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.

Endarterectomy, Stenting, or Medical Treatment for Symptomatic Carotid Near-Occlusion: Results from CAOS, a Multicenter Registry Study.

BACKGROUND AND PURPOSE: The treatment of symptomatic carotid near-occlusion is controversial. Our aim was to analyze the results of carotid endarterectomy and carotid artery stent placement in patients with symptomatic carotid near-occlusion and to identify factors related to technical failure, periprocedural complications, and restenosis. MATERIALS AND METHODS: We conducted a multicenter, prospective nonrandomized study. Patients with angiography-confirmed carotid near-occlusion were included. We assessed the revascularization rate and periprocedural stroke or death. Twenty-four-month clinical and carotid imaging follow-up was performed, and rates of carotid restenosis or occlusion, ipsilateral stroke, and mortality were analyzed. Carotid artery stent placement, carotid endarterectomy, and medical treatment were compared. RESULTS: One hundred forty-one patients were included. Forty-four carotid artery stent placement and 23 carotid endarterectomy procedures were performed within 6 months after the event. Complete revascularization was achieved in 83.6%, 81.8% in the carotid artery stent placement group and 87% with carotid endarterectomy (P = .360). Periprocedural stroke or death occurred in 6% (carotid artery stent placement = 2.3%; carotid endarterectomy = 13%; P = .077) and was not related to revascularization failure. The carotid restenosis or occlusion rate was 8.3% (5% restenosis, 3.3% occlusion); with carotid artery stent placement it was 10.5%; and with carotid endarterectomy it was 4.5% (P = .419). The 24-month cumulative rate of ipsilateral stroke was 4.8% in the carotid artery stent placement group, 17.4% for carotid endarterectomy, and 13.1% for medical treatment (P = .223). Mortality was 12%, 4.5%, and 5.6%, respectively (P = .422). Revascularization failure and restenosis occurred more frequently in patients with full collapse compared with patients without full collapse (33.3% versus 5.6%, P = .009; 21.4% versus 2.9%, P = .032, respectively). CONCLUSIONS: Carotid artery stent placement and carotid endarterectomy are associated with high rates of failure and periprocedural stroke. Carotid near-occlusion with full collapse appears to be associated with an increased risk of technical failure and restenosis. Carotid near-occlusion revascularization does not seem to reduce the risk of stroke at follow-up compared with medical treatment.

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.

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.

A new protocol reduces median door-to-needle time to the benchmark of 30 minutes in acute stroke treatment.

INTRODUCTION: Recent analyses emphasise that The Benchmark Stroke Door-to-Needle Time (DNT) should be 30min. This study aimed to determine if a new in-hospital IVT protocol is effective in reducing door-to-needle time and correcting previously identified factors associated with delays. MATERIAL AND METHODS: In 2014, we gradually introduced a series of measures aimed to reduce door-to-needle time for patients receiving IVT, and compared it before (2009-2012) and after (2014-2017) the new protocol was introduced. RESULTS: The sample included 239 patients before and 222 after the introduction of the protocol. Median overall door-to-needle time was 27min after the protocol was fully implemented (a 48% reduction on previous door-to-needle time [52min], P<.001)]. Median door-to-needle time was lower when pre-hospital code stroke was activated (22min). We observed a 26-min reduction in the median time from onset to treatment (P<.001). After the protocol was implemented, the "3-hour-effect" did not affect door-to-needle time (P=.98). Computed tomography angiography studies performed before IVT were associated with increased door-to-needle time (P<.001); however, the test was performed after IVT was started in most cases. CONCLUSIONS: Hospital reorganisation and multidisciplinary collaboration brought median door-to-needle time below 30min and corrected previously identified delay factors. Furthermore, overall time from onset to treatment was also reduced and more stroke patients were treated within 90min of symptom onset.

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.

Ultrasonographic and hemodynamic characteristics of patients with symptomatic carotid near-occlusion: results from a multicenter registry study.

