Estudio unicéntrico del tratamiento con trombolíticos dirigidos por catéter en el tromboembolismo pulmonar agudo / Single center retrospective study of catheter directed thrombolysis in patients with acute pulmonary embolism

Resumen Se realizó un estudio unicéntrico retrospectivo para evaluar la eficacia y seguridad de trombolisis dirigida por catéter (TDC) en pacientes con tromboembolismo pulmonar agudo (TEP) de 2014 a 2020. Se analizó la efectividad (mejoría de presión pulmonar), y seguridad (sangrado intracraneal y grave definido por compromiso hemodinámico). Se incluyeron 43 pacientes, de 67(56-79) años, 5 (12%) con shock, 41 (95%) con dilatación del ventrículo derecho y TEP bilateral. La decis ión de TDC fue: tratamiento inicial (53%), escalada de anticoagulación (42%) y rescate de trombolisis sistémica (5%). Se utilizó TDC facilitada por ultrasonido en 40 casos (93%), utilizándose 30 (25-35) mg de activador tisular del plasminógeno recombinante (rtPA) durante 20 h. Se administró un bolo de rtPA en 38 (89%) casos, que fue 5 mg (95%) o 1 mg (5%). Se utilizó un solo catéter por paciente. En 4 (9%) se decidió recolocación (mismo pulmón) para continuar infusión en otro sector. Se observó una disminución significativa de la presión media pulmonar (pre 35 [29-41] mmHg vs. post 24 [20-34] mmHg, p<0.001). No se observó ningún caso de hemorragia intracraneal, y un caso (2%) de sangrado grave. Se observó hematoma del sitio de punción en 5 (12%) (incluyendo el sangrado grave), y requirió transfusiones en 3 (7%). La mortalidad intrahospitalaria fue 12%, siendo un solo c aso (2%) atribuido al TEP. El tratamiento con TDC fue efectivo asociándose a una reducción significativa de la presión pulmonar, sin observarse ningún sangrado intracraneal y con un sangrado grave. Nuestros resultados se asemejan a lo publicado en otros estudios.

Abstract We performed a single center retrospective study in patients with pulmonary embolism (PE) undergoing catheter directed thrombolysis (CDT) from 2014 to 2020. Efficacy was defined by mean pulmonary pressure drop, and safety was assessed by intracranial and severe bleeding (defined by GUSTO). Forty-three patients were included, aged 64 (56-79) years old, 5 (12%) with shock, most with right ventricle dilation (95%) and bilateral PE (95%) or unilateral (5%) in patients with only one functional lung. CDT was used as first treatment (53%), upscale after anticoagulation alone (42%), or after failed systemic thrombolytics (5%). Median recombinant tissue plasminogen activator (rtPA) dose was 30 (25-35) mg over 20 (20-20) hours, and rtPA bolus was used after catheter placement in 38 cases (89%), consisting of 5 mg (95%) or 1 mg (5%). Only one lung was treated for technical reasons, and 4 (9%) were repositioned in the same lung for continuation of infusion. A significant reduction in mean pulmonary pressure was observed (pre 35 [29-41] mmHg vs. post 24 [20-34] mmHg, p<0.001) with no intracranial bleeding. One patient (2%) experienced severe bleeding, while 5 (12%) presented access site bleeding, and 3 (7%) required blood transfusions. In-hospital mortality was 12% but only one case (2%) due to PE. Our results are similar to previously reported studies.

Prevalence of Imaging Targets in Patients With Minor Stroke Selected for IV tPA Treatment Using MRI: The Treatment of Minor Stroke With MRI Evaluation Study (TIMES).

