Inoperable Arteriovenous Malformations Research Articles

Stenting venous outflow gives symptomatic improvement in a patient with an inoperable brainstem arteriovenous malformation

The extent to which arterial steal or venous hypertension contributes to symptoms in patients with high flow brain arteriovenous malformations (AVMs) is not always clear. We describe a patient with an inoperable AVM of the pons, presenting with headache and neurological deficit where improving venous outflow by stenting produced substantial clinical benefit.

FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR THE TREATMENT OF LARGE ARTERIOVENOUS MALFORMATIONS WITH OR WITHOUT PREVIOUS PARTIAL EMBOLIZATION

Despite the success of stereotactic radiosurgery, large inoperable arteriovenous malformations (AVMs) of 14 cm3 or more have remained largely refractory to stereotactic radiosurgery, with much lower obliteration rates. We review treatment of large AVMs either previously untreated or partially obliterated by embolization with fractionated stereotactic radiotherapy (FSR) regimens using a dedicated linear accelerator (LINAC). Before treatment, all patients were discussed at a multidisciplinary radiosurgery board and found to be suitable for FSR. All patients were evaluated for pre-embolization. Those who had feeding pedicles amenable to glue embolization were treated. LINAC technique involved acquisition of a stereotactic angiogram in a relocatable frame that was also used for head localization during treatment. The FSR technique involved the use of six 7-Gy fractions delivered on alternate days over a 2-week period, and this was subsequently dropped to 5-Gy fractions after late complications in one of seven patients treated with 7-Gy fractions. Treatments were based exclusively on digitized biplanar stereotactic angiographic data. We used a Varian 600SR LINAC (Varian Medical Systems, Inc., Palo Alto, CA) and XKnife treatment planning software (Radionics, Inc., Burlington, MA). In most cases, one isocenter was used, and conformality was established by non-coplanar arc beam shaping and differential beam weighting. Thirty patients with large AVMs were treated between January 1995 and August 1998. Seven patients were treated with 42-Gy/7-Gy fractions, with one patient lost to follow-up and the remaining six with previous partial embolization. Twenty-three patients were treated with 30-Gy/5-Gy fractions, with two patients lost to follow-up and three who died as a result of unrelated causes. Of 18 evaluable patients, 8 had previous partial embolization. MeanAVM volumes at FSR treatment were 23.8 and 14.5 cm3, respectively, for the 42-Gy/7-Gy fraction and 30-Gy/5-Gy fraction groups. After embolization, 18 patients still had AVM niduses of 14 cm3 or more: 6 in the 7-Gy cohort and 12 in the 5-Gy cohort. For patients with at least 5-year follow-up, angiographically documented AVM obliteration rates were 83%for the 42-Gy/7-Gy fraction group, with a mean latency of 108 weeks (5 of 6 evaluable patients), and 22% for the 30-Gy/5-Gy fraction group, with an average latency of 191 weeks (4 of 18 evaluable patients) (P = 0.018). For AVMs that remained at 14 cm3 or more after embolization (5 of 6 patients), the obliteration rate remained 80% (4 of 5 patients) for the 7-Gy cohort and dropped to 9% for the 5-Gy cohort. A cumulative hazard plot revealed a 7.2-fold greater likelihood of obliteration with the 42-Gy/7-Gy fraction protocol (P = 0.0001), which increased to a 17-fold greater likelihood for postembolization AVMs of 14 cm3 or more (P = 0.003). FSR achieves obliteration for AVMs at a threshold dose, including large residual niduses after embolization. With significant treatment-related morbidities, further investigation warrants a need for better three-dimensional target definition with higher dose conformality.

Advances in the radiosurgical treatment of large inoperable arteriovenous malformations

