Failure in radiosurgery treatment of cerebral arteriovenous malformations

OBJECTIVE: The aim of this study was to retrospectively analyze the reasons for the failure of radiosurgical treatment of cerebral arteriovenous malformations (AVMs). METHODS: Seventeen cases of noncured AVMs were reviewed 3 years after radiosurgical treatment. Follow-up ranged from 33 to 54 months (mean, 44.3 mo). Lesion dimensions varied from 9 to 55 mm (mean, 29.2 mm). The lesions were located in critical or near-critical brain regions. Angiography was performed under Talairach's stereotactic conditions. Two large AVMs bled 36 and 39 months after receiving irradiation, respectively. These two AVMs had been incompletely irradiated. RESULTS: Retrospectively, in four cases (23.5%) we observed errors in determining AVM target shape and size because of inaccurate definition of the nidus and/or because of stereoangiographic incompleteness (absence of external carotid artery injections). In five large and/or irregularly shaped AVMs (29.4%), a strategy of partial volume irradiation had been used. In one patient (5.8%), we observed the recanalization of previously embolized AVMs. In another case (5.8%), the target had been partially missed. The AVMs in one case (5.8%) had been treated with an ineffective peripheral dose. In one (5.8%), the failure occurred because of the lesion angio-architecture. In four cases (23.5%), no evident reasons for failure were determined. CONCLUSION: The results of this study suggest the necessity of complete irradiation of the nidus. The strategy of partial volume irradiation might be avoided, even if it necessitates lowering the doses to treat large AVMs. Accuracy in the target determination is required, and complete stereoangiography is necessary.     

Spontaneous angiographic obliteration of cerebral arteriovenous malformations

OBJECTIVE: The factors associated with spontaneous angiographic obliteration of cerebral arteriovenous malformations (AVMs) are not well understood. We present a review of the literature and a report of our experience with six cases (four with no previous treatment intervention and two postoperative residual malformations) that were identified as having occurred during a 20-year period and describe the clinical and lesion features associated with this rare phenomenon. We present the first detailed histological study of a spontaneously thrombosed AVM specimen, including immunohistochemical analysis of angiogenesis factor expression. METHODS: A combined experience in the management of approximately 700 AVMs during 20 years identified six cases of spontaneous angiographic obliteration of cerebral AVMs. A literature review revealed another 24 cases with angiographic documentation of the initial AVMs and follow-up data showing nonfilling of the lesions. Histological analysis of a recently excised lesion included immunostaining with monoclonal antibodies to the antigens of Factor VIII, Tie, vascular endothelial growth factor, and its receptors, Flt-1 and Flk. RESULTS: A single draining vein was a feature in each of our 6 cases and in 12 of 14 (86%) cases from the literature. Hemorrhage as the presenting symptom was identified in 5 of our 6 (83%) cases and in 17 of 24 (71%) of the literature cases. The size of the AVM was less than 6 cm in each of our 6 cases and in 22 of 24 (92%) of the literature cases. A histological examination of a thrombosed AVM surgical specimen revealed persistent patent vascular channels within the lesion. Immunohistochemical analysis with angiogenesis and endothelia-specific factors showed expression of these factors within the lumen of the thrombosed nidus vessels. CONCLUSION: We propose that the occlusion of a single draining vein may lead to total venous outflow obstruction and lesion thrombosis. Hemorrhagic presentation and small nidus may also predispose to this phenomenon. Immunohistochemical analysis of a thrombosed AVM revealed possible ongoing angiogenic changes within the AVM vessels 1 month after angiographically documented thrombosis. It is possible that neovascularization within a thrombosed AVM may lead to lesion recanalization; however, this phenomenon seems to be clinically exceedingly rare.     

