Arteriovenous Malformations Nidus Research Articles

Embolisation of cerebral arteriovenous malformations to assure successful subsequent radiosurgery

This study investigated the angiographic changes in embolised arteriovenous malformations (AVMs) pre- and post-embolisation and preradiosurgery to clarify the usefulness of embolisation as a pretreatment for radiosurgery and the strategy of embolisation for the radiosurgical success. A total of 37 patients with cerebral AVMs treated over a period of 4 years was investigated. All the AVMs were embolised with N-butyl cyanoacrylate and 2 months later they were treated by radiosurgery. The size of AVM nidus reduced just following the embolisation (mean 21.9 ml to 3.9 ml). The angiogram taken in preparation for radiosurgery showed a further size reduction in the nidus of 16 AVMs, no change in 10 and regrowth in 11. In all the cases where size was reduced, the nidus was densely packed, while all the regrown AVMs were of the diffuse type. Five AVMs disappeared following radiosurgery, all of which were size-reduction or no-change cases. In conclusion, to achieve success in subsequent radiosurgery, nidus embolisation and the occlusion of fistulous and meningeal feeders are mandatory. Imprudent proximal feeder occlusion and the use of embolic materials with a risk of recanalisation should be avoided to prevent regrowth of the nidus, which may lead to errors in planning the radiosurgery to follow.

Repeated radiosurgery for incompletely obliterated arteriovenous malformations.

The goal of this study was to define treatment results of repeated arteriovenous malformation (AVM) radiosurgery, namely AVM obliteration and complications. The authors analyzed their experience with repeated AVM radiosurgery performed in 41 patients for whom follow-up review lasted at least 2 years. The median duration of follow up was 34 months (range 7-65 months) after repeated radiosurgery in this group. The residual nidus was located within the area of focus (in field) of the initial radiosurgery in 28 patients (68%). Initial doses to the margin varied from 12.5 to 20 Gy (median 18 Gy). During repeated treatment the dose to the margin varied from 12.5 to 20 Gy (median 17 Gy) and the retreated volumes ranged from 0.4 to 7 cm3 (median 2.1 cm3). Follow-up angiography performed at least 2 years postradiosurgery revealed complete AVM obliteration in 21 (70%) of 30 patients. The estimated overall 2-year obliteration rate, based on findings on magnetic resonance imaging (eight of 11 obliterated) and angiography (29 of 41 obliterated) was 71%. Obliteration rates correlated with margin doses (p = 0.0045) with a trend toward higher rates in cases with in-field nidus persistence (p = 0.0637). The dose-response curve for AVM nidus obliteration was not significantly different from that of the initial radiosurgery. In two patients (5%) intracranial AVM hemorrhage developed within 125.9 risk years after repeated radiosurgery (1.6% per patient year). Persistent symptomatic adverse radiation effects developed in two (5%) of 41 patients following repeated radiosurgery. Postradiosurgical imaging changes were identified in 11 (27%) of 41 patients, which correlated with a 12-Gy volume from repeated surgery (p = 0.019). When necessary, repeated AVM radiosurgery achieves obliteration with an acceptable risk. Despite the effects of previous irradiation, repeated radiosurgery required similar or slightly higher radiation doses to achieve the same in-field obliteration rates as those needed to obliterate an AVM that had not been treated by radiation previously.

Combining stereotactic angiography and 3D time-of-flight magnetic resonance angiography in treatment planning for arteriovenous malformation radiosurgery

