Arteriovenous Malformations and Fistulas (AVM/AVF) of the Spinal Cord

Spinal vascular malformations have been recognized as a potential cause of myelopathy for more than 100 years. In 1914, Charles Elsberg performed the first successful operation on a spinal cord malformation.

In the 1960s, significant advances were made in the technique of spinal angiography, which led to improved understanding of normal spinal vasculature and the pathophysiology of spinal cord malformations. Kendall and Loque used these modern imaging modalities to define a distinct subgroup of spinal AVMs classified as dural spinal AVFs. Kendall and Loque treated these lesions by performing the less invasive technique of directly ligating the fistula origin along the dural sleeve and achieved good results.[12]

Treatment approaches for spinal cord malformation are being expanded through the use of interventional neuroradiology. With improvements in spinal angiography and endovascular techniques, these lesions may be embolized either as primary treatment or as a complement to open microsurgical techniques.

Two treatment modalities are available: endovascular and surgical therapy. Endovascular treatment has improved over the years and offers the advantages of a less invasive approach; therefore, it is usually chosen as primary therapy.[10]  However, treatment should always be based on an accurate diagnosis.[9]  Eradication can often be incomplete, and risk for spinal cord ischemia may be increased. Stereotactic radiosurgery can be curative in some cases or can facilitate shrinking of the lesion.[7]

Spinal malformations can be separated into 2 subgroups: AVMs and AVFs. Spinal arteriovenous malformations (AVMs) are a rare form of spinal blood vessel defect that results in vessel engorgement leading to clinical signs secondary to mass effect and ischemia.[6]  These lesions represent an abnormal connection between the spinal radicular artery and the medullary vein of the spinal cord. This type of fistula creates a slow-flow vascular malformation that typically develops over months to years. High-pressure arterial flow from the radicular artery dilates the perimedullary venous system, causing venous stasis and hypertension. Venous hypertension results in a decreased arteriovenous gradient. The end result consists of venous outflow obstruction, hypoperfusion, and hypoxia of the spinal cord. Neurologic compromise is thought to occur secondary to this venous engorgement and resultant spinal cord ischemia.

Arteriovenous malformations are congenital high-flow vascular lesions that account for about 10-15% of all spinal vascular shunts. They may occur sporadically or in the setting of genetic syndromes. Intramedulary glomus-type AVMs consist of an intramedullary nidus of shunting vessels usually located in the anterior half of the spinal cord fed by 1 or more spinal arteries that drain into spinal veins. Most AVMs are confined to the thoracic spine; intranidal or arterial aneurysms are common and are responsible for subarachnoid hemorrhage or hematomyelia, which is experienced in more than half of patients with AVMs.[7]

The second subgroup is the spinal  arteriovenous fistulas (AVFs), which are congenital lesions that consist of abnormal vasculature. Spinal dural AVFs are produced via direct communication between arterial and venous systems of the spinal cord, causing hypertension in the latter with spinal cord dysfunction. This is a rare pathology with unknown etiology and nonspecific clinical symptoms, and diagnosis is usually delayed.[10]  These lesions recruit arterial blood vessels and have thin-walled venous vessels. Hemorrhage occurs when the high-flow arterial system overcomes the capacity of the abnormal venous vessels.

Patient history and presentation are important factors in distinguishing spinal vascular malformations from other neurologic disorders. Patients with the more common dural AVFs typically have presentations that are different from those of patients with intradural AVMs.

Typical characteristics of patients with dural AVF (type 1)

Patients with AVF are typically older than 40 years. Arteriovenous fistulas occur much more frequently in males than in females. Symptoms increase over an extended period of months to years and include progressive weakness of the legs and concurrent bowel or bladder difficulties. Typically, pain is located in the distal posterior thoracic region over the spine, without a significant radicular component. However, painful radiculopathy may be present. Activity or a change in position may exacerbate symptoms in the thoracic or lumbar region and can result in thoracic spinal cord venous congestion and lower extremity weakness.