OBJECTIVE: To determine the IV tissue plasminogen activator (tPA) treatment rate of patients with minor acute ischemic stroke (mAIS) at our centers and compare the frequency of MRI targets by treatment stratification and clinical severity, we evaluated clinical characteristics and baseline MRIs for tPA-treated and untreated patients. METHODS: Patients with ischemic stroke from 2015 to 2017 with admit NIH Stroke Scale (NIHSS) <6 were considered. The treated cohort received standard IV tPA and was screened with baseline MRI. The untreated cohort received no acute intervention and baseline MRI was <4 hours from onset. Patients were stratified into "clearly" and "not clearly" disabling deficits by NIHSS elements. Baseline MRI was evaluated by independent raters for AIS targets, with frequencies compared between groups. RESULTS: Of 255 patients with mAIS ≤4.5 hours from onset, 140 (55%) received IV tPA, accounting for 46% of all IV tPA patients (n = 305). Eighty-five percent (n = 119) were screened with baseline MRI and had significantly more frequent imaging targets compared to those untreated (n = 90). Of this treated cohort, 75% (n = 89) were not clearly disabling. Except for perfusion-diffusion mismatch (81% clearly disabling vs 56% not clearly disabling [p = 0.036]), there were no significant differences in the frequency of imaging targets across the treated cohort stratified by clinical severity. CONCLUSIONS: In MRI-screened mAIS, imaging targets were more frequently seen in patients treated with IV tPA, with similar frequencies even in those without clearly disabling deficits. MRI targets could be used to guide thrombolytic therapy in patients with mAIS; however, a randomized trial is needed to demonstrate efficacy.

Treatment of Acute Ischemic Stroke due to Large Vessel Occlusion With COVID-19: Experience From Paris.

BACKGROUND AND PURPOSE: Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking. We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19. METHODS: All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included. Baseline clinical and radiological findings, treatment, and short-term outcomes are reported. RESULTS: We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO. Eight were men, with a median age of 59.5 years. Seven had none or mild symptoms of COVID-19 at stroke onset. Median time from COVID-19 symptoms to stroke onset was 6 days. All patients had brain imaging within 3 hours from symptoms onset. Five patients had multi-territory LVO. Five received intravenous alteplase. All patients had mechanical thrombectomy. Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital. CONCLUSIONS: Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19. Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19.

Defying the paradigm - rescue thrombolysis in a postoperative patient with pulmonary embolism.

Parenteral anticoagulation is recommended for patients of intermediate - high early mortality risk pulmonary embolism. Rescue reperfusion is considered if signs of hemodynamic decompensation appear. Recent surgery is a contraindication to thrombolysis. Percutaneous catheter directed thrombolysis and surgical embolectomy can be done in such patients. However, they are not readily available. We hereby report a case of rescue thrombolysis in a post lower segment caesarean section (LSCS) patient with pulmonary thromboembolism. We could successfully achieve thrombolysis in our patient with improvement in clinical and hemodynamic parameters and with no major bleeding from any site.

Design of a thrombin inhibitory staphylokinase based plasminogen activator with anti-reocclusion potential.

In the quest of a therapeutically improved thrombolytic drug, we designed and expressed a Staphylokinase based, recombinant fusion protein with fibrin specific clot lysis and anti-thrombin activities derived from human thrombomodulin, a transmembrane glycoprotein with anticoagulant properties, known to form a complex with thrombin and then activating Protein C. The fusion construct was expressed in the yeast Pichia pastoris for cost effective and facile production. The purified construct had comparable plasminogen activation and clot lysis capability as compared to native SAK in that it showed plasmin dependent Plasminogen activation, but exhibited significantly lower fibrinogenolysis (an indicator of fibrin-specific action) even at much higher doses than SAK. In addition, its successful activation of the thrombin-mediated Protein C anticoagulant pathway was reflected in increased in vitro plasma clotting time, as well as inhibition of clot bound thrombin, which led to nearly 15-25% lesser re-formation of fibrin clots after initial successful clot lysis in a specially designed in vitro assay for re-occlusion. Thus, this novel chimeric protein could be of high therapeutic potential as a thrombolytic drug with enhanced fibrin specific clot dissolving properties along with lower bleeding and re-thrombosis complications- a dire need today, especially in the treatment of thrombotic strokes.