Reflections on the management of cerebral arteriovenous malformations

BACKGROUND: The authors report their personal experience in the management of cerebral arteriovenous malformations (AVMs), using the three techniques now available: surgical resection, endovascular embolization, and radiosurgery. They review the recent literature on this topic and present their current management algorithm based on this experience. METHODS: A series of 90 patients treated for cerebral AVMs is reported (68% Grade I-III and 32% Grade IV-V, Spetzler scale). The three methods of treatment were used, either individually or in combination, based on the size and the location of the malformation. The first intervention was surgical resection in 26% of cases, endovascular embolization in 57%, and radiosurgery in 17%. Surgery and embolization were followed by another technique in some cases and eventually single modality treatment was used in 58% of cases (surgical resection 21%, endovascular embolization 20%, radiosurgery 17%) and multimodality treatment in 42% (embolization + resection, 21%; embolization + radiosurgery, 17%; resection + radiosurgery, 4%). Embolization was used as reductive therapy in 38% of the overall series (65% of all embolized patients), and was followed by surgery in 56% of cases or by radiosurgery in 44%. Angiography was used to assess the cure rates. RESULTS: The following cure rates were obtained, when each technique was used as a first treatment: surgical resection, 82%; embolization, 6%; and radiosurgery, 83% (2-year angiographic follow-up). After combined treatment, embolization and resection resulted in a 100% cure rate, embolization and radiosurgery produced a 90% cure rate. The clinical outcome was evaluated in terms of deterioration attributable to treatment. Seventy-one percent of patients had no complication, minor complications were observed in 18%, and severe complications in 11%. Treatment mortality was 3%. All deaths were attributable to hemorrhage during the embolization procedure. CONCLUSIONS: In this management algorithm, AVMs submitted directly to surgery or to radiosurgery were considered "good risk" malformations, and the outcome for these cases was good in terms of clinical result and cure rate. AVMs submitted first to endovascular embolization were considered "poor risk" malformations, including a majority of Spetzler Grade IV-V lesions. Not surprisingly, the majority of severe complications occured in this group during embolization. Thus, the major risk of the treatment of AVMs has now shifted from surgery to endovascular techniques. Endovascular embolization as sole treatment gave a low rate of complete occlusion, but proved to be very useful as a reductive therapy, in preparation for further surgery or radiosurgery. Partial embolization permitted high rates of complete cure in difficult AVMs. Embolization should be used to the maximum extent possible as a reductive technique, despite the risks of the procedure. Because of its risks however, this technique of reductive embolization should be used only if absolutely necessary to allow the complete cure of the malformation. Thus, the use of embolization should be considered very cautiously in small malformations as well as in very large and complex AVMs in which partial embolization will not be sufficient to allow complete cure with either endovascular or surgical techniques.     

Surgical and embolic treatment of cerebral arteriovenous malformations

Twenty-eight cases of cerebral arteriovenous malformations in which the treatment consisted of embolization and/or surgical excision are reviewed. Embolization was considered an adjuvant procedure; carried out to reduce the size of the malformation or eliminate the deep arterial supply to it prior to excision. In sixteen of the cases the combined treatment was carried out with one death and one significant postoperative deficit. In the other twelve cases surgical operation or embolization alone was carried out. The anatomy of the lesion determined the applicability of embolization. Although embolization has a high degree of safety, certain pitfalls must be avoided. Changing patterns in the cerebral circulation following embolization and operation as well as the role of collateral circulation to cerebral arteriovenous malformations are discussed.     

Natural history and spontaneous prognosis of cerebral arteriovenous malformations

Eight large series of patients presenting with untreated cerebral arterio-venous malformations (A.V.M.) were reviewed. Data were gathered on 1134 patients who were followed for 20 years or more. The risk of rupture and the rate of other complications were estimated, in relation with other factors like age of patient, size of A.V.M., or hemodynamic stresses. The prevalence of A.V.M. at autopsy is 14 per 10,000 population. Fifty percent of A.V.M.s remain asymptomatic during the whole patient's life. The risk of hemorrhage from rupture of an A.V.M. is 2% per year and per patient. Hemorrhage is more frequent from small-sized A.V.M.s, mostly under certain hemodynamic factors. The risk of hemorrhage is also higher in children between 5 and 10 years of age, and in women to the end of pregnancy. The incidence of seizures and neurological impairment is approximately 1% per year and per patient, and these symptoms mostly occur in elder patients with large A.V.M.s. If the A.V.M. has not been revealed by hemorrhage, the risk of rupture is 1% per year and per patient. The incidence of complications from fortuitously diagnosed A.V.M.s seems very low, and even nil in some series. The risks of therapeutic procedures could not be determined, but in some A.V.M.s, the association of different therapeutic means seems mor advisable than isolated therapy. The analysis of natural history of A.V.M.s is desirable to provide a better information to the patient, and to define the limits of therapeutic indications.     

