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Resumen Introduccion La variabilidad glucemica (VG) hace referencia a las oscilaciones en los niveles de glucosa en sangre y podria influir en el pronostico del ictus. Objetivo: Analizar el efecto de la VG en la evolucion del infarto cerebral agudo (IC). Metodos Analisis exploratorio del estudio GLIAS-II (multicentrico, prospectivo y observacional). Se midieron los niveles de glucemia capilar cada cuatro horas durante las primeras 48 horas y la VG se definio como la desviacion estandar de los valores medios. Variables principales: mortalidad y muerte o dependencia a los tres meses. Variables secundarias: porcentaje de complicaciones intrahospitalarias y de recurrencia de ictus, e influencia de la via de administracion de insulina sobre la VG. Resultados Se incluyeron 213 pacientes. Los pacientes que fallecieron (N = 16;7,8%) presentaron mayores valores de VG (30,9 mg/dL vs. 23,3 mg/dL; p = 0,05). En el analisis de regresion logistica ajustado por edad y comorbilidad, tanto la VG (OR = 1,03; IC del 95%: 1,003-1,06: p = 0,03) como la gravedad del IC (OR = 1,12; IC del 95%: 1,04-1,2; p = 0,004) se asociaron de forma independiente con la mortalidad a los tres meses. No se encontro asociacion entre la VG y las demas variables de estudio. Los pacientes que recibieron tratamiento con insulina subcutanea mostraron una mayor VG que los tratados con insulina intravenosa (38,9 mg/dL vs. 21,3 mg/dL; p Conclusiones Valores elevados de VG durante las primeras 48 horas tras el IC se asociaron de forma independiente con la mortalidad. La administracion subcutanea de insulina podria condicionar una mayor VG que la via intravenosa.

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.

Acute, painless, monocular vision loss (APMVL) usually has a vascular aetiology. We conducted a prospective observational study from 2011 to 2018 to analyse the added value of colour Doppler imaging to assess orbital vessel blood flow in the diagnosis of APMVL. The study included 67 patients (39 [58.2%] men; mean age, 65.9 years [SD 13.7]) with APMVL evaluated at the Neurosonology Laboratory within the first 5 days of symptom onset, who were classified as having either transient or persistent monocular blindness. The blood flow in the ophthalmic and central retinal arteries was assessed using colour Doppler ultrasound with a linear 7.5-MHz transducer. Thirty-three (49.3%) patients presented transient monocular blindness, with reduced blood flow in either the ophthalmic or central retinal artery. The group with persistent vision loss included 24 cases of central retinal artery occlusion (CRAO) and 10 cases of ischaemic optic neuropathy (35.8% and 14.9%, respectively, of the total sample). These patients were older and had a higher prevalence of hypertension and mild carotid atherosclerosis. Orbital colour Doppler ultrasound (OCDUS) clarified the mechanism/cause of the ischaemia in 11 (16.4%) patients and showed abnormal flow in 46 (68.7%) patients, confirming the vascular origin in 19 (57.6%) of the transient monocular blindness cases. Lower peak systolic velocity was observed in patients with CRAO ( p < 0.001), and a velocity < 10 cm/s in the central retinal artery was independently associated with the diagnosis of CRAO. OCDUS can be helpful in confirming the vascular cause and identifying the aetiology of APMVL.

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up. Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change. Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence. Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence., This study was supported by grants from the Foundation for Biomedical Research of La Paz University Hospital (PI 1131)

Introduction: The degree of disability after stroke needs to be objectively measured to implement adequate rehabilitation programs. Here, we evaluate the feasibility of a custom-built software to assess motor status after stroke.Methods: This is a prospective, case–control pilot study comparing stroke patients with healthy volunteers. A workout evaluation that included trunk and upper limb movement was captured with Kinect® and kinematic metrics were extracted with Akira®. Trunk and joint angles were analyzed and compared between cases and controls. Patients were evaluated within the first week from stroke onset using the National Institutes of Health Stroke Scale (NIHSS), Fulg-Meyer Assessment (FMA), and modified Rankin Scale (mRS) scales; the relationship with kinematic measurements was explored.Results: Thirty-seven patients and 33 controls were evaluated. Median (IQR) NIHSS of cases was 2 (0–4). The kinematic metrics that showed better discriminatory capacity were body sway during walking (less in cases than in controls, p = 0.01) and the drift in the forearm–trunk angle during shoulder abduction in supination (greater in cases than in controls, p = 0.01). The body sway during walking was moderately correlated with NIHSS score (Rho = −0.39; p = 0.01) but better correlated with mRS score (Rho = −0.52; p < 0.001) and was associated with the absence of disability (mRS 0–1) (OR = 0.64; p = 0.02). The drift in the forearm–trunk angle in supination was associated with the presence of disability (mRS >1) (OR = 1.27; p = 0.04).Conclusion: We present a new software that detects even mild motor impairment in stroke patients underestimated by clinical scales but with an impact on patient functionality.

