACKGROUND AND PURPOSE: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. METHODS: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD-). RESULTS: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13-2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06-18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26-0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58-7.31] and 2.07 [95% CI, 1.06-4.03], respectively) in multivariable Cox proportional hazards analysis. CONCLUSIONS: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence.

Acute hematoma expansion after spontaneous intracerebral hemorrhage: risk factors and impact on long-term prognosis.

INTRODUCTION: Hematoma expansion (HE) after intracerebral hemorrhage (ICH) is associated with short-term mortality, but its impact on long-term prognosis is still unclear. The aim of this study was to evaluate the impact of HE on long-term survival and functional status after spontaneous ICH. METHODS: Consecutive patients admitted with spontaneous ICH were prospectively enrolled and followed up for a minimum of 2 years. We compared short-term (< 30 days) and long-term survival and functional status between ICH patients with HE (HE+) and those without (HE-). Main outcomes were mortality and poor outcome, defined as modified Rankin Scale ≥ 3. Secondary outcomes included recurrent ICH, admission to institutionalized care, and ischemic events (stroke, myocardial infarction, and systemic embolism). RESULTS: Overall, 140 patients were included (mean age 74.9 years, male 59.3%) and followed up for a mean of 2.25 years. HE+ patients (25.7%) had larger hematoma volume at admission (23.8 ml vs 15.3 ml, p < 0.05), higher NIHSS score (14.6 vs 10.5, p < 0.05) and higher cumulative mortality (59.3% vs 39.2%, p < 0.05) compared to HE- patients. Survival analysis showed that HE+ confers higher mortality and worse functional status at all time points. HE did not associate with secondary outcomes. DISCUSSION: HE translates into higher mortality and functional dependence over long-term follow-up. Strategies limiting HE might benefit long-term functional status.

Long-Term Risk of Stroke After Transient Global Amnesia in Two Prospective Cohorts.

Background and Purpose- Transient global amnesia (TGA) is known as a benign syndrome, but recent data from neuroradiological studies support an ischemic cause in some cases, which might suggest an increased susceptibility to cerebrovascular events. We determined the long-term risk of stroke after a first TGA in 2 independent prospective cohorts. Methods- In 2 independent prospective cohorts of patients with TGA (OXVASC [Oxford Vascular Study], population-based; NU (Northern Umbria) cohort, TGA registry), cardiovascular risk factors and long-term outcomes, including stroke and major cardiovascular events, were identified on follow-up. Cardiovascular risk factors were treated according to primary prevention guidelines. In OXVASC, the age-/sex-adjusted risk of stroke during follow-up was compared with that expected from the rate in the underlying study population. Results- Among 525 patients with TGA (425 NU and 100 OXVASC), mean (SD) age was 65.1 (9.5) years and 42.5% male. Hypertension (58.1%), dyslipidemia (40.4%), and smoking (36.4%) were the most frequent cardiovascular risk factors. The risk of stroke was similar in the 2 cohorts, with a pooled annual risk of 0.6% (95% CI, 0.4-0.9) and a 5-year cumulative risk of 2.7% (1.1-4.3). Moreover, the stroke risk in OXVASC cases was no greater than that expected in the underlying study population (adjusted relative risk=0.73; 0.12-4.54; P=0.74). Conclusions- TGA does not carry an increased risk of stroke, at least when cardiovascular risk factors are treated according to primary prevention guidelines.

Management of major bleeding and outcomes in patients treated with direct oral anticoagulants: results from the START-Event registry.

The management of major bleeding in patients treated with direct oral anticoagulants (DOACs) is still not well established. START-Events, a branch of the START registry (Survey on anTicoagulated pAtients RegisTer) (NCT02219984), aims to describe the actual management of bleeding or recurrent thrombotic events in routine clinical practice. We here present the results of the management of bleeding patients. The START-Event registry is a prospective, observational, multicenter, international study. Baseline characteristics (demographic, clinical, risk factors) of patients, laboratory data at admission and during follow-up, site of bleeding, therapeutic strategies, and outcomes at the time of hospital discharge and after 6 months were recorded on a web-based case report form. Between January 2015 and December 2016, 117 patients with major bleeding events were enrolled. Non-valvular atrial fibrillation (NVAF) was the indication for treatment in 84% (62% males); 53 patients had intracranial bleeding (13 fatal), 42 had gastrointestinal bleeding (1 fatal), and 22 had bleeding in other sites. Therapeutic interventions for the management of bleeding were performed in 71% of patients. Therapeutic strategies with/without surgery or invasive procedures included: fluid replacement or red blood cells transfusion, prothrombin complex concentrates (3 or 4 factors), antifibrinolytic drugs, and the administration of idarucizumab. Creatinine, blood cell count, and PT/aPTT were the most frequent tests requested, while specific DOAC measurements were performed in 23% of patients. Mortality during hospitalization was 11.9%, at 6-month follow-up 15.5%. Our data confirm a high heterogeneity in the management of bleeding complications in patients treated with DOACs.

