Santiago Ortega-Gutierrez

Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging

Background Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. Methods We conducted a multicenter, randomized, open‐label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle‐cerebral‐artery or internal‐carotid‐artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular‐therapy group) or standard medical therapy alone (medical‐therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90. Results The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular‐therapy group and 90 to the medical‐therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90‐day mortality rate was 14% in the endovascular‐therapy group and 26% in the medical‐therapy group (P=0.05), and there was no significant between‐group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18). Conclusions Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle‐cerebral‐artery or internal‐carotid‐artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415.)

Diagnosis and management of pediatric arterial ischemic stroke.

Pediatric stroke is among the top 10 causes of death in children and an important cause of chronic morbidity, with an incidence of 3.3/100,000 children/year. Risk factors associated with stroke in children include cardiac diseases, hematologic and vascular disorders, and infection. Clinical presentation varies depending on age, underlying cause, and stroke location. Antithrombotics and anticoagulants are used in the treatment of pediatric stroke; however, there are no established guidelines for the use of these agents in children. In this article we review the cause, pathophysiology, clinical presentation, diagnosis, acute management, secondary prevention, and outcome of children with stroke. The approach to patients with sickle cell disease and Moyamoya disease is also discussed. Up to date studies to determine the optimal acute treatment of childhood stroke and secondary prevention and risk factor modification are critically needed.

Measurement of Antiplatelet Inhibition during Neurointerventional Procedures: The Effect of Antithrombotic Duration and Loading Dose

Symptomatic thromboembolic events are the most common complications associated with aneurysm coiling, and carotid and intracranial stenting. Our objective is to assess the effect of aspirin (ASA) and clopidogrel dose and duration on platelet inhibition using a point of care assay in neurointerventional (NI) suite.

Status Epilepticus–Induced Hyperemia and Brain Tissue Hypoxia After Cardiac Arrest

OBJECTIVE To report changes of cerebral blood flow and metabolism associated with status epilepticus after cardiac arrest. DESIGN Case report. SETTING Neurological intensive care unit in a university hospital. PATIENT An 85-year-old man resuscitated from out-of-hospital cardiac arrest underwent brain multimodality monitoring and treatment with therapeutic hypothermia. MAIN OUTCOME MEASURES Changes of cerebral blood flow and metabolism. RESULTS Repetitive electrographic seizure activity detected at the start of monitoring was associated with dramatic reductions in brain tissue oxygen tension and striking surges in cerebral blood flow and brain temperature. Intravenous lorazepam and levetiracetam administration resulted in immediate cessation of the seizures and these associated derangements. The lactate to pyruvate ratio was initially elevated and trended down after administration of anticonvulsants. CONCLUSION Brain multimodality monitoring is a feasible method for evaluating secondary brain injury associated with seizure activity after cardiac arrest.

Melatonin improves deferoxamine antioxidant activity in protecting against lipid peroxidation caused by hydrogen peroxide in rat brain homogenates.

Deferoxamine (DF) is an antioxidant molecule because of its ability to chelate iron. This study compared the ability of DF alone or in combination with melatonin, 5-methoxytryptophol or pinoline in preventing lipid peroxidation due to hydrogen peroxide (H(2)O(2)) in rat brain homogenates. Malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) in the homogenates were measured as indices of lipid peroxidation. Incubation of homogenates with DF reduced, in a dose-dependent manner, MDA+4-HDA formation due to H(2)O(2). When melatonin, 5-methoxytryptophol or pinoline were added to the incubation medium, the efficacy of DF in preventing lipid peroxidation was enhanced. These cooperative effects between DF, melatonin, and related pineal products may be important in protecting tissues from the oxidative stress due to iron overload.

Melatonin reduces protein and lipid oxidative damage induced by homocysteine in rat brain homogenates

Numerous data indicate that hyperhomocysteinemia is a risk factor for cardio‐ and cerebrovascular diseases. At least in part, homocysteine (HCY) impairs cerebrovascular function because it generates large numbers of free radicals. Since melatonin is a well‐known antioxidant, which reduces oxidative stress and decreases HCY concentrations in plasma, the aim of this study was to investigate the effect of melatonin in preventing HCY‐induced protein and lipid oxidation in rat brain homogenates. Brain homogenates were obtained from Sprague–Dawley rats and were incubated with or without HCY (0.01–5 mM) or melatonin (0.01–3 mM). Carbonyl content of proteins, and malondialdehyde (MDA) and 4‐hydroxyalkenals (4‐HDA) concentrations in the brain homogenates were used as an index of protein and lipid oxidation, respectively. Under the experimental conditions used, the addition of HCY (0.01–5 mM) to the homogenates enhanced carbonyl protein and MDA+4‐HDA formation. Melatonin reduced, in a concentration‐dependent manner, protein and lipid oxidation due to HCY in the brain homogenates. These data suggest that preserving proteins from oxidative insults is an additional mechanism by which melatonin may act as an agent in potentially decreasing cardiovascular and cerebrovascular diseases related to hyperhomocysteinemia. J. Cell. Biochem. 102: 729–735, 2007.