These lesions can be mistakenly diagnosed as spinal stenosis and neurogenic claudication. The history of a patient with spinal claudication does not usually include lower extremity weakness, but it can include a significant pain component similar to that of spinal dural AVF.

Foix-Alajouanine syndrome is an extreme form of spinal dural AVF that affects a minority of patients. Patients present with rapidly progressive myelopathy due to venous thrombosis from spinal venous stasis.

Typical characteristics of patients with intradural AVM (types 2-4)

The typical patient is younger than 30 years and presents with subarachnoid or intraparenchymal hemorrhage, vascular steal phenomenon, and, rarely, mass effect on the spinal cord.

Individuals with subarachnoid hemorrhage may experience sudden onset of severe headache, meningismus, or photophobia. Acute subarachnoid hemorrhage with excruciating back pain is referred to as coup de poignard. A spinal AVM should be considered in the differential diagnosis of any patient with a subarachnoid hemorrhage who has negative cerebral angiography results.

If the hemorrhage is intraparenchymal, the patient presents with sudden neurologic deterioration, sudden onset of pain, and a distinct spinal level of neurologic dysfunction. Rarely, patients present because of vascular steal phenomenon, in which oxygenated arterial blood shunted through the AVM causes the surrounding normal parenchyma to become hypoperfused.

Lastly, patients with intradural lesions can present with mass effect caused by growth of the AVM. The enlarged vascular malformation compresses surrounding neural tissue, thereby impairing neurologic function.

These intradural spinal vascular malformations (types 2-4) develop during embryogenesis and are present in an even distribution throughout the spinal cord. Therefore, patients with intradural AVM may present with upper or lower extremity difficulties, as opposed to patients with dural AVF, who typically have only lower extremity involvement.

Physical examination findings in patients with spinal vascular malformation

Arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) are rare disorders that may cause neurologic deterioration. Accurate diagnosis is important because these lesions may represent a reversible cause of myelopathy. Improvements in spinal cord imaging, such as MRI and angiography, have provided insight into the anatomy and pathophysiology of these lesions. In addition, less invasive treatment options such as neuroendovascular surgical approaches offer promise for improved patient outcomes.

Specific physical examination findings are associated with different types of spinal malformations, as follows:

• Bruit over spinal cord: Intradural AVM

• Hyperreflexia caudal to lesion: Dural AVF and intradural AVM

• Upper motor signs: Dural AVF and intradural AVM

• Weakness: Dural AVF and intradural AVM

• Increased tone: Dural AVF and intradural AVM

• Saddle region sensory disturbance: Dural AVF

• Gait disturbance: Dural AVF

To understand and treat these arterial and venous malformations, knowledge of the normal spinal cord vascular supply is imperative. Unfortunately, the distribution of these spinal vessels is highly variable and inconsistent, but major vessels are more consistent.

The aorta contributes to blood flow through the segmental arteries, which, in turn, supply the spinal medullary and radicular arteries. The radicular artery provides circulation to the nerve root dural sleeve. This artery is typically involved in the formation of a spinal AVF via its connection to the medullary spinal veins. This medullary artery bifurcates into anterior and posterior divisions, which then merge to form the spinal arteries. The spinal cord includes 3 main spinal arteries (1 anterior and 2 posterior), which parallel the spinal cord.

Blood supply to the spinal cord is provided through 3 anatomic regions:

1. Cervicothoracic region: Receives segmental blood vessels from the vertebral arteries and the great vessels of the neck (ie, aorta, subclavian and carotid arteries).

2. Midthoracic region: Receives most of its segmental blood supply from the aorta. This region of the spinal cord receives most of its blood supply via collateral circulation (superior and inferior arteries) and therefore is susceptible to infarction as a watershed area. For example, an aortic dissection or an aortic atherosclerotic disease can send emboli to the anterior spinal artery (ASA); the patient presents with sudden onset of painless lower extremity paralysis with intact sensation. Spinal cord infarction affects the anterior motor portion because the ASA supply is lost, but the posterior spinal arteries still perfuse the posterior spinal cord and sensory tracts.

