Glycemic variability: prognostic impact on acute ischemic stroke and the impact of corrective treatment for hyperglycemia. The GLIAS-III translational study.

INTRODUCTION: Glycemic variability (GV) represents the amplitude of oscillations in glucose levels over time and is associated with higher mortality in critically ill patients. Our aim is to evaluate the impact of GV on acute ischemic stroke (IS) outcomes in humans and explore the impact of two different insulin administration routes on GV in an animal model. METHODS: This translational study consists of two studies conducted in parallel: The first study is an observational, multicenter, prospective clinical study in which 340 patients with acute IS will be subcutaneously implanted a sensor to continuously monitor blood glucose levels for 96 h. The second study is a basic experimental study using an animal model (rats) with permanent occlusion of the middle cerebral artery and induced hyperglycemia (through an intraperitoneal injection of nicotinamide and streptozotocin). The animal study will include the following 6 groups (10 animals per group): sham; hyperglycemia without IS; IS without hyperglycemia; IS and hyperglycemia without treatment; IS and hyperglycemia and intravenous insulin; and IS and hyperglycemia and subcutaneous insulin. The endpoint for the first study is mortality at 3 months, while the endpoints for the animal model study are GV, functional recovery and biomarkers. DISCUSSION: The GLIAS-III study will be the first translational approach analyzing the prognostic influence of GV, evaluated by the use of subcutaneous glucose monitors, in acute stroke. Trial registration https://www.clinicaltrials.gov (NCT04001049).

Impact of COVID-19 outbreak on ischemic stroke admissions and in-hospital mortality in North-West Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries heavily stricken by COVID-19. But this epidemic has not affected all regions equally. We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain. METHODS: Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality. RESULTS: In the study period, 2737 patients were admitted with ischemic stroke. There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001). In-hospital mortality of stroke patients increased significantly (9.9% vs. 6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs. 16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504). CONCLUSION: We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain. There were regional changes within the network, not fully explained by the severity of the pandemic in different regions.

PATJ Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome.

RATIONALE: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. OBJECTIVE: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. METHODS AND RESULTS: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, ß=0.40, P=1.70×10-9). CONCLUSIONS: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.

Combination of Thrombolysis and Statins in Acute Stroke Is Safe: Results of the STARS Randomized Trial (Stroke Treatment With Acute Reperfusion and Simvastatin).

BACKGROUND AND PURPOSE: The STARS trial (Stroke Treatment With Acute Reperfusion and Simvastatin) was conducted to demonstrate the efficacy and safety of simvastatin treatment in acute stroke. METHODS: STARS07 was a multicentre, phase IV, prospective, randomized, double-blind, placebo-controlled trial. Patients with Acute ischemic stroke recruited within 12 hours from symptom onset were randomized to oral simvastatin 40 mg or placebo, once daily for 90 days. Primary outcome was proportion of independent patients (modified Rankin Scale score of ≤2) at 90 days. Safety end points were hemorrhagic transformation, hemorrhagic events, death, infections, and serious adverse events. RESULTS: From April 2009 to March 2014, 104 patients were included. Fifty-five patients received intravenous tissue-type plasminogen activator. No differences were found between treatment arms regarding the primary outcome (adjusted odds ratio, 0.99 [0.35-2.78]; P=0.98). Concerning safety, no significant differences were found in the rate of hemorrhagic transformation of any type, nor symptomatic hemorrhagic transformation. There were no differences in other predefined safety outcomes. In post hoc analyses, for patients receiving tissue-type plasminogen activator, a favorable effect for simvastatin treatment was noted with higher proportion of patients experiencing major neurological recovery (adjusted odds ratio, 4.14 [1.18-14.4]; P=0.02). CONCLUSIONS: Simvastatin plus tissue-type plasminogen activator combination seems safe in acute stroke, with low rates of bleeding complications. Because of the low recruitment, the STARS trial was underpowered to detect differences in simvastatin efficacy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01073007.