Impact of Acute Ischemic Stroke Treatment in Patients >80 Years of Age The Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) Consortium Experience

Background and Purpose Few studies have addressed outcomes among patients ≥80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients ≥80 years compared to their younger counterparts, and (2) those over age 80 receiving intra-arterial therapy (IAT) compared to those treated with intravenous recombinant tissue plasminogen activator (IVrtPA).Background and Purpose— Few studies have addressed outcomes among patients ≥80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients ≥80 years compared with their younger counterparts; and (2) those over >80 years receiving intra-arterial therapy (IAT) compared with those treated with intravenous recombinant tissue-type plasminogen activator (IV rtPA). Methods— Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IV rtPA or IAT from January 1, 2005, to December 31, 2010. IAT was defined as receiving any endovascular therapy; IAT was further divided into bridging therapy when the patient received both IAT and IV rtPA and endovascular therapy alone. In-hospital mortality was compared in (1) all patients aged ≥80 years versus younger counterparts; and (2) IAT, bridging therapy, and endovascular therapy alone versus IV rtPA only among those age ≥80 years using multivariable logistic regression. An age-stratified analysis was also performed. Results— A total of 3768 patients were included in the study; 3378 were treated with IV rtPA alone and 808 with IAT (383 with endovascular therapy alone and 425 with bridging therapy). Patients ≥80 years (n=1182) had a higher risk of in-hospital mortality compared with younger counterparts regardless of treatment modality (OR, 2.13; 95% CI, 1.60–2.84). When limited to those aged ≥80 years, IAT (OR, 0.95; 95% CI, 0.60–1.49), bridging therapy (OR, 0.82; 95% CI, 0.47–1.45), or endovascular therapy alone (OR, 1.15; 95% CI, 0.64–2.08) versus IV rtPA were not associated with increased in-hospital mortality. Conclusions— IAT does not appear to increase the risk of in-hospital mortality among those aged >80 years compared with IV thrombolysis alone.

Endovascular treatment of intracranial aneurysms using the Pipeline Flex embolization device: a case series of 30 consecutive patients

Background The Pipeline Flex embolization device has some peculiarities in comparison with the previous generation device. Despite recent reports of the modified delivery system, its safety is still unknown. Objective To illustrate the intraprocedural and periprocedural complication rate with this new device in 30 consecutive patients. Material and methods Clinical, procedural, and angiographic data, including aneurysm size and location, device or devices used, angiographic and clinical data were analyzed. Results 30 patients harboring 30 aneurysms were analyzed. 39 devices were placed properly. Multiple Pipeline embolization devices (PEDs) were used in 7 cases. In 28 devices the distal end opened fully from the beginning with a complete wall apposition. In the remaining 11 devices, distal-end opening of the devices was instant but partial, but fully opened easily after recapture. Among the 30 procedures, recapture and reposition of the Pipeline Flex was performed four times owing to proximal migration/malposition of the device during delivery. Four intraprocedural/periprocedural complications occurred, of which 2 resulted in major complications, with neurologic deficits persisting for longer than 7 days. The 30-day morbidity rate was 6.6%, with no deaths. No aneurysm rupture or parenchymal hemorrhage was seen. Conclusions The Pipeline Flex embolization device allows more precise and controlled deployment than the first-generation device. The number of devices and the complication rate during the learning curve are lower than reported with the first-generation PED. The new delivery system and the resheathing maneuvers do not seem to increase the intraprocedural complication rate in comparison with the first-generation PED.

Melatonin and pinoline prevent aluminium-induced lipid peroxidation in rat synaptosomes

The serum concentrations of aluminum, a metal potentially involved in the pathogenesis of Alzheimers disease, increase with age. Also, intense and prolonged exposure to aluminum may result in dementia. Melatonin and pinoline are two well known antioxidants that efficiently reduce lipid peroxidation due to oxidative stress. Herein, we investigated the effects of melatonin and pinoline in preventing aluminum promotion of lipid peroxidation when the metal was combined with FeCl3 and ascorbic acid in rat synaptosomal membranes. Lipid peroxidation was estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA) concentrations in the membrane suspension. Under the experimental conditions used herein, the addition of aluminum (0.0001 to 1 mmol/L) enhanced MDA + 4-HDA formation in the synaptosomes. Melatonin and pinoline reduced, in a concentration-dependent manner, lipid peroxidation due to aluminum, FeCl3 and ascorbic acid in the synaptosomal membranes. These results suggest that the indoleamine melatonin and the beta-carboline pinoline may potentially act as neuroprotectant agents in the therapy of those diseases with elevated aluminum concentrations in the tissues.

Preliminary experience with Precipitating Hydrophobic Injectable Liquid (PHIL) in treating cerebral AVMs

Objective To describe our early experience in treating cerebral arteriovenous malformations (AVMs) with the new Precipitating Hydrophobic Injectable Liquid (PHIL) embolic material. Materials and methods Between June and August 2015 five patients with cerebral AVMs were treated at two tertiary university hospitals. PHIL was used as complementary treatment to Onyx liquid embolic material or as the sole endovascular treatment. Results Five patients (average age 39 years (range 19–73)) with ruptured plexiform AVMs were treated. The group included one patient with Spetzler–Martin grade II AVMs, three grade III, and one grade IV. One grade II and two grade III AVMs were cured. A total of nine pedicles were embolized with an average of two pedicles per session. There were no procedural complications. One patient had a seizure after embolization but a brain CT scan showed no hemorrhage. Conclusions PHIL is a new embolic agent that can be used for the treatment of cerebral AVMs.