Brain retraction injury after elective aneurysm clipping: a retrospective single-center cohort study.

BACKGROUND: BRI is estimated to occur in 10% of skull-base surgery and 5% of aneurysm surgery. These estimates are based on a few studies with unclear methodology. The purpose of this study is to assess the rate of BRI occurrence, its risk factors, and the association between BRI and postoperative focal neurological deficit in patients that underwent elective aneurysm surgery in a single institution. METHODS: All patients that underwent elective aneurysm surgery in a single tertiary center in the Netherlands were included. BRI was defined as cortical hypodensities in the surgical trajectory not matching areas of large arterial infarction. Risk ratios were calculated between BRI and (a) the use of temporary parent artery occlusion during clipping, (b) anterior communicating artery (ACom), and (c) middle cerebral artery (MCA) location of the aneurysm, (d) presence of mentioned CVA risk factors, (e) the clipping of > 1 aneurysm during the same procedure, and (f) new focal neurological deficit. Statistical analysis further included t-tests and binary logistical regression analysis on the correlation between age and BRI. RESULTS: BRI was identified postoperatively in 42 of the 94 patients included in this study. A new focal neurological deficit was found in 7 patients in the BRI group. A total of 5 patients had persisting symptoms at 3-month follow-up, of which 2 were caused by BRI. Increasing age is a risk factor for developing BRI. CONCLUSIONS: The high rate of BRI and significant risk of new postoperative focal neurological deficit in our patients should be considered when counseling patients for elective aneurysm surgery.

Long-term feasibility of the new sutureless excimer laser-assisted non-occlusive anastomosis clip in a pig model.

BACKGROUND: High flow bypass surgery can be a last resort procedure for patients suffering from complex neurovascular pathology. Temporary occlusion of a recipient artery in these patients could result in debilitating neurological deficits. We developed a sutureless, mechanical anastomotic connection device, the SELANA clip (Sutureless Excimer Laser-Assisted Non-occlusive Anastomosis clip: SEcl). In the present study, we aim to determine the long-term non-inferiority of the SEcl technique compared with historical data of the conventional ELANA anastomosis technique. METHODS: A total of 18 SEcl bypasses were created on the carotid artery in a porcine model in 6 different survival groups. Mean application times, flap retrieval rates, hemostasis, patency, flow, endothelialization, and remodeling were assessed. RESULTS: The mean application time of the SEcl anastomoses was 15.2 ± 9.6 min, which was faster compared with the conventional ELANA anastomoses. The flap retrieval rate of the SEcl anastomoses was 86% (32/37). Direct hemostasis was achieved in 89% (33/37) SEcl anastomoses. Patency in all surviving animals was 94% (17/18). Bypass flow after six months was 156.5 ± 24.7 mL/min. Full endothelialization of the SEcl pins was observed after 3 weeks. CONCLUSION: The SEcl technique is not inferior to the ELANA technique regarding patency, flap retrieval rate, flow, and endothelialization. On the basis of a significantly shorter application time and superior hemostasis, the SEcl technique could be preferable over the ELANA technique. A pilot study in patients is a logical next step based on our current results.

Correction of ankle valgus by hemiepiphysiodesis using the tension band principle in patients with multiple hereditary exostosis.

