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.     

Factors associated with successful arteriovenous malformation radiosurgery

OBJECTIVE: To analyze the clinical and angiographic variables that affect the results of arteriovenous malformation (AVM) radiosurgery and to propose a new method of reporting patient outcomes after AVM radiosurgery. This method incorporates both the obliteration status of the AVMs and the postoperative neurological condition of the patient. METHODS: Patient outcomes were defined as excellent (nidus obliteration and no new deficits), good (nidus obliteration with a new minor deficit), fair (nidus obliteration with a new major deficit), unchanged (incomplete nidus obliteration without a new deficit), poor (incomplete nidus obliteration with any new deficit), and dead. Two hundred twenty patients who underwent AVM radiosurgery at our center before 1992 were subjected to a multivariate analysis with patient outcomes as the dependent variable. RESULTS: Multivariate analysis determined four factors associated with successful AVM radiosurgery: smaller AVM volume (P=0.003), number of draining veins (P=0.001), younger patient age (P=0.0003), and hemispheric AVM location (P=0.002). Preradiosurgical embolization was a negative predictor of successful AVM radiosurgery (P=0.02). CONCLUSION: AVM obliteration without new neurological deficits can be achieved in at least 80% of patients with small volume, hemispheric AVMs after single-session AVM radiosurgery. Future studies on AVM radiosurgery should report patient outcomes in a fashion that incorporates all the factors involved in successful AVM radiosurgery.     

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.     

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.     

Intracavernous anterior cerebral artery origin with associated arteriovenous malformations: a developmental analysis: case report

OBJECTIVE AND IMPORTANCE: This case demonstrates an unusual association between arteriovenous malformations and an intracavernous anterior cerebral artery origin. To the best of our knowledge, this relationship has not been previously described. Identification and understanding of this relationship are important in pre-embolization and surgical planning and in offering some insight into neurovascular development. CLINICAL PRESENTATION: The patient presented with severe recurring headaches and an otherwise nonfocal neurological examination. He maintained a stable neurological course throughout evaluation and therapy. INTERVENTION: The patient underwent endovascular embolization of the arteriovenous malformations without consequence. He was then scheduled for radiosurgical treatment planning. CONCLUSION: This case demonstrates an unusual neurovascular anomaly with associated arteriovenous malformations. To the best of our knowledge, this is the first reported case of such an association. An understanding of anomalous angioarchitecture and neurovascular development is essential for prudent endov ascular and surgical planning.     

Shear stress in cerebral arteries supplying arteriovenous malformations

Arteries supplying cerebral arteriovenous malformations (AVMs) are known to dilate with time. These changes are reversible, and the feeders have been shown to slowly decrease in calibre after removal of the AMV. There is evidence that arteries alter their internal diameters in response to sustained changes of blood flow so that shear stress is kept constant. This implies that blood flow-induced shear stress might be the driving force for remodelling of the cerebral vascular network in the presence of an AVM, and for reversion of these changes after radical operation. The objective of this study is to examine the hypothesis that the shear stress in cerebral arteries supplying AMVs is of the same magnitude as in arteries supplying normal brain tissue in spite of larger blood flow rate. Fifteen patients with supratentorial cerebral AVMs admitted for endovascular treatment were examined with transcranial Doppler ultrasound in the distal Willisian vessels. Vessel calibres were measured in angiograms with magnification correction. Shear stress was estimated assuming a constant value for blood viscosity. Corresponding arteries in the cerebral hemisphere with AVM and in the contralateral one were compared in pairs. Thirty-four pairs of homonymous arteries were studied. The arteries on the AVM side presented larger calibres, higher axial blood flow velocities, lower pulsatility index and larger blood flow rates than the contralateral side. There was a clear positive correlation between blood flow velocities and vessel calibres. The estimates of shear stress did not differ significantly in corresponding arteries of both hemispheres (p = 0.18). The results indicate a precise adjustment of cerebral arterial calibre and blood flow-induced shear stress that presumably induces the progressive dilation of AVM feeders, and the slow regression of the vessel calibres to average dimensions after removal of the lesion. Each vessel seems to remodel itself in response to long-term changes in blood flow rate so that the vessel calibre is reshaped to maintain a constant level of wall shear stress.     

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.     

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.     

Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: how location affects outcome

The present study evaluated the clinical significance of hepatocyte growth factor (HGF) in patients with pulmonary fibrosis. Twenty-one patients with a diagnosis of pulmonary fibrosis [14 with idiopathic pulmonary fibrosis (IPF) and seven with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD]) and 21 normal subjects as control were studied. HGF levels in sera of patients with pulmonary fibrosis (0.34 +/- 0.02 ng ml-1) were elevated significantly as compared with normal subjects (0.21 +/- 0.01 ng ml-1) (P < 0.0001). HGF/albumin levels in broncho-alveolar lavage fluid (BALF) of patients with pulmonary fibrosis (72 +/- 17 ng g-1 albumin) were also significantly elevated as compared with normal subjects (under the detection limit) (P < 0.01). HGF levels in sera correlated significantly with elastase levels in sera and C-reactive protein, and correlated negatively with PaO2. HGF levels in sera were significantly higher in smokers with pulmonary fibrosis (0.42 +/- 0.03 ng ml-1) as compared with non-smokers with pulmonary fibrosis (0.29 +/- 0.03 ng ml-1) (P < 0.005). HGF/albumin levels in BALF correlated significantly with elastase/albumin levels in BALF, lactate dehydrogenase/albumin in BALF, Immunoglobulin A/albumin in BALF, total cell count/albumin in BALF, total number of alveolar macrophage/albumin in BALF, total number of neutrophil/albumin in BALF, CEA/albumin in BALF, CA19-9/albumin in BALF, and SCC/albumin in BALF. These results suggest that following lung injury, HGF may be a mediator involved in the repair which leads to pulmonary fibrosis.     

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.     

Transluminal angioplasty and intra-arterial papaverine for the treatment of cerebral vasospasm after ruptured arteriovenous malformations

BACKGROUND: This is the first report on the use of intra-arterial papaverine and percutaneous transluminal angioplasty in two patients with severe, symptomatic cerebral vasospasm who suffered ruptured arteriovenous malformations (AVMs). CASE DESCRIPTIONS: The source of hemorrhage was a venous aneurysm in the first case and a pedicular aneurysm of the distal posterior inferior cerebellar artery in the second case. In both cases, the AVMs were located in the superior vermis and there was minimal subarachnoid hemorrhage. The first patient underwent removal of the AVM before the period of cerebral vasospasm and the second patient underwent removal of the AVM after the cerebral vasospasm had resolved. The outcome was excellent in the first patient and poor in the second patient. CONCLUSION: Arteriovenous malformation with ruptured aneurysms may be at high risk for cerebral vasospasm even when there is minimal subarachnoid hemorrhage. We recommend early treatment of AVMs with ruptured pedicular, intranidal, or venous aneurysms to avoid rebleeding and to allow for aggressive treatment of cerebral vasospasm. The management of cerebral vasospasm after AVM rupture is discussed.     

Treatment of arteriovenous malformations with stereotactic radiosurgery employing both magnetic resonance angiography and standard angiography as a database

Twenty-one arteriovenous malformations were prospectively evaluated using magnetic resonance angiography and compared with stereotactic angiography. The goals were to establish the feasibility of magnetic resonance angiography, compare it to stereotactic angiography, employ magnetic resonance angiography in follow-up, and semiquantify flow. A correlative evaluation between flow and response to stereotactic radiosurgery was carried out. Phase contrast angiograms were obtained at flow velocities of 400, 200, 100, 60, and 20 cm/sec. The fractionated velocities provided images that selectively demonstrated the arterial and venous components of the arteriovenous malformations. Qualitative assessment of the velocity within the arteriovenous malformations and the presence of fistulae were also determined by multiple velocity images. In addition, 3-dimensional time-of-flight magnetic resonance angiograms were obtained to define the exact size and shape of the nidus. This technique also permitted evaluation of the nidus and feeding arteries for the presence of low flow aneurysms. Correlation between the two imaging modalities was carried out by subjective and semiquantitative estimation of flow velocity and estimation of nidus size. The following velocity parameters were employed: fast, intermediate, slow, and none (arteriovenous malformation obliterated). In 19 of 21 (90.5%) arteriovenous malformations, magnetic resonance angiography was equal or superior to stereotactic angiography for flow quantification and visualization of the nidus. Only 2 of 21 arteriovenous malformations were better demonstrated by stereotactic angiography than by magnetic resonance angiography (failure rate of 9.5%). The nidus size in one case was clearly underestimated by stereotactic angiography and would have resulted in a geographic miss without magnetic resonance angiography. Seven post-radiosurgery arteriovenous malformations were evaluated for follow-up with both magnetic resonance angiography and stereotactic angiography. In 6 of 7 arteriovenous malformations, magnetic resonance angiography response matched stereotactic angiography response. Correlation of flow with outcome was carried out for 14 arteriovenous malformations using magnetic resonance angiography only. Interestingly, all nine arteriovenous malformations with intermediate or slow flow demonstrated partial or complete obliteration; whereas only 3 of 5 fast flow arteriovenous malformations achieved a response with a median follow-up of 10 months. This early analysis suggests that slower flowing arteriovenous malformations may obliterate faster after stereotactic radiosurgery and flow parameters could be employed to predict response. In conclusion, magnetic resonance angiography permits semiquantitative flow velocity assessment and may therefore be superior to stereotactic angiography. An additional advantage of magnetic resonance angiography is the generation of serial transverse images which can replace the conventional CT scan employed for stereotactic radiosurgery treatment planning.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relief of hemiballism from a basal ganglia arteriovenous malformation after radiosurgery

A patient with a 3-year history of progressive hemiballism presented with an unruptured arteriovenous malformation (AVM) in the contralateral caudate nucleus and putamen. PET demonstrated a matched reduction of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in the basal ganglia and adjacent frontal lobe. The patient underwent radiosurgery for the AVM. After a period of no clinical change for 6 months, the movement disorder resolved by month 7 post-treatment. The AVM was successfully obliterated 2 years after irradiation without any significant change in the regional CBF or CMRO2.     

