Eduardo Wajnberg

Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection

Cell-based treatments have been considered a promising therapy for neurological diseases. However, currently there are no clinically available methods to monitor whether the transplanted cells reach and remain in the brain. In this study we investigated the feasibility of detecting the distribution and homing of autologous bone-marrow mononuclear cells (BMMCs) labeled with Technetium-99 m ((99m)Tc) in a cell-based therapy clinical study for chronic ischemic stroke. Six male patients (ages 24-65 years) with ischemic cerebral infarcts within the middle cerebral artery (MCA) between 59 and 82 days were included. Cell dose ranged from 1.25x10(8) to 5x10(8). Approximately 2x10(7) cells were labeled with (99m)Tc and intra-arterially delivered together with the unlabeled cells via a catheter navigated to the MCA. None of the patients showed any complications on the 120-day follow-up. Whole body scintigraphies indicated cell homing in the brain of all patients at 2 h, while the remaining uptake was mainly distributed to liver, lungs, spleen, kidneys and bladder. Moreover, quantification of uptake in Single-Photon Emission Computed Tomography (SPECT) at 2 h showed preferential accumulation of radioactivity in the hemisphere affected by the ischemic infarct in all patients. However, at 24 h homing could only distinguished in the brains of 2 patients, while in all patients uptake was still seen in the other organs. Taken together, these results indicate that labeling of BMMCs with (99m)Tc is a safe and feasible technique that allows monitoring the migration and engraftment of intra-arterially transplanted cells for at least 24 h.

Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke

AIMS To assess the safety and feasibility of intra-arterial transplantation of autologous bone marrow mononuclear cells in patients with middle cerebral artery ischemic stroke within 90 days of symptom onset. PATIENTS & METHODS Six patients were included in the study, and they received 1-5 × 10(8) bone marrow mononuclear cell and were evaluated using blood tests, neurological and imaging examination before treatment, and 1, 3, 7, 30, 60, 90, 120 and 180 days after transplantation. Scintigraphies were carried out 2 and 24 h after the procedure to analyze the biodistribution of labeled cells. Electroencephalogram was conducted within 7 days after transplantation. RESULTS No patients exhibited any complication or adverse events during the procedure. There was no worsening in the neurological scales until the end of the follow-up. CONCLUSION Intra-arterial bone marrow mononuclear cell transplantation is feasible and safe in patients with nonacute ischemic strokes of the middle cerebral artery. Further studies are required to evaluate the efficacy of this therapy.

Biodistribution of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients

AIMS To assess the biodistribution of bone marrow mononuclear cells (BMMNC) delivered by different routes in patients with subacute middle cerebral artery ischemic stroke. PATIENTS & METHODS This was a nonrandomized, open-label Phase I clinical trial. After bone marrow harvesting, BMMNCs were labeled with technetium-99m and intra-arterially or intravenously delivered together with the unlabeled cells. Scintigraphies were carried out at 2 and 24 h after cell transplantation. Clinical follow-up was continued for 6 months. RESULTS Twelve patients were included, between 19 and 89 days after stroke, and received 1-5 × 10(8) BMMNCs. The intra-arterial group had greater radioactive counts in the liver and spleen and lower counts in the lungs at 2 and 24 h, while in the brain they were low and similar for both routes. CONCLUSION BMMNC labeling with technetium-99m allowed imaging for up to 24 h after intra-arterial or intravenous injection in stroke patients.

Early Tissue Distribution of Bone Marrow Mononuclear Cells After Intra-Arterial Delivery in a Patient With Chronic Stroke

A 24-year-old man with a cerebral infarct within the left middle cerebral artery (MCA) territory was enrolled in a study to assess the safety of autologous bone marrow mononuclear cell (BMMC) transplantation in patients with ischemic stroke (NCT00473057). His National Institutes of Health Stroke Scale score was 7. Computed tomography (Figure 1A) and technetium-99m ethyl cysteinate dimer (99mTc ECD) single photon emission computed tomography (SPECT) (Figures 1B and 2⇓ and Movie I in the online-only Data Supplement) indicated the location of the infarct. Sixty-seven days after onset of symptoms, the patient underwent BMMC transplantation. Bone marrow blood was aspirated under local anesthesia from both iliac crests and processed to isolate the mononuclear cell fraction. A total of 5×108 BMMCs was suspended into a volume of 10 mL, and 1 mL of the cell suspension was radiolabeled with 99mTc (radioactivity 111 MBq, physical …

Single-center experience with the Neuroform stent for endovascular treatment of wide-necked intracranial aneurysms.