Resumen El ictus criptogenico se define como aquel para el que no encontramos una etiologia. Sin embargo, existe cierta heterogeneidad en los criterios para definir un ictus criptogenico entre las diferentes clasificaciones etiologicas de uso habitual. Los avances en sistemas de monitorizacion y deteccion de fuentes cardioembolicas, el avance de las tecnicas de neuroimagen para la caracterizacion de la placa de ateroma, asi como la mayor evidencia de la implicacion del foramen oval permeable en el riesgo de ictus en pacientes jovenes, hacen que cada vez menos ictus queden sin un diagnostico etiologico. Realizamos una revision critica del concepto de ictus criptogenico como un «no diagnostico», resaltando la importancia de realizar un estudio diagnostico completo, evitando simplificaciones que pueden llevar a agrupar diferentes entidades que, aunque no identificadas, podrian subyacer al ictus criptogenico y, por tanto, a aplicar el mismo tratamiento preventivo a todas ellas, con resultados inciertos.

Background: Pre-clinical studies on adipose tissue-derived mesenchymal stem cells (AD-MSC) suggest its efficacy and safety for ischemic stroke (IS). Our aim was to evaluate the safety of a single dose of AD-MSC administered intravenously in acute IS patients. Methods: A phase II, randomised, double-blind, placebo-controlled, single-center, pilot clinical trial. We included patients aged ≥ 60 years, with moderate to severe IS. Patients were randomly assigned (1:1 ratio) to receive either 1M cells/kg AD-MSC or placebo within the first two weeks after the onset of an IS. The primary outcome measure was safety (adverse events, neurological and systemic complications, and tumor developments). Secondary outcomes explored efficacy (modified Rankin Scale (mRS) and NIHSS). Here we report the preliminary results at 6 months of follow-up. EudraCT: 2011-003551-18; NCT01678534. Findings: Recruitment was stopped in December 2017 after including 19 out of the 20 planned patients. Six patients did not receive the study treatment (3 for technical reasons and 3 because they presented exclusion criteria after randomisation). The final sample was composed of 13 patients (4 in the AD-MSC and 9 in the placebo group). One patient from the placebo group died within the first 7 days due to sepsis. Serious adverse events at 6 months were reported in 5.1% of the AD-MSC group and in 6.6% in the placebo group. No injection-related adverse events or tumour developments were reported. After 6 months of follow-up there were no significant differences between the groups in median NIHSS scores [2.5 (IQR 1.75, 3.50) vs. 5 (IQR 4.0, 7.50)] and median mRS [3 (IQR 3.0, 3.25) vs. 4 (IQR 3.0, 4.0)]. Interpretation: Intravenous administration of AD-MSC within the first 2 weeks from IS onset seems to be safe at 6-months of follow-up and shows a trend toward improving neurological and functional recovery. Trial Registration: The study was registered at Clinicaltrials.gov, under the number NCT01678534. Funding Statement: Spanish Ministry of Health (EC2010/171). Declaration of Interests: B Fuentes reports grants from Spanish Ministry of Health and European Commission (Horizon2020 program), during the conduct of the study; other from Daichi-Sankyo, other from Bayer, other from BMS-Pfizer, other from Novonordisk, other from Novartis, outside the submitted work; M Gutierrez-Fernandez rports grants from Spanish Ministry of Health and European Commission (Horizon2020 program), during the conduct of the study; non-financial support from Cellerix/Tigenix, non-financial support from Histocell, outside the submitted work.AM Borobia reports grants from Instituto de Salud Carlos III, during the conduct of the study; personal fees from Mundipharma, personal fees from Menarini, outside the submitted work; and Principal Investigator in Clinical Trials for GSK and Daiichi Sankyo. E Diez-Tejedor reports grants from Spanish Ministry of Health and European Commission (Horizon2020 program), during the conduct of the study; non-financial support from Cellerix/Tigenix, non-financial support from Histocell, other from Daichi-Sankyo, other from Bayer, other from Sanofy Aventis, other from Novartis outside the submitted work. R Gutierrez-Zuniga, M Alonso de Lecinana, JC Martinez Avila, G Ruiz-Ares, MC Gomez-de Frutos, F Laso-Garcia and L Otero-Ortega report nothing to disclosure. Ethics Approval Statement: It was approved by the La Paz University Hospital Research Ethics Committee and by the Spanish Agency of Medicines and Health Products (EudraCT: 2011-003551-18).