Cancer-associated ischemic stroke: A retrospective multicentre cohort study.

BACKGROUND: The association between stroke and cancer is well-known but insufficiently investigated. Aim of this multicentre retrospective cohort study was to estimate the prevalence of cancer-associated ischemic stroke, describe clinical outcomes in patients with cancer-associated ischemic stroke and investigate independent factors associated with active cancer. METHODS: Consecutive adult patients admitted for acute ischemic stroke were included. Included patients were admitted in the Stroke Unit of the Hospital of Perugia, Italy, from March 2005 to March 2015, and in a medical unit of the Hospital of Varese, Italy, from January 2010 till December 2011. Clinical and laboratory data of patients with and without active cancer were collected. Multivariate logistic regression analysis was performed to identify independent factors associated with active cancer. RESULTS: A total of 2209 patients admitted with acute ischemic stroke were included with a median hospital stay of 9 days (interquartile range 5.75-14). Mean age was 72.7 years (standard deviation +/- 13); 55% patients were male and 4.4% had active cancer. Factors significantly associated with the presence of active cancer were age > 65 years (odds ratio [OR] 3.34; 95% confidence interval [CI] 1.64-6.81), occurrence of venous thromboembolism [VTE] (OR 2.84; 95% CI 1.12-7.19), low-density lipoprotein (LDL) cholesterol level < 70 mg/dL (OR 1.92; 95% CI 1.06-3.47), cryptogenic stroke subtype (OR 1.93; 95% CI 1.22-3.04). Overall mortality rate during hospital stay was greater in patients with active cancer (21.5% vs. 10% P < 0.05). CONCLUSIONS: Older age, occurrence of VTE, low LDL level, and cryptogenic stroke subtype, are independently associated with active cancer. Overall, our findings suggest a possible prevalent role of hypercoagulability in the pathogenesis of cancer-associated ischemic stroke.

Risk Profile of Symptomatic Lacunar Stroke Versus Nonlobar Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level. METHODS: Consecutive patients with either acute symptomatic LS or dICH were prospectively enrolled as part of a multicenter Italian study. We compared the risk factor profile of the 2 subgroups using multivariable logistic regression. RESULTS: During a time course of 9.5 years, 1931 subjects (1434 LS and 497 dICH; mean age, 71.3±13.3 years; males, 55.5%) qualified for the analysis. Current smoking was associated with LS (odds ratio [OR], 2.17; P<0.001). Conversely, dICH cases were more likely to be hypertensive (OR, 1.87; P<0.001), excessive alcohol consumers (OR, 1.70; P=0.001), and more frequently under treatment with warfarin (OR, 2.05; P=0.010) and statins (OR, 3.10; P<0.001). Hypercholesterolemia, diabetes mellitus, and antiplatelet treatment were not associated with a specific small vessel disease manifestation. CONCLUSIONS: The risk factor profile of dICH differs from that associated with LS. This might be used for disease risk stratification at individual level.

Summary of Evidence on Early Carotid Intervention for Recently Symptomatic Stenosis Based on Meta-Analysis of Current Risks.

