Fatal intracerebral haemorrhage associated with thrombosis with thrombocytopenia syndrome after ChAdOx1-S vaccine. / Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.

INTRODUCTION: The COVID-19 pandemic has had a devastating impact on health, society and economics worldwide. Therefore, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have recently emerged as an important measure to fight the pandemic. ChAdOx1-S (Oxford-AstraZeneca) is an adenovirus-vectored vaccine that expresses the SARS-CoV-2 spike protein. It shows an acceptable safety profile. Nevertheless, several cases of unusual thrombosis and thrombocytopenia have been reported after initial vaccination with ChAdOx1-S mimicking autoimmune heparin-induced thrombocytopenia. This condition has been called thrombosis with thrombocytopenia syndrome (TTS) and complications such as intracerebral haemorrhage have been described. CASE REPORT: We present a case of intracerebral haemorrhage after ChAdOx1-S vaccination. Middle-aged patient with no prior medical history was seen in the emergency room 16 days after the first dose of ChAdOx1-S vaccine with sudden onset left hemiplegia and severe holocranial oppressive headache. She did not receive heparin treatment in the previous 100 days. Blood test showed moderate thrombocytopenia and a right frontal lobar haemorrhage was seen on computed tomography scan, computed tomography venography was negative for thrombosis. The presence of antibodies against platelet factor 4 was confirmed. The patient's neurological condition progressively worsened. She developed a treatment resistant intracranial hypertension syndrome and she died three weeks later. CONCLUSIONS: TTS is a rare adverse effect of ChAdOx1-S vaccine, defined by the presence of thrombosis in uncommon locations. In our case we report an spontaneous intracerebral haemorrhage probable due to the thrombocytopenia related to probable TTS. It represents a rare clinical presentation of TTS.

TITLE: Hemorragia intracerebral fatal asociada al síndrome de trombosis con trombocitopenia tras la vacuna ChAdOx1-S.Introducción. La pandemia por COVID-19 ha tenido un impacto devastador en la salud, la sociedad y la economía en el mundo. Por ello, las vacunas contra el coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) han surgido como medida importante para combatir la pandemia. ChAdOx1-S (Oxford-AstraZeneca) es una vacuna vectorizada por adenovirus que expresa la proteína de espiga del SARS-CoV-2. Se han notificado varios casos de trombosis y trombocitopenia inusuales tras la ChAdOx1-S que imitan la trombocitopenia autoinmune inducida por heparina. Esta situación se denomina síndrome de trombosis con trombocitopenia (STT), y se han descrito casos de hemorragia intracerebral secundaria. Caso clínico. Presentamos un caso de hemorragia intracerebral tras la vacunación con ChAdOx1-S. Una paciente de mediana edad sin antecedentes médicos de interés fue atendida en urgencias 16 días después de la primera dosis de ChAdOx1-S con una hemiplejía izquierda de inicio repentino y una cefalea opresiva holocraneal grave. No recibió heparina los 100 días anteriores. El análisis de sangre mostró trombocitopenia moderada y en la tomografía computarizada se observó una hemorragia lobar frontal derecha sin trombosis en la venografía por tomografía computarizada. Se confirmó la presencia de anticuerpos contra el factor 4 de las plaquetas en la sangre. La paciente presentó un síndrome de hipertensión intracraneal resistente al tratamiento y falleció tres semanas después. Conclusiones. El STT es un efecto adverso infrecuente de la vacuna ChAdOx1-S que se define por la presencia de trombosis en localizaciones infrecuentes. En nuestro caso, describimos una hemorragia intracerebral espontánea secundaria a la trombocitopenia desencadenada por el STT. Representa una presentación clínica poco frecuente del STT.

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.

Spanish adaptation of the 2016 European Guidelines on cardiovascular disease prevention in clinical practice. / Adaptación española de las guías europeas de 2016 sobre prevención de la enfermedad cardiovascular en la práctica clínica.

The VI European Guidelines for Cardiovascular Prevention recommend combining population and high-risk strategies with lifestyle changes as a cornerstone of prevention, and propose the SCORE function to quantify cardiovascular risk. The guidelines highlight disease specific interventions, and conditions as women, young people and ethnic minorities. Screening for subclinical atherosclerosis with noninvasive imaging techniques is not recommended. The guidelines distinguish four risk levels (very high, high, moderate and low) with therapeutic objectives for lipid control according to risk. Diabetes mellitus confers a high risk, except for subjects with type 2 diabetes with less than <10 years of evolution, without other risk factors or complications, or type 1 diabetes of short evolution without complications. The decision to start pharmacological treatment of arterial hypertension will depend on the blood pressure level and the cardiovascular risk, taking into account the lesion of target organs. The guidelines don't recommend antiplatelet drugs in primary prevention because of the increased bleeding risk. The low adherence to the medication requires simplified therapeutic regimes and to identify and combat its causes. The guidelines highlight the responsibility of health professionals to take an active role in advocating evidence-based interventions at the population level, and propose effective interventions, at individual and population level, to promote a healthy diet, the practice of physical activity, the cessation of smoking and the protection against alcohol abuse.

