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.
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.
BMMNC labeling with technetium-99m allowed imaging for up to 24 h after intra-arterial or intravenous injection in stroke patients.
BACKGROUND The safety and efficacy of the first generation of the Pipeline Embolization Device (PED; Medtronic Inc) have been proven in large case series. Ischemic events are one of the most common complications following treatment of aneurysms with flow diverters. The new PED Flex with Shield technology (PED Shield; Medtronic Inc) was introduced to minimize the rate of complications. OBJECTIVE To evaluate the outcomes of patients harboring aneurysms treated with the PED Shield. METHODS This was an observational, prospective, single-arm multicenter study of patients treated with the PED Shield. The primary safety endpoint was the absence of major neurological complications and death. The secondary effectiveness endpoint was angiographic occlusion at 6 and 12 mo. Technical complications were also reported. RESULTS Between November 2017 and December 2018, 151 patients from 7 centers with 182 aneurysms were enrolled. The mean aneurysm size was 7.0 mm; 27 (14.8%) aneurysms were large, and 7 (3.8%) were giant. In 141 of 151 patients (93.4%), the primary endpoint was reached. The overall rate of periprocedural complications was 7.3%. Of the aneurysms, 79.7% met the study's secondary endpoint of complete occlusion at 6 mo and 85.3% at 12 mo. CONCLUSION The PED Shield is a safe and effective treatment for intracranial aneurysms. The results regarding total occlusion and ischemic complications did not differ from those obtained in case series using previous versions of the PED. Long-term follow-up and comparative studies are required to provide stronger conclusions regarding the reduced thrombogenicity of this device.
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 ( 99m Tc 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 5ϫ10 8 BMMCs was suspended into a volume of 10 mL, and 1 mL of the cell suspension was radiolabeled with 99m Tc (radioactivity 111 MBq, physical half-life 6 hours), as described previously, 1,2 and then added back to the unlabeled cell suspension. After catheter navigation via femoral artery access under local anesthesia and conscious sedation, cells were injected into the M1 portion of the MCA, and the infusion was completed within Ϸ10 minutes. To monitor the fate of transplanted BMMCs, whole-body and planar scintigraphies were performed at 2, 24, and 48 hours after cell therapy. The patient had no complications during the procedure or follow-up.Planar and SPECT views revealed uptake and retention of the labeled BMMCs in the territory of the left MCA for up to 48 hours ( Figures 1C, 3, and 4 and Movie II in the online-only Data Supplement). The remaining uptake occurred mainly in the liver and spleen (Figure 4). To our knowledge, there has been only 1 report of BMMC homing in cerebral infarction, which indicated the retention of BMMCs 8 hours after intra-arterial injection in 1 patient in the subacute phase, 9 days after stroke. 3 We here report for the first time the migration and homing of BMMCs to the brain of a patient in the chronic phase of stroke, Ͼ2 months after the onset of symptoms. The mechanisms involved in the possible therapeutic effect of BMMC therapy are still largely unknown, but accumulating evidence from animal studies suggests that these cells may behave as minipumps producing cytokines and/or trophic factors that support cell survival in the penumbra area and stimulate neurogenesis and angiogenesis, increasing brain remodeling and functional regeneration after ischemia. 4 In vivo tracking of BMMCs after grafting is of great importance because the retention of transplanted cells at the site of the lesion may be critical for the success of cell therapy. 3,4 In animal models, different methods have been used to track the transplanted cells, and it has been suggested that signals that are involved in the transit of inflammatory cells to injured tissue may also direct the transplanted bone marrow-derived cells. 4 Our results indicate that labeling BMMCs with 99m Tc is feasible and that noninvasive imaging may be used ...
-Objetive: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.KEy WOrdS: infectious aneurysms, cerebral, embolization tratamento endovascular de aneurismas infecciosos intracranianosResumo -Objetivo: Enfatizar o método endovascular como uma opção de tratamento alternativa e menos agressiva no tratamento de aneurismas infecciosos intracranianos. Método: Apresentamos uma série de cinco pacientes com endocardite infecciosa e aneurismas infecciosos intra-cranianos (aneurismas micóticos) tratados através da via endovascular. Resultados: O tratamento endovascular teve sucesso técnico e sem intercorrências relacionadas ao cateterismo em todos os casos. Três pacientes tiveram desfecho clínico favorável: dois com escala de regeneração de Glasgow 4/5 e um com recuperação neurológica completa (GOS 5/5). dois pacientes tiveram desfecho desfavorável (GOS 1/5), um devido às conseqüências do sangramento intracraniano inicial e outro devido a complicações cardíacas da endocardite e cirurgia de troca valvar. Conclusão: As técnicas endovasculares são uma nova opção de tratamento dos aneurismas infecciosos intracranianos. Ela é especialmente útil em pacientes que serão submetidos à cirurgia cardíaca com circulação extra-corpórea e anticoagulação, com o conseqüente risco de hemorragia intracraniana.PAlAvrAS-chAvE: aneurismas infecciosos, cerebral, embolização.
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