BACKGROUND AND PURPOSE: This study aimed to assess the evidence on the periprocedural (<30 days) risks of carotid intervention in relation to timing of procedure in patients with recently symptomatic carotid stenosis. METHODS: A systematic literature review of studies published in the past 8 years reporting periprocedural stroke/death after carotid endarterectomy (CEA) and carotid stenting (CAS) related to the time between qualifying neurological symptoms and intervention was performed. Pooled estimates of periprocedural risk for patients treated within 0 to 48 hours, 0 to 7 days, and 0 to 15 days were derived with proportional meta-analyses and reported separately for patients with stroke and transient ischemic attack as index events. RESULTS: Of 47 studies included, 35 were on CEA, 7 on CAS, and 5 included both procedures. The pooled risk of periprocedural stroke was 3.4% (95% confidence interval [CI], 2.6-4.3) after CEA and 4.8% (95% CI, 2.5-7.8) after CAS performed <15 days; stroke/death rates were 3.8% and 6.9% after CEA and CAS, respectively. Pooled periprocedural stroke risk was 3.3% (95% CI, 2.1-4.6) after CEA and 4.8% (95% CI, 2.5-7.8) after CAS when performed within 0 to 7 days. In hyperacute surgery (<48 hours), periprocedural stroke risk after CEA was 5.3% (95% CI, 2.8-8.4) but with relevant risk differences among patients treated after transient ischemic attack (2.7%; 95% CI, 0.5-6.9) or stroke (8.0%; 95% CI, 4.6-12.2) as index. CONCLUSIONS: CEA within 15 days from stroke/transient ischemic attack can be performed with periprocedural stroke risk <3.5%. CAS within the same period may carry a stroke risk of 4.8%. Similar periprocedural risks occur after CEA and CAS performed earlier, within 0 to 7 days. Carotid revascularization can be safely performed within the first week (0-7 days) after symptom onset.

Determinants of premature familial arterial thrombosis in patients with juvenile ischaemic stroke. The Italian Project on Stroke in Young Adults (IPSYS).

Factors predicting family history (FH) of premature arterial thrombosis in young patients with ischaemic stroke (IS) have not been extensively investigated, and whether they might influence the risk of post-stroke recurrence is still unknown. In the present study we analysed 1,881 consecutive first-ever IS patients aged 18-45 years recruited from January 2000 to January 2012 as part of the Italian Project on Stroke in Young Adults (IPSYS). FH of premature arterial thrombosis was any thrombotic event [IS, myocardial infarction or other arterial events event] < 45 years in proband's first-degree relatives. Compared with patients without FH of premature arterial thrombosis, those with FH (n = 85) were more often smokers (odds ratio [OR], 1.94; 95 % confidence interval [CI], 1.21-3.09) and carriers of procoagulant abnormalities (OR, 3.66; 95 % CI, 2.21-6.06). Smoking (OR, 2.48; 95 % CI, 1.20-5.15), the A1691 mutation in factor V gene (OR, 3.64; 95 % CI, 1.31-10.10), and the A20210 mutation in the prothrombin gene (OR, 8.40; 95 % CI 3.35-21.05) were associated with FH of premature stroke (n = 33), while circulating anti-phospholipids to FH of premature myocardial infarction (n = 45; OR, 3.48; 95 % CI, 1.61-7.51). Mean follow-up time was 46.6 ± 38.6 months. Recurrent events occurred more frequently in the subgroup of patients with FH of premature stroke [19.4 %); p = 0.051] compared to patients without such a FH. In conclusion, young IS patients with FH of premature arterial thrombosis exhibit a distinct risk-factor profile, an underlying procoagulant state and have worse vascular prognosis than those with no FH of juvenile thrombotic events.

Antithrombotic therapy in carotid artery stenosis: an update.

Carotid stenosis is generally associated with high risks of stroke and vascular events. In asymptomatic and symptomatic patients, with or without revascularization, optimal managements of carotid artery stenosis require the use of medications or lifestyle modifications (stopping smoking and monitoring hypertension, hyperlipidemia, and diabetes) to control the processes associated with atheroma to reduce the risk of embolic events. Moreover, antiplatelet therapy should be considered. There is little evidence that antiplatelet therapy is beneficial in preventing stroke or the progression of stenosis in asymptomatic patients, whereas, evidence of a benefit from antiplatelet therapy for secondary prevention of recurrent stroke in symptomatic patients with carotid atherosclerosis is more robust. Also, in patients undergoing carotid endarterectomy, perioperative antithrombotic therapy should include aspirin, while the addition of clopidogrel should be decided case-by-case. Furthermore, perioperative antithrombotic therapy in patients undergoing carotid stenting should consist a combination of aspirin plus clopidogrel.

Secondary prevention of atherothrombotic cerebrovascular events.