BACKGROUND Stent-assisted coiling is an accepted endovascular treatment (EVT) for wide-necked intracranial aneurysms. The Neuroform stent (Target Therapeutics, Fremont, Calif) is a flexible nitinol self-expandable stent that was designed to potentially overcome the limitations of balloon expandable coronary stents in the intracranial circulation. The aim of this study was to reenforce the use of this stent for EVT of wide-necked cerebral aneurysms. METHODS Between March 2005 and March 2008, 24 patients harboring wide-necked cerebral aneurysms were treated with stent reconstruction of the aneurysm neck. Inclusion criteria restricted the group to adult patients with wide-necked intracranial aneurysms (ruptured and unruptured lesions). Immediate postprocedure angiography studies were performed to determine successful coil occlusion of the aneurysm as well as patency of the parent vessel. We assessed the clinical history, aneurysm dimensions, and technical detail of the procedures, including any difficulties with stent placement and deployment, degree of aneurysm occlusion, and complications. Clinical outcome was assessed with the Glasgow Outcome Scale (GOS). RESULTS The stent was easily navigated and precisely positioned in 24 of 26 cases. However, technical difficulties occurred in 9 patients, including difficulties in crossing the stents interstice in 6 cases, inadvertent stent delivery (n = 1), and incapacity of stent delivery (n = 1) and incapacity of crossing the neck (n = 1). These latter 2 cases were classified as failures of the stent-assisted technique. A single procedural complication occurred, involving transient nonocclusive intrastent thrombus formation, which was treated uneventfully with abciximab. Seventeen patients experienced excellent clinical outcomes (GOS 5), with good outcomes (GOS 4) in 5 patients and a poor outcome (GOS 3) in 2 patients. There were no treatment-related deaths or neurologic complications (mean clinical follow-up, 12 months). Angiographic results consisted of 17 complete occlusions, 4 neck remnants, and 3 incomplete occlusions. CONCLUSIONS The Neuroform stent is very useful for EVT of wide-necked intracranial aneurysms because it is easy to navigate and to deploy accurately. In most cases, the stent can be deployed precisely, even in very tortuous carotid siphons. Although in some cases delivery and deployment was challenging, clinically significant complications were not observed.

Endovascular treatment for intracranial infectious aneurysms

OBJECTIVE To re-enforce an alternative, less aggressive treatment modality in the management of intracranial infectious aneurysms. METHOD We present a series of five patients with infectious endocarditis and intracranial infectious aneurysms (mycotic aneurysms) managed by means of endovascular treatment. RESULTS Endovascular treatment was executed technically uneventfully in all patients. Three patients had favorable clinical outcome: two were classified as Glasgow Outcome Scale 4/5, and one had total neurological recovery (GOS 5/5). Two patients died (GOS 1/5), one in consequence of the initial intracranial bleeding and the other after cardiac complications from endocarditis and open-heart surgery. CONCLUSION Endovascular techniques are an expanding option for the treatment of IIAs. It has been especially useful for infectious endocarditis patients with IIA, who will be submitted to cardiac surgery with cardiopulmonary bypass and anticoagulation, with the risk of intracranial bleeding.

Progressive deconstruction: a novel aneurysm treatment using the pipeline embolization device for competitive flow diversion: case report.

