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Cheng-Chia Lee, Ching-Jen Chen, Benjamin Ball, David Schlesinger, Zhiyuan Xu, Chun-Po Yen, and Jason Sheehan

OBJECT

Onyx, an ethylene-vinyl alcohol copolymer mixed in a dimethyl sulfoxide solvent, is currently one of the most widely used liquid materials for embolization of intracranial arteriovenous malformations (AVMs). The goal of this study was to define the risks and benefits of stereotactic radiosurgery (SRS) for patients who have previously undergone partial AVM embolization with Onyx.

METHODS

Among a consecutive series of 199 patients who underwent SRS between January 2007 and December 2012 at the University of Virginia, 25 patients had Onyx embolization prior to SRS (the embolization group). To analyze the obliteration rates and complications, 50 patients who underwent SRS without prior embolization (the no-embolization group) were matched by propensity score method. The matched variables included age, sex, nidus volume before SRS, margin dose, Spetzler-Martin grade, Virginia Radiosurgery AVM Scale score, and median imaging follow-up period.

RESULTS

After Onyx embolization, 18 AVMs were reduced in size. Total obliteration was achieved in 6 cases (24%) at a median of 27.5 months after SRS. In the no-embolization group, total obliteration was achieved in 20 patients (40%) at a median of 22.4 months after SRS. Kaplan-Meier analysis demonstrated obliteration rates of 17.7% and 34.1% in the embolization group at 2 and 4 years, respectively. In the no-embolization group, the corresponding obliteration rates were 27.0% and 55.9%. The between-groups difference in obliteration rates after SRS did not achieve statistical significance. The difference in complications, including adverse radiation effects, hemorrhage episodes, seizure control, and patient mortality also did not reach statistical significance.

CONCLUSIONS

Onyx embolization can effectively reduce the size of many AVMs. This case-control study did not show any statistically significant difference in the rates of embolization or complications after SRS in patients who had previously undergone Onyx embolization and those who had not.

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Bhuvaneswara R. Basina, Claire Olson, Dibyendu Kumar Roy, Chun-Po Yen, David Schlesinger, Kazuki Nagayama, and Jason P. Sheehan

Object

Gamma Knife surgery (GKS) is frequently used to treat patients with metastasis to the brain. Radiosurgery seeks to limit radiation to the brain tissue surrounding the metastatic deposits. In patients with such lesions, a low radiation dose to the eloquent brain may help to prevent adverse effects. In this study the authors aimed to quantify the radiosurgical dose delivered to the anterior temporal structures in cases of metastatic brain lesions. They also evaluated the incidence and timing of new metastases in the anterior temporal lobes (ATLs) in patient cohorts that underwent GKS with or without whole-brain radiation therapy (WBRT).

Methods

The authors retrospectively analyzed 100 patients with metastatic brain lesions treated with GKS at the University of Virginia Health System. The anterior 5 cm of the temporal lobes and the hippocampi within the ATLs were contoured on the Gamma Knife planning station. Using the dose-volume histogram function in GammaPlan, treatment parameters for the metastases as well as radiation doses to the contoured ATLs and hippocampi were measured. Patients had clinical and MR imaging follow-ups at 3-month intervals. The ATLs and hippocampal regions were evaluated for the formation of new metastases on follow-up imaging.

Results

The demographic data—age, sex, Karnofsky Performance Scale score, number of temporal metastases at the time of GKS, total volume of metastatic tumors per patient, and number of intracranial metastatic deposits—were similar in the 2 cohorts. In patients without an ATL metastasis at the time of GKS, the mean maximum, 50% volume, and integral doses of radiation to the anterior temporal structures were very low: 2.6 Gy, 0.6 Gy, and 36.3 mJ in the GKS cohort and 2.1 Gy, 0.6 Gy, and 40.9 mJ in the GKS+WBRT cohort, respectively. Among the ATLs that had not shown a brain metastasis at the time of GKS, 8 of 92 temporal lobes in the GKS cohort and 10 of 89 in the GKS+WBRT cohort demonstrated a new anterior temporal lesion on follow-up MR imaging.