3. Thoracolumbar region: Receives segmental vessels from the abdominal aorta and the iliac arteries. The largest segmental vessel—the artery of Adamkiewicz—may be variably located between levels T9 and L2 and, in most cases, arises from the left side of the vertebral column.

The venous plexus in the spinal column—the Batson plexus—is unique compared to other venous plexuses in the body. This network of venous vessels does not include valves and thus does not prevent retrograde venous flow. This valveless system allows an arterial fistula from the radicular artery to create congestion through the entire venous plexus, which can manifest as spinal cord ischemia.

Imaging protocols are less standardized for the spine and spinal cord than for the brain. The most important difficulties for optimization of sequences are due to the many interfaces that exist in this region, such as bone–cerebrospinal fluid (CSF) and spinal cord–CSF, the proximity of the lungs, and the mobile character and size of the spinal cord and its adjacent structures.[13]

Plain radiography is not usually helpful for diagnosis. Computed tomography (CT) scanning may reveal dilated vessels in the thecal sac, but findings are usually normal. If a patient presents with symptoms of subarachnoid hemorrhage, CT scanning demonstrates blood in the spinal fluid.

Myelography findings, with or without CT, show dilated vessels in the intradural space. This imaging modality is very sensitive and shows these abnormalities in detail. This is an invasive procedure that requires injection of a contrast agent into the thecal sac. Postprocedural headache is not uncommon.

On magnetic resonance imaging (MRI), soft tissue and neural elements are visualized in detail. Dilated intradural vessels can be seen as flow voids or can be seen filling with contrast. Edema or hemorrhage in the spinal cord parenchyma can be assessed. The exact fistula site cannot be localized. Sequences indispensable to a basic MRI clinical protocol for any spine or spinal cord examination are fast spin echo (FSE) T2 and spin echo (SE) T1. All spinal investigations should have sequences in both sagittal and axial planes to identify exact location and to attain better visualization of lesions. Advanced sequences may be employed as well.[13]

Magnetic resonance angiography (MRA) and CT angiography (CTA) are noninvasive modalities that can be used to identify abnormal vessels. However, resolution of these modalities is not yet optimal. The pathology must be confirmed by spinal angiography.[10]

Spinal digital subtraction angiography (DSA) is the gold standard for the diagnosis of spinal AVM and is an indispensable tool for treatment planning.[8]

Arteriography is the criterion standard for visualizing AVMs. This dynamic study allows visualization of the pathology in real time, enabling assessment of high-flow versus low-flow AVMs. In addition, the location of the fistula can be visualized. Arteriography is an invasive procedure that may cause morbidity such as spinal cord ischemia, cerebrovascular accident, or vascular dissection. Comparison of a prospective series of consecutive right transradial diagnostic cerebral arteriograms versus a procedural staging system revealed that neurointerventionalists can achieve high success rates and low crossover rates after performing this procedure.[14]

Vascular malformations of the spine frequently have distinguishing characteristics on imaging that are imperative for the radiologist to recognize to provide proper guidance for diagnosis and treatment.[2]  Advances in neurovascular imaging, along with increased utilization of these advances, have resulted in more frequent identification of these lesions.[1]  Often, radiologists are the first to guide the clinician toward an adequate diagnosis.[10]  Clinical challenges that neuroradiologists may face include "when" and "where" concerning the use of each technique and for which pathology or clinical scenario each technique is most useful.[13]

Typically, spinal MRI is ordered as a first-line screening method to detect spinal vascular malformations. If a spinal vascular malformation is still suspected, digital subtraction angiography (DSA) must be performed to display the very small vessels of the spinal cord. Because of complications involved with DSA, MRA or CTA can be used to determine the spinal cord level of the feeding artery, thus limiting the amount of time needed before the DSA procedure is performed.[15]

No laboratory studies are useful for the diagnosis of spinal cord vascular malformations. However, if the patient presents with symptoms of subarachnoid hemorrhage, lumbar puncture or computed tomography (CT) scan reveals blood in the spinal fluid.

