Aggressive Vertebral Hemangiomas Causing Compression Fracture with Neurological De�cits: A Retrospective Cohort Study

Background:In rare instances, aggressive vertebral hemangiomas (VHs) can cause compression fracture, resulting in severe pain and neurological de�cits. But the diagnosis and treatment of these aggressive lesions are challenging because of these lesions are rare and atypical. This study aimed to evaluate the safety and e�cacy of surgical management for aggressive VHs with vertebral compression fracture by a modi�ed multimodality surgery. Methods:We retrospectively reviewed 6 cases suffering from aggressive VHs with compression fracture and neurological de�cits in our department from July 2011 to April 2016. These patients were treated by the multimodality surgery, includingpreoperative embolization, intraoperative injection of gelfoam mixed with cement, and laminectomy decompression.The follow-up period was at least 3 years. Perioperative parameters, clinical outcomes, and radiographical data were collected and analyzed. Results: The 6 patients involved 1 male and 5 females (mean age, 52.3 years).The levels involved were: in thoracic spine (5 cases) and lumbar spine (1 case).Preoperative CT-guided biopsy was conducted in all patients, with 5 patients had de�nitive pathologic diagnosis. All patients were treated successfully with the multimodal surgery, with no cement leakage and other severe complications. The mean operation time was 182.2 minutes, and the estimated blood loss was 908.3 ml.At an average follow-up of 49.8 months, clinical outcomes assessed by the visual analogue scale and Frankel grade were signi�cantly improved. The vertebral body height and kyphosis angle of the fractured vertebra were also corrected postoperatively. No affected vertebra re-fracture and adjacent vertebral fracture were developed, and none of the patients experienced recurrence of tumor at �nal follow-up. Conclusions:In cases of aggressive VHs causing compression fracture with neurological de�cits, CT-guided biopsy is indicated for the diagnosis. The multimodality surgery (preoperative embolization, intraoperative injection of gelfoam mixed with bone cement combined laminectomy decompression) is effective and safe, and can be considered as an acceptable surgical choice.


Background
Vertebral hemangiomas (VHs), one of the common benign spinal diseases, frequently affect the thoracic and lumbar spine [1,2].Most of these hemangiomas are incidentally discovered and have no obvious symptoms.For asymptomatic VHs, treatment is unnecessary.However, in rare instances, VHs can present as a locally aggressive behave way by enlarging and extending into the spinal canal and/or paravertebral space, leading to spinal cord compression [3][4][5][6].Aggressive VHs oftenexhibit several symptoms, including local back pain, radicular pain, or even neurological de cits.It has been reported that there are 0.9 to 1.2% of patients with symptomatic or aggressive VHs, which require medical treatment [1,7].
Usually, most aggressive VHs present typical radiographical ndings, such as a vertical striations sign, honeycomb morphology,or polka-dot change [8,9].Nevertheless,some aggressive lesionscan cause underlying bone resorption and even compression fracture [10,11].Wang et al. [12]recently demonstrated that compression fracture is one of the atypical features, which may result in misdiagnosis.As such, the diagnosis and treatment protocol for vertebral compression fracture by aggressive VHs deserves further investigation.
Although various non-surgical treatment modalities have been described for treating aggressive VHs [5,[13][14][15][16]], the outcome is sometimes unsatis ed.Surgical therapy is still the most radical method of clinical treatment of aggressive VHs.The surgical procedures mainly involved laminectomy decompression, intralesional vertebrectomy, and en-bloc spondylectomy; butthe formulation of ideal surgery for treating these lesions is still a matter of debate because of the rarity ofaggressive VHs [4,6,7,17].In this study, we reported 6 patients with compression fracture caused by aggressive VHs.These patients were treated with our modi ed multimodality surgery (preoperative embolization, intraoperative injection of gelfoam mixed with bone cement combined laminectomy decompression).The objective of this multimodality surgical technique was to minimize invasive, decompress spinal cord, and reduce the complication rate.

Patient population
This study was approved by the First A liated Hospital of Fujian Medical University Ethics Committee and written informed consent was obtained from all patients in this study.From July 2011 to April 2016, 6 consecutive adult patients suffering from aggressive VHs with compression fracture and neurological de cits were retrospective reviewed.These patients were treated with the multimodality surgery, which included preoperative embolization, intraoperative injection of gelfoam with vertebroplasty, and laminectomy.The follow-up period was at least 3 years.Patients with incomplete medical records or lost to follow-up were excluded.All patients received complete preoperative radiological examinations,including X-ray radiography, computed tomography (CT), and magnetic resonance imaging (MRI) of the spine.Because compression fracture of the aggressive VHs is a relatively atypical radiographical feature, CT-guided percutaneous biopsy was indicated and conducted in all patients.

