Operative nuances of surgery for cortical arteriovenous malformations: A safe solution and permanent cure
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.178061
Source of Support: None, Conflict of Interest: None
"The surgical history of most of the reported cases shows not only the futility of an operative attack upon one of these angiomas, but the extreme risk of serious cortical damage which is entailed. The lesions, in short when accidentally exposed by the surgeon, had better be left alone".
Harvey Cushing 1928 
"When one inspects a cortically based AVM, one can immediately appreciate the beauty of these lesions. In addition to the striking aesthetics of bright red veins and the tortuous vascularity, the observer has a clear sense of the ominous nature of these lesions".
Batjer HH et al. 2012 
Although cerebral cortical arteriovenous malformations (AVMs) are regarded as challenging pathologies, most of these lesions can be treated safely and effectively by microneurosurgery. , The lesions generally present in early adulthood, with hemorrhage being the principal presentation, closely followed by seizures. Despite advances in radiosurgery and embolization of these lesions, microsurgical extirpation remains the answer in quest for the final cure for these lesions. These lesions can be life threatening, and there is a strong case for actively treating them. With a rupture rate of 2-4% per year, hemorrhage is the principal presentation. , Brown's equation (105 - age in years = percentage of lifetime risk of hemorrhage) is a useful bedside tool to predict the lifetime risk of hemorrhage.  Ruptured and untreated Grade IV and Grade V AVMs carry a high risk of rupture and heightened neurological morbidity and mortality, necessitating prompt and well considered decision making.  A recent study has concluded that surgery offers a favorable outcome in AVM-associated epilepsy, and epilepsy should be considered as an indication for AVM removal.  Female patients of childbearing age with ruptured or unruptured brain AVMs should be treated proactively, due to heighted risk of rupture during pregnancy. 
Cerebral arteriovenous malformations are a heterogeneous group of lesions, each one with its own individual characteristic features related to the arterial feeders, relation of nidus with the eloquent cortex and the venous drainage. The extent of neurological involvement is an important factor and must be taken into account while advising and planning surgery. The aim of surgical intervention should be zero additional neurological morbidity, while achieving complete AVM removal. Preoperative neuroimaging - four vessel cerebral digital subtraction angiography (DSA), computed tomography (CT) scans and magnetic resonance imaging (MRI) scans - provide the surgeon with sufficient data to plan the surgical approach, keeping in mind the possible pitfalls and problems during surgery. The Spetzler-Martin grading system  that grades the AVMs according to size, eloquent cortex involvement and venous drainage has served the neurosurgeons well in devising their plan to tackle these lesions, as well as for effectively communicating the status of the AVM with other specialists involved in their management [Table 1]. If anticipated and unanticipated intraoperative problems can be effectively managed, surgical treatment is strongly recommended as a definitive treatment option. Endovascular techniques to embolize the AVM, and radiosurgery are additional tools available for their effective management. These tools also help to convert the high grade AVMs to low grade ones that can be excised completely by microsurgery. Step-by-step procedures include making of an adequate flap, extensive dissection utilizing sulcal and subarachnoid spaces, following the venous drainage to the nidus, securing the feeding arteries, dissecting the nidus, and finally division of the venous drainage to remove the specimen. In an exhaustive analysis, Davidson and Morgan  concluded that it is reasonable to offer microsurgery as the preferred treatment for Spetzler-Martin grade 1-2 AVMs. Even the seemingly large AVMs abutting the eloquent cortex can be removed with success. Thus, the decision to offer surgery to patients has to factor in variables like the clinical profile, anatomy, hemodynamic and imaging characteristics and the surgeon's experience.
The Spetzler-Martin grading system for cerebral AVMs proposed more than a quarter of a century ago, has withstood the test of time, and has become the most widely used parameter for quantifying AVMs for the purpose of decision making and surgical approach [Table 1]. The AVMs receive a grade of I to V depending on the three parameters (size, eloquent cortex involvement and venous drainage). By straightforward implications, the lower grade lesions can be excised successfully, while the high-grade lesions carry a greater morbidity, with or without surgery. This grading system allows risk analysis for surgical treatment. Grade I patients have a probability of a favorable outcome in 92-100%, , while grade II lesions have favorable outcome in approximately 95% cases.  In grade III lesions, there is good outcome in 62% patients on short term assessment, and in nearly 86% on long term assessment.  For Grade IV lesions, outcome is favorable in 62% cases and in grade V lesions, it drops to 57%, with a 4.8% mortality in the latter. [11.12]
The limitation of the Spetzler Martin system of AVM grading is that it takes into account the anatomic location of the eloquent cortex, as opposed to preoperatively determining the actual functional cortex. It is essential that functional brain mapping be done to locate the eloquent areas in relation to the AVM nidus.
