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.

Analysis of stroke care resources in Spain in 2012: have we benefitted from the Spanish Health System's stroke care strategy?

INTRODUCTION: The Spanish Health System's stroke care strategy (EISNS) is a consensus statement that was drawn up by various government bodies and scientific societies with the aim of improving quality throughout the care process and ensuring equality among regions. Our objective is to analyse existing healthcare resources and establish whether they have met EISNS targets. MATERIAL AND METHODS: The survey on available resources was conducted by a committee of neurologists representing each of Spain's regions; the same committee also conducted the survey of 2008. The items included were the number of stroke units (SU), their resources (monitoring, neurologists on call 24h/7d, nurse ratio, protocols), SU bed ratio/100,000 inhabitants, diagnostic resources (cardiac and cerebral arterial ultrasound, advanced neuroimaging), performing iv thrombolysis, neurovascular interventional radiology (neuro VIR), surgery for malignant middle cerebral artery (MCA) infarctions and telemedicine availability. RESULTS: We included data from 136 hospitals and found 45 Stroke Units distributed unequally among regions. The ratio of SU beds to residents ranged from 1/74,000 to 1/1,037,000 inhabitants; only the regions of Cantabria and Navarre met the target. Neurologists performed 3,237 intravenous thrombolysis procedures in 83 hospitals; thrombolysis procedures compared to the total of ischaemic strokes yielded percentages ranging from 0.3 to 33.7%. Hospitals without SUs showed varying levels of available resources. Neuro VIR is performed in every region except La Rioja, and VIR is only available on a 24h/7 d basis in 17 cities. Surgery for malignant MCA infarction is performed in 46 hospitals, and 5 have telemedicine. CONCLUSION: Stroke care has improved in terms of numbers of participating hospitals, the increased use of intravenous thrombolysis and endovascular procedures, and surgery for malignant MCA infarction. Implementation of SUs and telemedicine remain insufficient. The availability of diagnostic resources is good in most SUs and irregular in other hospitals. Regional governments should strive to ensure better care and territorial equality, which would achieve the EISNS objectives.

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.

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.

Stroke treatment outcomes in hospitals with and without Stroke Units. / Resultados en el tratamiento del ictus en hospitales con y sin Unidad de Ictus.

INTRODUCTION: Organisational capacity in terms of resources and care circuits to shorten response times in new stroke cases is key to obtaining positive outcomes. This study compares therapeutic approaches and treatment outcomes between traditional care centres (with stroke teams and no stroke unit) and centres with stroke units. METHODS: We conducted a prospective, quasi-experimental study (without randomisation of the units analysed) to draw comparisons between 2 centres with stroke units and 4 centres providing traditional care through the neurology department, analysing a selection of agreed indicators for monitoring quality of stroke care. A total of 225 patients participated in the study. In addition, self-administered questionnaires were used to collect patients' evaluations of the service and healthcare received. RESULTS: Centres with stroke units showed shorter response times after symptom onset, both in the time taken to arrive at the centre and in the time elapsed from patient's arrival at the hospital to diagnostic imaging. Hospitals with stroke units had greater capacity to respond through the application of intravenous thrombolysis than centres delivering traditional neurological care. CONCLUSION: Centres with stroke units showed a better fit to the reference standards for stroke response time, as calculated in the Quick study, than centres providing traditional care through the neurology department.

A set of care quality indicators for stroke management. / Conjunto de indicadores de calidad asistencial en el abordaje del ictus.

OBJECTIVE: This study proposes a set of quality indicators for care outcomes in patients with acute cerebral infarction. These indicators are understandable and relevant from a clinical viewpoint, as well as being acceptable and feasible in terms of time required, ease of data capture, and interpretability. METHOD: The method consisted of reaching consensus among doctors after having reviewed the literature on quality indicators in stroke. We then designed and conducted a field study to assess the understandability and feasibility of the set of indicators. RESULTS: Consensus yielded 8 structural indicators, 5 process indicators, and 12 result indicators. Additionally, standards of reference were established for each indicator. CONCLUSION: This set of indicators can be used to monitor the quality care for stroke patients, identify strengths, and potentially to identify areas needing improvement.

[Ophthalmological manifestations of cerebrovascular disease]. / Manifestaciones oftalmológicas de la enfermedad cerebrovascular.