Purpose: This study was initiated to evaluate the advantages of using three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA), as an adjuvant to conventional stereotactic angiography, in obtaining three-dimensional information about an arteriovenous malformation (AVM) nidus and in optimizing radiosurgical treatment plans. Methods and Materials: Following angiography, contrast-enhanced MRI and MRA studies were obtained in 22 consecutive patients undergoing Gamma Knife radiosurgery for AVM. A treatment plan was designed, based on the angiograms and modified as necessary, using the information provided by MRA. The quantitative analysis involved calculation of the ratio of the treated volume to the MRA nidus volume (the tissue volume ratio [TVR]) for the initial and final treatment plans. Results: In 12 cases (55%), the initial treatment plans were modified after including the MRA information in the treatment planning process. The mean TVR for the angiogram-based plans was 1.63 (range 1.17–2.17). The mean coverage of the MRA nidus by the angiogram-based plans was 93% (range 73–99%). The mean MRA nidus volume was 2.4 cc (range 0.6–5.3 cc). The MRA-based modifications resulted in increased conformity with the mean TVR of 1.46 (range 1.20–1.74). These modifications were caused by MRA revealing irregular nidi and/or vascular components superimposed on the angiographic projections of the nidi. In a number of cases, the information from MRA was essential in defining the nidus when the projections of the angiographic outlines showed different superior and/or inferior extent of the nidus. In two cases, MRA revealed irregular nidi, correlating well with the angiograms and showed that the angiographically acceptable plans undertreated 27% of the MRA nidus in one case and 18% of the nidus in the other case. In the remaining 10 cases (45%), both MRI and MRA failed to detect the nidus due to surgical clip artifacts and the presence of embolizing glue. Conclusions: The 3D TOF MRA provided information on irregular AVM shape, which was not visualized by angiography alone, and it was superior to MRI for defining the AVM nidus. However, when imaging artifacts obscured the AVM nidus on MRI and MRA, angiography permitted detection of AVM. Utilizing MRA as a complementary imaging modality to angiography increased accuracy of the AVM radiosurgery and allowed for optimal dose planning.

Radiosurgery for Intracranial Arteriovenous Malformations in Children

Background: The objective of this retrospective study is to determine the value of radiosurgery in the management of arteriovenous malformations (AVM) in the pediatric age group. Methods: From January 1994 through January 1999, thirty-one children with arteriovenous malformations (AVMs) were treated with radiosurgery. All patients were treated on an outpatient basis at the same institution by the same team. The Leksell Gamma Knife unit was used. Workup included angiography, MRI, and MRA. Follow-up ranged from 7 months to 67 months, with a median of 33 months. Minimum doses of radiation, depending on the size of the lesion, ranged from 20 Gy to 25 Gy. Treatment volumes for all the vascular malformations ranged from 0.6 cc to 17 cc with a mean volume of 4.7 cc. The mean number of isocenters was 4.8. Results: Total obliteration of AVM nidus was obtained in 22 of 31 (71%) patients, while 9 patients had partial obliteration. Stabilization of the benign lesions was obtained in all the patients treated. None had rebleeding after the procedure and, as of this writing, no patient required retreatment. Conclusion: Radiosurgery is an effective noninvasive and safe therapeutic modality for the management of vascular malformations independent of location, size, or grade.

Efficacy of Diluted NBCA Mixture for Embolization of Arteriovenous Malformations

The purpose of this study is to evaluate the efficacy and problems of the embolization for cerebral arteriovenous malformations (AVMs) with diluted cyanoacrylate adhesives. Twelve consecutive AVM cases were treated with N-butyl-2-cyanoacrylate (NBCA) glues between January 1997 and July 1998. The mean age of the patients was 37 years old. Intracerebral hemorrhage was the presenting symptom in seven cases, seizure in three, headache in one and mental deterioration in one. According to the classification of Spetzler and Martin, seven were Grade II, five were Grade III. We used a mixture of NBCA (normally 25% Histoacryl, 75% Ethidol) for embolization. Microcatheter was navigated into the nidus and the tip of the catheter was set in a wedged position. Then the glue was injected using complete column technique. Nineteen sessions of embolization were performed in 12 patients. The mean volume of each nidus was reduced from 22.5 ml to 3.4 ml (85%) after embolization. Four cases were cured by embolization alone. Surgical resection was performed after embolization without any residual nidus in three cases. Five were treated with stereotactic radiosurgery following embolization. One was completely cured in 18 months after and the other four have been decreasing their sizes of nidus. One case was suffered from delayed intracerebral hemorrhage three days after embolization, and resulted in mild hemiparesis and memory disturbance. The others had no complications and were clinically improved or unchanged after embolization. It is possible to embolize the nidus of AVMs more accurately and safely with diluted mixture of NBCA, compared with the method using relatively higher concentration of NBCA glues. This technique is useful and effective method for the treatment of AVMs.