The endovascular treatment of cerebral arteriovenous aneurysms and malformations

Despite the progress made in cerebral aneurysm microneurosurgery, some morphologic and anatomic characteristics, or also clinical reasons, make surgical clipping of the aneurysmatic column difficult or unfeasible, justifying an endovascular therapeutic alternative. Despite the great progress made, the risk of endovascular intervention with microballoons is significant, particularly in the acute post-haemorrhagic phase: 17.9% mortality and 10.7% morbidity in endosaccular embolisation therapy with the detachable balloon maintaining the arterial lumen permeable. The use of the GDC system (Guglielmi Detachable Coil) has permitted the treatment of proximal and distal aneurysms in the carotid and vertebrobasilar arterial regions. Microcatheterisation also allows intravascular treatment of the vasospasm, by mechanical means--angioplasty, or by pharmacological vasodilatation. With the GDC system one can obtain a complete occlusion of small and medium aneurysms in over 85% of cases, definitive morbidity of 5% to 7% and mortality of 1% to 3%. The objective of AVM endarterial occlusions is to obliterate the nidus through the arterial pedicles that can be microcatheterised by means of a certain embolic agent (Cyanocrilate, PVA or other embolic products). Thus, it is possible to reduce the dimension of the nidus as well as diminish the severity of the arteriovenous shunt, later facilitating the operation or radiosurgery, with the possibility of complete surgical removal in 96% of patients after embolisation. The mortality directly related to this endovascular therapy is approximately 0.9% with severe morbidity below 2%. Complete obliteration of a cerebral AVM can be achieved with endovascular techniques in 15% to 20% of cases, particularly in small lesions, sustain AVMs require careful multidisciplinary discussion aimed at finding the best treatment for each case.     

Mass effect caused by clinically unruptured cerebral arteriovenous malformations

OBJECTIVE: It is generally considered that mass effect caused by arteriovenous malformations (AVMs) is evidence of ruptures. In the present study, the incidence of mass effect in clinically unruptured AVMs was evaluated, and the underlying causative factors and pathophysiological mechanisms were studied. METHODS: Twenty-seven patients with clinically unruptured supratentorial pial AVMs were examined. The majority were suffering from epilepsy, and frontal lobe involvement was revealed in approximately half of the patients. Angiographic studies, computed tomographic scans, and magnetic resonance images were obtained for all patients. Twenty-one patients underwent removal of AVMs. In 10 of the surgically treated patients, intraoperative vascular pressure measurements were obtained before removal of the AVMs. RESULTS: Mass effect was detected in 12 (44%) of the 27 patients. Cortical sulci obliteration (eight patients) and lateral ventricle displacement (seven patients) were frequently noted. The volume of AVMs was significantly larger in patients with mass effect than in those without mass effect (P < 0.001). Large dilated venous sacs or ectatic veins were observed to be associated with mass effect (P < 0.001). In only one patient was gross displacement related to a surrounding massive brain edema. Draining vein pressure in patients with mass effect was significantly elevated as compared to the average value in patients without mass effect (22 +/- 5 versus 12 +/- 3 mm Hg) (P < 0.01). CONCLUSION: The present study suggests that mass effect is not infrequent in clinically unruptured AVMs. Furthermore, multiple causative factors were detected, including the large size of AVMs, marked draining vein dilatation, and brain edema around the AVMs. Findings also indicated that a pathophysiologically high pressure in the venous drainage system may contribute to mass effect.     

