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.     

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.     

Effectiveness of intra-arterially infused papaverine solutions of various concentrations for the treatment of cerebral vasospasm

We evaluated the effect of intra-arterially infused papaverine solutions of various concentrations on cerebral vasospasm following subarachnoid haemorrhage. A total of 90 vascular territories in 46 patients with symptomatic cerebral vasospasm after subarachnoid haemorrhage were treated with intra-arterial infusions of papaverine. In all patients, papaverine was infused at the top of the internal carotid artery (ICA). Of the 90 vascular territories, 30 vascular territories in 14 patients were treated with an infusion of 0.1-0.2% (weight/volume) papaverine (Group 1), 30 vascular territories in 16 patients were treated with a 0.4% (w/v) papaverine infusion (Group 2), and 30 vascular territories in 16 patients were treated with an infusion of 0.8-2.0% (w/v) papaverine (Group 3). Among the three groups, we compared the vasodilatory effects of papaverine by assessing the angiographical and clinical improvements following the treatment. When 0.4% (w/v) papaverine was infused, 24 vascular territories (80%) were successfully dilated and 7 patients (44%) showed a marked reversal of neurological deficits due to vasospasm. Therefore, 80 mg/20 ml (0.4% (w/v)) papaverine infused over a 10-minute period proved to be a beneficial concentration. Transient focal neurological deficits due to the infusion of papaverine occurred in 1 Group 1 patient (7%), 1 Group 2 patient (6%), and 7 Group 3 patients (44%). Highly concentrated papaverine had a higher risk of temporary deterioration. In conclusion, the papaverine concentration of 0.4% (w/v) infused at the top of the ICA was a safe and adequate concentration for treating cerebral vasospasm.     

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.     

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.     

Intracranial pressure monitoring during intraarterial papaverine infusion for cerebral vasospasm

PURPOSE: Intraarterial papaverine infusions are performed to reverse cerebral arterial vasospasm resulting from subarachnoid hemorrhage, but such infusions may lead to increases in intracranial pressure (ICP). This study was undertaken to determine when ICP monitoring is indicated during papaverine treatment. METHODS: Seventy-eight vessels were treated in 51 sessions in 28 patients with symptomatic vasospasm. ICP, papaverine doses, and infusion rates were recorded during treatment sessions. The procedural data, Hunt and Hess scores, Fisher grades, Glasgow Coma Scale scores, and ages for all subjects were reviewed and analyzed retrospectively. RESULTS: Baseline ICP ranged from 0 to 34 mm Hg. With typical papaverine doses of 300 mg per territory and infusion times ranging from 5 to 60 minutes per vessel, ICP increases above baseline during papaverine infusion ranged from 0 to 60 mm Hg. Significant (> or = 20 mm Hg) ICP increases during therapy were observed even in patients with low baseline ICP and with papaverine infused at the slowest rate. Patients with a baseline ICP of more than 15 mm Hg were much more likely to have significant ICP increases than were patients with a baseline ICP of 0 to 15 mm Hg. Hunt and Hess scores, Fisher grades, age, and Glasgow Coma Scale scores on admission and immediately before treatment did not correlate with ICP increases during papaverine infusion. Patients with ICP increases of more than 10 mm Hg during therapy were more likely to experience adverse clinical events than were patients with ICP increases of < or = 10 mm Hg. Reduction in the rate of papaverine infusion, or termination of infusion, resulted in reversal of drug-induced ICP elevation. CONCLUSION: ICP monitoring during intraarterial papaverine infusions for cerebral vasospasm is recommended for all patients and is particularly important for patients with elevated baseline ICP. Continuous ICP monitoring facilitates safe and time-efficient drug delivery.     

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.     

Intraarterial papaverine as an adjunct to transluminal angioplasty for vasospasm induced by subarachnoid hemorrhage

Basilar artery vasospasm refractory to medical therapy was confirmed by clinical deterioration and angiography in a 47-year-old man; successful passage of a nondetachable balloon system and angioplasty were facilitated by intraarterial papaverine.     

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.     

Prophylactic effect of papaverine prolonged-release pellets on cerebral vasospasm in dogs

OBJECTIVE: A drug delivery system using copoly(lactic/glycolic acid) was developed for the intracranial administration of papaverine. A rod-shaped implant prepared by a heat compression method was tested to determine its efficacy in preventing cerebral vasospasm in dogs. METHODS: Sixteen dogs were randomly assigned to one of two groups, i.e., placebo or papaverine. Control angiography was performed, followed by right craniectomy and the induction of subarachnoid hemorrhage by the placement of a clot in the Sylvian fissure. Two pellets, containing either 25 mg of papaverine or no papaverine, were placed in the cistern. In in vitro studies, 56% of the actual papaverine loading was released in the first 4 days and 78% within 8 days. On Day 7, angiography was repeated and the animals were killed. A similar experiment using low-dose pellets containing 5 mg of papaverine, half of which was released within 7 days, was performed with 16 mongrel dogs. RESULTS: There were significant differences between the papaverine- and placebo-treated groups in the reductions of vessel diameters of the internal carotid, middle cerebral, and anterior cerebral arteries on the clot side. The mean concentration of papaverine in the clot was 4.5 x 10(-4) mol/L. The low-dose pellet failed to prevent cerebral vasospasm, although the mean concentration of papaverine in the clot was 2.3 x 10(-5) mol/L. CONCLUSION: A prolonged-release preparation of papaverine that could be implanted intracranially at the time of surgery prevented vasospasm significantly while maintaining an appropriate concentration of papaverine in the cistern.     

