Littérature scientifique sur le sujet « Artero-venous Malformation »

Abstract Abstract 5066 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by two common criteria: angiodysplastic mucocutaneous telangiectasies, and epistaxis; hematemesis, melena, hemoptysis, stroke and visceral artero-venous malformation (AVMv) have also been associated with a significant risk of morbidity and mortality; HHT is divided into two forms: HHT-1 which is caused by a mutation in ENG (endoglin) gene mapping on chromosome 9q33–34, and HHT-2 which is caused by a mutation in ALK1 (activin receptor-like kinase 1) gene mapping on the pericentromeric region of chromosome 12q12–13. Endoglin is an homodimeric disulphide-linked integral membrane glycoprotein (CD105) expressed on endothelial cells of all vessels; it binds TGF-beta 1 and 3, and it is very important to mediate vascular remodelling, the increase of blood flow, cellular migration and adhesion, extracellular matrix synthesis, through the modulation on endothelial cells, smooth muscle cells, fibroblasts and pericytes. ALK1 increases in response to vessel wall stress or injury, and has a specific role in the differentiation of new vessels. The majority of mutations in both genes are null, nonsense or splite-site and are non coding; the spectrum of mutations that have been reported of the two genes are short insertions, deletions, or missense and are present with a high level of consanguinity; homozygous patients with these mutations have severe haemorrhages. We have identified on chromosome 12 a large deletion in exon 7, (8.4 kbp long fragment) of ALK1 encoding for the extracellular ligand-bindig domain involved in the TGF-beta/kinase activity signalling pathway, and in exon 8 (6.4 kbp long fragment) of ALK1 encoding serine-threonine kinase activity. The latter was a 28-year-old woman showing skin telangiectasies, recurrent and significant nosebleeds; the typical puntiform telangiectasies were evident since the age of 16, she also demonstrated with gastrointestinal endoscopy numerous gastric telangiectasies; abdominal and thoracic CT were performed and pulmonary involvement was present with a single artero-venous malformation and minimal respiratory symptoms (dyspnea, cyanosis); on the other hand, MRN did not revealed any cerebrovascular damage. Mutations that disrupt ALK1 affect endothelial cells development and the process of angiogenesis; they are associated with mild clinical manifestation, and it has been observed that pulmonary arteriovenous malformations occur less frequently. Disclosures: No relevant conflicts of interest to declare.

Up to now, the possibility of neurosurgical approach remains one of the main key points in acute management of non traumatic intracranial haemorrhage. The aims of neurosurgical evacuation are represented by stopping bleeding, reducing haematoma enlargement, endocranial hypertension and mass effect, and improving cerebral perfusion. In the acute phase of intracranial bleeding, neurosurgeons are called to take critical decisions about the indication or exclusion of surgical approach and this kind of choices can be very difficult. Only a minority of patients suffering from intraparenchimal bleeding undergo urgent surgical evacuation. This decision is based on the presence or the absence of mass effect, occlusion of liquoral flow associated to impairment of vigilance, sites of hematoma surgically accessible and good performance status. In patients suffering for subarachnoid haemorrhage, mainly due to rupture of aneurisms or artero-venous malformations, the percentage of surgery increases together with the possibility of the elective approach.

Up to now, the possibility of neurosurgical approach remains one of the main key points in acute management of non traumatic intracranial haemorrhage. The aims of neurosurgical evacuation are represented by stopping bleeding, reducing haematoma enlargement, endocranial hypertension and mass effect, and improving cerebral perfusion. In the acute phase of intracranial bleeding, neurosurgeons are called to take critical decisions about the indication or exclusion of surgical approach and this kind of choices can be very difficult. Only a minority of patients suffering from intraparenchimal bleeding undergo urgent surgical evacuation. This decision is based on the presence or the absence of mass effect, occlusion of liquoral flow associated to impairment of vigilance, sites of hematoma surgically accessible and good performance status. In patients suffering for subarachnoid haemorrhage, mainly due to rupture of aneurisms or artero-venous malformations, the percentage of surgery increases together with the possibility of the elective approach.