Rosiglitazone ameliorates tissue plasminogen activator-induced brain hemorrhage after stroke.

OBJECTIVE: Delayed thrombolytic therapy with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier (BBB) breakdown after ischemic stroke and lead to catastrophic hemorrhagic transformation (HT). Rosiglitazone(RSG), a widely used antidiabetic drug that activates peroxisome proliferator-activated receptor-γ (PPAR-γ), has been shown to protect against cerebral ischemia through promoting poststroke microglial polarization toward the beneficial anti-inflammatory phenotype. However, whether RSG can alleviate HT after delayed tPA treatment remains unknown. In this study, we sort to examine the role of RSG on tPA-induced HT after stroke. METHODS AND RESULTS: We used the murine suture middle cerebral artery occlusion (MCAO) models of stroke followed by delayed administration of tPA (10 mg/kg, 2 hours after suture occlusion) to investigate the therapeutic potential of RSG against tPA-induced HT. When RSG(6 mg/kg) was intraperitoneally administered 1 hour before MCAO in tPA-treated MCAO mice, HT in the ischemic territory was significantly attenuated 1 day after stroke. In the tPA-treated MCAO mice, we found RSG significantly mitigated BBB disruption and hemorrhage development compared to tPA-alone-treated stroke mice. Using flow cytometry and immunostaining, we confirmed that the expression of CD206 was significantly upregulated while the expression of iNOS was down-regulated in microglia of the RSG-treated mice. We further found that the expression of Arg-1 was also upregulated in those tPA and RSG-treated stroke mice and the protection against tPA-induced HT and BBB disruption in these mice were abolished in the presence of PPAR-γ antagonist GW9662 (4 mg/kg, 1 hour before dMCAO through intraperitoneal injection). CONCLUSIONS: RSG treatment protects against BBB damage and ameliorates HT in delayed tPA-treated stroke mice by activating PPAR-γ and favoring microglial polarization toward anti-inflammatory phenotype.

Persistent trigeminal artery in a patient with posterior circulation stroke treated with rt-PA: case report.

BACKGROUND: A persistent trigeminal artery (PTA) is a non-involuted embryonic vessel that connects the cavernous part of the internal carotid artery with the posterior circulation. In the adult it is associated with multiple pathological conditions including trigeminal neuralgia, ophthalmoplegia, hypopituitarism, intracavernous fistula, brain aneurysms and posterior circulation strokes. The latter may occur through steal phenomena or thrombosis in the anterior circulation. PTA associated vertebrobasilar hypoplasia has yet to be associated to TIA like events, however, in the reported case, that seems to be the case with reported vertigo being probably linked to vertebrobasilar insufficiency. CASE REPORT: We present a case of an 82-year-old man with sudden onset neurological deficits, including left hemiparesis with crural predominance, vertical nystagmus, right internuclear ophthalmoplegia, dysarthria and dysmetria on the left arm. CT angiography disclosed basilar artery hypoplasia in the proximal two thirds and a persistent trigeminal artery. He was diagnosed with acute ischemic stroke. He was submitted to rt-PA with partial reversion of deficits. CONCLUSION: The ischemic events related to PTA remain a rare cause of stroke with specific pathophysiological mechanisms and implications. They may occur through steal phenomena or thrombosis in the anterior circulation. Upon literature review, in the described case both mechanisms seem possible, however the transient episodes of vertigo could have been the first sign of vertebrobasilar insufficiency.

Real-World Treatment Trends in Endovascular Stroke Therapy.