BACKGROUND: Ankle valgus is a common deformity in patients with multiple hereditary exostoses (MHE) and a potential risk factor for early degenerative arthritis. In children, medial hemiepiphysiodesis of the distal tibia is a relatively simple surgical technique used to correct this deformity. We present here the first results of applying this procedure using the eight-Plate guided growth system (eight-Plate) for growth guidance. METHODS: Between 2006 and 2011 we performed hemiepiphysiodesis of the distal medial tibia in 30 ankles of 18 children with MHE using the eight-Plate. Weight-bearing total leg radiographs were obtained preoperatively, during follow-up and at the time of implant removal or when the distal tibial physis had closed. The lateral distal tibia angle (LDTA) was measured and fibular shortening assessed using the Malhotra classification. To evaluate the effect of hemiepiphysiodesis, we correlated the LDTA with age. RESULTS: The mean age at time of surgery was 12.6 (range 9.5-15.0) years, and the mean preoperative LDTA was 76.9° (range 68.5°-83.5°). During follow-up, the implant was removed in 12 extremities and the physis had closed in 18 extremities. The mean LDTA at the time of implant removal or at closure of the physis was 83.6° (range 76.5°-90.0°). Mean correction of LDTA was 6.9° after a mean follow-up period of 22 (range 3-43) months. During follow-up, no changes in the Malhotra classification were found in any of the patients. Correction of the valgus deformity of the ankle was significantly correlated (r = -0.506) (p = 0.004) with age in all patients. CONCLUSION: Temporary medial hemiepiphyseodesis of the distal tibia seems to be an effective strategy for correcting ankle valgus in children with MHE. Timing of the intervention is, however, of importance. Hemiepiphyseodesis alone has no effect on the Malhotra classification. LEVEL OF EVIDENCE: IV, retrospective review.

Cerebral revascularization.

During the last 10 years, there has been a revival of interest in cerebral revascularization procedures. Not only have significant progressions in surgical techniques been published, the use of more advanced diagnostic methods has led to a widening of the indications for cerebral bypass surgery. The purpose of this review is to outline the current techniques for extracranial-to-intracranial (EC/IC) and intracranial-to-intracranial (IC/IC) bypass surgery, as well as to identify the current indications for revascularization procedures based on the available literature. The excimer laser-assisted non-occlusive anastomosis (ELANA) technique is described in more detail because we think that this technique almost completely eliminates the risk of cerebral ischemia due to the temporary vessel occlusion which is currently used in conventional anastomosis techniques.

Flow quantification of the non-occlusive excimer laser-assisted EC-IC bypass.

BACKGROUND: For six years, we used the Excimer laser-assisted nonocclusive anastomosis technique for high-flow revascularization of the brain in patients with either nonclippable and noncoilable giant aneurysms of the internal carotid or basilar artery or progressive stroke associated with occlusive disease of the internal carotid artery. The aim of this study is to assess the blood flow capacity of this type of Extra-Intracranial bypass and its haemodynamic behaviour over time. METHODS: Twenty-six patients with a giant aneurysms and 8 patients with occlusive disease of the internal carotid artery were treated with the nonocclusive Excimer laser assisted EC-IC bypass. intra-operatively, direct measurements of flow in the EC-IC bypass were performed in all patients (Transonic Systems, Inc., Ithaca. NY). Postoperatively, follow up measurements of flow were performed with MR angiography in 14 patients with a giant aneurysm after occluding the internal carotid artery, and 7 patients with occlusive carotid disease. RESULTS: The mean flow in the laser assisted bypasses in the group of patients with a giant aneurysm was 158 ml/min after ligation or balloon occlusion of the ICA. The mean flow of the laser assisted bypass in the group of patients with ICA occlusive disease was 130 ml/min. A comparison with data on flow capacity of conventional EC IC bypasses is made. A demonstrated increase of flow in the bypass during follow up is discussed from a haemodynamic point of view. CONCLUSIONS: The results of this study demonstrate that the flow capacity of the nonoccluding excimer laser assisted bypass is much higher than the capacity of the conventional, more peripherally located conventional EC IC bypass, and should therefore be denoted as High-Flow EC IC bypass. Consequently, this type of bypass can be a powerful and safe tool in new revascularization strategies.

Repeated quantitative perfusion and contrast permeability measurement in the MRI examination of a CNS tumor.

This study reports on the results of quantitative MRI perfusion and contrast permeability measurement on two occasions in one patient. The measurements were separated 81 days in time. The tumor grew considerably in this period, but no change was found with respect to perfusion and contrast permeability. Non-involved white matter values were reproduced to demonstrate repeatability. The presented approach to dynamic susceptibility contrast MRI allows fast and repeatable quantitative assessment of perfusion and is easily integrated in a conventional brain tumor protocol.