As the limitations of the predictive value of Spetzler-Martin grading system became apparent, a supplementary grading system was introduced and recently validated.  In addition to the three factors namely size, venous system and eloquent cortex, the modified scale takes into consideration age of the patient as well as bleeding and compactness of the AVM [Table 2].
There are other factors too that can influence the natural history and the management approach. Batjer et al.,  devised a scale that takes into account the patient related factors, the lesion morphology and imaging [Table 3]. The patient related factors included age, gender, neurology, patient's general health, and, the patient's and his/her family's understanding of the management approach. The lesion variables included the size, lobe, mapping by fMRI and the appearances on fluid attenuation inversion recovery (FLAIR) imaging. Hyperintensity seen on FLAIR images denotes gliosis or inflammation around the lesion.
Only one study has systematically compared the two modalities for treating cerebral AVMs.  While surgery offers immediate cure, there is an additional risk in the form of hemorrhage and operative morbidity. Radiosurgery, on the other hand, offers a safe alternative, with the risk of rebleeding rate being about 10% as compared with nearly 0% with that of surgery; the comparative obliteration rates for the two modalities are 91% (microsurgery) and 81% (radiosurgery).  Radiosurgery can often eliminate the high-risk component of the AVM, and can convert an inoperable lesion into an operable one.  As experience with gamma knife radiosurgery for cerebral AVMs has increased, complications like cyst formation and radionecrosis too, have become apparent.  Recent studies have established the safety and efficacy of microsurgery for unruptured or silent AVMs with evidence of hemorrhage. ,,
Embolization may be utilized in the entire spectrum of AVMS from a large AVM, (one with the potential to cause exsanguination in the patient during attempted removal) with the aim to reduce the large lesion; to a small, relatively straightforward lesion, to obliterate it completely. In addition, embolization can help to occlude the deeply situated, inaccessible vascular supply and components of the AVM. However, failure to occlude the nidus while occluding the feeder artery may result in development of dural transmedullary collaterals, making subsequent excision of the nidus more difficult.  A residual AVM after incomplete embolization may present with hemorrhage [Figure 1]. Repeated attempts at embolization increase the risk of stroke or hemorrhage.  Besides its presurgical application, embolization using cyanaoacrylate has been carried out prior to radiosurgery to reduce the lesion size to less than three centimeters across. However, there is no evidence that reduction of flow of the AVM without reduction in the volume of the lesion serves to provide any advantage when subsequent radiosurgery is planned. In fact, it may make it difficult to plan a conformal dose of radiosurgery. 
Brain AVMs are dynamic entities that can change their morphology, size and risk of bleeding. Probably a milieu of disturbed angiogenesis exists during embryogenesis, and dysplastic vessels are formed around the nidus. , There is probably a embryo-biological dysfunction at the capillary-vein interface.  Formation and growth of these lesions appear to be an interplay of genetic predisposition, growth and environmental influences, and angiogenic factors. There is the possibility of a 'two-hit mechanism' in mutations leading to vascular dysplasia, an explanation valid for other neurological conditions like neurofibromatosis.  Capillary formation within the cerebrum begins during the seventh week of gestation and continues till the end of first trimester.  Probably the vascular anomalies originate during this period,  causing disturbed capillary formation and retention of primordial vascular connections between the artery and vein. The underlying etiology, however, remains unknown. AVMs have the biological potential to develop angiogenesis, and endovascular treatment can trigger this activity, causing regrowth and recurrence of the AVM after apparently successful embolization. 
Cerebral cortical AVMs are conical lesions made up of dysplastic vessels, with their apex towards the ventricle [Figure 2]. There are three distinct morphological components of an AVM: The feeding arteries, a dysplastic vascular nidus and draining veins. The nidus is a compact lesion, separated from the normal brain by a thin zone of gliosis, and consists of a meshwork of dysplastic vessels that shunts blood from the arterial to venous system. The nidus may sometimes be more diffuse with a wider area of brain parenchyma intervening in between the meshwork. The arteries and draining veins undergo progressive dilatation due to exposure to high-pressure gradients, since there is no regular arteriolar and capillary network. Absence of blood-brain barrier in the meshwork and in the perinidal capillaries can lead to extravasation of red blood cells and deposit of hemosiderin around the nidus, with varying degree of gliosis and inflammation.  Expression of SM2 (a marker for smooth muscle) is seen in veins indicating that venous component can show arterialization.  The arteries demonstrate smooth muscle hyperplasia, arterial stenosis and formation of prenidal aneurysms.