Background and Purpose- Recent landmark trials provided overwhelming evidence for effectiveness of endovascular stroke therapy (EST). Yet, the impact of these trials on clinical practice and effectiveness of EST among lower volume centers remains poorly characterized. Here, we determine population-level patterns in EST performance in US hospitals and compare EST outcomes from higher versus lower volume centers. Methods- Using validated diagnosis codes from data on all discharges from hospitals and Emergency Rooms in Florida (2006-2016) and the National Inpatient Sample (2012-2016) we identified patients with acute ischemic stroke treated with EST. The primary end point was good discharge outcome defined as discharge to home or acute rehabilitation facility. Multivariate regressions adjusted for medical comorbidities, intravenous tPA (tissue-type plasminogen activator) usage and annual hospital stroke volume were used to evaluate the likelihood of good outcome over time and by annual hospital EST volume. Results- A total of 3890 patients (median age, 73 [61-82] years, 51% female) with EST were identified in the Florida cohort and 42 505 (median age, 69 [58-79], 50% female) in the National Inpatient Sample. In both Florida and the National Inpatient Sample, the number of hospitals performing EST increased continuously. Increasing numbers of EST procedures were performed at lower annual EST volume hospitals over the studied time period. In adjusted multivariate regression, there was a continuous increase in the likelihood of good outcomes among patients treated in hospitals with increasing annual EST procedures per year (odds ratio, 1.1; 95% CI, 1.1-1.2 in Florida and odds ratio, 1.3; 95% CI, 1.2-1.4 in National Inpatient Sample). Conclusions- Analysis of population-level datasets of patients treated with EST from 2006 to 2016 demonstrated an increase in the number of centers performing EST, resulting in a greater number of procedures performed at lower volume centers. There was a positive association between EST volume and favorable discharge outcomes in EST-performing hospitals.

Rapid Alteplase Administration Improves Functional Outcomes in Patients With Stroke due to Large Vessel Occlusions.

Background and Purpose- We report the relation of onset-to-treatment time and door-to-needle time with functional outcomes and mortality among patients with ischemic stroke with imaging-proven large vessel occlusion treated with intravenous alteplase. Methods- Individual patient-level data from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration were pooled from 7 trials that randomized patients to mechanical thrombectomy added to best medical therapy versus best medical therapy alone. Analysis was restricted to patients who received alteplase directly at the endovascular hospital. The primary outcome was disability defined on the modified Rankin Scale at 3 months. Results- Among 601 patients, mean age was 66.0 years (SD, 13.9), 50% were women, and median National Institutes of Health Stroke Scale score was 17. Onset-to-treatment time was median 125 minutes (interquartile range, 90-170). Door-to-treatment time was median 38 minutes (interquartile range, 26-55). Each 60-minute onset-to-treatment time delay was associated with greater disability at 90 days; the odds of functional independence (modified Rankin Scale, 0-2) at 90 days was 0.82 (95% CI, 0.66-1.03). With each 60-minute delay in door-to-needle time; the odds of functional independence was 0.55 (95% CI, 0.37-0.81) at 90 days. The absolute decline in the rate of excellent outcome (modified Rankin Scale, 0-1 at 90 days) was 20.3 per 1000 patients treated per 15-minute delay in door-to-needle time. The adjusted absolute risk difference for a door-to-needle time <30 minutes versus 30 to 60 minutes was 19.3% for independent outcome (number-needed-to-treat ≈5 to gain 1 additional good outcome). Symptomatic intracranial hemorrhage occurred in 3.4% of patients, without a significant time dependency: odds ratio, 0.74 (95% CI, 0.43-1.28). Conclusions- Faster intravenous thrombolysis delivery is associated with less disability at 3 months among patients with large vessel occlusion.

Prehospital Triage of Acute Ischemic Stroke Patients to an Intravenous tPA-Ready versus Endovascular-Ready Hospital: A Decision Analysis.

