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.

Feasibility of the new sutureless excimer laser-assisted non-occlusive anastomosis clip in a rabbit model.

BACKGROUND: The excimer laser-assisted non-occlusive anastomosis (ELANA) technique facilitates the construction of anastomoses without temporary occlusion of the recipient artery. Experiments aimed at simplifying the technique eventually resulted in a sutureless ELANA slide (SEsl) anastomosis. After the first clinical use, new insights lead to the application of a clip at the back of the device, the SELANA clip (SEcl). The SEcl offers a distinct advantage over the SEsl since no sealant is necessary. In this study, we determine the feasibility of the SEcl anastomosis in an in vivo rabbit model. METHODS: 15 SEcl anastomoses and 15 conventional ELANA anastomoses were created on the abdominal aorta in 5 rabbits. Mean application times, flap retrieval rates, hemostasis, and burst pressures were assessed. RESULTS: The mean application time of the SEcl anastomoses was 11.4 min versus 39.0 min for the ELANA anastomoses (mean difference, 27.6 min; 95% CI, 20.6-34.7). The flap retrieval rate of the SEcl anastomoses (14/15) was not inferior to the flap retrieval rate of the ELANA anastomoses (13/15). Direct hemostasis was achieved in 13/15 (87%) SEcl anastomoses and in 14/15 (94%) ELANA anastomoses. All SEcl anastomoses were resistant to provoked pressures until 250 mmHg. CONCLUSION: The SEcl anastomosis is technically feasible in in vivo experiments. Mean application time, flap retrieval rate, hemostasis, and burst pressure are not inferior to the conventional ELANA anastomosis. Further long term experiments should be performed to assess safety, patency, and reendothelialization.

Preclinical success but clinical failure of the sutureless excimer laser-assisted non-occlusive anastomosis (SELANA) slide.

BACKGROUND: The excimer laser-assisted non-occlusive anastomosis (ELANA) has been developed for intracranial bypass without the need for temporary recipient occlusion. We designed and tested a sutureless variant of the ELANA-the SELANA slide (SEsl). OBJECTIVE: This study aims to evaluate the SEsl preclinical results and describe its first clinical application. METHODS: First, in a cadaver study, 28 SEsl anastomoses were compared with 28 ELANA anastomoses. Second, in an acute rabbit model, 90 SEsl anastomoses were compared with 30 ELANA anastomoses. Finally, in a surviving pig model, 38 SEsl bypasses were created. To evaluate the clinical efficacy of the SEsl, we then treated one patient with a giant, right-sided middle cerebral artery (MCA) aneurysm with an intracranial-intracranial SEsl bypass and parent vessel occlusion. RESULTS: In preclinical studies, the SEsl anastomosis was shown to be equivalent or superior to the ELANA in terms of associated ease, patency, and bleeding complications. However, clinical application in rigid and arteriosclerotic receiving arteries was problematic. Although bypass creation and aneurysm occlusion were technically successful and the patient was postoperatively well, a pseudoaneurysm formed postoperatively at the internal carotid artery anastomosis and bled. Subsequent treatment failed and the patient did not survive. CONCLUSION: The SEsl showed promising preclinical results across three models. However, in its present form, it is not suitable for clinical application. TRIAL NUMBER: IRB UMCU 10/154.

Towards sutureless non-occlusive cerebral revascularization.

Sutureless vascular anastomoses have been the subject of extensive research for decades. In neurosurgery the need for a safe and fast technique is high, because temporary occlusion of cerebral arteries may rapidly lead to brain ischemia. Conventional sutured anastomoses have always been the golden standard. Limited working space and difficult suturing techniques were reasons to find alternatives. Many artificial devices to create anastomoses have been engineered over the years like tissue sealants, clips and automated suturing sets with variable success. For all previous options, temporary occlusion of the recipient artery was necessary. The Excimer Laser Assisted Non-Occlusive Anastomosis (ELANA) technique™ facilitates the construction of an end-to-side anastomosis without temporary occlusion of the recipient artery using a platinum ring and a laser. However, the technical challenge of intracranial micro-sutures remained. Experiments using less sutures eventually resulted in a sutureless ELANA (SELANA) anastomosis. After in vitro and in vivo experiments, the SELANA slide was considered feasible for intracranial use although some concrete improvements, like the inclusion of a clip at the back of the device, were needed. Therefore, the development of an ideal sutureless anastomosis is still ongoing. This process is an evolution rather than a revolution.

Neuronavigation and surgery of intracerebral tumours.