Transvenous retrograde nidus sclerotherapy under controlled hypotension (TRENSH): a newly proposed treatment for brain arteriovenous malformations--concepts and rationale.

An alternative endovascular treatment to conventional transarterial embolization of cerebral arteriovenous malformations (AVMs) is proposed. According to this proposed treatment, selected AVMs could undergo transvenous retrograde nidus sclerotherapy under controlled hypotensive anesthesia (TRENSH). It is hypothesized that TRENSH may provide the means of avoiding delivery of embolic agents via arterial feeders (thus preventing ischemic complications), in addition to a possible more complete permeation of an AVM nidus with a sclerosant than can otherwise be obtained with current agents via arterial feeders. Instead of relying on access to an AVM nidus from the arterial side (with its usual complexity), TRENSH would require retrograde access to the lesion via much larger and anatomically simpler draining veins. Retrograde permeation of the AVM nidus may then be possible with a liquid sclerosant (to effect a "chemical embolization") provided that the arterial inflow is reduced sufficiently by temporary controlled systemic hypotension, with or without the aid of temporary balloon occlusion of the main arterial feeder(s). Retrograde spread of sclerosant within the nidus that falls short of filling arterial feeders and their branches to normal brain tissue may then be possible. Angioarchitectural and hemodynamic considerations are addressed, as are the potential role and limitations of TRENSH in the management of cerebral pial AVMs. Future implementation of this new technique in some specific selected cases in which the anatomic configuration of the AVM and its draining veins might be favorable could prove to be a potentially useful addition to the armamentarium of AVM therapies, which currently includes microsurgery, radiosurgery, and transarterial embolotherapy. Experimental studies directed at assessing the feasibility of TRENSH before potential future clinical application seem justified.

Changes of MR Images in Arteriovenous Malformations of Brain after Gamma-knife Radiosurgery

Purpose: To evaluate the changes in arteriovenous malformation(AVM) of the brain revealed by follow-up MR images after gamma-knife surgery. Materials and Methods: In 25 patients with AVM of the brain who had undergone gamma-knife radiosurgery, 39 MR images were obtained during follow-up between 6 and 46 months later, and were reviewed. We evalu-ated changes volume of the nidus and in its enhancement patterns, changes in T1- and T2-weighted images of the regions in which the nidus had disappeared, and changes in adjacent brain. Conventional follow-up cere-bral angiography was performed in seven patients, and the results were correlated with those obtained by M-RI. Results: On the MR images obtained as described, disappearance of signal void lesion within the nidus was observed in 16 of the 25 patients. In five of 16, the nidus was obliterated within 1 year of gamma-kinfe radio-surgery, and in the remaining 11 patients this happened after 1 year. In nine cases in which the nidus re-mained and 16 in which it was obliterated, follow-up examination of MR images revealed spot and mixed spot-nodular enhancement, with signal void lesion. Within the nidus, serial follow-up MR images showed in-creased enhancement, which was nodule-like. As seen on T1-weighted images, the lesions of obliterated nidus showed slightly lower or iso- signal intensity to gray matter in all 25 cases, while T2-weighted images revealed high signal intensity in 21 cases and iso-signal intensity in four. Abnormal high signal intensity adjacent to the brain was seen on T2 weighted images in nine of 25 cases. In six of seven cases in which cerebral angiography was performed, AVM was obliterated on both MRI and angiography. In one case, however, MR imaging showed that a signal void lesion remained. Cerebral angiography in this case revealed arteriovenous shunting. Conclusion: After gamma-knife surgery, early follow-up revealed that in AVM of the brain, a spot and mixed spot and nodular enhancement pattern was visible, with a reduced volume of signal void lesions. During later follow-up, an enhanced nodular pattern was revealed. Nodular enhancement without signal void lesion proba-bly indicates complete regression of the nidus of AVM.