BACKGROUND: American Stroke Association guidelines for prehospital acute ischemic stroke recommend against bypassing an intravenous tPA-ready hospital (IRH), if additional transportation time to an endovascular-ready hospital (ERH) exceeds 15-20 min. However, it is unknown when the benefit of potential endovascular therapy at an ERH outweighs the harm from delaying intravenous therapy at a closer IRH, especially since large vessel occlusion (LVO) status is initially unknown. We hypothesized that current time recommendations for IRH bypass are too short to achieve optimal outcomes for certain patient populations. METHODS: A decision analysis model was constructed using population-based databases, a detailed literature review, and interventional trial data containing time-dependent modified Rankin Scale distributions. The base case was triaged by Emergency Medical Services (EMS) 110 min after stroke onset and had a 23.6% LVO rate. Base case triage choices were (1) transport to the closest IRH (12 min), (2) transport to the ERH (60 min) bypassing the IRH, or (3) apply the Cincinnati Stroke Triage Assessment Tool and transport to the ERH if positive for LVO. Outcomes were assessed using quality-adjusted life years (QALYs). Sensitivity analyses were performed for all major variables, and alternative prehospital stroke scales were assessed. RESULTS: In the base case, transport to the IRH was the optimal choice with an expected outcome of 8.47 QALYs. Sensitivity analyses demonstrated that transport to the ERH was superior until bypass time exceeded 44 additional minutes, or when the onset to EMS triage interval exceeded 99 min. As the probability of LVO increased, ERH transport was optimal at longer onset to EMS triage intervals. The optimal triage strategy was highly dependent on specific interactions between the IRH transportation time, ERH transportation time, and onset to EMS triage interval. CONCLUSIONS: No single time difference between IRH and ERH transportation optimizes triage for all patients. Allowable IRH bypass time should be increased and acute ischemic stroke guidelines should incorporate the onset to EMS triage interval, IRH transportation time, and ERH transportation time.

Acute basilar thrombosis: Recanalization following intravenous thrombolysis is dependent on thrombus length.

INTRODUCTION: We investigated whether thrombus length measured in Computed Tomography Angiography (CTA) is predictive of the success rate of intravenous thrombolysis (IVT) in acute basilar occlusion and whether recanalization can be achieved by additional mechanical endovascular thrombectomy. METHODS: In 51 patients with acute basilar thrombosis thrombus length was measured on CTA images before intravenous thrombolysis (IVT) with rt-PA was started. After 114 minutes on average success of IVT was evaluated either by CTA or DSA. Patients with persistent basilar occlusion and no major brainstem infarction on CT underwent endovascular recanalization. RESULTS: 87% of patients had no recanalization of basilar artery after IVT alone. The average thrombus length was 15 mm in patients with persistent basilar occlusion after IVT and 7 mm in patients with recanalization after IVT. Thrombi longer than 13 mm did not resolve after IVT alone and 80% of thrombi shorter than 13 mm did not resolve either. 41 patients were transferred to endovascular recanalization; endovascular therapy was performed successfully in 90% (37 / 41). CONCLUSIONS: Recanalization rates in acute basilar occlusion after IVT alone are low and dependent on thrombus length. Additional mechanical endovascular thrombectomy showed to be a very successful recanalization therapy.

Safety and Feasibility of Temporary Superior Vena Cava Filter Combined with Balloon Dilatation and Catheter-Directed Thrombolysis for Catheter-Related Thrombosis.

BACKGROUND: The objective was to evaluate the safety and feasibility of temporary superior vena cava (SVC) filter combined with balloon dilatation and catheter-directed thrombolysis for the treatment of catheter-related thrombosis (CRT) caused by implanted ports. METHODS: Between February 2014 and October 2016, 13 patients with implanted port-related CRT in internal jugular vein, brachiocephalic vein, and/or subclavian vein were treated by temporary SVC filter, balloon dilatation, and catheter-directed thrombolysis. Clinical data were retrospectively analyzed with respect to clinical characteristics, SVC filter placement and retrieval, balloon dilatation, and catheter-directed thrombolysis. RESULTS: Filter placement and retrieval, balloon dilatation, and catheter-directed thrombolysis were successful in all patients with complete patency of the suffered vessels. No complications such as local infection, filter migration, bleeding, and pulmonary embolism were found. CONCLUSIONS: Based on the small number of patients, it appears that temporary SVC filter combined with balloon dilatation and catheter-directed thrombolysis is a safe and effective method for the treatment of CRT associated with malfunction of the implanted ports and complete obstruction of affected veins. Further studies are required to demonstrate the cost-effectiveness and complications compared to conventional therapy.

