Odpowiedź na dożylne podawanie rt-PA u pacjentów w podeszłym wieku z udarem mózgu

Użycie rekombinowanego tkankowego aktywatora plazminogenu (rt-PA, recombined tissue plasminogen activator) u pacjentów powyżej 80. roku życia z udarem mózgu pozostaje kontrowersyjne i wciąż trwa debata nad istnieniem różnic w odpowiedzi na rt-PA, zależnych od płci. Autorzy ocenili kliniczną wartość terapii trombolitycznej u osób powyżej 80. roku życia (grupa osób starszych) w porównaniu z grupą osób młodszych oraz oszacowali obecność różnic w odpowiedzi na rt-PA wynikających z różnicy płci. Wszystkich kolejno przyjmowanych pacjentów (n = 157), leczonych rt-PA, oceniano prospektywnie od lipca 2001 roku, włączając 49 chorych w podeszłym wieku, którzy spełnili kryteria Narodowego Instytutu Zaburzeń Neurologicznych i Udaru (NINDS, National Institute of Neurological Disorders and Stroke). Grupy starszych i młodszych osób porównano pod kątem: zmian w punktacji Skali Udaru Narodowego Instytutu Zdrowia (NIHSS, National Institute of Health Stroke Scale) w 1. godzinie, w 24. godzinie oraz 7. dnia po podaniu rt-PA; korzystnego rezultatu 90. dnia ([wg zmodyfikowanej Skali Rankina {mRS, modified Rankin Scale}] mRS 0–1 lub 2, jeżeli mRS = 2 przed udarem); objawowych krwawień oraz odsetka zgonów. Za pomocą regresji logistycznej wykazano, że wyjściowa punktacja w NIHSS (iloraz szans [OR, odds ratio] 0,59; 95-procentowy przedział ufności [CI, confidence interval] 0,41-0,84) była niezależnym czynnikiem prognostycznym korzystnego rezultatu, ale nie płeć (OR 0,72; 95% CI 0,33-1,56) lub wiek powyżej 80 lat (OR 0,74; 95% CI 0,32-1,70). Wskaźniki poprawy klinicznej, śmiertelności czy objawowego krwawienia do ośrodkowego układu nerwowego również nie wiązały się z wiekiem ani z płcią. Podsumowując, odpowiedź na dożylne podanie rt-PA nie jest upośledzona u starszych pacjentów z udarem mózgu, a wrażliwość na leczenie jest taka sama u mężczyzn i u kobiet. Polski Przegląd Neurologiczny 2008; 4 (1): 36-3

Dyslipidemias and stroke prevention: recommendations of the Study Group of Cerebrovascular Diseases of the Spanish Society of Neurology

Objetivo: Actualizar las recomendaciones de la Sociedad Española de Neurología para la prevención del ictus, tanto primaria como secundaria, en pacientes con dislipidemia. Desarrollo: Se ha realizado una revisión sistemática en Pubmed evaluando los principales aspectos relacionados con el manejo de las dislipidemias en la prevención primaria y secundaria del ictus, elaborándose una serie de recomendaciones relacionadas con los mismos. Conclusiones: En prevención primaria se recomienda determinar el riesgo vascular del paciente con el fin de definir los objetivos de LDLc. En prevención secundaria tras un ictus de origen aterotrombótico se recomienda un objetivo de LDLc < 55 mg/dl, mientras que en ictus isquémicos de origen no aterotrombótico, dado que su relación con dislipidemias es incierta, se establecerán los objetivos en función del grupo de riesgo vascular de cada paciente. Tanto en prevención primaria como secundaria las estatinas son los fármacos de primera elección, pudiendo asociarse ezetimiba y/o inhibidores de PCSK9 en aquellos casos que no alcancen los objetivos terapéuticosObjective 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 valu

Workflow times and outcomes in patients triaged for a suspected severe stroke

Introduction: Current recommendations for regional stroke destination suggest that patients with severe acute stroke in non-urban areas should be triaged based on the estimated transport time to a referral thrombectomy-capable center. Methods: We performed a post hoc analysis to evaluate the association of pre-hospital workflow times with neurological outcomes in patients included in the RACECAT trial. Workflow times evaluated were known or could be estimated before transport allocation. Primary outcome was the shift analysis on the modified Rankin score at 90 days. Results: Among the 1,369 patients included, the median time from onset to emergency medical service (EMS) evaluation, the estimated transport time to a thrombectomy-capable center and local stroke center, and the estimated transfer time between centers were 65 minutes (interquartile ratio [IQR] = 43–138), 61 minutes (IQR = 36–80), 17 minutes (IQR = 9–27), and 62 minutes (IQR = 36–73), respectively. Longer time intervals from stroke onset to EMS evaluation were associated with higher odds of disability at 90 days in the local stroke center group (adjusted common odds ratio (acOR) for each 30-minute increment = 1.03, 95% confidence interval [CI] = 1.01–1.06), with no association in the thrombectomy-capable center group (acOR for each 30-minute increment = 1.01, 95% CI = 0.98–1.01, pinteraction = 0.021). No significant interaction was found for other pre-hospital workflow times. In patients evaluated by EMS later than 120 minutes after stroke onset, direct transport to a thrombectomy-capable center was associated with better disability outcomes (acOR = 1.49, 95% CI = 1.03–2.17). Conclusion: We found a significant heterogeneity in the association between initial transport destination and neurological outcomes according to the elapse of time between the stroke onset and the EMS evaluation (ClinicalTrials.gov: NCT02795962). ANN NEUROL 2022;92:931–942