Conclusions

Gamma Knife surgery delivered a low dose of background radiation to the ATLs and hippocampi. The incidence of a new ATL metastasis in the GKS cohort was not higher than in the GKS+WBRT cohort. Gamma Knife surgery in the management of brain metastases limits the delivery of radiation to eloquent brain tissue without evidence of an appreciable propensity to develop new metastatic disease in the ATLs or hippocampi. This therapeutic approach may help to avoid unintended neurological dysfunction due to nonspecific delivery of radiation to eloquent brain tissues.

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Jason P. Sheehan, Dibyendu Kumar Ray, Stephen Monteith, Chun Po Yen, James Lesnick, Ronald Kersh, and David Schlesinger

Object

Trigeminal neuralgia is believed to be related to vascular compression of the affected nerve. Radiosurgery has been shown to be reasonably effective for treatment of medically refractory trigeminal neuralgia. This study explores the rate of occurrence of MR imaging–demonstrated vascular impingement of the affected nerve and the extent to which vascular impingement affects pain relief in a population of trigeminal neuralgia patients undergoing Gamma Knife radiosurgery (GKRS).

Methods

The authors performed a retrospective analysis of 106 cases involving patients treated for typical trigeminal neuralgia using GKRS. Patients with or without single-vessel impingement on CISS MR imaging sequences and with no previous surgery were included in the study. Pain relief was assessed according to the Barrow Neurological Institute (BNI) pain intensity score at the last follow-up. Degree of impingement, nerve diameter preand post-impingement, isocenter placement, and dose to the point of maximum impingement were evaluated in relation to the improvement of BNI score.

Results

The overall median follow-up period was 31 months. Overall, a BNI pain score of 1 was achieved in 59.4% of patients at last follow-up. Vessel impingement was seen in 63 patients (59%). There was no significant difference in pain relief between those with and without vascular impingement following GKRS (p > 0.05).

In those with vascular impingement on MR imaging, the median fraction of vessel impingement was 0.3 (range 0.04–0.59). The median dose to the site of maximum impingement was 42 Gy (range 2.9–79 Gy). Increased dose (p = 0.019) and closer proximity of the isocenter to the site of maximum vessel impingement (p = 0.012) correlated in a statistically significant fashion with improved BNI scores in those demonstrating vascular impingement on the GKRS planning MR imaging

Conclusions

Vascular impingement of the affected nerve was seen in the majority of patients with trigeminal neuralgia. Overall pain relief following GKRS was comparable in those with and without evidence of vascular compression on MR imaging. In subgroup analysis of those with MR imaging evidence of vessel impingement of the affected trigeminal nerve, pain relief correlated with a higher dose to the point of contact between the impinging vessel and the trigeminal nerve. Such a finding may point to vascular changes affording at least some degree of relief following GKRS for trigeminal neuralgia.

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Dale Ding, Chun-Po Yen, Robert M. Starke, Zhiyuan Xu, Xingwen Sun, and Jason P. Sheehan

Object

Intracranial arteriovenous malformations (AVMs) are most commonly classified based on their Spetzler-Martin grades. Due to the composition of the Spetzler-Martin grading scale, Grade III AVMs are the most heterogeneous, comprising 4 distinct lesion subtypes. The management of this class of AVMs and the optimal treatment approach when intervention is indicated remain controversial. The authors report their experience with radiosurgery for the treatment of Grade III AVMs in a large cohort of patients.

Methods

All patients with Spetzler-Martin Grade III AVMs treated with radiosurgery at the University of Virginia over the 20-year span from 1989 to 2009 were identified. Patients who had less than 2 years of radiological follow-up and did not have evidence of complete obliteration during that period were excluded from the study, leaving 398 cases for analysis. The median patient age at treatment was 31 years. The most common presenting symptoms were hemorrhage (59%), seizure (20%), and headache (10%). The median AVM volume was 2.8 cm3, and the median prescription dose was 20 Gy. The median radiological and clinical follow-up intervals were 54 and 68 months, respectively. Univariate and multivariate Cox proportional hazards and logistic regression analysis were used to identify factors associated with obliteration, postradiosurgery radiation-induced changes (RIC), and favorable outcome.