Surgical techniques
Preoperative super-selective trans-arterial embolization was performed in all patients to reduce risk of uncontrollable intraoperative bleeding.The surgical method included following steps: (1) preinjection of gelfoam to further reduce blood loss; (2) vertebroplasty to obliterate the tumor and offer stability of affected vertebra; (3) decompressive laminectomy to remove the extensive tumor and decompress the spinal cord.All operations were performed by the same experienced surgeon.
The surgery was performed with a prone position under general anesthesia.After the affected vertebra, adjacent laminae and facet joint were exposed, a puncture needle was placed into the center of affected vertebral body through the unilateral transpedicular approach under the C-arm uoroscopic guidance.Two pieces of 6 cm × 2cm × 0.5 cm of sterile absorbable gelfoam (Jinling Pharmaceutical Co., Ltd., Nanjing, China) were scraped into 1.5 mm × 1.5 mm × 1.5 mm pieces.We mixed these small pieces of gelfoam with 20 mL of contrast medium (iohexol) (Fig. 1), and injected into the vertebral body via the channel of the needle.Then, the bone cement was injected to ll the entire lesion as much as possible with C-arm uoroscopy to prevent cement leakage.After injection, the puncture needle was extracted when the cement was solidi ed.Laminectomy decompression was then performed to excise the epidural lesion and remove the bone cement leaked into the spinal canal.Posterior pedicle screws and both pre-bent rods were installed nally.

Postoperative management and follow-up
Typically, we routinely used intravenous antibiotics and hemostatic drug within 24 hours after surgery to prevent deep infection and delayed hemorrhage.The negative drainage was taken out when drainage ow less than 50 ml/24 h.Patients were allowed to start exercising and walking gradually with their thoracic or lumbar brace one week postoperatively.
Immediately after surgery, lateral and anteroposterior X-rays were obtained routinely to evaluate the extent ofdecompression and position of cement and instrumentations.Then, the X-ray examinations were carried out at 3-, 6-, and 12-month follow-up and then once per year.The CT scan was taken on at the 3-month follow-up and examined annually after that.If the patient showed any symptoms and signs of recurrence, MRI and CT were performed immediately.

Outcome assessment
The perioperative parameters included operation time, blood loss, fused segments, complications, and pathologic diagnosis.Clinical assessment was evaluated using the visual analogue scale (VAS) and the modi ed Frankel grade.The VAS score was used to assess pain intensity.The Frankel grade was used to evaluate neurological status.The anterior vertebral body height (ABH), middle vertebral body height (MBH), and kyphosis angle were measured on lateral X-ray radiography.Kyphosis angle was de ned as the angle formed by 2 lines parallel to the superior and inferior endplate of the fracturedvertebrae, using the Cobb method [18].

Review of the literature
Aggressive VHs causing compression fracture are relatively rare.For further study, a brief literature review was conducted of the management of aggressive VHs with vertebral fracture in the PubMed, EBSCO, OVID, and Springer databases.The search criteria were publications related to aggressive VHs in recent years.Cases who had aggressive features (Enneking Stage 3, spinal cord compression, paravertebral extension or neurological de cits) with compression fracture were enrolled.

Statistical analyses
Statistical analyses were performed through SPSS version 22.0 (SPSS Inc., Chicago, IL, USA).Continuous data were presented as mean ± standard deviation.Comparisons between post-and preoperative parameters were conducted by using the ttest; a P-value < 0.05 was considered statistically signi cant.

