Collateralization and ischemia in hemodynamic cerebrovascular insufficiency.

BACKGROUND: Moyamoya disease and atherosclerotic cerebrovascular occlusive disease lead to hemodynamic impairment of cerebral blood flow. One major differentiation between both disease entities lies in the collateralization pathways. The clinical implications of the collateralization pathways for the development of hemodynamic ischemia remain unknown. The aim was to characterize collateralization and ischemia patterns in patients with chronic hemodynamic compromise. METHODS: Hemodynamic compromise was verified using acetazolamide-stimulated xenon-CT or SPECT in 54 patients [30 moyamoya and 24 atherosclerotic cerebrovascular disease (ACVD)]. All patients received MRI to differentiate hemodynamic ischemia into anterior/posterior cortical border zone infarction (CBI), inferior border zone infarction (IBI) or territorial infarction (TI). Digital subtraction angiography was applied to evaluate collateralization. Collateralization was compared and correlated with the localization of ischemia and number of vascular territories with impaired cerebrovascular reserve capacity (CVRC). RESULTS: MM patients showed collateralization significantly more often via pericallosal anastomosis and the posterior communicating artery (flow in the anterior-posterior direction; MM: 95%/95% vs. ACVD: 23%/12%, p < 0.05). ACVD patients demonstrated collateralization via the anterior and posterior communicating arteries (flow in the posterior-anterior direction, MM: 6%/5% vs. ACVD: 62%/88%, p < 0.05). Patterns of infarction were comparable (aCBI: MM: 36% vs. ACVD: 35%; pCBI: MM: 10% vs. ACVD: 20%; IBI: MM: 35% vs. ACVD: 41%; TI: MM: 13% vs. ACVD: 18%). The number and localization of vascular territories with impaired CVRC were comparable. CONCLUSIONS: Despite significant differences in collateralization, the infarct patterns and severity of CVRC impairment do not differ between MMV and ACVD patients. Cerebral collateralization does not allow reaching conclusions about the localization of cerebral ischemia or severity of impaired CVRC in chronic hemodynamic impairment.

Finite Element Analysis of Patient-Specific 3D-Printed Cranial Implant Manufactured with PMMA and PEEK: A Mechanical Comparative Study.

This article reports on a patient who required a cranial protection system. Using additive manufacturing techniques and surgical planning with the help of bio-models, a patient-specific bone implant solution was proposed that allows aesthetic restoration of the affected area and provides an adequate level of protection. In addition, through a comparative analysis with finite elements, the mechanical response to external actions of the medical device, printed with two materials: polymethylmethacrylate (PMMA) and polyether-ether-ketone (PEEK), is simulated. The tested materials have recognized biocompatibility properties, but their costs on the market differ significantly. The results obtained demonstrate the similarities in the responses of both materials. It offers the possibility that low-income people can access these devices, guaranteeing adequate biomechanical safety, considering that PMMA is a much cheaper material than PEEK.

Surgical planning and finite element analysis for the neurocraneal protection in cranioplasty with PMMA: A case study.

New developments in terms of additive manufacturing, computational tools and mathematical simulation techniques have favored the development of successful methodologies for the restoration or restitution of bone structures in the human body. Likewise, achievements in Materials Science have allowed the development of biocompatible composites capable of achieving mechanical characteristics and biological similarities comparable to those of natural bone. Without considering the advantages and disadvantages of some biomaterials with respect to others, this research aims to evaluate the surgical planning, the design process, the impact resistance and the critical deflection of a customized cranial implant manufactured from polymethylmethacrylate (PMMA). With the support of finite element methods (FEM), the level of neurocranial protection offered by the implant is assessed.

Increased levels of circulating endothelial progenitor cells in patients with Moyamoya disease.