Approximately four decades after the successful clinical introduction of framebased stereotactic neurosurgery by Spiegel and Wycis, frameless stereotaxy emerged to enable more elaborate image guidance in open neurosurgical procedures. Frameless stereotaxy, or neuronavigation, relies on one of several different localizing techniques to determine the position of an operative instrument relative to the surgical field, without the need for a coordinate frame rigidly fixed to the patients' skull. Currently, most systems are based on the optical triangulation of infrared light sources fixed to the surgical instrument. In its essence, a navigation system is a three-dimensional digitiser that correlates its measurements to a reference data set, i.e. a preoperatively acquired CT or MRI image stack. This correlation is achieved through a patient-to-image registration procedure resulting in a mathematical transformation matrix mapping each position in 'world space' onto 'image space'. Thus, throughout the remainder of the surgical procedure, the position of the surgical instrument can be demonstrated on a computer screen, relative to the CT or MRI images. Though neuronavigation has become a routinely used addition to the neurosurgical armamentarium, its impact on surgical results has not yet been examined sufficiently. Therefore, the surgeon is left to decide on a case-by-case basis whether to perform surgery with or without neuronavigation. Future challenges lie in improvement of the interface between the surgeon and the neuronavigator and in reducing the brainshift error, i.e. inaccuracy introduced by changes in tissue positions after image acquisition.

[The current MRSA policy in the Netherlands is doing more harm than good]. / Het Nederlandse MRSA-beleid doet meer kwaad dan goed.

The current policy concerning methicillin-resistant Staphylococcus aureus (MRSA) in hospitals needs to be altered because there is no reliable proof that the isolation policy that is currently in force actually leads to any reduction in the prevalence of MRSA. Conversely, it has been proved that these isolation measures lead to poorer patient care, sometimes resulting in death.

Neurobehavioral status and health-related quality of life in newly diagnosed high-grade glioma patients.

PURPOSE: To evaluate the health-related quality of life (HRQOL) and cognitive functioning of high-grade glioma patients in the postneurosurgical period. PATIENTS AND METHODS: The HRQOL, as assessed by the Short-Form Health Survey-36, tumor-specific symptoms, and objective and subjective neuropsychologic functioning, of 68 newly diagnosed glioma patients were compared with that of 50 patients with non-small-cell lung cancer (NSCLC) and to age- and sex-matched healthy controls. The association between tumor lateralization, extent of resection, and use of medication, and the HRQOL outcomes was also investigated. RESULTS: The HRQOL of the two patient groups was similar but significantly lower than that of the healthy controls. Glioma patients reported significantly more neurologic symptoms and poorer objective and subjective neuropsychologic functioning than the NSCLC patients. Using healthy controls as the reference group, cognitive impairment assessed at the individual patient level was observed in all glioma patients and 52% of the NSCLC patients. Poor performance on timed tasks in the glioma group could be attributed, in large part, to visual and motor deficits. Tumor lateralization was found to affect neuropsychologic functioning in a predictable manner. The extent of resection was not related significantly to neuropsychologic functioning. Corticosteroid use was associated with better recognition memory, whereas antiepileptic drug use was correlated negatively with working memory capacity. CONCLUSION: The general HRQOL of glioma patients is similar to that of patients with NSCLC. However, they suffer from a number of condition-specific neurologic and neuropsychologic problems that have a significant impact on their daily lives in the postsurgical period, before treatment with radiotherapy.

Coronary artery bypass grafting without cardiopulmonary bypass and without interruption of native coronary flow using a novel anastomosis site restraining device ("Octopus").

OBJECTIVE: This study assessed the feasibility of coronary artery bypass grafting on the beating heart without interruption of native coronary blood flow using a novel anastomosis site restraining device. BACKGROUND: Recently, an end-to-side bypass technique was described that does not require interruption of flow in the recipient artery. METHODS: By means of a suction device ("Octopus"), in 31 pigs the epicardium was grasped and immobilized through an arm contraption fixed to the operating table. In the first 15 consecutive pigs (study I), the two-dimensional motion of an epicardial beacon was monitored. In 16 subsequent pigs (study II), an internal mammary artery was grafted under the microscope in two steps to a proximal coronary artery segment, without cardiopulmonary bypass. First, the internal mammary artery was sutured end-to-side to the outside of the coronary artery. Secondly, an orifice was punched in the partitioning coronary wall by an excimer laser catheter introduced through a temporary side-branch of the internal mammary artery. RESULTS: Study II: During 43 suction periods in four anastomosis areas, immobilization was achieved for 15 to 169 min (>30 h in total) in 13 open- and 9 closed-chest procedures without hemodynamic deterioration. The area circumscribed by the edges of the beacon trajectory (area in which the anastomosis is to be tracked) was reduced from 73.0 +/- 43.0 mm(2) (mean +/- SD) to 1.3 +/- 0.5 mm(2) (p<0.001) in the open-chest and to 0.2 +/- 0.2 mm(2) in the closed-chest procedure. At 6 weeks, no myocardial or coronary suction lesions were found. Study II: Nonocclusive anastomosis surgery required 25 +/- 3 min. No leakage, serious arrhythmias, graft closure or hemodynamic deterioration occurred during the procedure or for 2 h after ligating the coronary artery proximally. At 6 weeks, all seven grafts were patent. CONCLUSIONS: Coronary bypass on the beating heart without interruption of coronary flow is feasible. In both open- and in closed-chest procedures, the "Octopus" reduced anastomosis site motion to about 1 X 1 mm without adverse consequences.