The basis for interest in proton beams by clinical radiation oncologists lies in reduction in treatment volume. The yields from employing a smaller treatment volume are the increase of tumor control probability and the reduction of normal tissues complication probability. The clinical use of proton therapy began in 1954 at Uppsala University in Sweden and in 1961 at Harvard Cyclotron Laboratory in Boston, USA. So far, the total number of worldwide patients treated by protons is about 20,000. In this paper attention will be given to the treatment of patients at the Massachusetts General Hospital-Massachusetts Eye and Ear Infirmary-Harvard Cyclotron Laboratory, and at the Loma Linda University Medical Center. In particular, a review of the literature about the techniques and the results of treatment of skull base and cervical spine chordoma and low-grade chondrosarcoma, skull base meningioma, pituitary tumors, paranasal sinus carcinoma, glioblastoma multiforme, artero-venous malformations, uveal melanoma, macular degeneration, retinoblastoma, thoracic spine-sacrum tumors, and prostate carcinoma is presented. In order to verify and improve the clinical results, the conduct of prospective trials on an inter-institutional basis is essential. To facilitate the conduct of such studies the US National Cancer Institute and the American College of Radiology have established the Proton Therapy Oncology Group (PROG). Several phase III and some phase I-II trials are active at the Massachusetts General Hospital, Harvard Cyclotron Laboratory, and at the Loma Linda University Medical Center.

Foetal cardiac surgery is the ultimate goal in the treatment of congenital cardiac malformations. The aim of our research is to elucidate some of the features of the necessarily invasive experimental protocol to be used in an animal model of foetal cardiac surgery. In particular, we assessed the foetal placentar reactivity to prolonged cardiac bypass in steady-flow conditions. Methods Two cases were selected to show the outcome of prolonged (> 30 minutes) extracorporeal circulation (ECC) instituted without oxygenator under steady-flow assistance. Following the instrumentation of the animal (placement of pressure, flow and myocardial fiber length transducers) and the baseline recordings, a 60-minute bypass period was established with an axial turbopump (Hemopump 14 Fr), after systemic heparinisation and artero-venous cannulation. At the end of the circulatory assistance, the cannulae were removed and a 90 minute observation period followed. The cardiac function was assessed by means of indirectly obtained P-V loops. Results Case A showed a marked reduction in the end-systolic pressure-volume relationship (ESPVR) during ECC, corresponding to a rightward shift of the P-V loop, with a gradual recovery after the assisted circulation. On the contrary, case B was subjected to progressive placental dysfunction, as evidenced by haemogasanalytical data. Consequently, the haemodynamic data also outlined a negative outcome, with high ESPVR values after bypass. Conclusions The present study, while confirming the possibility of cardiac intervention in the foetus, underlines the critical role of minimally invasive protocol to limit both foetal stress and placental dysfunction.