There are nno acceptable pharmacologic means to treat spinal vascular malformations. Use of glucocorticoids may improve the patient's neurologic function for a short period. These steroids decrease vasogenic edema, but they do not treat the underlying pathology of the disorder. Unfortunately, these medications have long-term adverse effects. Prolonged use of steroids is associated with adverse systemic effects such as gastric ulceration, elevated blood glucose levels, and suppression of the immune system.

Open surgical treatment

Each spinal vascular malformation is a unique lesion; therefore, an individualized treatment algorithm must be tailored to each patient. Surgical treatment options include open surgical ligation or resection of the malformation, endovascular occlusion, spinal radiation, and a combination of these techniques.

Dural arteriovenous fistulas (AVFs) can be treated via open or endovascular ligation. Both techniques yield excellent results, with occlusion rates higher than 80% reported. The benefit of the endovascular technique is that it is less invasive than the open surgical technique. If a patient has multiple sites of fistula formation, open ligation is more appropriate because all feeding vessels may be ligated under direct vision. Open surgery is necessary if the arterial feeding vessel is impossible to access because of tortuous vascular anatomy or if the vessel supplies blood to healthy regions of the spinal cord.[16, 17, 18, 19, 20, 21]

Intradural AVMs typically are best treated via endovascular surgery and, if required, by open surgery and resection.

Endovascular treatment

Treatment options are dictated by the location of the lesion, the patient's medical condition, and the risk-versus-benefit ratio. The most important factor in determining treatment options is the presence of intramedullary or extramedullary shunting. Malformations that are subpial in location are less likely to be cured. These are usually supplied by subcommissural branches of the anterior spinal artery (ASA). The role of partial embolization is not clear. Long-term clinical results in patients with symptomatic spinal AVMs have included a lower incidence of recurrent hemorrhage; this may have a role in treatment of difficult lesions. Lesions on the surface of the spinal cord that are supplied by circumferential branches of the ASA may be safely treated with either embolization or surgery.

The new generation of liquid embolic materials and microcatheters has made interventional treatment for spinal AVMs safer, yielding better results.[22, 23] The goal of any intervention is to eliminate the shunt. Microcatheterization is of paramount necessity in achieving effective results. Delivery of embolic material to the nidus of the lesion reduces the AVM and lowers the risk of inadvertent embolization of normal vessels.

Liquid embolic agents are the first choice for treatment of most spinal AVMs because they are most likely to fill the distal nidus and they are associated with a low recanalization rate. The authors' agents of choice are n-butyl cyanoacrylate (n-BCA) and Onyx (ethylene vinyl alcohol copolymer). Embolization of lesions supplied by the ASA requires selective catheterization and deposition of embolic material. Permanent deficits due to embolizations in the ASA territory occur in up to 11% of patients.[24]

Manipulation of the viscosity of the liquid embolic material as in the case of n-BCA or use of different viscosity Onyx (Onyx-18 vs Onyx-34) helps to ensure more precise deposition. Polymerization should occur in transit through the arteriovenous shunt. For higher-flow lesions, hypotension is pharmacologically induced, typically with a mean arterial pressure of 50 mm Hg. With larger draining vessels, the Valsalva maneuver helps to delay transit time.

When preoperative embolization is planned, polyvinyl alcohol microparticles (PVAs) are a reasonable choice of embolic material. They are also useful for embolization of type 2 AVMs. Advantages of PVAs are that embolization may be performed at a more proximal location and the size of the particles can be determined according to the size of the lesion and its collaterals. The goal of treatment with either agent is to provide distal occlusion of the nidus. Proximal occlusion results in collateral reconstitution, with little hope of cure.

Regardless of the material chosen for embolization, all procedures should be performed with the patient under general anesthesia with neurophysiologic monitoring, depending on the location of the lesion. Somatosensory-evoked potentials (SSEPs) are highly accurate in assessing spinal cord function. Motor-evoked potentials (MEPs) are useful when a spinal AVM is supplied by the ASA.