BACKGROUND AND PURPOSE: Chronic cerebral ischemia leads to higher risk for strokes attributable to insufficient collateralization, resulting from inadequate capacity for arteriogenesis and angiogenesis. Patients with Moyamoya disease (MMD) have similar transient ischemic attack frequencies compared to patients with chronic cerebral ischemia with other etiologies, but a strong capacity for arteriogenesis and angiogenesis. The mechanisms involved in the upregulation of the arteriogenesis and angiogenesis in MMD still remain unknown. In the present study we investigated if circulating endothelial progenitor cells are increasingly mobilized during MMD. METHODS: Twenty MMD patients, 8 patients with atherosclerotic cerebrovascular disease, and 15 healthy individuals were included in this study. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and circulating endothelial progenitor cells were characterized by triple staining using antibodies against CD133, CD34, and vascular endothelial growth factor receptor-2. Serum concentrations of vascular endothelial growth factor and granulocyte-macrophage colony-stimulating factor were determined by enzyme-linked immunosorbent assay. RESULTS: In MMD patients the number of circulating endothelial progenitor cells was significantly higher than in atherosclerotic cerebrovascular disease patients (P<0.002) and healthy controls (P<0.0001). Serum vascular endothelial growth factor concentrations in MMD patients and in atherosclerotic cerebrovascular disease patients were significantly higher compared to those in healthy controls (P<0.0001). Similar findings were observed for granulocyte-macrophage colony-stimulating factor. An inverse correlation between circulating endothelial progenitor cell numbers and serum levels of vascular endothelial growth factor (r=-0.53; P<0,02) was found in the MMD group. CONCLUSIONS: Our results show increased circulating endothelial progenitor cell numbers in MMD, which may play a role in the increased arteriogenesis and angiogenesis in MMD. Moreover, our results suggest that increased circulating endothelial progenitor cell mobilization in MMD may not be entirely mediated by vascular endothelial growth factor or granulocyte-macrophage colony-stimulating factor.

Characterization of cortical microvascularization in adult moyamoya disease.

BACKGROUND AND PURPOSE: Increased cortical microvascularization has been proposed to be a Moyamoya disease (MMD)-specific characteristic. It was the aim of our study to characterize the anatomic pattern and microhemodynamics of cortical microvascularization in MMD. METHODS: Intraoperative indocyanine green videoangiography was performed in 16 adult MMD patients, 15 patients with atherosclerotic cerebrovascular disease (ACVD), and 10 control patients. Cortical microvascularization and microvascular hemodynamics were categorized and analyzed according to anatomic and functional indocyanine green angiographic aspects. Anatomic analysis included microvascular density, microvascular diameter, and microvascular surface per analyzed area. Microhemodynamic analysis included microvascular transit time, arterial microvascular transit time, and venous microvascular transit time. RESULTS: Microvascular density and diameter were significantly increased in MMD patients (1.8+/-0.2 mm/mm(2) and 0.24+/-0.03 mm, respectively) compared with those in ACVD patients (1.5+/-0.2 mm/mm(2) and 0.20+/-0.02 mm, respectively) and controls (1.5+/-0.1 mm/mm(2) and 0.19+/-0.03 mm, respectively). This resulted in significantly increased microvascular surface per analyzed area in MMD (67+/-13%) vs ACVD patients (47+/-7%) and controls (45+/-6%). Anatomic changes were paralleled by significantly increased microvascular and arterial microvascular transit times in MMD patients (11.55+/-3.50 and 6.79+/-2.96 seconds, respectively) compared with those in ACVD patients (8.13+/-1.78 and 4.34+/-1.30 seconds, respectively) and controls (8.04+/-2.16 and 4.50+/-1.87 seconds, respectively). CONCLUSIONS: Cortical microvascularization in MMD is characterized by significantly increased microvascular density and microvascular diameter, leading to increased microvascular surface. These anatomic alterations are accompanied by prolonged microvascular hemodynamics. These observations might represent an MMD-specific compensation mechanism for impaired cerebral blood flow.

Risk of intraoperative ischemia due to temporary vessel occlusion during standard extracranial-intracranial arterial bypass surgery.

OBJECT: Standard extracranial-intracranial (EC-IC) arterial bypass surgery represents a well-recognized procedure in which the aim is to augment distal cerebral circulation. The creation of the bypass requires temporary occlusion of the recipient vessel. Thus, there exists controversy about the risk of standard EC-IC arterial bypass surgery causing ischemic complications due to temporary vessel occlusion. In this prospective study, the incidence of intraoperative ischemia was investigated in symptomatic patients with steno-occlusive cerebrovascular disease and existing hemodynamic insufficiency. METHODS: Twenty consecutive patients (14 women and 6 men; mean age 46 +/- 11 years) suffering from recurrent transient ischemic attacks due to occlusive cerebrovascular disease and proven hemodynamic compromise in functional blood flow studies were enrolled in this study. The underlying pathological condition was internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion in 6 cases and ICA or MCA stenosis in 3 cases, whereas 11 patients presented with moyamoya syndrome or moyamoya disease. The surgical procedure consisted of the establishment of a standard superficial temporal artery (STA)-MCA bypass, and was performed while a strict intraoperative management protocol was applied. Patients underwent clinical examination and magnetic resonance (MR) imaging within 48 hours before and after surgery. RESULTS: The incidence of reversible clinical signs of ischemia was 2 (10%) of 20 patients. Postoperative MR imaging revealed signs of diffusion disturbances in 2 (10%) of 20 cases. The observed diffusion-weighted imaging changes, however, were situated within the dependent vascular territory at risk for ischemia in 1 patient only. No permanent neurological deficit occurred. The temporary vessel occlusion time ranged between 25 and 42 minutes (mean 33 +/- 7 minutes). All means are expressed +/- the standard deviation. CONCLUSIONS: Temporary vessel occlusion during standard STA-MCA arterial bypass surgery carries a low risk of intraoperative ischemia when a strict perioperative management protocol is applied.