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.     

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 value of intraoperative angiography for surgical treatment of cerebral arteriovenous malformations in eloquent brain areas

Intraoperative digital subtraction angiography (DSA) allows intraoperative assessment of outcome of cerebral arteriovenous malformations (AVM). This study reports on 21 patients with AVMs in eloquent areas of the brain extirpated between July 1995 to March 1998. Extirpation was always followed by intraoperative DSA. Intraoperative angiography disclosed an occult residual nidus in 4 cases (19%). Complete extirpation of the AVM was achieved in all cases. Following surgery the neurological condition improved in 15 cases (71%), remained unchanged in 5 (24%), and worsened in 1. There were no secondary postoperative haemorrhages, nor complications related to the angiography. These results indicate that intraoperative DSA should be considered in the course of surgical treatment of cerebral AVMs in eloquent areas of the brain.     

Balloon angioplasty for the treatment of vasospasm: results of first 50 cases

OBJECTIVE: To report the results of the first 50 consecutive patients with vasospasm secondary to subarachnoid hemorrhage treated with balloon angioplasty after failure of medical management. METHODS: Retrospective uncontrolled study of 50 consecutive patients treated with balloon angioplasty between February 1988 and July 1992. Forty-six had objective clinical deterioration despite maximal medical therapy, whereas four were treated on the basis of rapidly accelerating transcranial Doppler velocities and decreased regional blood perfusion detected by technetium-99m-exametazime brain single photon emission computed tomography. All patients had evidence of marked vasospasm demonstrated by angiography. Thirty-two (64%) and 46 (92%) patients underwent angioplasty within 12 and 18 hours, respectively. RESULTS: Of the patients with clinical evidence of vasospasm-induced ischemia, 28 (61%) showed sustained neurological improvement within 72 hours of angioplasty. Three (6%) patients deteriorated within 72 hours after angioplasty, with two (4%) patients dying immediately after angioplasty as a result of vessel rupture and the other patient's Glasgow Coma Scale score decreasing by 2. Two additional patients in poor condition with Hunt and Hess Grade V at the time of angioplasty subsequently died during hospitalization. Two other patients died as a result of unclipped aneurysms that subsequently bled 4 and 12 days after angioplasty, respectively. The improvement demonstrated clinically, angiographically, and by transcranial Doppler after angioplasty was sustained, with only one patient requiring subsequent angioplasty of a previously dilated segment (total, 170 vessel segments dilated). Two patients developed vasospasm in previously undilated segments. CONCLUSION: Timely balloon angioplasty can reverse delayed ischemic deficit caused by vasospasm in patients for whom medical therapy has failed.     

Experimental cerebral vasospasm after subarachnoid hemorrhage: development and degree of vasospasm

Vasospasm of the basilar artery in 57 cats was induced by application of fresh blood, or a blood and cerebrospinal fluid (CSF) mixture incubated at 37 degrees C for 2 to 16 days. In animals treated with fresh blood or mixtures incubated for over 15 days, the severity of induced vasoconstriction is slight and duration short. Mixtures incubated 5 to 10 days induced severe and prolonged vasoconstriction. This incubation period for blood and CSF mixtures inducing severe vasospasm coincides with the developmental period of vasospasm after the onset of subarachnoid hemorrhage in our clinical experience. The prolongation of severe vasoconstriction induced by mixtures incubated for 7 days with clotted components is definitely greater than one induced by a mixture without clotted components. This experimental study suggests the existence of a vasospasmogenic substance in the blood in the subarachnoid space. Activity begins about 3 days after subarachnoid hemorrhage, increases strongly at 5 to 10 days, and disappears after 15 days.     

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.     

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.     

Successful surgical treatment of intraorbital arteriovenous malformations: case report

OBJECTIVE: Our purpose was to establish whether obstetric ultrasonography interpreted by a live video telemedicine link is comparable to interpretation by videotape review in a low-risk patient population. STUDY DESIGN: An Integrated Services Digital Network (ISDN 6) was established from three satellite offices to our central prenatal diagnostic center. Patients seen at these satellite offices had a complete fetal anatomic survey recorded onto videotape by a trained ultrasonographer. A live interactive video telemedicine link was then established to our center by the digital network, and a perinatologist directed the ultrasonographer through the anatomy survey. Subsequently a different perinatologist, blinded to the telemedicine interpretation, reviewed the videotaped examination. The reports from the videotaped and telemedicine scans were then compared on the basis of a score of 33 anatomic items. RESULTS: The first 200 patients seen at the satellite offices were included. Telemedicine and videotape interpretations provided similar scores in 84% of scans. In 17 of the 33 anatomic categories telemedicine provided significantly better scores than videotape, whereas in the remaining 16 anatomic categories the scores were equivalent. More videotape than telemedicine examinations required repeat ultrasonography because of suboptimal imaging (10% vs 3%, p = 0.003). CONCLUSIONS: The interpretation of obstetric ultrasonography with use of live video telemedicine is comparable to videotape review. Fetal telemedicine may prove to be a useful tool for providing ultrasonographic interpretation of fetal anatomy to a network of low-risk obstetric practices.