Preoperative

Preoperative evaluation consists of a detailed neurologic examination, a baseline urodynamic evaluation, and appropriate imaging studies that confirm the diagnosis of a vascular malformation. Magnetic resonance imaging (MRI) of dural AVFs at the thoracolumbar junction usually shows serpiginous vessels in the intradural compartment, along with vasogenic edema in the spinal cord. Intradural vascular spinal malformations appear as lesions in the spinal parenchyma.

Once the diagnosis is considered, the anatomy of the malformation can be further defined with the use of spinal arteriography. Spinal arteriography illustrates detailed anatomy through dynamic images, providing the surgical team with the information necessary to decide the best treatment option.

(See the images below.)

Spinal malformation. This is a sagittal T2-weighted MRI of the thoracic spine of a 68-year-old woman with a 9-month history of back pain and sensory loss, progressing to the point of loss of bowel and bladder function along with a sudden onset of paraparesis. Note the thoracolumbar junction with an edematous spinal cord and dilated serpiginous intradural venous plexus.

Spinal malformation. This is an axial T2-weighted MRI of the thoracic spine of a 68-year-old woman with a 9-month history of back pain and sensory loss, progressing to the point of loss of bowel and bladder function along with a sudden onset of paraparesis. Note the lumbar spine with an edematous spinal cord and dilated intradural venous plexus.

Intraoperative

Once the lesion has been defined and the surgical treatment plan (endovascular, open surgical, or a combination of the two) has been determined, the patient is taken to the operating room or to the endovascular suite. The procedure is performed with the patient under general anesthesia with the use of neurophysiologic monitoring. Intraoperative monitoring allows analysis of ischemia to the spinal cord, so that normal vascular channels are not inadvertently permanently disturbed. Arteriography may be performed in the operating room via an endovascular or an open technique to confirm closure of the fistula.

Indocyanine green videoangiography has been used at some neurologic surgery centers during treatment of spinal dural AVFs. This technology allows surgeons to view, in real time, the vasculature within the operating field to ensure that the AVF has been obliterated.[25]

Postoperative

When surgery has been completed, the patient is awakened from anesthesia and is taken to a monitored setting, where serial neurologic examinations can be performed. With ligation of the dural AVF, most patients show neurologic improvement and can begin physical therapy. Improvement in neurologic examination findings may take several weeks. If arteriography was not performed in the operating room, it should be performed during the immediate postoperative period to document closure of the fistula.

Follow-up

Patients should be monitored with serial neurologic examinations and imaging studies in an outpatient setting to confirm closure of the fistula. With intradural lesions, a procedure is deemed successful based on intraoperative assessment of complete resection and a postoperative arteriogram that shows no arteriovenous shunting. If patients experience any worsening from their neurologic baseline, appropriate evaluation with imaging studies is completed to rule out fistula recurrence.

Postoperative MRI findings do not necessarily correlate with clinical outcomes. It is not uncommon for spinal cord abnormalities to persist on MRI for many months, even when treatment is successful.[26]

Open surgical or endovascular treatment

Risks of this procedure include the following:

• Skin infection or cellulitis

• Bleeding

• Injury to nervous tissue, causing paralysis, bladder or bowel dysfunction, or sexual dysfunction

• Chronic pain syndromes

• Thrombosis of epidural veins and neurologic loss

• Recurrence of fistula

• Spinal cord infarction

Open surgical ligation or resection

Complications include the following:

• Infection of meninges (meningitis)

• Cerebrospinal fluid leak

• Wound dehiscence

Endovascular technique

The following complications have been noted:

• Femoral hematoma

• Pseudoaneurysm and thrombosis

• Arterial dissection

Vascular disorders of the spine are more rare than cerebral vascular entities but can result in significant morbidity.[2]  Prompt recognition and timely management of vascular disorders of the spinal cord can improve patient outcomes.[27]  Advances in neurovascular imaging, along with increased utilization of these advances, have resulted in more frequent and timely identification of these lesions.[1]  Treatment modalities include endovascular and surgical therapy. Endovascular treatment offers the advantages of a less invasive approach; therefore, it is usually chosen as primary therapy.[10]