Criteria to define HLA haplotype loss in human solid tumors.

Short tandem repeat (STR) markers are currently used to define loss of heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and chromosome 15 STR markers are applied to define loss of HLA and related genes (e.g. TAP and beta2m). The number of STR identified in the HLA region is still increasing. In this study, seven representative STR markers covering the 6p/6q arms of chromosome 6 including the HLA region and two for chromosome 15 flanking the beta2m gene, were selected as minimally required for reliable LOH studies. A multiplex polymerase chain reaction (PCR) strategy is proposed when small number of cells are available in microdissected tumor samples.

Microsatellite analysis of microdissected tumor cells and 6p high density microsatellite analysis in head and neck squamous cell carcinomas with down-regulated human leukocyte antigen class I expression.

Down-regulated human leukocyte antigen (HLA) class I expression is frequently correlated with allelic loss at 6p21.3, which is the location of the HLA coding sequence, in head and neck squamous cell carcinomas (HNSCCs). Previously, we have demonstrated loss of heterozygosity (LOH) at 6p21.3 for at least one locus in 49% of the HNSCCs using 5 microsatellite markers spanning the 4 megabase HLA region. In the present study, the detection threshold (25%) to assign LOH was addressed by laser-assisted microdissection of tumor cells from tumors containing marginal loss. In addition, we describe high density microsatellite analysis of chromosome 6p21.3 in HNSCC with down-regulated HLA class I expression. The purpose of this study was to refine the identification of genetic alterations at 6p21.3 and to pinpoint allelic loss to individual HLA class I genes, using additional markers closely located to the HLA-A, -B, and -C loci and the transporter associated with antigen processing (TAP) genes. LOH analysis by amplification of microsatellite markers and subsequent fluorescent detection is a rapid and sensitive technique to predict HLA class I loss phenotypes in tumors. LOH can be identified at 25% relative signal reduction. Analysis of heterogeneous tumor samples and samples containing a small amount of tumor cells is facilitated by laser-assisted microdissection of tumor cells. In addition, we showed that accurate HLA LOH analysis requires application of microsatellite markers in close proximity to HLA class I and TAP genes.

Scanning electron microscopic evaluation of nonocclusive excimer laser-assisted anastomosis in rabbits.

BACKGROUND: The nonocclusive Excimer laser-assisted bypass technique has been described in previous studies and proved to be a promising bypass operation in vascular brain surgery. Little is known about the morphological regeneration process of the laser-assisted anastomosis in time. By way of a scanning electron microscopic study we examined the way in which the anastomosis site created by the nonocclusive Excimer laser-assisted anastomosis technique becomes endothelialized. METHODS: In 14 rabbits the internal jugular vein was placed in a loop on the abdominal aorta. The distal anastomosis was made using the nonocclusive Excimer laser-assisted technique. The proximal anastomosis was made either laser-assisted or conventional end-to-side. After clipping of the aorta between the two anastomoses sites the vein served as a bypass. To evaluate the endothelialization at the laser-assisted anastomosis site in time, a scanning electron microscopic study was performed. RESULTS: In the first hours after the bypass operation a new intimal surface is formed by fibrin and activated platelets. Some leukocytes are seen during the first days. The endothelialization process of the laser-assisted anastomosis site begins one day after the operation. The gradual endothelialization process evolved along two lines. First, endothelial cells grow from the side of the aorta to the bypass. Second, after one day solitary (blood-borne) endothelial cells deposit on the laser edge and the sutures, covering the platelet aggregates. CONCLUSIONS: The endothelialization of the Excimer laser-assisted anastomosis is more or less completed 9 days after the operation. The edge created by the laser becomes smoother after a few days and is gone for the most part after 9 days.

[High-flow transcranial bypass for prevention of brain ischemia]. / Transcraniële bypass met grote doorstroming ter preventie van hersenischemie.

