Functional and topographical considerations in the surgical management of cerebral vascular malformations.

Cerebral vascular malformations with potential surgical consequences mainly consist of arteriovenous malformations (AVM) and cavernous malformations. The standard preoperative workup of these lesions includes basic neuroradiological investigation, such as computed tomography, magnetic resonance imaging (MRI), and magnetic resonance angiography, and conventional angiography, to assess the exact neurotopographical relationships of the nidus, arterial feeding pedicles, and venous drainage. In cases where lesions are located near or within eloquent areas, precise documentation of the anatomy can be obtained using various functional tests including functional MRI, activated positron emission tomoqraphy, and magnetoencephalography (MEG), which may then be integrated into a neuronavigational system allowing for selective, image-guided surgery, thus potentially reducing surgical morbidity. Preoperative embolization may in certain cases improve the surqical excision by reducinq blood flow throuqh the AVM. Cavernous malformations may also be removed with minimally invasive and highly selective techniques.

Hemorrhage from intracranial cerebral vascular malformations accounts for only approximately 10% to 15% of all intracranial hemorrhages and is eight times less frequent than bleeding from berry aneurysms.[1,2] Cerebrovascular malformations can be classified according to their pathology into arteriovenous, capillary, and venous malformations (Table I). Arteriovenous malformations (AVM) and cavernous malformations (CM) are the most frequent lesions requiring surgical attention due to their propensity to bleed. Dural AVMs account for 10% of hemorrhages from vascular malformations.[3]

Arteriovenous malformations

AVMs are believed to result from faulty maturation of the embryonic vascular system through lack of involution of the primary vascular plexus between the 37th and 40th intrauterine day, thus resulting in an absent capillary bed.[4] They are composed of dilated thin-walled arteriovenous channels devoid of an internal elastic lamina (. The structure of an AVM consists of one or several arterial feeders supplying a nidus of varying size, usually conical in shape with the large base at the convexity and the extremity reaching towards the ependymal surface of the ventricular system.[2,4] Most AVMs are located within the distribution territory of the middle cerebral artery (MCA) and therefore affect mostly the frontal, parietal, and temporal lobes; in rarer cases, they affect deeper portions of the brain, such as the corpus callosum, basal ganglia, cerebellum, and brainstem. The nidus is a plexiform structure composed of arterioles, venules, and dilated vascular channels that drain into larger veins. The Spetzler-Martin classification of AVMs[5] into six grades according to their size, deep venous drainage, and relationship to eloquent brain lesions has introduced a means of standardizing the predictability of technical difficulty and morbidity (Table II).

It is estimated that 30% to 40% of AVMs will bleed during an individual's lifetime, but the exact natural history is still controversial: while some authors estimate the mortality rate at 15% to 20% over a 15-year period of observation,[1,6,7] the current cumulative risk of hemorrhage of an unruptured AVM is estimated at 2% per year, and at 6% per year for a previously ruptured AVM.[8] Besides hemorrhage, AVMs may present with chronic headaches, seizures, and, in rarer cases (mainly large AVMs), with progressive cognitive changes due to the hemodynamic steal depriving surrounding brain parenchyma.

Present day treatment of cerebral AVMs includes surgery, endovascular embolization, and stereotactic radiosurgery, which may be used in combination as part of a multimodality treatment or alone in selected cases. The aim of AVM therapy is to exclude the nidus completely, either by excision or thrombosis, in order to eliminate the source of bleeding and to spare the surrounding brain tissue by preserving the transit vessels that may participate in the feeding of the nidus but are responsible for blood supply to normal surrounding brain.

Cavernous malformations (cavernous angioma, cavernoma)

These lesions are congenital vascular hamartomas consisting of a collection of dilated sinusoidal vascular spaces (caverns) separated by thin walls devoid of muscle and elastic fibers, lined by a single layer of endothelial cells, without any intervening cerebral parenchyma, which distinguish them from AVMs and capillary telangiectasias ( They are most frequently located in the cerebral hemispheres (85%) and are associated with seizures as the presenting symptom in 50% of the cases. The introduction of magnetic resonance imaging (MRI) means they are more frequently diagnosed based on the typical mixed signal characteristics with high Tl and low T2 signals (“salt and pepper” or “popcorn” appearance) due to the presence of hemosiderin within the caverns producing hyper-Tl signals and calcifications and mural fibrosis producing hypo-T2 signals.[9,10] The natural history of cavernous angiomas involves a risk of rupture that varies between 2% and 3% per year.[11] Symptomatic lesions presenting with epilepsy or with MRI signs of perilesional hemorrhage are considered candidates for surgical removal. In spite of some reports of beneficial results with radiation therapy, CMs are not usually candidates for stereotactic radiosurgery.[10,12]

Illustrative case histories

Three relevant case histories are presented in order to illustrate some of the surgical management strategies and problems.