Bottlenecks in the Acute Stroke Care System during the COVID-19 Pandemic in Catalonia

Introduction: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view. Methods: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. Results: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period. Conclusion: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately

Effectiveness of thrombectomy in stroke according to baseline prognostic factors: inverse probability of treatment weighting analysis of a population-based registry

Background and Purpose In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. Methods Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score 3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups’ criteria). Results Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). Conclusions Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors

Identificación de la presencia de antígenos neurales en el tejido linfoide de los pacientes con ictus y análisis de su eventual implicación patogénica en la respuesta inmune adaptativa tras el daño cerebral

[spa] INTRODUCCION: En condiciones fisiológicas existe un drenaje de solutos y células del sistema inmune desde el sistema nervioso central hacia el tejido linfoide secundario, pudiendo desarrollarse una respuesta inmune de tipo adaptativo frente a dichos antígenos. Ciertas moléculas coadyuvantes como heat shock protein 70(Hsp-70) pueden facilitar y modular los procesos de presentación antigénica y la propia respuesta inmune. Hsp-70 es producida en gran cantidad durante la isquemia cerebral. En los pacientes con ictus isquémico podría haber una mayor llegada de antígenos cerebrales y moléculas coadyuvantes al tejido linfoide secundario que en sujetos controles y de este modo favorecerse respuestas inmunes que influyan en la evolución y pronóstico del ictus. MÉTODOS: Estudio de tejido linfoide en pacientes con ictus agudo mediante toma de biopsias de amígdala palatina y análisis de muestras de sangre, así como en sujetos control. Así mismo, toma de muestras de amígdala palatina y ganglio linfático cervical en necropsias de pacientes con ictus y necropsias control. Se estudiaron las diferentes subpoblaciones linfocitarias, marcadores de activación linfocitaria, presencia de antígenos cerebrales y la proteína Hsp-70, y estructura del tejido linfoide mediante técnicas de citometría de flujo, inmunofluorescencia y western blot, realizándose un análisis cuantitativo. Se analizó la síntesis local tanto de antígenos como Hsp-70 mediante técnica de PCR. RESULTADOS: No se observaron diferencias ni en la estructura del tejido linfoide ni en las diferentes subpoblaciones linfocitarias entre pacientes y controles. Los antígenos cerebrales y Hsp-70 se encontraron en mayor cantidad en pacientes con ictus. Ambos estaban localizados en células presentadoras de antígenos con capacidad para activar el sistema inmune. Dichas células portadoras de antígenos cerebrales se encuentran preferentemente localizadas próximas a la trama fibroreticular del tejido linfoide y podían llevar a cabo algún grado de activación linfocitaria. Los pacientes que presentaban mas antígenos neurales presentaban mejor pronostico, mientras que aquellos con mayor presencia de antígenos mielínicos tenían un mayor volumen de infarto y peor pronóstico. CONCLUSIONES: En los pacientes con ictus isquémico se observa un incremento de antígenos cerebrales en el tejido linfoide secundario. La respuesta inmune frente a ellos puede influir en la evolución y pronóstico de la enfermedad.[eng] INTRODUCTION: Under physiological conditions solutes and immune system cells drain from the central nervous system to the secondary lymphoid tissue. An immune response against these antigens can be developed. Certain adjuvant molecules as heat shock protein 70 (HSP -70) can facilitate and modulate the process of antigen presentation and the immune responses. Hsp -70 is produced in large quantities during cerebral ischemia . In patients with ischemic stroke there could be a increased arrival of brain antigens and adjuvant molecules to the secondary lymphoid tissue and this could favor the development of immune responses that could have a role in the evolution and prognosis of stroke. METHODS: We performed a biopsy of palatine tonsil to acute stroke patients and control subjects. We also obtained samples of palatine tonsil and cervical lymph node from necropsies of patients with stroke and controls. Different lymphocyte subsets, lymphocyte activation markers, presence of brain antigens and Hsp -70 protein, and lymphoid tissue structure were studied by flow cytometry, immunofluorescence and western blot techniques. RESULTS: No differences were observed in either the structure of lymphoid tissue or in different lymphocyte subpopulations between patients and controls. Brain antigens and Hsp -70 were increased in the lymphoid tissue of patients with stroke. Both were located on antigen-presenting cells with ability to activate the immune system. These antigen-presenting cells carrying brain antigens were preferably located near the fibroreticular mesh of the lymphoid tissue and performed some degree of lymphocyte activation. Patients who had more neural antigens showed better prognosis, whereas those with greater presence of myelinated antigens had an increased infarct volume and worse prognosis. CONCLUSIONS: We observed that brain antigens were increased in the secondary lymphoid tissue of stroke patients . The development of an immune response against them could influence the evolution and prognosis of the disease

