J.A. Egido

Risk of ischemic stroke and lifetime estrogen exposure

Background: Estrogen loss has been related to higher incidence of stroke in postmenopausal women, but randomized trials have demonstrated an increased risk of stroke in women receiving hormone replacement therapy (HRT). Objective: To assess the relationship between exposure to endogenous ovarian hormones and the risk of noncardioembolic ischemic stroke. Methods: We conducted a multicenter, age-matched, case-control study in postmenopausal women (case: nonembolic ischemic stroke; control: no stroke) comparing duration of ovarian activity or lifetime estrogen exposure, which was defined as age at menarche to age at menopause. Embolic cardiopathy and unreliable gynecologic data were exclusion criteria. Cardiovascular disease risk factors were recorded. The relationships of the principal variables to the risk of stroke were assessed using a conditional logistic regression analysis. Results: There were 430 cases and 905 controls in the study. In the multivariate analysis, hypertension (odds ratio [OR]: 2.73; 95% CI: 2.09 to 3.58; p < 0.0001), diabetes (OR: 3.38; 95% CI: 2.53 to 4.52; p < 0.0001), hyperlipidemia (OR: 1.31; 95% CI: 1.01 to 1.7; p = 0.045), lifespan of ovarian activity <34 years (OR: 1.51; 95% CI: 1.13 to 2.03; p = 0.005), and menarche at <13 years of age (OR 1.49; 95% CI: 1.15 to 1.92; p = 0.002) were independently related to an increased risk of stroke. Obesity (OR: 0.73; 95% CI: 0.56 to 0.95; p = 0.021) was related to a lower risk of stroke. Conclusions: Longer lifetime exposure to ovarian estrogens may protect against noncardioembolic ischemic stroke. However, a very early age of exposure onset could be disadvantageous.

Prediction of early stroke recurrence in transient ischemic attack patients from the PROMAPA study: a comparison of prognostic risk scores.

Background: Several clinical scales have been developed for predicting stroke recurrence. These clinical scores could be extremely useful to guide triage decisions. Our goal was to compare the very early predictive accuracy of the most relevant clinical scores [age, blood pressure, clinical features and duration of symptoms (ABCD) score, ABCD and diabetes (ABCD2) score, ABCD and brain infarction on imaging score, ABCD2 and brain infarction on imaging score, ABCD and prior TIA within 1 week of the index event (ABCD3) score, California Risk Score, Essen Stroke Risk Score and Stroke Prognosis Instrument II] in consecutive transient ischemic attack (TIA) patients. Methods: Between April 2008 and December 2009, we included 1,255 consecutive TIA patients from 30 Spanish stroke centers (PROMAPA study). A neurologist treated all patients within the first 48 h after symptom onset. The duration and typology of clinical symptoms, vascular risk factors and etiological work-ups were prospectively recorded in a case report form in order to calculate established prognostic scores. We determined the early short-term risk of stroke (at 7 and 90 days). To evaluate the performance of each model, we calculated the area under the receiver operating characteristic curve. Cox proportional hazards multivariate analyses determining independent predictors of stroke recurrence using the different components of all clinical scores were calculated. Results: We calculated clinical scales for 1,137 patients (90.6%). Seven-day and 90-day stroke risks were 2.6 and 3.8%, respectively. Large-artery atherosclerosis (LAA) was observed in 190 patients (16.7%). We could confirm the predictive value of the ABCD3 score for stroke recurrence at the 7-day follow-up [0.66, 95% confidence interval (CI) 0.54–0.77] and 90-day follow-up (0.61, 95% CI 0.52–0.70), which improved when we added vascular imaging information and derived ABCD3V scores by assigning 2 points for at least 50% symptomatic stenosis on carotid or intracranial imaging (0.69, 95% CI 0.57–0.81, and 0.63, 95% CI 0.51–0.69, respectively). When we evaluated each component of all clinical scores using Cox regression analyses, we observed that prior TIA and LAA were independent predictors of stroke recurrence at the 7-day follow-up [hazard ratio (HR) 3.97, 95% CI 1.91–8.26, p < 0.001, and HR 3.11, 95% CI 1.47–6.58, p = 0.003, respectively] and 90-day follow-up (HR 2.35, 95% CI 1.28–4.31, p = 0.006, and HR 2.20, 95% CI 1.15–4.21, p = 0.018, respectively). Conclusion: All published scores that do not take into account vascular imaging or prior TIA when identifying stroke risk after TIA failed to predict risk when applied by neurologists. Clinical scores were not able to replace extensive emergent diagnostic evaluations such as vascular imaging, and they should take into account unstable patients with recent prior transient episodes.