The ELANA technique: high flow revascularization of the brain.

High flow revascularization of the brain is hampered by the fact that temporary occusion of a major cerebral artery is necessary to create the distal anastomosis, which may result in brain ischemia. The excimer laser-assisted non-occlusive anastomosis (ELANA) technique circumvents this problem. In this paper we elucidate the development of a non-occlusive way to make anastomoses to the major cerebral arteries.

Magnetic resonance techniques for the identification of patients with symptomatic carotid artery occlusion at high risk of cerebral ischemic events.

BACKGROUND AND PURPOSE: We sought to assess whether MRI, MR angiography, or (1)H MR spectroscopy can be used to identify patients with symptomatic carotid artery occlusion (CAO) who are at high risk of recurrent ipsilateral cerebral ischemic events. METHODS: In 115 consecutive patients with transient or moderately disabling symptoms of cerebral or retinal ischemia and ipsilateral CAO, we studied the prognostic value of (1) presence of a border-zone infarct; (2) quantitative flow in the middle cerebral artery (MCA) ipsilateral to the CAO; and (3) metabolic ratios in the centrum semiovale ipsilateral to the CAO. RESULTS: Presence of a border-zone infarct and the rate of flow in the MCA did not have a significant relationship with recurrence of cerebral ischemic events. Patients with a low N:-acetyl aspartate (NAA)/choline ratio had an annual risk of recurrent, ipsilateral, cerebral ischemic events of 16.0% (95% CI, 9.5 to 27.0), whereas this risk was 4.2% (95% CI, 2.2 to 8.0) in those with a normal NAA/choline ratio (hazard ratio, 0. 43; 95% CI, 0.19 to 1.00). Patients who on entry had had only retinal symptoms had on average a higher NAA/choline ratio (mean difference, 0.25; 95% CI, 0.13 to 0.37) and a lower risk of recurrent cerebral ischemic events (odds ratio, 0.0; 95% CI, 0.0 to 0.6) than those with cerebral ischemic symptoms. CONCLUSIONS: NAA/choline ratio measured by (1)H MRS, but not the presence of a border-zone infarct or the amount of flow in the MCA, can identify patients with symptomatic CAO who are at risk of future ipsilateral cerebral ischemic events.

Familial association of intracranial aneurysms and multiple congenital anomalies.

The familial occurrence of intracranial aneurysms and the possible relationship with connective tissue disease are discussed. We studied a large family in which seven members presented with aneurysms. Another family member presented with a subarachnoidal hemorrhage. Two other family members each presented with Marfan's syndrome and an unclassified multiple congenital anomalies syndrome, respectively. The multiplicity of the aneurysms in four members is in excess of that found in sporadic or familial cases with intracranial aneurysms. We suggest a common cause, eg, a connective tissue disorder for both the intracranial aneurysms, the Marfan's syndrome, and the unclassified syndrome.

Recurrent ischemia in symptomatic carotid occlusion: prognostic value of hemodynamic factors.

OBJECTIVE: To identify hemodynamic factors that predict recurrence of ipsilateral cerebral ischemic events in patients with symptomatic carotid artery occlusion (CAO). PATIENTS AND METHODS: The authors studied 117 consecutive patients with CAO and corresponding recent (

Experimentally induced autonomic neuropathy: beneficial effect of a systemic ACTH4-9 analogue on oculomotor nerve regeneration.

