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

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.(AU)

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.(AU)

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.

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.

Un nuevo protocolo intrahospitalario reduce el tiempo puerta-aguja en el ictus agudo tratado con trombolisis intravenosa a menos de 30 minutos / A new protocol reduces median door-to-needle time to the benchmark of 30 minutes in acute stroke treatment

Introducción: El objetivo del tiempo puerta-aguja en el ictus isquémico agudo tratado con trombólisis intravenosa (TIV) tiende a situarse actualmente en los 30 min. Determinamos si un nuevo protocolo de actuación intrahospitalario es eficaz para reducir el intervalo puerta-aguja y corregir los factores de demora previamente identificados.Material y métodosEn 2014 se implantaron gradualmente unas medidas diseñadas para acortar los tiempos de actuación intrahospitalarios en los pacientes tratados con TIV. Se compararon los tiempos de actuación antes (2009-2012) y después (febrero 2014-abril 2017) de la introducción del nuevo protocolo.ResultadosSe incluyeron 239 pacientes antes y 222 después. Cuando todas las medidas fueron introducidas, la mediana global de tiempo puerta-aguja fue de 27 min (previa 52 min, 48% menos, p < 0,001) y de 22 min cuando se activó el código ictus extrahospitalario. El tiempo global al tratamiento (inicio-aguja) se redujo en 26 min de mediana (p < 0,001). En el período postintervención ya no se objetivó el «efecto de fin de ventana» (p = 0,98). Aunque la angio-TC antes de la TIV continuó retrasando los tiempos de actuación (p < 0,001), tras el nuevo protocolo, esta prueba se realizó después del inicio del tratamiento en la mayoría de los casos.ConclusionesLa reorganización intrahospitalaria y la colaboración multidisciplinar han situado la mediana de tiempo puerta-aguja por debajo de los 30 min y han corregido los factores de demora identificados previamente. Además, se ha reducido el tiempo global al tratamiento y una mayor proporción de pacientes son tratados en los primeros 90 min desde el inicio de los síntomas. (AU)

Introduction: Recent analyses emphasize that The Benchmark Stroke Door-to-Needle Time (DNT) should be 30 min. 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 methodsIn 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.ResultsThe sample included 239 patients before and 222 after the introduction of the protocol. Median overall door-to-needle time was 27 min after the protocol was fully implemented (a 48% reduction on previous door-to-needle time [52 minutes], P<.001)]. Median door-to-needle time was lower when pre-hospital code stroke was activated (22 min). 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 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.ConclusionsHospital reorganisation and multidisciplinary collaboration brought median door-to-needle time below 30 min and corrected previously identified delay factors. Furthermore, overall time from onset to treatment was also reduced and more stroke patients were treated within 90 min of symptom onset. (AU)

[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.

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.

Spontaneous spinal epidural haematoma: a retrospective study of a series of 13 cases.

INTRODUCTION: Spontaneous spinal epidural haematoma (SSEH) has an estimated incidence of one per million inhabitants. It is classified as spontaneous when no identifiable cause can be linked to its onset. OBJECTIVE: To describe a sample of patients with SSEH and analyse variables related to its functional prognosis. PATIENTS AND METHODS: Retrospective study carried out in patients diagnosed with SSEH between 2001 and 2013 in our hospital. RESULTS: We included 13 subjects (7 men) with a mean age of 71 years. Of the total, 62% had hypertension and 54% were treated with oral anticoagulants; of the latter, 57% had an International Normalised Ratio above 3. The most frequent manifestation was spinal column pain (85%). Nearly all subjects presented an associated neurological deficit, whether sensory-motor (70%), pure motor (15%), or pure sensory (7%). Five patients underwent surgical treatment and 8 had conservative treatment. After one year, 3 of the patients treated surgically and 4 of those on conservative treatment had a score of 2 or lower on the modified Rankin Scale. Poorer prognosis was observed in patients with anticoagulant therapy, large haematomas, location in the lumbar region, and more pronounced motor disability at onset. CONCLUSIONS: Old age, hypertension, and anticoagulant therapy are the main risk factors for SSEH. The typical presentation consists of back pain with subsequent motor deficit. In patients with established motor symptoms, surgical treatment within the first 24hours seems to be the best option.

Workload of on-call emergency room neurologists in a Spanish tertiary care centre. A one-year prospective study.

INTRODUCTION: Population ageing, the rising demand for healthcare, and the establishment of acute stroke treatment programs have given rise to increases in the number and complexity of neurological emergency cases. Nevertheless, many centres in Spain still lack on-call emergency neurologists. METHODS: We conducted a retrospective study to describe the role of on-call neurologists at Hospital General Universitario Gregorio Marañón, a tertiary care centre in Madrid, Spain. Sociodemographic characteristics, most common pathologies, diagnostic tests, and destination of the patients attended were recorded daily using a computer database. Results were compared with the general care data from the emergency department. RESULTS: The team attended 3234 patients (3.48% of the emergency department total). The mean number of patients seen per day was 11.15. The most frequent pathologies were stroke (34%), epilepsy (16%) and headache (8%). The mean stay in the emergency department was 7.17 hours. Hospital admission rate was 40% (7.38% of emergency hospital admissions). The main destinations for admitted patients were the stroke unit (39.5%) and the neurology department (33%). Endovascular or thrombolytic therapies were performed on 76 occasions. Doctors attended 70% of the patients during on-call hours. CONCLUSIONS: Emergency neurological care is varied, complex, and frequently necessary. Neurological cases account for a sizeable percentage of both patient visits to the emergency room and the total number of emergency admissions. The current data confirm that on-call neurologists available on a 24-hour basis are needed in emergency departments.