Results
Table 1 shows the clinical features of the 6 patients.There were 1 male and 5 females.Their mean age was 52.3 ± 9.0 years (range from 41 to 63 years).Five patients had VH lesions in the thoracic spine, and 1 in the lumbar spine.In 5 cases, high-intensity signals on T2-weighted MRI were found, and the remaining was iso-intensity signal.Based on Tomita classi cation, 3 patients were type IV, and 3 were type V.The mean Spinal Instability Neoplastic Score (SINS) was 10.2 ± 1.6 (range from 8 to 12).All 6 patients presented with obviously neurological de cits preoperatively, including 1 patient with Frankel B grade, 1 with Frankel C grade, and 4 with Frankel D grade.These 6 patients had varying degrees of unsteady walking, limb numbness or weakness, radiculopathy and muscle atrophy.The mean duration of symptoms was 10.2 ± 7.9 months (range from 2 to 24 months).Physical examination found percussion pain in the paravertebral or spinous processes, decreased lower-limb sensation, weakened muscle strength and tender hyperre exia.Neurological function examination showed positive Babinski's sign in 2 patients.Preoperative CT-guided percutaneous biopsy was conducted in all patients.Of them, 5patients had de nitive pathologic diagnosis.In the remaining patient, the samples consist of only osteocyte and blood cells, and this case was diagnosed by postoperative pathology examination.All patients were treated successfully with the multimodality surgery, and the incision healed well.The average operation time was 182.2 ± 64.3 minutes (range from 120 to 300 minutes) (Table 2).The estimated intraoperative blood loss was 908.3 ± 349.9 ml (range from 500 to 1400 ml), and the average bone cement amount was 5.0 ± 1.7 ml (range from 3 to 7 ml).No bone cement leaked into the spinal canal was recorded.After surgery, the neurological symptoms were relieved for all patients, by varying degrees.The average follow-up period was 49.8 ± 12.6 months (range from 38 to 71 months).At nal follow-up, the VAS score was signi cantly improved from 7.0 ± 1.5 to 1.

Discussion
VHs are histologically spinal benign vascular malformations consisting of newly formed blood vessels [1].Occasionally, VHs can become aggressive to present as resorption of underlying bone, resulting in pathological compression fracture and then neurological de cit.The mechanism of aggressive VHs causing vertebral pathological fracture is that hemangiomas might cause diffuse bone in ltration, erode the horizontal trabeculae, and weaken bone mineral density [19].Furthermore, the enlargement of the affected vertebra and the consequently compression fracture can yield spinal canal narrowing and spinal cord compression.The diagnosis and treatment of these lesions are challenging.But there is little literature focusing on the aggressive VHs with compression fracture and neurological de cits because of the rarity of these cases.In this report, we reviewed the patients who had aggressive VHs with compression fracture in our department from 2011 to 2016.We aimed to share our experience in the diagnosis and treatment of these patients.
Recently, Wang et al. [12]conducted a radiological analysis of 95 cases with aggressive VHs and reported more than 1/3 of aggressive lesions exhibit at least 1 atypical feature.Among these atypical ndings, approximately 17% caseshad a vertebral compression fracture sign; the author also indicated that some patients may have atypical MRI signals (e.g., hypointense to isointense in T2-weighted images).Atypical VHs have more vascular but fewer fatty content so that these lesions can appear atypical MRI signals [9].Therefore, the radiological diagnosis of compression fracture by aggressive VHs is di cult because atypical lesions can mimic other conditions, such as osteoporotic vertebral compression fracture, primary spinal malignancy, or metastatic disease [5,9].The misdiagnosis of aggressive VHs may cause uncontrollable intraoperative hemorrhages.In our study, CT-guided percutaneous biopsy was conducted in all patients before surgery (Fig. 2).Previous studies reported CT-guided biopsy has high value in the diagnosis of suspected atypical spinal malignancy and the overall diagnostic accuracy of CT-guided biopsy is up to 89% [20].Our ndings showed only one case had negative pathological diagnose, the false negative rate was in accordance with the literature.In this case, a diagnosis of VHs was still suspected because only osteocyte and blood cells were detected on biopsy, and postoperative pathological diagnosis of VHs was nally con rmed.
Surgery is still the primary but the most radical treatment for aggressive VHs, but the choice of surgery is still debated.The surgical method mainly involved decompression surgery, intralesional vertebrectomy, and total en-bloc spondylectomy [2-4, 6, 7, 9, 17].Decompression surgeryby laminectomy is widely used because it is relatively simple and less technically demanding, but this procedure is reported to have higher recurrence rate.Combined with the intraoperative vertebroplasty, decompressive laminectomy can achieve less incidence of recurrence and complication, but also less blood loss [7,11].Vertebroplasty can provide immediate strong spinal column stabilization, shrink the blood vessels and cause sclerosis of the VH lesions.According to our experience and the literature review (Table 3) [5, 11, 15-17, 19, 21-29], the indication of surgical decompression is that cases with severe or rapidly developing neurological de cits.In a multicenter study conducted by Goldstein et al. [3], no recurrence of VHs was found in patients after en bloc resection and decompression with an average 3.9 years follow-up.The author suggested en bloc resection is not required because symptomatic VHs are benign spinal tumor, the excellent local control rate of and long-term survival can be due to aggressive intralesional resection during index surgery.In our clinical practice, we used preoperative trans-arterial embolization and intraoperative injection of gelfoam to further reduce blood loss.After injection of gelfoam and cement, the visualization of operative eld was clearer, and the tumor tissue can be removed more effectively and thoroughly.We previously found the intraoperative injection of absorbable gelfoam is associated with fewer blood loss and surgery duration [30].Because the size of gelfoam particlesare small, the communicating blood vessels of the tumor body can be embolized by the gelfoam particles, and the mixed contrast medium injected at the same step can demonstrate the effect of embolization.Besides, injecting gelfoam before vertebroplasty may effectively minimize the cement leakage into the spinal canal and paraspinal soft tissues.The gelfoam mixed contrast offers a relatively closed space for the diffusion of the bone cement, which can prevent the cement leaking into the spinalcanal, especially for patients with the destruction of the posterior vertebral body.In our series, the mean blood loss was observed to be 908.3ml, with no bleeding-and cement-related complications occurred.We performed laminectomy decompression and internal xation inthe last step, the cement escaped into the spinal canal can also be removed during the decompression, which can also decrease the complication of cement leakage.On the other hand,the instrumentations can offer stability to protect the affected vertebra from re-fracture and decrease the trend of adjacent segment fracture following vertebroplasty [31].Clinical outcomes assessed by the VAS score and Frankel grade were signi cantly improved after surgery, without severe complications.The ABH, MBH and kyphosis angle of the fractured vertebra were all signi cantly corrected at nal follow-up.The results indicated that this multimodality surgery is an effective and safe technique.
Each case of aggressive VHs needs to be evaluated individually, because controversy remains as to the optimal surgical method.We suggest that the limitation of this multimodality surgery may be aggressive VHs caused by circumferential spinal compression or adjacent vertebral extension.For these cases, we still recommend complete tumor resection (total en bloc spondylectomy or intralesional vertebrectomy).Although none of patients in the present study experienced recurrence at nal follow-up, the average 49.8 months follow-up period is relatively short to evaluate recurrence of tumor.
Other limitations of this study included small number of cases from a single center.Future prospective multicenter studies with large sample sizes are needed to con rm our results.