While the regenerating capacity of peripheral nerves has been the subject of intensive study, little is known about the regenerative capacity of the autonomic nervous system. Using an animal model, where the pupil diameter of the eye in the rat serves as a parameter of autonomic function, we studied whether systemic treatment with the neuropeptide Org 2766, a synthetic ACTH4-9, analogue, facilitates the functional recovery of parasympathetic nerve fibres after transection, and after a crush lesion of the oculomotor nerve. By simply photographing the rat's pupil under standardised conditions, we show that sectioning the oculomotor nerve leads to an immediate mydriasis, followed by spontaneous regeneration in 30 days. Systemic treatment with an ACTH4-9 analogue had no effect on the rate or quality of recovery. However, systemic treatment with an ACTH4-9 analogue after a crush lesion of the oculomotor nerve (spontaneous regeneration time 16 days) did enhance the speed of recovery of the parasympathetic nerve fibres in the oculomotor nerve, especially in the initial stages of regeneration. We conclude that the animal model used in this study is valuable for studying the regenerative capacity of the autonomic nervous system and the influence of neurotrophic peptides on autonomic neuropathies. Evidence is presented that synthetic ACTH4-9 analogue exerts beneficial neurotrophic effects, not only in peripheral sensorimotor neuropathies but also in autonomic neuropathies.

Frontal lobe damage and thalamic volume changes.

The aim of this study was to investigate whether frontal lobe damage affects thalamic volume in humans. Ipsilateral and contralateral thalamic areas were measured in 0.5T T1-weighted sagittal magnetic resonance images in 12 patients, first at the time of their surgery for relief of a unilateral frontal lobe brain tumor and at follow-up approximately 2 years later. A 5% decrease in ipsilateral and 4.5% increase in contralateral thalamic area was found over time (F(1,11) = 6.15, p < 0.05). We conclude that unilateral frontal lobe damage results in a decrease in the ipsilateral thalamus and an increase in the contralateral thalamus in humans in vivo. The findings may have implications for the interpretation of the reported changes in thalamic volume in neuropsychiatric diseases.

Nonocclusive excimer laser-assisted end-to-side anastomosis.

BACKGROUND: High-flow extraintracranial bypass operation on the brain is a risky procedure because of the temporary occlusion of the intracranial portion of the internal carotid artery. We therefore developed a nonocclusive anastomosis technique in the experimental animal laboratory in 100 chronic and acute experiments in rabbits. METHODS: In 40 patients we interposed a venous transplant between the external carotid artery or one of its branches and the intracranial portion of the internal carotid artery. During the construction of the distal anastomosis the recipient artery was not occluded. The donor vessel was stitched to the exterior of the recipient vessel and an Excimer laser catheter (Medolas GmbH, Amberg, Germany) was introduced by way of an artificial side branch. The tip of the laser catheter created a hole in the wall of the recipient artery just inside the anastomosis. The cut-out full-thickness portion of recipient vessel wall remained attached to the tip of the laser catheter by way of high vacuum suction and was removed together with the laser catheter. The artificial side branch was occluded with a hemostatic clip. No interruption of blood flow in the recipient artery was induced during the making of the anastomosis. RESULTS: The procedure was well tolerated by the patients and a high patency rate was observed. CONCLUSIONS: The nonocclusive Excimer laser-assisted anastomosis technique is safe and yields a high long-term patency rate in neurosurgical patients. It cannot be excluded that there are indications for this method in coronary bypass surgery.

Chronic brain ischemia in the monkey assessed by somatosensory evoked potentials and local blood flow measurements.

Physiological changes occurring in experimentally induced chronic ischemic areas of the brain in monkeys have been investigated by measuring local cerebral blood flow (lCBF) and recording somatosensory evoked potentials (SEPs) to median nerve stimulation in the cortex and thalamus (VPL). Ischemia was produced by occlusion of the middle cerebral artery (MCA). Its development was followed for weeks in the unanesthetized monkey. SEPs in VPL and cortex were shown to be useful indicators of neuronal activity in the course of brain ischemia. The most reliable parameters were found to be the amplitude of components P10, P12 and P20 of the cortical SEP, generated around the central sulcus. The relationship between the changes in spontaneous recovery of the SEPs, lCBF and behavioral signs, in the course of time, revealed characteristic patterns. Different components of the cortical SEP provide useful information on the localization of the ischemic cortical area. In addition, the amplitude of the VPL SEP may also change significantly after the occlusion of the MCA. Clear evidence for the phenomenon of diaschisis in terms of SEPs, was found in only one animal. An analysis of the relationship between lCBF and the amplitude of the SEPs showed that cortical SEPs could be measured at local CBF levels as low as 15 ml/100 g X min. The relationship between lCBF and cortical SEP amplitude was approximately linear in the range from about 60 ml/100 g X min down to 15 ml/100 g X min.

Temporal evolution of NMDA-induced excitoxicity in the neonatal rat brain measured with 1H nuclear magnetic resonance imaging.