Results

Complete AVM obliteration was observed in 69% of Grade III AVM cases at a median time of 46 months after radiosurgery. The actuarial obliteration rates at 3 and 5 years were 38% and 60%, respectively. The obliteration rate was higher in ruptured AVMs than in unruptured ones (p < 0.001). Additionally, the obliteration rate for Grade III AVMs with small size (< 3 cm diameter), deep venous drainage, and location in eloquent cortex was higher than for the other subtypes (p < 0.001). Preradiosurgery AVM rupture (p = 0.016), no preradiosurgery embolization (p = 0.003), increased prescription dose (p < 0.001), fewer isocenters (p = 0.006), and a single draining vein (p = 0.018) were independent predictors of obliteration. The annual risk of postradiosurgery hemorrhage during the latency period was 1.7%. Two patients (0.5%) died of hemorrhage during the radiosurgical latency period. The rates of symptomatic and permanent RIC were 12% and 4%, respectively. Absence of preradiosurgery AVM rupture (p < 0.001) and presence of a single draining vein (p < 0.001) were independent predictors of RIC. Favorable outcome was observed in 63% of patients. Independent predictors of favorable outcome were no preradiosurgery hemorrhage (p = 0.014), increased prescription dose (p < 0.001), fewer isocenters (p = 0.014), deep location (p = 0.014), single draining vein (p = 0.001), and lower Virginia radiosurgery AVM scale score (p = 0.016).

Conclusions

Radiosurgery for Spetzler-Martin Grade III AVMs yields relatively high rates of obliteration with a low rate of adverse procedural events. Small and ruptured lesions are more likely to become obliterated after radiosurgery than large and unruptured ones.

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Thomas J. Buell, Ulas Yener, Tony R. Wang, Avery L. Buchholz, Chun-Po Yen, Mark E. Shaffrey, Christopher I. Shaffrey, and Justin S. Smith

OBJECTIVE

Sacral insufficiency fracture after lumbosacral (LS) arthrodesis is an uncommon complication. The objective of this study was to report the authors’ operative experience managing this complication, review pertinent literature, and propose a treatment algorithm.

METHODS

The authors analyzed consecutive adult patients treated at their institution from 2009 to 2018. Patients who underwent surgery for sacral insufficiency fractures after posterior instrumented LS arthrodesis were included. PubMed was queried to identify relevant articles detailing management of this complication.

RESULTS

Nine patients with a minimum 6-month follow-up were included (mean age 73 ± 6 years, BMI 30 ± 6 kg/m2, 56% women, mean follow-up 35 months, range 8–96 months). Six patients had osteopenia/osteoporosis (mean dual energy x-ray absorptiometry hip T-score −1.6 ± 0.5) and 3 received treatment. Index LS arthrodesis was performed for spinal stenosis (n = 6), proximal junctional kyphosis (n = 2), degenerative scoliosis (n = 1), and high-grade spondylolisthesis (n = 1). Presenting symptoms of back/leg pain (n = 9) or lower extremity weakness (n = 3) most commonly occurred within 4 weeks of index LS arthrodesis, which prompted CT for fracture diagnosis at a mean of 6 weeks postoperatively. All sacral fractures were adjacent or involved S1 screws and traversed the spinal canal (Denis zone III). H-, U-, or T-type sacral fracture morphology was identified in 7 patients. Most fractures (n = 8) were Roy-Camille type II (anterior displacement with kyphosis). All patients underwent lumbopelvic fixation via a posterior-only approach; mean operative duration and blood loss were 3.3 hours and 850 ml, respectively. Bilateral dual iliac screws were utilized in 8 patients. Back/leg pain and weakness improved postoperatively. Mean sacral fracture anterolisthesis and kyphotic angulation improved (from 8 mm/11° to 4 mm/5°, respectively) and all fractures were healed on radiographic follow-up (mean duration 29 months, range 8–90 months). Two patients underwent revision for rod fractures at 1 and 2 years postoperatively. A literature review found 17 studies describing 87 cases; potential risk factors were osteoporosis, longer fusions, high pelvic incidence (PI), and postoperative PI-to–lumbar lordosis (LL) mismatch.