A venous aneurysm is an interesting yet rare finding in the vascular pathoanatomy of AVMs [Figure 3]a-d. Venous morphology in an AVM usually shows a single or more than one large veins, draining into the superficial or deep venous systems. The changes in venous angioarchitecture in such high flow situations with high intramural pressure lead to:
Venous aneurysmal dilatation can be thick walled and yet be prone to hemorrhage.  The presence of this lesion has been regarded as an indication for urgent intervention considering the risk of hemorrhage. A large saccular aneurysm, on the other hand, is likely to be thick-walled and fibrotic, containing an organized clot with lesser risk of hemorrhage from the sac itself.
Usually, computed tomography (CT) scan is the first investigation carried out when the patient presents with hemorrhage and/or seizures with or without alteration in sensorium. Depending upon the size and location of bleed, the CT scan may show a lobar or interhemispheric location, with varying degrees of subarachnoid hemorrhage and intraventricular hemorrhage. Calcification may be evident in long-standing AVMs, as would be evidence of embolic material in patients having undergone embolization earlier. Edema may compound the mass effect, and an emergency surgical procedure may have to be undertaken to reduce the intracranial pressure and to improve cerebral perfusion. A CT scan is an important tool in situations of immediate postoperative neurological worsening.
Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) are often done in the same sitting in a patient suspected of having a cerebral AVM. MRI is a sensitive tool for evaluation, which shows inhomogenous signal voids on T1- and T2-weighted images [Figure 2], with evidence of hemosiderin, indicating an earlier hemorrhage or seepage of red blood cells in the perinidal white matter. Although the nidus may be difficult to delineate, MRI gives its fairly exact anatomical localization to plan a surgical approach while taking into consideration the proximity of the eloquent cortex. Flow voids visible within the lesion or in the periphery of the AVM may be helpful in surgical planning. Presence of inflammation may show varying degrees of white matter edema. We have encountered one instance of post-embolization brain abscess, which was diagnosed on MRI. The role of functional MRI (fMRI) and tractography is important to map out the eloquent cortex (especially the language and motor areas) for an appropriate treatment planning. Interpreting of signal in the vicinity of AVM can be challenging  and may require measures like breath-holding or hypercapnia to establish the baseline of blood-oxygen dependent signals on fMRI,  which allows pre-treatment evaluation of 'at risk' eloquent areas. Moreover, efforts to delineate the eloquent areas are important since these patients may have an unconventional functional organization around the AVMs. 
Four vessel digital subtraction angiography (DSA) remains the gold standard for diagnosing, delineating and treating AVMs. DSA gives an assessment regarding the size of the lesion. This may be correlated with the MRI data to assign the precise Spetzler-Martin grade to the AVM. The exact vascular anatomy can be outlined in three dimensional orientation, and the large feeding arteries as well as the prominent draining veins may be identified [Figure 4]a-d, [Figure 5]a-d. Other lesions like a prenidal aneurysm and a post-nidal venous anomaly or aneurysm can be visualized. The extent of the contralateral contribution to the vascular supply, especially in interhemispheric AVMs, can be appreciated. Endovascular interventions can be carried out in the same sitting, if these options have been considered. Postoperative DSA is mandatory in all patients undergoing surgical excision to document the completeness of AVM excision, and to assess for any residual AVM. The DSA has an immense value as a factor for predicting hemorrhage. On univariate analysis, the predictors of hemorrhage include deep venous drainage, intranidal aneurysms, multiple arterial feeders, basal ganglia location, feeders from vertebrobasilar system and a single draining vein. ,
CT angiography can also be done to appreciate the relation of the AVM to the skull base [Figure 6]a-c. However, CT angiography is more useful in the treatment planning of intracranial aneurysms than that for AVMs. 