The aim of this study is to characterize the evolution of excitotoxic damage in neonatal rat brain by diffusion-weighted and T2-weighted magnetic resonance imaging. Results are compared with histological findings. Magnetic resonance imaging was performed at various times (15 min, 24 h, 3 days and 5 days) after intrastriatal microinjection of N-methyl-D-aspartate (NMDA) at postnatal day 8. The transverse relaxation time (T2) and apparent diffusion coefficient of water were determined. The results show an acute reduction of the apparent diffusion coefficient, reflected by an ipsilateral hyperintensity in the diffusion-weighted images, within 15 min after intrastriatal NMDA injection. At this time no changes in the T2-weighted images were apparent. The volume of the hyperintensity was relatively large with a radius of approximately 2 mm and coincided with histological signs of pronounced karyo-dendritic swelling. Subcutaneous administration of MK-801 25 min after the intracerebral NMDA injection readily reversed the hyperintensity and resulted in complete protection as verified by histology. Areas with increased T2 values were observed 1 day after NMDA microinjection and corresponded to regions with obvious cell necrosis. Five days after NMDA injection the lesion was evident using both diffusion- and T2-weighted images and coincided with an overt lesion comprising areas of cell loss and dilatation of the ipsilateral ventricle. In conclusion, this study illustrates the possibility of using diffusion-weighted imaging as a tool to monitor efficacy of treatment strategies at an early stage of excitotoxic injury.

Local as well as remote functional and metabolic changes after focal ischemia in cats.

Behavior and limb placing ability were analyzed acutely and subacutely (up to 21 days) following unilateral occlusion of the middle cerebral artery (MCA) in cats. Immediately following occlusion, all tested cats started to display a sequence of different behaviors, characteristic for 1) an ipsilateral inhibition of dopaminergic activity in the caudate nucleus (CN); 2) an inhibition of GABAergic activity in the reticular substantia nigra (SNR); 3) a stimulation of GABA receptors in the deeper layers of the colliculus superior (CSDL) (starting-time of these phases: about 4, 12 and 25 min, respectively). The latter behavior was also present subacutely. In addition, unilateral orofacial dyskinetic movements were observed acutely as well as subacutely. Contralateral limb placing was deficient in all cats 60 min postocclusion; it was at least partly restored subacutely. Twenty-one days after the occlusion, [14C]-2-D-deoxyglucose uptake was relatively reduced in the ipsilateral CN (especially in its posterior part), the ipsilateral SNR and the ipsilateral CSDL. The anterior CN appeared to be less affected than the posterior CN. Metabolism was relatively reduced in the sensorimotor cortex only in part of the tested cats. The data show that unilateral MCA occlusion produces consistent functional changes in all structures studied apart from the sensorimotor cortex, viz. the CN, the SNR and the CSDL.

New type of end-to-side anastomosis for small arteries: a technical and scanning electron microscopic study in rats.

A new type of end-to-side anastomosis between small arteries is described. The anastomosis is made for three-quarters of its circumference with a nonoccluded recipient artery. The recipient artery must be occluded for only 3 to 5 minutes to complete the anastomosis. The anastomosis site was studied with the scanning electron microscope at different times (1 hour to 3 months) after the operation in 20 rats. In every case, the anastomosis was widely patent and a gradual endothelialization of the anastomosis site was observed. After 7 to 10 days, the endothelialization was more or less complete and, during the following weeks, a further smoothing of the ridge protruding into the anastomosis was noted. As an addendum, the authors describe an improvement of this technique that was developed after the sapphire tip of the neodymium: YAG laser became available. Now the anastomosis is fully completed and the connection between the two vessels is made by the laser tip introduced via a side branch of the donor vessel. The recipient artery need not be occluded at all. The results are promising.

Experimentally-induced autonomic neuropathy: beneficial effect of a topical ACTH4-9 analogue on oculomotor nerve regeneration.

Melanocortins, peptides related to corticotropin (ACTH) and melanocyte-stimulating hormone, are known to exert beneficial neurotrophic effects in peripheral sensorimotor neuropathies. This has been demonstrated after both systemic and local administration of the peptides. By photographing the rat's pupil under standardized conditions, the authors have previously shown that systemic administration of a synthetic ACTH4-9 analogue can also be beneficial in autonomic neuropathies. The present study demonstrates that topical application of a synthetic ACTH4-9 analogue incorporated in a two-component fibrin glue enhances the speed of recovery of the parasympathetic nerve fibers in the oculomotor nerve after a crush lesion. This may have implications for future use in neurosurgery.