Backgrounds: Diabetes Mellitus (DM) has been widely associated with poor outcome after an ischemic stroke (IS). However the underlying mechanisms are not well elucidated. We aim to study whether the outcome in stroke patients with DM is independent of comorbidity, the development of poststroke hyperglycaemia or due to higher glycaemic variability. Methods: Secondary analysis of the GLIAS-II study (multicenter, prospective, observational academic cohort study). We compared outcomes (in-hospital complications; mortality; death or dependence (mRS >2); and stroke recurrence at 3 months) in two study groups: patients with prior diagnosis of DM (DM group) vs. patients without DM (non DM group). We performed multivariate analysis in order to adjust the effect of DM on stroke outcomes by comorbidity (Charlson index), poststroke hyperglycaemia (>155 mg/dL) during the fist 48 h and glycaemic variability (standard deviation and coefficient of variation). Results: We included 213 patients, 64 (30%) with DM. The baseline characteristics (age, sex, stroke severity and the proportion of patients treated with intravenous thrombolysis) were similar between groups. There were no differences in in-hospital complications: pneumonia (4.7% vs. 3.4%; P=.699); urine infection (4.7% vs.1.3%; P =.161); cerebral edema (6.2% vs. 4%; P=.492); or symptomatic hemorrhagic transformation of the stroke (1.6 vs. 0.7%; P =.512) between DM and non DM groups. There was no difference between groups in mortality (12.7 vs. 5.7%; P=.096); death or dependency at 3 months (31.7% vs. 26.4%; P =.500), neither in stroke recurrence (3.1 vs. 4%; P =1.000) at 3 months. After adjusting for other prognostic factors, DM was not associated with any of the studied outcomes, whilst glycaemic variability was independently associated with mortality (p=0.032) and hyperglycemia within 48 hours with death or dependence (p=0.049). Conclusion: DM itself was not associated with poor outcome in acute stroke patients admitted to SU, being glycaemic variability and poststroke hyperglycemia risk factors for mortality and death or dependence respectively.

Motion capture systems (MCS) are used in neurological rehabilitation and for diagnosis of movement disorders. We aimed to explore the usefulness of MCS to obtain an objective measurement of functional status after stroke, especially in patients with minor or without deficit when measured by current motor clinical scales. Methods: Prospective observational case-control pilot study using Microsoft Kinect® analyzed with the software Akira®. Patients after acute stroke were included. All subjects performed the same exercises (standing, walking, sitting position, abduction of the upper limb in pronation and supination during 5 seconds each position and flexion of the upper limbs) that were recorded in a three-dimensional space. Joint angles and time of execution were registered and analyzed. The differences in execution between both sides of the body were compared between cases and controls. The relationship with the NIHSS score was analyzed with linear regression analysis and the mRS score with Pearson’s correlation coefficient (PCC). Results: 50 controls and 33 stroke patients were analyzed. The median NIHSS score was 2 (rank 0-12) and the median mRS was 0 (rank 0-4). The measurements that showed better discrimination capacity were those obtained from abduction of the upper limb: shift of the joint angles were different between cases and controls in the frontal plane for the elbow in pronation (p=0.01) and in supination (p< 0.001); and for the shoulder both in pronation and supination (p=0.01). These differences were independent of the NIHSS score, but were moderately correlated to the mRS score at the moment of the evaluation: elbow in pronation (PCC=0.48 IC=0.051-0.12) and in supination (PCC=0.61 IC=0.16-0.29); and shoulder in pronation (PCC=0.39 IC=0.02-0.08) and in supination (PCC=0.63 IC=0.13-0.25). Conclusion: Computational analysis of movement could be a useful tool for evaluation of upper limb function in stroke patients with slight deficit underestimated using current motor clinical scales and this is correlated with mRS. Further studies are needed to determine the better exercises to be considered and the relationship with functional outcome.

The term cryptogenic stroke refers to a stroke for which there is no specific attributable cause after a comprehensive evaluation. However, there are differences between the diagnostic criteria of etiological classifications used in clinical practice. An improvement in diagnostic tools such advances in monitoring for atrial fibrillation, advances in vascular imaging and evidence regarding the implication of patent foramen oval on the risk of stroke specially in young patients are reducing the proportion of stroke patients without etiological diagnosis. We carried out a critical review of the current concept of cryptogenic stroke, as a non-diagnosis, avoiding the simplification of it and reviewing the different entities that could fall under this diagnosis and reviewing the different entities that could fall under this diagnosis; and therefore avoid the same treatment for differents entities with uncertains results.