Control of epilepsy associated with cerebral arteriovenous malformations after radiosurgery

The autocorrelation function pertaining to spatial distributions of ultrasonic scatterers in soft tissue is believed to contain useful information related to tissue morphology. A simple processing method applied to radio-frequency echo signals estimates this function for a sample having isotropic scattering conditions. It utilizes backscattered echo signals from the sample and echo signals from a reference object having defined scattering properties. The ratio of the echo signal power spectrum from the sample to the echo signal power spectrum from the reference object is obtained, and corrected for attenuation differences between the two media. This yields a "form factor" for the sample, whose inverse Fourier transform is the autocorrelation function. The method was tested using tissue-mimicking samples for which spatial autocorrelation functions could be modeled from the dimensions of embedded scatterers. The shapes of the measured autocorrelation functions were in reasonable agreement with those estimated, although measured functions overestimated the function at small lag distances. Scatterer diameters estimated from the zeros of the autocorrelation function agreed to within 6% of expected values when the measurement system bandwidth satisfied minimal criteria.     

Pulmonary arteriovenous malformations

This investigation examined reaching and grasping at speed in children with hemiplegic cerebral palsy. Of particular interest was the effect of the movement of the less affected limb on the more affected one. Using 3D kinematic analysis and standard video recordings, 11 children with hemiplegia of varying degrees of severity were examined performing three reaching tasks at speed. The data were analysed and the extent and nature of the interlimb coupling occurring in each child were assessed using a number of different variables. The results are discussed in terms of spatial, temporal, and postural coupling. All children coupled to some degree but differed in the degree and type of coupling. Speed facilitated coupling which was stronger during the first part of the movement in all three tasks. The variables affecting coupling included the type of coupling, the nature of the task, the importance of context, and the stage in the movement.     

Spinal arteriovenous malformations

Spinal cord arteriovenous malformations encompass a variety of distinct lesions with aberrant connections between the arterial and venous circulation. Symptomatology and clinical presentation of such lesions are directly related to their location and particular pathophysiology. In the authors' surgical experience, 90% of patients have had the same or improved neurologic function and long-term follow-up.     

Semi-quantitative scintigraphic follow-up studies of cerebral arteriovenous malformations after radiosurgical treatment

An evaluation of semi-quantitative 99Tcm-red blood cell scintigraphy (RBCS) was undertaken in patients with cerebral arteriovenous malformations (AVM) during follow-up after radiosurgical treatment. Twenty-seven patients were studied with an initial dynamic imaging sequence of 32 frames each lasting 2 s, planar images in four projections beginning 15 min post-injection and single photon emission tomography immediately following the planar imaging. A 2 ml cubital vein blood sample was imaged to obtain an extracorporeal equivalent of the intravascular activity. The counts within the AVM on a planar image were divided by the counts obtained from the image of the blood sample (corrected for the same acquisition time and radioactive decay). This value yielded the 'volume index' (VI), which was proportional to the volume of the AVM. The VI obtained from the first RBCS served as the initial reference value and was set at 100%. The VIs obtained from the follow-up investigations of the same patient in the same projection were expressed as the percentage of the initial VI. We found RBCS identified the AVM in all patients. The VIs obtained from the follow-up studies demonstrated a decrease in blood volume at different time intervals after radiosurgical treatment. RBCS provides a sensitive, relatively non-invasive, semi-quantitative method for measuring the relative volume and follow-up of the degree of obliteration of AVMs after radiosurgical treatment.     

Aneurysms related to cerebral arteriovenous malformations: superselective angiographic assessment in 58 patients

PURPOSE: To report the comprehensive superselective angiographic characteristics of aneurysms associated with cerebral arteriovenous malformations. METHOD: One hundred consecutive patients referred for cerebral arteriovenous malformation embolization underwent preembolization superselective angiography. Superselective angiograms were obtained after microcatheterization of arteriovenous malformation pedicles, and assessed for number and location of aneurysms related to the malformation. A chi 2 test was conducted to correlate these parameters with the onset of intracranial hemorrhage. RESULTS: Aneurysms were demonstrated in 58 of 100 patients. Single aneurysms were found in 24 patients and multiple aneurysms in 34. Presence and number of aneurysms were found to correlate significantly with a clinical presentation of hemorrhage. CONCLUSION: Superselective angiography was found to be of paramount importance in elucidating the precise and detailed angioarchitecture of brain arteriovenous malformations.     