Identification of the optimal cortical target point for extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular insufficiency.

OBJECT: The objective of this report is to describe a new approach to identify the optimal cortical target point for extracranial-intracranial (EC-IC) bypass surgery, to reliably find suitable recipient vessels for the anastomosis. METHODS: Thirty consecutive patients (17 men and 13 women; mean age 54.6 +/- 11.79 years [+/- standard deviation]) with hemodynamic cerebrovascular insufficiency due to stenoocclusive arterial disease underwent EC-IC bypass surgery. The end of the Sylvian fissure was identified preoperatively using a specially designed template and external landmarks. At surgery, a 3-cm trephination was made, centered over the target point as determined by the template. The number, diameter, and length of the exposed cortical arteries were assessed using photographs and indocyanine green (ICG) angiograms. RESULTS: At least 1 recipient artery appropriate for anastomosis (>or= 1 mm) was found in every craniectomy. The mean number of suitable recipient arteries per craniotomy was 2.09 +/- 0.87, the mean diameter was 1.28 +/- 0.24 mm, and the mean length 10.83 +/- 4.87 mm. Bypass patency was confirmed by intraoperative ICG angiography, postoperative computed tomography angiography, and digital subtraction angiography, and reached 100%. CONCLUSIONS: Performing a 3-cm craniectomy over the described target point, reliably allows access to suitable recipient arteries for EC-IC bypass surgery.

Validity of a PCR assay in CSF for the diagnosis of neurocysticercosis.

OBJECTIVE: To prospectively evaluate the validity of a PCR assay in CSF for the diagnosis of neurocysticercosis (NC). METHODS: We conducted a multicenter, prospective case-control study, recruiting participants from 5 hospitals in Cuenca, Ecuador, from January 2015 to February 2016. Cases fulfilled validated diagnostic criteria for NC. For each case, a neurosurgical patient who did not fulfill the diagnostic criteria for NC was selected as a control. CT and MRI, as well as a CSF sample, were collected from both cases and controls. The diagnostic criteria to identify cases were used as a reference standard. RESULTS: Overall, 36 case and 36 control participants were enrolled. PCR had a sensitivity of 72.2% (95% confidence interval [CI] 54.8%-85.8%) and a specificity of 100.0% (95% CI 90.3%-100.0%). For parenchymal NC, PCR had a sensitivity of 42.9% (95% CI 17.7%-71.1%), and for extraparenchymal NC, PCR had a sensitivity of 90.9% (95% CI 70.8%-98.9%). CONCLUSIONS: This study demonstrated the usefulness of this PCR assay in CSF for the diagnosis of NC. PCR may be particularly helpful for diagnosing extraparenchymal NC when neuroimaging techniques have failed. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CSF PCR can accurately identify patients with extraparenchymal NC.

Cortical perfusion measurement by indocyanine-green videoangiography in patients undergoing hemicraniectomy for malignant stroke.

BACKGROUND AND PURPOSE: Assessment of cerebral perfusion during neurosurgical procedures would be beneficial to identify areas at risk and to guide placement of monitoring probes. Therefore, we have adapted near-infrared indocyanine-green (ICG) videoangiography to assess cortical perfusion intraoperatively. METHODS: ICG videoangiography was performed intraoperatively in 6 patients after decompressive hemicraniectomy for middle cerebral artery stroke. Flow maps of cortical perfusion were generated with IC-CALC 1.1 software by calculating the ratio of difference in fluorescence intensity and rise time. RESULTS: Excellent visualization of cerebral arteries, cortical perfusion and collateral circulation via leptomeningeal anastomoses could be demonstrated in all cases. Flow maps revealed high spatial resolution and showed heterogeneous maple-leaf-shaped hypoperfusion. 26.5+/-13.7% and 29.0+/-9.1% of the exposed cortical surface (141+/-18 cm2) demonstrated core and penumbral flow, respectively. CONCLUSIONS: ICG videoangiography appears to be a valuable tool to precisely detect relative cortical tissue perfusion. Thus, it may provide useful research data on the pathophysiology of human stroke, help surgeons to maintain adequate brain perfusion intraoperatively, and simplify adequate placement of tissue probes to monitor critically hypoperfused brain tissue.