PURPOSE: The ultrasonographic and hemodynamic features of patients with carotid near-occlusion (CNO) are still not well known. Our aim was to describe the ultrasonographic and hemodynamic characteristics of a cohort of patients with CNO. METHODS: A prospective, observational, nationwide, and multicenter study was conducted from January/2010 to May/2016. Patients with digital subtraction angiography (DSA)-confirmed CNO were included. We collected information on clinical and demographic characteristics, carotid and transcranial ultrasonography and DSA findings, presence of full-collapse, collateral circulation, and cerebrovascular reactivity (CVR). RESULTS: One hundred thirty-five patients were analyzed. Ultrasonographic and DSA diagnosis of CNO were concordant in only 44%. This disagreement was related to the presence/absence of full-collapse: 45% of patients with CNO with full-collapse were classified as a complete carotid occlusion, and 40% with a CNO without full-collapse were interpreted as severe stenosis (p < 0.001). Mean velocities (mV) and pulsatility indexes (PIs) were significantly lower in the ipsilateral middle cerebral artery compared with the contralateral (43 cm/s vs 58 cm/s, p < 0.001; 0.80 vs 1.00, p < 0.001). Collateral circulation was identified in 92% of patients, with the anterior communicating artery (73%) being the most frequent. CVR was decreased or exhausted in 66% of cases and was more frequent in patients with a poor or absent collateral network compared with patients with ≥ 2 collateral arteries (82% vs 56%, p = 0.051). CONCLUSION: The accuracy of carotid ultrasonography in the diagnosis of CNO seems to be limited, with significant discrepancies with DSA. Decreased ipsilateral mV, PI, and CVR suggest a hemodynamic compromise in patients with CNO.

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).

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.

[Treatment of alteplase-induced orolingual angioedema by means of icatibant]. / Tratamiento del angioedema orolingual inducido por alteplasa mediante icatibant.

TITLE: Tratamiento del angioedema orolingual inducido por alteplasa mediante icatibant.

The risk of recurrent stroke at 24 months in patients with symptomatic carotid near-occlusion: results from CAOS, a multicentre registry study.

BACKGROUND AND PURPOSE: The risk of recurrent stroke amongst patients with symptomatic carotid near-occlusion (SCNO) has not been clearly established, and its management remains controversial. The aim was to define the 24-month risk of recurrent stroke and to analyse the effect of the different treatment modalities (medical treatment and revascularization) in a population of patients with SCNO. METHODS: A multicentre, nationwide, prospective study from January 2010 to May 2016 was performed. Patients with angiography-confirmed SCNO were included. The primary end-point was ipsilateral ischaemic stroke including periprocedural events within 24 months following the presenting event. Revascularization results and periprocedural complications, ipsilateral transient ischaemic attack, disabling or fatal stroke, and mortality were also noted. RESULTS: The study population comprised 141 patients from 17 Spanish centres. Seventy patients (49.6%) were treated by revascularization (carotid stenting in 47, endarterectomy in 23). Complete revascularization was achieved in 58 patients (83%). Periprocedural stroke or death occurred in 5.7%. The 24-month cumulative incidence of the primary end-point was 11.1% (95% confidence interval 5.8-16.4; n = 15), 12% in the medical treatment group and 10.2% in the revascularization group, log-rank P = 0.817. The cumulative rates of ipsilateral ischaemic stroke or transient ischaemic attack, disabling or fatal stroke, and mortality, were 17%, 4.5% and 7.5%, respectively. CONCLUSIONS: The rate of ipsilateral ischaemic stroke in patients with SCNO seems to be lower than the known rate associated with severe carotid stenosis without near-occlusion. The potential benefit of revascularization in the prevention of stroke in patients with SCNO may be influenced by the effectiveness and safety of the procedure.

The neurologist's approach to cerebral infarct and transient ischaemic attack in patients receiving anticoagulant treatment for non-valvular atrial fibrillation: ANITA-FA study.

BACKGROUND AND PURPOSE: The aim of this study was to describe the clinical and epidemiological characteristics of acute ischaemic stroke (AIS) in patients with atrial fibrillation (AF) previously treated with oral anticoagulants (OACs) according to the type of OAC prescribed. Also, to analyze the outcomes of the patients and the therapeutic approach adopted by the neurologist in the acute phase and for secondary prevention. METHODS: We performed a multicenter, observational study based on prospective registries. We included patients with AF treated with OACs admitted for AIS over a 1-year period. Detailed clinical data and functional outcome at 3 months (modified Rankin Scale score) were collected. Patients were divided into two groups according to their pre-AIS anticoagulant therapy: vitamin K antagonists (AIS-VKA) and direct-acting OACs (AIS-DOAC). RESULTS: We recruited 1240 patients (80.4% AIS-VKA and 19.6% AIS-DOAC). In the AIS-DOAC group, transient ischaemic attack was more frequent (18.1% vs. 10.8%; P = 0.001), symptomatic hemorrhagic transformation was less frequent (1.6% vs. 4.6%; P = 0.035) and hospital stay was shorter (median 6 vs. 7 days; P = 0.03). Intravenous thrombolysis was more commonly used in AIS-VKA (9.2% vs. 1.6%; P < 0.001). There were no differences between the groups with respect to mechanical thrombectomy, mortality and modified Rankin Scale score at 3 months. At 3 months, 54% of patients required a DOAC as antithrombotic treatment for secondary prevention. CONCLUSIONS: Patients with AF treated with DOACs who experienced AIS more frequently had transient symptoms (transient ischaemic attack), less symptomatic hemorrhagic transformation and a shorter mean stay than those treated with VKAs. Most patients who had been previously anticoagulated with AIS received long-term treatment with DOACs.