Secondary prevention of atherosclerotic stroke and transient ischemic attack includes both conventional approaches to vascular risk factor management (blood pressure lowering, cholesterol reduction with statins and smoking cessation), antiplatelet therapy and more specific interventions, such as carotid revascularization. The objective of this review is to discuss effective interventions for optimal secondary prevention of atherosclerotic stroke.

Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: the ICARO-2 study.

BACKGROUND AND PURPOSES: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. METHODS: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. RESULTS: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0-1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9-11.1) and mortality or disability (OR 5.0; 95% CI 2.9-8.7) at 90 days. CONCLUSIONS: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.

Perioperative stroke risk in nonvascular surgery.

BACKGROUND: Perioperative stroke is an ischemic or hemorrhagic cerebrovascular accident that can arise intraoperatively or from 3 to 30 days after surgery. This relatively rare complication deserves attention because of its high mortality and serious disability, the latter of which can lead to prolonged hospital stay as well as discharge to long-term care facilities. The aim of this article was to review the literature on perioperative stroke in general surgery, excluding carotid and cardiac surgeries because these have already been thoroughly investigated in previous papers. METHODS: A search strategy was designed to identify all relevant studies on perioperative stroke in the English language. This search was restricted to papers published up to December 5, 2011. Studies were initially identified from the Medline/PubMed database, EMBASE and the Cochrane Database using the search terms 'surgery', 'perioperative stroke', 'risk factors', 'anticoagulation treatment' and 'antiplatelet treatment'. RESULTS: The incidence of perioperative stroke among patients who undergo nonvascular surgery is reported to be about 0.08-0.7%. This depends on the type and complexity of the surgical procedure along with patient risk factors. The reported perioperative mortality is 18-26%. One of the main issues is the management of patients taking anticoagulant or antiplatelet drugs, as the risk of bleeding has to be counterbalanced with the risk of arterial thrombosis due to discontinuation. Additionally, the presence of symptomatic carotid stenosis should be taken into account in the risk evaluation. CONCLUSIONS: To date, current guidelines are incomplete regarding the management of patients with vascular disease undergoing nonvascular surgery. It is recommended to stop oral anticoagulation approximately 5 days before major surgery to adequately allow the INR to normalize, and at the same time subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin should be started. Regarding new anticoagulants, dabigatran does not need to be withheld for minor procedures. Currently, there are no clear recommendations on the use of rivaroxaban and apixaban. Data concerning the management of patients undergoing antiplatelet therapy are lacking. To date, neurologists discourage the perioperative withdrawal of aspirin (acetylsalicylic acid, ASA) especially in patients in secondary prevention. The 'Antiplatelet Agents in the Perioperative Management of Patients Trial' is ongoing to assess the safety and determine the optimal use of ASA in the perioperative management of patients undergoing general and abdominal surgery. In the meantime an individualized, accurate, multidisciplinary (surgical, neurological, cardiological and anesthesiological) risk/benefit assessment remains the best basis for treatment decision.

High diastolic blood pressure is a risk factor for in-hospital mortality in complete MCA stroke patients.

Complete middle cerebral artery (MCA) stroke is a life-threatening condition, which can lead to death in the form of "malignant MCA syndrome"; characterized by massive brain edema and cerebral herniation. Moreover, patients with complete MCA infarct have high mortality due to complications. The aim of this study was to evaluate the clinical predictors of in-hospital mortality in patients with complete MCA stroke. Consecutive patients with complete MCA stroke were enrolled in a prospective single center in-hospital outcome study having mortality as its end point. Among 780 ischemic stroke patients, 125 had complete MCA strokes (16%) and 44 (35.2%) of these died in hospital. A high NIHSS-score (OR 1.17 95%CI 1.03-1.34, P=0.013) and high diastolic blood pressure on admission (OR 1.05 95%CI 1.01-1.09) resulted being independent predictors of in-hospital mortality in patients with complete MCA stroke. The median value of diastolic blood pressure at admission was 90 mmHg in patients who died and 80 mmHg in survivors (P=0.01). The risk of death increased by 5% for each mmHg increase in diastolic blood pressure on admission after adjusting for other risk factors. The rate of mortality was 22% in patients with diastolic blood pressure lower than 90 mmHg, 56% for those with diastolic blood pressure between 90 and 109 mmHg and 67% for those with diastolic blood pressure higher than 110 mmHg. This study suggests that high diastolic blood pressure on admission in acute MCA stroke patients is linearly correlated with in-hospital mortality.

