Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.

The effect of post-stroke hyperglycaemia on the levels of brain damage and repair-related circulating biomarkers: the Glycaemia in Acute Stroke Study II.

BACKGROUND AND PURPOSE: The aim was to identify whether post-stroke hyperglycaemia (PSH) influences the levels of circulating biomarkers of brain damage and repair, and to explore whether these biomarkers mediate the effect of PSH on the ischaemic stroke (IS) outcome. METHODS: This was a secondary analysis of the Glycaemia in Acute Stroke II study. Biomarkers of inflammation, prothrombotic activity, endothelial dysfunction, blood-brain barrier rupture, cell death and brain repair processes were analysed at 24-48 h (baseline) and 72-96 h (follow-up) after IS. The associations of the biomarkers and stroke outcome (modified Rankin Scale score at 3 months) based on the presence of PSH were compared. RESULTS: A total of 174 patients participated in this sub-study. Brain-derived neurotrophic factor (BDNF) at admission was negatively correlated with glucose levels. PSH was associated with a trend toward higher levels of endothelial progenitor cells (EPCs) at baseline. The EPCs in the PSH group then decreased in the follow-up samples (-8.5 ± 10.3) compared with the non-PSH group (4.7 ± 7.33; P = 0.024). However, neither BDNF nor EPC values had correlation with the 3-month outcome. Higher interleukin-6 at follow-up was associated with poor outcomes (modified Rankin Scale > 2) independently of PSH. CONCLUSION: Post-stroke hyperglycaemia appears to be associated with a negative regulation of BDNF and a different reaction in EPC levels. However, neither BDNF nor EPCs showed significant mediation of the PSH association with IS outcome, and only higher interleukin-6 in the follow-up samples (72-96 h) was related to poor outcomes, independently of PSH status. Further studies are needed to achieve definite conclusions.

Glycemia in Acute Stroke II study: a call to improve post-stroke hyperglycemia management in clinical practice.

BACKGROUND AND PURPOSE: The aim of the study was to analyze the effect of conventional glucose management, which aimed to maintain glucose levels <155 mg/dL (8.5 mmol/L), on glucose control and the outcomes of patients with acute ischaemic stroke (IS) in a clinical practice setting. METHODS: This was a multicenter, prospective cohort study of patients with acute IS. Patients were classified into four groups based on their initial 48-h capillary glucose levels and the administration of and response to corrective treatment: (i) untreated and maximum glucose levels <155 mg/dL (8.5 mmol/L) within the first 48 h; (ii) treated and good responders [glucose levels persistently <155 mg/dL (8.5 mmol/L)]; (iii) treated and non-responders [any glucose values ≥155 mg/dL (8.5 mmol/L) during the 24 h after the start of corrective treatment]; and (iv) untreated with any glucose value ≥155 mg/dL (8.5 mmol/L). The primary outcome was death or dependence at 3 months (blinded rater). RESULTS: A total of 213 patients were included. Ninety-seven (45.5%) patients developed glucose levels ≥155 mg/dL (8.5 mmol/L), 69 (71.1%) underwent corrective treatment and 31 patients underwent no corrective treatment at the physician's discretion [28 of whom had isolated values ≥155 mg/dL (8.5 mmol/L)]. Only 11 (16%) patients responded to conventional treatment, whereas 58 (84%) patients were non-responsive. Non-responders showed a twofold higher risk of death or dependence at 3 months (odds ratio, 2.472; 95% confidence interval, 1.096-5.576; P = 0.029). CONCLUSIONS: Lack of response to conventional treatment for glucose management in acute IS is frequent and associated with poor outcomes.

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.

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.

Beyond hyperglycemia: glycaemic variability as a prognostic factor after acute ischemic stroke.

INTRODUCTION: Glycaemic variability (GV) refers to variations in blood glucose levels, and may affect stroke outcomes. This study aims to assess the effect of GV on acute ischaemic stroke progression. METHODS: We performed an exploratory analysis of the multicentre, prospective, observational GLIAS-II study. Capillary glucose levels were measured every 4 hours during the first 48 hours after stroke, and GV was defined as the standard deviation of the mean glucose values. The primary outcomes were mortality and death or dependency at 3 months. Secondary outcomes were in-hospital complications, stroke recurrence, and the impact of the route of insulin administration on GV. RESULTS: A total of 213 patients were included. Higher GV values were observed in patients who died (n = 16; 7.8%; 30.9 mg/dL vs 23.3 mg/dL; p = 0.05). In a logistic regression analysis adjusted for age and comorbidity, both GV (OR = 1.03; 95% CI, 1.003-1.06; p = 0.03) and stroke severity (OR = 1.12; 95% CI, 1.04-1.2; p = 0.004) were independently associated with mortality at 3 months. No association was found between GV and the other outcomes. Patients receiving subcutaneous insulin showed higher GV than those treated with intravenous insulin (38.95 mg/dL vs 21.34 mg/dL; p < 0.001). CONCLUSIONS: High GV values during the first 48 hours after ischaemic stroke were independently associated with mortality. Subcutaneous insulin may be associated with higher VG levels than intravenous administration.

Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy.

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-ß (Aß) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aß is also accumulated in Alzheimer's disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins. Methods: The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. Results: We observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS. Discussion: This study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral ß-amyloidosis.

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.

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.

Dyslipidemias and stroke prevention: Recommendations of the Study Group of Cerebrovascular Diseases of the Spanish Society of Neurology.

OBJECTIVE: We present an update of the Spanish Society of Neurology's recommendations for prevention of both primary and secondary stroke in patients with dyslipidaemia. DEVELOPMENT: We performed a systematic review to evaluate the main aspects of the management of dyslipidaemias in primary and secondary stroke prevention and establish a series of recommendations. CONCLUSIONS: In primary prevention, the patient's vascular risk should be determined in order to define target values for low-density lipoprotein cholesterol. In secondary prevention after an atherothrombotic stroke, a target value <55 mg/dL is recommended; in non-atherothombotic ischaemic strokes, given the unclear relationship with dyslipidaemia, target value should be established according to the vascular risk group of each patient. In both primary and secondary prevention, statins are the drugs of first choice, and ezetimibe and/or PCSK9 inhibitors may be added in patients not achieving the target value.

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.

Recommendations of the Spanish Society of Neurology for the prevention of stroke. Interventions on lifestyle and air pollution.

OBJECTIVE: To update the recommendations of the Spanish Society of Neurology regarding lifestyle interventions for stroke prevention. DEVELOPMENT: We reviewed the most recent studies related to lifestyle and stroke risk, including randomised clinical trials, population studies, and meta-analyses. The risk of stroke associated with such lifestyle habits as smoking, alcohol consumption, stress, diet, obesity, and sedentary lifestyles was analysed, and the potential benefits for stroke prevention of modifying these habits were reviewed. We also reviewed stroke risk associated with exposure to air pollution. Based on the results obtained, we drafted recommendations addressing each of the lifestyle habits analysed. CONCLUSIONS: Lifestyle modification constitutes a cornerstone in the primary and secondary prevention of stroke. Abstinence or cessation of smoking, cessation of excessive alcohol consumption, avoidance of exposure to chronic stress, avoidance of overweight or obesity, a Mediterranean diet supplemented with olive oil and nuts, and regular exercise are essential measures in reducing the risk of stroke. We also recommend implementing policies to reduce air pollution.

Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage.

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA-ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 ± 18.6 months) and long-term (38.5 ± 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as ≥2 lobar ICHs and ≥5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH.

Stroke prevention in patients with arterial hypertension: Recommendations of the Spanish Society of Neurology's Stroke Study Group.

OBJECTIVE: To update the recommendations of the Spanish Society of Neurology on primary and secondary stroke prevention in patients with arterial hypertension. DEVELOPMENT: We proposed several questions to identify practical issues for the management of blood pressure (BP) in stroke prevention, analysing the objectives of blood pressure control, which drugs are most appropriate in primary prevention, when antihypertensive treatment should be started after a stroke, what levels we should aim to achieve, and which drugs are most appropriate in secondary stroke prevention. We conducted a systematic review of the PubMed database and analysed the main clinical trials to address these questions and establish a series of recommendations. CONCLUSIONS: In primary stroke prevention, antihypertensive treatment should be started in patients with BP levels >  140/90 mmHg, with a target BP of < 130/80 mmHg. In secondary stroke prevention, we recommend starting antihypertensive treatment after the acute phase (first 24 hours), with a target BP of < 130/80 mmHg. The use of angiotensin-II receptor antagonists or diuretics alone or in combination with angiotensin-converting enzyme inhibitors is preferable.