Presence of heat shock protein 70 in secondary lymphoid tissue correlates with stroke prognosis

Heat shock protein 70 (Hsp-70) can act as a danger signal and activate immune responses. We studied the presence of Hsp-70 in lymphoid tissue and plasma of acute stroke patients and asymptomatic controls free of neurological disease. Immunofluorescence, Western blotting, qRT-PCR and flow cytometry studies were performed. Plasma Hsp-70 concentration at day 7 was similar in patients and controls, whereas patients disclosed stronger immunoreactivity to Hsp-70 in lymphoid tissue than controls. Most Hsp-70. + cells were antigen presenting cells located in T cell zones. Stronger immunoreactivity to Hsp-70 was associated with smaller infarctions and better functional outcome. © 2014 Elsevier B.V.This work was supported by grants from the ‘Instituto de Salud Carlos III’ (ISCIII) (PI09/1313), the Spanish Ministry of Science and Innovation (SAF2011-30492), the ERANET-NEURON project (PRI-PIMNEU-2011-1342) of the European Community, and a donation by the Doctor Melchor Colet Foundation. We are indebted to IDIBAPS Biobank, Xarxa de Bancs de Tumors de Catalunya (XBTC) financed by ‘Pla Director d’Oncologia de Catalunya’ and Red Nacional de Biobancos (RNBB, ReTBioH) financed by ISCIII (RETIC RD09-0076/0038)Peer Reviewe

Uric acid levels are relevant in patients with stroke treated with thrombolysis

Background and Purpose: Uric acid (UA) is a neuroprotective antioxidant that improves the benefits of alteplase in experimental ischemia. However, it is unknown whether endogenous UA also influences the response to thrombolysis in patients with stroke. Methods-A total of 317 consecutive patients treated with thrombolysis were included in a prospective stroke registry. Demographics, laboratory data, neurological course, and infarction volume were prospectively collected. Excellent outcome was defined as achieving a modified Rankin Scale score <2 at 90 days. Binary and ordinal logistic regression models were used to analyze modified Rankin Scale score at 90 days. Results-UA levels were significantly higher in patients with an excellent outcome than in patients with a poor outcome (5.82 [1.39] versus 5.42 [1.81], P=0.029). In multivariate models, increased UA levels (OR, 1.23; 95% CI, 1.03 to 1.49; P=0.025) were associated with an excellent outcome and with an increased risk of shifting to a better category across the modified Rankin Scale (OR, 1.19; 95% CI, 1.04 to 1.38; P=0.014) independently of the effect of confounders. The levels of UA and the volume of final infarction were inversely correlated (r=-0.216, P<0.001) and the inverse correlation remained after adjustment for age, sex, and baseline National Institutes of Health Stroke Scale score (t value=-2.54, P=0.01). Significantly lower UA levels were found in patients with malignant middle cerebral artery infarction and parenchymal hemorrhage postthrombolysis. Conclusions: Increased UA serum levels are associated with better outcome in patients with stroke treated with reperfusion therapies. These results support the assessment of the potential neuroprotective role of the exogenous administration of UA in patients with stroke treated with thrombolysis. © 2010 American Heart Association, Inc.The study was supported by the Fondo de Investigaciones Sanitarias (FIS) of the Spanish Ministry of Health EC07-90276 and the Fundación Melchor Colet. Xabier Urra is a Fellow of the FIS.Peer Reviewe

Monocyte subtypes predict clinical course and prognosis in human stroke

et al.The number of circulating monocytes increases after stroke. In this study, we assessed the time course and phenotype of monocyte subsets and their relationship with the clinical course and outcome in 46 consecutive stroke patients and 13 age-matched controls. The proportion of the most abundant ‘classical’ CD14highCD16− monocytes did not change after stroke, whereas that of CD14highCD16+ monocytes increased and CD14dimCD16+ monocytes decreased. CD14highCD16+ monocytes had the highest expression of TLR2, HLA-DR and the angiogenic marker, Tie-2; CD14dimCD16+ monocytes had the highest expression of costimulatory CD86 and adhesion molecule CD49d. Platelet–monocyte interactions were highest in CD14highCD16− monocytes and lowest in CD14dimCD16+ monocytes. In adjusted models, 1/CD14highCD16− monocytes were associated with poor outcome (OR: 1.38), higher mortality (OR: 1.40) and early clinical worsening (OR: 1.29); 2/CD14highCD16+ monocytes were inversely related to mortality (OR: 0.32); and 3/CD14dimCD16+ monocytes were inversely related to poor outcome (OR: 0.74) and infarction size (r=−0.45; P=0.02). These results illustrate that the predominant monocyte subtype conveys harmful effects after stroke, which include stronger interaction with platelets. Alternatively, rarer subpopulations of monocytes are beneficial with a phenotype that could promote tissue repair and angiogenesis. Therefore, monitoring of monocyte subtypes may emerge as a useful tool at the bedside for stroke patients.Peer reviewe