CONCLUSIONS

A high index of suspicion is needed to diagnose sacral insufficiency fracture after LS arthrodesis. A trial of conservative management is reasonable for select patients; potential surgical indications include refractory pain, neurological deficit, fracture nonunion with anterolisthesis or kyphotic angulation, L5–S1 pseudarthrosis, and spinopelvic malalignment. Lumbopelvic fixation with iliac screws may be effective salvage treatment to allow fracture healing and symptom improvement. High-risk patients may benefit from prophylactic lumbopelvic fixation at the time of index LS arthrodesis.

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Ching-Jen Chen, Srinivas Chivukula, Dale Ding, Robert M. Starke, Cheng-Chia Lee, Chun-Po Yen, Zhiyuan Xu, and Jason P. Sheehan

Object

Seizures are a common presentation of cerebral arteriovenous malformations (AVMs). The authors evaluated the efficacy of stereotactic radiosurgery (SRS) for the management of seizures associated with AVMs and identified factors influencing seizure outcomes following SRS for AVMs.

Methods

A systematic literature review was performed using PubMed. Studies selected for review were published in English, included at least 5 patients with both cerebral AVMs and presenting seizures treated with SRS, and provided post-SRS outcome data regarding obliteration of AVMs and/or seizures. Demographic, radiosurgical, radiological, and seizure outcome data were extracted and analyzed. All seizure outcomes were categorized as follows: 1) seizure free, 2) seizure improvement, 3) seizure unchanged, and 4) seizure worsened. Systematic statistical analysis was conducted to assess the effect of post-SRS AVM obliteration on seizure outcome.

Results

Nineteen case series with a total of 3971 AVM patients were included for analysis. Of these, 28% of patients presented with seizures, and data for 997 patients with available seizure outcome data who met the inclusion criteria were evaluated. Of these, 437 (43.8%) patients achieved seizure-free status after SRS, and 530 (68.7%) of 771 patients with available data achieved seizure control (seizure freedom or seizure improvement) following SRS. Factors associated with improved seizure outcomes following SRS for AVMs were analyzed in 9 studies. Seizure-free status was achieved in 82% and 41.0% of patients with complete and incomplete AVM obliteration, respectively. Complete AVM obliteration offered superior seizure-free rates compared with incomplete AVM obliteration (OR 6.13; 95% CI 2.16–17.44; p = 0.0007).

Conclusions

Stereotactic radiosurgery offers favorable seizure outcomes for AVM patients presenting with seizures. Improved seizure control is significantly more likely with complete AVM obliteration.

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Jay Jagannathan, Chun-Po Yen, Dibyendu Kumar Ray, David Schlesinger, Rod J. Oskouian, Nader Pouratian, Mark E. Shaffrey, James Larner, and Jason P. Sheehan

Object

This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis.

Methods

A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2–115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75–35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery.

Results

The mean radiographic follow-up duration was 14 months (median 10 months, range 4–37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p = 0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p = 0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40–100).

Conclusion:

Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

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Shayan Moosa, Ching-Jen Chen, Dale Ding, Cheng-Chia Lee, Srinivas Chivukula, Robert M. Starke, Chun-Po Yen, Zhiyuan Xu, and Jason P. Sheehan

Object

The aim in this paper was to compare the outcomes of dose-staged and volume-staged stereotactic radio-surgery (SRS) in the treatment of large (> 10 cm3) arteriovenous malformations (AVMs).

Methods

A systematic literature review was performed using PubMed. Studies written in the English language with at least 5 patients harboring large (> 10 cm3) AVMs treated with dose- or volume-staged SRS that reported post-treatment outcomes data were selected for review. Demographic information, radiosurgical treatment parameters, and post-SRS outcomes and complications were analyzed for each of these studies.