Guías de actuación clínica en la hemorragia intracerebral

Intracerebral haemorrhage accounts for 10%-15% of all strokes; however it has a poor prognosis with higher rates of morbidity and mortality. Neurological deterioration is often observed during the first hours after onset and determines poor prognosis. Intracerebral haemorrhage, therefore, is a neurological emergency which must be diagnosed and treated properly as soon as possible. In this guide we review the diagnostic procedures and factors that influence the prognosis of patients with intracerebral haemorrhage and we establish recommendations for the therapeutic strategy, systematic diagnosis, acute treatment and secondary prevention for this condition.

Guía para el tratamiento preventivo del ictus isquémico y AIT (I). Actuación sobre los factores de riesgo y estilo de vida

OBJECTIVE To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA). METHODS We reviewed available evidence on risk factors and means of modifying them to prevent ischaemic stroke and TIA. Levels of evidence and recommendation grades are based on the classification of the Centre for Evidence-Based Medicine. RESULTS This first section summarises the recommendations for action on the following factors: blood pressure, diabetes, lipids, tobacco and alcohol consumption, diet and physical activity, cardio-embolic diseases, asymptomatic carotid stenosis, hormone replacement therapy and contraceptives, hyperhomocysteinemia, prothrombotic states and sleep apnea syndrome. CONCLUSIONS Changes in lifestyle and pharmacological treatment for hypertension, diabetes mellitus and dyslipidemia, according to criteria of primary and secondary prevention, are recommended for preventing ischemic stroke.

Safety and Outcomes following Thrombolytic Treatment in Stroke Patients Who Had Received Prior Treatment with Anticoagulants

Background: Information is scare regarding the safety of intravenous thrombolysis in patients under anticoagulant treatment, given that this is an exclusion criterion in clinical trials. We analyzed the risk of hemorrhagic complications following thrombolysis in patients under treatment with low-molecular-weight heparins (LMWH) and oral anticoagulants (OA). Methods: In a multicentered prospective study of consecutive acute stroke patients treated with intravenous alteplase we recorded age, gender, baseline NIHSS score, treatment delay, risk factors, etiology and previous therapy. The neurological progress (National Institutes of Health Stroke Scale at 7 days) and functional evolution at 3 months (modified Rankin Scale score), mortality and symptomatic intracerebral hemorrhage (SICH) were compared between patients with LMWH or OA and those without prior anticoagulant therapy. Results: Of the 1,482 patients, 21 (1.4%) had received LMWH and 70 (4.7%) OA (international normalized ratio, INR, 0.9-2.0). Patients on OA were older, presented higher basal glucose levels, had been treated later and had a higher prevalence of hypertension, dyslipidemia, prior stroke, atrial fibrillation and cardioembolic pathologies. The severity of stroke on admission was similar in the different groups. The percentages of patients achieving independence (mRS 0-2) at 3 months were 33, 44 and 58 (LMWH, OA and no prior anticoagulant treatment, respectively; p = 0.02 for both comparisons of LMWH vs. no treatment and OA vs. no treatment); the mortality rates were 30, 25 and 12% (p = 0.010, p = 0.001, respectively) and the SICH were 14, 3 and 2% (p < 0.0001 for comparison of LMWH vs. no treatment). In the case of treatment with OA, the outcomes were independent of the INR value. Following adjustment for confounding variables, the prior use of OA was associated with higher mortality (OR: 2.15, 95% CI: 1.1-4.2; p = 0.026) but not with SICH transformation or lower probability of independence. The use of LMWH was associated with higher mortality (OR: 5.3, 95% CI: 1.8-15.5; p = 0.002), risk of SICH (OR: 8.4, 95% CI: 2.2-32.2; p = 0.002) and lower probability of achieving independence (OR: 0.3, 95% CI: 0.1-0.97; p = 0.043). Conclusions: The use of intravenous thrombolysis appears to be safe in patients previously treated with OA with INR levels <2 since there is no increase in SICH. The prior use of LMWH appears to increase the risk of SICH, death and dependence and, as such, the decision for systemic treatment with thrombolytic agents needs to be taken with caution in these cases. Larger case series are necessary to confirm these findings.

Efficacy of intravenous thrombolysis according to stroke subtypes: the Madrid Stroke Network data

To identify possible differences in the early response to intravenous thrombolysis (IVT) or in stroke outcome at 3 months, based on stroke subtype in patients with acute ischaemic stroke (IS).