Conclusions
The diagnosis and treatment of aggressive VHs causing compression fracture with neurological de cits are a challenge for spinal surgeons.Preoperative CT-guided biopsy is of great value for the diagnosis and should be recommended for these patients.The multimodality surgery(preoperative embolization, intraoperative injection of gelfoam mixed with bone cement combined laminectomy decompression) is an effective and safe procedure, andcan be considered as an acceptable surgical choice.

Figures
Figures

Figure 1 A
Figure 1

Figure 2 A
Figure 2

Table 1
5 ± 0.8 (P< 0.01),and Frankel E grade was achieved in 5 patients.Only one patient with preoperatively intramedullary T2-weighted MRI increased signal intensity achieved Frankel D grade at nal follow-up, but this patient can su ciently return to activities of daily living.Radiographical analyses showed the ABH and MBH signi cantly increased from 14.6 ± 2.2 mm to 16.6 ± 3.0 mm (P= 0.21) and from 12.1 ± 5.3 mm to 16.3 ± 4.2 mm at nal follow-up (P= 0.01), respectively.The kyphosis angle was decreased from 12.2 ± 4.3°p reoperatively to 6.4 ± 1.6° (P= 0.01).Pre preoperative, FFU nal follow-up, ORT operation time, EBL estimated blood loss, ABH anterior vertebral body height, MBH middle vertebral body height,CSF cerebrospinal uid There were no severe complications such as intraspinal hematomas, deep infection and thrombosis occurred in any patient.One patient had cerebrospinal uid leakage postoperatively and recovered within 1 week by keeping the supine position and drainage.At nal follow-up, the radiological images showed that the internal implant was in good position.No loosening or breakage of instrumentations was detected.No affected vertebra refracture and adjacent vertebral fracture were developed, and none of the patients experienced recurrence of tumor.

Table 3
Summary of the treatment of patients with vertebral fracture caused by aggressive hemangiomas NONo. number, Pt patient, AVHs aggressive vertebral hemangiomas, SVHs symptomatic vertebral hemangiomas, VHs vertebral hemangiomas, PE preoperative embolization, RT radiation therapy, VP vertebroplasty