Spinal Dural Arteriovenous Fistulas Supplied from Multiple Segmental Arteries: Microsurgery Using Indocyanine Green Angiography and Radiosurgery with a Spine Tracking System

Endovascular occlusion and/or surgical disconnection are the first treatment of choice for spinal dural arteriovenous fistulas (d-AVFs) with venous flow reversal into the perimedullary veins. However, d-AVFs with multiple feeding arteries and fistula points are associated with various difficulties related with treatment. We herein describe three cases of AVFs supplied from multiple segmental arteries treated with surgery using indocyanine green (ICG) angiography or radiosurgery using a spine tracking system. ICG was administered via intravenous injection during and after the surgical disconnection procedures. As double d-AVFs or multi-segmental ventral epidural type AVFs require invasive spinal surgery, less invasive radiosurgery was performed using a CyberKnife with a spine tracking system. ICG angiography revealed changes in venous flow reversal during the surgical maneuvers as well as the disappearance of the AVF after disconnecting all draining veins in Case 1. Among the patients with double AVFs or multi-segmental ventral epidural type AVFs treated with radiosurgery, the fistula points received a marginal dose of 15 to 18 Gy at an isodose of 60% to 67%. The AVFs disappeared or almost disappeared on angiography one year after radiosurgery in Case 2. The signal void on T2-weighted images showing a venous pouch disappeared, the draining veins normalized, and the cord compression was alleviated two years after radiosurgery in Case 3.


Introduction
Spinal dural arteriovenous fistulas (d-AVFs) are classified into three groups: 1) ventral epidural (previously called "epidural", "osteodural", or "paravertebral" AVF), 2) dorsal epidural, and 3) lateral epidural (most common "classic type" of d-AVF). Symptoms in Group 2 appear suddenly, with epidural hematoma formation, and progressively in Group 3 as a result of abnormal drainage (flow reversal) into the perimedullary veins. In Group 1, symptoms develop slowly due to compression of the spinal cord and/or nerve roots by enlarged epidural venous pouches [1]. Treatment with endovascular occlusion and/or surgical disconnection of fistulas is required in patients with acute or rapidly progressive symptoms before the spinal cord damage becomes irreversible [2][3][4]. Benign fistulas are a developing indication for radiosurgery [5].
Endovascular intervention for spinal d-AVFs is a less invasive approach and primary treatment option [6]. A cure rate of 25-77% for endovascular embolization using liquid adhesive materials for classic type d-AVs has been reported [2,7], and rapid improvements in symptoms are obtained after endovascular treatment [4]. However, it is difficult to treat d-AVFs supplied from multiple segmental arteries or the same pedicle to the anterior spinal artery using endovascular intervention. Moreover, it is necessary to manage residual d-AVFs after embolization with surgery or radiosurgery, as symptoms may remain or recur and new anastomoses may develop.
Surgical disconnection of the draining veins is the first choice of treatment for spinal d-AVFs with venous flow reversal, in addition to endovascular occlusion. Patients with such AVFs experience progressive symptoms due to edema of the spinal cord or the sudden onset of symptoms as a result of subarachnoid hemorrhage (SAH) [8]. Early surgery is recommended in cases involving the rapid progression of symptoms ( Figure 1). The rate of a surgical cure is very high, with a low incidence of complications.

FIGURE 1: A d-AVF at the cervico-medullary junction
A: A MR proton density image showing edema in the medulla with a signal void around the brainstem. B, C: Vertebral angiogram demonstrating a d-AVF at the cervico-medullary junction. D: Following surgical disconnection of the fistula, the AVF disappeared on the angiogram. E: The patient's symptoms (tetraparesis, dysphagia, respiratory distress) rapidly improved, with no recurrence for 17 years after surgery.
However, surgical difficulties are often encountered in patients with large d-AVFs supplied from multiple segmental feeding arteries or d-AVFs with feeding arteries originating from a different level than the fistula point [3]. The recently developed indocyanine green (ICG) angiography technique is very useful for detecting feeding arteries or draining veins at different levels [9]. The intra-arterial administration of ICG has also been reported to have benefits with respect to the use of multiple and short interval injections versus intravenous administration, although it is necessary to place a catheter into the target artery prior to surgery [10]. At our facility, we use ICG angiography to detect feeders and drainers as well as confirm the complete disconnection of the fistulas during surgery.
Radiosurgery is a less invasive treatment option for benign cranial d-AVFs [5]. In cases of benign spinal d-AVFs, the ventral epidural type, AVFs with non-progressive symptoms, or non-symptomatic residual AVFs remaining after endovascular intervention are considered indications for radiosurgery, especially those with feeding arteries from multiple spinal segments. AVFs exhibiting flow reversal into the perimedullary veins are not indicated due to risks of bleeding (SAH) and the potential for progressive symptoms during the latent periods prior to total obliteration, similar to cranial d-AVFs with flow reversal into the cortical veins. However, patients with high risks for surgery (general anesthesia) and/or endovascular intervention, such as those with AVFs fed from the same pedicle supplying the anterior spinal artery, are indicated for radiosurgery as a less invasive treatment option.
In this report, we present three cases of spinal d-AVFs treated with microsurgery using ICG angiography and radiosurgery with a spine tracking system. Informed patient consent was obtained or waived for all subjects involved in this report.

