Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial.

BACKGROUND AND PURPOSE: Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated. METHODS: Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer. RESULTS: Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups. CONCLUSIONS: Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. www.clinicaltrials.gov (NCT02313909).

Plaque neovascularization detected with contrast-enhanced ultrasound predicts ischaemic stroke recurrence in patients with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Plaque neovascularization is a hallmark of carotid plaque vulnerability. With contrast-enhanced ultrasound (CEUS) it is possible to visualize plaque neovessels in vivo. Our aim was to determine if CEUS-detected neovessels were associated with stroke recurrences in patients with a recent stroke and carotid atherosclerosis. METHODS: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the internal carotid artery on the side consistent with symptoms. All of our patients underwent a carotid ultrasound examination including a CEUS study. Neovascularization was graded into three categories according to the extent of neovessels. During the follow-up, we recorded stroke recurrences. A multivariable Cox regression analysis was performed to evaluate predictors of recurrence. RESULTS: We included 78 patients whose mean age was 74.3 ± 10.4 years. There were 29 (37.2%) patients with a low-grade stenosis (<50%). The remainder presented moderate (50%-69%) or high-grade (≥70%) stenosis. CEUS was not interpretable in 35.9% of the patients, mainly due to calcium shadows. We detected neovascularization in 80% of the plaques. After a median follow-up of 14.1 (interquartile range, 9.5-19.6) months, there were 15 (19.2%) stroke recurrences. In the Cox regression analysis, CEUS-detected neovascularization was independently associated with the risk of stroke recurrence, even after adjusting for the degree of stenosis (hazard ratio, 6.57; 95% confidence interval, 1.66-26.01). CONCLUSION: In patients with an anterior circulation ischaemic stroke and carotid atherosclerosis, plaque neovascularization detected with CEUS was an independent predictor of stroke recurrence.

Insular damage, new-onset atrial fibrillation and outcome after acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Cortical insular damage is associated with cardiac arrhythmias and an increased risk of death. We investigated the influence of insular damage on the outcome of patients with acute intracerebral hemorrhage as well as the frequency and predictors of new-onset atrial fibrillation (nAF). METHODS: We studied consecutive patients with intracerebral hemorrhage from 2013 to 2016. We identified those patients who underwent continuous electrocardiographic monitoring (≥24 h), known atrial fibrillation and recent ischemic stroke. We prospectively collected demographic data, vascular risk factors, neurological severity, vital signs, radiological data, nAF and mortality at 3 months. Bivariate and multivariate regression analyses were performed. RESULTS: We evaluated 347 patients whose mean age was 73.5 ± 14.0 years (50.7% of them were men). We selected 183 patients to study the frequency and risk factors of nAF (mean age, 69.1 ± 14.7 years; 52.5% of them were men). We observed that 11/183 (6.0%) had nAF. Insular damage [odds ratio (OR), 7.6; 95% confidence interval (CI), 2.1-27.7] was associated with nAF. A total of 138/347 patients died within the first 3 months and insular damage was detected in 99/347 of them. Predictors of death were age (OR, 1.07; 95% CI, 1.04-1.10), blood glucose (OR, 1.00 per mg/dL;, 95% CI, 1.00-1.01), Glasgow Coma Scale score (OR, 0.85; 95% CI, 0.77-0.92), hematoma volume (OR, 1.02 per mL; 95% CI, 1.01-1.04), intraventricular hemorrhage (OR, 1.93; 95% CI, 1.03-3.64) and insular damage (OR, 3.98; 95% CI, 2.00-7.90). CONCLUSIONS: The frequency of nAF in our patients was 6.0%. Insular damage was a risk factor for nAF and an independent predictor of death at 3 months.

Does prior antiplatelet therapy influence hematoma volume and hematoma growth following intracerebral hemorrhage? Results from a prospective study and a meta-analysis.

BACKGROUND AND PURPOSE: Large baseline hematoma volume (HV) and hematoma growth (HG) are related to poor outcome in patients with intracerebral hemorrhage (ICH). It remains controversial whether prior antiplatelet therapy (APT) influences baseline HV and HG, and the outcome following ICH. METHODS: We collected clinical and radiological data from a prospective cohort of patients diagnosed with ICH within 24 h of symptom onset. Prior APT was ascertained from the clinical history. In patients for whom a follow-up computed tomography (CT) was available within 72 h, we assessed HG, defined as an increase of ≥33% and/or ≥12.5 mL in the HV. We assessed mortality and functional outcome during follow-up with the Rankin scale. To perform a meta-analysis, we searched for published studies reporting HG according to previous APT and pooled the available data. RESULTS: We included 223 patients (mean age 72.5 ± 13 years). Previous APT was reported in 74 patients (33.2%). The linear regression model showed that prior APT was independently associated with larger baseline HV. HG was detected in 49 of 130 patients (37.7%) and no differences related to prior APT were observed among our cohort. However, after pooling the data of seven studies in the meta-analysis, prior APT showed an increase in HG frequency (odds ratio, 1.85; 95% confidence interval, 1.37-2.5). Patients who received APT presented with worse outcome during follow-up, although this difference was not significant (P = 0.06). CONCLUSIONS: In the current study, prior APT was related to larger baseline HV in patients with ICH. Data from the meta-analysis also showed a higher risk of HG associated with APT.