脳動静脈奇形の塞栓術の到達点と近未来展望

Successful embolization can be achieved only when the follwing three factors are correct and in cooperation : catheter tip position, flow control, ant the setting time of normal-butyl cyanoacylate (NBCA) . Otherwise, the procedure may end with unsatisfactory results or complications. The current principle of safe and efficient embolization of cerebral arteriovenous malformation (AVM) is based on superselective cannulation of every strategically important feeding pedicle and injection of liquid embolic material under flow control. This study was based upon our experiences of embolizing 96 cases with cerebral AVM performed under the above conditions at our department. Results shows very encouraging new observations with implications for further procedures : total removal of the AVM nidus after embolization was achieved in 90% of the cases, preradio-surgical embolization achieved 52% volume reduction and successfully maneuvered all cases into the gamma knife focal spot. Recently improved microcatheters with increased flexibility and minimal friction made it possible to place the tip of the microcatheter into the nidus with a higher success rate and better safety factors. In order to obliterate a substantial amount of the AVM nidus and prevent penetration into the draining veins, the creation of optimal flow status, and optimal setting time of NBCA have paramount importance. Forthcoming complete microcatheter/guidewire units and new embolic materials will enable us to perform safer and more efficient embolization even though the AVM is located distally or fed by perforating arteries.

Mobile fluoroscopic open stereotaxy for MRI-negative angiographic microlesions

The approach to the deep-seated angiographic microlesion is often difficultl particularly when it is not demonstrated by computed tomography (CT) or magnetic resonance imaging (MR/). We have developed a method to localize these lesions for open stereotactic surgery employing mobile fluoroscopy. Prior to craniotomYI the patien(s head is fixed in a stereotactic frame in a position optimal for the routine microscopic surgery. Following the injection of contrast medial the location of the lesion is marked on the fluoroscope monitor. Under fluoroscopic controll the scalp is marked using radiopaque pointer on each side oft~e patientls head so that the scalp marks and the target lesion overlap each other on the fluoroscope monitor. Thus the imaginary line connecting these scalp marks passes through the lesion. An additional.pair of scalp marks is obtained by changing the projection angle of the fluoroscope. By simple calculationl the coordinates of the lesion are obtained as the nearest point to these two imaginary linesl each of which connects a pair of scalp marks. After craniotomYI the Insion is approached using an open stereotactic technique. The first patient had an aneurysm 7.5mm in diameter that arose from the feeder of the arteriovenous malformation. The second patient had a small residual nidus of arteriovenous malformation 7.5 cm in diameter in the deep frontal lobel not recognizable by CT or MRI because of artifacts from a previous surgery. Both patients were successfully operated by employing the present method. This method requires only a conventional stereotactic frame and a mobile fluoroscopel and provides simple and reliable localization of the small lesions recognizable only by cerebral angiography. [Neural Res 1998; 20: 713–718]

Embolization of Cerebral Arteriovenous Malformations to Enhance the Success of Subsequent Radiosurgery