Initial Single-Center Technical Experience With the BrainPath System for Acute Intracerebral Hemorrhage Evacuation.

BACKGROUND: Surgical intervention has been proposed as a means of reducing the high morbidity and mortality associated with acute intracerebral hemorrhage (ICH), but many previously reported studies have failed to show a clinically significant benefit. Newer, minimally invasive approaches have shown some promise. OBJECTIVE: We report our early single-center technical experience with minimally invasive clot evacuation using the BrainPath system. METHODS: Prospective data were collected on patients who underwent ICH evacuation with BrainPath at the Cleveland Clinic from August 2013 to May 2015. RESULTS: Eighteen patients underwent BrainPath evacuation of ICH at our center. Mean ICH volume was 52.7 mL ± 22.9 mL, which decreased to 2.2 mL ± 3.6 mL postevacuation, resulting in a mean volume reduction of 95.7% ± 5.8% (range 0-14 mL, P < .001). In 65% of patients, a bleeding source was identified and treated. There were no hemorrhagic recurrences during the hospital stay. In this cohort, only 1 patient (5.6%) died in the first 30 days of follow-up. Median Glasgow Coma Score improved from 10 (interquartile range 5.75-12) preoperation to 14 (interquartile range 9-14.25) postoperation. Clinical follow-up in this cohort is ongoing. CONCLUSION: Evacuation of ICH using the BrainPath system is safe and technically effective. The volume of clot removed compares favorably with other published studies. Early improved clinical outcomes are suggested by improvement in Glasgow Coma Score and reduced 30-day mortality. Ongoing analysis is necessary to elucidate long-term clinical outcomes and the subsets of patients who are most likely to benefit from surgery.

Can the benefits of rtPA treatment for stroke be improved?

Tissue-type plasminogen activator (tPA) is a serine protease well known to promote fibrinolysis. This is why: its recombinant form (rtPA) can be used, either alone or combined with thrombectomy, to promote recanalization/reperfusion following ischemic stroke. However, its overall benefits are counteracted by some of its side-effects, including incomplete lysis of clots, an increased risk of hemorrhagic transformation and the possibility of neurotoxicity. Nevertheless, better understanding of the mechanisms by which tPA influences brain function and promotes its alteration may help in the design of new strategies to improve stroke therapy.

Desmoteplase for Acute Ischemic Stroke: A Systematic Review and Metaanalysis of Randomized Controlled Trials.

INTRODUCTION: There is an unmet need to develop better treatments for acute ischemic stroke (AIS). Desmoteplase is a vampire bat saliva-derived analogue of human tissue plasminogen activator. It has higher fibrin selectivity and a longer half-life, compared to alteplase. We performed this metaanalysis to investigate the safety and efficacy of desmoteplase in AIS. METHOD: A computer literature search (PubMed, EMBASE, CENTRAL, Scopus, Web of science, and clinicaltrials.gov) was carried out. Data were extracted from eligible records and analyzed using RevMan software (version 5.3 for windows). Safety and efficacy endpoints were pooled as odds ratios (ORs) for the two groups. RESULT: Five randomized trials (n=821 patients) were pooled in the final analysis. The overall effect size favored desmoteplase over placebo in terms of reperfusion 4 to 24 hours posttreatment (OR 1.49, 95% CI [1.02, 2.19]). However, the pooled effect size did not favor either of the two groups in terms of good clinical outcome at 90 days (OR 1.16, 95% CI [0.86, 1.55]). Neither of the primary safety outcomes differed significantly between the two groups (symptomatic intracranial hemorrhage: OR 1.29, 95% CI [0.53, 3.16] and mortality within 90 days: OR 1.20, 95% CI [0.73, 1.97]). CONCLUSION: Current evidence suggests a favorable reperfusion effect for desmoteplase within 3 to 9 hours after AIS. Further large randomized trials, using a moderate dose between 90 µg/kg and 125 µg/kg, are required to translate this successful reperfusion into better clinical and quality of life outcomes for AIS patients.