Traumatic facial arteriovenous malformations

Traumatic arteriovenous malformations (AVM) represent an abnormal communication between arteries and veins and are usually complex. They occur most commonly in the extremities and are noted most often in military casualties. In the literature there are approximately 25 cases of traumatic AVM of the facial region which are angiographically documented. To these are added five documented cases from this paper, one which was proven at surgery, and one which was suspected from classical signs and symptoms but not diagnosed. The trauma leading to the AVM may be: penetrating, blunt, postsurgical, or inflammatory. A swelling of the face, pulsatile tinnitus, throbbing headache and bleeding comprise the main presenting symptoms. A bruit and thrill are usually present. Doppler ultrasonography and selective arteriography will provide the essential diagnostic information. Embolization therapy may be a helpful preoperative adjunct or may be the total therapy if surgery cannot be performed. Proper identification of the feeder vessels, surgical control of these vessels, total excision of the AVM with functional and cosmetic reconstruction of the tissue defect remain the basic principles of therapy.     

Radiosurgery of cerebral arteriovenous malformations with a linear accelerator: preliminary report

The authors present the results obtained in seven patients with arteriovenous malformations treated with radiosurgery on a linear accelerator. In four patients obliteration of the malformation was obtained after one year. Two of the patients had a transient period of acute brain oedema surrounding the radionecrotic nidus with neurological signs. The present position of radiosurgery in the treatment of arteriovenous malformations is discussed.     

Basic fibroblast growth factor impregnated hydrogel microspheres for embolization of cerebral arteriovenous malformations

To assess the prevention of recanalization at embolized sites in cerebral arteriovenous malformations, the authors devised a novel embolic material, hydrogel microspheres prepared from poly(ethylene glycol) diacrylate impregnated with basic fibroblast growth factor. In this article, preparation of the microspheres, and preliminary study of in vitro and in vivo performance are discussed. Poly(ethylene glycol) diacrylate, prepared from end capping of poly(ethylene glycol) (molecular weights, 1,000, 2,000, and 4,000) with acryloyl chloride and benzophenone derived poly(ethylene glycol), prepared from poly(ethylene glycol) (molecular weight, 2,000) with benzoyl benzoic acid chloride as a photoinitiator, were dissolved in a buffer solution with or without basic fibroblast growth factor. The mixed solution was dropped stepwise into liquid paraffin with stirring. Ultraviolet light irradiation resulted in the formation of relatively rigid hydrogel microspheres (diameter, 100-400 microm). The in vitro study showed that the higher the molecular weight of poly(ethylene glycol) diacrylate used, the faster the release rate of immobilized protein. Canine kidneys were embolized with these microspheres via the femoral artery using a microcatheter. Histologic examination showed that microspheres occluded arterioles. The degree of accumulation of fibroblasts and extracellular matrix were larger for basic fibroblast growth factor impregnated microspheres than for nonimpregnated ones. Basic fibroblast growth factor released from microspheres may help regenerate tissues at arteriovenous malformation sites, and recanalization is expected to be prevented.     