Guía para el tratamiento preventivo del ictus isquémico y AIT (II). Recomendaciones según subtipo etiológico

BACKGROUND AND OBJECTIVE To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and Transient Ischaemic Attack (TIA). METHODS We reviewed the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype. Levels of evidence and recommendation levels are based on the classification of the Centre for Evidence-Based Medicine. RESULTS In atherothrombotic IS, antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis (70%-90%) reduce the risk of recurrences. In cardioembolic IS (atrial fibrillation, valvular diseases, prosthetic valves and myocardial infarction with mural thrombus) prevention is based on the use of oral anticoagulants. Preventive therapies for uncommon causes of IS will depend on the aetiology. In the case of cerebral venous thrombosis oral anticoagulation is effective. CONCLUSIONS We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient.

Tratamiento endovascular en el ictus isquémico agudo. Plan de Atención al Ictus en la Comunidad de Madrid

INTRODUCTION Endovascular therapies (intra-arterial thrombolysis and mechanical thrombectomy) after acute ischaemic stroke are being implemented in the clinical setting even as they are still being researched. Since we lack sufficient data to establish accurate evidence-based recommendations for use of these treatments, we must develop clinical protocols based on current knowledge and carefully monitor all procedures. DEVELOPMENT After review of the literature and holding work sessions to reach a consensus among experts, we developed a clinical protocol including indications and contraindications for endovascular therapies use in acute ischaemic stroke. The protocol includes methodology recommendations for diagnosing and selecting patients, performing revascularisation procedures, and for subsequent patient management. Its objective is to increase the likelihood of efficacy and treatment benefit and minimise risk of complications and ineffective recanalisation. Based on an analysis of healthcare needs and available resources, a cooperative inter-hospital care system has been developed. This helps to ensure availability of endovascular therapies to all patients, a fast response time, and a good cost-to-efficacy ratio. It includes also a prospective register which serves to monitor procedures in order to identify any opportunities for improvement. CONCLUSIONS Implementation of endovascular techniques for treating acute ischaemic stroke requires the elaboration of evidence-based clinical protocols and the establishment of appropriate cooperative healthcare networks guaranteeing both the availability and the quality of these actions. Such procedures must be monitored in order to improve methodology.

Questionable reversal of anticoagulation in the therapeutic management of cerebral haemorrhage associated with vitamin K antagonists

Reversal of anticoagulation is recommended to correct the international normalised ratio (INR) for patients with intracranial haemorrhage (ICH) associated with vitamin K antagonists (VKA). However, the validity of such treatment is debated. We sought to identify, prospectively, the prognostic effect of VKA-ICH treatment in a cohort of patients (n=71; median age 78 years, range 20-89; 52% males). Data collated were: baseline characteristics, treatments, baseline and post-treatment INR, haematoma volume, and haematoma enlargement. Treatment effects and prognostic factor assessment were in relation to mortality and functional outcomes. On admission, the patients had a median score of 9 [p25; p75 of 5; 20] on the National Institute of Health Stroke Scale (NIHSS) and a mean INR of 2.7 (range: 0.9 - 10.8). Haematoma volume (34.6 cm³; SD: 24.9) correlated with NIHSS (r = 0.55; p<0.001) but not with INR. Anticoagulation reversal treatment was administered in 83% of patients. INR <1.5 was achieved in 60.7% of cases. Death or dependency at three months was 76%. Neither baseline INR, anticoagulation reversal nor haematoma enlargement were related to mortality or functional outcome. The only independent prognostic factor was clinical severity on admission. Baseline NIHSS predicted mortality (OR: 1.18; 95%CI: 1.09-1.27), independence (OR: 0.83; 95%CI: 0.74-0.94) and neurological recovery (NIHSS 0-1) (OR: 0.83; 95%CI: 0.73-0.95). The data indicate that VKA-ICH had a poor prognosis. Treatment and INR correction did not appear to affect outcomes.

Diabetes and previous stroke: hazards for intravenous thrombolysis?

Background and purpose:  Alteplase licensing approval in Europe does not advocate intravenous thrombolysis (IVT) for diabetic ischaemic stroke (IS) patients with previous cerebral infarction (PCI). Our aim was to assess whether concomitant diabetes mellitus (DM) and PCI are associated with symptomatic intracerebral haemorrhage (SICH) and poor outcome after IVT.