The Direct Referral to Endovascular Center criteria: a proposal for pre-hospital evaluation of acute stroke in the Madrid Stroke Network.

BACKGROUND AND PURPOSE: For patients with acute ischaemic stroke due to large-vessel occlusion, it has recently been shown that mechanical thrombectomy (MT) with stent retrievers is better than medical treatment alone. However, few hospitals can provide MT 24 h/day 365 days/year, and it remains unclear whether selected patients with acute stroke should be directly transferred to the nearest MT-providing hospital to prevent treatment delays. Clinical scales such as Rapid Arterial Occlusion Evaluation (RACE) have been developed to predict large-vessel occlusion at a pre-hospital level, but their predictive value for MT is low. We propose new criteria to identify patients eligible for MT, with higher accuracy. METHODS: The Direct Referral to Endovascular Center criteria were defined based on a retrospective cohort of 317 patients admitted to a stroke center. The association of age, sex, RACE scale score and blood pressure with the likelihood of receiving MT were analyzed. Cut-off points with the highest association were thereafter evaluated in a prospective cohort of 153 patients from nine stroke units comprising the Madrid Stroke Network. RESULTS: Patients with a RACE scale score ≥ 5, systolic blood pressure <190 mmHg and age <81 years showed a significantly higher probability of undergoing MT (odds ratio, 33.38; 95% confidence interval, 12-92.9). This outcome was confirmed in the prospective cohort, with 68% sensitivity, 84% specificity, 42% positive and 94% negative predictive values for MT, ruling out 83% of hemorrhagic strokes. CONCLUSIONS: The Direct Referral to Endovascular Center criteria could be useful for identifying patients suitable for MT.

[Diagnostic, prognostic and therapeutic implications of transcranial color-coded duplex sonography in acute ischemic stroke: TIBI and COGIF scores validation]. / Implicaciones diagnosticas, pronosticas y terapeuticas del duplex color transcraneal en el ictus isquemico agudo: validacion de los grados TIBI y COGIF.

AIM: To describe the information provided by transcranial color-coded duplex (TCCD) sonography for therapeutic decision-making in patients with acute ischemic stroke and to analyze the relationship between TCCD findings and the severity and prognosis of stroke. PATIENTS AND METHODS: TCCD performed within the six first hours after an acute ischemic stroke were analyzed in our institution. The presence of an arterial occlusion and its location were collected using TIBI (Thrombolysis in Brain Ischemia) and COGIF (Consensus on Grading Intracranial Flow Obstruction) criteria. Arterial recanalization within 24 hours after stroke was determined using TIBI and COGIF criteria. Favorable functional outcome was defined as a modified Rankin scale from 0 to 2 at three months. RESULTS: TCCD was performed in 104 patients, 85 were treated with intravenous thrombolysis. Arterial occlusion was detected in 79.8% of patients. The detection of arterial occlusion with TCCD allowed the selection for endovascular treatment in 23.1% of patients. Arterial occlusion was associated with a higher severity of stroke. Recanalization was detected in 44.1% using TIBI and 45.8% according to COGIF criteria. 80.8% of recanalized patients and only 39.5% of not recanalized had a favorable functional outcome at three months. Recanalization rate depended on the location of arterial occlusion. CONCLUSION: TCCD is a useful technique for the detection and location of arterial occlusion. It provides valuable prognostic information and allows selecting patients for endovascular recanalizing therapies. TIBI and COGIF scores provide a comparable information.