BACKGROUND AND IMPORTANCE: A variety of deconstructive and reconstructive therapies have been used to treat intracranial aneurysms. The Pipeline embolization device (PED) has become a quite successful option to treat aneurysms, while reconstructing and remodeling the parent vessel. We report a case of off-label PED use, where a flow diverter was placed across the parent vessel of a giant intracranial aneurysm in a novel deconstructive strategy. CLINICAL PRESENTATION: A 40-year-old man with a giant, slow-flow aneurysm of the distal middle cerebral artery (MCA) was treated with the placement of a PED across the vessel containing the aneurysm after superselective test balloon occlusion of that vessel failed. PED was successfully deployed in a competing MCA branch across the origin of the MCA branch supplying the giant aneurysm. The patient continued dual-antiplatelet therapy for 5 months and aspirin monotherapy thereafter. Follow-up angiography, performed 6 months after treatment, demonstrated complete and asymptomatic thrombosis of the aneurysm and its parent MCA branch. A collateral pial and leptomeningeal network developed, reconstructing the distal branches of the occluded MCA branch. After 18 months, the patient remains neurologically intact. CONCLUSION: This appears to be the first description of progressive deconstruction for aneurysm treatment by using PED. Despite not tolerating acute vessel occlusion with superselective test balloon occlusion, the patient was asymptomatic following long-term occlusion with PED secondary to the growth of pial and leptomeningeal collateral networks. ABBREVIATIONS: MCA, middle cerebral artery PED, Pipeline embolization device

Endovascular treatment of tentorial dural arteriovenous fistulae.

Tentorial dural arteriovenous fistula (DAVF) is a rare vascular disease, which accounts for less than 4% of all cases of intracranial DAVF. Because of the high risk of intracranial hemorrhage, patients with tentorial DAVF need aggressive treatment. Management approaches are still controversial, and endovascular treatment has emerged as an effective alternative. In the current work, we describe our experience with the endovascular approach in the treatment of these deep and complex DAVF of the tentorium. Eight patients were treated between January 2006 and July 2009. Six patients (75%) presented with intracranial hemorrhage related to the DAVF rupture. Four patients (50%) had subarachnoid bleeding and two had intraparenchymal hematoma. Endovascular treatment was performed via the transarterial route alone in five cases (62.5%), by the transvenous approach in two cases (25.0%) and in a combined procedure using both arterial and venous routes in one patient (12.5%). Complete obliteration of the fistula was achieved in all cases. The outcome at 15 months was favorable (modified Rankin scale 0–3) in seven (87.5%) patients. Complete cure of the lesion was confirmed in these cases. This paper reports on the effectiveness of endovascular treatment in tentorial DAVF management. The choice of the venous versus the arterial approach is determined by regarding different anatomical dispositions.

Frameless stereotactic navigation for intraoperative localization of infectious intracranial aneurysm.

Department of Radiology.Received 27 April 2009, received in final form 14 July 2009. Accepted 6 August 2009.Dr. Jorge Marcondes de Souza – Department of Neurosurgery / Hospital Universitario Clementino Fraga Fillho - Av. Rodolpho Rocco 250 - 21941-902 Rio de Janeiro RJ - Brasil. E-mail address: jmarcondes@hucff.ufrj.br

O uso de stents farmacológicos no tratamento da estenose das artérias vertebrais

OBJECTIVE: To report the feasibility and safety of percutaneous transluminal angioplasty with paclitaxel-eluting stents for management of vertebral artery stenosis in 14 patients, after two-year follow-up. MATERIALS AND METHODS: Fourteen patients with a mean age of 67.2 years were submitted to endovascular treatment with placement of paclitaxel-eluting stents. The primary objective of the present study was to evaluate the safety of the procedure. The clinical effectiveness was evaluated according to the rates of restenosis and recurrence of ischemic events. RESULTS: The initial stenosis degree ranged from 50% to 99% (mean, 73.3% ± 10.9%). The rate of technical success achieved 100%. Neither complications directly related to the procedure nor recurrence of symptoms were observed after 24-month follow-up. The rate of intra-stent restenosis was 7.1%, although asymptomatic in all the cases. CONCLUSION: The present study suggests that vertebral artery angioplasty with paclitaxel-eluting stents is a feasible and promising technique in terms of safety and effectiveness in the prevention of recurrent ischemia and restenosis.