Visual hallucinations in patients with acute stroke: a prospective exploratory study.

BACKGROUND AND PURPOSE: The incidence, underlying physiopathology, features and association with lesion topography of visual hallucinations in acute stroke have scarcely been investigated. METHODS: Patients with a diagnosis of acute stroke (ischaemic or haemorrhagic) in any vascular territory, admitted within 24 h after the onset of symptoms, were consecutively included in the study. Patients with a previous history of psychosis or cognitive impairment were excluded. They and/or their caregivers answered a structured hallucination and sleep questionnaire at admission, within the first 15 days and at the clinical follow-up 3-6 months after discharge. Lesion location (IMAIOS online atlas) and leukoaraiosis (Wahlund scale) were determined by magnetic resonance imaging or computed tomography scan. Subsets of patients also underwent a neuropsychological evaluation (N = 50) and an electroencephalogram (N = 33) before discharge. RESULTS: In all, 77 patients with a mean age of 71 ± 12 years were included of whom 57.1% were men. The incidence of visual hallucinations was 16.7%. These hallucinations were mostly complex, in black and white and self-limited. The appearance of hallucinations was not influenced by age, sex, neuropsychological performance during admission or modified Rankin scale score at discharge. Visual hallucinations were associated with occipital cortex lesions (P = 0.04), and with sleep disturbances during and before admission (P = 0.041 and P = 0.03 respectively). CONCLUSIONS: Visual hallucinations are relatively frequent in patients with acute stroke and they are self-limited. Patients with occipital lesions and sleep disturbances are more likely to suffer them.

Frequency and outcome of total anterior circulation strokes without intracranial large-vessel occlusion.

BACKGROUND AND PURPOSE: The percentage of patients with clinical total anterior circulation infarct (TACI) syndrome treated with reperfusion therapies in the absence of intracranial large-vessel occlusion (ILVO) was determined and their characteristics and outcome are described. METHODS: Data from a population-based, prospective, externally audited registry of all stroke patients treated with intravenous thrombolysis (IVT) and endovascular therapies in Catalonia from January 2011 to December 2013 were used. Patients with a baseline TACI and initial stroke severity measured by the National Institute of Health Stroke Scale (NIHSS) ≥ 8, evaluated less than 4.5 h post-onset, for whom a vascular study prior to treatment was available (n = 1070) were selected. Clinical characteristics, outcome and radiological data for patients treated with IVT alone (n = 605) were compared between those with detected ILVO (n = 474) and non-ILVO patients (n = 131). RESULTS: A total of 1070 patients met study criteria; non-ILVO was found in 131 (12.2%). Analysing the 605 patients treated only with IVT, no significant differences were found between non-ILVO and ILVO patients in age, sex, risk factors, time-to-treatment and type of radiological studies performed. Although non-ILVO patients had lower initial stroke severity (P < 0.001) and a better prognosis (P = 0.001), 51.3% had a poor outcome and 16% were deceased at 90 days. In 66.4% of patients without ILVO, a recent anterior territorial infarct was detected. CONCLUSIONS: Intracranial artery patency was observed in 12.2% of TACI patients evaluated within 4.5 h. Although absence of ILVO was associated with slightly better prognosis, more than half had a poor outcome at 3 months.

Guidelines for the preventive treatment of ischaemic stroke and TIA (II). Recommendations according to aetiological sub-type.

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.

Guidelines for the treatment of acute ischaemic stroke.