Radiosurgery has proven useful in the treatment of small arteriovenous malformations (AVMs) of the brain. However, the volume of healthy tissue irradiated around large lesions is rather significant, necessitating reduced radiation doses to avoid complications. As a consequence, this can produce poorer obliteration rates. Several strategies have been developed in the past decade to circumvent dose-volume problems with large AVMs, including repeated treatments as well as dose, and volume fractionation schemes. Although success on par with that achieved in lesions smaller than 3 ml remains elusive, improvements over the obliteration rate, the complication rate or both have been reported after conventional single-dose stereotactic radiosurgery (SRS). Radiosurgery with a marginal dose or peripheral dose < 15 Gy rarely obliterates AVMs, yet most lesions diminish in size posttreatment. Higher doses may then be reapplied to any residual nidi after an appropriate follow-up period. Volume fractionation divides AVMs into smaller segments to be treated on separate occasions. Doses > 15 Gy irradiate target volumes of only 5-15 ml, thereby minimizing the radiation delivered to the surrounding brain tissue. Fewer adverse radiological effects with the use of fractionated radiosurgery over standard radiosurgery have been reported. Advances in AVM localization, dose delivery, and dosimetry have revived interest in hypofractionated SRS. Investigators dispensing >or= 7 Gy per fraction minimum doses have achieved occlusion with an acceptable number of complications in 53-70% of patients. The extended latency period between treatment and occlusion, about 5 years for emerging techniques (such as salvage, staged volume, and hypofractionated radiotherapy), exposes the patient to the risk of hemorrhage during that period. Nevertheless, improvements in dose planning and target delineation will continue to improve the prognosis in patients harboring inoperable AVMs.

Arteriovenous Malformations of the Body and Extremities: Analysis of Therapeutic Outcomes and Approaches According to a Modified Angiographic Classification

To propose a modified angiographic classification for peripheral arteriovenous malformations (AVMs) and to determine its value for assessing therapeutic outcomes and approaches to ethanol embolization of AVMs in the body and extremities. AVMs of the trunk and extremities were categorized according to the angiographic morphology of the nidus: type I (arteriovenous fistulae), type II (arteriolovenous fistulae), type IIIa (arteriolovenulous fistulae with non-dilated fistula), and type IIIb (arteriolovenulous fistulae with dilated fistula). Sixty-six patients (41 women; mean age 28.3 years, range 5-53) with inoperable AVMs in the body and extremities who underwent staged ethanol embolizations were retrospectively analyzed. Therapeutic outcomes and approaches were evaluated according the above classification system. The 66 AVMs were composed of 30 (45%) type IIIb, 13 (20%) type II, 12 (18%) mixed types IIIa and IIIb, 9 (14%) mixed types II and IIIb, and 2 (3%) type IIIa. Ethanol embolization was most effective for type II (100%), and more effective for type IIIb (83%) than for type IIIa or mixed types (< or = 50%). Despite the use of the transarterial approach, direct puncture and transvenous approaches were more relevant for treating type II AVMs. Only the transarterial approach was used for treating type IIIa; both direct puncture and transarterial approaches were used for treating the other types. The described angiographic classification provides considerable information concerning the characteristics of AVMs in the body and extremities, the optimal therapeutic approach, and the likely therapeutic outcome.

Ethanol Embolization of Arteriovenous Malformations: Interim Results

To assess retrospectively the interim results and the complications of ethanol embolization treatment of arteriovenous malformations (AVMs). Institutional review board approval was obtained for a retrospective review of patient medical and imaging records. Informed consent was not required by the institutional review board. Written consent for the procedure was obtained from all patients after a discussion about the advantages and risks of the procedure. After a general anesthetic was administered, 40 patients (16 male, 24 female; age range, 9-53 years) with inoperable AVMs in the body and extremities underwent staged ethanol embolizations (range, 1-24; median, 3). Pulmonary artery pressure and arterial blood pressure were monitored as ethanol was injected. Ethanol embolizations (50%-100% ethanol mixed with nonionic contrast material) were performed by using transcatheter and/or direct puncture techniques. Ten patients underwent additional coil deployment during ethanol embolization. Clinical follow-up (range, 2-48 months; mean, 14.6 months; median, 12 months) was performed in all patients, and results from imaging follow-up (range, 0-48 months; mean, 8.4 months; median, 6 months) were available from the last treatment session in 28 patients. Therapeutic outcomes were established by evaluating the clinical outcome of symptoms and signs, as well as the degree of devascularization at follow-up angiography. One hundred seventy-five ethanol embolizations were performed in 40 patients. Sixteen (40%) of 40 patients were cured, 11 (28%) had partial remission, seven (18%) had no remission, and one (2%) experienced aggravation. Treatment failed in five patients (12%). Ethanol embolization was considered effective (cure, 16 patients; partial remission, 11 patients) in 27 patients (68%). Eleven patients will need further treatment sessions for residual AVMs. Twenty-one patients (52%) experienced complications. Twenty-seven minor complications (skin and transient peripheral nerve injuries) (27 [15%] of 175 procedures) occurred in 18 (45%) of 40 patients. All minor complications were healed with wound dressing and observation. Five major complications (five [3%] of 175 procedures) occurred in five (12%) of 40 patients, and four patients recovered completely. Ethanol embolization has the potential for cure in the management of AVMs of the body and extremities but with acceptable risk of minor and major complications.