In patients in whom the internal carotid artery has to be occluded because of the presence of an intracranial giant aneurysm or an infiltrating skull base tumour and in patients with brain ischaemia, whose internal carotid artery has been occluded spontaneously on the basis of atherosclerosis, a transcranial bypass can be created. Since the beginning of the seventies 'low-flow bypasses' are made in which a branch of the superficial temporal artery is connected with a cortical branch of the middle cerebral artery. Because of the small calibre of the blood vessels involved the desired effect on the brain circulation is limited. Thanks to the nonocclusive Excimer laser-assisted anastomosing technique, developed by Tulleken et al. in the last fifteen years, it is now possible to create a high-flow bypass in a safe way. A donor vessel, e.g. the V. saphena magna, is connected at one end to the external carotid artery and at the other to the intracranial part of the internal carotid artery beyond the pathological lesion. The mean flow through the bypass was 140 ml/min in about 90 patients. For example, in three patients, a woman aged 45 with rightsided progressive ophthalmoplegia due to a giant aneurysm, a woman aged 31 years with an aneurysm in the right middle ear and a man with a chemodectoma at the base of the skull, a transcranial high-flow bypass was created nonocclusively, after which the internal carotid artery was closed without any problems.

An alternative conditioning regimen for induction of specific skin graft tolerance across full major histocompatibility complex barriers.

Previously, we developed a well-tolerated single-day protocol for induction of stable multilineage chimerism and permanent donor-specific tolerance across major histocompatibility complex (MHC) barriers, with preservation of the host's normal immune responses. In our murine model, recipient mice were treated with a single dose of anti-CD3, anti-CD4, low dose total body irradiation (TBI; 3-6 Gy) and allogeneic bone marrow cells. An alternative cytoreductive strategy that is well-recognized in bone marrow transplantation, but has not been evaluated extensively in organ allograft recipients, involves the use of a combined chemotherapeutic drug treatment. The present data show that conditioning with low dose TBI, in a MHC-disparate donor-recipient combination, can be successfully substituted by a combined single low-dose dimethyl myleran (DMM)/cyclophosphamide (CY) therapy, resulting in both stable, mixed chimerism and specific skin graft tolerance.

Specific tolerance induction and organ transplantation.

Induction of tolerance to histocompatibility antigens of an organ donor would eliminate the need for long-term administration of nonspecific immunosuppressive drugs associated with an increased risk of infection and malignancies. Recently, we established a murine model in which recipient mice were treated with a single dose of anti-CD3, anti-CD4, low dose of total body irradiation (TBI) and allogeneic bone marrow cells. Our results clearly demonstrate that stable multilineage mixed chimerism, immunocompetence and permanent donor-specific skin graft tolerance across full major histocompatibility (MHC) barriers can be successfully achieved in this way. The observations that the preparative regimen and skin transplantation can be performed on the same day, and that a significant reduction in irradiation dose is sufficient in haploidentical donor-recipient combinations (MHC-sharing effect), bring our protocol closer to clinical use.

Haematopoietic stem cells can induce specific skin graft acceptance across full MHC barriers.

Previously, we and others have demonstrated in several animal models that the establishment of stable haematopoietic chimerism through allogeneic bone marrow transfusion provides an effective means for the development of specific transplantation tolerance. However, a major limitation to the clinical application of allogeneic bone marrow transfusion in immunosuppressed recipients for induction of tolerance to solid grafts, is the risk of graft-versus-host disease (GVHD). Therefore, it is important to identify the cell population needed for the induction of mixed chimerism and tolerance. Haematopoietic stem cells have the capacity of self-renewal and multilineage differentiation, and have been shown to reduce the risk of GVHD. We studied transfusion of two rich sources of stem cells, namely allogeneic fetal liver cells and a subset of purified bone marrow-derived progenitor cells (c-kit+) into anti-T cell monoclonal antibody-treated, low-dose irradiated recipient mice. Our data revealed that stable multilineage mixed chimerism and permanent donor-specific tolerance for skin, even when transplanted directly following conditioning, can be successfully achieved in this way, with no signs of GVHD.