Results

The mean complete obliteration rates for the dose- and volume-staged groups were 22.8% and 47.5%, respectively. Complete obliteration was demonstrated in 30 of 161 (18.6%) and 59 of 120 (49.2%) patients in the dose- and volume-staged groups, respectively. The mean rates of symptomatic radiation-induced changes were 13.5% and 13.6% in dose- and volume-staged groups, respectively. The mean rates of cumulative post-SRS latency period hemorrhage were 12.3% and 17.8% in the dose- and volume-staged groups, respectively. The mean rates of post-SRS mortality were 3.2% and 4.6% in dose- and volume-staged groups, respectively.

Conclusions

Volume-staged SRS affords higher obliteration rates and similar complication rates compared with dose-staged SRS. Thus, volume-staged SRS may be a superior approach for large AVMs that are not amenable to single-session SRS. Staged radiosurgery should be considered as an efficacious component of multimodality AVM management.

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Thomas J. Buell, Ching-Jen Chen, James H. Nguyen, Peter A. Christiansen, Saikiran G. Murthy, Avery L. Buchholz, Chun-Po Yen, Mark E. Shaffrey, Christopher I. Shaffrey, and Justin S. Smith

OBJECTIVE

Prior reports have demonstrated the efficacy of surgical correction for adult lumbar scoliosis. Many of these reports focused on mild to moderate scoliosis. The authors’ objective was to report their experience and to assess outcomes and complications after deformity correction for severe adult scoliosis.

METHODS

The authors retrospectively analyzed consecutive adult scoliosis patients with major thoracolumbar/lumbar (TL/L) curves ≥ 75° who underwent deformity correction at their institution. Those eligible with a minimum 2 years of follow-up were included. Demographic, surgical, coronal and sagittal plane radiographic measurements, and health-related quality of life (HRQL) scores were analyzed.

RESULTS

Among 26 potentially eligible patients, 22 (85%) had a minimum 2 years of follow-up (range 24–89 months) and were included in the study (mean age 57 ± 11 years; 91% women). The cohort comprised 16 (73%), 4 (18%), and 2 (9%) patients with adult idiopathic scoliosis, de novo degenerative scoliosis, and iatrogenic scoliosis, respectively. The surgical approach was posterior-only and multistage anterior-posterior in 18 (82%) and 4 (18%) patients, respectively. Three-column osteotomy was performed in 5 (23%) patients. Transforaminal and anterior lumbar interbody fusion were performed in 14 (64%) and 4 (18%) patients, respectively. All patients had sacropelvic fixation with uppermost instrumented vertebra in the lower thoracic spine (46% [10/22]) versus upper thoracic spine (55% [12/22]). The mean fusion length was 14 ± 3 levels. Preoperative major TL/L and lumbosacral fractional (L4–S1) curves were corrected from 83° ± 8° to 28° ± 13° (p < 0.001) and 34° ± 8° to 13° ± 6° (p < 0.001), respectively. Global coronal and sagittal balance significantly improved from 5 ± 4 cm to 1 ± 1 cm (p = 0.001) and 9 ± 8 cm to 2 ± 3 cm (p < 0.001), respectively. Pelvic tilt significantly improved from 33° ± 9° to 23° ± 10° (p < 0.001). Significant improvement in HRQL measures included the following: Scoliosis Research Society (SRS) pain score (p = 0.009), SRS appearance score (p = 0.004), and SF-12/SF-36 physical component summary (PCS) score (p = 0.026). Transient and persistent neurological deficits occurred in 8 (36%) and 2 (9%) patients, respectively. Rod fracture/pseudarthrosis occurred in 6 (27%) patients (supplemental rods were utilized more recently in 23%). Revisions were performed in 7 (32%) patients.

CONCLUSIONS

In this single-center surgical series for severe adult scoliosis (major curves ≥ 75°), a posterior-only or multistage anterior-posterior approach provided major curve correction of 66% and significant improvements in global coronal and sagittal spinopelvic alignment. Significant improvements were also demonstrated in HRQL measures (SRS pain, SRS appearance, and SF-12/SF-36 PCS). Complications and revisions were comparable to those of other reports involving less severe scoliosis. The results of this study warrant future prospective multicenter studies to further delineate outcomes and complication risks for severe adult scoliosis correction.