We studied angiographic changes in embolized arteriovenous malformations (AVMs) by comparing pre- and postembolization angiograms and angiograms preceding radiosurgery. This study sought factors determining the usefulness of embolization as a pretreatment to enhance the success of subsequent radiosurgery. Thirty patients with cerebral AVMs treated in this manner over 4 years were studied. In these cases AVMs were embolized with cyanoacrylate and were treated with Gamma-knife radiosurgery. The mean size of the AVM nidus was reduced by a fraction of seven following embolization. The subsequent angiogram for planning radiosurgery showed further nidus reduction in 10 AVMs, no change in 12, and regrowth in 8. In all size-reduction cases the nidus was sufficiently packed, and 2 AVMs had thrombosed completely before radiosurgery. All the regrowing AVMs were of diffuse type; 6 were associated with already-developed leptomeningeal channels, and the remaining 3 were fed by newly sprouted meningeal feeders. Five AVMs disappeared following radiosurgery, all representing size-reduction or nochange cases. Analysis of cases with regrowth showed increased risk of that event with feeder occlusion of a multi-axially supplied AVM, lack of reduction of shunt flow, or remaining meningeal feeders. On the other hand, when embolization as pretreatment prior to radiosurgery succeeds in producing a small, compacted, plexiform nidus with slow shunt flow, it furthers the likelihood of successful radiosurgery. Nidus embolization and occlusion of fistulous and meningeal feeders are mandatory, while proximal feeder occlusion and use of embolic materials which risk recanalization should be avoided to prevent nidus regrowth.

A novel approach to flow quantification in brain arteriovenous malformations prior to enbucrilate embolization: use of insoluble contrast (Ethiodol droplet) angiography

Successful therapeutic embolization of arteriovenous malformations (AVMs) of the brain with liquid polymers (glues) requires precise knowledge of highly variable AVM structure and flow velocities and transit times of blood through the AVM nidus. The goal of this study was to improve AVM flow measurement and visualization by the substitution of the insoluble Ethiodol (ethiodized oil) contrast agent for the soluble contrast media normally used in angiographic studies. Before enbucrilate embolization of 24 AVM feeding pedicles in 13 patients, standard contrast medium was superselectively injected into each target pedicle, followed by infusion of 20 μl of Ethiodol microdroplets. Transport of contrast material was assessed using high-speed biplane pulsed digital subtraction angiography (DSA) operating at 15 frames per second. The mean blood flow transit times through AVMs after administration of Ethiodol were found to be approximately half as long as in those measured after injection of soluble contrast materials (0.22 ± 0.10 seconds compared with 0.46 ± 0.19 seconds [mean ± standard deviation]; p < 0.0001). The discrete Ethiodol microdroplets travel with the core flow, more closely approximating the dynamic behavior of enbucrilate, allowing the AVM structure to be traced with high spatial and temporal resolution. There were no inadvertent vessel occlusions or pulmonary complications related to the use of Ethiodol for DSA. Because of diffusion and convection, forces that decrease concentration, visualization of the contrast front is reduced, often resulting in deceptively long transit times when soluble contrast materials are used. Overestimation may prove dangerous when planning embolizations. The Ethiodol droplet DSA method provides accurate transit time measurements and precise, detailed, and dynamic AVM visualization. Further development of this method will improve the safety and precision of AVM treatments.

Improved technique for liquid embolization of cerebral arteriovenous malformation: catheter-tip position and flow control

This paper outlines the problems currently limiting the success and safety of embolization of cerebral arteriovenous malformations (AVMs) based upon the experiences of 110 cases. In cases where liquid embolic material was deposited mainly in arterial feeders, there was a reconstitution of the nidus through residual primary feeders and recruitment of blood flow via collateral tracts. A recent improvement of flexible microcatheters with minimal friction has made it possible to place the tip of a microcatheter into the nidus with greater success and safety. In order to obtain better filling of the AVM nidus and slower penetration to the draining veins, it is important to perform a temporary balloon occlusion of another main feeding pedicle to reverse the dynamic balance in favor of the pedicle being injected. In order to successfully occlude arteriovenous shunts in the nidus, appropriate flow control and optimal setting time of n-butyl-2 cyanoacrylate have prime importance.

Expression of transforming growth factor-beta complex in arteriovenous malformations.