High-flow bypass using nonocclusive excimer laser-assisted end-to-side anastomosis of the external carotid artery to the P1 segment of the posterior cerebral artery via the sylvian route. Technical note.

In a patient with a giant aneurysm of the basilar artery trunk, a vein graft was interposed between the external carotid artery in the neck and the P1 segment of the posterior cerebral artery. Balloon occlusion of both vertebral arteries was performed 3 days later. The sylvian route was used for the grafting procedure and the connection to the posterior cerebral artery was made by using the excimer laser-assisted nonocclusive anastomosis technique.

Specific tolerance induction and transplantation: a single-day protocol.

Bone marrow transfusion is a well-established method for induction of mixed hematopoietic chimerism and donor-specific tolerance in animal models. This procedure, however, is inapplicable in clinical transplantation using cadaveric donors due to the interval (1 week to 7 months) between tolerance induction and organ transplantation. For clinical use, it is essential that allografts be placed at the time of bone marrow transfusion. In the present study, we performed skin transplantation within 1 hour after a nonlethal conditioning regimen. Recipient mice were treated with anti-CD3, anti-CD4, low-dose total body irradiation (3 to 6 Gy TBI) and fully mismatched or haploidentical donor bone marrow cells. Stable multilineage chimerism and specific T-cell nonresponsiveness developed. Donor skin grafts were permanently accepted. These results suggest that this single day protocol has clear potential for application in both cadaveric and living-related organ transplantation.

A substantial level of mixed chimerism is required for the induction of permanent transplantation tolerance.

The induction of donor-specific transplantation tolerance is a major goal in organ transplantation, in order to eliminate the requirement for lifelong immunosuppressive therapy. Previously, we have developed a murine bone marrow transplantation model in which recipient mice were treated with a single dose of anti-CD3 and low dose whole body irradiation (WBI). Transfusion of donor bone marrow cells across a full H-2 disparity resulted in induction of high levels of stable mixed chimerism, specific T cell non-responsiveness and indefinite skin allograft survival. The present study has focused on manipulation of the level of chimerism in this model by varying the number of infused bone marrow cells, varying the dose of WBI and addition of syngeneic bone marrow cells. Our results indicate that a substantial level of chimerism is needed for induction of transplantation tolerance. In addition, in the semi-allogeneic donor-recipient combination an even lower dose of WBI was sufficient of engraftment of bone marrow cells and subsequent tolerance induction. We suggest that sharing of MHC antigens between donor and recipient might play an important role in facilitating the development of chimerism and tolerance in organ transplantation.

Anti-CD3 treatment facilitates engraftment of full H-2-disparate donor bone marrow cells and subsequent skin allograft tolerance.

The aim of the present study was to induce engraftment of full H-2-disparate donor bone marrow cells and the development of subsequent transplantation tolerance. To this end, recipient H-2b mice were treated with anti-CD3 and on the same day received 6 Gy whole body irradiation as well as donor bone marrow cells (H-2d). Anti-CD3 treatment was chosen because it results in suppression of T cell function and in the release of CSF associated with enhancement of donor bone marrow engraftment. Stable, long-term chimerism measured in peripheral blood and mesenteric lymph nodes was obtained using this preparative regimen. In contrast, the use of anti-CD3 F(ab')2 fragments failed to induce donor bone marrow cell engraftment, suggesting indeed an important role of anti-CD3-mediated growth factor production in marrow engraftment. To overcome the side effects of anti-CD3 treatment (cytokine release syndrome), anti-CD4 was given 1 day before the treatment protocol. Omission of anti-CD3 resulted in failure of donor bone marrow engraftment, indicating the essential role of anti-CD3 treatment in marrow engraftment. Skin transplantation performed 2 and 6 months after this well-tolerated conditioning regimen showed indefinite survival of first and second grafts, respectively. In addition, specific CTL nonresponsiveness developed, demonstrating the presence of classical transplantation tolerance across a full H-2 barrier.