Guía de actuación clínica en la hemorragia subaracnoidea. Sistemática diagnóstica y tratamiento / Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and treatment

OBJETIVO: Actualización de la guía para el diagnóstico y tratamiento de la hemorragia subaracnoidea de la Sociedad Española de Neurología. MATERIAL Y MÉTODOS: Revisión y análisis de la bibliografía existente. Se establecen recomendaciones en función del nivel de evidencia que ofrecen los estudios revisados. RESULTADOS: La causa más frecuente de hemorragia subaracnoidea espontánea (HSA) es la rotura de un aneurisma cerebral. Su incidencia se sitúa en torno 9 casos por 100.000 habitantes/año y supone un 5% de todos los ictus. La hipertensión arterial y el tabaquismo son sus principales factores de riesgo. Se ha de realizar el tratamiento en centros especializados. Se debe considerar el ingreso en unidades de ictus de aquellos pacientes con HSA y buena situación clínica inicial (grados I y II en la escala de Hunt y Hess). Se recomienda la exclusión precoz de la circulación del aneurisma. El estudio diagnóstico de elección es la tomografía computarizada (TC) craneal sin contraste. Si esta es negativa y persiste la sospecha clínica se aconseja realizar una punción lumbar. Los estudios de elección para identificar la fuente de sangrado son la resonancia magnética (RM) y la angiografía. Los estudios ultrasonográficos son útiles para el diagnóstico y seguimiento del vasoespasmo. Se recomienda el nimodipino para la prevención de la isquemia cerebral diferida. La terapia hipertensiva y el intervencionismo neurovascular pueden plantearse para tratar el vasoespasmo establecido. CONCLUSIONES: La HSA es una enfermedad grave y compleja que debe ser atendida en centros especializados, con suficiente experiencia para abordar el proceso diagnóstico y terapéutico

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

Guía para el tratamiento preventivo del ictus isquémico y AIT (II). Recomendaciones según subtipo etiológico / Guidelines for the preventive treatment of ischaemic stroke and TIA (II). Recommendations according to aetiological sub-type

FUNDAMENTO Y OBJETIVO: Actualizar las guías terapéuticas del Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN en el tratamiento preventivo de ictus isquémico (II) y ataque isquémico transitorio (AIT). MÉTODOS: Revisión de evidencias disponibles sobre la prevención del ictus isquémico y AIT en función del subtipo etiológico. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia. RESULTADOS: En el II de origen aterotrombótico reducen el riesgo de recurrencias el tratamiento antiagregante y los procedimientos revascularizadores en casos seleccionados de estenosis carotidea ipsilateral (70-99%). La prevención de II de origen cardioembólico (fibrilación auricular, valvulopatías, prótesis valvulares y en infarto de miocardio con trombo mural) se basa en el uso de anticoagulantes orales. En el II de origen inhabitual, las terapias preventivas dependerán de la etiología; en la trombosis venosa cerebral la anticoagulación oral es eficaz. CONCLUSIONES: Se concluye con recomendaciones de práctica clínica en prevención de ictus isquémico y AIT adaptadas al subtipo etiológico de II que ha presentado el paciente

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

Infartos cerebrales intrahospitalarios: datos del registro multicéntrico de pacientes con infarto cerebral ingresados en Cardiología y Cirugía Cardiaca / In-hospital ischemic strokes in patients admitted to Cardiology and Cardiac Surgery departments. Multi-centre registry

Fundamento y objetivo: Los pacientes ingresados en Cardiología y Cirugía Cardiaca tienen un riesgo importante de sufrir un infarto cerebral (IC). Analizamos las características clínicas, calidad de la atención neurológica y la evolución de los ictus intrahospitalarios (IIH) en estos servicios. Pacientes y método:Registro prospectivo de IC en pacientes ingresados en Cardiología y Cirugía Cardiaca en 13 hospitales españoles durante 2008. Recogemos datos demográficos, clínicos, terapéuticos, evolutivos y de mortalidad. Resultados: Registramos 73 casos. La edad media (DE) fue de 72 (11,6) años. El 75,4% de los IC fueron cardioembólicos. Como factores de riesgo para ictus destacaron: presencia de cardiopatías embolígenas (86,3%), suspensión del tratamiento antitrombótico previo (22%) y procedimientos invasivos (65,7%). La evaluación neurológica se hizo en menos de 3 horas en el 49,5% y pasadas 24 horas del IC en el 20,5%. Diez pacientes fueron tratados con trombólisis intravenosa, 8 no pudieron ser tratados por el retraso en avisar a Neurología. Entre las contraindicaciones para trombólisis destacaron la anticoagulación en rango (38%) y la cirugía reciente (33,3%). A los 3 meses, la mortalidad fue del 15% y solamente el 53,7% eran independientes. Los pacientes tratados con trombólisis tuvieron mejor evolución (87,5% de pacientes independientes, p=0,04).Conclusiones: Los IC intrahospitalarios en Cardiología y Cirugía Cardiaca son fundamentalmente cardioembólicos y producen una gran proporción de pacientes dependientes. Los pacientes tratados con trombólisis tuvieron mejor evolución clínica. El retraso en la llamada a Neurología impidió que una proporción relevante de pacientes fueran tratados con trombólisis intravenosa (AU)