The factors responsible for the development of cerebral arteriovenous malformations (AVMs) are not well known. Patients with hereditary hemorrhagic telangiectasia (HHT) have cutaneous vascular dysplasia and a high propensity to develop systemic and cerebral AVMs. Transforming growth factor-beta (TGF-beta) complex has been implicated in HHT. The aim of this study was to evaluate the expression of TGF-beta 1, TGF-beta 2, TGF-beta 3, and their two receptors (R1 and R2) in AVMs and in normal brain vessels. Formalin-fixed, paraffin-embedded tissues from 20 patients with cerebral AVMs (including two patients with HHT) were sequentially sectioned into 6 microns sections. Similar sections from normal brain tissue were obtained from five patients without AVMs and no intracranial pathology, who had died from unrelated causes. The normal tissue sections included large intracranial arteries, small arteries, venous sinuses, cortical veins, and brain tissue containing arterioles, capillaries, and venules. All specimens underwent immunohistochemical analyses with polyclonal antibodies to the following antigens: TGF-beta 1, TGF-beta 2, TGF-beta 3, and R1 and R2. The immunoreactivity, when present, was consistently noted in endothelial cells and in the medial smooth muscle. The intensity of vessel wall immunostaining was graded on a scale from 0 to 3. The mean staining grades of normal vessels for TGF-beta 1, TGF-beta 2, TGF-beta 3, R1, and R2 were 0.6 (range 0-1), 3, 2.8 (range 2-3), 1.6 (range 0-2), and 3, respectively, whereas the mean staining grades of AVM vessels were 0.3 (range 0-1), 0.8 (range 0-1), 0.6 (range 0-1), 1.4 (range 0-2), and 0.9 (range 0-1), respectively. The study thus demonstrated that normal brain vessels (arteries, veins, small vessels) have strong (range 2.8-3) immunostaining for TGF-beta 2, TGF-beta 3, and R2, and that the AVM nidus vessels have a paucity (range 0.8-0.9) of staining for these factors. In AVM vessels that had zero immunoreactivity to the above three factors, the vessel wall was fibrocollagenous rather than muscular. Further studies to examine the TGF-beta complex behavior in AVMs are needed.

Embolization of Cerebral Arteriovenous Malformations (AVMs)

Successful embolization can be achieved only when the following three factors are correct and in co-operation: catheter tip position, flow control, and the setting time of normal-butyl cyanoacrylate (NBCA). Otherwise, the procedure may end with unsatisfactory results or complications. The current principle of safe and efficient embolization of cerebral arteriovenous malformation (AVM) is based on superselective cannulation of every strategically important feeding pedicle and injection of liquid embolic material under flow control. This study was based upon our experiences of embolizing 92 cases with cerebral AVM performed under the above conditions at our department. Results showed very encouraging new observations with implications for further procedures: total removal of the AVM nidus after embolization was achieved in 90% of the cases, preradiosurgical embolization achieved 52% volume reduction and successfully maneuvered all cases into the gamma knife focal spot. Recently improved microcatheters with increased flexibility and minimal friction made it possible to place the tip of the microcatheter into the nidus with a higher success rate and better safety factors. In order to obliterate a substantial amount of the AVM nidus and prevent penetration into the draining veins, the creation of optimal flow status, and optimal setting time of NBCA have paramount importance.

Embolization of the Nidus of Brain Arteriovenous Malformations with n-butyl Cyanoacrylate

