Spinal Arteriovenous Metameric Syndrome: Clinical Manifestations and Endovascular Management

Discussion

The concept of SAMS is spinal extension of the craniofacial arteriovenous metameric syndrome proposed by Bhattacharya et al.⁴ This was based on research on avian embryos demonstrating that mesoderm and neural crest cells from a given metameric level occupy the same territory in the face and brain and that these 2 cell types cooperate in myogenesis and vasogenesis.⁷ During vasogenesis, endothelial cells derive from the mesoderm and the tunica media derives from the neural crest cells. Therefore, a genetic defect or somatic mutation in the neural crest or adjacent mesoderm before migration causes development of >1 vascular malformation with a metameric distribution. Therefore, the causative event creating a vascular malformation such as a genetic mutation occurred earlier in the case of SAMS than in a solitary SCAVM.

Rodesch et al⁸ proposed a classification of spinal cord AVMs, considering the timing of the causative event responsible for creation of a vascular malformation such as gene mutation. They classified SAMS under the category of “genetic nonhereditary” along with multimyelomeric AVMs and syndromic AVMs such as Klippel-Trenaunay-Weber syndrome and Parkes Weber syndrome. In their series of 155 cases of spinal cord arteriovenous shunting, 20.6% belonged to the category of “genetic nonhereditary.” These consisted of 6.4% metameric, 11% multimyelomeric, and 3.2% syndromic cases. They classified cases of a SCAVM associated with a radicular AVM as “multimyelomeric,” which should be classified as “metameric” if the AVMs are at the same metameric level as the authors discussed in the article. This would probably make SAMS approximately 12% of SCAVMs in their series, judging from the earlier report of the same group. In their series, SAMS showed male dominance by 2:1, which is the opposite of our cases in which there was strong female dominance by 5:2.²

Berenstein et al⁵ performed a literature search and found that metameric lesions were reported to be 7%–14% of SCAVMs. SAMS may be underestimated because associated lesions, especially radicular AVMs, are frequently missed or excluded from the metameric lesions. In our series, there were a significant number of radicular AVMs, which may account for the higher number of SAMS (19%) compared with the report of Rodesch et al.⁸ The frequency of radicular AVMs should be noted in comparison with craniofacial arteriovenous metameric syndrome, in which cranial nerve AVMs are extremely rare.

Our series illustrates that most cases of SAMS have an intradural component but rarely manifest as a complete angiographic expression of the disease with involvement of all tissue elements that encompass the metamere. We experienced 1 additional patient who had cervical paraspinal and spinal AVMs associated with a muscle AVM at the same level without intradural malformation. This case can also be considered within a spectrum of SAMS.

The most common presenting symptom was spinal SAH or hematomyelia. The intradural lesions associated with SAMS were mostly nidus-type SCAVMs, which is probably one of the reasons for the higher incidence of hemorrhage for patients with SAMS compared with non-SAMS patients. Non-SAMS patients include those with a significant number of microfistulas that usually present with nonhemorrhagic progressive neurologic deficits in adults. Another explanation for the higher hemorrhage rate in SAMS supported by our experience is that intradural lesions of SAMS tend to develop a new aneurysm or enlargement of a pre-existing aneurysm. This observation also demonstrates the more dynamic nature of the SAMS compared with non-SAMS lesions, which is well-illustrated in the representative cases. Hemorrhagic episodes after the initial endovascular treatment occurred in 5 patients (22%) during follow-up, which was also higher than those in the non-SAMS population.

Nonhemorrhagic neurologic deterioration was the second most common clinical presentation. Acute thrombosis of the draining vein can cause acute neurologic deterioration often associated with pain, clinically mimicking hemorrhage. Venous ectasias or arterial aneurysms may cause mass effect and compressive spinal cord syndromes. Subacute or chronic deterioration of spinal cord function with progressive myelopathy is also common and may be secondary to venous hypertension of the spinal cord. An additional less frequent acute-to-subacute presentation is painful radiculopathy due to nerve root arteriovenous malformations. These lesions are postulated to cause pain due to compression of the nerve root by dilated venous structures in the neural foramen or from a steal phenomenon due to high-flow arteriovenous shunting. Careful assessment of the symptoms and correlation of these with the angioarchitecture of the lesions are the guiding principles for targeted embolization of these complex lesions. For this purpose, assessment of any shared venous drainage of the extra- and intradural portions of the lesion is also important. Symptoms in one patient may be initially attributable to the intramedullary compartment and later due to the extramedullary disease and vice versa, as demonstrated in case 1.

This longitudinal series of patients with SAMS demonstrates the progressive nature of the disease and poor long-term functional prognosis. However, this series also shows that these complex lesions can be treated safely by endovascular techniques with a palliative strategy focused on preventing hemorrhage, preserving spinal cord function, and relieving pain. Angiographic cure is the exception and only a realistic goal for limited lesions without significant intramedullary involvement.⁹ Even then, we believe that we can improve the natural history of this disease by performing target palliative embolization as illustrated in the representative cases. To maximize the effect of palliative treatment, periodic angiographic examination with intent to treat is important to prevent neurologic deterioration. Diagnostic cross-sectional imaging with CT or MR imaging is currently not sensitive enough to detect development or enlargement of spinal aneurysms of the anterior spinal artery or posterior spinal artery or within the nidus of the AVM. Our recent protocol for follow-up of clinically stable patients is yearly MR imaging without and with contrast administration and clinical examination, and spinal angiography with intent to treat every 3–5 years. If MR imaging changes or clinical deterioration occurs, we perform spinal angiography with intent to treat without delay. For those who have extensive bony or paraspinal lesions, CT is also a useful follow-up tool to assess the extent of bony destruction.

Regarding the technique of embolization, it is most important to close the lesion itself, such as an aneurysm, a fistula site, or a nidus, to obtain a long-lasting effect. Proximal feeder occlusion tends to result in an incomplete transient effect due to collateralization. n-BCA is the best embolic agent with a long-lasting occlusive effect for intradural lesions in our experience. Embolization can be safely performed in the anterior spinal artery,¹⁰ but the safety margin is further increased when posterior spinal artery access to the malformation is feasible. We use neurophysiologic monitoring and superselective provocative testing to add an extra safety margin before embolization. This testing has been demonstrated to have a very high negative predictive value.⁶ Introduction of the Onyx liquid embolic agent has added a useful adjunct in the treatment of SAMS. We have been successful in using this material to treat extensive high-flow extradural fistulas to reduce spinal cord venous hypertension or mass effect or to control bone destruction. Onyx is a suitable embolic agent for this purpose because of its ability to be injected in a large amount from 1 pedicle for a long time. However, poor visualization of the remnant lesion due to permanent high radiopacity of tantalum mixed in Onyx sometimes may complicate future treatments. We have avoided using Onyx in the intradural compartment due to the previously reported potential toxicity of Onyx/dimethyl-sulfoxide to neural and vascular tissue.^11,12 In addition, the so called “plug and push” technique used to make Onyx penetrate deep into the lesion often requires significant reflux into the feeding pedicle, which is not feasible for the spinal cord arteries.