Increased vessel diameter of leptomeningeal anastomoses after hypoxic preconditioning.

Recently, cerebral blood flow changes were re-discussed to contribute to tissue protection after preconditioning. In the present study, we demonstrate increased vessel diameters of the leptomeningeal anastomoses after hypoxic preconditioning by visualization of the brain angioarchitecture using the latex perfusion technique. This finding may display the anatomical correlate to previously described perfusion changes after preconditioning.

Serie de Casos Clínicos: Displasia Osteofibrosa Craneofacial. Resolución Quirúrgica / Case Series: Craniofacial Fibrous Dysplasia. Surgical Treatment

INTRODUCCIÓN: La Displasia Fibrosa Ósea Craneofacial es una lesión ósea benigna en la que se da una sustitución de tejido óseo normal por tejido fibro-óseo. Desarrollada a partir de una mutación genética. Subordinada en variantes: monostósica y polistósica. Escasos casos son reportados sobre malignización de la patología. El Diagnóstico se realiza con la sospecha clínica y se confirma mediante exámenes de imagen y anatomopatológicos. CASO CLÍNICO: El presente trabajo presenta una serie de tres casos diagnosticados de Displasia Osteofibrosa Craneofacial en el Hospital José Carrasco Arteaga y Hospital del Río, Cuenca-Ecuador, en los que por el cuadro clínico de los pacientes se decidió tratamiento quirúrgico. EVOLUCIÓN: En todos los casos, la evolución fue favorable. Se logró resultados positivos, reducción de síntomas y mejoría estética general en todos los casos. CONCLUSIÓN: Se obtienen mejores resultados con los tratamientos quirúrgicos actuales (remodelado más congelamiento óseo), entre ellos: buenos resultados estéticos, mejor calidad de vida, menor riesgo de infecciones. En el presente trabajo los tres participantes sometidos a resolución quirúrgica señalaron que el tratamiento reflejó positivamente en el ámbito funcional, estético y emocional. (au)

BACKGROUND: Craniofacial Bone Fibrous Dysplasia is a benign bone lesion where normal bone tissue is replaced with fibrous tissue. Developed from a genetic mutation. Subordinated in variants: monostotic and polyistotic. Few cases are reported on malignancy of the pathology. The diagnosis is determined with clinical suspicion and confirmed by imaging and pathology tests. CASE REPORT: In this paper, we present a series of three cases diagnosed with Craniofacial Fibrous Dysplasia at José Carrasco Arteaga Hospital and Hospital del Río, Cuenca-Ecuador. All of patients were treated with surgery, because of the clinical features. EVOLUTION: In all the cases, the patient evolution was favorable. Reduction of symptoms and general aesthetic improvement were achieved in all cases. CONCLUSION: Better results are obtained with the current surgical treatments (bone remodeling plus bone freezing), among them: good aesthetic results, better quality of life, lower risk of infections. In the present paper, the three patients treated with the surgical procedure indicated that the treatment reflected positively in the functional, aesthetic and emotional aspects.(au)

Caso Clínico: Uso de Biomodelos Tridimensionales para la Planificación Preoperatoria de Tumores Craneales Fronto - orbitarios / Case Report: Use of Tridimensional Biomodels for Surgical Planning in Fronto-orbital Bone Tumors

INTRODUCCIÓN: La impresión tridimensional de biomodelos ha demostrado en los últimos años ser de gran utilidad para el diagnóstico, tratamiento y planificación preoperatoria en prácticamente todas las especialidades quirúrgicas. En este reporte se presenta la experiencia inicial con el empleo de biomodelos tridimensionales, para la planificación pre quirúrgica de un paciente con displasia fibrosa fronto-orbitaria operado en Cuenca, Ecuador. CASO CLÍNICO: Paciente de sexo masculino de 11 años de edad que desde hace 4 años presentó una¿ masa frontal derecha dura, inmóvil, no dolorosa, de crecimiento progresivo, que produjo deformidad orbitaria con exoftalmia e hipotropia. La tomografía craneal demostró una lesión ósea de núcleo hipodenso, de 5 cm de diámetro mayor, con compromiso del techo de la órbita, porción lateral del seno paranasal frontal y extensión intracraneal extradural. EVOLUCIÓN: Para planificar la cirugía se elaboró un modelo óseo tridimensional que se usó para explicar al paciente y sus padres el objetivo del procedimiento y como se realizaría. El día de la intervención, se dibujaron las osteotomías y craneotomía en el modelo anatómico, plan que se aplicó exactamente en el paciente. El postoperatorio transcurrió sin novedades, la tomografía computarizada de control evidenció una resección completa de la lesión y una adecuada reconstrucción orbitaria. El paciente y sus familiares se mostraron muy satisfechos con las explicaciones dadas. CONCLUSIONES: La impresión 3D es una herramienta que cada vez gana más espacio en la docencia y también en la planificación quirúrgica pues permite disponer de modelos anatómicos muy precisos y simular el procedimiento operatorio, antes de realizar el procedimiento en el paciente real. (AU)