Case 1 (Microsurgery)
A 53-year-old male visited a former hospital due to paraparesis and urinary incontinence and was diagnosed with a spinal d-AVF. Endovascular intervention was intended; however, a provocation test revealed worsening of the paraparesis. The patient then visited our hospital for possible radiosurgery in June 2009. Due to his progressive symptoms, surgical disconnection of the AVF was planned and detailed imaging studies for microsurgery were performed. T2-weighted MR imaging showed edema extending from the lower thoracic spinal cord to conus medullaris and signal void in perimedullary areas ( Figure 2). CT angiography demonstrated perimedullary tortuous vascular structures identical to the void on MR imaging as well as vascular structures (suggesting the presence of feeding arteries) from the right L1 to L3 segment. Spinal angiography disclosed a d-AVF fed from the right L1 and L2 segmental arteries ( Figure 3). No feeding arteries were demonstrated from the bilateral Th12 segments. Surgical disconnection was performed in July 2009 at the level of L1-L2 (via hemi-laminectomy), and the intradural draining veins were disconnected by coagulation. The dura, including the fistula point and feeding artery, was coagulated simultaneously in the intra-and extradural spaces. Postoperative angiography showed the disappearance of the lower part of the AVF. However, the upper part of the AVF fed from the different segmental level of Th12 exhibited no changes on follow-up MR images. The residual AVF was subsequently treated in September 2009 at the level of Th12-L1 under guidance with ICG angiography during the procedure. As the right dorsal rootlets of Th12 segment were entirely involved with dilated draining veins and the subarachnoid space around the root exit zone was very difficult to open, the draining veins from the fistula were clipped in order based on the images of ICG angiography. The stepwise disappearance of the perimedullary draining veins was confirmed. Finally, the last residual shunt was coagulated and disconnected. ICG angiography confirmed the lack of flow reversal with a normal venous circulation (video).

VIDEO 1: Spinal dural arteriovenous fistula: ICG angiography
The draining veins from the fistula were clipped in order based on the images of ICG angiography and the stepwise disappearance of the flow reversal was confirmed. Finally, the last residual shunt was coagulated and disconnected. ICG angiography confirmed the lack of flow reversal with a normal venous circulation.
View video here: https://www.youtube.com/watch?v=KqidaW5_roU&feature=youtu.be The postoperative MR images showed the disappearance of the signal void and spinal cord edema (Figure 4), and postoperative angiography demonstrated the disappearance of the AVF. The patient's paraparesis and urinary incontinence gradually improved, allowing him to walk with a stick. No episodes of recurrence have been observed for five years after the surgery.

Case 2 (Radiosurgery)
A 66-year-old female visited a former hospital on July 2006 due to the sudden onset of severe neck pain and was diagnosed with SAH due to d-AVFs in the cervical region. Endovascular occlusion was performed; however, residual AVFs were recognized at the C2, C5, and C6 levels on follow-up angiography after treatment. The patient had no symptoms and was subsequently referred for radiosurgery. She visited our hospital in November 2006. Right vertebral angiography demonstrated spinal d-AVFs fed from the C2-C3 and C5-C6 segmental arteries ( Figure 5). These AVFs were treated with a dose of 18 Gy at an isodose of 60% and 63%, respectively, using fused image of angiography under a spine tracking system. The AVFs disappeared or almost disappeared one year after radiosurgery. Although no follow-up angiography is available yet, the patient has shown no deterioration in symptoms for seven years after treatment.

Case 3 (Radiosurgery)
A 43-year-old male, who had a history of a left leg arteriovenous malformation treated by endovascular intervention, visited a former hospital in April 2007 due to a gait disturbance and was diagnosed with multilevel paravertebral AVFs (ventral epidural type) in the thoraco-lumbar region. Endovascular occlusion was performed, and the symptoms improved. However, he suffered from back pain in June 2009, and the multilevel AVFs ( Figure 6) were again treated with endovascular embolization.  the Th10 to L3 level, identical to the dilated veins noted on the angiogram. The spinal cord was compressed at the Th11 level by the large venous pouch. The venous pouch, including the fistula point, was treated with a dose of 15 Gy at an isodose of 67% (C: axial, D: coronal). T2-weighted axial (E) and coronal (F) images revealed the disappearance of the signal void in the venous pouch and an improvement of the spinal cord compression two years after the radiosurgery procedure (large arrows). The dilated vein had also normalized (thin arrows). Angiography was not performed due to the patient's allergic anaphylactic shock reaction to iodine contrast material.
MR images obtained regularly after treatment revealed a gradual decrease in the signal void, while T2weighted images showed a decrease in the size of the pouch and draining veins two years after radiosurgery. The patient's symptoms of gait disturbance and urinary incontinence gradually improved and almost disappeared. He subsequently returned to his previous work one year after the radiosurgery treatment, with no deterioration in symptoms for four years after.