Abstract Abstract 4329 Chronic thromboembolic pulmonary hypertension (CTEPH) results from obstruction of the major pulmonary arteries by incompletely resolved or organized pulmonary emboli which have become incorporated into the pulmonary artery wall, eventually causing an increase in pulmonary vascular resistances. CTEPH is a condition that is recognised in an increased percentage of patients. Pulmonary endarterectomy (PEA) is recognized as being the only curative option for a subgroup of those patients, but anaesthesiologists and intensivists face many challenges in how they manage these patients perioperatively. Ultimately, it is the combination of skills in a multidisciplinary team that leads to a successful procedure and dramatically improves patient's quality of life and life expectancy. Careful pre- and post-operative management is therefore essential for such a successful outcome following PEA. In 1994 in Pavia was started a program in which members of a multidisciplinary team work in close interaction with the aim of increase experience in the challenging problems these patients present in the evaluative, surgical, and post-operative phases of their care. Pregnancy in women with pulmonary hypertension (PH) is reported to carry a maternal mortality rate of 30–56%. No report is available on the management of pregnancy and delivery in patients with CTPH. We report our experience of the management of a pregnancy in a patient previously submitted to PEA in whom pressures decreased significantly but remained higher than normal due to partial intervention. EFS, 29 yrs, had first hemoptysis in 2001. Since then, she suffered effort dyspnea. A second hemoptysis occurred in 2004. She was admitted to hospital as having “Multiple foci pneumonia, with pulmonary hypertension of unclear origin”. In 2005 patient was admitted to a different hospital. A CT scan showed: “Congenital right pulmonary artery agenesia associated with bilateral multiple artero-venous malformations. NYHA Class III”. Patients was transferred to our hospital. Thrombophilic workout resulted negative. PaO2: 79.9 mmHg, pulmonary artery pressures (PAP): 130/60/13 mmHg, pulmonary vascular resistances (PVR): 1.083 dynes/sec/min−5. CT angio-scan: Severe dilation of the common pulmonary artery (34 mm). Right pulmonary artery visible only at proximal level. Bronchial artery dilation, bilaterally. V/Q scan: Absent visualization of the right pulmonary artery. Perfusion absent. Arteriography: Clearcut thrombosis of the right pulmonary artery (initial tract). Multiple typical CTPH lesions of the left pulmonary artery. Lower limb compression ultrasound (CUS): No sign of deep or superficial vein thrombosis. On 11 april, 2005 PEA was performed on the left side, with an attempt on the right side. No agenesia of the right pulmonary artery was found. Probable occlusion in early age, with evolution in fibrosis. Post surgery, PaO2: 94.3 mmHg, PAP: 53/32/15 mmHg, PVR: 453 dynes/sec/min−5. On September 16, 2005 she was pregnant, seventh week. After careful multidisciplinary counseling, patient decided to continue pregnancy. Anticoagulant treatment was switched from warfarin to low molecular weight heparin (LMWH), therapeutic dosage. Two days before elective delivery, LMWH was reduced to prophylactic dosages. On march 2, 2006 after an uncomplicated Caesarean section under general anesthesia, she delivered a healthy baby girl. During the following months, PAPs and functional parameters normalized. Patient is today in relatively good health. Is under oral vitamin K antagonists treatment. In 2007, being pregnant again, opted for therapeutic abortion. Maternal mortality in parturients with PAH or CTPH remains prohibitively high, despite lower death rates than previous decades. Early advice on pregnancy risks, including contraception, remains paramount. Women with PAH or CTPH who become pregnant warrant a multidisciplinary approach with consideration of appropriate therapies. Disclosures: No relevant conflicts of interest to declare.