Pros, cons, and current indications of open craniotomy versus gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization

The successful treatment of an intracranial arteriovenous malformation poses both technical and conceptual problems to the neurosurgeon. Treatment decisions are made in light of current understanding of the natural history of these lesions. It is important to understand the pros, cons and current indication of open craniotomy vs. gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization. Surgical removal of an arteriovenous malformation is indicated when the operative risk is less than the morbidity and mortality associated with its natural history. The treatment goal of complete angiographic obliteration of arteriovenous malformations is achieved most effectively by microneurosurgery in low-grade lesions. Large lesions frequently require a combination of embolization and microsurgery. Although recent advances in technology and medical management have allowed previously inoperable arteriovenous malformations to be surgically excised, there is still a small group of arteriovenous malformations that cannot be excised safely due to their size and location. Stereotactic radiosurgery is clearly an important adjunct in the multimodality treatment approach for large arteriovenous malformations. Endovascular embolization can potentially increase safety and efficacy in the treatment of arteriovenous malformations when applied to selective cases with well-defined treatment goals. [Neurol Res 2002; 24: 347-353]

Stereotactic multiple arc radiotherapy. I. Vascular malformations of the brain: an analysis of the first 108 patients.

Between March 1989 and December 1993, 101 patients with inoperable arteriovenous malformations (AVMs) and seven patients with inoperable angiographically occult malformations (AOVMs) have been treated with stereotactic multiple arc radiotherapy (SMART). All patients (excluding one patient with a brain stem AOVM) were treated with a uniform dose of 1750 cGy prescribed to the 90% isodose. Fifty-two patients with AVMs have had follow-up angiographic studies performed 11-42 months after SMART. The complete angiographic obliteration rates were 75-77% for AVMs < 10 cm3 and 40-75% for AVMs > 10 cm3, when studied 18-30 months after SMART. Four patients re-bled prior to complete obliteration representing an actuarial 2-year incidence of re-bleeding of 5.1%. Seven patients developed a new neurological deficit after SMART after a median latent interval of 17 months (range 6-32). The actuarial 2-year incidence of neurological complications was 1.8% for lesions < 10 cm3. The actuarial 2-year incidence of neurological complications was 16% for lesions > 10 cm3 (10.5% for persisting deficit). Of seven patients with AOVM six have shown a reduction in size and degree of contrast enhancement, but in no patient has there been complete resolution shown by CT. Five patients with AOVMs developed symptomatic neurological deterioration at a median of 6 months after SMART (range 5-9). When viewed in the context of the natural history of conservatively managed inoperable AVMs, this series has demonstrated that our highly specialized irradiation technique is a safe and effective treatment for many patients.

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

Twenty-six patients with arteriovenous malformations (AVMs) were treated between 1965 and 1986 with conventional fractionated radiotherapy at the Royal Marsden Hospital. There were 14 male patients and 12 female, aged 11 to 57 years (median, 24 yr). Twenty-five patients completed radiotherapy with a localized treatment target volume of a dose of 40 to 54 Gy. The median follow-up was 14.5 years. Eleven patients had an additional hemorrhage. The actuarial annual risk of bleeding was 2.3%, which is similar to that found in untreated patients. Follow-up angiograms were performed in 11 patients, and 10 showed persistence of AVM. The results suggest that fractionated radiotherapy in conventional doses does not make a large impact on the risk of hemorrhage in patients with inoperable AVMs, and, where possible, stereotactic external beam radiotherapy/radiosurgery should be employed.

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

The Prospective Application of a Grading System for Arteriovenous Malformations

The decision-making process whereby treatment is offered to a patient with an arteriovenous malformation (AVM) must be supported by an understanding of the risks related to the natural history of the AVM and the risks related to the treatment of that particular AVM. The ability to estimate the treatment risk for an individual patient is hampered by the marked variability in the complexity of AVMs. In 1986, an AVM grading system was proposed to predict surgical morbidity and mortality. This system is based on the AVM size, the neurological eloquence of adjacent brain, and the pattern of venous drainage. Grade I malformations are small, superficial, and located in noneloquent cortex; Grade V lesions are large, deep, and situated in neurologically critical areas; and Grade VI lesions are considered inoperable AVMs. A retrospective application of this grading scheme demonstrated its correlation with the incidence of postoperative neurological complications. A prospective application of the AVM grading system has been performed in 120 consecutive patients who had a complete microsurgical excision of their AVM, with or without AVM embolization. The AVM grading system accurately correlated with both new-temporary (P < 0.0001) and new-permanent (P = 0.008) neurological deficits. The permanent major neurological morbidity rates for Grades I through III were 0%, increasing to 21.9% in patients with Grade IV and 16.7% in patients with Grade V AVMs (P < 0.0001). One patient with a Grade III AVM died from an esophageal hemorrhage 15 months after her AVM was treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Surgical Management of Intracranial Arteriovenous Malformations