Discussion
Most patients with spinal d-AVFs develop progressive symptoms comprising sensory abnormalities, motor weakness, and disturbances in urination due to edema of the spinal cord. Surgical disconnection is the gold standard treatment for such patients. However, endovascular intervention is also a first choice of treatment as a less invasive procedure [5][6]. Patients in whom complete disconnection or total obliteration are obtained show improvements in their symptoms immediately after treatment and are permanently cured. Providing an early diagnosis and proper treatment before irreversible changes in the spinal cord occur is therefore important. However, there are treatment difficulties associated with both surgery and endovascular intervention. Additional options are required in such cases, particularly those involving the incomplete obliteration of AVFs after surgery or embolization.
The use of ICG angiography during surgery plays an important role in achieving complete disconnection [11][12], especially in patients with AVFs supplied by multiple feeding arteries and/or fistula points at segmental levels different from that of the feeding artery. We herein demonstrated its usefulness in evaluating changes in the reversal flow during the procedures and confirming the total disappearance of the lesion following disconnection (video). As to disadvantages of ICG angiography, vascular structures lying within or behind the spinal cord can't be evaluated using this modality, in contrast to intraoperative DSA, which can be used to define structures outside of the operative field. The draining veins in the ventral direction should be defined directly under a microscope after cutting the dentate ligament and exposing the ventral roots anteriorly, as shown in the included video. The intra-arterial injection of ICG may help to evaluate the vascular structures in various operative fields, as repeat injections may be given within short times intervals [10], although this technique is difficult to use in cases of AVFs with multiple feeding arteries. The present patient required revision surgery for the residual AVF with a fistula point at the level of Th12, but not the level of L1, where the feeding artery was located. As all fistula points must be defined directly in the operative field for surgical disconnection, we believe that it was better to include the level of Th12 in the first operation in order to avoid the need for a two-step procedure in this case. However, the fistula point at the level of Th12 was atypical, and the dorsal rootlets and root exit zone were entirely involved and occupied by the enlarged perimedullary draining veins. Using a conventional small dural opening for the d-AVFs disconnection around the root exit zone seemed to be impossible in this case.
Spinal d-AVFs present at multiple segmental levels that are fed by multiple feeding arteries are difficult to treat with microsurgery [13]. Endovascular intervention is a first choice of treatment in such cases; however, it is not easy to obtain total obliteration in many cases, as shown in the current Cases 2 and 3. The purpose of embolization is to reduce the shunt flow of AVFs, and to prevent re-bleeding (SAH) and/or to improve symptoms, particularly progressive paraparesis. Residual or benign AVFs, such as ventral epidural type AVFs or AVFs with unrelated clinical symptoms [14], are also a developing indication for radiosurgery [5], and multi-segmental level AVFs are possible targets for radiosurgery using a spine tracking system, as shown in this report. D-AVFs (fistula points) are usually situated extradurally with some distances to the spinal cord. Hence, an effective marginal dose of 18 to 20 Gy is applicable in most cases. Radiosurgery apparently increases the number of treatment indications for d-AVFs, especially in combination with surgery or endovascular intervention. However, the use of radiosurgery requires a latency period of at least six to 12 months before effective changes and/or a desirable level of obliteration are obtained, with one to two years needed for total obliteration. The risks of re-bleeding or symptomatic deterioration must also be considered before and after radiosurgery up to the point of total obliteration, and providing regular follow-up studies after treatment is important. We intend to follow the current patients with d-AVFs using the newly developed spinal MR angiography technique due to its reduced invasiveness and lack of need for contrast materials. MR angiography may thus be used to treat and follow patients with d-AVFs, especially those similar to the patients described in the preset Case 3.

Conclusions
We herein reported three cases of residual AVFs supplied from multiple segmental arteries treated with microsurgery and/or radiosurgery. The use of ICG angiography during surgery is very helpful for obtaining and defining complete disconnection of the AVF. In addition, radiosurgery using a spine tracking system was found to be safe and effective for achieving obliteration of the AVFs with multiple feeding arteries in the present report. Although no episodes of recurrence have been noted four to seven years after treatment in our patients, long-term follow-up studies are required. The application of multidisciplinary and/or combination treatment with endovascular intervention, microsurgery, and radiosurgery increases the treatment indications for complex spinal d-AVFs, which were previously difficult to manage.

Additional Information Disclosures
Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.