Background and objective: Patients admitted to Cardiology and Cardiac Surgery Departments have an increased risk of ischemic stroke (IS). We analyzed clinical characteristics, quality of neurological care and mortality of in-hospital strokes (IHS) in these departments. Patients and method:Prospective registry of in-hospital ISs in Cardiology and Cardiac Surgery in 13 Spanish hospitals during 2008. Demographic, clinical and therapeutic data as well as mortality and functional evolution were recorded. Results: 73 patients were included. Mean age was 72±11.6 years. 75.4% of IS were cardioembolic. Special risk factors were presence of cardiac sources of embolism (86.3%), prior withdrawal of antithrombotic treatment (22%) and invasive procedures (65.7%). First neurological assessment was done in the first 3hours in 49.5% and beyond 24hours from IS onset in 20.5%. Ten patients were treated with intravenous thrombolysis, which was not possible in 8 patients because of the delay in calling the neurologist. Most frequent reasons for exclusion from thrombolytic therapy were recent major surgical procedures (33.3%) and anticoagulant therapy (38%). Three-month mortality was 15% and only 53.7% were functionally independent. Patients treated with thrombolysis had a better evolution (87.5% of independent patients, p=0.04). Conclusions: IS in Cardiology and Cardiac Surgery are mostly cardioembolic strokes and produce a high proportion of dependent patients. Patients treated with thrombolysis had a better evolution. Delays in contacting the neurologist led to exclusion from treatment an important proportion of patients who met thrombolysis criteria (AU)

[In-hospital ischemic strokes in patients admitted to Cardiology and Cardiac Surgery departments. Multi-centre registry]. / Infartos cerebrales intrahospitalarios: datos del registro multicéntrico de pacientes con infarto cerebral ingresados en Cardiología y Cirugía Cardiaca.

BACKGROUND AND OBJECTIVE: Patients admitted to Cardiology and Cardiac Surgery Departments have an increased risk of ischemic stroke (IS). We analyzed clinical characteristics, quality of neurological care and mortality of in-hospital strokes (IHS) in these departments. PATIENTS AND METHOD: Prospective registry of in-hospital ISs in Cardiology and Cardiac Surgery in 13 Spanish hospitals during 2008. Demographic, clinical and therapeutic data as well as mortality and functional evolution were recorded. RESULTS: 73 patients were included. Mean age was 72±11.6 years. 75.4% of IS were cardioembolic. Special risk factors were presence of cardiac sources of embolism (86.3%), prior withdrawal of antithrombotic treatment (22%) and invasive procedures (65.7%). First neurological assessment was done in the first 3hours in 49.5% and beyond 24hours from IS onset in 20.5%. Ten patients were treated with intravenous thrombolysis, which was not possible in 8 patients because of the delay in calling the neurologist. Most frequent reasons for exclusion from thrombolytic therapy were recent major surgical procedures (33.3%) and anticoagulant therapy (38%). Three-month mortality was 15% and only 53.7% were functionally independent. Patients treated with thrombolysis had a better evolution (87.5% of independent patients, p=0.04). CONCLUSIONS: IS in Cardiology and Cardiac Surgery are mostly cardioembolic strokes and produce a high proportion of dependent patients. Patients treated with thrombolysis had a better evolution. Delays in contacting the neurologist led to exclusion from treatment an important proportion of patients who met thrombolysis criteria.