[Spanish adaptation of the 2016 European Guidelines on cardiovascular disease prevention in clinical practice]. / Adaptación española de las guías europeas de 2016 sobre prevención de la enfermedad cardiovascular en la práctica clínica.

The VI European Guidelines for Cardiovascular Prevention recommend combining population and high-risk strategies with lifestyle changes as a cornerstone of prevention, and propose the SCORE function to quantify cardiovascular risk. The guidelines highlight disease specific interventions, and conditions as women, young people and ethnic minorities. Screening for subclinical atherosclerosis with noninvasive imaging techniques is not recommended. The guidelines distinguish four risk levels (very high, high, moderate and low) with therapeutic objectives for lipid control according to risk. Diabetes mellitus confers a high risk, except for subjects with type 2 diabetes with less than <10 years of evolution, without other risk factors or complications, or type 1 diabetes of short evolution without complications. The decision to start pharmacological treatment of arterial hypertension will depend on the blood pressure level and the cardiovascular risk, taking into account the lesion of target organs. The guidelines don't recommend antiplatelet drugs in primary prevention because of the increased bleeding risk. The low adherence to the medication requires simplified therapeutic regimes and to identify and combat its causes. The guidelines highlight the responsibility of health professionals to take an active role in advocating evidence-based interventions at the population level, and propose effective interventions, at individual and population level, to promote a healthy diet, the practice of physical activity, the cessation of smoking and the protection against alcohol abuse.

Statement of the Spanish Interdisciplinary Cardiovascular Prevention Committee (CEIPC for its Spanish acronym) on the 2012 European Cardiovascular Prevention Guidelines.

Based on the two main frameworks for evaluating scientific evidence (SEC and GRADE) European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions) led by health professionals and with the participation of the patient's family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions - such as smoking ban in public areas or the elimination of trans fatty acids from the food chain - are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure within the 130-139/80-85 mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses.

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.

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.

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.

[European Guidelines on Cardiovascular Disease Prevention in Clinical Practice. Spanish adaptation of the CEIPC 2008]. / Guía Europea de Prevención Cardiovascular en la Práctica Clínica. Adaptación Española del Comité Español Interdisciplinario para la Prevención Cardiovascular (CEIPC) 2008.

We present the Spanish adaptation made by the CEIPC of the European Guidelines on Cardiovascular Disease Prevention (CVD) in Clinical Practice 2008. This guide recommends the SCORE model for risk evaluation. The aim is to prevent premature mortality and morbidity due to CVD through the management of its related risk factors in clinical practice. The guide focuses on primary prevention and emphasizes the role of the nurses and primary care medical doctors in promoting a healthy life style, based on increasing physical activity, change dietary habits, and non smoking. The therapeutic goal is to achieve a Blood Pressure < 140/90 mmHg, but among patients with diabetes, chronic kidney disease, or definite CVD, the objective is <130/80 mmHg. Serum cholesterol should be < 200 mg/dl and cLDL<130 mg/dl, although among patients with CVD or diabetes, the objective is <100 mg/dl (80 mg/dl if feasible in very high-risk patients). Patients with type 2 diabetes and those with metabolic syndrome must lose weight and increase their physical activity, and drugs must be administered whenever applicable, to reach body mass index (BMI) guided and waist circumference objectives. In diabetic type 2 patients, the objective is glycated haemoglobin <7%. Allowing people to know the guides and developing implementation programs, identifying barriers and seeking solutions for them, are priorities for the CEIPC in order to transfer the recommendations established into the daily clinical practice.

[European Guidelines on Cardiovascular Disease Prevention in Clinical Practice. CEIPC 2008 Spanish adaptation]. / Guía Europea de Prevención Cardiovascular en la Práctica Clínica. Adaptación española del CEIPC 2008.

The present CEIPC Spanish adaptation of the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice 2008. This guide recommends the SCORE model for risk evaluation. The aim is to prevent premature mortality and morbidity due to CVD by means of dealing with its related risk factors in clinical practice. The guide focuses on primary prevention and emphasizes the role of the nurses and primary care doctors in promoting a healthy life style, based on increasing physical activity, changing dietary habits, and not smoking. The therapeutic goal is to achieve a Blood Pressure < 140/90 mmHg, but in patients with diabetes, chronic kidney disease, or definite CVD, the objective is < 130/80 mmHg. Serum cholesterol should be < 200 mg/dl and cLDL < 130 mg/dl, although in patients with CVD or diabetes, the objective is < 100 mg/dl (80 mg/dl if feasible in very high-risk patients). Patients with type 2 diabetes and those with metabolic syndrome must lose weight and increase their physical activity, and drugs must be administered whenever applicable, with the objective guided by body mass index and waist circumference. In diabetic type 2 patients, the objective is glycated haemoglobin < 7%. Allowing people to know the guides and developing implementation programs, identifying barriers and seeking solutions for them, are priorities for the CEIPC in order to put the recommendations into practice.