Assessment of neuropsychological changes in patients with arteriovenous malformation (AVM) after radiosurgery

PURPOSE: The purpose of this study was to investigate neuropsychological effects of radiosurgery in patients with cerebral arteriovenous malformation (AVM), with special focus on attention and memory. This report describes the study setup and presents the first results during a follow-up of up to 1 year. MATERIALS AND METHODS: Seventy-nine patients were studied before, acutely after radiosurgery, and during the regular follow-up (subacute phase: Weeks 6-12, chronic phase: Months 6-12). Radiosurgery was performed using a modified linear accelerator (minimum doses to the target volume: 15-22 Gy, median 20 Gy). Estimated whole brain dose was 0.5 to 2 Gy. Neuropsychological testing included assessment of general intelligence (Wechsler Adult Intelligence Scale), attention (modified Trail-Making Test A, Digit Symbol Test, D2 Test, Wiener Determination Machine) and memory (Rey Auditory Verbal Learning Test, Benton Visual Retention Test). During follow-up, alternate test versions were used. Neuropsychological deficits were defined as a test score of at least one standard deviation (SD) below the mean of the normal distribution. RESULTS: The pretherapeutic evaluation revealed marked deviations from the normal population; 24% had deficits in intelligence (range 23-31% in different subtests), attention (35%, 23-59%) and memory (48%, 31-61%). The overall percentage of aberrant results was reduced by 12% (memory) to 14% (attention) in the chronic phase up to 12 months after therapy. The improvement in test scores was significant (p < 0.05) in 3 of 4 subtests of attention functions. CONCLUSIONS: The acute tolerance of radiosurgery seems to be very good in these patients, showing no relevant increase in number of patients with neuropsychological deficits. Although the long-term follow-up needs to be further increased, our data indicate a tendency to slight improvement in the overall neuropsychological performance of AVM patients in the chronic phase after radiosurgery.     

Differential therapy of cerebral arteriovenous malformations. An analysis with reference to personal microsurgery experiences

A total of 126 patients (63 female, 63 male) underwent microsurgical removal of their cerebral arteriovenous malformations (AVMs) by the same surgeon. The mean age at surgery was 34.7 (6-72) years. The symptoms were intracerebral hemorrhage (37.3%), seizure disorder (34.9%) or focal neurological deficits and minor symptoms. According to the Spetzler/Martin scale, 20.6% of the AVMs were grade I, 28.6% grade II, 32.5% grade III, 14.3% grade IV and 4% grade V. In all, 78 AVMs (61.9%) were located in functionally important brain regions. The series was split into three different groups: small AVMs under 3 cm in diameter (n = 62/49.2%), medium-sized AVMs (n = 58/46%) and large AVMs (n = 6/4.8%). Seventeen patients had preoperative embolization of their AVM. All patients had postoperative angiographic control and 3- and 6-month follow-up. One patient died (0.8%), and another one (0.8%), in whom the AVM was incompletely resected, suffered a secondary hemorrhage. Seventeen (27.4%) of the patients with small AVMs developed transient neurological worsening post-operatively, which remained permanently significant in 3.2%. The respective numbers for the patients with medium-sized AVMs were 48.3% and 10.3% and for the large AVMs 83.3% and 33.3%. The results of microsurgical removal of cerebral AVMs can still be considered superior to the results of stereotactic radiosurgical treatment available from the literature-even for small AVMs. This is due to immediate exclusion of the AVM under direct local control of the angioarchitecture and thereby a reduced risk of secondary hemorrhaging and a decreasing morbidity rate with increasing time after the operation. Radiosurgical treatment requires a 2-year latency period for obliteration and carries a mortality rate of up to 12.5% and a rate of unexpected side effects of up to 20%. This treatment should be reserved for small, deep, surgically inaccessible AVMs or used as part of a multimodality treatment regimen consisting of partial embolization, partial excision and consecutive radiation of the residual nidus in initially very large AVMs. Embolization therapy-such as radiosurgery-carries a significant risk of morbidity (8%) and a mortality rate of up to 6%. It should only be considered for AVMs that are expected to be fully obliterated afterwards, or for primary inoperable AVMs that are to be changed into operable ones by embolization. Size reduction of otherwise operable AVMs does not justify the additional risk of embolization. Close collaboration of the specialties involved is desirable.     

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.