Case history 1

A 40-year-old lady with no previous medical historywas admitted following an acute headache and loss of consciousness with decreased sensorium and mild right hemiparesis. A computed tomography (CT) scan ( revealed a significant left intracerebral frontal hematoma. Following insertion of a ventriculostomy, her level of consciousness improved and she gradually recovered from all neurologic deficits. MRI confirmed a large AVM in the left fronlo-opercular region ( and a four- vessel conventional angiogram confirmed a 4-cm AVM nidus that was fed via the MCA, dilated branches of the anterior cerebral artery, and leniiculoslriate vessels with venous drainage mostly via a dilated basal vein of Rosenthal, thus accounting for a Spetzler-Martin grade IV ( The patient refused preoperative embolization, and, using a left frontotemporal craniotomy, the AVM was resected completely using standard microsurgical techniques. The patient did well postoperatively and had no speech disturbances in spite of the location close to or within the dominant Broca's area. An angiogram peformed 1 week postoperatively confirmed the complete resection and persistence of moderate vasospasm (

Case history 2

A 23-year-old previously healthy student was admitted to the emergency room following a severe headache accompanied by drowsiness and left hemiparesis. A CT scan revealed a significant intraparenchymal hematoma in the right parietal region ( Angiography revealed a high-flow AVM with a 4.5 x 5 cm nidus, a large intranidal aneurysm draining into the basal vein of Rosenthal, and arterial feeders from a large distal MCA branch and accessorily from the anterior choroidal artery ( After stabilization of the patient who recovered completely from his deficit, a preoperative embolization was performed (10 days after the initial hemorrhage) using a mixture of bucrylate and lipiodol, which allowed for substantial reduction of the nidus (

On the following day, a right temporal parietal craniotomy was performed and the lesion was entirelyremoved using the operating microscope ( Postoperative angiography confirmed complete resection of the AVM (.The patient recovered well from the surgery apart from a generalized convulsion 48 hours postoperatively and a temporary left inferior homonymous quadrantanopia.

Case history 3

A 28-year-old technician in a cardiac hemodynamic laboratory was admitted 48 hours after a generalized convulsion. ACT scan showed a 1.5-cm hemorrhaglc lesion in the left parietal lobe (. MRI confirmed the presence of a 1.5-cm CM located within the white matter just below the dominant supramar-ginal gyrus with signs of a recent perilesional bleed (. Preoperalively. an activated positron emission tomography (PET) scan was performed using intra-arterial injection of an 15O-loaded saline bolus. Using several functional tests of language including synonym generation and calculation, it was possible to detect increased cerebral blood flow (CBF) in the left superior parietal lobule quite remote from the lesion (. Additional tasks of reading and synonym generation in response to visual presentation showed a CBF increase in the left parietal region close to the area previously lighting up for calculation (.

Using integration of PET scanning and MRI data, a left parietal mini-craniotomy was performed using neu-ronavigational frameless stereotaxy guidance (Allegro-Viewing Wand System ISO. Toronto. Canada). After selecting the most appropriate cortical landmark (. the cortex was incised, the lesion appropriately identified (, and resected using the operating microscope. The postoperative course was very satisfactory and the patient was discharged home on the fifth postoperative day without any deficits.

Discussion

Functional neuroimaging and neuronavigation

Preoperative assessment of vascular malformations located within or near highly functional areas of the brain can be achieved using various mapping techniques including functional MRI, magnetoencephalography, PET, single photon emission tomography, and transcutaneous magnetic stimulation (Table III).[13,14]

Functional areas of the brain, such as primary motor cortex or primary somatosensory cortex, can be precisely located and their topographical relationships may be integrated on MRI or CT scan and translated into 3D reconstruction images using frameless stereotaxy with high spatial accuracy.[15, 16]

Localization of speech function is best performed using activated PET scanning, since functional MRI is more sensitive to activation of motor areas. Interestingly, functional cortical reorganization has been observed in patients with AVMs: in some patients, the primary motor cortex may undergo a certain shift towards the premotor cortex and language areas may even migrate from the dominant hemisphere to the contralateral side.[17-19]

Results of surgical treatment of AVMs

Excellent results and high obliteration rates can be achieved after microsurgical resection of small AVMs (less than 3 cm in diameter). According to Pikus et al,[8] a 98% postoperative removal rate was achieved on postoperative angiography with less than 8.3% permanent morbidity and no mortality in 74 cases. Similar figures were obtained by Schaller and Schramm[20] in 62 cases of small AVMs with 98% angiographic exclusion and only 3.2% permanent neurologic deficit.