Non-neurological complications of acute stroke: frequency and influence on clinical outcome.

Understanding the nature and clinical relevance of non-neurological complications is crucial to provide an appropriate management to patients with acute stroke. The aims of this study in patients with acute stroke were to assess the in-hospital frequency of non-neurological complications and the correlation between these complications and adverse outcome (death or disability) at 3 months. Patients with acute ischemic or hemorrhagic stroke admitted to the Stroke Unit of the University of Perugia were included in a prospective cohort study. Pre-defined non-neurological complications were considered for study purposes. Study outcomes were 3-month death and composite of death and disability. Stroke was defined as not disabling (mRS 0-2) or disabling (mRS 3-5) or leading to death (mRS 6). Multiple logistic regression analysis was used to identify predictors for study outcomes. 1,101 consecutive patients (mean age 72.2 ± 13.1 years; 57.1% males; 926 ischemic and 175 hemorrhagic) were included in the study; 338 patients (30.7%) experienced at least one non-neurological complication. 269 patients (24.4%) had fever, 210 patients (19.1%) infection in one or more sites, 86 patients (7.8%) venous thromboembolism (VTE) and 34 patients (3.0%) myocardial infarction. At 3 months, 511 patients (46.4%) were disabled and 123 had died (11.2%). Regression logistic analysis found that: (1) age (OR 1.06 for 1 added year; 95% CI 1.03-1.08), NIHSS score on admission (OR 1.31 for 1 added point; 95% CI 1.25-1.38), current smoking (OR 1.92; 95% CI 1.08-3.39), infection in any site (OR 4.13; 95% CI 1.51-11.28) and VTE (OR 6.03; 95% CI 1.44-25.11) were associated with death and/or disability (mRS ≥ 3) and that (2) age (OR 1.06 for 1 added year; 95% CI 1.02-1.09), high NIHSS score on admission (OR 1.21 for 1 added point; 95% CI 1.15-1.27), male gender (OR 1.93; 95% CI 1.04-3.62), fever (OR 2.29; 95% CI 1.08-4.86) and myocardial infarction (OR 6.57; 95% CI 2.30-18.74) were associated with increased mortality. In conclusions, patients with acute stroke are at high risk of non-neurological complications, such as fever with or without infections, venous thromboembolism and myocardial infarction. Non-neurological complications are associated with increased long-term disability and death.

Did Jean-Martin Charcot contribute to stroke?

Stroke was never identified as a significant, autonomous field of activity of the emerging school of neurology at La Salpêtrière, which developed after the appointment of Jean-Martin Charcot (1825-1893) during the last days of 1861. However, stroke was already present in Charcot's first paper (1851), which dealt with a case of multiple organ cardiac embolism, including middle cerebral artery infarction, at a time when the studies of Rudolf Virchow on thromboembolism were unknown in France. A few years later, Charcot made a still up-to-date description of vascular intermittent claudication, which had only been reported in the horse. In the 1860s, Charcot and his pupils presented several major works dealing with cerebrovascular disease, including famous studies on miliary aneurysms in cerebral hemorrhage. This work was done with Charles Bouchard, at the time Charcot's 'interne', but who would become one of his 'political' opponents 2 decades later, when in 1892, as president of the 'agrégation' jury, he rejected the professorship application of 4 protégés of Charcot, including Joseph Babinski and Georges Gilles de la Tourette. Further work on cerebrovascular disease by Charcot included histological studies of brain 'softening', paraneoplastic cerebral arterial occlusion and consequences of stroke (e.g. arthropathies, vegetative changes, contractures and abnormal movements). Brain localization, one of Charcot's major neurological topics, was also largely based on stroke case studies. Charcot's work on stroke remains poorly recognized, but it demonstrates his unique skills in stimulating scientific work in younger colleagues, many of whom subsequently became major figures of neurology and psychiatry.

Primary and secondary prevention of ischemic stroke.

Prevention of stroke and transient ischemic attack includes both conventional approaches to vascular risk factor management (blood pressure lowering, cholesterol reduction with statins, smoking cessation and antiplatelet therapy) and more specific interventions, such as carotid revascularization or anticoagulation for atrial fibrillation. The objective of this review is to discuss effective interventions for optimal primary and secondary stroke prevention.