OBJECTIVE : To demonstrate that nidus embolization of brain arteriovenous malformations (AVMs) with Histoacryl (B. Braun, Melsungen, Germany) is effective and yields low morbidity and mortality rates. METHODS : We present a retrospective analysis of 54 brain AVMs treated at the University of Illinois at Chicago from April 1994 to December 1995. Treatment modalities included embolization in all cases and then surgical resection or radiosurgery. INSTRUMENTATION : The nidus was reached with the combined use of a Magic microcatheter (Balt, Montmorency, France) and a Terumo 0.010-inch guidewire. TECHNIQUE : Embolization was performed only when the tip of the microcatheter was wedged into the nidus of the AVMs with no reflux of contrast proximally. The embolization was performed using simultaneous biplane roadmapping with the patient under general anesthesia without Amytal testing. RESULTS : Twenty-six of 54 patients are still waiting for more radical treatment. Two deaths and two minor and one severe permanent neurological deficit occurred. Three patients were cured with embolization alone ; 11 patients were cured after surgical resection. Three patients underwent radiosurgery, with one cure after 1 year. CONCLUSION : Nidus embolization with Histoacryl is an effective technique that permits complete cure of a large number of brain AVMs, with or without surgical resection and/or radiosurgery.

Histopathology of arteriovenous malformations after gamma knife radiosurgery.

Stereotactic radiosurgery effectively obliterates many arteriovenous malformations (AVMs). Hemodynamic changes in AVMs after radiosurgery have been illustrated using magnetic resonance imaging and angiography, but there have been no detailed reports describing the underlying histopathological changes. This study examines AVMs at various times after gamma knife radiosurgery (GKRS) and describes the histopathological changes that lead to vessel occlusion. The authors examined nine AVM specimens obtained 10 months to more than 5 years after GKRS, by using routine histopathological stains as well as immunohistochemical techniques to detect smooth-muscle actin, factor VIII, and type IV collagen. Blood vessels within the AVMs showed progressive changes leading to narrowing or obliteration of the lumen. The earliest changes after gamma knife irradiation appear to be damage to endothelial cells, followed by progressive thickening of the intimal layer caused by proliferation of smooth-muscle cells that elaborate an extracellular matrix that includes type IV collagen. Finally, cellular degeneration and hyaline transformation occur. For statistical correlation analyses, the specimens were graded according to the degree of histopathological change and the relative number of vessels showing such changes. Both of these parameters were significantly correlated with time after GKRS and with AVM size reduction shown on follow-up imaging studies. Gamma knife radiosurgery of AVMs causes endothelial damage, which induces the proliferation of smooth-muscle cells and the elaboration of extracellular collagen by these cells, which leads to progressive stenosis and obliteration of the AVM nidus. This series of pathological changes in AVMs after GKRS is essentially similar to the response-to-injury model of atherosclerosis.

Intra-arterial nitrovasodilators do not increase cerebral blood flow in angiographically normal territories of arteriovenous malformation patients.

The mechanism of adaptation to chronic cerebral hypotension in normal brain adjacent to cerebral arteriovenous malformations (AVMs) is unknown. To clarify these mechanisms, we performed cerebral blood flow (CBF) studies in structurally and functionally normal vascular territories during 53 distal cerebral angiographic procedures in 37 patients with AVMs. CBF was measured using the superselective intra-arterial 133Xe method before and after a 3-minute infusion of either verapamil (1 mg.min-1, n = 23), acetylcholine (1.33 micrograms.kg-1.min-1, n = 7), nitroprusside (0.5 microgram.kg-1.min-1, n = 16) or nitroglycerin (0.5 microgram.kg-1.min-1, n = 7). Mean +/- SD systemic (76 +/- 13 mm Hg) and distal cerebral arterial (55 +/- 16 mm Hg; range, 20 to 97 mm Hg) pressures were not different among groups. Verapamil increased CBF (45 +/- 12 to 65 +/- 21 mL.100 g-1.min-1, P < .001). There was no effect of acetylcholine (no change [46 +/- 9 to 46 +/- 9 mL.100 g-1.min-1], NS) or nitroglycerin (36 +/- 14 to 36 +/- 13 mL.100 g-1.min-1, NS). Nitroprusside decreased CBF (40 +/- 12 to 31 +/- 11 mL.100 g-1.min-1, P < .001). The percent change in CBF after drug administration was proportional to cerebral arterial pressure for verapamil only (r = .57, P = .0051). When infused intra-arterially in clinically relevant doses in both hypotensive and normotensive normal vascular territories remote from an AVM nidus, calcium channel blockade caused vasodilation, but there was an absence of response to nitric oxide-mediated vasodilators. These data suggest that (1) the nitric oxide pathway probably is not involved in the adaptation to chronic cerebral hypotension in AVM patients and (2) if our findings in vessels remote from or contralateral to the AVM are applicable to vessels of patients with other forms of cerebrovascular disease, clinically relevant doses of intra-arterial nitrovasodilators may not be useful in the manipulation of cerebrovascular resistance.