The majority of intracranial arteriovenous malformations (AVMs) do not require acute surgical intervention. Some patients, however, require emergent surgical treatment because of a profound neurological deterioration from a mass effect. We report 10 patients who underwent emergency AVM surgery after experiencing neurological deterioration from an intracranial hemorrhage. Two patients bled spontaneously, whereas eight had an intracranial hemorrhage secondary to an embolization procedure. When the patients demonstrated neurological deterioration, they were intubated, hyperventilated, and underwent osmotic diuresis. Barbiturate anesthesia was initiated, and surgery was performed within 30 minutes in most cases. The hematomas were evacuated, and an attempt was made to excise the AVMs at the same time. Postoperatively, intracranial pressure was monitored, and barbiturate coma was maintained until the intracranial pressure returned to normal. Cerebral perfusion pressure was maintained above 55 mm Hg. The operation was confined to evacuating the hematoma in two patients with inoperable AVMs. The other eight patients underwent concomitant total AVM resection. Because of the severity of neurological deterioration, one patient who bled spontaneously underwent surgery based only on a computed tomographic scan of the brain. Nine patients made a good-to-excellent recovery. One patient with a large motor-strip AVM remained hemiplegic. We conclude that in patients presenting with profound neurological deterioration after a spontaneous intracranial hemorrhage or one associated with an embolization procedure, prompt hematoma evacuation with simultaneous AVM excision as well as perioperative intracranial pressure control with mannitol and barbiturates can yield a good-to-excellent outcome.

Failure of conventionally fractionated radiotherapy to decrease the risk of hemorrhage in inoperable arteriovenous malformations.

Twenty-six patients with arteriovenous malformations (AVMs) were treated between 1965 and 1986 with conventional fractionated radiotherapy at the Royal Marsden Hospital. There were 14 male patients and 12 female, aged 11 to 57 years (median, 24 yr). Twenty-five patients completed radiotherapy with a localized treatment target volume of a dose of 40 to 54 Gy. The median follow-up was 14.5 years. Eleven patients had an additional hemorrhage. The actuarial annual risk of bleeding was 2.3%, which is similar to that found in untreated patients. Follow-up angiograms were performed in 11 patients, and 10 showed persistence of AVM. The results suggest that fractionated radiotherapy in conventional doses does not make a large impact on the risk of hemorrhage in patients with inoperable AVMs, and, where possible, stereotactic external beam radiotherapy/radiosurgery should be employed.

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

Failure of Conventionally Fractionated Radiotherapy to Decrease the Risk of Hemorrhage in Inoperable Arteriovenous Malformations

An Experimental Compartmental Flow Model for Assessing the Hemodynamic Response of Intracranial Arteriovenous Malformations to Stereotactic Radiosurgery

Abstract Stereotactic radiosurgery has proven to be an effective method of treating selected inaccessible or inoperable arteriovenous malformations (AVMs) of the brain. Radiation-induced obliteration of successfully-treated AVMs, however, occurs only after some latent period after treatment, depending on size, location, and dose. An experimental compartmental flow model is proposed to describe the hemodynamic alterations in the AVM as a result of the pathophysiological changes after radiosurgery, and to analyze temporal alterations in AVM blood flow rates and pressure gradients before complete obliteration. In representative small (low-flow, 150 ml/min) and large (high-flow, 440 ml/min) AVMs, it is found that increases in pressure gradients across certain vascular structures within the AVM occur during the normal course of radiation-induced flow decrease and AVM obliteration. The magnitude of these pressure alterations, however, may be within the normal physiological variations in cerebrovascular blood pressure. The effects of partial-volume irradiation of the AVM is examined by limiting radiosurgical treatment to varying portions of the flow compartments within the model. It is found that alterations in pressure gradients persist in unirradiated vascular shunts, even after complete obliteration of the treated AVM volume. These pressure alterations may increase the probability of hemorrhage from the untreated shunts of the AVM and cause redistribution of regional cerebral blood flow resulting in increased flow through these untreated shunts.

An experimental compartmental flow model for assessing the hemodynamic response of intracranial arteriovenous malformations to stereotactic radiosurgery

Stereotactic radiosurgery has proven to be an effective method of treating selected inaccessible or inoperable arteriovenous malformations (AVMs) of the brain. Radiation-induced obliteration of successfully-treated AVMs, however, occurs only after some latent period after treatment, depending on size, location, and dose. An experimental compartmental flow model is proposed to describe the hemodynamic alterations in the AVM as a result of the pathophysiological changes after radiosurgery, and to analyze temporal alterations in AVM blood flow rates and pressure gradients before complete obliteration. In representative small (low-flow, 150 ml/min) and large (high-flow, 440 ml/min) AVMs, it is found that increases in pressure gradients across certain vascular structures within the AVM occur during the normal course of radiation-induced flow decrease and AVM obliteration. The magnitude of these pressure alterations, however, may be within the normal physiological variations in cerebrovascular blood pressure. The effects of partial-volume irradiation of the AVM is examined by limiting radiosurgical treatment to varying portions of the flow compartments within the model. It is found that alterations in pressure gradients persist in unirradiated vascular shunts, even after complete obliteration of the treated AVM volume. These pressure alterations may increase the probability of hemorrhage from the untreated shunts of the AVM and cause redistribution of regional cerebral blood flow resulting in increased flow through these untreated shunts.

Results of Neutron Radiosurgery for Inoperable Arteriovenous Malformations of the Brain

Twenty patients with inoperable arteriovenous malformations (AVMs) of the brain were treated with neutron radiosurgery. A 50 MeV cyclotron was used to deliver 9 Gy in a single fraction through 7 to 14 isocentric portals. The size and shape of the portals were customized to each treatment site. Nineteen patients have been followed for a median duration of 24 months following neutron radiosurgery. A radiographically demonstrable partial response was seen in 8 patients (42%). No complete responses were observed. There has been one post-treatment hemorrhage, no fatalities, and no evidence of radiation toxicity. The low response rate and absence of toxicity suggest that the appropriate dose for neutron radiosurgical treatment of AVMs is higher than the dose of 9 Gy at isocenter used in this initial study.

Delayed Biologic Reactions to Stereotactic Charged-Particle Radiosurgery in the Human Brain

Over 350 patients have been treated for inoperable intracranial arteriovenous malformations with charged-particle radiosurgery. Focussed accelerated helium ion beams derived from charged-particle cyclotrons are stereotactically directed into the brain to obliterate abnormal shunts. Treated patients demonstrate delayed changes in brain anatomy and function that occur months to years after radiosurgery. The underlying mechanisms of the brain's delayed reaction to charged-particle radiosurgery involve complex perturbations in cerebrovascular and metabolic function. This report describes the wide range of delayed reactions that may occur in the brain after radiosurgery, including hemodynamic changes, blood-brain barrier disruption and vasogenic edema, metabolic suppression, and parenchymal necrosis. These delayed reactions to injury in the brain involve potential target cells that include cerebral endothelial cells, oligodendroglia and astrocytes.

Radiosurgery of cerebral arteriovenous malformations with the dynamic stereotactic irradiation

From December 1986 through December 1988, 33 patients with inoperable arteriovenous malformation (AVM) were treated in our center with the dynamic stereotactic radiosurgery, which uses a standard 10 MV isocentric linear accelerator. There were 18 females and 15 males with a median age of 26 years (range: 9–69) and a median follow-up time of 16 months (range: 7–32). The arteriovenous malformation volumes treated ranged from 0.2 to 42 cm 3. The prescribed doses at the isocenter varied from 50 to 55 Gy and were given as a single fraction in the majority of the patients ( 31 33 ). Late complications consisting of intracranial bleeding and/or hemiparesis were observed in three patients. To date, 21 patients underwent repeat angiographic studies at 1 year post-treatment. A complete obliteration of the lesion was achieved in 38% of these patients. For the patients whose arteriovenous malformation nidus was covered by a minimum dose of 25 Gy, the total obliteration rate was 61.5% (8/13), whereas none of the patients who had received less than 25 Gy at the edge of the nidus obtained a total obliteration. Our preliminary analysis at I year post-radiosurgery reveals results comparable to those previously reported for other radiosurgical techniques for the same follow-up period.