BACKGROUND: 3Dprinting of biomodels has shown in recent years to be very useful for diagnosis,treatmentandpreoperativeplanninginpracticallyall surgical specialties. Inthis reportispresentedthe initial experiencewiththeuseoftridimensionalbiomodels,forpre-surgicalplanninginapatientwithfronto-orbital fibrous dysplasia operated in Cuenca, Ecuador. CASE REPORT: An 11 years old boy presented with a 4-year history of a slow-growing, hard, non-mobile, painless rightfrontalmass which caused orbital deformity, proptosis, and hypotropia. Cranial Computer Tomography showed a 5 cm bone tumor with hypodense center compromising the orbital roof and the lateral aspect ofthe frontal paranasal sinus with intracranial extradural expansion. EVOLUTION: To design the surgery, a tridimensional bone model was elaborated and used to explain the patient and his parents the aim of the procedure and how it will be performed. The day of the intervention, the osteotomies and craniotomy were drawn on the anatomical model, plan that was exactly applied to the patient. The postoperative period was uneventful, control CT scan showed a complete resection of the lesion and an adequate orbital reconstruction. The patient and his relatives were very satisfied with the explanations given. CONCLUSIONS: 3D printing is a very useful surgical tool with wide applications in planning and education that allows simulate in very accurate biomodels an operative procedure before it was done in the actual patient(AU)

Myoblast-mediated gene therapy via encephalomyosynangiosis--a novel strategy for local delivery of gene products to the brain surface.

An encephalomyosynangiosis (EMS) is a temporal muscle graft that is placed onto the surface of the brain to serve as a source for collateral vessel growth for brain revascularization in patients with Moyamoya Disease (MMD). To facilitate an EMS in patients with occlusive cerebrovascular diseases other than MMD, the transfer of pro-angiogenic genes via transplantation of retrovirally transduced myoblasts into the temporal muscle may represent an innovative approach to augment collateralization. Thus, we tested whether retrovirally transfected myoblasts can spontaneously fuse with the non-ischemic and uninjured muscle tissue and if a reporter gene can be stably expressed within the temporal muscle of the EMS. Primary mouse myoblasts expressing a reporter gene were implanted into the temporal muscle prior to an EMS being performed on C57/BL6 mice. Three different implantation modalities were evaluated: (a) intramuscular injection, (b) application of a cell pellet and (c) a combination of both techniques. Myoblast implantation resulted in spontaneous fusion with the host muscle fibers and stable reporter gene expression at both the muscle/brain interface and within the non-ischemic and uninjured temporal muscle in all animals. The mean number of fused hybrid myofibers was 59±28 after injection, 37±30 after pellet application and 60±23 after a combination of both techniques. Regardless of the implantation modality, an abundant extracellular expression of the reporter gene was evident at the muscle/brain interface; in the case of myoblast delivery by injection, expression was also observed around the needle tract marking the implantation site. This method could be used in the future to deliver angiogenic growth factors to the muscle/brain interface in order to improve revascularization after an EMS.

Clinical implications of cortical microvasculature in adult Moyamoya disease.

We analyzed cortical microvascular parameters using intraoperative ICG (Indocyaninegreen)-Videoangiography in 13 patients with Moyamoya disease, and carried out correlative studies by comparing them with clinical parameters obtained by digital subtraction angiography, physical examination, and regional cerebral blood flow studies. Patients with reduced cerebrovascular reserve capacity were characterized by increased microvascular surface area (MVSA). In addition, MVSA correlated positively with arterial microvascular transit time. Asymptomatic patients were characterized by increased arterial microvascular transit time. We show that patients with a higher arteriogenic potential to alter cortical microvasculature are characterized by a more favorable hemodynamic situation and reduced clinical symptoms.