Favorable safety profiles and cure rates can be achieved with appropriate patient selection and judicious use of different treatment modalities.[28]  Surgery and, to a lesser extent, stereotactic radiosurgery are used when endovascular approaches are impossible or have proved unsuccessful.[29]

Typically, the clinical presentation of a spinal vascular malformation is insidious, and patients' symptoms are regularly attributed to other conditions. Although previous studies have characterized neurologic outcomes after treatment for these lesions, little is known about the pretreatment patient characteristics associated with poor and/or positive patient outcomes. Misdiagnosis has been relatively common among patients with spinal vascular malformation and has contributed to delays in treatment, which appear to be associated with worse clinical outcomes for patients who, ultimately, do receive treatment.[30]

Patient outcome is directly related to neurologic function at the time of surgical intervention. Patients who are able to ambulate when treated tend to remain ambulatory and may increase their strength with physical therapy. Patients who do not have antigravity strength in the lower extremities before treatment are unlikely to regain neurologic function to the point of ambulation. Patients who present with bowel or bladder dysfunction have limited return of neurologic function.

Diagnosing these lesions early and providing appropriate treatment are important if patients are to achieve optimal neurologic outcomes.

Magnetic resonance imaging (MRI) should be the first diagnostic modality used when a spinal vascular malformation is suspected. If a lesion is found, spinal angiography is considered the criterion standard for optimal analysis of angioarchitectural features.

With rapid advancements in endovascular therapy, treatment for spinal arteriovenous malformations (AVMs) continues to evolve. The decision to use endovascular versus surgical therapy largely depends on the type of lesion identified and its anatomic location. Studies have shown that endovascular treatment is effective for extradural arteriovenous fistulas (AVFs), intradural ventral (perimedullary) AVMs, and intramedullary spinal AVMs. Surgery and, to a lesser extent, stereotactic radiosurgery are used when endovascular approaches are impossible or have proved unsuccessful.[29]  Extradural-intradural (juvenile) AVMs and conus AVMs remain difficult-to-treat lesions.[30, 31]

Spinal AVMs are rare disorders with a low prevalence; treatment for patients with this complex diagnosis usually requires the collaboration of professionals from several neuroscience disciplines.[32]  Because delayed initial diagnosis leads to irreversible damage of the spinal cord, neurosurgeons should always include spinal AVM in the the differential diagnosis.[8]

Embolization with a liquid embolic agent is the first-choice treatment for type 2-4 malformations, whereas surgery may be a better option for type 1 malformations. The prognosis for patients with these lesions seems to be better than was previously thought, especially with advances in endovascular techniques and available embolic agents that offer a high success rate with low morbidity.

Further advances in endovascular and microneurosurgical techniques should include smaller, more navigable catheters that can be manipulated through tortuous anatomy. 

The Society of NeuroInterventional Surgery (SNIS) has produced the following guidelines for management of brain AVMs[33] :

• Digital subtraction catheter cerebral angiography (DSA), including 2D, 3D, and reformatted cross-sectional views when appropriate, is recommended in the pretreatment assessment of cerebral AVMs.
• It is recommended that endovascular embolization of cerebral AVMs be performed in the context of a complete multidisciplinary treatment plan aiming for obliteration of the AVM and cure. 
• Embolization of brain AVMs before surgical resection can be useful to reduce intraoperative blood loss, morbidity, and surgical complexity.
• The role of primary curative embolization of cerebral AVMs is uncertain, particularly as compared with microsurgery and radiosurgery with or without adjunctive embolization. Further research is needed, particularly with regard to risk for AVM recurrence. 
• Targeted embolization of high-risk features of ruptured brain AVMs may be considered to reduce the risk for recurrent hemorrhage.
• Palliative embolization may be useful to treat symptomatic AVMs in which curative therapy is otherwise not possible.
• The role of AVM embolization as an adjunct to radiosurgery is not well-established. Further research is needed.
• Imaging follow-up after apparent cure of brain AVMs is recommended to assess for recurrence. Although noninvasive imaging may be used for longitudinal follow-up, DSA remains the gold standard for residual or recurrent AVM detection in patients with concerning imaging and/or clinical findings.