Endovascular Treatment of Thrombosis and Embolism.

Deep venous thrombosis (DVT) is a common disorder with a significant mortality rate. Successful endovascular treatment of acute DVT is most likely to be achieved in patients with recently formed thrombus, (<10-14 days) with acute iliofemoral DVT. Endovascular treatment options include: Catheter-directed thrombolysis (CDT), pharmacomechanical catheter-directed thrombolysis (PCDT), percutaneous aspiration thrombectomy (PAT), vena cava filter protection, venous balloon dilatation and venous stent implantation. Current practice shows strong clinical tendency for the use of PCDT with or without other endovascular methods and an individualized approach for each DVT patient. PMT has not received general acceptance because of the associated risk of PE and damage to venous valves caused by thrombectomy devices. PAT is most commonly used as an adjunctive endovascular technique like balloon maceration to fragment thrombus, balloon angioplasty, stent implantation and vena cava filter placement. Interventional endovascular therapies for DVT have the potential to provide PE protection and prevention of PTS. Patient centered individualized approach for endovascular DVT treatment is recommended to optimize the ideal clinical result.Acute stroke is the leading cause of death for people above the age of 60 and the fifth leading cause in people aged 15-59. Mortality during the first 30 days of ischemic stroke is 20 % and 30 % of survivors will remain permanently disabled. Acute stroke patients within the therapeutic window must receive IVrtPA unless there is a contraindication. In case of contraindication to IVrtPA or for patients out of the therapeutic window for thrombolytics, standart of care is the intraarterial treatment. Patients have to be transferred to a comprehensive stroke center with capacity of dedicated neurovascular imaging and interventional neuroradiology. Noncontrast head CT that is used to rule out hemorrhage is followed by imaging studies dedicated to show if there is reasonable penumbra to save. Intraarterial thrombolysis has the main advantage of extended therapy window, earlier and more efficient recanalization and less risk of hemorrhage due to lower doses of thrombolytics. Mechanical thrombectomy has several advantages over IV/IA fibrinolysis including faster recanalization and less risk of hemorrhage especially in large artery occlusions. ASA guidelines recommend choosing stent retrievers over other devices for mechanical thrombectomy. Better recanalization rates and less infarct volume after mechanical thrombectomy result in higher numbers of functionally independent patients compared with other treatments. Two landmark studies that were published recently, SWIFT PRIME and MR CLEAN, showed that IA treatment especially with the new stent retrievers lead to a significant increase in functional recovery and independence in daily life after an acute stroke.Cerebral venous and sinus thrombosis (CVST) comprises nearly 0.5-1 % of all stroke cases. CVST causes different neurological deficits depending on the sinus/cortical vein involved. CVST may cause death and dependency in 13.4 % of patients. CT/CT venography and MR/MR venography can be effectively used to diagnose and to follow up CVT cases. Anticoagulation with heparin is the most widely accepted therapy to prevent the expansion of the thrombus. Patients deteriorating despite heparinization and patients presenting with very severe neurological deficits must receive endovascular treatment. Endovascular methods include intrasinus infusion of thrombolytics or heparin, balloon angioplasty, mechanical thrombectomy or a combination of different techniques. There is a higher rate or recanalization with endovascular methods compared to other medical therapies.