TITLE: Implicaciones diagnosticas, pronosticas y terapeuticas del duplex color transcraneal en el ictus isquemico agudo: validacion de los grados TIBI y COGIF.Objetivo. Describir la informacion aportada por el duplex color transcraneal (DCTC) en pacientes con ictus isquemico agudo, analizando la relacion entre los hallazgos del DCTC, la gravedad y el pronostico, asi como su utilidad en la toma de decisiones terapeuticas. Pacientes y metodos. Analizamos los DCTC realizados a pacientes con ictus agudo de menos de seis horas de evolucion. Recogimos la existencia de oclusion arterial empleando las clasificaciones TIBI (Thrombolysis in Brain Ischemia) y COGIF (Consensus on Grading Intracranial Flow Obstruction). Determinamos la recanalizacion arterial a las 24 horas del ictus empleando criterios TIBI y COGIF. Consideramos buena evolucion funcional puntuaciones en la escala de Rankin de 0 a 2 a los tres meses. Resultados. Realizamos DCTC en 104 pacientes, 85 tratados con trombolisis intravenosa. Objetivamos oclusion arterial en el 79,8%. La deteccion de una oclusion arterial mediante DCTC permitio indicar tratamiento endovascular en el 23,1% de los pacientes. La presencia de oclusion arterial se asocio a mayor gravedad del ictus. Detectamos recanalizacion arterial en el 44,1% segun los criterios TIBI y en el 45,8% segun los criterios COGIF. El 80,8% de los pacientes que recanalizaron y solo el 39,5% de los que no recanalizaron obtuvieron una buena evolucion funcional a los tres meses. La recanalizacion dependio de la localizacion de la oclusion arterial. Conclusiones. El DCTC es util para deteccion y localizacion de oclusion arterial, aporta informacion pronostica valiosa y permite seleccionar pacientes para el empleo de terapias endovasculares. La informacion aportada por las clasificaciones TIBI y COGIF es equiparable.

Endovascular treatment of cerebral venous sinus thrombosis (CVST): Is a complete recanalization required for a good clinical outcome?

The usual therapy in cerebral venous sinus thrombosis (CVST) is based on anticoagulant treatment with adjusted-dose unfractionated heparin. When medical treatment fails, endovascular techniques, such as mechanical thrombectomy, are available. We report a case of a 21-year-old woman with a diagnosis of left CVST, treated by a neurointerventional approach with mechanical thrombectomy using the Penumbra(®) System. Despite the fact that only incomplete recanalization was achieved, a gradual resolution of the thrombus and a progressive clinical improvement occurred.

Factors associated with in-hospital delays in treating acute stroke with intravenous thrombolysis in a tertiary centre. / Identificación de los factores que influyen en el retraso intrahospitalario del inicio de trombólisis intravenosa en el ictus agudo en un hospital terciario.

OBJECTIVE: This study aims to determine which factors are associated with delays in door-to needle (DTN) time in our hospital. This will help us design future strategies to shorten time to treatment with intravenous thrombolysis (IVT). METHODS: Retrospective analysis of a prospective cohort of patients with ischaemic stroke treated with IVT in our hospital between 2009 and 2012. We analysed the relationship between DTN time and the following variables: age, sex, personal medical history, onset-to-door time, pre-hospital stroke code activation, blood pressure and blood glucose level, National Institutes of Health Stroke Scale (NIHSS), computed tomography angiography (CTA) and/or doppler/duplex ultrasound (DUS) performed before IVT, time to hospital arrival, and day of the week and year of stroke. RESULTS: Our hospital treated 239 patients. Median time to treatment in minutes (IQR): onset-to-door, 84 (60-120); door-to-CT, 17 (13-24.75); CT-to needle, 34 (26-47); door-to-needle, 52 (43-70); onset-to-needle, 145 (120-180). Door-to-needle time was significantly shorter when code stroke was activated, at 51 vs. 72min (P=0.008), and longer when CTA was performed, at 59 vs. 48.5min (P=0.004); it was also longer with an onset-to-door time<90min, at 58 vs. 48min (P=0.003). The multivariate linear regression analysis detected 2 factors affecting DTN: code stroke activation (26.3% reduction; P<0.001) and onset-to-door time (every 30min of onset-to-door delay corresponded to a 4.7min increase in DTN time [P=0.02]). On the other hand, CTA resulted in a 13.4% increase in DTN (P=0.03). No other factors had a significant influence on door-to-needle time. CONCLUSIONS: This study enabled us to identify CTA and the «3-hour effect¼ as the 2 factors that delay IVT in our hospital. In contrast, activating code stroke clearly reduces DTN. This information will be useful in our future attempts to reduce door-to-needle times.