Transient or persistent loss of vision in one eye is a common and distinctive manifestation of occlusive vascular disease. Occasionally, both eyes are involved together or sequentially, with temporary or even permanent blindness. The internal carotid arteries supply blood to the organ of vision; therefore pathologies of those arteries caused by arteriosclerosis may have a direct influence on its functioning. The most common syndromes are temporary (amaurosis fugax) or constant reduction of visual acuity. In fundus examination central retinal artery occlusion and branch retinal artery occlusion are the most common diagnosis, while retinal vein occlusion, anterior ischemic optic neuropathy, ocular ischemic syndrome are less common. There are many clinical ophtlamological manifestations due to vascular brain damage. Proper recognition and diagnosis of the disease may protect the patient against serious life-threatening complications such as stroke.

Prognostic factors and analysis of mortality due to brain haemorrhages associated with vitamin K antagonist oral anticoagulants. Results from the TAC registry. / Factores pronósticos y análisis de la mortalidad de las hemorragias cerebrales asociadas a anticoagulantes orales antagonistas de la vitamina K. Resultados del Estudio TAC Registry.

INTRODUCTION: Intracranial haemorrhages (ICH) represent a severe and frequently lethal complication in patients treated with vitamin K antagonists (VKA). The purpose of our study is to describe the factors and clinical features associated with mortality in these patients. METHODS: We conducted an observational, retrospective, multi-centre study based on prospective stroke registries in Spain. We included all patients admitted to neurology departments during a one-year period who met the following inclusion criteria: being 18 or older, having a diagnosis of ICH, and receiving VKA. Clinical and radiological parameters and 3-month outcomes were analysed. RESULTS: A total of 235 patients from 21 hospitals were included. Mortality rate at 90 days was 42.6%. Bivariate analysis showed a significant association between death and the following factors: median NIHSS score at admission (5 [IQR = 9] vs 17 [IQR = 14] points, P<.01) and presence of an extensive hemispheric haemorrhage (4.9% vs 35%, P < .01; χ2). Extensive hemispheric haemorrhages, in addition to being the most lethal type, were associated with a shorter time to death (mean of 16.5 days; 95% CI: 7.1-26). A logistic regression model showed that only baseline NIHSS scores independently predicted death (odds ratio=1.13 [95% CI: 1.08-1.17] for each point in the scale). CONCLUSION: ICH in patients treated with VKA is associated with high mortality rates; mortality in these patients is mainly and independently associated with the clinical situation at stroke onset.

Healthcare resources and needs in anticoagulant therapy for patients with nonvalvular atrial fibrillation. SAMOA Study. / Recursos y necesidades asistenciales en el tratamiento anticoagulante de los pacientes con fibrilación auricular no valvular. Estudio SAMOA.

INTRODUCTION AND OBJECTIVES: To determine, in the various medical specialties, the healthcare process for anticoagulated patients with nonvalvular atrial fibrillation, to determine the available and necessary resources and to identify potential areas of improvement in the care of these patients. METHODS: We performed a cross-sectional survey of primary care and specialised physicians involved in the care of anticoagulated patients. The questionnaires referred to the healthcare process, the indication and prescription of anticoagulant therapy and the barriers and deficiencies present for these patients. RESULTS: A total of 893 physicians participated in the study, 437 of whom worked in primary care and 456 of whom were specialists (mostly cardiologists). Forty-two percent of the family doctors indicated that they assessed and prescribed anticoagulant therapy, and 66% performed the regular follow-up of these patients. In both healthcare settings, the physicians noted the lack of standardised protocols. There was also a lack of quality control in the treatment. CONCLUSIONS: The role of primary care in managing anticoagulated patients has grown compared with previous reports. The responses of the participating physicians suggest marked gaps in the standardisation of the healthcare process and several areas for improvement in these patients' follow-up. The promotion of training in direct-acting anticoagulant drugs remains pivotal.

[Neuro-radiological findings in probable moyamoya disease]. / Hallazgos neurorradiológicos en probable enfermedad de moyamoya.

INTRODUCTION: Unilateral moyamoya disease presents as unilateral stenosis or obstruction of the supraclinoid internal carotid artery, which causes cerebral hypoperfusion resulting in seizures or transitorial ischemic accidents (TIA). CLINICAL CASE: Atypical moyamoya disease was diagnosed as the cause of intraventricular hemorrhage in a 41 year-old-woman. The cerebral angiography, CT, MR and brain SPECT are reported. CONCLUSION: We discuss the clinic course and diagnostic techniques in this unilateral, atypical moyamoya disease and which steps are necessary toward an acceptable method for diagnosis and pursuit.

[Current situation of neuroprotection in stroke]. / Situación actual de la neuroprotección en el ictus.