Results of stereotactic radiosurgery and AVMs

Radiosurgery consists of stereotactic application of a single high-dose irradiation of the AVM nidus producing a progressive thrombosis of the lesion over a period of several months. The currently used methods include gamma knife, linear accelerator, and heavy particles such as proton beam therapy.[21-24] It is thought that ionizing radiation induces a proliferation of myofibroblasts within the connective tissue stroma of the AVM nidus as well as some endothelial proliferation.[25,26] AVM obliteration has been achieved in 80% of lesions smaller than 3 cm in diameter with a hemispheric localization: using gamma knife radiosurgery in 220 patients with adequate follow-up as defined by a postoperative angiogram 24 months after treatment, excellent results were obtained by Pollock et al[22] in 73 patients with hemispheric localization and lesions smaller than 4 cm3 (diameter 2 cm or less) with low morbidity and mortality. Recently, Chang et al[21] have developed a mathematical model for decision making in AVMs that takes into account several variables, such as age, size, presence of previous rupture, and life expectancy for both surgery and radiosurgery.

Endovascular treatment of AVMs

Embolization techniques have evolved considerably during recent years in becoming both safer and more efficacious.[27,28] More refined, flow-directed microcatheters can deliver polymerizing acrylic substances such as V-butyl-cyanoacrylate into even distal portions of the nidus. Using the superselectivc catheterization methods, most AVMs cannot be permanently occluded, since recanalization of the nidus occurs in the periphery of the lesions. Morbidity related to endovascular treatment consists of distal embolization and hemorrhage which remain below 8% in most series.[29] Most often, embolization is used to reduce the size of the nidus either preoperatively, thus facilitating the surgery by decreasing blood flow substantially, or before radiosurgery in large AVMs that would otherwise have a lower obliteration potential.

Cavernous malformations

In spite of some reports of successful treamtent of CMs with stereotactic radiosurgery,[10,30] the management of symptomatic lesions remains surgical: in a recent review of 97 CMs treated surgically at the Massachusetts General Hospital, only 4.1% of patients had permanent neurologic deficits and the vast majority were rendered seizure-free.[9] Risk factors for increased postoperative deficits included location within the brainstem and basal ganglia. Due to the relatively small size of these lesions and their localization within the subcortical areas making their visualization difficult on the cortical surface, neuronavigational techniques are particularly well suited for surgery of CMs.

Conclusions

Functional neuronavigation represents one of the most interesting advances in recent adjunctive technology in neurosurgery: the possibility of integrating functional information about anatomical localization of eloquent areas into a 3D frameless stereotaxy system enhances the accuracy of the surgical procedure in helping localize the lesion and its immediate topographical relationships. Navigational systems are mostly represented by three different types of “pointer systems”: (i) the mechanically directed “viewing wand” type, transmitting the spatial information through an arm to the computer; (ii) instrument-based pointers using infrared light-emitting diodes and spatial sensors that transmit the information to the computer and reconstruct it as 3D images; and (iii) microscope-based pointer systems where the automated focus represents the target of the system allowing the superimposed reconstructed images to be seen directly through the microscope.[16,31]

The management of vascular malformations of the brain remains to some extent controversial but the following conclusions can be drawn: small volume malformations (less than 3 cm in diameter) that have bled can be safely removed using microsurgical techniques with excellent results, and the utilization of functional neuronavigation for lesions located in eloquent areas adds even further safety in preserving function. Larger AVMs that have presented with hemorrhage can be treated surgically after preliminary embolization but will have higher morbidity rates.[32] Stereotactic radiosurgery can be offered to patients with relatively small lesions who present with symptoms other than hemorrhage, such as epilepsy, or for lesions located in the basal ganglia or brainstem. For CMs, the present trend is to remove the lesion surgically if hemorrhage has been demonstrated or if epilepsy cannot be controlled.

The combined management of cerebral vascular malformations is best achieved by a well-integrated multidisciplinary team that includes neurosurgeons, interventional neuroradiologists, neurologists, and radiation oncologists.[33] Refinement of neurosurgical techniques and pre- and intraoperative neurophysiological monitoring have led to a reduction in surgical morbidity and mortality in selected cases. Radiosurgical techniques are also to be considered although they do not immediately remove the source of bleeding due to the progressive intranidal myoendothelial and fibroblastic proliferation. Patients should be given detailed information about the natural history of their lesions and the various therapeutic alternatives.

Table I.

Classification of intracranial vascular malformations

1. Arteriovenous malformations (AVM)

2. Cavernous malformations (cavernous angioma)

3. Dural arteriovenous fistula (dural AVM)

4. Capillary telanglectasia

5. Developmental venous anomaly (venous angloma)

Table II.

Spetzler-Martin grading system for arteriovenous malformations.

Size	Small (less thnn 3 cm)	1
	Medium (3-6 cm)	2
	Large (greater than 6 cm)	3
Eloquence of involved brain	Noneloquent	0
	Eloquent	1
Type of venous drainage	Superficial	0
	Deep	1

Table III.

Surgical adjuncts for cerebral vascular malformations.

Preoparative embolization

Electrophysiological monitoring (somatosensory evoked potential, direct cortical stimulation)

Surgery on awake patient

Intraoperative angiography

Image-guided surgery

Ultrasound localization

Endoscopy