Stroke prevention in patients with type 2 diabetes or prediabetes. Recommendations from the Cerebrovascular Diseases Study Group, Spanish Society of Neurology. / Prevención de ictus en pacientes con diabetes mellitus tipo 2 o prediabetes. Recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for stroke prevention in patients with type 2 diabetes or prediabetes, analysing the available evidence on the effect of metabolic control and the potential benefit of antidiabetic drugs with known vascular benefits in addition to conventional antidiabetic treatments in stroke prevention. DEVELOPMENT: PICO-type questions (Patient, Intervention, Comparison, Outcome) were developed to identify practical issues in the management of stroke patients and to establish specific recommendations for each of them. Subsequently, we conducted systematic reviews of the PubMed database and selected those randomised clinical trials evaluating stroke as an independent variable (primary or secondary). Finally, for each of the PICO questions we developed a meta-analysis to support the final recommendations. CONCLUSIONS: While there is no evidence that metabolic control reduces the risk of stroke, some families of antidiabetic drugs with vascular benefits have been shown to reduce these effects when added to conventional treatments, both in the field of primary prevention in patients presenting type 2 diabetes and high vascular risk or established atherosclerosis (GLP-1 agonists) and in secondary stroke prevention in patients with type 2 diabetes or prediabetes (pioglitazone).

The I/D polymorphism of the ACE1 gene is not associated with ischaemic stroke in Spanish individuals.

BACKGROUND: The angiotensin-converting enzyme 1 (ACE1) gene has been extensively studied in stroke, yet generating conflicting results. The goal of our study was thus to clarify the influence of the ACE1 on the risk of suffering an ischaemic stroke (IS). METHODS: We genotyped the rs4341 (in linkage disequilibrium with the I/D polymorphism) of the ACE1 gene in 531 patients with IS and 549 healthy controls, and the rs1799752 (I/D polymorphism) in a subset of 68 patients with IS and 27 controls. We also performed functional studies by measuring serum ACE protein levels and enzymatic activity in 27 controls, 68 patients with IS at baseline and 35 patients with IS 24 h after onset of stroke symptoms. RESULTS: There was no association of the ACE1 variant with IS, although it affected ACE protein levels (P = 0.001). Indeed, patients with IS showed lower ACE levels than controls in the acute phase (115.9 } 38.9 vs. 174.1 } 56.1 ng/ml, P < 0.001), but not in the chronic phase (168.2 } 51.2, P = 0.673), and ACE protein levels did not differ between IS etiologies. Similar results were found for ACE activity. CONCLUSIONS: The D allele of the ACE1 I/D and ACE protein levels was not associated with a higher risk of IS in Spanish individuals.

Beyond hyperglycemia: glycaemic variability as a prognostic factor after acute ischemic stroke. / Más allá de la hiperglucemia: la variabilidad glucémica como factor pronóstico en el infarto cerebral agudo.

INTRODUCTION: Glycaemic variability (GV) refers to variations in blood glucose levels, and may affect stroke outcomes. This study aims to assess the effect of GV on acute ischaemic stroke progression. METHODS: We performed an exploratory analysis of the multicentre, prospective, observational GLIAS-II study. Capillary glucose levels were measured every 4 hours during the first 48 hours after stroke, and GV was defined as the standard deviation of the mean glucose values. The primary outcomes were mortality and death or dependency at 3 months. Secondary outcomes were in-hospital complications, stroke recurrence, and the impact of the route of insulin administration on GV. RESULTS: A total of 213 patients were included. Higher GV values were observed in patients who died (n = 16; 7.8%; 30.9 mg/dL vs 23.3 mg/dL; p = 0.05). In a logistic regression analysis adjusted for age and comorbidity, both GV (OR = 1.03; 95% CI, 1.003-1.06; p = 0.03) and stroke severity (OR = 1.12; 95% CI, 1.04-1.2; p = 0.004) were independently associated with mortality at 3 months. No association was found between GV and the other outcomes. Patients receiving subcutaneous insulin showed higher GV than those treated with intravenous insulin (38.95 mg/dL vs 21.34 mg/dL; p < 0.001). CONCLUSIONS: High GV values during the first 48 hours after ischaemic stroke were independently associated with mortality. Subcutaneous insulin may be associated with higher VG levels than intravenous administration.

Dyslipidemias and stroke prevention: recommendations of the Study Group of Cerebrovascular Diseases of the Spanish Society of Neurology. / Dislipidemias y prevención del ictus: recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología.

OBJECTIVE: We present an update of the Spanish Society of Neurology's recommendations for prevention of both primary and secondary stroke in patients with dyslipidaemia. DEVELOPMENT: We performed a systematic review to evaluate the main aspects of the management of dyslipidaemias in primary and secondary stroke prevention and establish a series of recommendations. CONCLUSIONS: In primary prevention, the patient's vascular risk should be determined in order to define target values for low-density lipoprotein cholesterol. In secondary prevention after an atherothrombotic stroke, a target value <55mg/dL is recommended; in non-atherothombotic ischaemic strokes, given the unclear relationship with dyslipidaemia, target value should be established according to the vascular risk group of each patient. In both primary and secondary prevention, statins are the drugs of first choice, and ezetimibe and/or PCSK9 inhibitors may be added in patients not achieving the target value.