Focal and global brain ischemic injury represents one of the most important causes of human neurological disability and mortality in developed countries. It has been long recognized that the two major therapeutic approaches to ischemic stroke involve improving blood flow and the reduction or blockade of the cellular and subcellular consequences of ischemic injury. The important advances experienced during the last decade on the knowledge of pathophysiological mechanisms of brain ischemia and the development of new drugs give us a glimmer of hope in the treatment and they allow us to reject the nihilistic attitudes. We review the new pharmacological approaches to cytoprotective therapy for acute ischemic stroke and the results of reported clinical trials.

[Multiple sclerosis and epileptic seizures]. / Esclerosis múltiple y crisis epilépticas.

INTRODUCTION: Although epileptic seizures are uncommon in multiple sclerosis they are more prevalent than in the general population, which supports an aetiological relationship. Similarly in a considerable proportion of patients with multiple sclerosis and epileptic seizures, alterations in magnetic resonance and electroencephalogram studies which could be correlated with the clinical features of epilepsy were observed. Nevertheless, it is difficult to establish definite clinical characteristics in these patients since the underlying pathogenic mechanisms are poorly understood and there is great variability with regard to the type of seizure, point at which this occurs during the course of the disease, degree of recurrence and other aspects. CLINICAL CASE: We report the clinical, electroencephalographical and neuroimaging findings of seven patients with multiple sclerosis who had epileptic seizures and those in whom there was no evidence of other potentially epileptogenic pathology. In two patients the epileptic seizures formed part of the first episode of their illness. One patient presented more than one type of epileptic seizure. These seizures were generalized in two cases, partial sensory and/or motor with secondary generalization in three, simple partial motor in one and partial complex in two. The epileptic seizures coincided with other clinical features of episodes in three cases and the electroencephalogram showed anomalies in five cases. CONCLUSIONS: The findings observed were of a wide variety, as was found in other reported series. We point out certain correlations between the clinical data, magnetic resonance and electroencephalogram which may help to orientate the management of these patients.

[Central anticholinergic syndrome]. / Sindrome anticolinérgico central.

Two new cases of anticolinergic central syndrome are described. The first case, a 8 year old girl, suffered a severe encefalopathy after topical application of mydriatic cholirio as an aid in a rutine study of ocular refraction. The second case, 67 year old man presented a severe neurological picture after accidental intake of a silvester plantground (Atropa belladonna). His neurological condition returned quickly to normal whith administration of physostigmine. Differents aspects of the etiology, clinical picture and diagnosis are discussed with special emphasis in patients with delirium or acute confusional states. Finally, attention is drawn in the necessity of a properly use of anticholinergic drugs overcoat in aged or children.

[Epidemiology and clinical evolutionary aspects of multiple sclerosis in Navarra]. / Epidemiología y aspectos clinicoevolutivos de la esclerosis múltiple en Navarra.

In the present study 84 patients with the diagnosis of multiple sclerosis were identified as living in Navarra on the date of prevalence (December 31, 1986). The raw yearly incidence rate was 0.49/100000, which is similar to that in Mediterranean countries. A significant increase of this rate was found between 1951 and 1986, which was interpreted as a consequence of higher economic status and/or progressive industrialization. The raw prevalence rate was 16.4/100000 and age-specific prevalence was 26.5. Therefore, Navarra is a medium risk area for MS. Mean age at onset was 29.3 years, with a significant female predominance. In addition, MS presented earlier in females. The relationship between MS and latitude of the residence area was confirmed. The most common presenting symptoms were motor (paresia) and sensory (paresthesia). Cerebrospinal fluid was abnormal in 86.5% of patients, evoked potentials (mostly visual) in 85.9%, and magnetic resonance in 100%. Demyelinizing signs were detected with CT in 29.4% of patients. The diagnostic criteria of the Boston University Workshop were highly reliable. The most common evolutive pattern was the pure remitting one. The mean degree of disability was 3.6 in Kurtzke's scale. The evolutive form and the duration of the disease were identified as predictive of disability. 43.5% of benign forms and 13.1% of late onset forms were identified.

Situación actual de la neuroprotección en el ictus / Current situation of neuroprotection in stroke

La isquemia cerebral focal o global representa en los países desarrollados una de las causas más importantes de muerte y deterioro neurológico. Las dos orientaciones terapéuticas más importantes en el paciente con isquemia cerebral aguda consisten en mejorar el flujo sanguíneo cerebral y reducir o bloquear las consecuencias metabólicas a nivel subcelular y celular. Los importantes avances producidos en la última década en el conocimiento de los mecanismos fisiopatológicos de la isquemia cerebral y en el desarrollo de nuevos fármacos ha planteado expectativas reales de tratamiento y el rechazo de actitudes nihilistas. Se revisan las nuevas tendencias en neuroprotección en isquemia cerebral focal y los resultados de los ensayos clínicos publicados