Obiettivo. Lo scopo di questa ricerca era dimostrare la fattibilità tecnica e l’utilità clinica dell’integrazione della trattografia basata sull’Imaging del Tensore di Diffusione (DTI) nei piani di trattamento con Gamma Knife (GK) per le malformazioni artero-venose, al fine di calcolare la dose che interessa il fascio corticospinale. Ci siamo proposti di raccogliere dati per valutare la tolleranza alle radiazioni del fascio corticospinale e per sviluppare modelli di rischio riguardanti i deficit motori conseguenti al trattamento. Materiale e Metodi. Lo studio di DTI è stato realizzato con una Risonanza Magnetica (RM) a 3 Tesla con tecnica di imaging parallelo in 34 pazienti affetti da malformazione artero-venosa cerebrale situata in prossimità del fascio corticospinale e sottoposti a radiochirurgia con Gamma Knife. Dopo l’elaborazione dei dati di RM, la via motoria bilaterale veniva ricostruita tridimensionalmente. Un software specifico per la registrazione multimodale è stato sviluppato. I tratti di fibre ricostruiti erano registrati sui dati di RM T1 volumetrici, entrambi ottenuti a 3 Tesla. Quindi le risultanti immagini venivano registrate con lo studio di RM ad 1 Tesla, eseguito in condizioni stereotassiche, per realizzare l’integrazione della trattografia nel piano di trattamento. In 14 pazienti la valutazione dell’esposizione radiante del fascio corticospinale è stata realizzata in maniera retrospettiva successivamente alla procedura radiochirurgica; nei rimanenti pazienti l’integrazione della trattografia è stata applicata in maniera prospettica durante la realizzazione del piano di cura. Risultati. Le fibre del fascio corticospinale sono state visualizzate sia nel caso di malformazioni artero-venose emorragiche che non emorragiche. Il numero di fibre ricostruite dal lato affetto era significativamente più basso nei pazienti con un deficit motorio preesistente al trattamento. Le complicazioni motorie post-radiochirurgiche erano significativamente correlate con il volume del fascio corticospinale ricevente una dose ≥ 12 Gy (P = 0,010). La dose integrale del fascio corticospinale era parimenti significativamente correlata allo sviluppo di deficit motori (P = 0,048). Sono stati elaborati modelli di dose-risposta per stimare la probabilità di sviluppare complicazioni motorie utilizzando l’analisi mediante regressione logistica. La sede della malformazione artero-venosa nei nuclei della base e la dislocazione del fascio corticospinale rispetto al suo decorso anatomico erano correlati con volumi più alti di fascio corticospinale esposti ad una dose ≥ 12 Gy. L’incidenza di complicazioni motorie è risultata più bassa nel gruppo prospettico rispetto al retrospettivo (5,0% contro 14,2%, rispettivamente). Conclusioni. L’integrazione della trattografia basata su DTI a 3 Tesla nei piani di trattamento con GK per malformazioni artero-venose localizzate in prossimità del fascio corticospinale è una procedura realizzabile ed attendibile e può essere compatibile con un impiego routinario. Il volume del fascio corticospinale che riceve una dose ≥ 12 Gy e la dose integrale del fascio corticospinale sono fattori predittivi per lo sviluppo di deficit motori. La visualizzazione del fascio corticospinale permette di ottimizzare la pianificazione del trattamento radiochirurgico, realizzando così trattamenti specifici per il paziente con una riduzione della morbidità.
Objective. The aim of this research was to demonstrate the technical feasibility and the clinical usefulness of Diffusion Tensor Imaging (DTI) tractography integration in the Gamma Knife (GK) treatment planning for arterio-venous malformations (AVMs) in order to calculate the dose delivery involving the corticospinal tract (CST). We purposed to collect data for the assessment of the CST radiation tolerance and for the development of risk models concerning treatment-related motor deficits. Material and Methods. DTI study was performed using a 3 Tesla Magnetic Resonance (MR) unit with parallel imaging technique in 34 patients harbouring cerebral AVMs in proximity of the CST undergoing GK radiosurgery. After the data processing, three-dimensional tracking of the bilateral motor pathway was carried out. An in-house software for multimodal registration was developed. The reconstructed fiber tracts were matched on T1 volumetric data set, both obtained at 3 Tesla. Then the resulting images were registered with the 1 Tesla MR study performed under stereotactic conditions for the integration in the treatment planning. In 14 patients the evaluation of CST radiation exposure was retrospectively performed after the radiosurgical procedure; in the remaining patients the integration of CST tractography was prospectively applied during the realization of the treatment planning. Results. The fibers of CST were highlighted in both non-hemorrhagic and hemorrhagic AVMs. The amount of reconstructed fibers on the affected side was significantly lower in patients with a preoperative motor deficit. Post-radiosurgical motor complications were strongly correlated to the volume of the CST receiving ≥ 12 Gy (P = 0.010). The integral dose of the CST was significantly related to the development of motor deficits as well (P = 0.048). Dose-response models were elaborated to estimate the probability of developing motor complications using logistic regression analyses. The location of the AVM in the basal ganglia and the displacement of the CST from its anatomical course were correlated with higher volumes of the CST receiving ≥ 12 Gy. The rate of motor complications resulted lower in the prospective group than in the retrospective (5.0% vs 14.2%, respectively). Conclusions. The integration of tractography based on 3 Tesla DTI in the GK treatment planning for AVMs in proximity of the CST is feasible and reliable and can be compatible within a routine clinical setting. The volume of the CST receiving ≥ 12 Gy and the integral dose of the CST are predictors of developing motor deficits. The visualization of the CST allows to optimize the radiosurgical planning, realizing patient-tailored treatments with a reduction of the morbidity.