Comprehensive management of arteriovenous malformations

The treatment of arteriovenous malformations depends on the efforts of a multidisciplinary team whose ultimate goal is to achieve better results when compared to the natural history of the pathology. The role of adjuvant treatment modalities such as radiosurgery and endovascular embolization is discussed. Treatment strategies and surgical results from a personal series of 344 patients operated in a ten-year period are reviewed. The Spetzler and Martin classification was modified to include subgroups IIIA (large size grade III AVMs) and IIIB (small grade III AVMs in eloquent areas) to assist the surgical resection criteria. The treatment strategy followed was surgery for grades I and II, embolization plus surgery for grades IIIA, radiosurgery for grades IIIB, and conservative for grades IV and V. According to the new proposed classification 45 (13%) patients were grade I, 96 (28%) were grade II, 44 (13%) grade IIIA, 97 (28%) grade IIIB, 45 (13%) grade IV, and 17 (5%) were grade V. As for surgical results 85.8% of the patients had a good outcome (no additional neurological deficit), 12.5% had a fair outcome (minor neurological deficit), 0.6% had a bad outcome (major neurological deficit), and 1.2% died. These figures indicate that the treatment of arteriovenous malformations can achieve better results compared to the natural history if managed by a well trained group of specialists led by an experienced neurosurgeon.     

Nonadhesive liquid embolic agent for cerebral arteriovenous malformations: preliminary histopathological studies in swine rete mirabile

OBJECTIVE: To assess acute and chronic histopathological changes observed in a swine arteriovenous malformation model after endovascular delivery of Embolyx E (Micro Therapeutics Inc., San Clemente, CA) and its organic solvent dimethyl sulfoxide (DMSO). To develop standard endovascular delivery techniques of Embolyx through microcatheters into swine rete mirabile (RMB). METHODS: Forty RMBs in 22 swine were used to analyze acute and chronic angiographic and histological changes after superselective delivery of Embolyx E and/or its organic solvent (DMSO). Four RMBs (two for DMSO and two for Embolyx E study) were used as control specimens. Angiographic and histological evaluations were obtained 18 days, 1 month, 3 months, and 6 months after the procedure. Particular attention was paid to the presence of focal or diffuse angionecrosis, arterial revascularization, and perivascular inflammatory response. RESULTS: Staged and/or continuous delivery of Embolyx E were performed through the DMSO-compatible microcatheters without untoward catheter "gluing." All subacute/chronic specimens embolized with Embolyx E showed no evidence of angiographic recanalization. Twelve RMBs were used in acute studies, and all specimens showed no evidence of angionecrosis or aggressive inflammatory reaction. Subacute and chronic (total, n = 14) histological examinations of the RMBs showed mild inflammatory response manifested by monocellular infiltration and scattered foreign body giant cell reaction. In the 9 of 14 subacute and chronic specimens, focal disruption of elastica was observed along with embolic materials. Fourteen RMBs in eight swine were used to determine the safety range for DMSO injection. Two RMBs were used as control specimens. Rapid intra-arterial delivery (0.5 ml/5-15 s, n = 6) of DMSO caused angiographic vasospasm and histological endothelial necrosis. Slow injection (0.5 ml/30-120 s, n = 8) of DMSO showed minimum or no angiographic vasospasm, minimal adventitial inflammatory response, and no clinical complications. CONCLUSION: Embolyx E, an occlusive and nonadhesive embolic agent, is capable of producing permanent occlusion of swine RMB with the development of mild intra- and perivascular inflammatory changes and no clinical complications. The slow endovascular delivery of DMSO produces no untoward angiographic, pathological, or clinical changes. A fast injection of DMSO causes endothelial necrosis and severe inflammatory response in the arterial wall. This embolic material seems to have appropriate biochemical, anatomic, and histopathological characteristics to be used in the treatment of cerebral arteriovenous malformations or vascular cranial base tumors.     

Therapy of cerebral aneurysms and arteriovenous vascular malformations in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease)

Little is known about the course of cerebral aneurysms in hereditary hemorrhagic teleangiectasia (Rendu-Osler-Weber's disease). Thus, therapeutic decisions are often difficult. For the first time, we report the successful embolization of an arteriovenous fistula and multiple aneurysms of the posterior inferior cerebellar artery (PICA) of a patient with Rendu-Osler-Weber's disease after subarachnoid hemorrhage. Two years later she suffered another severe intracranial hemorrhage. Angiography revealed an aneurysm in the same artery (PICA), which spontaneously disappeared within 2 months. Spontaneous regression of aneurysms in Rendu-Osler-Weber's disease has not been reported before.