When a patient presents with hemorrhage, management is focused on the reduction of intracranial pressure. This can be achieved by cerebral decongestants, and if the hematoma is large, then by evacuation of the hematoma. More often, external ventricular drainage can be instituted to drain out cerebrospinal fluid and blood, and keep the intracranial pressure low. The patient is assessed by neuroimaging that involves performance of an initial CT and/or MRI scan and a DSA. Surgery for AVMs is aimed at stopping future hemorrhages, reduction of mass effect (including in those lesions that have been subjected to prior embolisation), and seizure control. The risk of surgical intervention depends upon the extent of the neuraxial incision required to expose, dissect and finally, excise the nidus. The success in the excision of AVMs requires a firm commitment towards formulating and adhering to a definite operative plan. A surgical plan is chalked out after viewing the entire neuroimaging profile. This also includes a detailed discussion with the neuro-anesthesiologist, since hypotensive anesthesia or a temporary vascular clip placement may be required during surgery. The challenges for the neuroanesthesia team include blood pressure and blood loss monitoring, optimization of intraoperative parameters and immediate management of unexpected events like brain swelling. AVMs near eloquent areas may require considerations for an awake craniotomy. Positioning is based on the anatomical localization of the AVM. Head flexion in supine position and elevation of the head end are required in most cases of the supratentorial cortical and interhemispheric/callosal AVMs [Figure 4]a-c. Image guidance can help in the accurate planning of the flap. The head is usually fixed in a head clamp. Proper positioning is a must for adequate and limitation-free exposure. At times, the scalp flap may show hypervascularity due to the presence of abnormal vascular channels, and the bone too may show an abnormal vasculature with vessels traversing through it. A large craniotomy is centered on the nidus, with access to arterial feeder(s), as well as venous drainage. The bone flap should be wide, and is so designed that it will give an early control of the principal arterial feeder.
The identification of the AVM and commencement of dissection is based on certain important principles. The first visual appearance of the AVM is that of strikingly red vessels with varying degrees of arachnoidal thickening. Arterial feeders may be identified and correlated with the DSA picture [Figure 7]a-c. Following an arterial feeder, the AVM is reached by the trans-sulcal approach. One of these arterial feeders may be followed distally towards the AVM nidus, and it is often appreciated that the AVM nidus occupies only a small area of the cortex and white matter. Dissection is progressed circumferentially along the branches from the arterial feeders, along the often definable gliotic plane or along the plane of recent hemorrhage. Feeders are coagulated and divided as they arborize around the AVM. Usually there is one principal arterial feeder, which can be clipped temporarily and the AVM defined. Other arterial feeders can be identified and occluded close to the AVM nidus. If one stays in the gliotic plane, fewer vessels need to be coagulated. While there are feeders in the white matter, we have never encountered arteries emanating from the AVM that supply distally. We, have, however, encountered, on three occasions, prenidal aneurysms, two of which were excised with the AVM nidus, while one was clipped, being too proximal on the feeder artery. Coagulation of the surface of the AVM is avoided at all times, since many of the vessels on the surface may be veins, the occlusion of which may lead to hemorrhage from the congested AVM.
In case the AVM is entirely subcortical, the draining vein may be followed distally from the subarachnoid space through the cortex to its proximal emergence from the AVM nidus.
Dissection of the AVM is a slow, deliberate process, each step being carried out under magnified vision. Concurrent hemostasis ensures a clear field. Packing of the field or the plane of dissection with cotton patties is best avoided. Deep feeders in the white matter often retract and one needs patience to control them. Temporary clipping on the principal arterial feeder, close to the nidus, often aids in the identification and control of deep-seated feeders. Clips can be released intermittently to confirm devascularization of the nidus, and to perfuse the brain that has been rendered temporarily ischemic. Temporary occlusion of the principal arterial feeder(s) is well tolerated without any side effects.  Periventricular feeders arise from the choroidal arteries, and may be difficult to visualize and control. These arteries are often the culprits in situations where persistent bleeding from the AVM occurs during the deeper stage of the dissection. Apparently difficult to coagulate, they require continuous saline irrigation with suction while attempts are being made to identify and control them. Application of miniclips has been advocated to control them, but these often crowd the operating space and are, therefore, best avoided. One must stay in the plane of dissection and control the bleeding by temporarily tamponading it with cotton patties and a slight pressure either using a suction or a retractor, while shifting to another area for dissection. One must be aware of a vessel that loops in and out of the nidus, giving an impression of a subcortical feeder, which may actually be an important supply to a nearby eloquent region. The dissection plane should be developed in a circumferential or spiral manner, so that there is no lack of space if there is sudden bleeding from one of the components of the AVM. As the dissection ends, the AVM is left attached only by a single vein, which now appears distinctly blue [Figure 8]a and b. Circumferential dissection ensures that no arterial feeders are missed, for if such vessels are missed, they can lead to sudden swelling and bleeding from the AVM when the venous drainage is detached.
As opposed to other cortical AVMs that occur in the grey and/or white matter, Sylvian fissure AVMs are unique in being in the subarachnoid plane. Surgery for these lesions mandates a thorough knowledge of anatomy of the vasculature, so that the AVM can be excised with no morbidity, sparing the major cortical branches and perforators.
Arterial aneurysms may be seen in 7% to 17% of the patients with cerebral AVMs.  These often occur on the prenidal feeding arteries, and can involute after resection of the AVM.  These can be clipped or excised with the AVM.
As the dissection progresses, the venous drainage and/or the venous aneurysm is defined and preserved, by often working around it [Figure 9]a and b. The intact vein provides a reassuring handle to visualize different aspects of the AVM. In fact, at the beginning of dissection, one prominent draining vein is identified and a firm commitment is made to preserve it until the end. Constant exposure to a high blood pressure often changes the thin-walled veins into thick-walled arterialized vessels. Though arterialized, these vessels can be differentiated from arteries as the latter are slimmer and relatively straight, appear more red or pink, and correlate with the angiographic picture. Veins on the other hand appear slightly darker, and as the arterial feeders are divided, they assume the usual blue color of the veins. Veins may be dilated and have a wide lumen as they open into the draining sinuses. Venous aneurysmal dilatation and ectasia have been observed on a number of occasions. Such veins may often require clip occlusion at the end of the dissection. Venous drainage is the last component of the AVM to be occluded and divided as close to the draining sinus as possible. The 'test occlusion' of a suspected arterialized vein is usually to be avoided because the maneuver may precipitate a sudden swelling of the AVM/surrounding brain and hemorrhage. Thus, a thorough knowledge of both the arterial and venous anatomy on DSA and its adequate correlation with the actual situation in the operative field are the hallmarks for the successful extirpation of the entire AVM.
Intraoperative vascular imaging has been considered to aid in the dissection, and for ensuring the complete elimination of the brain AVMs. However, if the information given by the preoperative DSA is well appreciated and the feeders correctly identified, there is little or no justification in carrying out an intraoperative DSA or an indocyanine green (ICG) fluorescent angiography. The usefulness of the latter procedures has not yet been well-established and the yield is low, especially in the cases of deep-seated, subcortical AVMs. Hence, a high resolution postoperative DSA rather than an intraoperative ICG angiography should be used as the best imaging modality to assess for the completeness of AVM resection. 
On occasions, there may be sudden brain swelling or brisk hemorrhage. In this situation, the venous drainage should be checked. In case any distortion of the draining vein is detected, it is rectified and the vein is straightened. Jugular venous occlusion is looked for and excessive neck flexion is corrected. Cerebrospinal fluid pathway occlusion should be checked for, and if needed, the ventricle may be tapped. Basal cisterns are opened to let out the cerebrospinal fluid. A hematoma below the nidus is a frequent cause of brain swelling, indicating a missed feeder or injury to the nidus meshwork either by an instrument or by bipolar coagulation. The hematoma is evacuated, and the offending vessel is controlled by coagulation or by tamponade. It is vital to have a free communication with the anesthesiologist during the surgical excision of AVM. The need for hypotension should be discussed and if required, necessary preparations should be made before hand. An induced hypotension can be effectively used to control intraoperative bleeding from the AVM.
An occult nidus or a 'hidden compartment' is regarded as a valid etiology in patients with an unexplained intraoperative bleeding, or when there is postoperative recurrence of the AVM (presenting with hemorrhage), after its apparently successful extirpation by the surgeon. These are angiographically occult lesions that manifest after surgery as recurrent intraparenchymal bleed, or as regrowth of the pre-existing AVM. 
An intraoperative hyperemic state, or a normal perfusion pressure breakthrough is a well documented but ill-explained phenomenon that may be seen during surgery for a large AVM. Elevated plasma renin and epinephrine levels have been observed during the intraoperative hyperemic state, and alpha adrenergic blockers have been used to control the condition. , It should, however, be a diagnosis of exclusion, after other causes of hyperemia and hemorrhage have been looked for and excluded.
Although spontaneous obliteration of small pial arteriovenous malformations is reported, , surgical excision should be the first line of management for cerebral AVMs. A definite surgical plan can be made based on the integration of the available imaging [which includes a CT scan, MRI scan (often with fMRI, MR angiography, FLAIR images and tractography) as well as DSA] with the clinical profile of the patient. An adequate sized craniotomy, followed by identification of the arterial feeders and principal venous drainage puts the neurosurgeon on course to dissect and occlude the arterial feeders, and preserve of venous drainage of the AVM until the final stages of dissection. A gliotic plane may be identified in the majority of patients, which aids in the circumferential dissection and also in the coagulation and division of smaller feeders. The end point of surgery is the reestablishment of blue appearance of the surrounding veins; and, the dissected nidus of the AVM being attached only by its last major venous component. The AVM is detached by coagulating and resecting this draining vein, and closure is affected after ensuring a complete hemostasis.
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Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
[Table 1], [Table 2]ni_2016_64_7_101_178061_t11.jpg, [Table 3]ni_2016_64_7_101_178061_t12.jpg