Deliberate systemic hypotension to facilitate endovascular therapy of cerebral arteriovenous malformations: a computer modeling study

With the aid of a computer model, this investigation describes the relationship between mean arterial pressure (MAP) reduction and its effect on total arteriovenous malformation (AVM) shunt flow, feeding artery velocities, and cerebral blood flow in hypotensive, structurally normal vascular beds adjacent to the AVM nidus. Simulations were performed for two feeding artery sizes (2 and 4 mm in diameter) and two AVM shunt flows (500 and 1000 ml/minute) with and without the presence of autoregulation in normal brain. Systemic arterial hypotension was simulated in a stepwise fashion by reducing aortic pressure from 100 to 10 mm Hg in 10-mm Hg steps. The percentage of MAP that resulted in a 50% reduction of shunt flow was calculated (%MAP reduction at half-maximal shunt flow). As the MAP decreased, the shunt flow decreased in a nearly linear fashion; the cerebral blood flow remained constant in neighboring brain until the MAP dropped below 60 and 80 mm Hg for the medium and large AVMs, respectively. The %MAP reductions at half-maximal shunt flow for the medium and large AVMs were not significantly different from 50%: 44% and 47%, respectively. Results for 2 and 4 mm AVM feeding artery sizes were similar. The decrease in both total shunt flow and flow velocity in feeding artery pedicles, potentially embolized by glue injection, were nearly linear with the institution of systemic hypotension. The presence or absence of autoregulation in normal brain, or different variations in the simulated angioarchitecture of the AVMs, did not affect this relationship in the model.

脳動静脈奇形の臨床病理学的検討-とくにHEMA-MMAおよびEVAL塞栓術後摘出例の比較検討-

We studied the clinical and pathological aspects of 4 arteriovenous malformations (AVM) that were removed totally after preoperative embolization using poly (HEMA-co-MMA) or EVAL. Histopathological examination of AVM nidus embolized with poly (HEMA-co-MMA) showed mild inflammatory cell infiltrations in the vessel wall and small hemorrhages within the nidus and its surrounding brain tissue. On the other hand, EVAL-embolized AVM nidus demonstrated embolic materials within the vessels and inflammatory reaction of the vessel wall and its surrounding tissue, and patchy hemorrhages were also observed within the AVM nidus and its surrounding brain tissue. The difference of inflammatory response between two liquid embolic substances may reflect the difference of organic solvents. In conclusion, poly (HEMA-co-MMA) may be a superior embolic liquid for AVM before excision or radiosurgery because of less inflammatory response to AVM's vascular wall.

Nontoxic embolic liquids for treatment of arteriovenous malformations.

Interventional radiology is becoming one of the standard treatments of arteriovenous malformation (AVM). Cyanoacrylate derivatives and polymer solutions are widely used to occlude the AVM nidus by their injection through a catheter, but they are far from satisfactory embolic liquids. For instance, cyanoacrylate derivatives sometimes glue the catheter to the artery, resulting in serious complications; in addition, the organic solvents used to dissolve polymers cause damage to the surrounding brain tissue of the AVM. Therefore, we attempted to develop embolic liquids by dissolving poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) in Iopamiron with an addition of a small amount of ethyl alcohol. This new embolic liquid is not cytotoxic and is easily injected into the AVM through a thin, long catheter to effectively occlude the AVM.