INTRODUCTION: Update of Acute Ischaemic Stroke Treatment Guidelines of the Spanish Neurological Society based on a critical review of the literature. Recommendations are made based on levels of evidence from published data and studies. DEVELOPMENT: Organized systems of care should be implemented to ensure access to the optimal management of all acute stroke patients in stroke units. Standard of care should include treatment of blood pressure (should only be treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155 mg/dl, and treatment of body temperature with antipyretic drugs if it rises above 37.5 °C. Neurological and systemic complications must be prevented and promptly treated. Decompressive hemicraniectomy should be considered in cases of malignant cerebral oedema. Intravenous thrombolysis with rtPA should be administered within 4.5 hours from symptom onset, except when there are contraindications. Intra-arterial pharmacological thrombolysis can be considered within 6 hours, and mechanical thrombectomy within 8 hours from onset, for anterior circulation strokes, while a wider window of opportunity up to 12-24 hours is feasible for posterior strokes. There is not enough evidence to recommend routine use of the so called neuroprotective drugs. Anticoagulation should be administered to patients with cerebral vein thrombosis. Rehabilitation should be started as early as possible. CONCLUSION: Treatment of acute ischaemic stroke includes management of patients in stroke units. Systemic thrombolysis should be considered within 4.5 hours from symptom onset. Intra-arterial approaches with a wider window of opportunity can be an option in certain cases. Protective and restorative therapies are being investigated.

Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and treatment.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. MATERIAL AND METHODS: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. RESULTS: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. CONCLUSIONS: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes.

Predictive value of brain and vascular imaging including intracranial vessels in transient ischaemic attack patients: external validation of the ABCD3-I score.

BACKGROUND AND PURPOSE: Recently, brain and vascular imaging have been added to clinical variables to identify patients with transient ischaemic attack (TIA) with a high risk of stroke recurrence. The aim of our study was to externally validate the ABCD3-I score and the same score taking into account intracranial circulation. METHODS: We analyzed data from 1137 patients with TIA from the PROMAPA study who underwent diffusion-weighted magnetic resonance imaging (DWI) within 7 days of symptom onset. Clinical variables and diagnostic work-up were recorded prospectively. The end-points were subsequent stroke at 7 and 90 days follow-up. RESULTS: A total of 463 (40.7%) subjects fulfilled all inclusion criteria. During follow-up, eight patients (1.7%) had a stroke within 7 days, and 14 (3.1%) had a stroke within 3 months. In the Cox proportional hazard multivariate analyses, the combination of large-artery atherosclerosis and positive DWI remained as independent predictors of stroke recurrence at 7- and 90-day follow-up [HR 8.23, 95% confidence interval (CI) 2.89-23.46, P < 0.001]. The ABCD3-I score was a powerful predictor of subsequent stroke. The area under the receiver operating characteristic curve was 0.83 (95% CI 0.72-0.93) at 7 days and 0.69 (95% CI 0.53-0.85) at 90 days. When we include intracranial vessel disease in the score, the area under the curve increases but the difference observed was non-significant. CONCLUSION: The inclusion of vascular and neuroimaging information to clinical scales (ABCD3-I score) provides important prognostic information and also helps management decisions, although it cannot give a complete distinction between high-risk and low-risk groups.

Clinical practice guidelines in intracerebral haemorrhage.

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.

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.

[Limitations of anticoagulant therapy]. / Limitaciones del tratamiento anticoagulante.

Vitamin K antagonists have been shown to be effective in the primary and secondary prevention of systemic and cerebral emboli in patients with cardiac causes of embolism, especially atrial fibrillation. The reduced risk of stroke is greater in secondary prevention, although this reduction is accompanied by an inherent risk of hemorrhagic complications, among which cerebral hemorrhage is especially serious. The therapeutic window of these agents is limited and the best benefit/risk profile is obtained with an INR of between 2 and 3. The anticoagulant effect obtained shows marked variability, requiring frequent clinical and laboratory monitoring of the treatment. The introduction of oral anticoagulants that would aid the administration of these agents with equal or greater efficacy and lower risk is required.

[Intracerebral hemorrhage in anticoagulated patients: what do we do afterwards?]. / Hemorragias intracerebrales en pacientes anticoagulados, ¿qué hacemos después?

INTRODUCTION: The management of antithrombotic therapy after intracerebral hemorrhage (ICH) in anticoagulated patients is not well defined. We analyzed the risks and benefits of antiplatelet therapy (AG) against the resumption of anticoagulation with vitamin K antagonists (AVK) in a series of patients. MATERIAL AND METHODS: Retrospective study of ICH in anticoagulated patients. We registered demographic data, history of hypertension (HT), time of follow-up and new cerebral vascular events (ICH, stroke [IC]). RESULTS: We evaluated 88 patients, mean age 69±9 years, 50% men, 73% hypertensive. During the acute phase 18 patients died and the follow-up was lost in 31. Of the remaining (n=39), AVKs were resumed in 25 and changed to AG in 14. Comparing the characteristics of both groups, the anticoagulated group was younger (P=.005) and the embolic sources were more often of higher risk (P=.003). After an average follow-up of 54±31 months, the distribution of events was: IC (AVKs 8%, AG 14.3%, P=.6), ICH (AVKs 24%, AG 7.1%, P=.38), IC or ICH (AVKs 32%, AG 21.4%, P=.48) and death (AVKs 29%, AG 7.1%, P=.21). This trend of increased risk of new events in patients with AVKs was confirmed by Kaplan-Meier curves, although without statistical differences. CONCLUSIONS: Restarting AVK treatment after ICH in anticoagulated patients could increase the risk of new bleeding events and mortality. Prospective studies are needed to define a better and appropriate antithrombotic therapy after ICH related with anticoagulation.

Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update on risk factors and life style.

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.

In-hospital stroke: a multi-centre prospective registry.

BACKGROUND: in-hospital strokes (IHS) are relatively frequent. Avoidable delays in neurological assessment have been demonstrated. We study the clinical characteristics, neurological care and mortality of IHS. METHODS: multi-centre 1-year prospective study of IHS in 13 hospitals. Demographic and clinical characteristics, admission diagnosis, quality of care, thrombolytic therapy and mortality were recorded. RESULTS: we included 273 IHS patients [156 men; 210 ischaemic strokes (IS), 37 transient ischaemic attacks (TIA) and 26 cerebral haemorrhages]. Mean age was 72 ± 12 years. Cardiac sources of embolism were present in 138 (50.5%), withdrawal of antithrombotic drugs in 77 (28%) and active cancers in 35 (12.8%). Cardioembolic stroke was the most common subtype of IS (50%). Reasons for admission were programmed or urgent surgery in 70 (25%), cardiac diseases in 50 (18%), TIA or stroke in 30 (11%) and other medical illnesses in 71 (26%). Fifty-two per cent of patients were evaluated by a neurologist within 3 h of stroke onset. Thirty-three patients received treatment with tPA (15.7%). Thirty-one patients (14.7%) could not be treated because of a delay in contacting the neurologist. During hospitalization, 50 patients (18.4%) died, 41 of them because of the stroke or its complications. CONCLUSIONS: cardioembolic IS was the most frequent subtype of stroke. Cardiac sources of embolism, active cancers and withdrawal of antithrombotic drugs constituted special risk factors for IHS. A significant proportion of patients were treated with thrombolysis. However, delays in contacting the neurologist excluded a similar proportion of patients from treatment. IHS mortality was high, mostly because of stroke.

Diagnosis of CADASIL disease in normotensive and non-diabetics with lacunar infarct.

BACKGROUND: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is characterized by recurrent cerebral ischemic episodes of the lacunar subtype usually without traditional vascular risk factors. We investigated the frequency of CADASIL among selected patients with cerebral ischemia of the lacunar subtype. METHODS: we studied patients under 65 years old who presented cerebral ischemia of the lacunar subtype without hypertension, diabetes mellitus or other causes that explained the cerebral ischemia. On the skin biopsies, we performed immunostaining analysis on 5µm frozen sections with monoclonal antibody anti-Notch 3 (1E4). We also performed a genetic analysis of the Notch 3 gene (exons 3,4,5,6,11 and 19). RESULTS: of 1.519 patients analyzed, only 57 (3.7%) fulfilled the selection criteria, and 30 of them accepted to participated in the study. We studied 30 patients, mean age was 53 years (range 34 to 65), 50% were men and all patients suffered a lacunar stroke. Immunostaining analysis was positive in two patients (6.6%) and the genetic analysis confirmed a mutation characteristic of CADASIL in exon 4 nt 622C/T (Arg 182 Cys) and 694 T/C (Cys206Arg) respectively. CONCLUSIONS: CADASIL disease was present in 6.6% of patients younger than 65 years with a lacunar stroke and without hypertension or diabetes mellitus. Screening for CADASIL should be considered in these patients.

European Stroke Organisation (ESO) standard operating procedure for the preparation and publishing of guidelines.

The first European Stroke Organization (ESO) standard operating procedure (SOP) published in 2015 aimed at the implementation the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to provide evidence-based guidelines for stroke management. This second ESO-SOP is aiming at further increase of the practicability of ESO guidelines and its technical implications. Authors comprised of the members of the ESO guideline Board and ESO Executive Committee. The final document was agreed on by several internal reviews. The second SOP comprises of the following aspects: rational for the SOP, the introduction of expert consensus statements, types of guideline documents, structures involved and detailed description of the guideline preparation process, handling of financial and intellectual conflicts of interest (CoI), involvement of ESO members in the guideline process, review process, authorship and publication policy, updating of guidelines, cooperation with other societies, and dealing with falsified data. This second SOP supersedes the first SOP published in 2015.