Rapid Systematic Review: Intra-Arterial Thrombectomy ("Clot Retrieval") for Selected Patients with Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of morbidity and mortality. However, precisely defining the optimal treatment for individual patients early after AIS onset remains elusive. There has recently been a surge in published studies documenting the effectiveness of mechanical intra-arterial thrombectomy for treatment of a subset of patients with AIS. This therapy has been proposed and studied for the small (<1.2%) subgroup of patients with ischemic strokes who have "large vessel" strokes or strokes that fail to improve after the administration of tissue plasminogen activator (t-PA). The current rapid systematic review provides practicing emergency physicians updated information regarding mechanical thrombectomy as a treatment option for carefully selected AIS patients. METHODS: A PubMed literature search was conducted from January 1996 to June 2016 and limited to human clinical trials written in English with relevant keywords. High-quality randomized controlled studies identified then underwent a structured review. RESULTS: In total, 179 papers fulfilling the search criteria were screened and 8 appropriate articles were rigorously reviewed in detail and recommendations given on the effectiveness and indication of mechanical intra-arterial thrombectomy for the treatment of AIS. CONCLUSIONS: Mechanical intra-arterial thrombectomy reduces long-term disability in a properly selected subset of patients who have an AIS caused by large vessel occlusion. Many of these patients will have failed to improve after intravenous administration of t-PA, and mortality is not increased when combined with t-PA. Careful screening criteria should be in place to identify the limited subset of patients to whom this therapy is delivered to derive optimal treatment benefits.

Outpatient management of transient ischaemic attack.

Stroke is a significant cause of death and disability in Singapore; in 2014, it was the fourth most common cause of death. Transient ischaemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischaemia without evidence of acute infarction. The diagnosis of TIA/acute stroke needs to be considered in all patients who present with sudden focal neurological dysfunction. Prompt referral for assessment, neuroimaging and intervention provides the best chance for neurological recovery and/or minimising further neurological damage. Primary care physicians have a crucial role in TIA/stroke prevention and management. This includes referring patients with suspected acute TIA/stroke to hospitals with stroke treatment facilities immediately; managing the modifiable risk factors of cerebral ischaemia; continuing prescription of antiplatelet agents and/or anticoagulation where indicated; and teaching patients to recognise and respond to suspected cerebral ischaemia using the FAST (face, arm, speech, time) acronym.

Mecanismos epigenéticos en el desarrollo de la memoria y su implicación en algunas enfermedades neurológicas / Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases

Introducción: Hoy en día se acepta que el sistema nervioso central adulto posee una enorme flexibilidad morfofuncional que le permite realizar procesos de remodelación estructural aún después de haber alcanzado su desarrollo y maduración. Además del enorme número de genes que participan en el desarrollo de la memoria, los diferentes mecanismos epigenéticos conocidos también han sido involucrados en procesos de modificación neuronal normal y patológica y, por ende, en los mecanismos de desarrollo de la memoria. Desarrollo: Este trabajo fue llevado a cabo a través de una sistemática revisión de las bases de datos de publicaciones biomédicas sobre los aspectos genéticos y epigenéticos que participan en la función sináptica y la memoria. Conclusiones: La activación de la expresión génica, en respuesta a estímulos extrínsecos, ocurre también en células nerviosas diferenciadas. La actividad neuronal induce formas específicas de plasticidad sináptica que permiten la formación y almacenamiento de la memoria a largo plazo. Los mecanismos epigenéticos tienen un papel crucial en los procesos de modificación sináptica y en la formación y desarrollo de la memoria. Alteraciones en estos mecanismos producen déficit cognitivo y de memoria en padecimientos neurodegenerativos (enfermedad de Alzheimer y Huntington) así como en trastornos del desarrollo neurológico (síndrome de Rett, X-frágil y esquizofrenia). Los resultados obtenidos en diferentes modelos muestran, sin embargo, un escenario promisorio con tratamientos potenciales para algunos de estos padecimientos

Introduction: Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. Development: This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. Conclusions: The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases