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Arteriovenous malformations (AVMs) are haemodynamically active, fast-flow vascular malformations composed of a tangled anastomosis of arteries and veins with a central nidus, which is the point where the supplying arteries converge and from which the draining veins leave (McCormick 1966). Brain AVMs are located solely within the brain parenchyma, thus distinguishing them from other AVMs. They are morphologically different from cavernous and venous intracranial vascular malformations, and also have a different prognosis and response to medical interventions (Al-Shahi et al. 2001; Tu et al. 2009). Brain AVMs are thought to be due to a combination of both genetic polymorphisms and environmental factors although the precise cause remains unknown (Lasjaunias 1997). Molecular growth factors including vascular endothelial growth factor and basic fibroblast growth factor are thought to be important (Moftakhar et al. 2009). In addition, there may be a high recurrence rate after treatment as the AVM originates from mesenchymal cells at an early stage of embryogenesis (Lee et al. 2004).
Most AVMs present in adolescence, however they can present in early childhood or remain asymptomatic. Recent advances in brain imaging and catheter angiography has increased detection of brain AVMs (Brown et al. 1996), however the prevalence is believed to be about 18 per 100,000 adults (Al-Shahi et al. 2006). Brain AVMs account for a total of 4% of intracerebral haemorrhages; however they are responsible for up to 33% of intracerebral haemorrhages in young adults (Al-Shahi et al. 2006). The most common clinical presentation of an AVM is brain haemorrhage, and there is inconsistent data about age and risk of bleeding (Graf et al. 1983; Crawford et al. 1986; Stapf et al. 2003). Furthermore they are responsible for up to 2% of strokes and can cause focal and secondary generalised seizures (Perret et al. 1966). There is also some evidence that brain AVMs may cause transient, persistent or progressive focal neurological deficits without the presence of haemorrhage, migraine or epileptic seizure (Stahl et al. 1980; Lazar et al. 1999).
Indications for Surgical Treatment of AVMs
Most AVMs will bleed at least once if left untreated, and there is an overall risk of haemorrhage which approximates 2-4% per year which is associated with a 50% chance of permanent neurological deficit and up to 10% chance of mortality (Graf et al. 1983; Ondra et al. 1990; ApSimon et al. 2002). In general, if the AVM is located deep within the brain or if there is an associated aneurysm, drainage to deep venous sinuses, venous stenosis or a single draining vein then the chance of haemorrhage is significantly increased (Spetzler et al. 1992; Pritz 1994; Redekop et al. 1998; Al-Shahi et al. 2001; Stapf et al. 2006). Currently, a decision on the management of a patient is reached by weighing the potential risks of any surgical intervention against the risk of leaving the AVM untreated.
Lee et al proposed a multidisciplinary approach to the treatment of patients with AVM, and in their cohort of 76 patients found that most AVMs were "diffuse infiltrating extratruncular AVMs accompanied by a macro-arteriovenous (AV) shunting nidus" (Lee et al. 2004). Each case was subject to an MDT review following diagnosis, and a consensus reached about treatment. Absolute indications for treatment include major or minor bleeds, gangrene, arterial or venous ulceration, ischaemic complications due to acute or chronic arterial insufficiency or progressive venous complication caused by chronic venous insufficiency (Lee et al. 2004; Kim et al. 2006). In addition, congestive cardiac failure and lesions located at life-threatening vital areas of the brain which may compromise vision, hearing, breathing or eating are also consider to be absolute indications for surgical intervention (Lee et al. 2004). Suggested relative indications include disabling, reduced quality of life (which includes severe cosmetic deformity), vascular-bone syndrome with a discrepancy in limb length, and lesions with a potentially high risk of complication (Lee et al. 2004; Kim et al. 2006).
Management of AVMs
Medical or conservative management includes the treatment of epileptic seizures and headaches, and alleviating symptoms of the AVM. However medical management does not treat the underlying pathology of this condition. The treatment of AVMs differs in adults and children, and in addition is dependent on the clinical staging of the AVM based on the Spetzler-Martin classification (Table 1). Hence in order to grade an AVM it is necessary to determine the size, venous drainage and eloquence of the surrounding brain using CT and MRI imaging. However angiography remains the gold-standard method of evaluating the structure of an AVM (Horton 2007). The Spetzler-Martin grading system ranges from Grade I to V, and in general Grade I and II lesions are resected with a very low incidence of surgically induced neurological deficit (Spetzler et al. 1986). Neurosurgery for Grade IV and V arteriovenous malformations has been shown to be associated with a significant number of neurological complications (Spetzler et al. 1986; Chang et al. 2003; Han et al. 2003), whilst Grade III AVMs are a heterogeneous group with variable outcomes (Lawton 2003).
Table 1: The Spetzler-Martin Grading System of Arteriovenous Malformations
Size of AVM
Eloquence of Adjacent
Pattern of Venous
â€ Eloquent areas of the brain include sensorimotor, language, visual, thalamus, hypothalamus, internal capsule, brain stem, cerebellar peduncles, and deep cerebellar nuclei
â€¡ Superficial lesions drain entirely through the cortical drainage system
The mainstay of treatment of brain AVMs are interventional radiology and surgical procedures including embolisation, sclerotherapy, surgical resection and reconstruction (Marler et al. 2005). Complete elimination of the brain AVM nidus is likely to cause a reduction in case fatality and the incidence of haemorrhage or epilepsy, and is the aim of treatment (Ogilvy et al. 2001; Chen et al. 2006). However, the benefit of treatment may be outweighed by the risk of surgical intervention depending on the grade of lesion and its location within the brain parenchyma. Superficial, uncomplicated, small lesions which drain to non-eloquent cortical areas of the brain may be treated using microsurgical excision. Gamma knife and linear accelerator stereotactic radiotherapy or radiosurgery can be used, but it is limited to AVMs which are under 3cm in diameter and are composed of a compact nidus. Another surgical option is endovascular embolisation, which can potentially completely occlude brain AVMs or can be used as a neoadjuvant before neurosurgery and radiosurgery. In addition, aneurysm treatment can be mediated through the use of detachable coils or glue. These surgical treatments can be used in isolation or in combination to attempt to achieve resolution of the AVM.
Complete surgical resection of the AVM results in immediate cure, although there are risks associated with surgery and this technique is not appropriate in all cases. The surgical resection approach involves coagulating the arterial supply to the AVM followed by a circumferential dissection around the lesion, working from superficial to deep layers within the gliotic gray plane (ref, ref). Venous drainage is maintained until after the arterial supply is removed. High-resolution digital angiography can be used during the operation to evaluate the extent of the AVM resection, minimising the risk of incomplete resection of the nidus (ref, ref). Stereotactic guidance can also be used to localise bone and scalp flaps, facilitate localisation and dissection of deep AVMs as well as planning surgical trajectories (ref, ref).
Both microsurgery and the stereotactic techniques have significantly reduced the risk associated with surgical resection of an AVM (ref, ref). Surgical resection is considered appropriate for Spetzler-Martin Grade I and II AVMs (ref, ref), and this carries a good prognosis as a single stage operation (Pikus et al. 1998) (ref). AVMs which extend into the basal ganglia or thalamus have a greater risk of bleeding and rebleeding, and even low grade AVMs with this anatomy are treated with multistage endovascular embolisation followed by resection or radiosurgery (Sasaki et al. 1998; Paulsen et al. 1999). Grade III AVMs are also often surgically resected after embolisation (ref, ref). In addition, patient age and state of health should also be considered when deciding to perform surgical resection, along with the patient's preference for treatment. It is important to completely remove the AVM, as partial resection may not only lead to relapse and offers no protection against bleeding and may in fact increase the chance of haemorrhage (ref, ref).
There is a relatively high risk of haemorrhage during microsurgical resection, and therefore planned intra-operative monitoring should account for this and adequate amounts of blood made available for transfusion (ref, ref). In addition there is a significant risk of damage to adjacent tissues and ischaemic stroke. It is therefore important that surgical intervention for AVM should be normally be elective operations (Ogilvy et al. 2001) as this should allow time for pre-existing medical conditions to be optimised, and the arranged peri-operative management plan can take into account any existing neurological deficit of the patient (ref, ref).
Additionally surgical resection of an AVM is associated with risks due to the anaesthesia used during the operation. No anaesthetic regimen has been shown to confer absolute cerebral protection during neurosurgery (ref, ref), but an agent must be selected which allows for excellent control of blood pressure, rapid emergence and brain relaxation along with euvolaemia, isotonicity and mild hypocapnia (ref, ref). Intracranial compliance may be abnormal and therefore anaesthetic agents which cause cerebral vasodilatation should be avoided (ref, ref). Induced hypotension is often used during resection of an AVM, especially those with a deep blood supply (Szabo et al. 1989; Langer et al. 1998). Diffuse bleeding from the operative site or brain swelling with postoperative swelling and haemorrhage may be due to normal perfusion pressure breakthrough, which may be treated and prevented by Î±-adrenergic receptor blockers may be used to prevent and treat this condition (Bloomfield et al. 1996; Olsen et al. 2002). However this cause of bleeding or malignant brain swelling should be diagnosed by exclusion of all other correctable causes.
The literature reports a serious adverse event risk of permanent paralysis or weakness, aphasia or hemianopsia ranging from 0 to 15% (Hamilton et al. 1994; Pikus et al. 1998). There has been a low mortality rate reported in these case studies. However, surgical resection on Spetzler-Martin Grade IV or V AVMs has been found to have much greater rates of complications and death, and hence surgical resection is often not used on these grade AVMs (Hamilton et al. 1994; Ogilvy et al. 2001).
Endovascular embolisation currently plays an important role in the surgical treatment of AVMs within the brain. It is rare for endovascular embolisation to be used alone in brain AVM treatment, and generally it is used as an adjunct to surgical resection or radiosurgery (ref, ref). Preoperative endovascular embolisation is used to reduce the risk of blood loss and surgical risk by decreasing the volume of the arteriovenous shunt and the vascularity of an AVM. Multiple embolisations may be required, and this is dependent on the size and complexity of the AVM (ref, ref). Large AVMs with multiple feeding arteries may need many embolisations (ref, ref). In comparison, preradiosurgical embolisation aims to reduce the AVM nidus to a total volume less than 10ml as well as removing aneurysms, fistulae and varices which are potential sources of bleeding after radiosurgery (ref, ref).
Endovascular embolisation carries multiple risks, including technical complications during the embolisation as a result of the AVM architecture or blood flow within the AVM (ref, ref). Significant morbidity and mortality can occur, especially when the venous drainage of the AVM is occluded before the arteriovenous shunt (ref, ref). If embolisation is being used as an adjunct to surgical resection then it is important that the combined risk of both techniques is not greater than the risk of surgical resection alone.
Stereotactic radiosurgery attempts to achieve complete obliteration of the AVM within the brain whilst maintaining neurological function. A focused volume of radiation is delivered to a defined target within the brain and is usually used for AVMs that are not amenable to surgical resection (ref, ref). In addition, stereotactic radiosurgery is used in AVMs which are located in deep areas of the brain, where the surgical approach is likely to be very hazardous, or in small AVMs (Kurita et al. 2000). Stereotactic radiotherapy is most effective when treating AVMs which have a diameter of under 3.5cm and in these cases is between 64% and 95% curative (Colombo et al. 1994; Friedman et al. 1995; Pollock et al. 1998). Small AVMs, young patients, few draining veins and a hemispheric location of the AVM are associated with successful radiotherapy treatment (Pollock et al. 1998). Stereotactic radiosurgery can be used in isolation or as an adjunct therapy after surgery and/or endovascular embolisation (Maruyama et al. 2005) (ref). However, the larger the AVM the smaller the chance of cure using radiosurgery (Friedman et al. 1995; Fleetwood et al. 2002; Maruyama et al. 2005).
Stereotactic radiation delivers a high dose of radiation to the target area of the brain without delivering such large doses to other areas of the brain. Multiple beams of external radiation are focused on a stereotactically defined intracranial target area. The various beams intersect within the area of the AVM and the particle beams are engineered to deposit a well-defined maximal dose of radiation in the target area, a phenomenon known as the Bragg Peak effect (ref, ref).
Stereotactic radiosurgery causes gradual obliteration of the brain AVM over a period of up to 3 years, through thrombosis induced by gradual vascular changes including vessel wall thickening within the AVM nidus (ref, ref). However, because the changes leading to AVM obliteration are gradual, radiosurgery does not affect the risk of haemorrhage from an AVM immediately after the procedure (Pikus et al. 1998; Pollock et al. 1998). In addition, multiple studies have found the stereotactic radiotherapy does not guarantee complete obliteration of brain AVMs (Pikus et al. 1998; Kurita et al. 2000; Pollock et al. 2003; Pollock et al. 2004; Ross et al. 2010; Sun et al. 2010).
Patients who have a residual and patent AVM nidus despite radiosurgery should undergo surgical resection, endovascular embolisation or repeated stereotactic radiotherapy to eliminate the risk of bleeding from the AVM (ref, ref). Failure of stereotactic radiotherapy is associated with many factors including high or increasing Spetzler-Martin grades, decreasing treatment dose or increasing size of the AVM (ref, ref). Further risks of radiosurgery depend on the size and complexity of the AVM treated, the location of the AVM within the brain, and the dose of radiation given (ref, ref). Local alopecia of the scalp, seizures, oedema around the AVM, neurological deficits can occur following radiosurgery and additionally children treated using radiosurgery are at risk of developing secondary tumour formation (ref, ref). Reappearance of brain AVMs following complete obliteration by radiosurgery has also been reported in the literature (Ellis et al. 1998).